Academic Appointments

Honors & Awards

  • Henry S. Kaplan Memorial Prize for Teaching in Radiation Oncology, Stanford University (2013)
  • Teacher of the Year Award, Association of Residents in Radiation Oncology (2009)
  • Orsak Innovation Fund, Stanford Cancer Center (2006)
  • Young Investigator Travel Scholarship, Academy of Molecular Imaging (2004)
  • Young Investigator Fellowship, German Academic Exchange Program (2000)
  • Student Investigator Fellowship, Nachwuchs Foerderungs Gesetz, Germany (1998)

Professional Education

  • DABR, The American Board of Radiology, Therapeutic Radiologic Physics (2008)
  • Dr. rer. nat. (PhD), Humboldt University, Berlin, Biophysics (2003)
  • Dipl. Phys. (MSc), Technical University, Berlin, Physics (1997)

Research & Scholarship

Current Research and Scholarly Interests

My research is focused on developing optical imaging technologies for the early detection and characterization of malignant tissue.
Furthermore, I am interested in the design and implementation of novel radiation delivery approaches.

Clinical Trials

  • 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.

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  • Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma Not Recruiting

    This multi-institutional trial aims to evaluate the potential benefit and side effects of adding fractionated stereotactic body radiotherapy/surgery (SBRT) before and after chemotherapy with gemcitabine for locally advanced pancreatic cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laurie Ann Columbo, 650-736-0792.

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  • Phase II Trial of Individualized Lung Tumor Stereotactic Ablative Radiotherapy (iSABR) Recruiting

    Stereotactic ablative radiotherapy has emerged as an important and effective new treatment modality for lung tumors, but optimal dose regimens have not been fully established. Significant toxicity can be observed with the most commonly used dose regimens, implying that developing treatment regimens that optimize treatment based on tumor-specific factors could be of clinical benefit. This study will test a risk-adapted approach to SABR delivery aimed at maximizing tumor control while minimizing toxicity.

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  • 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.

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  • 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.

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2013-14 Courses


Journal Articles

  • 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


    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)


    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

  • 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-?


    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

  • 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., Quynh-Thu Le, Q. T., Diehn, M., Sze, D. Y., Loo, B. W., Kothary, N., Maxim, P. G. 2013; 14 (2): 77-89
  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • Orthovoltage Intraoperative Radiotherapy for Locally Advanced and Recurrent Colorectal Cancer DISEASES OF THE COLON & RECTUM Daly, M. E., Kapp, D. S., Maxim, P. G., Welton, M. L., Tran, P. T., Koong, A. C., Chang, D. T. 2012; 55 (6): 695-702


    Locally advanced and recurrent colorectal cancers pose a significant therapeutic challenge. Orthovoltage intraoperative radiotherapy provides one potential means of improving disease control at the time of surgery.This study sought to analyze outcomes and identify prognostic factors of patients treated with orthovoltage intraoperative radiotherapy for locally advanced or recurrent colorectal cancer.This study is a retrospective chart review conducted at a tertiary medical center.Between January 1990 and July 2009, 55 patients underwent intraoperative radiotherapy to a total of 61 sites for locally advanced (n = 14) or recurrent (n = 41) cancers of colon (n = 18) or rectum/rectosigmoid junction (n = 37).Median dose was 12 Gy (range, 7.5-20 Gy). Among locally advanced rectal/rectosigmoid cases, surgery included abdominoperineal resection (n = 3) or low anterior resection (n = 9). Seven treated sites had gross residual (R2) disease, 28 had pathologic or clinical microscopic residual disease (R1), and 15 were complete resections (R0). Treated sites included sacrum (n = 22), anterior pelvis/pelvic sidewall (19), sacrum and sidewall (n = 1), aortic bifurcation (n = 2), vaginal cuff (n = 2), psoas (n = 3), perivesicular region (n = 2), and other (n = 10).Outcomes measures included in-field local control, locoregional control, overall survival, and grade ?3 toxicity.At a median follow-up of 27 months (range, 4-237) among living patients, 2-year Kaplan-Meier estimates of in-field local control, locoregional control, and overall survival were 69%, 51%, and 59%. Margin status predicted for improved locoregional control (p = 0.01) and overall survival (p = 0.01). Seventeen patients (31%) developed a grade 3 to 5 toxicity following surgery with intraoperative radiotherapy.This study was limited by its retrospective nature and relatively small sample size.Local control with intraoperative radiotherapy for locally advanced and recurrent colorectal cancers is good despite the high risk of residual disease. Among carefully selected patients, multimodality regimens including intraoperative radiotherapy may permit long-term survival.

    View details for DOI 10.1097/DCR.0b013e31824d464c

    View details for Web of Science ID 000304368500011

    View details for PubMedID 22595850



    To investigate the radiotherapy dose perturbations caused by esophageal stents in patients undergoing external beam treatments for esophageal cancer.Four esophageal stents were examined (three metallic stents: WallFlex, Ultraflex, and Alveolus; one nonmetallic stent with limited radiopaque markers for visualization: Polyflex). All experiments were performed in a liquid water phantom with a custom acrylic stent holder. Radiochromic film was used to measure the dose distributions adjacent to the stents at locations proximal and distal to the radiation source. The stents were placed in an air-filled cavity to simulate the esophagus. Treatment plans were created and delivered for photon energies of 6 and 15 MV, and data analysis was performed on uniform regions of interest, according to the size and geometric placement of the films, to quantify the dose perturbations.The three metallic stents produced the largest dose perturbations with distinct patterns of "hot" spots (increased dose) measured proximal to the radiation source (up to 15.4%) and both "cold" (decreased dose) and hot spots measured distal to the radiation source (range, -6.1%-5.8%). The polymeric Polyflex stent produced similar dose perturbations when the radiopaque markers were examined (range, -7.6%-15.4%). However, when the radiopaque markers were excluded from the analysis, the Polyflex stent produced significantly smaller dose perturbations, with maximum hot spots of 7.3% and cold spots of -3.2%.The dose perturbations caused by esophageal stents during the treatment of esophageal cancer using external beam radiotherapy should be understood. These perturbations will result in hot and cold spots in the esophageal mucosa, with varying magnitudes depending on the stent. The nonmetallic Polyflex stent appears to be the most suitable for patients undergoing radiotherapy, but further studies are necessary to determine the clinical significance of the dose perturbations.

    View details for DOI 10.1016/j.ijrobp.2011.02.020

    View details for Web of Science ID 000301891300031

    View details for PubMedID 21514064

  • Modern Radiation Therapy Techniques for Pancreatic Cancer GASTROENTEROLOGY CLINICS OF NORTH AMERICA Trakul, N., Koong, A. C., Maxim, P. G., Chang, D. T. 2012; 41 (1): 223-?


    Radiation therapy is a rapidly evolving field, and recent technical advances have spurred an increasing number of new treatments as well as marked improvements in previously existing treatments. Despite a growing body of published evidence demonstrating that radiotherapy for the treatment of pancreatic cancer is improving in efficacy and safety, the ultimate effect on patient outcomes remains to be seen. It is an unfortunate fact that the majority of pancreatic cancer patients will ultimately have metastases and succumb to distant disease. Thus, improvements in local tumor control engendered by these recent advances will have little impact on overall survival without the coincident development of better systemic treatment regimens.

    View details for DOI 10.1016/j.gtc.2011.12.011

    View details for Web of Science ID 000301989100016

    View details for PubMedID 22341260

  • 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-?


    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

  • 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): 170-180
  • 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


    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



    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

  • SINGLE-FRACTION STEREOTACTIC BODY RADIATION THERAPY AND SEQUENTIAL GEMCITABINE FOR THE TREATMENT OF LOCALLY ADVANCED PANCREATIC CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schellenberg, D., Kim, J., Ciristman-Skieller, C., Chun, C. L., Columbo, L. A., Ford, J. M., Fisher, G. A., Kunz, P. L., Van Dam, J., Quon, A., Desser, T. S., Norton, J., Hsu, A., Maxim, P. G., Xing, L., Goodman, K. A., Chang, D. T., Koong, A. C. 2011; 81 (1): 181-188


    This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT).Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT.All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year.Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

    View details for DOI 10.1016/j.ijrobp.2010.05.006

    View details for Web of Science ID 000294093300025

    View details for PubMedID 21549517



    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



    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



    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

  • 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


    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

  • 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


    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



    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



    To identify the technical aspects of image-guided intensity-modulated radiation therapy (IMRT) for localized prostate cancer that could result in a clinically meaningful incidental dose to the testes.We examined three sources that contribute incidental dose to the testes, namely, from internal photon scattering from IMRT small field and large pelvic nodal fields with 6 or 15 MV, from neutrons when >10-MV photons are used, and from daily image-guided fiducial-based portal imaging. Using clinical data from 10 patients who received IMRT for prostate cancer, and thermo-luminescent dosimeter measurements in phantom, we estimated the dose to the testes from each of these sources.A mean testicular dose of 172 and 220 cGy results from internal photon scatter for pelvic nodal fields and 68 and 93 cGy for prostate-only fields, for 6- and 15-MV energies, respectively. For 15-MV photon energies, the mean testicular dose from neutrons is 60 cGy for pelvic fields and 31 cGy for prostate-only fields. From daily portal MV image guidance, the testes-in-field mean dose is 350 cGy, whereas the testes-out-of-field scatter dose is 16 cGy. Dosimetric comparisons between IMRT using 6-MV and 15-MV photon energies are not significantly different. Worst-case scenarios can potentially deliver cumulative incidental mean testicular doses of 630 cGy, whereas best-case scenarios can deliver only 84 cGy.Incidental dose to the testes from prostate IMRT can be minimized by opting to restrict the use of elective pelvic nodal fields, by choosing photon energies <10 MV, and by using the smallest port sizes necessary for daily image guidance.

    View details for DOI 10.1016/j.ijrobp.2009.04.083

    View details for Web of Science ID 000278167500023

    View details for PubMedID 19733013



    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

  • Commissioning and quality assurance for a respiratory training system based on audiovisual biofeedback JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS Cui, G., Gopalan, S., Yamamoto, T., Berger, J., Maxim, P. G., Keall, P. J. 2010; 11 (4): 42-56
  • Particle size, magnetic field, and blood velocity effects on particle retention in magnetic drug targeting MEDICAL PHYSICS Cherry, E. M., Maxim, P. G., Eaton, J. K. 2010; 37 (1): 175-182


    A physics-based model of a general magnetic drug targeting (MDT) system was developed with the goal of realizing the practical limitations of MDT when electromagnets are the source of the magnetic field.The simulation tracks magnetic particles subject to gravity, drag force, magnetic force, and hydrodynamic lift in specified flow fields and external magnetic field distributions. A model problem was analyzed to determine the effect of drug particle size, blood flow velocity, and magnetic field gradient strength on efficiency in holding particles stationary in a laminar Poiseuille flow modeling blood flow in a medium-sized artery.It was found that particle retention rate increased with increasing particle diameter and magnetic field gradient strength and decreased with increasing bulk flow velocity.The results suggest that MDT systems with electromagnets are unsuitable for use in small arteries because it is difficult to control particles smaller than about 20 microm in diameter.

    View details for DOI 10.1118/1.3271344

    View details for Web of Science ID 000273172100021

    View details for PubMedID 20175479

  • Commissioning and quality assurance for a respiratory training system based on audiovisual biofeedback. Journal of applied clinical medical physics Cui, G., Gopalan, S., Yamamoto, T., Berger, J., Maxim, P. G., Keall, P. J. 2010; 11 (4): 3262-?


    A respiratory training system based on audiovisual biofeedback has been implemented at our institution. It is intended to improve patients' respiratory regularity during four-dimensional (4D) computed tomography (CT) image acquisition. The purpose is to help eliminate the artifacts in 4D-CT images caused by irregular breathing, as well as improve delivery efficiency during treatment, where respiratory irregularity is a concern. This article describes the commissioning and quality assurance (QA) procedures developed for this peripheral respiratory training system, the Stanford Respiratory Training (START) system. Using the Varian real-time position management system for the respiratory signal input, the START software was commissioned and able to acquire sample respiratory traces, create a patient-specific guiding waveform, and generate audiovisual signals for improving respiratory regularity. Routine QA tests that include hardware maintenance, visual guiding-waveform creation, auditory sounds synchronization, and feedback assessment, have been developed for the START system. The QA procedures developed here for the START system could be easily adapted to other respiratory training systems based on audiovisual biofeedback.

    View details for PubMedID 21081883

  • 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


    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

  • Pancreatic Tumor Motion on a Single Planning 4D-CT Does Not Correlate With Intrafraction Tumor Motion During Treatment AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Minn, A. Y., Schellenberg, D., Maxim, P., Suh, Y., McKenna, S., Cox, B., Dieterich, S., Xing, L., Graves, E., Goodman, K. A., Chang, D., Koong, A. C. 2009; 32 (4): 364-368


    To quantify pancreas tumor motion on both a planning 4D-CT and during a single fraction treatment using the CyberKnife linear accelerator and Synchrony respiratory tracking software, and to investigate whether a single 4D-CT study is reliable for determining radiation treatment margins for patients with locally advanced pancreas cancer.Twenty patients underwent fiducial placement, biphasic pancreatic protocol CT scan and 4D-CT scan in the treatment position while free-breathing. Patients were then treated with a single 25 Gy fraction of stereotactic body radiotherapy. Predicted pancreas motion in the superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions was calculated from the maximum inspiration and maximum expiration 4D-CT scan. For CyberKnife treatments, mean respiratory cycle motion and maximum respiratory cycle motion was determined in the SI, LR, and AP directions.The range of centroid movement based on 4D-CT in the SI, LR, and AP directions were 0.9 to 28.8 mm, 0.1 to 13.7 mm, and 0.2 to 7.6 mm, respectively. During CyberKnife treatment, in the SI direction, the mean motion of the centroid ranged from 0.5 to 12.7 mm. In the LR direction, the mean motion range was 0.4 to 9.4 mm. In the AP direction, the mean motion range was 0.6 to 5.5 mm. The maximum range of movement (mean) during CyberKnife treatment in the SI, LR, and AP directions were 4.5 to 48.8 mm (mean 20.8 mm), 1.5 to 41.3 mm (mean 11.3 mm), and 1.6 to 68.1 mm (mean 13.4 mm), respectively. Neither the maximum or mean motion correlated with the 4D-CT movement.There is substantial respiratory associated motion of pancreatic tumors. The 4D-CT planning scans cannot accurately predict the movement of pancreatic tumors during actual treatment on CyberKnife.

    View details for DOI 10.1097/COC.0b013e31818da9e0

    View details for Web of Science ID 000268761600007

    View details for PubMedID 19398901

  • 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


    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


    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

  • Absence of ischemia in telangiectasias of chronic radiation proctopathy ENDOSCOPY Friedland, S., Benaron, D., Maxim, P., Parachikov, I., Soetikno, R. 2006; 38 (5): 488-492


    It has been postulated that chronic radiation proctopathy, clinically manifested by hematochezia and by the appearance of multiple telangiectasias, is caused by ischemia. This theory is based on reports that appeared in the 1980s which described obliterative endarteritis in patients with chronic radiation-induced ulcers. However, bleeding from radiation proctopathy is typically successfully treated endoscopically by widespread tissue coagulation, and the complications that would be expected to occur if the tissue was ischemic, such as poor wound healing, generally do not arise. We therefore hypothesized that the ischemia theory is incorrect and that rectal capillary oxygen saturation is normal in patients with telangiectasias of chronic radiation proctopathy.We developed a visible-light spectroscopy device that measures mucosal capillary hemoglobin oxygen saturation during endoscopy (having reported its operating characteristics previously). We prospectively studied 20 patients who had typical findings of multiple rectal telangiectasias, 1 - 20 years after undergoing external-beam irradiation for prostate or rectal carcinoma. We measured and compared the mucosal capillary oxygen saturations in the affected areas of the distal rectum and in endoscopically normal areas in the rectosigmoid colon.Mucosal oxygenation was normal in all 20 patients in affected areas (64 % - 80 %) and in unaffected areas (63 % - 75 %). The mean mucosal hemoglobin oxygen saturation was actually slightly higher in the affected areas of the rectum than in the uninvolved rectosigmoid colon (73 % vs. 69 %, P < 0.01).The common form of chronic radiation proctopathy, characterized by multiple telangiectasias without ulcers or strictures, is not associated with ongoing mucosal ischemia. This finding may explain why endoscopic treatment of this disorder, in which large areas of the mucosa are coagulated with argon plasma or other treatment modalities that cause widespread ulceration, does not typically result in complications from poor wound healing.

    View details for DOI 10.1055/s-2005-921175

    View details for Web of Science ID 000237922000009

    View details for PubMedID 16767584

  • 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


    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

  • Enhanced effectiveness of radiochemotherapy with tirapazamine by local application of electric pulses to tumors RADIATION RESEARCH Maxim, P. G., Carson, J. J., Ning, S. C., Knox, S. J., Boyer, A. L., Hsu, C. P., Benaron, D. A., Walleczek, J. 2004; 162 (2): 185-193


    Tumor hypoxia is associated with resistance to radiotherapy and anticancer chemotherapy. However, it can be exploited to therapeutic advantage by concomitantly using hypoxic cytotoxins, such as tirapazamine (TPZ). Tumor electroporation offers the means to further increase tumor hypoxia by temporarily reducing tumor blood flow and therefore increase the cytotoxicity of TPZ. The primary objective of this work was to determine whether electric pulses combined with TPZ and radiotherapy (electroradiochemotherapy) was more efficacious than radiochemotherapy (TPZ + radiation). In these studies using the SCCVII tumor model in C3H mice, electroradiochemotherapy produced up to sixfold more tumor growth delay (TGD) than TPZ + radiation. In these studies, (1) large tumors (280 +/- 15 mm3) responded better to electroradiochemotherapy than small tumors (110 +/- 10 mm3), (2) TGD correlated linearly with tumor volume at the time of electroradiochemotherapy, (3) electric pulses induced a rapid but reversible reduction in O2 saturation, and (4) the electric field was highest near the periphery of the tumor in a 3D computer model. The findings suggested that electroradiochemotherapy gained its therapeutic advantage over TPZ + radiation by enhancing the cytotoxic action of TPZ through reduced tumor oxygenation. The greater antitumor effect achieved in large tumors may be related to tumor morphology and the electric-field distribution. These results suggest that electro-pulsation of large solid tumors may be of benefit to patients treated with radiation in combination with agents that kill hypoxic cells.

    View details for Web of Science ID 000223159500011

    View details for PubMedID 15387146

  • Continuous, noninvasive, and localized microvascular tissue oximetry using visible light spectroscopy ANESTHESIOLOGY Benaron, D. A., Parachikov, I. H., Friedland, S., Soetikno, R., Brock-Utne, J., van der Starre, P. J., Nezhat, C., Terris, M. K., Maxim, P. G., Carson, J. J., Razavi, M. K., Gladstone, H. B., Fincher, E. F., Hsu, C. P., Clark, F. L., Cheong, W. F., Duckworth, J. L., Stevenson, D. K. 2004; 100 (6): 1469-1475


    The authors evaluated the ability of visible light spectroscopy (VLS) oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike near-infrared spectroscopy or pulse oximetry (SpO2), VLS tissue oximetry uses shallow-penetrating visible light to measure microvascular hemoglobin oxygen saturation (StO2) in small, thin tissue volumes.In pigs, StO2 was measured in muscle and enteric mucosa during normoxia, hypoxemia (SpO2 = 40-96%), and ischemia (occlusion, arrest). In patients, StO2 was measured in skin, muscle, and oral/enteric mucosa during normoxia, hypoxemia (SpO2 = 60-99%), and ischemia (occlusion, compression, ventricular fibrillation).In pigs, normoxic StO2 was 71 +/- 4% (mean +/- SD), without differences between sites, and decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31 +/- 11%; P < 0.001). In patients, mean normoxic StO2 ranged from 68 to 77% at different sites (733 measures, 111 subjects); for each noninvasive site except skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects; buccal, 77% +/- 3%, 21 subjects). During hypoxemia, StO2 correlated with SpO2 (animals, r2 = 0.98; humans, r2 = 0.87). During ischemia, StO2 initially decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r2 = 0.94). Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35% during ischemia).VLS oximetry provides a continuous, noninvasive, and localized measurement of the StO2, sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow StO2 normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.

    View details for Web of Science ID 000221551300018

    View details for PubMedID 15166566

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