Publications by authors named "Jean-Claude M Rwigema"

44 Publications

Initial Experience with Proton Beam Therapy for Differentiated Thyroid Cancer.

Int J Part Ther 2021 25;8(1):311-318. Epub 2021 Jun 25.

Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA.

Purpose: External beam radiotherapy is used in a subset of high-risk patients with differentiated thyroid cancer (DTC). Recurrent, radioactive iodine (RAI)-refractory DTC carries a poor prognosis. We report our initial experience of intensity-modulated proton therapy (IMPT) for recurrent, RAI-refractory DTC.

Patients And Methods: Fourteen patients with recurrent, RAI-refractory DTC were consecutively treated with IMPT from November 2016 to March 2020 at our multisite institution. Patient, tumor, and treatment characteristics were recorded. Overall survival and local-regional recurrence-free survival were recorded and estimated using the Kaplan-Meier method. Acute and late treatment-related toxicities were recorded based on the Common Terminology Criteria for Adverse Events version 5.0. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module at baseline and after IMPT. Eleven patients were included in the final analysis.

Results: Median follow-up was 8 months (range, 3-40) for all patients. Median age at treatment with IMPT was 64 years (range, 40-77), and the majority were men (64%). Recurrent histologies included papillary (55%), Hurthle cell (36%), and poorly differentiated (9%) carcinoma; 1 patient had tall cell variant. Concurrent chemotherapy was not administered for any patient in this cohort. At 8 months, all patients were alive without local-regional failure. Acute grade 3 toxicities were limited to 1 patient with dysphagia, requiring feeding tube placement. Two patients experienced late grade 3 esophageal stenosis requiring dilation. There were no grade 4 or 5 toxicities. There were no differences in pretreatment versus posttreatment patient-reported outcomes in terms of dysphagia or hoarseness.

Conclusion: In our early experience, IMPT provided promising local-regional control for recurrent, RAI-refractory DTC. Further study is warranted to evaluate the long-term efficacy and safety of IMPT in this patient population.
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http://dx.doi.org/10.14338/IJPT-D-20-00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270099PMC
June 2021

Oncologic Outcomes for Head and Neck Skin Malignancies Treated with Protons.

Int J Part Ther 2021 25;8(1):294-303. Epub 2021 Jun 25.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: Radiation therapy (RT) is the standard treatment for patients with inoperable skin malignancies of the head and neck region (H&N), and as adjuvant treatment post surgery in patients at high risk for local or regional recurrence. This study reports clinical outcomes of intensity-modulated proton therapy (IMPT) for these malignancies.

Materials And Methods: We retrospectively reviewed cases involving 47 patients with H&N malignancies of the skin (squamous cell, basal cell, melanoma, Merkel cell, angiosarcoma, other) who underwent IMPT for curative intent between July 2016 and July 2019. Overall survival was estimated via Kaplan-Meier analysis, and oncologic outcomes were reported as cumulative incidence with death as a competing risk.

Results: The 2-year estimated local recurrence rate, regional recurrence rate, local regional recurrence rate, distant metastasis rate, and overall survival were 11.1% (95% confidence interval [CI], 4.1%-30.3%), 4.4% (95% CI, 1.1%-17.4%), 15.5% (95% CI, 7%-34.3%), 23.4% (95% CI, 5.8%-95.5%), and 87.2% (95% CI, 75.7%-100%), respectively. No patient was reported to have a grade 3 or higher adverse event during the last week of treatment or at the 3-month follow-up visit.

Conclusion: IMPT is safe and effective in the treatment of skin malignancies of the H&N.
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http://dx.doi.org/10.14338/IJPT-20-00045.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270091PMC
June 2021

A Systematic Review on Re-irradiation with Charged Particle Beam Therapy in the Management of Locally Recurrent Skull Base and Head and Neck Tumors.

Int J Part Ther 2021 25;8(1):131-154. Epub 2021 Jun 25.

Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA.

Purpose: To evaluate the clinical outcomes and treatment related toxicities of charged particle-based re-irradiation (reRT; protons and carbon ions) for the definitive management of recurrent or second primary skull base and head and neck tumors.

Materials And Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied for the conduct of this systematic review. Published work in English language evaluating the role of definitive charged particle therapies in the clinical setting of reRT for recurrent or second primary skull base and head and neck tumors were eligible for this analysis.

Results: A total of 26 original studies (15 protons, 10 carbon ions, and 1 helium/neon studies) involving a total of 1,118 patients (437 with protons, 670 with carbon ions, and 11 with helium/neon) treated with curative-intent charged particle reRT were included in this systematic review. All studies were retrospective in nature, and the majority of them (n=23, 88 %) were reported as single institution experiences (87% for protons, and 90% for carbon ion-based studies). The median proton therapy reRT dose was 64.5 Gy (RBE 1.1) (range, 50.0 - 75.6 Gy ), while the median carbon ion reRT dose was 53.8 Gy (RBE 2.5 - 3.0) (range, 44.8 - 60 Gy ). Induction and/or concurrent chemotherapy was administered to 232 (53%) of the patients that received a course of proton reRT, and 122 (18%) for carbon ion reRT patients. ReRT with protons achieved 2-year local control rates ranging from 50% to 86%, and 41% to 92% for carbon ion reRT. The 2-year overall survival rates for proton and carbon ion reRT ranged from 33% to 80%, and 50% to 86% respectively. Late ≥ G3 toxicities ranged from 0% to 37%, with brain necrosis, ototoxicity, visual deficits, and bleeding as the most common complications. Grade 5 toxicities for all treated patients occurred in 1.4% (n= 16/1118) with fatal bleeding as the leading cause.

Conclusions: Based on current data, curative intent skull base and head and neck reRT with charged particle radiotherapy is feasible and safe in well-selected cases, associated with comparable or potentially improved local control and toxicity rates compared to historical reRT studies using photon radiotherapy. Prospective multi-institutional studies reporting oncologic outcomes, toxicity, and dosimetric treatment planning data are warranted to further validate these findings and to improve the understanding of the clinical benefits of charged particle radiotherapy in the reRT setting.
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http://dx.doi.org/10.14338/IJPT-20-00064.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270105PMC
June 2021

Exploratory Investigation of Dose-Linear Energy Transfer (LET) Volume Histogram (DLVH) for Adverse Events Study in Intensity Modulated Proton Therapy (IMPT).

Int J Radiat Oncol Biol Phys 2021 07 20;110(4):1189-1199. Epub 2021 Feb 20.

Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona. Electronic address:

Purpose: We proposed a novel tool-a dose linear energy transfer (LET)-volume histogram (DLVH)-and performed an exploratory study to investigate rectal bleeding in prostate cancer treated with intensity modulated proton therapy.

Methods And Materials: The DLVH was constructed with dose and LET as 2 axes, and the normalized volume of the structure was contoured in the dose-LET plane as isovolume lines. We defined the DLVH index, DLv%(d,l) (ie, v% of the structure) to have a dose of ≥d Gy and an LET of ≥l keV/μm, similar to the dose-volume histogram index Dv%. Nine patients with prostate cancer with rectal bleeding (Common Terminology Criteria for Adverse Events grade ≥2) were included as the adverse event group, and 48 patients with no complications were considered the control group. A P value map was constructed by comparison of the DLVH indices of all patients between the 2 groups using the Mann-Whitney U test. Dose-LET volume constraints (DLVCs) were derived based on the P value map with a manual selection procedure facilitated by Spearman's correlation tests. The obtained DLVCs were further cross-validated using a multivariate support vector machine (SVM)-based normal tissue complication probability (NTCP) model with an independent testing data set composed of 8 adverse event and 13 control patients.

Results: We extracted 2 DLVC constraints. One DLVC was obtained, Vdose/LETboundary:2.5keVμmat 75 Gy to 3.2keVμmat8.65Gy <1.27% (DLVC1), revealing a high LET volume effect. The second DLVC, V(72.2Gy,0keVμm) < 2.23% (DVLC2), revealed a high dose volume effect. The SVM-based NTCP model with 2 DLVCs provided slightly superior performance than using dose only, with an area under the curve of 0.798 versus 0.779 for the testing data set.

Conclusions: Our results demonstrated the importance of rectal "hot spots" in both high LET (DLVC1) and high dose (DLVC2) in inducing rectal bleeding. The SVM-based NTCP model confirmed the derived DLVCs as good predictors for rectal bleeding when intensity modulated proton therapy is used to treat prostate cancer.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.024DOI Listing
July 2021

The Importance of Verification CT-QA Scans in Patients Treated with IMPT for Head and Neck Cancers.

Int J Part Ther 2020 3;7(1):41-53. Epub 2020 Aug 3.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: To understand how verification computed tomography-quality assurance (CT-QA) scans influenced clinical decision-making to replan patients with head and neck cancer and identify predictors for replanning to guide intensity-modulated proton therapy (IMPT) clinical practice.

Patients And Methods: We performed a quality-improvement study by prospectively collecting data on 160 consecutive patients with head and neck cancer treated using spot-scanning IMPT who underwent weekly verification CT-QA scans. Kaplan-Meier estimates were used to determine the cumulative probability of a replan by week. Predictors for replanning were determined with univariate (UVA) and multivariate (MVA) Cox model hazard ratios (HRs). Logistic regression was used to determine odds ratios (ORs).  < .05 was considered statistically significant.

Results: Of the 160 patients, 79 (49.4%) had verification CT-QA scans, which prompted a replan. The cumulative probability of a replan by week 1 was 13.7% (95% confidence interval [CI], 8.82-18.9), week 2, 25.0% (95% CI, 18.0-31.4), week 3, 33.1% (95% CI, 25.4-40.0), week 4, 45.6% (95% CI, 37.3-52.8), and week 5 and 6, 49.4% (95% CI, 41.0-56.6). Predictors for replanning were sinonasal disease site (UVA: HR, 1.82,  = .04; MVA: HR, 3.64,  = .03), advanced stage disease (UVA: HR, 4.68,  < .01; MVA: HR, 3.10,  < .05), dose > 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99,  < .01; MVA: HR, 2.20,  < .01), primary disease (UVA: HR, 2.00 versus recurrent,  = .01; MVA: HR, 2.46,  = .01), concurrent chemotherapy (UVA: HR, 2.05,  < .01; MVA: not statistically significant [NS]), definitive intent treatment (UVA: HR, 1.70 versus adjuvant,  < .02; MVA: NS), bilateral neck treatment (UVA: HR, 2.07,  = .03; MVA: NS), and greater number of beams (5 beam UVA: HR, 5.55 versus 1 or 2 beams,  < .02; MVA: NS). Maximal weight change from baseline was associated with higher odds of a replan (≥3 kg: OR, 1.97,  = .04; ≥ 5 kg: OR, 2.13,  = .02).

Conclusions: Weekly verification CT-QA scans frequently influenced clinical decision-making to replan. Additional studies that evaluate the practice of monitoring IMPT-treated patients with weekly CT-QA scans and whether that improves clinical outcomes are warranted.
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http://dx.doi.org/10.14338/IJPT-20-00006.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574830PMC
August 2020

Early Outcomes of Patients With Locally Advanced Non-small Cell Lung Cancer Treated With Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiation Therapy: The Mayo Clinic Experience.

Adv Radiat Oncol 2020 May-Jun;5(3):450-458. Epub 2019 Aug 21.

Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona.

Purpose: There are very little data available comparing outcomes of intensity-modulated proton therapy (IMPT) to intensity-modulated radiation therapy (IMRT) in patients with locally advanced NSCLC (LA-NSCLC).

Methods: Seventy-nine consecutively treated patients with LA-NSCLC underwent definitive IMPT ( = 33 [42%]) or IMRT ( = 46 [58%]) from 2016 to 2018 at our institution. Survival rates were calculated using the Kaplan-Meier method and compared with the log-rank test. Acute and subacute toxicities were graded based on Common Terminology Criteria for Adverse Events, version 4.03.

Results: Median follow-up was 10.5 months (range, 1-27) for all surviving patients. Most were stage III (80%), received median radiation therapy (RT) dose of 60 Gy (range, 45-72), and had concurrent chemotherapy (65%). At baseline, the IMPT cohort was older (76 vs 69 years,  < .01), were more likely to be oxygen-dependent (18 vs 2%,  = .02), and more often received reirradiation (27 vs 9%,  = .04) than their IMRT counterparts. At 1 year, the IMPT and IMRT cohorts had similar overall survival (68 vs 65%,  = .87), freedom from distant metastasis (71 vs 68%,  = .58), and freedom from locoregional recurrence (86 vs 69%,  = .11), respectively. On multivariate analyses, poorer pulmonary function and older age were associated with grade +3 toxicities during and 3 months after RT, respectively (both  ≤ .02). Only 5 (15%) IMPT and 4 (9%) IMRT patients experienced grade 3 or 4 toxicities 3 months after RT ( = .47). There was 1 treatment-related death from radiation pneumonitis 6 months after IMRT in a patient with idiopathic pulmonary fibrosis.

Conclusions: Compared with IMRT, our early experience suggests that IMPT resulted in similar outcomes in a frailer population of LA-NSCLC who were more often being reirradiated. The role of IMPT remains to be defined prospectively.
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http://dx.doi.org/10.1016/j.adro.2019.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276663PMC
August 2019

N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial.

Mayo Clin Proc 2019 09 9;94(9):1814-1824. Epub 2019 Aug 9.

Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, AZ. Electronic address:

Objective: To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy.

Patients And Methods: We designed a prospective pilot double-blind, placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%.

Results: Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall.

Conclusion: Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required.

Trial Registration: clinicaltrials.gov Identifier: NCT02123511.
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http://dx.doi.org/10.1016/j.mayocp.2019.03.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742495PMC
September 2019

A Model-Based Approach to Predict Short-Term Toxicity Benefits With Proton Therapy for Oropharyngeal Cancer.

Int J Radiat Oncol Biol Phys 2019 07 6;104(3):553-562. Epub 2019 Jan 6.

Perelman School of Medicine, University of Pennsylvania, Department of Radiation Oncology, Philadelphia, Pennsylvania. Electronic address:

Purpose: The aim of this study was to generate normal tissue complication probability (NTCP) models in patients treated with either proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) for oropharynx cancer and to use a model-based approach to investigate the added value of PBT in preventing treatment complications.

Methods And Materials: For patients with advanced-stage oropharynx cancer treated with curative intent (PBT, n = 30; IMRT, n = 175), NTCP models were developed using multivariable logistic regression analysis with backward selection. For PBT-treated patients, an equivalent IMRT plan was generated to serve as a reference to determine the benefit of PBT in terms of NTCP. The models were then applied to the PBT-treated patients to compare predicted and observed clinical outcomes (calibration-in-the-large). Five binary endpoints were analyzed at 6 months after treatment: dysphagia ≥ grade 2, dysphagia ≥ grade 3, xerostomia ≥ grade 2, salivary duct inflammation ≥ grade 2, and feeding tube dependence. Corresponding toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4. Paired t tests and Wilcoxon rank tests were used to compare mean NTCP results for endpoints between PBT and IMRT.

Results: NTCP models developed based on outcomes from all patients were applied to those receiving PBT. NTCP values were calculated for the equivalent IMRT plans for all PBT-treated patients, revealing significantly higher NTCP values with IMRT. PBT was associated with statistically significant reductions in the mean NTCP values for each endpoint at 6 months after treatment, with the largest absolute differences in rates of ≥grade 2 dysphagia and ≥grade 2 xerostomia.

Conclusions: NTCP models predict significant improvements in the probability of short-term, treatment-related toxicity with PBT compared with IMRT for oropharyngeal cancer. This study demonstrates an NTCP model-based approach to compare predicted patient outcomes when randomized data are not available.
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http://dx.doi.org/10.1016/j.ijrobp.2018.12.055DOI Listing
July 2019

Treatment outcomes of squamous cell carcinoma of the oral cavity in young adults.

Oral Oncol 2018 12 22;87:43-48. Epub 2018 Oct 22.

Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, AZ, United States. Electronic address:

Objectives: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger.

Materials And Methods: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts.

Results: Median patient age was 35 years (range, 19-40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001).

Conclusion: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.
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http://dx.doi.org/10.1016/j.oraloncology.2018.10.014DOI Listing
December 2018

Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221): A Pilot Double-Blind Randomized Trial.

Int J Radiat Oncol Biol Phys 2019 03 2;103(3):686-696. Epub 2018 Nov 2.

Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida.

Purpose: Chemoradiation (CRT) is an integral treatment modality for patients with locally advanced lung cancer. It has been hypothesized that current use of an angiotensin-converting enzyme inhibitor during CRT may be protective for treatment-related lung damage and pneumonitis.

Methods And Materials: We conducted a pilot, double-blind, placebo-controlled, randomized trial. Study-eligible patients receiving curative thoracic radiation therapy (RT) were randomly assigned to 20 mg of lisinopril or placebo once daily during and up to 3 months after RT. All patients received concurrent chemotherapy. The primary endpoint was adverse event profiling. Multiple patient-reported outcome (PRO) surveys, including the Lung Cancer Symptom Scale, Function Assessment of Cancer Therapy-Lung, and the European Organisation for Research and Treatment of Cancer Lung Cancer Questionnaire, were applied with a symptom experience questionnaire. Exploratory comparative statistics were used to detect differences between arms with χ and Kruskal-Wallis testing.

Results: Five institutions enrolled 23 patients. However, accrual was less than expected. Eleven and 12 patients were in the placebo and lisinopril arms, respectively (mean age, 63.5 years; male, 62%). Baseline characteristics were balanced. Eighteen patients (86%) were former or current smokers. The primary endpoint was met; neither arm had grade 3 or higher hypotension, acute kidney injury, allergic reaction (medication-induced cough), or anaphylaxis (medication-related angioedema). Few PRO measures suggested that compared with the placebo arm, patients receiving lisinopril had less cough, less shortness of breath, fewer symptoms from lung cancer, less dyspnea with both walking and climbing stairs, and better overall quality of life (for all, P < .05).

Conclusions: Although underpowered because of low accrual, our results suggest that there was a clinical signal for safety-and possibly beneficial by limited PRO measures-in concurrently administering lisinopril during thoracic CRT to mitigate or prevent RT-induced pulmonary distress. Our results showed that a definitive, larger-scale, randomized phase 3 trial is needed in the future.
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http://dx.doi.org/10.1016/j.ijrobp.2018.10.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431240PMC
March 2019

Dosimetric comparison of advanced radiotherapy approaches using photon techniques and particle therapy in the postoperative management of thymoma.

Acta Oncol 2018 12 28;57(12):1713-1720. Epub 2018 Sep 28.

a Department of Radiation Oncology , Heidelberg University Hospital , Heidelberg , Germany.

Background: The purpose of this study was to compare dosimetric differences related to target volume and organs-at-risk (OAR) using 3D-conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), TomoTherapy (Tomo), proton radiotherapy (PRT), and carbon ion radiotherapy (CIRT) as part of postoperative thymoma irradiation.

Material And Methods: This single-institutional analysis included 10 consecutive patients treated with adjuvant radiotherapy between December 2013 and September 2016. CT-datasets and respective RT-structures were anonymized and plans for all investigated RT modalities (3DCRT, VMAT, Tomo, PRT, CIRT) were optimized for a total dose of 50 Gy in 25 fractions. Comparisons between target volume and OAR dosimetric parameters were performed using the Wilcoxon rank-sum test.

Results: The best target volume coverage (mean PTV V for all patients) was observed for Tomo (97.9%), PRT (97.6%), and CIRT (96.6%) followed by VMAT (85.4%) and 3DCRT (74.7%). PRT and CIRT both significantly reduced mean doses to the lungs, breasts, heart, and esophagus, as well as the spinal cord maximum dose compared with photon modalities. Among photon-based techniques, VMAT showed improved OAR sparing over 3DCRT. Tomo was associated with considerable low-dose exposure to the lungs, breasts, and heart.

Conclusions: Particle radiotherapy (PRT, CIRT) showed superior OAR sparing and optimal target volume coverage. The observed dosimetric advantages are expected to reduce toxicity rates. However, their clinical impact must be investigated prospectively.
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http://dx.doi.org/10.1080/0284186X.2018.1502467DOI Listing
December 2018

Systematic assessment of clinical outcomes and toxicities of proton radiotherapy for reirradiation.

Radiother Oncol 2017 10 20;125(1):21-30. Epub 2017 Sep 20.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, USA. Electronic address:

Reirradiation (reRT) for locoregional recurrences poses unique challenges and risks; re-treatment using proton beam radiotherapy (PBT) could prove advantageous. Assessing clinical outcomes and toxicity profiles, this systematic review comprehensively evaluated available evidence regarding PBT reRT. Fourteen original investigations across central nervous system (CNS) (n=6), head/neck (H&N) (n=4), lung (n=2), and gastrointestinal (n=2) malignancies were analyzed. PBT for recurrent uveal melanoma achieved 5-year eye retention of 55%; for chordomas, reRT afforded a 2-year local control and overall survival (OS) of 85% and 80%, respectively. Multiple PBT reRT studies for adult gliomas illustrate no grade ≥3 toxicities. Two pediatric CNS tumor studies demonstrated the safety and efficacy of reRT, with one total grade 3 toxicity and achievement of longer-term OS. PBT for H&N malignancies shows appropriate local/locoregional control and favorable toxicity profiles versus historical photon-based methods, including low (9-10%) rates of feeding tube placement. PBT for recurrent lung cancer can achieve favorable survival with expected toxicities/complications of reRT, especially with concurrent chemotherapy and centrally located recurrences. Lastly, PBT reRT in gastrointestinal malignancies induced very few high-grade complications. Hence, based on the limited existing data, PBT is a notably safe reRT modality for effective salvage of recurrent disease. Institutional experiences must continue to be reported: dosimetric correlations, late toxicities, and advanced PBT techniques.
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http://dx.doi.org/10.1016/j.radonc.2017.08.005DOI Listing
October 2017

Predictors of prolongation in radiation treatment time in a veteran population treated with chemoradiation for oropharyngeal cancer.

Acta Otolaryngol 2018 Jan 12;138(1):80-84. Epub 2017 Sep 12.

c Department of Radiation Oncology , UCLA David Geffen School of Medicine , Los Angeles , CA , USA.

Background: Prolonged radiation treatment time (RTT) is associated with worse tumor control. Here we identify and determine the implications of factors that predict treatment prolongation in Veterans Affairs (VA) patients undergoing chemoradiation.

Methods: Chart review from July 2000 to October 2013. 81 patients with advanced stage oropharyngeal cancer treated with chemoradiation.

Results: Twenty-nine patients (35.8%) had RTT prolonged by ≥10 days. Prolongation mainly resulted from acute treatment toxicity (n = 22, 76%). There was no significant difference in RTT for patients treated with concurrent cisplatin versus cetuximab, or in patients treated with or without induction chemotherapy. One-/three-year locoregional control and overall survival rates of 83.4%/76.3% and 83.5%/63.6% for patients without prolonged RTT versus 61.8%/61.8% and 82.8%/73.8% for those with prolongation (p >.05).

Conclusions: Prolonged RTT is a significant predictor of worse locoregional control and predominantly resulted from treatment side effects. More aggressive regimens with induction and concurrent chemotherapy did not predispose to prolonged RTT.
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http://dx.doi.org/10.1080/00016489.2017.1371331DOI Listing
January 2018

Prospective study of proton-beam radiation therapy for limited-stage small cell lung cancer.

Cancer 2017 Nov 5;123(21):4244-4251. Epub 2017 Jul 5.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland.

Background: Existing data supporting the use of proton-beam therapy (PBT) for limited-stage small cell lung cancer (LS-SCLC) are limited to a single 6-patient case series. This is the first prospective study to evaluate clinical outcomes and toxicities of PBT for LS-SCLC.

Methods: This study prospectively analyzed patients with primary, nonrecurrent LS-SCLC definitively treated with PBT and concurrent chemotherapy from 2011 to 2016. Clinical backup intensity-modulated radiotherapy (IMRT) plans were generated for each patient and were compared with PBT plans. Outcome measures included local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates and toxicities.

Results: Thirty consecutive patients were enrolled and evaluated. The median dose was 63.9 cobalt gray equivalents (range, 45-66.6 cobalt gray equivalents) in 33 to 37 fractions delivered daily (n = 18 [60.0%]) or twice daily (n = 12 [40.0%]). The concurrent chemotherapy was cisplatin/etoposide (n = 21 [70.0%]) or carboplatin/etoposide (n = 9 [30.0%]). In comparison with the backup IMRT plans, PBT allowed statistically significant reductions in the cord, heart, and lung mean doses and the volume receiving at least 5 Gy but not in the esophagus mean dose or the lung volume receiving at least 20 Gy. At a median follow-up of 14 months, the 1-/2-year LC and RFS rates were 85%/69% and 63%/42%, respectively. The median OS was 28.2 months, and the 1-/2-year OS rates were 72%/58%. There was 1 case each (3.3%) of grade 3 or higher esophagitis, pneumonitis, anorexia, and pericardial effusion. Grade 2 pneumonitis and esophagitis were seen in 10.0% and 43.3% of patients, respectively.

Conclusions: In the first prospective registry study and largest analysis to date of PBT for LS-SCLC, PBT was found to be safe with a limited incidence of high-grade toxicities. Cancer 2017;123:4244-4251. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30870DOI Listing
November 2017

Re-Irradiation Therapy for Locally Recurrent Head and Neck Cancer: A National Survey of Practice Patterns.

Cancer Invest 2017 Jul 24;35(6):393-402. Epub 2017 Apr 24.

a Department of Radiation Oncology, David Geffen School of Medicine , University of California Los Angeles , Los Angeles , CA , USA.

Using a customized survey consisting of two de-identified clinical scenarios with a total of 86 questions, we showed that substantial variability exists regarding recommendations for therapy of recurrent head and neck cancer. For inoperable gross recurrence arising in a previously irradiated field, recommendations were re-irradiation with curative intent (73%), re-irradiation with palliative intent (4%), chemotherapy alone (5%), and referral to tertiary center (18%). After salvage surgery, only 33% recommended adjuvant re-irradiation, with the remainder preferring observation (46%), chemotherapy alone (10%), and referral to tertiary center (11%). Significant differences were observed with respect to dose, fractionation, technique, and systemic therapy recommendations.
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http://dx.doi.org/10.1080/07357907.2017.1310222DOI Listing
July 2017

Enrollment of Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer in Multi-institutional Trials of Proton Beam Radiation Therapy.

Clin Lung Cancer 2017 09 16;18(5):441-443. Epub 2017 Mar 16.

Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD. Electronic address:

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http://dx.doi.org/10.1016/j.cllc.2017.03.007DOI Listing
September 2017

Discord Among Radiation Oncologists and Urologists in the Postoperative Management of High-Risk Prostate Cancer.

Am J Clin Oncol 2018 08;41(8):739-746

Departments of Radiation Oncology.

Objective: To query specialty-specific differences regarding postoperative radiotherapy (RT) for high-risk prostate cancer.

Materials And Methods: Electronic mail survey of radiation oncologists (ROs) and urologists. We sought to maximize absolute response number to capture contemporary practice ethos. The outcome of interest was association between response and specialty. Training level/expertise, practice setting, percentage of consultation caseload consisting of high-risk prostate cancer, and nationality were set as effect modifiers for multivariate logistic regression.

Results: In total, 846 ROs and 407 urologists responded. ROs were more likely to prefer adjuvant radiotherapy (ART). ART or early salvage radiotherapy (SRT, with early SRT defined as that delivered at prostate-specific antigen<0.2), whereas urologists were more likely to prefer early or delayed SRT (P<0.0001). ROs were more likely to prefer lower PSA thresholds for initiating SRT (P<0.0001), and more likely to recommend ART in the setting of adverse pathologic features or node-positive disease (P<0.0001). Significantly more ROs would recommend concurrent androgen deprivation therapy or pelvic nodal RT in the setting of node-positive or Gleason score 8 to 10 disease (P<0.0001).

Conclusions: Specialty-specific differences were readily elucidated with respect to timing and indications for ART and SRT, as well as for indications for androgen deprivation therapy and nodal RT. These differences are likely to create a sense of dissonance for patients, which may in turn explain the underutilization of postoperative RT in general practice.
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http://dx.doi.org/10.1097/COC.0000000000000381DOI Listing
August 2018

Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer?

Am J Clin Oncol 2018 06;41(6):549-557

Departments of Radiation Oncology.

Objective: The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence.

Methods: A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers.

Results: One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005).

Conclusions: Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias.
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http://dx.doi.org/10.1097/COC.0000000000000323DOI Listing
June 2018

Cost-comparativeness of proton versus photon therapy.

Chin Clin Oncol 2016 Aug 27;5(4):56. Epub 2016 Jul 27.

Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Proton beam radiotherapy (PBT) offers great promise in the treatment of a wide variety of cancers owing to the sharp drop-off in radiation dose at a defined point, known as the Bragg peak, beyond which there is no appreciable dose. However, it is also well-understood that PBT is associated with large economic costs, including both capital investment and operating costs. From a medical as well as societal perspective, therefore, it is important to be aware of the economic implications of new technologies such as PBT, and to evaluate the cost effectiveness based on different clinical and treatment scenarios. This review examines PBT from a health economics perspective, evaluating both the design and results of costeffectiveness (CE) studies that have been performed previously. We further examine several salient variables that can affect CE of PBT, including patient, tumor, treatment, and logistical factors. We discuss the implication of technological advances on PBT delivery, and its impact on overall healthcare delivery costs. Additionally, we evaluate the status of economic analyses for PBT and discuss the role of ongoing and future CE studies in better defining the economic role of PBT as part of modern cancer therapy.
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http://dx.doi.org/10.21037/cco.2016.06.03DOI Listing
August 2016

Is staging mediastinoscopy necessary before stereotactic body radiotherapy for inoperable early stage lung cancer?

J Thorac Dis 2015 Dec;7(12):E612-4

Department of Radiation Oncology, University of California, Los Angeles, CA 90095, USA.

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http://dx.doi.org/10.3978/j.issn.2072-1439.2015.12.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703637PMC
December 2015

A treatment planning comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based stereotactic body radiotherapy for central early-stage non-small cell lung cancer.

Med Dosim 2016 2;41(1):87-91. Epub 2016 Jan 2.

Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address:

We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early-stage non-small cell lung cancer with a tri-cobalt-60 (tri-(60)Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)-based SBRT. In all, 20 patients with large central early-stage non-small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-(60)Co system for a prescription dose of 50Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R100 values were calculated as the total tissue volume receiving 100% of the dose (V100) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-(60)Co SBRT plans were performed using Student׳s t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3cc (range: 12.1 to 139.4cc). Of the tri-(60)Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R100 values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-(60)Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-(60)Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while improving normal tissue sparing, which warrants further investigation in a prospective feasibility clinical trial.
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http://dx.doi.org/10.1016/j.meddos.2015.09.002DOI Listing
December 2016

Feasibility of magnetic resonance imaging-guided liver stereotactic body radiation therapy: A comparison between modulated tri-cobalt-60 teletherapy and linear accelerator-based intensity modulated radiation therapy.

Pract Radiat Oncol 2015 Sep-Oct;5(5):330-337. Epub 2015 Mar 29.

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: The purpose of this study was to investigate the dosimetric feasibility of liver stereotactic body radiation therapy (SBRT) using a teletherapy system equipped with 3 rotating (60)Co sources (tri-(60)Co system) and a built-in magnetic resonance imager (MRI). We hypothesized tumor size and location would be predictive of favorable dosimetry with tri-(60)Co SBRT.

Methods And Materials: The primary study population consisted of 11 patients treated with SBRT for malignant hepatic lesions whose linear accelerator (LINAC)-based SBRT plans met all mandatory Radiation Therapy Oncology Group (RTOG) 1112 organ-at-risk (OAR) constraints. The secondary study population included 5 additional patients whose plans did not meet the mandatory constraints. Patients received 36 to 60 Gy in 3 to 5 fractions. Tri-(60)Co system SBRT plans were planned with ViewRay system software.

Results: All patients in the primary study population had tri-(60)Co SBRT plans that passed all RTOG constraints, with similar planning target volume coverage and OAR doses to LINAC plans. Mean liver doses and V10Gy to the liver, although easily meeting RTOG 1112 guidelines, were significantly higher with tri-(60)Co plans. When the 5 additional patients were included in a univariate analysis, the tri-(60)Co SBRT plans were still equally able to pass RTOG constraints, although they did have inferior ability to pass more stringent liver and kidney constraints (P < .05). A multivariate analysis found the ability of a tri-(60)Co SBRT plan to meet these constraints depended on lesion location and size. Patients with smaller or more peripheral lesions (as defined by distance from the aorta, chest wall, liver dome, and relative lesion volume) were significantly more likely to have tri-(60)Co plans that spared the liver and kidney as well as LINAC plans did (P < .05).

Conclusions: It is dosimetrically feasible to perform liver SBRT with a tri-(60)Co system with a built-in MRI. Patients with smaller or more peripheral lesions are more likely to have optimal liver and kidney sparing, with the added benefit of MRI guidance, when receiving tri-(60)Co-based SBRT.
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http://dx.doi.org/10.1016/j.prro.2015.02.014DOI Listing
June 2016

4π noncoplanar stereotactic body radiation therapy for head-and-neck cancer: potential to improve tumor control and late toxicity.

Int J Radiat Oncol Biol Phys 2015 Feb 5;91(2):401-9. Epub 2014 Dec 5.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California. Electronic address:

Purpose: To evaluate the potential benefit of 4π radiation therapy in recurrent, locally advanced, or metastatic head-and-neck cancer treated with stereotactic body radiation therapy (SBRT).

Methods And Materials: Twenty-seven patients with 29 tumors who were treated using SBRT were included. In recurrent disease (n=26), SBRT was delivered with a median 44 Gy (range, 35-44 Gy) in 5 fractions. Three patients with sinonasal mucosal melanoma, metastatic breast cancer, and primary undifferentiated carcinoma received 35 Gy, 22.5 Gy, and 40 Gy in 5 fractions, respectively. Novel 4π treatment plans were created for each patient to meet the objective that 95% of the planning target volume was covered by 100% of the prescription dose. Doses to organs at risk (OARs) and 50% dose spillage volumes were compared against the delivered clinical SBRT plans. Local control (LC), late toxicity, tumor control probability (TCP), and normal tissue complication probability were determined.

Results: Using 4π plans, mean/maximum doses to all OARs were reduced by 22% to 89%/10% to 86%. With 4π plans, the 50% dose spillage volume was decreased by 33%. Planning target volume prescription dose escalation by 10 Gy and 20 Gy were achieved while keeping doses to OARs significantly improved or unchanged from clinical plans, except for the carotid artery maximum dose at 20-Gy escalation. At a median follow-up of 10 months (range, 1-41 months), crude LC was 52%. The 2-year LC of 39.2% approximated the predicted mean TCP of 42.2%, which increased to 45.9% with 4π plans. For 10-Gy and 20-Gy dose escalation, 4π plans increased TCP from 80.1% and 88.1% to 85.5% and 91.4%, respectively. The 7.4% rate of grade ≥3 late toxicity was comparable to the predicted 5.6% mean normal tissue complication probability for OARs, which was significantly reduced by 4π planning at the prescribed and escalated doses.

Conclusions: 4π plans may allow dose escalation with significant and consistent improvements in critical organ sparing, tumor control, and coverage.
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http://dx.doi.org/10.1016/j.ijrobp.2014.09.043DOI Listing
February 2015

Stereotactic body radiation therapy for abdominal and pelvic oligometastases: Dosimetric targets for safe and effective local control.

Pract Radiat Oncol 2015 May-Jun;5(3):e183-e191. Epub 2014 Oct 24.

Department of Radiation Oncology, UCLA Medical Center, Los Angeles, California. Electronic address:

Purpose: To investigate correlates and predictors of outcomes of stereotactic body radiation therapy (SBRT) for patients with abdominal and pelvic oligometastases from different primary tumors.

Methods And Materials: We evaluated outcomes of 38 consecutive patients with 44 unresectable nodal and soft-tissue oligometastases in the abdominal pelvic region who were treated with SBRT between November 2008 and April 2014. Thirty-two patients had solitary lesions and 6 patients had 2 lesions. The median prescription dose was 40 Gy (24-50 Gy) delivered in 4-5 fractions. The median gross tumor volume was 18.7 mL (0.7-194.1 mL). We evaluated tumor response, local control (LC), and overall survival (OS) rates as well as acute and chronic toxicities.

Results: At a median follow-up of 19 months (0.9-53.4 months), tumor responses were: complete response 31.8%, partial response 38.6%, standard deviation 20.5%, and progressive disease 9.1%. The overall 1- to 2-year LC and OS rates were 100%/75.1% (95% confidence interval [CI], 54.4%-88.4%) and 95.2% (95% CI, 82.8%-98.8%)/88.9% (95% CI, 68.1%-95.1%), respectively. On univariate analysis, increasing SBRT dose, smaller gross tumor volume, and asymptomatic lesions were associated with improved LC (P = .01, P<.001, and P = .01, respectively). On multivariate analysis, advanced original primary disease stage predicted for worse OS (P = .001). One patient developed a colovesicular fistula at 20.9 months in the setting of local tumor progression with a volume of bowel receiving 20 Gy (V(20Gy)) = 26.9 mL. The overall mean bowel V(20Gy) achieved was 16 ± 22.9 mL. Another patient had grade 2 proctitis at 13 months after SBRT. Pain relief was achieved in 81.8% of patients with symptomatic lesions (N = 11).

Conclusions: Our results suggest that SBRT doses 40-50 Gy in 5 fractions (biological effective dose 72-100 Gy10) with bowel V(20Gy) ≤20 mL are efficacious and associated with minimal toxicity for abdominal pelvic nodal and soft-tissue oligometastases. Palliation of symptoms is achievable in most patients with symptomatic lesions. SBRT for oligometastases may be a good alternative to systemic therapy in selected patients.
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http://dx.doi.org/10.1016/j.prro.2014.09.006DOI Listing
April 2016

Feasibility of extreme dose escalation for glioblastoma multiforme using 4π radiotherapy.

Radiat Oncol 2014 Nov 7;9:239. Epub 2014 Nov 7.

Department of Radiation Oncology, University of California, Los Angeles, 200 Medical Plaza Way, Suite B265, Los Angeles, USA.

Background: Glioblastoma multiforme (GBM) frequently recurs at the same location after radiotherapy. Further dose escalation using conventional methods is limited by normal tissue tolerance. 4π non-coplanar radiotherapy has recently emerged as a new potential method to deliver highly conformal radiation dose using the C-arm linacs. We aim to study the feasibility of very substantial GBM dose escalation while maintaining normal tissue tolerance using 4π.

Methods: 11 GBM patients previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the NovalisTx™ platform to a prescription dose of either 59.4 Gy or 60 Gy were included. All patients were replanned with 30 non-coplanar beams using a 4π radiotherapy platform, which inverse optimizes both beam angles and fluence maps. Four different prescriptions were used including original prescription dose and PTV (4πPTVPD), 100 Gy to the PTV and GTV (4πPTV100Gy), 100 Gy to the GTV only while maintaining prescription dose to the rest of the PTV (4πGTV100Gy), and a 5 mm margin expansion plan (4πPTVPD+5mm). OARs included in the study are the normal brain (brain - PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical nerves, and cochleae.

Results: The 4π plans resulted in superior dose gradient indices, as indicated by >20% reduction in the R50, compared to the clinical plans. Among all of the 4π cases, when compared to the clinical plans, the maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01-98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non-brain OARs. Both the 4πPTVPD and 4π GTV100GYplans reduced the mean normal brain mean doses.

Conclusions: 4π non-coplanar radiotherapy substantially increases the dose gradient outside of the PTV and better spares critical organs. Dose escalation to 100 Gy to the GTV or additional margin expansion while meeting clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in higher normal brain doses but may be tolerated when delivered in proportionally increased treatment fractions. Therefore, 4π non-coplanar radiotherapy on C-arm gantry may provide an accessible tool to improve the outcome of GBM radiotherapy through extreme dose escalation.
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http://dx.doi.org/10.1186/s13014-014-0239-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230756PMC
November 2014

Incidental mediastinal dose does not explain low mediastinal node recurrence rates in patients with early-stage NSCLC treated with stereotactic body radiotherapy.

Clin Lung Cancer 2014 Jul 4;15(4):287-93. Epub 2014 Feb 4.

Department of Radiation Oncology, Ronald Reagan UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address:

Background: Patients with stage I non-small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) do not undergo a staging mediastinoscopy, yet reported mediastinal recurrence rates appear lower than in patients undergoing surgical resection. We determined incidental SBRT doses to assess whether this could account for the low rates of recurrence.

Patients And Methods: Between March 2009 and September 2012, we reviewed cases of patients with inoperable lung tumors (n = 136) treated with SBRT at our institution. The SBRT regimen was 54 Gy in 3 fractions with positron emission tomography/computed tomography (PET/CT) staging. Incidental doses to the mediastinal lymph node stations (MLNSs), primary tumor control, locoregional (LR), distant control (DC), and overall survival (OS) rates were determined.

Results: Forty-six patients with stage I NSCLC met the inclusion criteria. The calculated median incidental SBRT dose to all MLNSs was < 5 Gy for the majority of patients (75%). At a median follow-up of 16.8 months (0.6-38.9 months), the 1- and 2-year primary tumor control, LR, OS, and DC rates were 100% and 95.5%, 97.4% and 81.7%, 88.1% and 81%, and 96.9% and 86.9%, respectively. Only 2 patients (4.9%) had mediastinal recurrence, with incidental SBRT doses to MLNSs that were similar to the rest of patients (P > .05).

Conclusion: Low mediastinal recurrence rates in stage I NSCLC treated with SBRT validates the omission of staging mediastinoscopy. The low incidental dose to MLNSs does not seem to explain the low mediastinal recurrence in the majority of patients. Our findings also confirm that prophylactic radiation to the mediastinum is not necessary and support the hypothesis that local ablation of the primary lesion could indirectly affect subclinical nodal disease through unknown mechanisms.
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http://dx.doi.org/10.1016/j.cllc.2014.01.004DOI Listing
July 2014

Examining tumor control and toxicity after stereotactic body radiotherapy in locally recurrent previously irradiated head and neck cancers: implications of treatment duration and tumor volume.

Head Neck 2014 Sep 13;36(9):1349-55. Epub 2014 Jan 13.

Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

Background: Stereotactic body radiotherapy (SBRT) has been studied in locally recurrent previously-irradiated head and neck cancers; however, the optimum fractionation and patient selection continues to be defined.

Methods: Patients (n = 132) with locally recurrent head and neck cancer salvaged via SBRT ± cetuximab (median, 44 Gy/5 fractions) from November 2004 to May 2011 were retrospectively reviewed. Disease outcomes and toxicity were analyzed by predictive factors including treatment duration and tumor volume.

Results: At a median 6-month follow-up (range, 0-55 months), treatment duration <14 days was associated with significantly improved recurrence-free survival (RFS) at the expense of increased late toxicity (p = .029). Tumor volume >25 cc remained a significant predictor of inferior survival and tumor control, and was associated with significantly more acute toxicity (p = .017) but no difference in late toxicity.

Conclusion: SBRT ± cetuximab achieves promising tumor control and survival with low rates of acute/late toxicity even for recurrences >25 cc. Prolongations in treatment time may decrease late toxicity at the expense of disease control.
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http://dx.doi.org/10.1002/hed.23462DOI Listing
September 2014

Target delineation in stereotactic body radiation therapy for recurrent head and neck cancer: a retrospective analysis of the impact of margins and automated PET-CT segmentation.

Radiother Oncol 2013 Jan 17;106(1):90-5. Epub 2013 Jan 17.

Department of Radiation Oncology, University of Pittsburg Cancer Institute, Pittsburg, PA, USA.

Background: Few guidelines exist on stereotactic body radiation therapy (SBRT) treatment planning for recurrent head and neck cancer. We assessed the impact of retrospectively adding margins/automated PET volumes to the gross tumor volume (GTV) in patients with post-SBRT recurrences.

Materials And Methods: We reviewed 89 patients with recurrent head and neck cancer treated with SBRT using no margin around the GTV. GTVs were recontoured with 1-5mm margins. PET-CT planned GTVs were also recontoured by adding PET-standardized uptake value (SUV)(3.5), SUV(4.5), SUV(40% max), and signal/background ratio (SBR) to the original GTV. We deformably registered recontoured GTVs to post-SBRT scans and assessed fraction of recurrence volume (RV) falling within the GTV, the "RV-GTV overlap."

Results: With non-PET-CT planning, median RV-GTV overlap increased from 11.7% to 48.2% using 5mm margins, and median GTV size increased by 41.8 cc (156%). With PET-CT planning, RV-GTV overlap increased from 45% to 93.6% using 5mm margins, and GTV size increased by 34.8 cc (140%). Adding SUV(3.5) and SBR increased RV-GTV overlap from 45% to 73.3% and 73.6%, with GTV size increases of 0.8 (3%) and 3.1 cc (11%), respectively.

Conclusions: Recontouring increased recurrence coverage and also GTV size. Margins up to 5mm may reduce failures but could possibly increase toxicities. Automated PET contours may reduce near-miss failures with smaller increases in GTV size.
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http://dx.doi.org/10.1016/j.radonc.2012.11.008DOI Listing
January 2013
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