Bio

Clinical Focus


  • Radiation Oncology
  • Head and Neck Cancer
  • Cancer > Thoracic Oncology
  • Radiation Therapy
  • Lung Cancer
  • Cancer > Radiation Oncology
  • Cancer > Head and Neck Cancer

Academic Appointments


Administrative Appointments


  • Co-Chair, New Technologies Committee, Radiation Oncology (2011 - Present)
  • Thoracic Radiation Oncology Program Leader, Radiation Oncology (2005 - Present)

Honors & Awards


  • Educator of the Year Award, Association of Residents in Radiation Oncology (2012)
  • Henry S. Kaplan Memorial Prize for Teaching in Radiation Oncology, Stanford University (2009)
  • Young Investigator Travel Grant, ECOG (2005)
  • Basic Science Travel Grant, ASTRO (2005)
  • Roentgen Resident/Fellow Research Award, RSNA (2004)
  • Travel Grant Award, Best of ASCO Meeting, Denver, ASCO (2004)
  • Molecular Biology in Clinical Oncology Workshop Scholarship, AACR (2004)
  • Malcolm A. Bagshaw Award, Stanford Radiation Oncology (2003)
  • Graduate Student Research Award, University of California, San Francisco (1996)
  • Regents Fellowship, University of California (1996)
  • Laboratory Graduate Fellowship, Associated Western Universities (1994, 1995)
  • Research Scholarship, California Medical Education and Research Foundation (1992)
  • Rapp/Rummelsberg Research Scholarship, - (1991)

Professional Education


  • Internship:Kaiser Found Hosp San Fran (2001) CA
  • Board Certification: Radiation Oncology, American Board of Radiology (2006)
  • Residency:Stanford University Medical Center (2005) CA
  • Ph.D., U.C.S.F., U.C. Berkeley, Bioengineering (2000)
  • Medical Education:UC Davis School of Medicine (2000) CA
  • A.B., U.C. Berkeley, Biophysics (1989)

Research & Scholarship

Current Research and Scholarly Interests


My main clinical specialties are radiation treatment of lung cancer and head & neck cancer, and I serve as the Thoracic Radiation Oncology Program Leader.

My clinical research interests include 4-D multimodality imaging of tumor and organ motion using CT, PET, and MR; novel functional/metabolic imaging of tumor hypoxia and lymphatic drainage; and implementation and clinical trials of high-precision image-guided radiation therapy including 4-D IMRT, dynamic conformal arc radiotherapy (DCART) and volumetric modulated arc therapy (VMAT), and stereotactic ablative radiotherapy (SABR). My preclinical and translational research interests include novel functional imaging of inflammation as a mechanism of late normal tissue radiation injury, novel reconstruction and processing methods for 4-D imaging data to reduce artifacts and extract functional/physiologic information, and the radiobiology of tumor hypoxia and SABR.

Clinical Trials


  • Specialized Radiation Therapy in Treating Patients With Stage II, Stage III, Stage IV, or Recurrent Non-Small Cell Lung Cancer and Poor Performance Status Not Recruiting

    RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase I trial is studying the side effects and best dose of specialized radiation therapy in treating patients with stage II, stage III, stage IV, or recurrent non-small cell lung cancer and poor performance status.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

    View full details

  • Feasibility of Using Real-time Cine-MRI for Treating Moving & Deforming Tumors Not Recruiting

    This study aims to investigate and optimize imaging sequences and parameters of rapid real-time MRI in order to obtain adequate guidance for accurately and precisely delivering radiation to moving abdominal and thoracic tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melody Chung, (650) 736 - 0798.

    View full details

  • Three Different Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide Recruiting

    Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.

    View full details

  • Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which regimen of stereotactic body radiation therapy is more effective in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying the side effects of two radiation therapy regimens and to see how well they work in treating patients with stage I non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact laura gable, (650) 736 - 0798.

    View full details

  • CyberKnife Radiosurgical Treatment of Inoperable Early Stage Non-Small Cell Lung Cancer Not Recruiting

    The purpose of this study is to assess the short and long-term outcomes after CyberKnife stereotactic radiosurgery for early stage non-small cell lung cancer (NSCLC) in patients who are medically inoperable.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

    View full details

  • 4D-CT-based Ventilation Imaging for Adaptive Functional Guidance in Radiotherapy Recruiting

    To determine the appropriate class of deformable image registration algorithm and metric best suited for four-dimensional (4D) CT-based ventilation assessment.

    View full details

  • Indirect Magnetic Resonance Lymphangiography of the Head and Neck Region Using Conventional Gadolinium-based Contrast Not Recruiting

    To determine the ability of magnetic resonance lymphangiography using conventional gadolinium injected directly into the tumor site and PET scan in detecting microscopic nodal metastasis in patients with newly diagnosed H&N cancers

    Stanford is currently not accepting patients for this trial. For more information, please contact Bill Loo, (650) 736 - 7143.

    View full details

  • Surgery With or Without Internal Radiation Therapy Compared With Stereotactic Body Radiation Therapy in Treating Patients With High-Risk Stage I Non-Small Cell Lung Cancer Not Recruiting

    RATIONALE: Surgery with or without internal radiation therapy may be an effective treatment for non-small cell lung cancer. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known whether stereotactic body radiation therapy is more effective than surgery with or without internal radiation therapy in treating non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying how well surgery with or without internal radiation therapy works compared with stereotactic body radiation therapy in treating patients with high-risk stage IA or stage IB non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

    View full details

  • Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer (Cetuximab Closed as of 05/14/10) Recruiting

    RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without panitumumab in treating patients with non-small cell lung cancer. (cetuximab closed as of 05/14/10) PURPOSE: This randomized phase II trial is studying chemotherapy and radiation therapy to see how well they work when given with or without panitumumab in treating patients with stage IIIA non-small cell lung cancer. (cetuximab closed as of 05/14/10)

    View full details

  • Phase II Docetaxel / Carboplatin / XRT + Surgical Resection in Stage III NSCLC Not Recruiting

    The purpose of this study is to assess how well this particular combination of chemotherapy, radiation and surgery works to help people with locally advanced lung cancer, how well PET scans indicates whether someone has responded to chemotherapy and radiation, and gene expression patterns related to outcomes in patients with locally advanced lung cancer who receive this treatment regimen.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

    View full details

  • Stereotactic Body Radiation Therapy in Treating Patients With Stage I or Stage II Non-Small Cell Lung Cancer That Can Be Removed By Surgery Not Recruiting

    RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue near the tumor. PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with stage I or stage II non-small cell lung cancer that can be removed by surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Melody Chung, (650) 736 - 0798.

    View full details

  • High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

    View full details

  • BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery Recruiting

    RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vaccine therapy together with bevacizumab after chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving BLP25 liposome vaccine together with bevacizumab after chemotherapy and radiation therapy in treating patients with newly diagnosed stage IIIA or stage IIIB non-small cell lung cancer that cannot be removed by surgery.

    View full details

  • Randomized Study to Compare CyberKnife to Surgical Resection In Stage I Non-small Cell Lung Cancer Not Recruiting

    Lung cancer remains the most frequent cause of cancer death in both men and women in the world. Surgical resection using lobectomy with mediastinal lymph node dissection or sampling has been a standard of care for operable early stage NSCLC. Several studies have reported high local control and survival using SBRT in stage I NSCLC patients. SBRT is now an accepted treatment for medically inoperable patients with stage I NSCLC and patients with operable stage I lung cancer are entered on clinical protocols. The purpose of this study is to conduct a phase III randomized study to compare CyberKnife SBRT with surgery, the current standard of care for stage I operable NSCLC.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

    View full details

  • Imaging and Biomarkers of Hypoxia in Solid Tumors Recruiting

    To establish PET imaging with the tracer FMISO as an accurate and reliable method for measuring the oxygen content of a tumor and to establish the measurement of secreted markers in blood as an accurate and reliable method for measuring the oxygen content of a tumor.

    View full details

  • A Longitudinal Study of Plasma EBV DNA in Nasopharyngeal Carcinoma From Both Endemic and Non-Endemic Patient Populations Not Recruiting

    1. To determine the prognostic implication of plasma Epstein-Bar Virus (EBV) DNA concentrations, as measured by quantitative polymerase chain reaction (PCR) in patients with nasopharyngeal carcinoma (NPC). 2. To relate pretreatment plasma EBV DNA concentration to WHO classification of these tumors both in endemic and non-endemic areas. 3. To determine whether pretreatment plasma EBV DNA can serve as a prognostic factor for both endemic and non-endemic patient populations.

    Stanford is currently not accepting patients for this trial. For more information, please contact Quynh-Thu Le, 650-498-6184.

    View full details

  • Novel Serum Markers for Monitoring Response to Anti-Cancer Therapy Recruiting

    The purpose of this trial is to collect blood serum from cancer patients with tumors at different disease sites (such as pancreas, head and neck, and breast) prior to and at subsequent points following anti-cancer therapy to discover novel serum markers of response.

    View full details

  • Endoscopic Capillary Oximetry for Tumor Diagnosis in Head and Neck Cancer Not Recruiting

    Endoscopy is a standard part of the evaluation of patients with head and neck cancer used for determining the extent of tumor involvement. However, not all areas involved by tumor are apparent visually. Preliminary results indicate that compared with normal tissues, tumors have abnormal levels of capillary oxygenation. The purpose of this study is to determine the ability of non-pulsatile visible light tissue oxygen monitoring to differentiate normal and tumor tissue based on capillary oxygenation during endoscopy Should this be possible, this method could be used to mark tumor extent and invasion, even when that invasion is up to 5mm blow the tissue surface.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peter Maxim, (650) 724 - 3018.

    View full details

  • Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer Not Recruiting

    RATIONALE: Manuka honey may prevent or reduce esophagitis-related pain caused by chemotherapy and radiation therapy. It is not yet known whether Manuka honey is more effective than standard care in preventing pain. PURPOSE: This randomized phase II clinical trial is studying Manuka honey to see how well it works in preventing esophagitis-related pain in patients receiving chemotherapy and radiation therapy for lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

    View full details

  • Radiation Therapy in Preventing CNS Metastases in Patients With Non-Small Cell Lung Cancer Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if giving radiation therapy to the head is effective in preventing CNS metastases in patients who have stage III non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying how well radiation therapy to the head works in preventing CNS metastases in patients who have been previously treated for stage III non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Derek Huang, (650) 725 - 0203.

    View full details

  • Phase I Trial of Metabolic Reprogramming Therapy for Treatment of Recurrent Head and Neck Cancers Recruiting

    To determine the maximum tolerated dose of DCA in patients with recurrent head and neck cancer who have failed first-line therapy. The purpose of this study is to study the effect of the drug DCA (dichloroacetate) on recurrent head and neck cancers. Part of this study will also use EF5 PET scan to study tumor hypoxia.

    View full details

  • Radiation Therapy in Treating Patients With Extensive Stage Small Cell Lung Cancer Recruiting

    RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. This may be an effective treatment for extensive stage small cell lung cancer. PURPOSE: This randomized phase II trial is comparing how well radiation therapy to the brain works when given with or without radiation therapy to other areas of the body in treating patients with extensive stage small cell lung cancer.

    View full details

  • Cervical Nodal Mets in Squamous Cell Carcinoma of H&N - MRI, FDG-PET, & Histopathologic Correlation Not Recruiting

    The purpose of this study is to determine the value of novel non-invasive medical imaging methods for detecting the spread of head and neck squamous cell carcinoma to the lymph nodes in the neck by comparing their results to findings at the time of surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Quynh-Thu Le, (650) 498 - 6184.

    View full details

  • Pulmonary Interstitial Lymphography in Early Stage Lung Cancer Not Recruiting

    Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world. NSCLC annually causes 150,000 deaths in the US and greater than 1 million worldwide. The standard treatment for early stage NSCLC is lobectomy with lymphadenectomy. However, many patients are poor operative candidates or decline surgery. An emerging alternative is Stereotactic Body Radiation Therapy (SBRT). Mounting evidence from Phase I/II studies demonstrates that SBRT offers excellent local control. Most SBRT trials focused on small, peripheral tumors in inoperable patients. Increasingly, clinical trials study SBRT in operable patients, often with larger, central tumors. Using clinical staging, a significant proportion of patients harbor occult nodal metastases when undergoing SBRT to the primary tumor alone. Subgroups of patients carry even higher risk of nodal metastases. These nodal metastases frequently would be removed by surgical intervention. However, SBRT, at present, is only directed at the primary tumor, potentially leading to regional failures in otherwise curable patients. To increase the effectiveness of SBRT for lung tumors, the next logical step is to explore whether the highest risk areas of disease spread can be identified and targeted. Regional failure could be reduced and outcome improved in a significant proportion of patients treated with SBRT if the primary nodal drainage (PND) were identified, targeted and treated in addition to the primary tumor. We propose to conduct a study to determine how well water soluble iodinated contrast material when injected directly into the tumor can be visualized on CT scan and integrated into radiation therapy treatment planning.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

    View full details

  • Identification of Secreted Markers for Tumor Hypoxia in Patients With Head and Neck or Lung Cancers Recruiting

    To correlate tumor oxygenation as measured by the Eppendorf electrode with the serum level of secreted proteins known to be induced by tumor hypoxia.

    View full details

  • Study of Positron Emission Tomography and Computed Tomography in Guiding Radiation Therapy in Patients With Stage III Non-Small Cell Lung Cancer Recruiting

    This randomized phase II trial studies how well positron emission tomography (PET)/computed tomography (CT) scan work in guiding radiation therapy compared to standard radiation therapy treatment in patients with stage III non-small cell lung cancer. Imaging procedures, such as PET scan and CT scan, may help doctors plan radiation therapy for patients with non-small cell lung cancer.

    View full details

  • Breath Analysis for Evaluation of Radiation Exposure in Lung Cancer Patients Treated With Radiation Not Recruiting

    Patients treated with radiation therapy for lung tumors can experience inflammation after treatment. This study hopes to evaluate the use of breath analysis to evaluate changes in the composition of exhaled breath in patients undergoing radiotherapy. If changes can be detected, this may ultimately serve as biomarkers for identifying patients at highest risk for radiation-induced lung injury (radiation pneumonitis).

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

    View full details

  • The Role of FDG PET in Radiation Treatment Planning for Head and Neck Cancers Not Recruiting

    In patients with cancer of the head and neck and rectum, knowing the exact location of the tumor is important for designing the radiation field to ensure delivery of high dose of radiation to the tumor while sparing surrounding normal tissues. A new medical imaging method which is a combination of positron emission tomography (PET) and computed tomography (CT) scan, has shown promise in helping the radiation oncologist in defining the exact location and extent of the tumor in certain cancers such as lung cancers. Therefore the purpose of this study is to determine if these imaging methods can be used in combination with the standard radiation treatment planning procedure to improve the accuracy to targeting your tumor with radiation. In addition the PET-CT scan, similar to the PET scan alone with better resolution, can be used to determine whether the tumor has spread to any part of the body outside of the head and neck sites.

    Stanford is currently not accepting patients for this trial. For more information, please contact Quynh-Thu Le, (650) 498 - 6184.

    View full details

  • Evaluation of Cyberknife Precision Radiation Delivery System for Unresectable Malignant Lung Cancer Not Recruiting

    This study has two primary objectives. The first objective is to determine the maximal tolerated dose (MTD) that can be delivered with stereotactic radiosurgery in patients with inoperable malignant lung tumors. Once the MTD is established, the second objective is to determine the efficacy of radiosurgical ablation of lung tumors in terms of symptoms and radiographic responses.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

    View full details

  • Molecular Analysis of Thoracic Malignancies Recruiting

    Primary Objective: To collect detailed clinical information on patients with thoracic malignancies via the electronic medical record and a detailed patient questionnaire, collect blood samples, retrieve paraffin embedded tissue if not collected at Stanford, and perform exploratory molecular analysis of tumor tissues.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • PET Imaging of Stroke-Induced Neuroinflammation in Mice Using [F-18]PBR06 MOLECULAR IMAGING AND BIOLOGY Lartey, F. M., Ahn, G., Shen, B., Cord, K., Smith, T., Chua, J. Y., Rosenblum, S., Liu, H., James, M. L., Chernikova, S., Lee, S. W., Pisani, L. J., Tirouvanziam, R., Chen, J. W., Palmer, T. D., Chin, F. T., Guzman, R., Graves, E. E., Loo, B. W. 2014; 16 (1): 109-117

    Abstract

    The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [(18)F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([(18)F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model.Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later. PET data were correlated with immunohistochemistry (IHC) for the activated microglial markers TSPO and CD68 and with autoradiography.[(18)F]PBR06 accumulation peaked within the first 5 min postinjection, then decreased gradually, remaining significantly higher in infarct compared to noninfarct regions. Displacement or preblocking with PK11195 eliminated the difference in [(18)F]PBR06 uptake between infarct and noninfarct regions. Autoradiography and IHC correlated well spatially with uptake on PET.[(18)F]PBR06 PET specifically images TSPO in microglial neuroinflammation in a mouse model of stroke and shows promise for imaging and monitoring microglial activation/neuroinflammation in other disease models.

    View details for DOI 10.1007/s11307-013-0664-5

    View details for Web of Science ID 000329793200014

    View details for PubMedID 23836504

  • Clinical implementation of intrafraction cone beam computed tomography imaging during lung tumor stereotactic ablative radiation therapy. International journal of radiation oncology, biology, physics Li, R., Han, B., Meng, B., Maxim, P. G., Xing, L., Koong, A. C., Diehn, M., Loo, B. W. 2013; 87 (5): 917-923

    Abstract

    To develop and clinically evaluate a volumetric imaging technique for assessing intrafraction geometric and dosimetric accuracy of stereotactic ablative radiation therapy (SABR).Twenty patients received SABR for lung tumors using volumetric modulated arc therapy (VMAT). At the beginning of each fraction, pretreatment cone beam computed tomography (CBCT) was used to align the soft-tissue tumor position with that in the planning CT. Concurrent with dose delivery, we acquired fluoroscopic radiograph projections during VMAT using the Varian on-board imaging system. Those kilovolt projections acquired during millivolt beam-on were automatically extracted, and intrafraction CBCT images were reconstructed using the filtered backprojection technique. We determined the time-averaged target shift during VMAT by calculating the center of mass of the tumor target in the intrafraction CBCT relative to the planning CT. To estimate the dosimetric impact of the target shift during treatment, we recalculated the dose to the GTV after shifting the entire patient anatomy according to the time-averaged target shift determined earlier.The mean target shift from intrafraction CBCT to planning CT was 1.6, 1.0, and 1.5 mm; the 95th percentile shift was 5.2, 3.1, 3.6 mm; and the maximum shift was 5.7, 3.6, and 4.9 mm along the anterior-posterior, left-right, and superior-inferior directions. Thus, the time-averaged intrafraction gross tumor volume (GTV) position was always within the planning target volume. We observed some degree of target blurring in the intrafraction CBCT, indicating imperfect breath-hold reproducibility or residual motion of the GTV during treatment. By our estimated dose recalculation, the GTV was consistently covered by the prescription dose (PD), that is, V100% above 0.97 for all patients, and minimum dose to GTV >100% PD for 18 patients and >95% PD for all patients.Intrafraction CBCT during VMAT can provide geometric and dosimetric verification of SABR valuable for quality assurance and potentially for treatment adaptation.

    View details for DOI 10.1016/j.ijrobp.2013.08.015

    View details for PubMedID 24113060

  • 4D CT lung ventilation images are affected by the 4D CT sorting method MEDICAL PHYSICS Yamamoto, T., Kabus, S., Lorenz, C., Johnston, E., Maxim, P. G., Diehn, M., Eclov, N., Barquero, C., Loo, B. W., Keall, P. J. 2013; 40 (10)

    Abstract

    Four-dimensional (4D) computed tomography (CT) ventilation imaging is a novel promising technique for lung functional imaging. The current standard 4D CT technique using phase-based sorting frequently results in artifacts, which may deteriorate the accuracy of ventilation imaging. The purpose of this study was to quantify the variability of 4D CT ventilation imaging due to 4D CT sorting.4D CT image sets from nine lung cancer patients were each sorted by the phase-based method and anatomic similarity-based method, designed to reduce artifacts, with corresponding ventilation images created for each method. Artifacts in the resulting 4D CT images were quantified with the artifact score which was defined based on the difference between the normalized cross correlation for CT slices within a CT data segment and that for CT slices bordering the interface between adjacent CT data segments. The ventilation variation was quantified using voxel-based Spearman rank correlation coefficients for all lung voxels, and Dice similarity coefficients (DSC) for the spatial overlap of low-functional lung volumes. Furthermore, the correlations with matching single-photon emission CT (SPECT) ventilation images (assumed ground truth) were evaluated for three patients to investigate which sorting method provides higher physiologic accuracy.Anatomic similarity-based sorting reduced 4D CT artifacts compared to phase-based sorting (artifact score, 0.45 ± 0.14 vs 0.58 ± 0.24, p = 0.10 at peak-exhale; 0.63 ± 0.19 vs 0.71 ± 0.31, p = 0.25 at peak-inhale). The voxel-based correlation between the two ventilation images was 0.69 ± 0.26 on average, ranging from 0.03 to 0.85. The DSC was 0.71 ± 0.13 on average. Anatomic similarity-based sorting yielded significantly fewer lung voxels with paradoxical negative ventilation values than phase-based sorting (5.0 ± 2.6% vs 9.7 ± 8.4%, p = 0.05), and improved the correlation with SPECT ventilation regionally.The variability of 4D CT ventilation imaging due to 4D CT sorting was moderate overall and substantial in some cases, suggesting that 4D CT artifacts are an important source of variations in 4D CT ventilation imaging. Reduction of 4D CT artifacts provided more physiologically convincing and accurate ventilation estimates. Further studies are needed to confirm this result.

    View details for DOI 10.1118/1.4820538

    View details for Web of Science ID 000325394400023

    View details for PubMedID 24089909

  • Radiotherapy for nonadenoid cystic carcinomas of major salivary glands. American journal of otolaryngology Chung, M. P., Tang, C., Chan, C., Hara, W. Y., Loo, B. W., Kaplan, M. J., Fischbein, N., Le, Q., Chang, D. T. 2013; 34 (5): 425-430

    Abstract

    PURPOSE: To report outcomes in patients treated with postoperative radiotherapy for nonadenoid cystic carcinomas of the major salivary glands. MATERIALS AND METHODS: From 1998-2011, 37 patients with nonadenoid cystic carcinomas of the major salivary gland underwent postoperative radiotherapy. The median radiation dose was 60Gy (range, 45-70Gy). TNM distribution included T1-2 (n=16, 44%), T3-T4 (n=21, 56%), N0 (n=19, 51%), and N+ (n=18, 49%). Histologies included adenocarcinoma (n=13, 35%), squamous cell carcinoma (n=8, 22%), mucoepidermoid carcinoma (n=8, 22%), and other (n=8, 21%). Median follow-up was 4.7years for all patients (range, 0.3-14.1years) and 5.0years for living patients (range, 1.2-12.2years). RESULTS: Five-year local-regional control, overall survival (OS), and cancer-specific survival (CSS) were 97%, 76%, and 84%. On univariate analysis, OS was significantly worse for patients ≥65years old (p=0.04). CSS was significantly worse for positive perineural invasion (p=0.02), extraparenchymal extension (p=0.04), and in patients who received no chemotherapy (p=0.02). Doses >60Gy was significantly worse for OS (p=0.003) and CSS (p=0.003), although these patients had higher TNM (>T2, p=0.01) and trended towards a higher rate of extraparenchymal extension (p=0.08). Four patients (11%) developed ≥grade 2 toxicities; 3 patients developed early toxicities and one patient developed late toxicities. CONCLUSIONS: Radiotherapy for salivary gland tumors provides excellent local-regional control when combined with surgery. Distant metastasis is the predominant pattern of failure, although chemotherapy seemed to improve cancer-specific survival.

    View details for DOI 10.1016/j.amjoto.2013.03.007

    View details for PubMedID 23583094

  • An Observational Study of Circulating Tumor Cells and F-18-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer PLOS ONE Nair, V. S., Keu, K. V., Luttgen, M. S., Kolatkar, A., Vasanawala, M., Kuschner, W., Bethel, K., Iagaru, A. H., Hoh, C., Shrager, J. B., Loo, B. W., Bazhenova, L., Nieva, J., Gambhir, S. S., Kuhn, P. 2013; 8 (7)

    Abstract

    We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

    View details for DOI 10.1371/journal.pone.0067733

    View details for Web of Science ID 000321425300025

    View details for PubMedID 23861795

  • Non-small cell lung cancer, version 2.2013. Journal of the National Comprehensive Cancer Network Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Govindan, R., Grannis, F. W., Grant, S. C., Horn, L., Jahan, T. M., Komaki, R., Kong, F. S., Kris, M. G., Krug, L. M., Lackner, R. P., Lennes, I. T., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pinder-Schenck, M. C., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Shapiro, T. A., Swanson, S. J., Tauer, K., Wood, D. E., Yang, S. C., Gregory, K., Hughes, M. 2013; 11 (6): 645-653

    Abstract

    These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.

    View details for PubMedID 23744864

  • Thymomas and Thymic Carcinomas Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Riely, G. J., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Govindan, R., Grannis, F. W., Grant, S. C., Horn, L., Jahan, T. M., Komaki, R., (Spring) Kong, F., Kris, M. G., Krug, L. M., Lackner, R. P., Lennes, I. T., Loo, B. W., Martins, R., Otterson, G. A., Patel, J. D., Pinder-Schenck, M. C., Pisters, K. M., Reckamp, K., Rohren, E., Shapiro, T. A., Swanson, S. J., Tauer, K., Wood, D. E., Yang, S. C., Gregory, K., Hughes, M. 2013; 11 (5): 562-576

    Abstract

    Masses in the anterior mediastinum can be neoplasms (eg, thymomas, thymic carcinomas, or lung metastases) or non-neoplastic conditions (eg, intrathoracic goiter). Thymomas are the most common primary tumor in the anterior mediastinum, although they are rare. Thymic carcinomas are very rare. Thymomas and thymic carcinomas originate in the thymus. Although thymomas can spread locally, they are much less invasive than thymic carcinomas. Patients with thymomas have 5-year survival rates of approximately 78%. However, 5-year survival rates for thymic carcinomas are only approximately 40%. These guidelines outline the evaluation, treatment, and management of these mediastinal tumors.

    View details for Web of Science ID 000318752600007

    View details for PubMedID 23667206

  • Migration of implanted markers for image-guided lung tumor stereotactic ablative radiotherapy. Journal of applied clinical medical physics Hong, J. C., Eclov, N. C., Yu, Y., Rao, A. K., Dieterich, S., Le, Q., Diehn, M., Sze, D. Y., Loo, B. W., Kothary, N., Maxim, P. G. 2013; 14 (2): 4046-?

    Abstract

    The purpose of this study was to quantify postimplantation migration of percutaneously implanted cylindrical gold seeds ("seeds") and platinum endovascular embolization coils ("coils") for tumor tracking in pulmonary stereotactic ablative radiotherapy (SABR). We retrospectively analyzed the migration of markers in 32 consecutive patients with computed tomography scans postimplantation and at simulation. We implanted 147 markers (59 seeds, 88 coils) in or around 34 pulmonary tumors over 32 procedures, with one lesion implanted twice. Marker coordinates were rigidly aligned by minimizing fiducial registration error (FRE), the root mean square of the differences in marker locations for each tumor between scans. To also evaluate whether single markers were responsible for most migration, we aligned with and without the outlier causing the largest FRE increase per tumor. We applied the resultant transformation to all markers. We evaluated migration of individual markers and FRE of each group. Median scan interval was 8 days. Median individual marker migration was 1.28 mm (interquartile range [IQR] 0.78-2.63 mm). Median lesion FRE was 1.56 mm (IQR 0.92-2.95 mm). Outlier identification yielded 1.03 mm median migration (IQR 0.52-2.21 mm) and 1.97 mm median FRE (IQR 1.44-4.32 mm). Outliers caused a mean and median shift in the centroid of 1.22 and 0.80 mm (95th percentile 2.52 mm). Seeds and coils had no statistically significant difference. Univariate analysis suggested no correlation of migration with the number of markers, contact with the chest wall, or time elapsed. Marker migration between implantation and simulation is limited and unlikely to cause geometric miss during tracking.

    View details for DOI 10.1120/jacmp.v14i2.4046

    View details for PubMedID 23470933

  • Metabolic Tumor Volume Predicts Disease Progression and Survival in Patients with Squamous Cell Carcinoma of the Anal Canal JOURNAL OF NUCLEAR MEDICINE Bazan, J. G., Koong, A. C., Kapp, D. S., Quon, A., Graves, E. E., Loo, B. W., Chang, D. T. 2013; 54 (1): 27-32

    Abstract

    PET imaging has become a useful diagnostic tool in patients with anal cancer. We evaluated the prognostic value of metabolic tumor volume (MTV) in patients with anal cancer treated with definitive chemoradiotherapy.Patients with anal cancer who underwent PET imaging for pretreatment staging or radiation therapy planning from 2003 to 2011 were included. PET parameters included MTV and maximum standardized uptake value (SUVmax). Total MTV (MTV-T) was defined as the sum of the volumes above a standardized uptake value 50% of the SUVmax within the primary tumor and involved nodes. Kaplan-Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and overall survival (OS), progression-free survival (PFS), and event-free survival (EFS). Results: Thirty-nine patients were included. Median follow-up for the cohort was 22 mo. Overall, 6 patients died and 9 patients had disease progression. The 2-y OS, PFS, and EFS for the entire cohort were 88%, 74%, and 69%, respectively. Higher MTV-T was associated with worse OS (P = 0.04), PFS (P = 0.004), and EFS (P = 0.002) on univariate analysis. Patients with an MTV greater than 26 cm(3) had worse PFS than did those with an MTV of 26 cm(3) or less (33% vs. 82%, P = 0.003). SUVmax was not prognostic for any outcome. Higher T classification (T3/T4 vs. T1/T2) was associated with worse PFS and EFS. When adjusting for T classification, MTV-T remained a significant predictor for PFS (P = 0.01) and EFS (P = 0.02).MTV-T yields prognostic information on PFS and EFS beyond that of established prognostic factors in patients with anal cancer.

    View details for DOI 10.2967/jnumed.112.109470

    View details for Web of Science ID 000313606800026

    View details for PubMedID 23236018

  • Small Cell Lung Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Kalemkerian, G. P., Akerley, W., Bogner, P., Borghaei, H., Chow, L. Q., Downey, R. J., Gandhi, L., Ganti, A. K., Govindan, R., Grecula, J. C., Hayman, J., Heist, R. S., Horn, L., Jahan, T., Koczywas, M., Loo, B. W., Merritt, R. E., Moran, C. A., Niell, H. B., O'Malley, J., Patel, J. D., Ready, N., Rudin, C. M., Williams, C. C., Gregory, K., Hughes, M. 2013; 11 (1): 78-98

    Abstract

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (?15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

    View details for Web of Science ID 000313575200011

    View details for PubMedID 23307984

  • The Optimal Use of Radiotherapy in Small Cell Lung Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Shultz, D. B., Grecula, J. C., Hayman, J., Diehn, M., Loo, B. W. 2013; 11 (1): 107-114
  • American College of Chest Physicians and Society of Thoracic Surgeons Consensus Statement for Evaluation and Management for High-Risk Patients With Stage I Non-small Cell Lung Cancer CHEST Donington, J., Ferguson, M., Mazzone, P., Handy, J., Schuchert, M., Fernando, H., Loo, B., Lanuti, M., de Hoyos, A., Detterbeck, F., Pennathur, A., Howington, J., Landreneau, R., Silvestri, G. 2012; 142 (6): 1620-1635

    Abstract

    The standard treatment of stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not candidates for lobectomy because of severe medical comorbidity.A panel of experts was convened through the Thoracic Oncology Network of the American College of Chest Physicians and the Workforce on Evidence-Based Surgery of the Society of Thoracic Surgeons. Following a literature review, the panel developed 13 suggestions for evaluation and treatment through iterative discussion and debate until unanimous agreement was achieved.Pretreatment evaluation should focus primarily on measures of cardiopulmonary physiology, as respiratory failure represents the greatest interventional risk. Alternative treatment options to lobectomy for high-risk patients include sublobar resection with or without brachytherapy, stereotactic body radiation therapy, and radiofrequency ablation. Each is associated with decreased procedural morbidity and mortality but increased risk for involved lobe and regional recurrence compared with lobectomy, but direct comparisons between modalities are lacking.Therapeutic options for the treatment of high-risk patients are evolving quickly. Improved radiographic staging and the diagnosis of smaller and more indolent tumors push the risk-benefit decision toward parenchymal-sparing or nonoperative therapies in high-risk patients. Unbiased assessment of treatment options requires uniform reporting of treatment populations and outcomes in clinical series, which has been lacking to date.

    View details for DOI 10.1378/chest.12-0790

    View details for Web of Science ID 000312283800041

    View details for PubMedID 23208335

  • Metabolic imaging metrics correlate with survival in early stage lung cancer treated with stereotactic ablative radiotherapy. Lung cancer Abelson, J. A., Murphy, J. D., Trakul, N., Bazan, J. G., Maxim, P. G., Graves, E. E., Quon, A., Le, Q., Diehn, M., Loo, B. W. 2012; 78 (3): 219-224

    Abstract

    To test whether (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging metrics correlate with outcomes in patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR).Fifty-four patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR PET within 6 months. We analyzed maximum standardized uptake value (SUV(max)) and metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7, and 10). Endpoints included primary tumor control (PTC), progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). We performed Kaplan-Meier, competing risk, and Cox proportional hazards survival analyses.Patients received 25-60 Gy in 1 to 5 fractions. Median follow-up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83, 87 and 94%, respectively. Pre-treatment SUV(max) (p=0.014), MTV(7) (p=0.0077), and MTV(10) (p=0.0039) correlated significantly with OS. In the low-MTV(7)vs. high-MTV(7) sub-groups, 1-year estimated OS was 100 vs. 78% (p=0.0077) and CSS was 100 vs. 88% (p=0.082).In this hypothesis-generating study we identified multiple pre-treatment PET-CT metrics as potential predictors of OS and CSS in patients with NSCLC treated with SABR. These could aid risk-stratification and treatment individualization if validated prospectively.

    View details for DOI 10.1016/j.lungcan.2012.08.016

    View details for PubMedID 23009727

  • Reproducibility of Four-dimensional Computed Tomography-based Lung Ventilation Imaging ACADEMIC RADIOLOGY Yamamoto, T., Kabus, S., von Berg, J., Lorenz, C., Chung, M. P., Hong, J. C., Loo, B. W., Keall, P. J. 2012; 19 (12): 1554-1565

    Abstract

    A novel ventilation imaging method based on four-dimensional (4D) computed tomography (CT) has been applied to the field of radiation oncology. Understanding its reproducibility is a prerequisite for clinical applications. The purpose of this study was to quantify the reproducibility of 4D CT ventilation imaging over different days and the same session.Two ventilation images were created from repeat 4D CT scans acquired over the average time frames of 15 days for 6 lung cancer patients and 5 minutes for another 6 patients. The reproducibility was quantified using the voxel-based Spearman rank correlation coefficients for all lung voxels and Dice similarity coefficients (DSC) for the spatial overlap of segmented high-, moderate-, and low-functional lung volumes. Furthermore, the relationship between the variation in abdominal motion range as a measure of the depth of breathing and variation in ventilation was evaluated using linear regression.The voxel-based correlation between the two ventilation images was moderate on average (0.50 ± 0.15). The DSCs were also moderate for the high- (0.60 ± 0.08), moderate- (0.46 ± 0.06), and low-functional lung (0.58 ± 0.09). No patients demonstrated strong correlations. The relationship between the motion range variation and ventilation variation was found to be moderate and significant.We investigated the reproducibility of 4D CT ventilation imaging over the time frames of 15 days and 5 minutes and found that it was only moderately reproducible. Respiratory variation during 4D CT scans was found to deteriorate the reproducibility. Improvement of 4D CT imaging is necessary to increase the reproducibility of 4D CT ventilation imaging.

    View details for DOI 10.1016/j.acra.2012.07.006

    View details for Web of Science ID 000311654800016

    View details for PubMedID 22975070

  • Non-Small Cell Lung Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Ganti, A. K., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Jahanzeb, M., Kessinger, A., Komaki, R., Kong, F. (., Kris, M. G., Krug, L. M., Lennes, I. T., Loo, B. W., Martins, R., O'Malley, J., Osarogiagbon, R. U., Otterson, G. A., Patel, J. D., Pinder-Schenck, M. C., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Swanson, S. J., Wood, D. E., Yang, S. C., Hughes, M., Gregory, K. M. 2012; 10 (10): 1236-1271

    Abstract

    Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.

    View details for Web of Science ID 000309901900007

    View details for PubMedID 23054877

  • Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

    Abstract

    Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

    View details for DOI 10.1111/j.1442-2050.2011.01295.x

    View details for Web of Science ID 000308712300008

    View details for PubMedID 22168251

  • Stereotactic Ablative Radiotherapy for Reirradiation of Locally Recurrent Lung Tumors JOURNAL OF THORACIC ONCOLOGY Trakul, N., Harris, J. P., Le, Q., Hara, W. Y., Maxim, P. G., Loo, B. W., Diehn, M. 2012; 7 (9): 1462-1465

    Abstract

    Patients with thoracic tumors that recur after irradiation currently have limited therapeutic options. Retreatment using stereotactic ablative radiotherapy (SABR) is appealing for these patients because of its high conformity but has not been studied extensively. Here we report our experience with SABR for lung tumors in previously irradiated regions.We conducted a retrospective study of patients with primary lung cancer or metastatic lung tumors treated with SABR. We identified 17 such tumors in 15 patients and compared their outcomes with those of a cohort of 135 previously unirradiated lung tumors treated with SABR during the same time period.Twelve-month local control (LC) for retreated tumors was 65.5%, compared with 92.1% for tumors receiving SABR as initial treatment. Twelve-month LC was significantly worse for reirradiated tumors in which the time interval between treatments was 16 months or less (46.7%), compared with those with longer intertreatment intervals (87.5%). SABR reirradiation did not lead to significant increases in treatment-related toxicity.SABR for locally recurrent lung tumors arising in previously irradiated fields seems to be feasible and safe for appropriately selected patients. LC of retreated lesions was significantly lower, likely owing to the lower doses used for retreatment. Shorter time to retreatment was associated with increased risk of local failure, suggesting that these tumors may be particularly radioresistant. Our findings suggest that dose escalation may improve LC while maintaining acceptable levels of toxicity for these patients.

    View details for DOI 10.1097/JTO.0b013e31825f22ce

    View details for Web of Science ID 000308073300024

    View details for PubMedID 22895143

  • Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Trakul, N., Chang, C. N., Harris, J., Chapman, C., Rao, A., Shen, J., Quinlan-Davidson, S., Filion, E. J., Wakelee, H. A., Colevas, A. D., Whyte, R. I., Dieterich, S., Maxim, P. G., Hristov, D., Tran, P., Quynh-Thu Le, Q. T., Loo, B. W., Diehn, M. 2012; 84 (1): 231-237

    Abstract

    Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy.We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume ?12 mL) received multifraction regimens with BED ?100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2).The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02).A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

    View details for DOI 10.1016/j.ijrobp.2011.10.071

    View details for Web of Science ID 000308061900060

    View details for PubMedID 22381907

  • Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head-and-Neck Cancer Outcomes INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chu, K. P., Murphy, J. D., La, T. H., Krakow, T. E., Iagaru, A., Graves, E. E., Hsu, A., Maxim, P. G., Loo, B., Chang, D. T., Quynh-Thu Le, Q. T. 2012; 83 (5): 1521-1527

    Abstract

    We previously showed that metabolic tumor volume (MTV) on positron emission tomography-computed tomography (PET-CT) predicts for disease recurrence and death in head-and-neck cancer (HNC). We hypothesized that increases in MTV over time would correlate with tumor growth and biology, and would predict outcome. We sought to examine tumor growth over time in serial pretreatment PET-CT scans.From 2006 to 2009, 51 patients had two PET-CT scans before receiving HNC treatment. MTV was defined as the tumor volume ? 50% of maximum SUV (SUV(max)). MTV was calculated for the primary tumor, nodal disease, and composite (primary tumor + nodes). MTV and SUV velocity were defined as the change in MTV or SUV(max) over time, respectively. Cox regression analyses were used to examine correlations between SUV, MTV velocity, and outcome (disease progression and overall survival).The median follow-up time was 17.5 months. The median time between PET-CT scans was 3 weeks. Unexpectedly, 51% of cases demonstrated a decrease in SUV(max) (average, -0.1 cc/week) and MTV (average, -0.3 cc/week) over time. Despite the variability in MTV, primary tumor MTV velocity predicted disease progression (hazard ratio 2.94; p = 0.01) and overall survival (hazard ratio 1.85; p = 0.03).Primary tumor MTV velocity appears to be a better prognostic indicator of disease progression and survival in comparison to nodal MTV velocity. However, substantial variability was found in PET-CT biomarkers between serial scans. Caution should be used when PET-CT biomarkers are integrated into clinical protocols for HNC.

    View details for DOI 10.1016/j.ijrobp.2011.10.022

    View details for Web of Science ID 000306128100047

    View details for PubMedID 22270168

  • Intrafraction Verification of Gated RapidArc by Using Beam-Level Kilovoltage X-Ray Images INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, R., Mok, E., Chang, D. T., Daly, M., Loo, B. W., Diehn, M., Quynh-Thu Le, Q. T., Koong, A., Xing, L. 2012; 83 (5): E709-E715

    Abstract

    To verify the geometric accuracy of gated RapidArc treatment using kV images acquired during dose delivery.Twenty patients were treated using the gated RapidArc technique with a Varian TrueBeam STx linear accelerator. One to 7 metallic fiducial markers were implanted inside or near the tumor target before treatment simulation. For patient setup and treatment verification purposes, the internal target volume (ITV) was created, corresponding to each implanted marker. The gating signal was generated from the Real-time Position Management (RPM) system. At the beginning of each fraction, individualized respiratory gating amplitude thresholds were set based on fluoroscopic image guidance. During the treatment, we acquired kV images immediately before MV beam-on at every breathing cycle, using the on-board imaging system. After the treatment, all implanted markers were detected, and their 3-dimensional (3D) positions in the patient were estimated using software developed in-house. The distance from the marker to the corresponding ITV was calculated for each patient by averaging over all markers and all fractions.The average 3D distance between the markers and their ITVs was 0.8 ± 0.5 mm (range, 0-1.7 mm) and was 2.1 ± 1.2 mm at the 95th percentile (range, 0-3.8 mm). On average, a left-right margin of 0.6 mm, an anterior-posterior margin of 0.8 mm, and a superior-inferior margin of 1.5 mm is required to account for 95% of the intrafraction uncertainty in RPM-based RapidArc gating.To our knowledge, this is the first clinical report of intrafraction verification of respiration-gated RapidArc treatment in stereotactic ablative radiation therapy. For some patients, the markers deviated significantly from the ITV by more than 2 mm at the beginning of the MV beam-on. This emphasizes the need for gating techniques with beam-on/-off controlled directly by the actual position of the tumor target instead of external surrogates such as RPM.

    View details for DOI 10.1016/j.ijrobp.2012.03.006

    View details for Web of Science ID 000306128100022

    View details for PubMedID 22554582

  • Validation that metabolic tumor volume predicts outcome in head-and-neck cancer. International journal of radiation oncology, biology, physics Tang, C., Murphy, J. D., Khong, B., La, T. H., Kong, C., Fischbein, N. J., Colevas, A. D., Iagaru, A. H., Graves, E. E., Loo, B. W., Le, Q. 2012; 83 (5): 1514-1520

    Abstract

    We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment (18)F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16(INK4a) status as a surrogate marker for human papillomavirus (HPV).The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUV(max)) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV.Similarly to our prior findings, an increase in total MTV of 17 cm(3) (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUV(max) was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16(INK4a)-positive oropharyngeal cancer.This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC.

    View details for DOI 10.1016/j.ijrobp.2011.10.023

    View details for PubMedID 22270174

  • The Management of Patients With Stage IIIA Non-Small Cell Lung Cancer With N2 Mediastinal Node Involvement JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Martins, R. G., D'Amico, T. A., Loo, B. W., Pinder-Schenck, M., Borghaei, H., Chaft, J. E., Ganti, A. K., Kong, F. (., Kris, M. G., Lennes, I. T., Wood, D. E. 2012; 10 (5): 599-613

    Abstract

    Patients with stage IIIA non-small cell lung cancer, determined based on involvement of ipsilateral mediastinal lymph nodes, represent the most challenging management problem in this disease. Patients with this stage disease may have very different degrees of lymph node involvement. The pathologic confirmation of this involvement is a key step in the therapeutic decision. The difference in the degree of lymph node compromise has prognostic and treatment implications. Based on multiple considerations, patients can be treated with induction chemotherapy, chemoradiotherapy followed by surgery, or definitive chemoradiotherapy without surgery. Data derived from clinical trials have provided incomplete guidance for physicians and their patients. The best therapeutic plan is achieved through the multidisciplinary cooperation of a team specialized in lung cancer.

    View details for Web of Science ID 000303557700006

    View details for PubMedID 22570291

  • Interim-treatment quantitative PET parameters predict progression and death among patients with hodgkin's disease RADIATION ONCOLOGY Tseng, D., Rachakonda, L. P., Su, Z., Advani, R., Horning, S., Hoppe, R. T., Quon, A., Graves, E. E., Loo, B. W., Tran, P. T. 2012; 7

    Abstract

    We hypothesized that quantitative PET parameters may have predictive value beyond that of traditional clinical factors such as the International Prognostic Score (IPS) among Hodgkin's disease (HD) patients.Thirty HD patients treated at presentation or relapse had staging and interim-treatment PET-CT scans. The majority of patients (53%) had stage III-IV disease and 67% had IPS ? 2. Interim-treatment scans were performed at a median of 55 days from the staging PET-CT. Chemotherapy regimens used: Stanford V (67%), ABVD (17%), VAMP (10%), or BEACOPP (7%). Hypermetabolic tumor regions were segmented semiautomatically and the metabolic tumor volume (MTV), mean standardized uptake value (SUV mean), maximum SUV (SUV max) and integrated SUV (iSUV) were recorded. We analyzed whether IPS, absolute value PET parameters or the calculated ratio of interim- to pre-treatment PET parameters were associated with progression free survival (PFS) or overall survival (OS).Median follow-up of the study group was 50 months. Six of the 30 patients progressed clinically. Absolute value PET parameters from pre-treatment scans were not significant. Absolute value SUV max from interim-treatment scans was associated with OS as determined by univariate analysis (p < 0.01). All four calculated PET parameters (interim/pre-treatment values) were associated with OS: MTV int/pre (p < 0.01), SUV mean int/pre (p < 0.05), SUV max int/pre (p = 0.01), and iSUV int/pre (p < 0.01). Absolute value SUV max from interim-treatment scans was associated with PFS (p = 0.01). Three calculated PET parameters (int/pre-treatment values) were associated with PFS: MTV int/pre (p = 0.01), SUV max int/pre (p = 0.02) and iSUV int/pre (p = 0.01). IPS was associated with PFS (p < 0.05) and OS (p < 0.01).Calculated PET metrics may provide predictive information beyond that of traditional clinical factors and may identify patients at high risk of treatment failure early for treatment intensification.

    View details for DOI 10.1186/1748-717X-7-5

    View details for Web of Science ID 000301710700001

    View details for PubMedID 22260710

  • Metabolic Tumor Volume is an Independent Prognostic Factor in Patients Treated Definitively for Non-Small-Cell Lung Cancer CLINICAL LUNG CANCER Lee, P., Bazan, J. G., Lavori, P. W., Weerasuriya, D. K., Quon, A., Quynh-Thu Le, Q. T., Wakelee, H. A., Graves, E. E., Loo, B. W. 2012; 13 (1): 52-58

    Abstract

    Fluorine-18 flurodeoxyglucose positron emission tomography (FDG-PET) imaging has rapidly become the standard of care for staging patients with lung cancer. We evaluated the prognostic value of metabolic tumor volume (MTV), a measure of tumor burden on FDG-PET imaging, in patients with non-small-cell lung cancer (NSCLC) treated definitively.A retrospective review identified 61 patients with NSCLC who underwent FDG-PET imaging for pretreatment staging. Metabolically active tumor regions were segmented on the PET scans semiautomatically to calculate the total body MTV. We determined the relationship of overall survival (OS) and progression-free survival (PFS) with MTV in the entire cohort, and in the subgroup treated definitively.The estimated median PFS and OS for the entire cohort were 11.1 months and 18.9 months. Higher MTV was significantly associated with worse OS (P = 0.00075) and PFS (P = 0.00077). For definitively treated patients, when MTV was analyzed as a binary value above or below the median value, 2-year PFS was 60% versus 39.7% (median PFS 34.9 vs. 11.9 months) and 2-year OS was 79.7% versus 33.3% (median OS 41.9 vs. 18.9 months), respectively (log-rank P = 0.12 for PFS and P = 0.066 for OS). When MTV was analyzed as a continuous variable, multivariate Cox proportional hazards analysis demonstrated a trend to worse PFS (hazard ratio [HR] = 1.31; P = 0.12) and significantly worse OS (HR = 1.53; P = 0.018) with increasing MTV after controlling for known prognostic variables.Tumor burden as assessed by MTV yields prognostic information on survival beyond that of established prognostic factors in patients with NSCLC treated definitively.

    View details for DOI 10.1016/j.cllc.2011.05.001

    View details for Web of Science ID 000299270900008

    View details for PubMedID 21703935

  • An automated method for comparing motion artifacts in cine four-dimensional computed tomography images. Journal of applied clinical medical physics Cui, G., Jew, B., Hong, J. C., Johnston, E. W., Loo, B. W., Maxim, P. G. 2012; 13 (6): 3838-?

    Abstract

    The aim of this study is to develop an automated method to objectively compare motion artifacts in two four-dimensional computed tomography (4D CT) image sets, and identify the one that would appear to human observers with fewer or smaller artifacts. Our proposed method is based on the difference of the normalized correlation coefficients between edge slices at couch transitions, which we hypothesize may be a suitable metric to identify motion artifacts. We evaluated our method using ten pairs of 4D CT image sets that showed subtle differences in artifacts between images in a pair, which were identifiable by human observers. One set of 4D CT images was sorted using breathing traces in which our clinically implemented 4D CT sorting software miscalculated the respiratory phase, which expectedly led to artifacts in the images. The other set of images consisted of the same images; however, these were sorted using the same breathing traces but with corrected phases. Next we calculated the normalized correlation coefficients between edge slices at all couch transitions for all respiratory phases in both image sets to evaluate for motion artifacts. For nine image set pairs, our method identified the 4D CT sets sorted using the breathing traces with the corrected respiratory phase to result in images with fewer or smaller artifacts, whereas for one image pair, no difference was noted. Two observers independently assessed the accuracy of our method. Both observers identified 9 image sets that were sorted using the breathing traces with corrected respiratory phase as having fewer or smaller artifacts. In summary, using the 4D CT data of ten pairs of 4D CT image sets, we have demonstrated proof of principle that our method is able to replicate the results of two human observers in identifying the image set with fewer or smaller artifacts.

    View details for DOI 10.1120/jacmp.v13i6.3838

    View details for PubMedID 23149777

  • Malignant Pleural Mesothelioma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A., Cheney, R. T., Chirieac, L. R., D'Amico, T. A., Demmy, T. L., Ganti, A. K., Govindan, R., Grannis, F. W., Horn, L., Jahan, T. M., Jahanzeb, M., Kessinger, A., Komaki, R., Kong, F. (., Kris, M. G., Krug, L. M., Lennes, I. T., Loo, B. W., Martins, R., O'Malley, J., Osarogiagbon, R. U., Otterson, G. A., Patel, J. D., Pinder-Schenck, M., Pisters, K. M., Reckamp, K., Riely, G. J., Rohren, E., Swanson, S. J., Wood, D. E., Yang, S. C. 2012; 10 (1): 26-41

    View details for Web of Science ID 000299007500006

    View details for PubMedID 22223867

  • Correlation between metabolic tumor volume and pathologic tumor volume in squamous cell carcinoma of the oral cavity RADIOTHERAPY AND ONCOLOGY Murphy, J. D., Chisholm, K. M., Daly, M. E., Wiegner, E. A., Truong, D., Iagaru, A., Maxim, P. G., Loo, B. W., Graves, E. E., Kaplan, M. J., Kong, C., Le, Q. 2011; 101 (3): 356-361

    Abstract

    To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer.Twenty-three patients with squamous cell carcinoma of the oral tongue had PET-CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET-CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques.Multiple MTV's were associated with pathologic tumor volume; however the correlation was poor (R(2) range 0.29-0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p=0.0005) and tumor grade (p=0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R(2)=0.63).Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET-CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV.

    View details for DOI 10.1016/j.radonc.2011.05.040

    View details for Web of Science ID 000298894700003

    View details for PubMedID 21665308

  • ON-BOARD IMAGING VALIDATION OF OPTICALLY GUIDED STEREOTACTIC RADIOSURGERY POSITIONING SYSTEM FOR CONVENTIONALLY FRACTIONATED RADIOTHERAPY FOR PARANASAL SINUS AND SKULL BASE CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Maxim, P. G., Loo, B. W., Murphy, J. D., Chu, K. P., Hsu, A., Quynh-Thu Le, Q. T. 2011; 81 (4): 1153-1159

    Abstract

    To evaluate the positioning accuracy of an optical positioning system for stereotactic radiosurgery in a pilot experience of optically guided, conventionally fractionated, radiotherapy for paranasal sinus and skull base tumors.Before each daily radiotherapy session, the positioning of 28 patients was set up using an optical positioning system. After this initial setup, the patients underwent standard on-board imaging that included daily orthogonal kilovoltage images and weekly cone beam computed tomography scans. Daily translational shifts were made after comparing the on-board images with the treatment planning computed tomography scans. These daily translational shifts represented the daily positional error in the optical tracking system and were recorded during the treatment course. For 13 patients treated with smaller fields, a three-degree of freedom (3DOF) head positioner was used for more accurate setup.The mean positional error for the optically guided system in patients with and without the 3DOF head positioner was 1.4 ± 1.1 mm and 3.9 ± 1.6 mm, respectively (p <.0001). The mean positional error drifted 0.11 mm/wk upward during the treatment course for patients using the 3DOF head positioner (p = .057). No positional drift was observed in the patients without the 3DOF head positioner.Our initial clinical experience with optically guided head-and-neck fractionated radiotherapy was promising and demonstrated clinical feasibility. The optically guided setup was especially useful when used in conjunction with the 3DOF head positioner and when it was recalibrated to the shifts using the weekly portal images.

    View details for DOI 10.1016/j.ijrobp.2010.08.049

    View details for Web of Science ID 000296823600035

    View details for PubMedID 21543166

  • What the Diagnostic Radiologist Needs to Know about Radiation Oncology RADIOLOGY Terezakis, S. A., Heron, D. E., Lavigne, R. F., Diehn, M., Loo, B. W. 2011; 261 (1): 30-44

    Abstract

    Substantial technologic advances in radiation treatment planning and delivery have made possible exquisite tailoring of three-dimensional radiation dose distributions that conform to the tumor treatment volume while avoiding adjacent normal tissues. Although such highly precise treatment can increase the therapeutic ratio, it also introduces the potential that tumor extension outside the target is missed because it is unrecognized at the time of radiation treatment planning. As a result, accurate targeting of the tumor with radiation is of utmost importance to the radiation oncologist. Communication between diagnostic radiologists and radiation oncologists is essential, particularly given the subtleties that accompany image interpretation, to optimize the care of the cancer patient.

    View details for DOI 10.1148/radiol.11101688

    View details for Web of Science ID 000295039000006

    View details for PubMedID 21931140

  • Molecular Imaging with C-11-PD153035 PET/CT Predicts Survival in Non-Small Cell Lung Cancer Treated with EGFR-TKI: A Pilot Study JOURNAL OF NUCLEAR MEDICINE Meng, X., Loo, B. W., Ma, L., Murphy, J. D., Sun, X., Yu, J. 2011; 52 (10): 1573-1579

    Abstract

    Outcomes are suboptimal when molecularly targeted therapies are used in patient populations unselected for the molecular target. This pilot study examines the correlation of PET using (11)C-labeled 4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035), an imaging biomarker of epidermal growth factor receptor (EGFR), with outcomes in patients with non-small cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor erlotinib.Patients with advanced chemotherapy-refractory NSCLC were prospectively enrolled on a trial of erlotinib at a dose of 150 mg daily and imaged by (11)C-PD153035 PET/CT at baseline, after 1-2 wk, and after 6 wk from the start of treatment. Overall survival and progression-free survival (OS and PFS, respectively) times were correlated with the (11)C-PD153035 standardized uptake value (SUV) at each of the imaging times.Twenty-one patients were enrolled. Follow-up to progression was complete in all patients and to death in 18 of 21. By Cox regression analysis, baseline maximum SUV correlated strongly with OS and PFS (hazard ratio = 0.40, P = 0.002, and hazard ratio = 0.044, P < 0.001, respectively) independent of histology. Patients with higher maximum SUV (?median) survived more than twice as long as patients with lower maximum SUV (median OS = 11.4 vs. 4.6 mo, P = 0.002; PFS = 4.4 vs. 1.8 mo, P < 0.001). However, (11)C-PD153035 uptake on follow-up scans was less well correlated with survival.Our preliminary results suggest (11)C-PD153035 PET/CT may be a noninvasive and rapid method for identifying patients with refractory advanced NSCLC of adenocarcinoma or squamous histology likely to respond to the EGFR tyrosine kinase inhibitor but not for monitoring treatment response.

    View details for DOI 10.2967/jnumed.111.092874

    View details for Web of Science ID 000295537800016

    View details for PubMedID 21903741

  • Stereotactic ablative radiotherapy (SABR) for lung cancer: What does the future hold? Journal of thoracic disease Loo, B. W. 2011; 3 (3): 150-152
  • Results from a Single Institution Phase II Trial of Concurrent Docetaxel/Carboplatin/Radiotherapy Followed by Surgical Resection and Consolidation Docetaxel/Carboplatin in Stage III Non-Small-Cell Lung Cancer CLINICAL LUNG CANCER Das, M., Donington, J. S., Murphy, J., Kozak, M., Eclov, N., Whyte, R. I., Hoang, C. D., Zhou, L., Le, Q., Loo, B. W., Wakelee, H. 2011; 12 (5): 280-285

    Abstract

    The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity.We enrolled 13 patients with resectable stage III NSCLC on a prospective phase II trial of trimodality therapy. Induction treatment consisted of weekly docetaxel 20 mg/m(2) and weekly carboplatin at an area under curve (AUC) of 2 concurrent with 45 Gy thoracic radiotherapy. Resection was performed unless felt to be unsafe or if patients had progressive disease. Postoperative consolidation consisted of docetaxel 75 mg/m(2) and carboplatin at an AUC of 6 every 3 weeks for 3 cycles with growth factor support.All patients responded to induction chemoradiotherapy as measured by total gross tumor volume reductions of 43% on average (range, 27%-64%). Twelve patients underwent resection of the tumor and involved nodes, yielding a resectability rate of 92%. The primary endpoint of 2-year overall survival (OS) was 72% (95% confidence interval [CI], 36%-90%), and 2-year progression-free survival (PFS) was 36% (95% CI, 9%-64%). The maximal toxicity observed per patient was grade II in 5 patients (38%); grade III in 7 patients (54%); grade IV in 1 patient (8%); and grade V in none.This trimodality approach resulted in promising outcomes with reasonable toxicity in carefully selected patients with stage III NSCLC at a single institution.

    View details for DOI 10.1016/j.cllc.2011.06.003

    View details for Web of Science ID 000294600800003

    View details for PubMedID 21752720

  • HIGH RETENTION AND SAFETY OF PERCUTANEOUSLY IMPLANTED ENDOVASCULAR EMBOLIZATION COILS AS FIDUCIAL MARKERS FOR IMAGE-GUIDED STEREOTACTIC ABLATIVE RADIOTHERAPY OF PULMONARY TUMORS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hong, J. C., Yu, Y., Rao, A. K., Ditererich, S., Maxim, P. G., Le, Q., Diehn, M., Sze, D. Y., Kothary, N., Loo, B. W. 2011; 81 (1): 85-90

    Abstract

    To compare the retention rates of two types of implanted fiducial markers for stereotactic ablative radiotherapy (SABR) of pulmonary tumors, smooth cylindrical gold "seed" markers ("seeds") and platinum endovascular embolization coils ("coils"), and to compare the complication rates associated with the respective implantation procedures.We retrospectively analyzed the retention of percutaneously implanted markers in 54 consecutive patients between January 2004 and June 2009. A total of 270 markers (129 seeds, 141 coils) were implanted in or around 60 pulmonary tumors over 59 procedures. Markers were implanted using a percutaneous approach under computed tomography (CT) guidance. Postimplantation and follow-up imaging studies were analyzed to score marker retention relative to the number of markers implanted. Markers remaining near the tumor were scored as retained. Markers in a distant location (e.g., pleural space) were scored as lost. CT imaging artifacts near markers were quantified on radiation therapy planning scans.Immediately after implantation, 140 of 141 coils (99.3%) were retained, compared to 110 of 129 seeds (85.3%); the difference was highly significant (p<0.0001). Of the total number of lost markers, 45% were reported lost during implantation, but 55% were lost immediately afterwards. No additional markers were lost on longer-term follow-up. Implanted lesions were peripherally located for both seeds (mean distance, 0.33 cm from pleural surface) and coils (0.34 cm) (p=0.96). Incidences of all pneumothorax (including asymptomatic) and pneumothorax requiring chest tube placement were lower in implantation of coils (23% and 3%, respectively) vs. seeds (54% and 29%, respectively; p=0.02 and 0.01). The degree of CT artifact was similar between marker types.Retention of CT-guided percutaneously implanted coils is significantly better than that of seed markers. Furthermore, implanting coils is at least as safe as implanting seeds. Using coils should permit implantation of fewer markers and require fewer repeat implantation procedures owing to lost markers.

    View details for DOI 10.1016/j.ijrobp.2010.04.037

    View details for Web of Science ID 000294093300012

    View details for PubMedID 20675070

  • IN REGARD TO BROWN ET AL. (INT J RADIAT ONCOL BIOL PHYS 2010;78:323-327) REPLY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Brown, J. M., Loo, B. W., Diehn, M., Carlson, D. J. 2011; 80 (5): 1605-1605
  • INTENSITY-MODULATED RADIOTHERAPY FOR ORAL CAVITY SQUAMOUS CELL CARCINOMA: PATTERNS OF FAILURE AND PREDICTORS OF LOCAL CONTROL INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Quynh-Thu Le, Q. T., Kozak, M. M., Maxim, P. G., Murphy, J. D., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Chang, D. T. 2011; 80 (5): 1412-1422

    Abstract

    Few studies have evaluated the use of intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report clinical outcomes and failure patterns for these patients.Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87 months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7 weeks).Thirteen patients experienced local-regional failure at a median of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced local recurrence between surgery and RT. Seven local failures occurred in-field (one with simultaneous nodal and distant disease) and two at the margin. Four regional failures occurred, two in-field and two out-of-field, one with synchronous metastases. Six patients experienced distant failure. The 3-year actuarial estimates of local control, local-regional control, freedom from distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive patients. Four patients developed Grade ? 2 chronic toxicity. Increased surgery to RT interval predicted for decreased LRC (p = 0.04).Local-regional control for SCC of the OC treated with IMRT with or without surgery remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity profiles. A surgery-to-RT interval of < 6 weeks improves local-regional control. The predominant failure pattern was local, suggesting that both improvements in target delineation and radiosensitization and/or dose escalation are needed.

    View details for DOI 10.1016/j.ijrobp.2010.04.031

    View details for Web of Science ID 000293207600020

    View details for PubMedID 20675073

  • POSTRADIATION METABOLIC TUMOR VOLUME PREDICTS OUTCOME IN HEAD-AND-NECK CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, J. D., La, T. H., Chu, K., Quon, A., Fischbein, N. J., Maxim, P. G., Graves, E. E., Loo, B. W., Le, Q. 2011; 80 (2): 514-521

    Abstract

    To explore the prognostic value of metabolic tumor volume measured on postradiation (18)F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with head-and-neck cancer.Forty-seven patients with head-and-neck cancer who received pretreatment and posttreatment PET/computed tomography (CT) imaging along with definitive chemoradiotherapy were included in this study. The PET/CT parameters evaluated include the maximum standardized uptake value, metabolic tumor volume (MTV(2.0)-MTV(4.0); where MTV(2.0) refers to the volume above a standardized uptake value threshold of 2.0), and integrated tumor volume. Kaplan-Meier and Cox regression models were used to test for association between PET endpoints and disease-free survival and overall survival.Multiple postradiation PET endpoints correlated significantly with outcome; however, the most robust predictor of disease progression and death was MTV(2.0). An increase in MTV(2.0) of 21 cm(3) (difference between 75th and 25th percentiles) was associated with an increased risk of disease progression (hazard ratio [HR] = 2.5, p = 0.0001) and death (HR = 2.0, p = 0.003). In patients with nonnasopharyngeal carcinoma histology (n = 34), MTV(2.0) <18 cm(3) and MTV(2.0) ?18 cm(3) yielded 2-year disease-free survival rates of 100% and 63%, respectively (p = 0.006) and 2-year overall survival rates of 100% and 81%, respectively (p = 0.009). There was no correlation between MTV(2.0) and disease-free survival or overall survival with nasopharyngeal carcinoma histology (n = 13). On multivariate analysis, only postradiation MTV(2.0) was predictive of disease-free survival (HR = 2.47, p = 0.0001) and overall survival (HR = 1.98, p = 0.003).Postradiation metabolic tumor volume is an adverse prognostic factor in head-and-neck cancer. Biomarkers such as MTV are important for risk stratification and will be valuable in the future with risk-adapted therapies.

    View details for DOI 10.1016/j.ijrobp.2010.01.057

    View details for Web of Science ID 000290837100028

    View details for PubMedID 20646870

  • Tumor Volume as a Potential Imaging-Based Risk-Stratification Factor in Trimodality Therapy for Locally Advanced Non-small Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Kozak, M. M., Murphy, J. D., Schipper, M. L., Donington, J. S., Zhou, L., Whyte, R. I., Shrager, J. B., Hoang, C. D., Bazan, J., Maxim, P. G., Graves, E. E., Diehn, M., Hara, W. Y., Quon, A., Quynh-Thu Le, Q. T., Wakelee, H. A., Loo, B. W. 2011; 6 (5): 920-926

    Abstract

    The role of trimodality therapy for locally advanced non-small cell lung cancer (NSCLC) continues to be defined. We hypothesized that imaging parameters on pre- and postradiation positron emission tomography (PET)-computed tomography (CT) imaging are prognostic for outcome after preoperative chemoradiotherapy (CRT)/resection/consolidation chemotherapy and could help risk-stratify patients in clinical trials.We enrolled 13 patients on a prospective clinical trial of trimodality therapy for resectable locally advanced NSCLC. PET-CT was acquired for radiation planning and after 45 Gy. Gross tumor volume (GTV) and standardized uptake value were measured at pre- and post-CRT time points and correlated with nodal pathologic complete response, loco-regional and/or distant progression, and overall survival. In addition, we evaluated the performance of automatic deformable image registration (ADIR) software for volumetric response assessment.All patients responded with average total GTV reductions after 45 Gy of 43% (range: 27-64%). Pre- and post-CRT GTVs were highly correlated (R² = 0.9), and their respective median values divided the patients into the same two groups. ADIR measurements agreed closely with manually segmented post-CRT GTVs. Patients with GTV ? median (137 ml pre-CRT and 67 ml post-CRT) had 3-year progression-free survival (PFS) of 14% versus 75% for GTV less than median, a significant difference (p = 0.049). Pre- and post-CRT PET-standardized uptake value did not correlate significantly with pathologic complete response, PFS, or overall survival.Preoperative CRT with carboplatin/docetaxel/45 Gy resulted in excellent response rates. In this exploratory analysis, pre- and post-CRT GTV predicted PFS in trimodality therapy, consistent with our earlier studies in a broader cohort of NSCLC. ADIR seems robust enough for volumetric response assessment in clinical trials.

    View details for DOI 10.1097/JTO.0b013e31821517db

    View details for Web of Science ID 000289554100012

    View details for PubMedID 21774104

  • Reducing 4D CT artifacts using optimized sorting based on anatomic similarity MEDICAL PHYSICS Johnston, E., Diehn, M., Murphy, J. D., Loo, B. W., Maxim, P. G. 2011; 38 (5): 2424-2429

    Abstract

    Four-dimensional (4D) computed tomography (CT) has been widely used as a tool to characterize respiratory motion in radiotherapy. The two most commonly used 4D CT algorithms sort images by the associated respiratory phase or displacement into a predefined number of bins, and are prone to image artifacts at transitions between bed positions. The purpose of this work is to demonstrate a method of reducing motion artifacts in 4D CT by incorporating anatomic similarity into phase or displacement based sorting protocols.Ten patient datasets were retrospectively sorted using both the displacement and phase based sorting algorithms. Conventional sorting methods allow selection of only the nearest-neighbor image in time or displacement within each bin. In our method, for each bed position either the displacement or the phase defines the center of a bin range about which several candidate images are selected. The two dimensional correlation coefficients between slices bordering the interface between adjacent couch positions are then calculated for all candidate pairings. Two slices have a high correlation if they are anatomically similar. Candidates from each bin are then selected to maximize the slice correlation over the entire data set using the Dijkstra's shortest path algorithm. To assess the reduction of artifacts, two thoracic radiation oncologists independently compared the resorted 4D datasets pairwise with conventionally sorted datasets, blinded to the sorting method, to choose which had the least motion artifacts. Agreement between reviewers was evaluated using the weighted kappa score.Anatomically based image selection resulted in 4D CT datasets with significantly reduced motion artifacts with both displacement (P = 0.0063) and phase sorting (P = 0.00022). There was good agreement between the two reviewers, with complete agreement 34 times and complete disagreement 6 times.Optimized sorting using anatomic similarity significantly reduces 4D CT motion artifacts compared to conventional phase or displacement based sorting. This improved sorting algorithm is a straightforward extension of the two most common 4D CT sorting algorithms.

    View details for DOI 10.1118/1.3577601

    View details for Web of Science ID 000290625700016

    View details for PubMedID 21776777

  • Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions PHYSICS IN MEDICINE AND BIOLOGY Yamamoto, T., Kabus, S., Klinder, T., Lorenz, C., von Berg, J., Blaffert, T., Loo, B. W., Keall, P. J. 2011; 56 (7): 2279-2298

    Abstract

    A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIR(sur)) and volumetric (DIR(vol)), and two metrics: Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. V(HU) resulted in statistically significant differences for both DIR(sur) (0.14 ± 0.14 versus 0.29 ± 0.16, p = 0.01) and DIR(vol) (0.13 ± 0.13 versus 0.27 ± 0.15, p < 0.01). However, V(Jac) resulted in non-significant differences for both DIR(sur) (0.15 ± 0.07 versus 0.17 ± 0.08, p = 0.20) and DIR(vol) (0.17 ± 0.08 versus 0.19 ± 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A further study is needed to confirm these results.

    View details for DOI 10.1088/0031-9155/56/7/023

    View details for Web of Science ID 000288506600026

    View details for PubMedID 21411868

  • HYPOFRACTIONATION RESULTS IN REDUCED TUMOR CELL KILL COMPARED TO CONVENTIONAL FRACTIONATION FOR TUMORS WITH REGIONS OF HYPOXIA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Carlson, D. J., Keall, P. J., Loo, B. W., Chen, Z. J., Brown, J. M. 2011; 79 (4): 1188-1195

    Abstract

    Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation.A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions.Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 ?m. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ?10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively.Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia.

    View details for DOI 10.1016/j.ijrobp.2010.10.007

    View details for Web of Science ID 000288471500031

    View details for PubMedID 21183291

  • Four-dimensional computed tomography pulmonary ventilation images vary with deformable image registration algorithms and metrics MEDICAL PHYSICS Yamamoto, T., Kabus, S., Klinder, T., von Berg, J., Lorenz, C., Loo, B. W., Keall, P. J. 2011; 38 (3): 1348-1358

    Abstract

    A novel pulmonary ventilation imaging technique based on four-dimensional (4D) CT has advantages over existing techniques and could be used for functional avoidance in radiotherapy. There are various deformable image registration (DIR) algorithms and two classes of ventilation metric that can be used for 4D-CT ventilation imaging, each yielding different images. The purpose of this study was to quantify the variability of the 4D-CT ventilation to DIR algorithms and metrics.4D-CT ventilation images were created for 12 patients using different combinations of two DIR algorithms, volumetric (DIR(vol)) and surface-based (DIR(sur)), yielding two displacement vector fields (DVFs) per patient (DVF(voI) and DVF(sur)), and two metrics, Hounsfield unit (HU) change (V(HU)) and Jacobian determinant of deformation (V(Jac)), yielding four ventilation image sets (V(HU)(vol), V(HU)(sur), V(Jac)(voI), and V(Jac)(sur). First DVF(vol) and DVF(sur) were compared visually and quantitatively to the length of 3D displacement vector difference. Second, four ventilation images were compared based on voxel-based Spearman's rank correlation coefficients and coefficients of variation as a measure of spatial heterogeneity. V(HU)(vol) was chosen as the reference for the comparison.The mean length of 3D vector difference between DVF(vol) and DVF(sur) was 2.0 +/- 1.1 mm on average, which was smaller than the voxel dimension of the image set and the variations. Visually, the reference V(HU)(vol) demonstrated similar regional distributions with V(HU)(sur); the reference, however, was markedly different from V(Jac)(vol) and V((Jac)(sur). The correlation coefficients of V(HU)(vol) with V(HU)(sur), V(Jac)(vol) and V(Jac)(sur) were 0.77 +/- 0.06, 0.25 +/- 0.06 and 0.15 +/- 0.07, respectively, indicating that the metric introduced larger variations in the ventilation images than the DIR algorithm. The spatial heterogeneities for V(HU)(vol), 'V(HU)(sur), V(Jac)(vol), and V(Jac)(sur) were 1.8 +/- 1.6, 1.8 +/- 1.5 (p = 0. 85), 0.6 +/- 0.2 (p = 0.02), and 0.7 +/- 0.2 (p = 0.03), respectively, also demonstrating that the metric introduced larger variations.4D-CT pulmonary ventilation images vary widely with DIR algorithms and metrics. Careful physiologic validation to determine the appropriate DIR algorithm and metric is needed prior to its applications.

    View details for DOI 10.1118/1.3547719

    View details for Web of Science ID 000287879400022

    View details for PubMedID 21520845

  • Stereotactic ablative radiotherapy: what's in a name? Practical Radiation Oncology BW Loo Jr, JY Chang, LA Dawson, BD Kavanagh, AC Koong, S Senan, RD Timmerman 2011; 1 (1): 38-39
  • Motion Management and Image Guidance for Thoracic Tumor Radiotherapy: Clinical Treatment Programs IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY Loo, B. W., Kavanagh, B. D., Meyer, J. L. 2011; 43: 271-291

    Abstract

    Managing target motion first requires understanding the nature of the motion characteristic of the tumor in the individual patient. It is important to have effective immobilization and patient training strategies to help reduce motion, and then to design appropriate margins and compensation for the residual motion that is quantified. Especially when considering complex, technically demanding treatments that require a degree of patient cooperation, careful patient selection is needed to ensure that the potential benefits of the treatment design are actually realized. Finally, accurate treatment hinges critically on verification - of overall positioning, of target and organ motion at the time of treatment, and of the performance of the selected treatment strategy. Properly selected imaging methods are central to this verification process. This discussion will present practical solutions for motion management and image guidance of radiotherapy for thoracic tumors, and most of these concepts are widely applicable to treatment of other tumor sites as well.

    View details for Web of Science ID 000292117400013

    View details for PubMedID 21625158

  • INTENSITY-MODULATED RADIOTHERAPY FOR LOCALLY ADVANCED CANCERS OF THE LARYNX AND HYPOPHARYNX HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Daly, M. E., Le, Q., Jain, A. K., Maxim, P. G., Hsu, A., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Colevas, A. D., Pinto, H., Chang, D. T. 2011; 33 (1): 103-111

    Abstract

    Limited data evaluate intensity-modulated radiotherapy (IMRT) for cancers of the hypopharynx and larynx. We report clinical outcomes and failure patterns for these patients.Between September 2001 and December 2007, 42 patients with squamous cell carcinoma (SCC) of the hypopharynx (n = 23) and larynx (n = 19) underwent IMRT, 11 postoperatively and 31 definitively. Thirty-six received systemic therapy. Median follow-up was 30 months among surviving patients.Three local failures occurred within the high-dose region and 3 occurred in regional nodes. Seven patients developed distant metastasis as the initial failure. Three-year actuarial estimates of locoregional control, freedom from distant metastasis, and overall survival rates were, respectively, 80%, 72%, and 46%.IMRT provides good locoregional control for SCC of the hypopharynx and larynx compared with historical controls. Locoregional relapses occurred in the high-dose volumes, suggesting adequate target volume delineation. Hypopharyngeal tumors, which fare worse than laryngeal tumors, warrant investigation of more aggressive treatment.

    View details for DOI 10.1002/hed.21406

    View details for Web of Science ID 000286290400017

    View details for PubMedID 20848427

  • CyberKnife Stereotactic Ablative Radiotherapy for Lung Tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Gibbs, I. C., Loo, B. W. 2010; 9 (6): 589-596

    Abstract

    Stereotactic ablative radiotherapy (SABR) has emerged as a promising treatment for early stage non-small cell lung cancer, particularly for patients unable to tolerate surgical resection. High rates of local tumor control have been demonstrated with acceptable toxicity and the practical advantage of a short course of treatment. The CyberKnife image-guided robotic radiosurgery system has unique technical characteristics that make it well suited for SABR of tumors that move with breathing, including lung tumors. We review the qualities of the CyberKnife platform for lung tumor SABR, and provide a summary of clinical data using this system specifically.

    View details for Web of Science ID 000284971100007

    View details for PubMedID 21070081

  • STEREOTACTIC ABLATIVE RADIOTHERAPY SHOULD BE COMBINED WITH A HYPOXIC CELL RADIOSENSITIZER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Brown, J. M., Diehn, M., Loo, B. W. 2010; 78 (2): 323-327

    Abstract

    To evaluate the effect of tumor hypoxia on the expected level of cell killing by regimens of stereotactic ablative radiotherapy (SABR) and to determine the extent to which the negative effect of hypoxia could be prevented using a clinically available hypoxic cell radiosensitizer.We have calculated the expected level of tumor cell killing from regimens of SABR, both with and without the assumption that 20% of the tumor cells are hypoxic, using the standard linear quadratic model and the universal survival curve modification. We compare the results obtained with our own clinical data for lung tumors of different sizes and with published data from other studies. We also have calculated the expected effect on cell survival of adding the hypoxic cell sensitizer etanidazole at clinically achievable drug concentrations. Modeling tumor cell killing with any of the currently used regimens of SABR produces results that are inconsistent with the majority of clinical findings if tumor hypoxia is not considered. However, with the assumption of tumor hypoxia, the expected level of cell killing is consistent with clinical data. For only some of the smallest tumors are the clinical data consistent with no tumor hypoxia, but there could be other reasons for the sensitivity of these tumors. The addition of etanidazole at clinically achievable tumor concentrations produces a large increase in the expected level of tumor cell killing from the large radiation doses used in SABR.The presence of tumor hypoxia is a major negative factor in limiting the curability of tumors by SABR at radiation doses that are tolerable to surrounding normal tissues. However, this negative effect of hypoxia could be overcome by the addition of clinically tolerable doses of the hypoxic cell radiosensitizer etanidazole.

    View details for DOI 10.1016/j.ijrobp.2010.04.070

    View details for Web of Science ID 000282147000002

    View details for PubMedID 20832663

  • Alternatives to Surgery for Early Stage Non-Small Cell Lung Cancer-Ready for Prime Time? CURRENT TREATMENT OPTIONS IN ONCOLOGY Das, M., Abdelmaksoud, M. H., Loo, B. W., Kothary, N. 2010; 11 (1-2): 24-35

    Abstract

    Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC), with lobectomy being the most oncologically sound resection. Medically inoperable patients and high-risk surgical candidates require effective alternatives to surgery; even operable patients may opt for less invasive options if they are proven to achieve similar outcomes to surgery. Minimally invasive local treatment modalities including dose-intensified conformal radiation therapy, most notably stereotactic ablative radiotherapy (SABR; also known as stereotactic body radiation therapy), and thermal ablation methods such as radiofrequency ablation (RFA) and microwave ablation (MWA) are emerging as promising treatment options whose roles in the treatment of early stage lung cancer are being defined. Early clinical experience and a rapidly growing body of prospective clinical trials, primarily in medically inoperable patients, are demonstrating encouraging effectiveness and safety outcomes in some cases approaching historical results with surgery. Given the very poor prognosis of the medically inoperable patient population, these alternatives to surgery, particularly SABR, are starting to be considered appropriate first-line therapy in properly selected patients, and prospective cooperative group trials to evaluate and optimize RFA and SABR in specific patient subsets are being conducted. For operable patients, prospective multi-center and cooperative groups trials of SABR are ongoing or completed, and international randomized trials of SABR vs. surgery have been initiated. Thus, promising alternatives to surgery for early stage NSCLC are ready for prime time evaluation in the setting of clinical trials, and participation in ongoing trials for both operable and medically inoperable patients is strongly encouraged.

    View details for DOI 10.1007/s11864-010-0119-z

    View details for Web of Science ID 000281247200003

    View details for PubMedID 20577833

  • Stereotactic body radiation therapy (stereotactic ablative radiotherapy) for stage I non-small cell lung cancer--updates of radiobiology, techniques, and clinical outcomes. Discovery medicine Hadziahmetovic, M., Loo, B. W., Timmerman, R. D., Mayr, N. A., Wang, J. Z., Huang, Z., Grecula, J. C., Lo, S. S. 2010; 9 (48): 411-417

    Abstract

    Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), has emerged as one of the standard treatment options for stage I non-small cell lung cancer (NSCLC), mainly in medically inoperable patients. Its use has also been explored in operable patients. A large body of experience, either from retrospective studies or clinical trials, has been accumulated over the years and more is known about the radiobiology, cancer biology, technical aspects, clinical outcomes, and toxicities of SBRT. This article provides updates of these aspects of SBRT for stage I NSCLC.

    View details for PubMedID 20515609

  • INTENSITY-MODULATED RADIOTHERAPY IN THE TREATMENT OF OROPHARYNGEAL CANCER: CLINICAL OUTCOMES AND PATTERNS OF FAILURE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Le, Q., Maxim, P. G., Loo, B. W., Kaplan, M. J., Fischbein, N. J., Pinto, H., Chang, D. T. 2010; 76 (5): 1339-1346

    Abstract

    To report outcomes, failures, and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma of the oropharynx.Between Aug 2001 and Oct 2007, 107 patients were treated with IMRT with curative intent at Stanford University. Twenty-two patients were treated postoperatively, and 85 were treated definitively. Concurrent platinum-based chemotherapy was administered to 86 patients (80%) and cetuximab to 8 patients (7%). The prescribed dose was 66 Gy at 2.2 Gy/fraction for definitively treated cases and 60 Gy at 2 Gy/fraction for postoperative cases. Median follow-up was 29 months among surviving patients (range, 4-105 months).Eight patients had persistent disease or local-regional failure at a median of 6.5 months (range, 0-9.9 months). Six local failures occurred entirely within the high-risk clinical target volume (CTV) (one with simultaneous distant metastasis). One patient relapsed within the high- and intermediate-risk CTV. One patient had a recurrence at the junction between the IMRT and low-neck fields. Seven patients developed distant metastasis as the first site of failure. The 3-year local-regional control (LRC), freedom from distant metastasis, overall survival, and disease-free survival rates were 92%, 92%, 83%, and 81%, respectively. T stage (T4 vs. T1-T3) was predictive of poorer LRC (p = 0.001), overall survival (p = 0.001), and disease-free survival (p < 0.001) rates. Acute toxicity consisted of 58% grade 3 mucosal and 5% grade 3 skin reactions. Six patients (6%) developed grade >or=3 late complications.IMRT provides excellent LRC for oropharyngeal squamous cell carcinoma. Distant metastases are a major failure pattern. No marginal failures were observed.

    View details for DOI 10.1016/j.ijrobp.2009.04.006

    View details for Web of Science ID 000276675300012

    View details for PubMedID 19540068

  • Marked Tumor Response and Fatal Hemoptysis During Radiation for Lung Cancer in a Human Immunodeficiency Virus-Positive Patient Taking Nelfinavir JOURNAL OF THORACIC ONCOLOGY Chapman, C. H., Shen, J., Filion, E. J., Tran, P. T., Hara, W., Asuncion, A., Marko, D., Wakelee, H., Berry, G. J., Dimmick, K. W., Loo, B. W., Green, J. 2009; 4 (12): 1587-1589

    View details for Web of Science ID 000272095500025

    View details for PubMedID 20009915

  • Re: "The safety and efficacy of robotic image-guided radiosurgery system treatment for intra- and extracranial lesions: A systematic review of the literature" [Radiotherapy and Oncology 89 (2009) 245-253] RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Levendag, P. C., Fariselli, L., Bondiau, P., Lartigau, E., Loo, B. W., Gagnon, G. J., Koong, A. 2009; 93 (3): 656-657

    View details for DOI 10.1016/j.radonc.2009.08.024

    View details for Web of Science ID 000272762900048

    View details for PubMedID 19748142

  • Cooperative Group Research Efforts in Thoracic Malignancies 2009: A Review From the 10th Annual International Lung Cancer Congress CLINICAL LUNG CANCER Wakelee, H., Loo, B. W., Kernstine, K. H., Putnam, J. B., Edelman, M. J., Vokes, E. E., Schiller, J. H., Baas, P., Saijo, N., Adjei, A., Goss, G., Choy, H., Gandara, D. R. 2009; 10 (6): 395-404

    Abstract

    Critical advances in the treatment of patients with lung cancer have occurred in the past few years. The cooperative groups in North America and internationally have played crucial roles in these advances. The leaders of the groups meet on a regular basis to review the progress of their trials. However, they rarely have a chance to discuss all ongoing and planned trials, except at the annual Lung Cancer Congress held each June. This article captures this exchange from the 10th Annual Lung Cancer Congress held in June 2009. Exciting efforts are ongoing for all stages of non-small-cell lung cancer, small-cell lung cancer, and mesothelioma. A major focus of the groups at this time is a push toward more personalized medicine, as reflected in the selection criteria for many of the trials, along with planned correlates to better define populations most likely to benefit. Agents targeting the vascular endothelial growth factor (VEGF) pathway, including many tyrosine kinase inhibitors against the VEGF receptor, and those targeting the epidermal growth factor receptor pathway, are under extensive development with many combination trials ongoing.

    View details for DOI 10.3816/CLC.2009.n.075

    View details for Web of Science ID 000271378500002

    View details for PubMedID 19900856

  • METABOLIC TUMOR VOLUME PREDICTS FOR RECURRENCE AND DEATH IN HEAD-AND-NECK CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS La, T. H., Filion, E. J., Turnbull, B. B., Chu, J. N., Lee, P., Nguyen, K., Maxim, P., Quon, A., Graves, E. E., Loo, B. W., Le, Q. 2009; 74 (5): 1335-1341

    Abstract

    To evaluate the prognostic value of metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head-and-neck cancer (HNC) at a single institution.Between March 2003 and August 2007, 85 patients received positron emission tomography (PET)/computed tomography-guided chemoradiotherapy for HNC. Metabolically active tumor regions were delineated on pretreatment PET scans semiautomatically using custom software. We evaluated the relationship of (18)F-fluorodeoxyglucose-PET maximum standardized uptake value (SUV) and total metabolic tumor volume (MTV) with disease-free survival (DFS) and overall survival (OS).Mean follow-up for surviving patients was 20.4 months. The estimated 2-year locoregional control, DFS, and OS for the group were 88.0%, 69.5%, and 78.4%, respectively. The median time to first failure was 9.8 months among the 16 patients with relapse. An increase in MTV of 17.4 mL (difference between the 75th and 25th percentiles) was significantly associated with an increased hazard of first event (recurrence or death) (1.9-fold, p < 0.001), even after controlling for Karnofsky performance status (KPS) (1.8-fold, p = 0.001), and of death (2.1-fold, p < 0.001). We did not find a significant relationship of maximum SUV, stage, or other clinical factors with DFS or OS.Metabolic tumor volume is an adverse prognostic factor for disease recurrence and death in HNC. MTV retained significance after controlling for KPS, the only other significant adverse prognostic factor found in this cohort. MTV is a direct measure of tumor burden and is a potentially valuable tool for risk stratification and guiding treatment in future studies.

    View details for DOI 10.1016/j.ijrobp.2008.10.060

    View details for Web of Science ID 000268346100006

    View details for PubMedID 19289263

  • Safety and Efficacy of Percutaneous Fiducial Marker Implantation for Image-guided Radiation Therapy JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Kothary, N., Heit, J. J., Louie, J. D., Kuo, W. T., Loo, B. W., Koong, A., Chang, D. T., Hovsepian, D., Sze, D. Y., Hofmann, L. V. 2009; 20 (2): 235-239

    Abstract

    To evaluate the safety and technical success rate of percutaneous fiducial marker implantation in preparation for image-guided radiation therapy.From January 2003 to January 2008, we retrospectively reviewed 139 percutaneous fiducial marker implantations in 132 patients. Of the 139 implantations, 44 were in the lung, 61 were in the pancreas, and 34 were in the liver. Procedure-related major and minor complications were documented. Technical success was defined as implantation enabling adequate treatment planning and computed tomographic simulation.The major and minor complication rates were 5% and 17.3%, respectively. Pneumothorax after lung implantation was the most common complication. Pneumothoraces were seen in 20 of the 44 lung implantations (45%); a chest tube was required in only seven of the 44 lung transplantations (16%). Of the 139 implantations, 133 were successful; in six implantations (4.3%) the fiducial markers migrated and required additional procedures or alternate methods of implantation.Percutaneous implantation of fiducial marker is a safe and effective procedure with risks that are similar to those of conventional percutaneous organ biopsy.

    View details for DOI 10.1016/j.jvir.2008.09.026

    View details for Web of Science ID 000263075000012

    View details for PubMedID 19019700

  • Stereotactic body radiotherapy for primary and oligometastatic cancers Community Oncology MT Spiotto, BW Loo Jr, DT Chang 2009; 6 (10): 456-462
  • Post-Operative Radiation Therapy (PORT) in Completely Resected Non-Small-Cell Lung Cancer CURRENT TREATMENT OPTIONS IN ONCOLOGY Krupitskaya, Y., Loo, B. W. 2008; 9 (4-6): 343-356

    Abstract

    High-level evidence to guide the optimal postoperative management of patients with completely resected non-small-cell lung cancer (NSCLC) is lacking. Large randomized controlled trials have established postoperative chemotherapy as the standard of care for patients with pathologically involved lymph nodes. Recent retrospective and non-randomized studies provide evidence of the benefit of post-operative radiation therapy (PORT) in patients with mediastinal nodal involvement (N2 stage). A large multi-institutional randomized trial of PORT in this patient population is now underway. Based on currently available data, PORT may be considered for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy. At this point, PORT is not recommended for patients with less than N2 nodal stage. Ideally, modern three-dimensional conformal radiation technique should be used, with attention to normal organ sparing, particularly lung and heart. Appropriate image guidance tools are encouraged to individualize treatment margins, account for breathing-induced motion, and minimize irradiation of normal tissues. The target volume should include at a minimum the bronchial stump, ipsilateral hilum, and involved nodal stations, and covering adjacent mediastinal nodal stations is recommended. A total dose of 50-54 Gy in 1.8-2 Gy fractions is appropriate.

    View details for DOI 10.1007/s11864-009-0090-8

    View details for Web of Science ID 000267146600010

    View details for PubMedID 19387842

  • RETROSPECTIVE ANALYSIS OF ARTIFACTS IN FOUR-DIMENSIONAL CT IMAGES OF 50 ABDOMINAL AND THORACIC RADIOTHERAPY PATIENTS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Yamamoto, T., Langner, U., Loo, B. W., Shen, J., Keall, P. J. 2008; 72 (4): 1250-1258

    Abstract

    To quantify the type, frequency, and magnitude of artifacts in four-dimensional (4D) CT images acquired using a multislice cine method.Fifty consecutive patients who underwent 4D-CT scanning and radiotherapy for thoracic or abdominal cancers were included in this study. All the 4D-CT scans were performed on the GE multislice PET/CT scanner with the Varian Real-time Position Management system in cine mode. The GE Advantage 4D software was used to create 4D-CT data sets. The artifacts were then visually and quantitatively analyzed. We performed statistical analyses to evaluate the relationships between patient- or breathing-pattern-related parameters and the occurrence as well as magnitude of artifacts.It was found that 45 of 50 patients (90%) had at least one artifact (other than blurring) with a mean magnitude of 11.6 mm (range, 4.4-56.0 mm) in the diaphragm or heart. We also observed at least one artifact in 6 of 20 lung or mediastinal tumors (30%). Statistical analysis revealed that there were significant differences between several breathing-pattern-related parameters, including abdominal displacement (p < 0.01), for the subgroups of patients with and without artifacts. The magnitude of an artifact was found to be significantly but weakly correlated with the abdominal displacement difference between two adjacent couch positions (R = 0.34, p < 0.01).This study has identified that the frequency and magnitude of artifacts in 4D-CT is alarmingly high. Significant improvement is needed in 4D-CT imaging.

    View details for DOI 10.1016/j.ijrobp.2008.06.1937

    View details for Web of Science ID 000260592600040

    View details for PubMedID 18823717

  • Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hara, W., Loo, B. W., Goffinet, D. R., Chang, S. D., Adler, J. R., Pinto, H. A., Fee, W. E., Kaplan, M. J., Fischbein, N. J., Le, Q. 2008; 71 (2): 393-400

    Abstract

    To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

    View details for DOI 10.1016/j.ijrobp.2007.10.027

    View details for Web of Science ID 000255971100013

    View details for PubMedID 18164839

  • Complications of ablative therapies in lung cancer CLINICAL LUNG CANCER Padda, S., Kothary, N., Donington, J., Cannon, W., Loo, B. W., Kee, S., Wakelee, H. 2008; 9 (2): 122-126

    Abstract

    Two cases of complications secondary to the use of microwave ablation (MWA) in non-small-cell lung cancer (NSCLC) are discussed herein. The first case involves a 62-year-old man with stage IB NSCLC who declined surgery and pursued MWA. Within 7 months, he had residual disease at the MWA treatment site, and surgery was performed. The patient was found to have pleural and chest wall involvement, making complete resection impossible. The second case involves an 86-year-old woman with a second local recurrence of NSCLC and previous treatment including surgery and chemoradiation therapy. She was initially a surgical candidate but declined surgery and pursued MWA. Within 6 months, she had residual disease at the MWA treatment site. A second MWA was performed, and she developed a large cavitary abscess at the MWA site and had subsequent clinical decline. Less invasive ablation therapies and stereotactic radiosurgery are being developed for patients with inoperable lung cancer. Because these modalities have recently been developed, trials that clearly show efficacy and survival benefit are yet to be completed. Ablation procedures can result in complications, including residual disease and cavitary lesions susceptible to infection. These cases highlight the caution that should still be observed when recommending lung ablation strategies and the importance of selecting appropriate patients.

    View details for Web of Science ID 000255039000010

    View details for PubMedID 18501100

  • Initial evaluation of F-18-fluorothymidine (FLT) PET/CT scanning for primary pancreatic cancer EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Quon, A., Chang, S. T., Chin, F., Kamaya, A., Dick, D. W., Loo, B. W., Gambhir, S. S., Koong, A. C. 2008; 35 (3): 527-531

    Abstract

    The aim of this study was to evaluate the potential of (18)F-fluorothymidine (FLT) PET/CT for imaging pancreatic adenocarcinoma.This was a pilot study of five patients (four males, one female) with newly diagnosed and previously untreated pancreatic adenocarcinoma. Patients underwent FLT PET/CT, (18)F-fluorodeoxyglucose (FDG) PET/CT, and contrast-enhanced CT scanning before treatment. The presence of cancer was confirmed by histopathological analysis at the time of scanning in all five patients. The degree of FLT and FDG uptake at the primary tumor site was assessed using visual interpretation and semi-quantitative SUV analyses.The primary tumor size ranged from 2.5 x 2.8 cm to 3.5 x 7.0 cm. The SUV of FLT uptake within the primary tumor ranged from 2.1 to 3.1. Using visual interpretation, the primary cancer could be detected from background activity in two of five patients (40%) on FLT PET/CT. By comparison, FDG uptake was higher in each patient with a SUV range of 3.4 to 10.8, and the primary cancer could be detected from background in all five patients (100%).In this pilot study of five patients with primary pancreatic adenocarcinoma, FLT PET/CT scanning showed poor lesion detectability and relatively low levels of radiotracer uptake in the primary tumor.

    View details for DOI 10.1007/s00259-007-0630-z

    View details for Web of Science ID 000254402800010

    View details for PubMedID 17960376

  • Quantification of motion of different thoracic locations using four-dimensional computed tomography: Implications for radiotherapy planning INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Maxim, P. G., Loo, B. W., Shirazi, H., Thorndyke, B., Luxton, G., Le, Q. 2007; 69 (5): 1395-1401

    Abstract

    To assess the respiratory motion of different thoracic nodal locations and its dependence on the presence of enlarged nodes; to assess the respiratory motion of different parenchymal tumor locations; and to determine the appropriate margins to cover the respiratory motion of targets at these locations.We reviewed the four-dimensional computed tomography scans of 20 patients with thoracic tumors treated at our institution. The motion of four central thoracic locations (aortic arch, carina, and bilateral hila), parenchymal tumor locations (upper vs. lower, and anterior vs. middle vs. posterior thorax), and bilateral diaphragmatic domes was measured.For the central thoracic locations, the largest motion was in the superoinferior (SI) dimension (>5 mm for bilateral hila and carina, but <4 mm for aortic arch). No significant difference was found in the motion of these locations in the absence or presence of enlarged nodes. For parenchymal tumors, upper tumors exhibited smaller SI motion than did lower tumors (3.7 vs. 10.4 mm, p = 0.029). Similarly, anterior tumors exhibited smaller motion than did posterior tumors in both the SI (4.0 vs. 8.0 mm, p = 0.013) and lateral (2.8 vs. 4.6 mm, p = 0.045) directions. The margins that would be needed to encompass the respiratory motion of each of the evaluated locations in 95% of patients were tabulated and range from 3.4 to 37.2 mm, depending on the location and direction.The results of our study have provided data for appropriate site-specific internal target volume expansion that could be useful in the absence of four-dimensional computed tomography-based treatment planning. However, generalizing the results from a small patient population requires discretion.

    View details for Web of Science ID 000251561100008

    View details for PubMedID 17869025

  • Metabolic tumor burden predicts for disease progression and death in lung cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lee, P., Weerasuriya, D. K., Lavori, P. W., Quon, A., Hara, W., Maxim, P. G., Le, Q., Wakelee, H. A., Donington, J. S., Graves, E. E., Loo, B. W. 2007; 69 (2): 328-333

    Abstract

    In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging.We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV).The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant (p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS.In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively.

    View details for DOI 10.1016/j.ijrobp.2007.04.036

    View details for Web of Science ID 000249796100002

    View details for PubMedID 17869659

  • RT_Image: An open-source tool for investigating PET in radiation oncology TECHNOLOGY IN CANCER RESEARCH & TREATMENT Graves, E. E., Quon, A., Loo, B. W. 2007; 6 (2): 111-121

    Abstract

    Positron emission tomography (PET) has emerged as a valuable imaging modality for the diagnosis and staging of cancer. However, despite evidence that PET may be useful for defining target volumes for radiation therapy, no standardized methodology for accomplishing this task exists. To facilitate the investigation of the utility of PET imaging in radiotherapy treatment planning and accelerate its integration into clinical radiation oncology, we have developed software for exploratory analysis and segmentation of functional imaging datasets. The application, RT_Image, allows display of multiple imaging datasets and associated three-dimensional regions-of-interest (ROIs) at arbitrary view angles and fields of view. It also includes semi-automated image segmentation tools for defining metabolically active tumor volumes that may aid creation of target volumes for treatment planning. RT_Image is DICOM compliant, permitting the transfer of imaging data and DICOM-RT structure sets between the application and treatment planning software. RT_Image has been used by radiation oncologists, nuclear medicine physicians, and radiation physicists to analyze over 200 PET datasets. Novel segmentation techniques have been implemented within this programming framework for therapy planning and for evaluation of molecular imaging-derived parameters as prognostic indicators. RT_Image represents a freely-available software base on which further investigations of the utlity of PET and molecular imaging in radiation oncology may be built. The development of tools such as this is critical in order to realize the potential of molecular imaging-guided radiation therapy.

    View details for Web of Science ID 000245969900007

    View details for PubMedID 17375973

  • Impact of integrated PET/CT on variability of target volume delineation in rectal cancer TECHNOLOGY IN CANCER RESEARCH & TREATMENT Patel, D. A., Chang, S. T., Goodman, K. A., Quon, A., Thorndyke, B., Gambhir, S. S., McMillan, A., Loo, B. W., Koong, A. C. 2007; 6 (1): 31-36

    Abstract

    Several studies have demonstrated substantial variability among individual radiation oncologists in defining target volumes using computed tomography (CT). The objective of this study was to determine the impact of combined positron emission tomography and computed tomography (PET/CT) on inter-observer variability of target volume delineation in rectal cancer. We also compared the relative concordance of two PET imaging tracers, 18F-fluorodeoxyglucose (FDG) and 18F-fluorodeoxythymidine (FLT), against conventional computed tomography (CT). Six consecutive patients with locally advanced rectal cancer were enrolled onto an institutional protocol involving preoperative chemoradiotherapy and correlative studies including FDG- and FLT-PET scans acquired in the treatment position. Using these image data sets, four radiation oncologists independently delineated primary and nodal gross tumor volumes (GTVp and GTVn) for a hypothetical boost treatment. Contours were first defined based on CT alone with observers blinded to the PET images, then based on combined PET/CT. An inter-observer similarity index (SI), ranging from a value of 0 for complete disagreement to 1 for complete agreement of contoured voxels, was calculated for each set of volumes. For primary gross tumor volume (GTVp), the difference in estimated SI between CT and FDG was modest (CT SI = 0.77 vs. FDG SI = 0.81), but statistically significant (p = 0.013). The SI difference between CT and FLT for GTVp was also slight (FLT SI = 0.80) and marginally non-significant (p < 0.082). For nodal gross tumor volume, (GTVn), SI was significantly lower for CT based volumes with an estimated SI of 0.22 compared to an estimated SI of 0.70 for FDG-PET/CT (p < 0.0001) and an estimated SI of 0.70 for FLT-PET/CT (p < 0.0001). Boost target volumes in rectal cancer based on combined PET/CT results in lower inter-observer variability compared with CT alone, particularly for nodal disease. The use of FDG and FLT did not appear to be different from this perspective.

    View details for Web of Science ID 000244732600005

    View details for PubMedID 17241098

  • Clinical role of F-18-FDG PET/CT in the management of squamous cell carcinoma of the head and neck and thyroid carcinoma JOURNAL OF NUCLEAR MEDICINE Quon, A., Fischbein, N. J., McDougall, I. R., Le, Q., Loo, B. W., Pinto, H., Kaplan, M. J. 2007; 48: 58S-67S

    Abstract

    18F-FDG PET/CT has rapidly become a widely used imaging modality for evaluating a variety of malignancies, including squamous cell carcinoma of the head and neck and thyroid cancer. Using both published data and the multidisciplinary experience at our institution, we provide a practical set of guidelines and algorithms for the use of 18F-FDG PET/CT in the evaluation and management of head and neck cancer and thyroid cancer.

    View details for Web of Science ID 000243420900008

    View details for PubMedID 17204721

  • Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors JOURNAL OF THORACIC ONCOLOGY Le, Q., Loo, B. W., Ho, A., Cotrutz, C., Koong, A. C., Wakelee, H., Kee, S. T., Constantinescu, D., Whyte, R. I., Donington, J. 2006; 1 (8): 802-809

    Abstract

    The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy (RT) in patients with inoperable lung tumors.Eligible patients included those with inoperable T1-2N0 non-small cell lung cancer (NSCLC) or solitary lung metastases. Treatments were delivered by means of the CyberKnife. All patients underwent computed tomography-guided metallic fiducial placement in the tumor for image-guided targeting. Nine to 20 patients were treated per dose cohort starting at 15 Gy/fraction followed by dose escalation of 5 to 10 Gy to a maximal dose of 30 Gy/fraction. A minimal 3-month period was required between each dose level to monitor toxicity.Thirty-two patients (21 NSCLC and 11 metastatic tumors) were enrolled. At 25 Gy, pulmonary toxicity was noted in patients with prior pulmonary RT and treatment volumes greater than 50 cc; therefore, dose escalation to 30 Gy was applied only to unirradiated patients and treatment volume less than 50 cc. Ten patients received doses less than 20 Gy, 20 received 25 Gy, and two received 30 Gy. RT-related complications were noted for doses greater than 25 Gy and included four cases of grade 2 to 3 pneumonitis, one pleural effusion, and three possible treatment-related deaths. The 1-year freedom from local progression was 91% for dose greater than 20 Gy and 54% for dose less than 20 Gy in NSCLC (p = 0.03). NSCLC patients had significantly better freedom from relapse (p = 0.003) and borderline higher survival than those with metastatic tumors (p = 0.07).Single-fraction stereotactic RT is feasible for selected patients with lung tumors. For those with prior thoracic RT, 25 Gy may be too toxic. Higher dose was associated with improved local control. Longer follow-up is necessary to determine the treatment efficacy and toxicity.

    View details for Web of Science ID 000241649300008

    View details for PubMedID 17409963

  • Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: A pilot study in humans INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Loo, B. W., Draney, M. T., Sivanandan, R., Ruehm, S. G., Pawlicki, T., Xing, L., Herfkens, R. J., Le, Q. 2006; 66 (2): 462-468

    Abstract

    To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites.We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence.The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer.We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.

    View details for DOI 10.1016/j.ijrobp.2006.05.045

    View details for Web of Science ID 000240699500024

    View details for PubMedID 16965993

  • Four-dimensional cone-beam computed tomography using an on-board imager MEDICAL PHYSICS Li, T., Xing, L., Munro, P., McGuinness, C., Chao, M., Yang, Y., Loo, B., Koong, A. 2006; 33 (10): 3825-3833

    Abstract

    On-board cone-beam computed tomography (CBCT) has recently become available to provide volumetric information of a patient in the treatment position, and holds promises for improved target localization and irradiation dose verification. The design of currently available on-board CBCT, however, is far from optimal. Its quality is adversely influenced by many factors, such as scatter, beam hardening, and intra-scanning organ motion. In this work we quantitatively study the influence of organ motion on CBCT imaging and investigate a strategy to acquire high quality phase-resolved [four-dimensional (4D)] CBCT images based on phase binning of the CBCT projection data. An efficient and robust method for binning CBCT data according to the patient's respiratory phase derived in the projection space was developed. The phase-binned projections were reconstructed using the conventional Feldkamp algorithm to yield 4D CBCT images. Both phantom and patient studies were carried out to validate the technique and to optimize the 4D CBCT data acquisition protocol. Several factors that are important to the clinical implementation of the technique, such as the image quality, scanning time, number of projections, and radiation dose, were analyzed for various scanning schemes. The general references drawn from this study are: (i) reliable phase binning of CBCT projections is accomplishable with the aid of external or internal marker and simple analysis of its trace in the projection space, and (ii) artifact-free 4D CBCT images can be obtained without increasing the patient radiation dose as compared to the current 3D CBCT scan.

    View details for DOI 10.1118/1.2349692

    View details for Web of Science ID 000241424100024

    View details for PubMedID 17089847

  • Optical detection of tumors in vivo by visible light tissue oximetry TECHNOLOGY IN CANCER RESEARCH & TREATMENT Maxim, P. G., Carson, J. J., Benaron, D. A., Loo, B. W., Xing, L., Boyer, A. L., Friedland, S. 2005; 4 (3): 227-234

    Abstract

    Endoscopy is a standard procedure for identifying tumors in patients suspected of having gastrointestinal (G.I.) cancer. The early detection of G.I. neoplasms during endoscopy is currently made by a subjective visual inspection that relies to a high degree on the experience of the examiner. This process can be difficult and unreliable, as tumor lesions may be visually indistinguishable from benign inflammatory conditions and the surrounding mucosa. In this study, we evaluated the ability of local ischemia detection using visible light spectroscopy (VLS) to differentiate neoplastic from normal tissue based on capillary tissue oxygenation during endoscopy. Real-time data were collected (i) from human subjects (N = 34) monitored at various sites during endoscopy (enteric mucosa, malignant, and abnormal tissue such as polyps) and (ii) murine animal subjects with human tumor xenografts. Tissue oximetry in human subjects during endoscopy revealed a tissue oxygenation (StO2%, mean +/- SD) of 46 +/- 22% in tumors, which was significantly lower than for normal mucosal oxygenation (72 +/- 4%; P < or = 0.0001). No difference in tissue oxygenation was observed between normal and non-tumor abnormal tissues (P = N.S.). Similarly, VLS tissue oximetry for murine tumors revealed a mean local tumor oxygenation of 45% in LNCaP, 50% in M21, and 24% in SCCVII tumors, all significantly lower than normal muscle tissue (74%, P < 0.001). These results were further substantiated by positive controls, where a rapid real-time drop in tumor oxygenation was measured during local ischemia induced by clamping or epinephrine. We conclude that VLS tissue oximetry can distinguish neoplastic tissue from normal tissue with a high specificity (though a low sensitivity), potentially aiding the endoscopic detection of gastrointestinal tumors.

    View details for Web of Science ID 000229787600001

    View details for PubMedID 15896077

  • Plasmablastic lymphoma presenting in a human immunodeficiency virus-negative patient: a case report ANNALS OF HEMATOLOGY Nguyen, D. D., Loo, B. W., Tillman, G., Natkunam, Y., Cao, T. M., Vaughan, W., Dorfman, R. F., Goffinet, D. R., Jacobs, C. D., Advani, R. H. 2003; 82 (8): 521-525

    Abstract

    Plasmablastic lymphoma (PBL), an aggressive non-Hodgkin's lymphoma that carries a poor prognosis, previously has been identified almost exclusively in patients infected with the human immunodeficiency virus (HIV). We present a case of a 42-year-old HIV-negative patient presenting with an isolated nasal cavity mass, the typical presentation for PBL. The patient was given systemic chemotherapy, central nervous system prophylaxis, and consolidative locoregional radiotherapy and achieved a complete clinical response. This case suggests PBL should be considered in HIV-negative patients with characteristic findings.

    View details for DOI 10.1007/s00277-003-0684-3

    View details for Web of Science ID 000184757100013

    View details for PubMedID 12783213

  • A new sample preparation method for biological soft X-ray microscopy: nitrogen-based contrast and radiation tolerance properties of glycol methacrylate-embedded and sectioned tissue JOURNAL OF MICROSCOPY-OXFORD Loo, B. W., Sauerwald, I. M., Hitchcock, A. P., Rothman, S. S. 2001; 204: 69-86

    Abstract

    We describe the preparation of a biological tissue for imaging in a transmission soft X-ray microscope. Sections of exocrine pancreas embedded in glycol methacrylate polymer, an embedding medium widely used in visible light and electron microscopy, were examined. Contrast was based primarily on the nitrogen content of the tissue, and dual-wavelength imaging at the nitrogen K-shell absorption edge was used to map the distribution and provide quantitative densitometry of both the protein and embedding matrix components of the sample. The measurements were calibrated by obtaining the absorption spectrum of protein near the nitrogen edge. The contrast was consistent and reproducible, making possible the first large-scale X-ray microscopic study on sections of plastic-embedded soft tissue. At radiation doses of up to 10(8) Gray, much more than required for routine imaging, no distortion and little mass loss were observed. This sample preparation method should permit routine imaging of tissues in X-ray microscopes, previously a difficult task, as well as multimodal imaging (using visible light, X-ray, electron, and scanned probe microscopies) on the same sample.

    View details for Web of Science ID 000171285700009

    View details for PubMedID 11580815

  • Automatic image acquisition, calibration and montage assembly for biological X-ray microscopy JOURNAL OF MICROSCOPY-OXFORD Loo, B. W., Meyer-Ilse, W., Rothman, S. S. 2000; 197: 185-201

    Abstract

    We describe a system for the automatic acquisition and processing of digital images in a high-resolution X-ray microscope, including the formation of large-field high-resolution image montages. A computer-controlled sample positioning stage provides approximate coordinates for each high-resolution subimage. Individual subimages are corrected to compensate for time-varying, non-uniform illumination and CCD-related artefacts. They are then automatically assembled into a montage. The montage assembly algorithm is designed to use the overlap between each subimage and multiple neighbours to improve the performance of the registration step and the fidelity of the result. This is accomplished by explicit use of recorded stage positions, optimized ordering of subimage insertion, and registration of subimages to the developing montage. Using this procedure registration errors are below the resolution limit of the microscope (43 nm). The image produced is a seamless, large-field montage at full resolution, assembled automatically without human intervention. Beyond this, it is also an accurate X-ray transmission map that allows the quantitative measurement of anatomical and chemical features of the sample. Applying these tools to a biological problem, we have conducted the largest X-ray microscopical study to date.

    View details for Web of Science ID 000085459300007

    View details for PubMedID 10652011

  • X-RAY STEREOMICROSCOPY - HIGH-RESOLUTION 3-D IMAGING OF HUMAN SPERMATOZOA IN AQUEOUS SUSPENSION WITH NATURAL CONTRAST JOURNAL OF MICROSCOPY-OXFORD Loo, B. W., Williams, S., Meizel, S., Rothman, S. S. 1992; 166: RP5-RP6

    View details for Web of Science ID A1992HW41100010

    View details for PubMedID 1625335

  • An environmental sample chamber for x-ray microscopy J Microsc Goncz KK, Batson P, Ciarlo D, Loo BW Jr, Rothman SS 1992; 168: 101-110

Conference Proceedings


  • Postchemoradiotherapy Positron Emission Tomography Predicts Pathologic Response and Survival in Patients With Esophageal Cancer Jayachandran, P., Pai, R. K., Quon, A., Graves, E., Krakow, T. E., La, T., Loo, B. W., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: 471-477

    Abstract

    To correlate the prechemoradiotherapy (CRT) and post-CRT metabolic tumor volume (MTV) on positron emission tomography (PET) scanning with the pathologic response and survival in patients receiving preoperative CRT for esophageal cancer.The medical records of 37 patients with histologically confirmed Stage I-IVA esophageal cancer treated with CRT with or without surgical resection were reviewed. Of the 37 patients, 21 received preoperative CRT (57%) and 16 received definitive CRT (43%). All patients had a pre-CRT and 32 had a post-CRT PET scan. The MTV was measured on the pre-CRT PET and post-CRT PET scan, respectively, using a minimum standardized uptake value (SUV) threshold x, where x = 2, 2.5, 3, or the SUV maximum × 50%. The total glycolytic activity (TGA(x)) was defined as the mean SUV × MTV(x). The MTV ratio was defined as the pre-CRT PET MTV/post-CRT MTV. The SUV ratio was defined similarly. A single pathologist scored the pathologic response using a tumor regression grade (TRG) scale.The median follow-up was 1.5 years (range, 0.4-4.9). No significant correlation was found between any parameters on the pre-CRT PET scan and the TRG or overall survival (OS). Multiple post-CRT MTV values and post-TGA values correlated with the TRG and OS; however, the MTV(2.5(Post)) and TGA(2.5(Post)) had the greatest correlation. The MTV(2) ratio correlated with OS. The maximum SUV on either the pre-CRT and post-CRT PET scans or the maximum SUV ratio did not correlate with the TRG or OS. Patients treated preoperatively had survival similar compared with those treated definitively with a good PET response (p = 0.97) and significantly better than that of patients treated definitively with a poor PET response (p < 0.0001).The maximum SUV was not a predictive or prognostic parameter. The MTV(2.5) and TGA(2.5) were useful markers for predicting the response and survival on the post-CRT PET scan. The MTV(2) ratio also correlated with survival. Post-CRT PET can potentially guide therapy after CRT.

    View details for DOI 10.1016/j.ijrobp.2011.12.029

    View details for Web of Science ID 000308062700055

    View details for PubMedID 22381904

Stanford Medicine Resources: