Publications

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  • KEAP1/NFE2L2 mutations to predict local recurrence after radiotherapy but not surgery in localized non-small cell lung cancer. Binkley, M. S., Jeon, Y., Nesselbush, M., Moding, E. J., Nabet, B., Almanza, D. S., Yoo, C., Kurtz, D., Owen, S., Backhus, L., Berry, M. F., Shrager, J. B., Ramchandran, K., Padda, S., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2020
  • Stage I-II Nodular Lymphocyte-Predominant Hodgkin Lymphoma: a Multi-institutional Experience of Adult Patients by ILROG. Blood Binkley, M. S., Rauf, M. S., Milgrom, S. A., Pinnix, C. C., Tsang, R. W., Dickinson, M., Ng, A., Roberts, K. B., Gao, S., Balogh, A. G., Ricardi, U., Levis, M., Casulo, C., Stolten, M., Specht, L., Plastaras, J. P., Wright, C., Kelsey, C. R., Brady, J. L., Mikhaeel, N. G., Hoppe, B. S., Terezakis, S., Picardi, M., Della Pepa, R., Kirova, Y., Akhtar, S., Maghfoor, I., Koenig, J. L., Jackson, C., Song, E., Sehgal, S., Advani, R., Natkunam, Y., Constine, L. S., Eich, H. T., Wirth, A., Hoppe, R. T. 2020

    Abstract

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment for stage I-II NLPHL is undefined. We conducted a multi-center retrospective study including patients ?16 years with stage I-II NLPHL diagnosed from 1995-2018 receiving all forms of management including radiotherapy (RT), combined modality therapy (CMT=RT+chemotherapy), chemotherapy (CT), observation after excision, rituximab and RT, and single agent rituximab (R). End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age 39 years, 72.3% being male, and 54.9% having stage I disease. Median follow up was 5.5 years (IQR=3.1-10.1). 5-year PFS and OS for the entire cohort were 87.1% (95%CI=83.6-90.0%) and 98.3% (95%CI=96.4-99.2%), respectively. Primary management was RT alone (n=257, 46.0%), CMT (n=184, 32.9%), CT alone (n=47, 8.4%), observation (n=37, 6.6%), rituximab and RT (n=19, 3.4%), and rituximab alone (n=15, 2.7%). 5-year PFS rates were 91.1% (95%CI=85.3-94.7%) after RT, 90.5% (95%CI=84.8-94.1%) after CMT, 77.8% (95%CI=61.3-88.0%) after chemotherapy, 73.5% (95%CI=50.6-87.0%) after observation, 80.8% (95%CI=41.0-95.1%) after rituximab and RT, and 38.5% (95%CI=14.0-62.8%) after rituximab alone. For the RT cohort but not the CMT cohort, variant immunoarchitectural pattern and number of sites>2 were associated with worse PFS (P<0.05). Overall, 21 patients (3.8%) developed large cell transformation, with a significantly higher transformation rate for those with variant immunoarchitectural pattern (P=0.049) and number of involved sites >2 (P=0.0006). OS for patients with stage I-II NLPHLwas excellent following all managements.

    View details for DOI 10.1182/blood.2019003877

    View details for PubMedID 32211877

  • Predicting per-lesion local recurrence in locally advanced non-small cell lung cancer following definitive radiation therapy using pre- and mid-treatment metabolic tumor volume. Radiation oncology (London, England) Binkley, M. S., Koenig, J. L., Kashyap, M., Xiang, M., Liu, Y., Sodji, Q., Maxim, P. G., Diehn, M., Loo, B. W., Gensheimer, M. F. 2020; 15 (1): 114

    Abstract

    We evaluated whether pre- and mid-treatment metabolic tumor volume (MTV) predicts per lesion local recurrence (LR) in patients treated with definitive radiation therapy (RT, dose?60?Gy) for locally advanced non-small cell lung cancer (NSCLC).We retrospectively reviewed records of patients with stage III NSCLC treated from 2006 to 2018 with pre- and mid-RT PET-CT. We measured the MTV of treated lesions on the pre-RT (MTVpre) and mid-RT (MTVmid) PET-CT. LR was defined per lesion as recurrence within the planning target volume. Receiver operating characteristic (ROC) curves, cumulative incidence rates, and uni- and multivariable (MVA) competing risk regressions were used to evaluate the association between MTV and LR.We identified 111 patients with 387 lesions (112 lung tumors and 275 lymph nodes). Median age was 68?years, 69.4% were male, 46.8% had adenocarcinoma, 39.6% had squamous cell carcinoma, and 95.5% received concurrent chemotherapy. Median follow-up was 38.7?months. 3-year overall survival was 42.3%. 3-year cumulative incidence of LR was 26.8% per patient and 11.9% per lesion. Both MTVpre and MTVmid were predictive of LR by ROC (AUC?=?0.71 and 0.76, respectively) and were significantly associated with LR on MVA (P =?0.004 and P =?7.1e-5, respectively). Among lesions at lower risk of LR based on MTVpre, higher MTVmid was associated with LR (P =?0.001).Per-lesion, larger MTVpre and MTVmid predicted for increased risk of LR. MTVmid was more highly predictive of LR than MTVpre and if validated may allow for further discrimination of high-risk lesions at mid-RT informing dose painting strategies.

    View details for DOI 10.1186/s13014-020-01546-y

    View details for PubMedID 32429982

  • Salvage Treatment and Survival for Relapsed Follicular Lymphoma Following Primary Radiation Therapy: A Collaborative Study on Behalf of ILROG INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Brady, J. L., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A., Jones, M., Ahmed, S., MacManus, M., Wirth, A., Oguchi, M., Vistisen, A., Andraos, T., Ng, A. K., Aleman, B. P., Choi, S., Kirova, Y. M., Hardy, S., Reinartz, G., Eich, H. T., Bratman, S., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T. C., Hodgson, D. C., Ricardi, U., Yahalom, J., Mikhaeel, G., Hoppe, R. T. 2019; 104 (3): 522?29
  • Detection of Solid Tumor Molecular Residual Disease(MRD) Using Circulating Tumor DNA (ctDNA) MOLECULAR DIAGNOSIS & THERAPY Chin, R., Chen, K., Usmani, A., Chua, C., Harris, P. K., Binkley, M. S., Azad, T. D., Dudley, J. C., Chaudhuri, A. A. 2019; 23 (3): 311?31
  • Salvage treatment and survival for relapsed follicular lymphoma following primary radiotherapy: A collaborative study on behalf of ILROG. International journal of radiation oncology, biology, physics Binkley, M. S., Brady, J. L., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A. R., Jones, M., Ahmed, S., MacManus, M., Wirth, A., Oguchi, M., Vistisen, A. K., Andraos, T. Y., Ng, A., Aleman, B. M., Choi, S. H., Kirova, Y., Hardy, S., Reinartz, G., Eich, H., Bratman, S., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T., Hodgson, D., Ricardi, U., Yahalom, J., Mikhaeel, N. G., Hoppe, R. T. 2019

    Abstract

    PURPOSE/OBJECTIVE(S): We previously reported 30% of patients with localized follicular lymphoma (FL) staged by 18F-FDG-PET-CT (PET-CT) receiving primary radiotherapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed.MATERIALS/METHODS: We conducted a multicenter retrospective study of patients who received RT?24Gy for stage I-II FL grade 1-3A FL, with age?18 years, and PET-CT staging. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier, and uni- and multivariable analyses (MVA) with Cox regression.RESULTS: Of 512 patients with median follow up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median 23 months (range, 1-143) after primary RT. Median follow up was 33 months post relapse. 3-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ?12 months from date of diagnosis versus all others, 88.7% versus 95.8%, respectively (p=0.01), and remained significantly worse on MVA (FLIPI-adjusted HR=3.61, p=0.009). Histology at relapse included: 93 indolent (grade 1-3A), 3 FL grade 3B/NOS, 18 diffuse large B-cell lymphoma (DLBCL); 35 patients were not biopsied. Of those with follow up ?3 months and biopsied (n=74) or presumed (n=23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) RT, and 4 (4.1%) systemic therapy+RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n=59, including 20 initially observed) 3-year FFP was 73.9%.CONCLUSIONS: Prognosis for patients with relapsed FL following primary radiotherapy is excellent supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival to those with longer disease-free interval.

    View details for PubMedID 30858143

  • Definitive radiotherapy for localized follicular lymphoma staged by F-18-FDG PET-CT: a collaborative study by ILROG BLOOD Brady, J. L., Binkley, M. S., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A., Jones, M., Mac Manus, M., Wirth, A., Oguchi, M., Vistisen, A., Andraos, T., Ng, A. K., Aleman, B. P., Choi, S., Kirova, Y., Hardy, S., Reinartz, G., Eich, H. T., Bratman, S. V., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T. C., Hodgson, D. C., Ricardi, U., Yahalom, J., Hoppe, R. T., Mikhaeel, G. 2019; 133 (3): 237?45
  • Detection of Solid Tumor Molecular Residual Disease (MRD) Using Circulating Tumor DNA (ctDNA). Molecular diagnosis & therapy Chin, R. I., Chen, K., Usmani, A., Chua, C., Harris, P. K., Binkley, M. S., Azad, T. D., Dudley, J. C., Chaudhuri, A. A. 2019

    Abstract

    Circulating tumor DNA (ctDNA) is a component of cell-free DNA that is shed by malignant tumors into the bloodstream and other bodily fluids. Levels of ctDNA are typically low, particularly in patients with localized disease, requiring highly sophisticated methods for detection and quantification. Multiple liquid biopsy methods have been developed for ctDNA analysis in solid tumor malignancies and are now enabling detection and assessment of earlier stages of disease, post-treatment molecular residual disease (MRD), resistance to targeted systemic therapy, and tumor mutational burden. Understanding ctDNA biology, mechanisms of release, and clearance and size characteristics, in conjunction with the application of molecular barcoding and targeted error correction, have increased the sensitivity and specificity of ctDNA detection techniques. Combinatorial approaches including integration of ctDNA data with circulating protein biomarkers may further improve assay sensitivity and broaden the scope of ctDNA applications. Circulating viral DNA may be utilized to monitor disease in some virally induced malignancies. In spite of increasingly accurate methods of ctDNA detection, results need to be interpreted with caution given that somatic mosaicisms such as clonal hematopoiesis of indeterminate potential (CHIP) may give rise to genetic variants in the bloodstream unrelated to solid tumors, and the limited concordance observed between different commercial platforms. Overall, highly precise ctDNA detection and quantification methods have the potential to transform clinical practice via non-invasive monitoring of solid tumor malignancies, residual disease detection at earlier timepoints than standard clinical and/or imaging surveillance, and treatment personalization based on real-time assessment of the tumor genomic landscape.

    View details for PubMedID 30941670

  • Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG. Blood Brady, J. L., Binkley, M. S., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A. R., Jones, M., Mac Manus, M., Wirth, A., Oguchi, M., Krog Vistisen, A., Andraos, T. Y., Ng, A. K., Aleman, B. M., Choi, S. H., Kirova, Y., Hardy, S., Reinartz, G., Eich, H. T., Bratman, S. V., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T. C., Hodgson, D. C., Ricardi, U., Yahalom, J., Hoppe, R. T., Mikhaeel, N. G. 2018

    Abstract

    Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40-50%. As 18F-FDG PET-CT upstages 10-60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study. Inclusion criteria were: RT alone for untreated stage I-II FL (grade 1-3A) with dose equivalent ?24 Gy, staged by PET-CT, age ?18 years, and follow up ?3 months. Endpoints were freedom from progression (FFP), local control, and overall survival (OS). FFP and OS were estimated with Kaplan-Meier, and uni- and multivariable analyses of prognostic factors performed with Cox Regression. 512 patients treated from 2000-2017 at 16 centres were eligible for analysis. Median age was 58 years (range 20-90). 410 patients (80.1%) had stage I disease. Median RT dose was 30 Gy (24-52). Median follow up was 52 months (3.2-174.6). 5y-FFP and OS were 68.9% and 95.7%. For stage I, 5y-FFP was 74.1%, vs 49.1% for stage II (p<0.0001). 8 patients relapsed infield (1.6%).4 had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (HR=2.11, 95%CI=1.44-3.10) and BCL2 expression (HR =1.62, 95%CI 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

    View details for PubMedID 30446493

  • F-18-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Qian, Y., Von Eyben, R., Liu, Y., Chin, F. T., Miao, Z., Apte, S., Carter, J. N., Binkley, M. S., Pollom, E. L., Harris, J. P., Prionas, N. D., Kissel, M., Simmons, A., Diehn, M., Shultz, D. B., Brown, J., Maxim, P. G., Koong, A. C., Graves, E. E., Loo Jr, B. W. 2018; 102 (4): 1183?92
  • 18F-EF5 Pet-Based Imageable Hypoxia Predicts for Local Control in Tumors Treated With Conformal Radiotherapy Qian, Y., Liu, Y., Von Eyben, R., Carter, J. N., Pollom, E. L., Harris, J. P., Prionas, N. D., Binkley, M. S., Simmons, A., Diehn, M., Chin, F. T., Shultz, D. B., Brown, J., Maxim, P. G., Koong, A. C., Graves, E. E., Loo, B. W. ELSEVIER SCIENCE INC. 2018: E17?E18
  • 18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy. International journal of radiation oncology, biology, physics Qian, Y., Von Eyben, R., Liu, Y., Chin, F. T., Miao, Z., Apte, S., Carter, J. N., Binkley, M. S., Pollom, E. L., Harris, J. P., Prionas, N. D., Kissel, M., Simmons, A., Diehn, M., Shultz, D. B., Brown, J. M., Maxim, P. G., Koong, A. C., Graves, E. E., Loo, B. W. 2018

    Abstract

    Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18F-pentafluorinated etanidazole (18F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18F-EF5 PET with clinical outcomes after radiation therapy remains limited.Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18F-EF5 PET imaging. Depending on the level of 18F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18F-EF5 uptake than the 95th percentile of 18F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ? 10% on baseline 18F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment.At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P < .01).Noninvasive hypoxia imaging by 18F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation therapy was higher in tumors with imageable hypoxia.

    View details for PubMedID 29859786

  • Circulating Tumor DNA Detects Residual Disease and Anticipates Tumor Progression Earlier Than CT Imaging Chaudhuri, A. A., Chabon, J. J., Lovejoy, A. F., Newman, A. M., Stehr, H., Azad, T. D., Zhou, L., Liu, C., Scherer, F., Kurtz, D. M., Esfahani, M. S., Say, C., Carter, J. N., Merriott, D., Dudley, J., Binkley, M. S., Modlin, L., Padda, S. K., Gensheimer, M., West, R. B., Shrager, J. B., Neal, J. W., Wakelee, H. A., Billy, W., Alizadeh, A. A., Diehn, M. ELSEVIER SCIENCE INC. 2017: E4
  • Pulmonary function after lung tumor stereotactic ablative radiotherapy depends on regional ventilation within irradiated lung. Radiotherapy and oncology Binkley, M. S., King, M. T., Shrager, J. B., Bush, K., Chaudhuri, A. A., Popat, R., Gensheimer, M. F., Maxim, P. G., Henry Guo, H., Diehn, M., Nair, V. S., Loo, B. W. 2017; 123 (2): 270-275

    Abstract

    To determine if regional ventilation within irradiated lung volume predicts change in pulmonary function test (PFT) measurements after stereotactic ablative radiotherapy (SABR) of lung tumors.We retrospectively identified 27 patients treated from 2007 to 2014 at our institution who received: (1) SABR without prior thoracic radiation; (2) pre-treatment 4-dimensional computed tomography (4-D CT) imaging; (3) pre- and post-SABR PFTs <15months from treatment. We defined the ventilation ratio (VR20BED3) as the quotient of mean ventilation (mean Jacobian-based per-voxel volume change on deformably registered inhale/exhale 4-D CT phases) within the 20Gy biologically effective dose (?/?=3Gy) isodose volume and that of the total lung volume (TLV).Most patients had moderate to very severe COPD by GOLD criteria (n=19, 70.1%). Higher VR20BED3 significantly predicted worse change in Forced Expiratory Volume/s normalized by baseline value (?FEV1/FEV1pre, p=0.04); n=7 had VR20BED3>1 (high regional ventilation) and worse ?FEV1/FEV1pre (median=-0.16, range=-0.230 to -0.20). Five had VR20BED3<1 (low regional ventilation) and improved ?FEV1/FEV1pre (median=0.13, range=0.07 to 0.20). In a multivariable linear model, increasing VR20BED3 and time to post-SABR PFT predicted decreasing ?FEV1/FEV1pre (R(2)=0.25, p=0.03).After SABR to high versus low functioning lung regions, we found worsened or improved global pulmonary function, respectively. If pre-SABR VR20BED3 is validated as a predictor of eventual post-SABR PFT in larger studies, it may be used for individualized treatment planning to preserve or even improve pulmonary function after SABR.

    View details for DOI 10.1016/j.radonc.2017.03.021

    View details for PubMedID 28460826

  • Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer discovery Chaudhuri, A. A., Chabon, J. J., Lovejoy, A. F., Newman, A. M., Stehr, H., Azad, T. D., Khodadoust, M. S., Esfahani, M. S., Liu, C. L., Zhou, L., Scherer, F., Kurtz, D. M., Say, C., Carter, J. N., Merriott, D. J., Dudley, J. C., Binkley, M. S., Modlin, L., Padda, S. K., Gensheimer, M. F., West, R. B., Shrager, J. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Alizadeh, A. A., Diehn, M. 2017

    Abstract

    Identifying molecular residual disease (MRD) after treatment of localized lung cancer could facilitate early intervention and personalization of adjuvant therapies. Here we apply Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) circulating tumor DNA (ctDNA) analysis to 255 samples from 40 patients treated with curative intent for stage I-III lung cancer and 54 healthy adults. In 94% of evaluable patients experiencing recurrence, ctDNA was detectable in the first post-treatment blood sample, indicating reliable identification of MRD. Post-treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months and 53% of patients harbored ctDNA mutation profiles associated with favorable responses to tyrosine kinase inhibitors or immune checkpoint blockade. Collectively, these results indicate that ctDNA MRD in lung cancer patients can be accurately detected using CAPP-Seq and may allow personalized adjuvant treatment while disease burden is lowest.

    View details for PubMedID 28899864

  • Partial orbit irradiation achieves excellent outcomes for primary orbital lymphoma. Practical radiation oncology Binkley, M. S., Hiniker, S. M., Donaldson, S. S., Hoppe, R. T. 2016; 6 (4): 255-261

    Abstract

    Primary radiation therapy (RT) achieves excellent local control and overall survival when treating localized orbital lymphoma. However, evidence supporting irradiation of partial orbit volumes to spare nearby critical structures is lacking. We sought to investigate outcomes for patients with localized orbital lymphoma treated with partial orbit irradiation.We retrospectively reviewed patients with orbital lymphoma treated with RT at our institution who met our inclusion criteria: biopsy-confirmed, low-grade lymphoma, localized disease, partial orbit treatment volumes, and follow-up >3months. The Kaplan-Meier method was used to measure overall survival (OS), and the cumulative incidence function adjusted for the competing risk of death was used to measure local failure (LF), contralateral orbit recurrence (COR), and progression. Patient characteristics were compared with outcomes using Fisher exact test for dichotomous variables and Wilcoxon rank-sum test for continuous variables.Thirty-two patients meeting inclusion criteria were identified with median follow-up of 45.8months (range, 3.6-171.9). The majority had stage IEA disease; their sites included conjunctiva (n=20) and retrobulbar or lacrimal gland (n=12). Median partial orbit RT dose was 30.6Gy (range, 22.5-36). Five-year OS was 100%. Five-year cumulative incidence of LF, COR, and overall disease progression was 5.3%, 5.9%, and 21.4%, respectively. Five-year cumulative incidence of LF was 8.3% for conjunctival disease versus 0.0% for retrobulbar or lacrimal gland involvement (P=.15). No significant association was observed between the outcomes of LF, COR, or progression and pretreatment characteristics. Acute and late toxicity included grade 2 periorbital edema (n=3, 9.4%), dry eye (n=3, 9.4%), retinal vascular disorder (n=1, 3.1%), conjunctivitis (n=2, 6.3%), and grade 3 cataract (n=1, 3.1%).Use of partial orbit irradiation in treating low-grade, localized orbital lymphoma achieves excellent survival with low rates of LF, COR, or progression.

    View details for DOI 10.1016/j.prro.2015.11.013

    View details for PubMedID 26935235

  • Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR). Radiotherapy and oncology Chaudhuri, A. A., Binkley, M. S., Rigdon, J., Carter, J. N., Aggarwal, S., Dudley, S. A., Qian, Y., Kumar, K. A., Hara, W. Y., Gensheimer, M., Nair, V. S., Maxim, P. G., Shultz, D. B., Bush, K., Trakul, N., Le, Q., Diehn, M., Loo, B. W., Guo, H. H. 2016; 119 (3): 454-460

    Abstract

    To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR).We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade ? 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake.Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001).Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.

    View details for DOI 10.1016/j.radonc.2016.05.007

    View details for PubMedID 27267049

  • Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

    Abstract

    Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using ?/? = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

    View details for DOI 10.1016/j.semradonc.2015.11.008

    View details for Web of Science ID 000373242700003

  • Tracheal Diverticulum Following Paratracheal Hypofractionated Radiotherapy in the Setting of Prior and Subsequent Bevacizumab CUREUS Chaudhuri, A. A., Chen, J., Carter, J. N., Binkley, M. S., Kumar, K. A., Dudley, S. A., Sung, A. W., Loo, B. W. 2016; 8 (4)

    View details for DOI 10.7759/cureus.578

    View details for Web of Science ID 000453611400028

  • Dosimetric Factors and Toxicity in Highly Conformal Thoracic Reirradiation. International journal of radiation oncology, biology, physics Binkley, M. S., Hiniker, S. M., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W., Shultz, D. B. 2016; 94 (4): 808-815

    Abstract

    We determined cumulative dose to critical structures, rates of toxicity, and outcomes following thoracic reirradiation.We retrospectively reviewed our institutional database for patients treated between 2008 and 2014, who received thoracic reirradiation with overlap of 25% prescribed isodose lines. Patients received courses of hyperfractionated (n=5), hypofractionated (n=5), conventionally fractionated (n=21), or stereotactic ablative radiation therapy (n=51). Doses to critical structures were converted to biologically effective dose, expressed as 2 Gy per fraction equivalent dose (EQD2; ?/? = 2 for spinal cord; ?/? = 3 for other critical structures).We identified 82 courses (44 for retreatment) in 38 patients reirradiated at a median 16 months (range: 1-71 months) following initial RT. Median follow-up was 17 months (range: 3-57 months). Twelve- and 24-month overall survival rates were 79.6% and 57.3%, respectively. Eighteen patients received reirradiation for locoregionally recurrent non-small cell lung cancer with 12-month rates of local failure and regional recurrence and distant metastases rates of 13.5%, 8.1%, and 15.6%, respectively. Critical structures receiving ?75 Gy EQD2 included spinal cord (1 cm(3); n=1), esophagus (1 cm(3); n=10), trachea (1 cm(3); n=11), heart (1 cm(3); n=9), aorta (1 cm(3); n=16), superior vena cava (1 cm(3); n=12), brachial plexus (0.2 cm(3); n=2), vagus nerve (0.2 cm(3); n=7), sympathetic trunk (0.2 cm(3); n=4), chest wall (30 cm(3); n=12), and proximal bronchial tree (1 cm(3); n=17). Cumulative dose-volume (D cm(3)) toxicity following reirradiation data included esophagitis grade ?2 (n=3, D1 cm(3) range: 41.0-100.6 Gy), chest wall grade ?2 (n=4; D30 cm(3) range: 35.0-117.2 Gy), lung grade 2 (n=7; V20combined-lung range: 4.7%-21.7%), vocal cord paralysis (n=2; vagus nerve D0.2 cm(3) range: 207.5-302.2 Gy), brachial plexopathy (n=1; D0.2 cm(3) = 242.5 Gy), and Horner's syndrome (n=1; sympathetic trunk D0.2 cm(3) = 130.8 Gy). No grade ?4 toxicity was observed.Overlapping courses of reirradiation can be safely delivered with acceptable toxicity. Some toxicities occurred acutely at doses considered safe for a single course of therapy (esophagus). We observed rib fracture, brachial plexopathy, and Horner's syndrome for patients receiving high cumulative doses to corresponding critical structures.

    View details for DOI 10.1016/j.ijrobp.2015.12.007

    View details for PubMedID 26831903

  • Time course and predictive factors for lung volume reduction following stereotactic ablative radiotherapy (SABR) of lung tumors RADIATION ONCOLOGY Binkley, M. S., Shrager, J. B., Chaudhuri, A., Popat, R., Maxim, P. G., Shultz, D. B., Diehn, M., Loo, B. W. 2016; 11

    Abstract

    Stereotactic ablative volume reduction (SAVR) is a potential alternative to lung-volume reduction surgery in patients with severe emphysema and excessive surgical risk. Having previously observed a dose-volume response for localized lobar volume reduction after stereotactic ablative radiotherapy (SABR) for lung tumors, we investigated the time course and factors associated with volume reduction.We retrospectively identified 70 eligible patients receiving lung tumor SABR during 2007-2013. We correlated lobar volume reduction (relative to total, bilateral lung volume [TLV]) with volume receiving high biologically effective doses (VXXBED3) and other pre-treatment factors in all patients, and measured the time course of volume changes on 3-month interval CT scans in patients with large V60BED3 (n?=?21, V60BED3 ?4.1 % TLV).Median CT follow-up was 15 months. Median volume reduction of treated lobes was 4.5 % of TLV (range 0.01-13.0 %), or ~9 % of ipsilateral lung volume (ILV); median expansion of non-target adjacent lobes was 2.2 % TLV (-4.6-9.9 %; ~4 % ILV). Treated lobe volume reduction was significantly greater with larger VXXBED3 (XX?=?20-100 Gy, R (2) ?=?0.52-0.55, p?

    View details for DOI 10.1186/s13014-016-0616-8

    View details for Web of Science ID 000372776500001

    View details for PubMedCentralID PMC4791793

  • A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy LEUKEMIA & LYMPHOMA Binkley, M. S., Hiniker, S. M., Wu, S., Natkunam, Y., Mittra, E. S., Advani, R. H., Hoppe, R. T. 2016; 57 (3): 604-608

    Abstract

    As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes.

    View details for DOI 10.3109/10428194.2015.1067700

    View details for Web of Science ID 000372499800016

  • A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy. Leukemia & lymphoma Binkley, M. S., Hiniker, S. M., Wu, S., Natkunam, Y., Mittra, E. S., Advani, R. H., Hoppe, R. T. 2016; 57 (3): 604-608

    Abstract

    As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes.

    View details for DOI 10.3109/10428194.2015.1067700

    View details for PubMedID 26159046

  • Severe Chest Wall Toxicity From Cryoablation in the Setting of Prior Stereotactic Ablative Radiotherapy CUREUS Chaudhuri, A. A., Binkley, M. S., Aggarwal, S., Qian, Y., Carter, J. N., Shah, R., Loo, B. W. 2016; 8 (2)

    View details for DOI 10.7759/cureus.477

    View details for Web of Science ID 000453610500005

  • Severe Chest Wall Toxicity From Cryoablation in the Setting of Prior Stereotactic Ablative Radiotherapy. Cure¯us Chaudhuri, A. A., Binkley, M. S., Aggarwal, S., Qian, Y., Carter, J. N., Shah, R., Loo, B. W. 2016; 8 (2)

    Abstract

    We present the case of a 42-year-old woman with metastatic synovial sarcoma of parotid origin, treated definitively with chemoradiation, who subsequently developed oligometastatic disease limited to the lungs. She underwent multiple left and right lung wedge resections and left lower lobectomy, followed by right lower lobe stereotactic ablative radiotherapy (SABR), 54 Gy in three fractions to a right lower lobe lesion abutting the chest wall. Two years later, she was treated with cryoablation for a separate right upper lobe nodule abutting the chest wall. Two months later, she presented with acute shortness of breath, pleuritic chest pain, decreased peripheral blood O2 saturation, and productive cough. A computed tomography (CT) scan demonstrated severe chest wall necrosis in the area of recent cryoablation that, in retrospect, also received a significant radiation dose from her prior SABR. This case demonstrates that clinicians should exercise caution in using cryoablation when treating lung tumors abutting a previously irradiated chest wall. Note: Drs. Loo and Shah contributed equally as co-senior authors.

    View details for DOI 10.7759/cureus.477

    View details for PubMedID 27004154

    View details for PubMedCentralID PMC4780688

  • Tracheal Diverticulum Following Paratracheal Hypofractionated Radiotherapy in the Setting of Prior and Subsequent Bevacizumab. Cure¯us Chaudhuri, A. A., Chen, J. J., Carter, J. N., Binkley, M. S., Kumar, K. A., Dudley, S. A., Sung, A. W., Loo, B. W. 2016; 8 (4)

    Abstract

    We present the case of a 63-year-old woman with limited metastatic colorectal cancer to the lungs and liver treated with FOLFIRI-bevacizumab, followed by consolidative hypofractionated radiotherapy to right paratracheal metastatic lymphadenopathy. We treated the right paratracheal site with 60 Gy in 15 fractions (70 Gy equivalent dose in 2 Gy fractions). The patient tolerated the treatment well, and six months later started a five-month course of FOLFIRI-bevacizumab for new metastatic disease. She presented to our clinic six months after completing this, complaining of productive cough with scant hemoptysis, and was found to have localized tracheal wall breakdown and diverticulum in the region of prior high-dose radiation therapy, threatening to progress to catastrophic tracheovascular fistula. This was successfully repaired surgically after a lack of response to conservative measures. We urge caution in treating patients with vascular endothelial growth factor (VEGF) inhibitors in the setting of hypofractionated radiotherapy involving the mucosa of tubular organs, even when these treatments are separated by months. Though data is limited as to the impact of sequence, this may be particularly an issue when VEGF inhibitors follow prior radiotherapy.

    View details for DOI 10.7759/cureus.578

    View details for PubMedID 27226939

  • Time course and predictive factors for lung volume reduction following stereotactic ablative radiotherapy (SABR) of lung tumors. Radiation oncology Binkley, M. S., Shrager, J. B., Chaudhuri, A., Popat, R., Maxim, P. G., Shultz, D. B., Diehn, M., Loo, B. W. 2016; 11 (1): 40-?

    Abstract

    Stereotactic ablative volume reduction (SAVR) is a potential alternative to lung-volume reduction surgery in patients with severe emphysema and excessive surgical risk. Having previously observed a dose-volume response for localized lobar volume reduction after stereotactic ablative radiotherapy (SABR) for lung tumors, we investigated the time course and factors associated with volume reduction.We retrospectively identified 70 eligible patients receiving lung tumor SABR during 2007-2013. We correlated lobar volume reduction (relative to total, bilateral lung volume [TLV]) with volume receiving high biologically effective doses (VXXBED3) and other pre-treatment factors in all patients, and measured the time course of volume changes on 3-month interval CT scans in patients with large V60BED3 (n?=?21, V60BED3 ?4.1 % TLV).Median CT follow-up was 15 months. Median volume reduction of treated lobes was 4.5 % of TLV (range 0.01-13.0 %), or ~9 % of ipsilateral lung volume (ILV); median expansion of non-target adjacent lobes was 2.2 % TLV (-4.6-9.9 %; ~4 % ILV). Treated lobe volume reduction was significantly greater with larger VXXBED3 (XX?=?20-100 Gy, R (2) ?=?0.52-0.55, p?

    View details for DOI 10.1186/s13014-016-0616-8

    View details for PubMedID 26975700

  • Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery. Seminars in radiation oncology Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97?104

    Abstract

    Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using ?/? = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

    View details for PubMedID 27000505

  • Predicting Radiotherapy Responses and Treatment Outcomes Through Analysis of Circulating Tumor DNA. Seminars in radiation oncology Chaudhuri, A. A., Binkley, M. S., Osmundson, E. C., Alizadeh, A. A., Diehn, M. 2015; 25 (4): 305-312

    Abstract

    Tumors continually shed DNA into the blood where it can be detected as circulating tumor DNA (ctDNA). Although this phenomenon has been recognized for decades, techniques that are sensitive and specific enough to robustly detect ctDNA have only become available recently. Quantification of ctDNA represents a new approach for cancer detection and disease burden quantification that has the potential to revolutionize response assessment and personalized treatment in radiation oncology. Analysis of ctDNA has many potential applications, including detection of minimal residual disease following radiotherapy, noninvasive tumor genotyping, and early detection of tumor recurrence. Ultimately, ctDNA-based assays could lead to personalization of therapy based on identification of somatic alterations present in tumors and changes in ctDNA concentrations before and after treatment. In this review, we discuss methods of ctDNA detection and clinical applications of ctDNA-based biomarkers in radiation oncology, with a focus on recently developed techniques that use next-generation sequencing for ctDNA quantification.

    View details for DOI 10.1016/j.semradonc.2015.05.001

    View details for PubMedID 26384278

    View details for PubMedCentralID PMC4575502

  • Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Trakul, N., Jacobs, L. R., von Eyben, R., Quynh-Thu Le, Q. T., Maxim, P. G., Loo, B. W., Shultz, D. B., Diehn, M. 2015; 92 (5): 1044-1052

    Abstract

    Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes.We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses.We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at ?/? = 10 (BED10) of <100 Gy versus BED10 of ?100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed.SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.

    View details for DOI 10.1016/j.ijrobp.2015.04.004

    View details for Web of Science ID 000357900600024

    View details for PubMedID 26025776

  • Stereotactic ablative radiotherapy (SABR) for treatment of central and ultra-central lung tumors LUNG CANCER Chaudhuri, A. A., Tang, C., Binkley, M. S., Jin, M., Wynne, J. F., von Eyben, R., Hara, W. Y., Trakul, N., Loo, B. W., Diehn, M. 2015; 89 (1): 50-56

    Abstract

    Treatment of central and ultra-central lung tumors with stereotactic ablative radiotherapy (SABR) remains controversial due to risks of treatment-related toxicities compared with peripheral tumors. Here we report our institution's experience in treating central and ultra-central lung tumor patients with SABR.We retrospectively reviewed outcomes in 68 patients with single lung tumors, 34 central and 34 peripheral, all treated with SABR consisting of 50 Gy in 4-5 fractions. Tumor centrality was defined per the RTOG 0813 protocol. We defined "ultra-central" tumors as those with GTV directly abutting the central airway.Median follow-up time was 18.4 months and median overall survival was 38.1 months. Two-year overall survival was similar between ultra-central, central, and peripheral NSCLC (80.0% vs. 63.2% vs. 86.6%, P=0.62), as was 2-year local failure (0% vs. 10.0% vs. 16.3%, P=0.64). Toxicity rates were low and comparable between the three groups, with only two cases of grade 3 toxicity (chest wall pain), and one case of grade 4 toxicity (pneumonitis) observed. Patients with ultra-central tumors experienced no symptomatic toxicities over a median follow-up time of 23.6 months. Dosimetric analysis revealed that RTOG 0813 central airway dose constraints were frequently not achieved in central tumor treatment plans, but this did not correlate with increased toxicity rate.Patients with central and ultra-central lung tumors treated with SABR (50 Gy in 4-5 fractions) experienced few toxicities and good outcomes, similar to patients with peripheral lung tumors.

    View details for DOI 10.1016/j.lungcan.2015.04.014

    View details for Web of Science ID 000356546300010

    View details for PubMedID 25997421

  • Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

    Abstract

    Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema.We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ?6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, ?/? = 3).27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ?3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, -0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, -3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ?60 Gy (r(2)=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r(2)=0.47, P<.0001).We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.

    View details for DOI 10.1016/j.ijrobp.2014.05.025

    View details for Web of Science ID 000341456500029

  • Lung volume reduction after stereotactic ablative radiation therapy of lung tumors: potential application to emphysema. International journal of radiation oncology, biology, physics Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

    Abstract

    Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema.We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ?6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, ?/? = 3).27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ?3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, -0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, -3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ?60 Gy (r(2)=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r(2)=0.47, P<.0001).We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.

    View details for DOI 10.1016/j.ijrobp.2014.05.025

    View details for PubMedID 25015205

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