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Objective:Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen.Methods:We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan–Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT.Results:10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3–12 fractions (BED range: 29–100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively.Conclusion:FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose–response relationship that should be explored in prospective trials. [ABSTRACT FROM AUTHOR]

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy. [ABSTRACT FROM AUTHOR]

Abstract: We describe our experience with adjuvant high dose rate brachytherapy (Ir-192) (HDRB) in patients, who failed surgery and post-operative external radiation therapy. The salvage treatment consisted of excision of the keloid and wound closure followed by HDRB (15Gy in three fractions given on three consecutive business days beginning the day of surgery). At the time of last follow up, 88% (15/17) of the keloids were without any evidence of recurrence. [Copyright &y& Elsevier]

: PurposeWe became concerned about our observation of the loss of the normal lordotic cervical spinal curvature during the course of radiotherapy (RT) for head-and-neck tumors. Our goal was to evaluate formally the cervical lordotic curve in 50 random patients by comparing the cervical spinal angles (CSAs) measured at the initiation of RT with the CSAs measured during the last week of RT.: Methods and materialsFifty patients treated mono-isocentrically for head-and-neck cancer were selected randomly for review. All patients had custom-made masks, shoulder pulls, and multiple tattoos to ensure reproducibility. The CSA was defined as the angle formed by the line projected parallel to the posterior surface of C2 and the line projected parallel to C6. The measurements were done on the simulation film and the first and last port films.: ResultsThe average decrease in the CSA was 2.26° (SD ±2.19°). In patients with the isocenter placed as low as possible, the change was significantly more compared with the remaining population. (3.8° vs. 1.7°, p = 0.004).: ConclusionDespite customized immobilization, the neck position changes during the course of RT for head-and-neck tumors. Patients with the isocenter placed very low have the least long-term reproducibility and a comfortable position may be best suited to intensity-modulated RT for such head-and-neck cancer patients. [Copyright &y& Elsevier]

Several dose metrics in the categories—homogeneity, coverage, conformity and gradient have been proposed in literature for evaluating treatment plan quality. In this study, we applied these metrics to characterize and identify the plan quality metrics that would merit plan quality assessment in lung stereotactic body radiation therapy (SBRT) dose distributions. Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our institution were retrospectively reviewed. Dose calculations were performed using anisotropic analytical algorithm (AAA) with heterogeneity correction. A literature review on published plan quality metrics in the categories—coverage, homogeneity, conformity and gradient was performed. For each patient, using dose-volume histogram data, plan quality metric values were quantified and analysed. For the study, the radiation therapy oncology group (RTOG) defined plan quality metrics were: coverage (0.90 ± 0.08); homogeneity (1.27 ± 0.07); conformity (1.03 ± 0.07) and gradient (4.40 ± 0.80). Geometric conformity strongly correlated with conformity index (p < 0.0001). Gradient measures strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol advocated conformity guidelines for prescribed dose in all categories were met in ≥94% of cases. The proportion of total lung volume receiving doses of 20 Gy and 5 Gy (V20 and V5) were mean 4.8% (±3.2) and 16.4% (±9.2), respectively. Based on our study analyses, we recommend the following metrics as appropriate surrogates for establishing SBRT lung plan quality guidelines—coverage % (ICRU 62), conformity (CN or CIPaddick) and gradient (R50%). Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN or CIPadddick in place of prescription isodose to target volume ratio for conformity index evaluation. Our study metrics are valuable tools for establishing lung SBRT plan quality guidelines. [ABSTRACT FROM AUTHOR]

There has recently been an increasing interest in model-based evaluation and comparison of different treatment options in radiation oncology studies. This is partly driven by the considerable technical advancements in radiation therapy of the last decade, leaving radiation oncologists with a multitude of options to consider. In lieu of randomized trials comparing all of these different treatment options for varying indications, which is unfeasible, treatment evaluations based on normal tissue complication probability (NTCP) models offer a practical alternative. The Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) effort, culminating in a number of reports published in 2010, provided a basis for many of the since-implemented dose-response models and dose-volume constraints and was a key component for model-based treatment evaluations. Given that 7 years have passed since the QUANTEC publications and that patient-reported outcomes have emerged as an important consideration in recent years, an updated summary of the published radiation dose-response literature, which includes a focus on patient-reported quality of life outcomes, is warranted. Here we provide a systematic review of quantitative dose-response models published after January 1, 2010 for endpoints relevant to radiation therapy for head and neck cancer, because these patients are typically at risk for a variety of treatment-induced normal tissue complications. [ABSTRACT FROM AUTHOR]

To evaluate the change in parotid glands at mid-treatment during IMRT and the association between radiation dose to the parotid gland stem cell (PGSC) region and patient-reported xerostomia for patients with head and neck cancer (HNC). Patients who were treated from 2006–2012 at our institution with patient-reported xerostomia outcomes available at least 9 months following RT were included. PG and PGSC regions were delineated and the dose was estimated from the treatment plan dose distribution, using contours from pre- and mid-treatment CT scans. The association between radiation dose and volumetric changes was assessed using linear regression. Univariable logistic regression, logistic dose-response curves, and receiver operating characteristics (ROC) were used to examine the relationship between radiation dose and patient-reported xerostomia. Sixty-three patients were included, most treated with 70 Gy in 33 fractions; 34 patients had mid-treatment CT scans. Both contralateral and ipsilateral PGs had considerable volume reduction from baseline to mid-treatment (25% and 27%, respectively, both p <.001), significantly associated with mean PG dose (−0.44%/Gy, p =.008 and −0.54%/Gy, p <.001, respectively). There was a > 5 Gy difference in mean PG and PGSC dose for 8/34 patients at mid-treatment, with 6/8 (75%) reporting severe xerostomia. Xerostomia prediction based on whole PG or PGSC region dose showed similar performance (ROC AUC 0.754 and 0.749, respectively). The corresponding dose-response models also predicted similar risk of patient-reported xerostomia with mean dose to the contralateral PG (32.5%) or PGSC region (31.4%) at the 20 Gy QUANTEC-recommended sparing level. The radiation dose to the PGSC region did not show stronger association with patient-reported xerostomia compared to that of whole PG, possibly due to considerable anatomical changes identified at mid-treatment. This shift in the size and position of the PG warrants adaptive planning strategies to evaluate the true benefit of parotid stem cell sparing. [ABSTRACT FROM AUTHOR]

Purpose Locoregional progression following definitive chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) is common. In this study, we explore the utility of pre-treatment PET for predicting sites of disease progression following CRT. Methods We identified patients treated at our institution with definitive, concurrent CRT for stage III NSCLC in the years 2007–2010 who underwent staging FDG-PET/CT. Using a semiautomatic gradient-based tool, visible thoracic hypermetabolic lesions were contoured on each patient's pre-treatment PET. Post-treatment imaging was reviewed to identify specific locations of disease progression. Patients’ maximum SUV (SUVmax_pat) and metabolic tumor volume (MTV_pat) were evaluated as predictors of clinical outcomes using logrank testing. Competing risks analysis was performed to examine the relationship between lesion (tumor or lymph node) MTV (MTV_les) and the risk of local disease progression. Patient death and progression in other sites were treated as competing risks. Results 28 patients with 82 hypermetabolic lesions (27 pulmonary tumors, 55 lymph nodes) met inclusion criteria. Median follow-up was 39.0 months for living patients. Median progression-free survival (PFS) was 12.4 months, and median overall survival (OS) was 31.8 months. Low MTV_pat was associated with improved PFS (median 14.3 months for MTV < 60 cc vs. 9.7 months for MTV > 60 cc, p = 0.039). MTV_les was strongly associated with the risk of local disease progression. The 2-year cumulative incidence rate (CIR) for progression in lesions larger than 25 cc was 45%, compared to 5% for lesions under 25 cc ( p < 0.001). Conclusion Pre-treatment PET can be used to identify specific lesions at high risk for treatment failure following definitive CRT for locally advanced NSCLC. Selective treatment intensification to high-risk lesions should be studied as a strategy to improve clinical outcomes in this patient population. [ABSTRACT FROM AUTHOR]

Background: Proton therapy is a promising advancement in radiation oncology especially in terms of reducing normal tissue toxicity, although it is currently expensive and of limited availability. Here we estimated the individual quality of life benefit and cost-effectiveness of proton therapy in patients with oropharyngeal cancer treated with definitive radiation therapy (RT), as a decision-making tool for treatment individualization.Methods and Materials: Normal tissue complication probability models were used to estimate the risk of dysphagia, esophagitis, hypothyroidism, xerostomia and oral mucositis for 33 patients, comparing delivered photon intensity-modulated RT (IMRT) plans to intensity-modulated proton therapy (IMPT) plans. Quality-adjusted life years (QALYs) lost were calculated for each complication while accounting for patient-specific conditional survival probability and assigning quality-adjustment factors based on complication severity. Cost-effectiveness was modeled based on upfront costs of IMPT and IMRT, and the cost of acute and/or long-term management of treatment complications. Uncertainties in all model parameters and sensitivity analyses were included through Monte Carlo sampling.Results: The incremental cost-effectiveness ratios (ICERs) showed considerable variability in the cost of QALYs spared between patients, with median $361,405/QALY for all patients, varying from $54,477/QALY to $1,508,845/QALY between individual patients. Proton therapy was more likely to be cost-effective for patients with p16-positive tumors ($234,201/QALY), compared to p16-negative tumors ($516,297/QALY). For patients with p16-positive tumors treated with comprehensive nodal irradiation, proton therapy is estimated to be cost-effective in ≥ 50% of sampled cases for 8/9 patients at $500,000/QALY, compared to 6/24 patients who either have p16-negative tumors or receive unilateral neck irradiation.Conclusions: Proton therapy cost-effectiveness varies greatly among oropharyngeal cancer patients, and highlights the importance of individualized decision-making. Although the upfront cost, societal willingness to pay and healthcare administration can vary greatly among different countries, identifying patients for whom proton therapy will have the greatest benefit can optimize resource allocation and inform prospective clinical trial design. [ABSTRACT FROM AUTHOR]

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS. Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan–Meier methods were used to compare actuarial survival estimates. Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3–4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68–0.96), p=.018). For patients with early stage disease (T1–2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86–1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30–45 Gy was seen for increasing doses up to 55–60 Gy, but not beyond 60 Gy. Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55–60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease. [ABSTRACT FROM AUTHOR]

Purpose: Developing a quantitative decision-support strategy estimating the impact of normal tissue complications from definitive radiation therapy (RT) for head and neck cancer (HNC). We developed this strategy to identify patients with oropharyngeal HNC who may benefit most from receiving proton RT.Methods and Materials: Recent normal tissue complication probability (NTCP) models for dysphagia, esophagitis, hypothyroidism, xerostomia, and oral mucositis were used to estimate NTCP for 33 patients with oropharyngeal HNC previously treated with photon intensity modulated radiation therapy (IMRT). Comparative proton therapy plans were generated using clinical protocols for HNC RT at a collaborating proton center. Organ-at-risk (OAR) doses from photon and proton RT plans were used to calculate NTCPs; Monte Carlo sampling 10,000 times was used for each patient to account for model parameter uncertainty. The latency and duration of each complication were modeled from calculated NTCP, accounting for age-, sex-, smoking- and p16-specific conditional survival probability. Complications were then assigned quality-adjustment factors based on severity to calculate quality-adjusted life years (QALYs) lost from each complication.Results: Based on our institutional-delivered photon IMRT doses and the achievable proton therapy doses, the average QALY reduction from all HNC RT complications for photon and proton therapy was 1.52 QALYs versus 1.15 QALYs, with proton therapy sparing 0.37 QALYs on average (composite 95% confidence interval, 0.27-2.53 QALYs). Long-term complications (dysphagia and xerostomia) contributed most to the QALY reduction. The QALYs spared with proton RT varied considerably among patients, ranging from 0.06 to 0.84 QALYs. Younger patients with p16-positive tumors who smoked ≤10 pack-years may benefit most from proton therapy, although this finding should be validated using larger patient series. A sensitivity analysis reducing photon IMRT doses to all OARs by 20% resulted in no overall estimated benefit with proton therapy with -0.02 QALYs spared, although some patients still had an estimated benefit in this scenario, ranging from -0.50 to 0.43 QALYs spared.Conclusions: This quantitative decision-support strategy allowed us to identify patients with oropharyngeal cancer who might benefit the most from proton RT, although the estimated benefit of proton therapy ultimately depends on the OAR doses achievable with modern photon IMRT solutions. These results can help radiation oncologists and proton therapy centers optimize resource allocation and improve quality of life for patients with HNC. [ABSTRACT FROM AUTHOR]

Purpose: To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer.Methods and Materials: A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5 Gy in 5 fractions, and doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60 cm3. Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5 years, respectively.Results: The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were 16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P = .013).Conclusions: SBRT doses ranging from 32.5 to 40 Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether a response assessment using mid-treatment computed tomography (CT) scans during definitive radiation therapy (RT) for oropharyngeal head and neck cancer can predict for locoregional recurrence (LRR).Methods and Materials: Head and neck cancer patients who receive RT at our institution undergo CT repeat scans at the 15th fraction, with treatment replanning in the case of an inadequate dose to gross disease or an increased dose to organs at risk. A retrospective cohort analysis was performed of 96 consecutive patients with oropharyngeal cancer treated from 2007 to 2015 with mid-treatment repeat CT scans available. The primary disease volume and involved lymph node volume were delineated on the pre- and mid-treatment CT scans. Univariable and multivariable Cox proportional hazards regression analyses were used to evaluate the efficacy of the mid-treatment reduction in tumor volume as a predictor of LRR. Risk stratification was performed by dichotomizing the patients into high- and low-risk groups according to the mid-treatment response and p16 status and smoking history.Results: With a median follow-up of 34 months, 14 patients experienced LRR. The median reduction in the total tumor volume was 18.7% (interquartile range 8.4%-30.9%). A reduction in total tumor volume greater than the median was an independent predictor of LRR (hazard ratio 0.22, 95% confidence interval 0.05-0.89; P = .020). The reduction in primary tumor volume was an even stronger predictor of LRR (hazard ratio 0.11, 95% confidence interval 0.02-0.57; P = .002). Stratifying patients into a high-risk group for those with a reduction in the total tumor volume at mid-treatment at or less than the median, p16 negative status, and smoking status of >10 pack-years and a low-risk group for those without these factors, we found a clear separation in Kaplan-Meier curves, with actuarial 3-year locoregional control, progression-free survival, and overall survival rates for the high-risk patients of 45.7%, 38.2%, and 71.8% compared with 90.7%, 70.6%, and 89.8% for low-risk patients, respectively (P ≤ .021 for all).Conclusions: Our results have shown that the treatment response from an early assessment using mid-treatment CT scans is an independent predictor of LRR and can be used to effectively distinguish high- and low-risk patients, allowing for risk-adaptive treatment stratification at the midway point. [ABSTRACT FROM AUTHOR]

Objective: To determine whether patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC) treated with Transoral Robotic Surgery (TORS) have similar survival to patients treated with definitive RT.Materials and Methods: Using the National Cancer Database (NCDB) registry, we identified patients with newly diagnosed clinical T1-T2, N0-N2b OPSCC between 2010 and 2014. A multivariable logistic regression was utilized to determine the association between chemotherapy use and primary treatment modality (TORS vs definitive RT). Kaplan Meier survival analysis was used to estimate overall survival. Propensity score matching was utilized to address selection bias.Results: We identified 17,150 patients, of which 14,470 (84.4%) received primary RT and 2,680 (15.6%) underwent TORS. The median follow-up for the cohort was 31.4 months. Propensity score matching demonstrated similar 5-year OS for patients treated with either definitive RT or TORS (81% vs 84%, log rank p = 0.10). There was no difference in survival outcomes by treatment selection (TORS or definitive RT) in either HPV positive or HPV negative subtypes. Patients treated with TORS were less likely to receive chemotherapy compared to patients treated with definitive RT and this was also demonstrated in a propensity matched analysis (OR: 0.09, 95%CI 0.078-0.12, p < 0.001). Only 68.4% of TORS treated patients underwent adjuvant RT, compared to 100% of patients in the primary RT cohort (p < 0.001).Conclusions and Relevance: For patients with OPSCC, TORS results in similar OS outcomes and is associated with decreased chemotherapy and RT use compared to definitive RT. Our results demonstrate the feasibility of TORS in a select subgroup of OPSCC patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze nutritional factors and compliance with dietary recommendations for associations with overall survival (OS) and progression-free survival (PFS) in patients receiving definitive RT for laryngeal and oropharyngeal cancers.Materials/methods: We identified 352 patients with non-metastatic laryngeal (146) and oropharyngeal (206) cancer treated with definitive RT between 2004 and 2013. Disease and patient characteristics, treatment information, sarcopenia based on muscle areas at L3 level on CT, compliance with the nutritional program, and clinical outcomes data were tabulated. Descriptive statistics, Kaplan-Meier survival analysis, and log rank tests were performed, and Cox regression models were used to examine predictors of OS and PFS.Results: The median follow-up for the entire cohort was 22.86 months. The actuarial rates for OS were 91, 86, and 73% at years 1, 2, and 5, respectively. Of patients with abdominal CT prior to starting RT, 70.9% (112/158) were sarcopenic with a median muscle mass index of 48.2 (range 30.4-70.9) for males and 35.9 (range 24.6-53.2) for females. The majority (85.8%) of patients met with a dietitian during their course of RT and 62.6% of these patients were compliant with the nutritional program. Compliance with the nutritional program resulted in 27% (HR 0.73, 95% CI 0.43-1.26) protection from death (did not reach significance) and 31% (HR 0.69, 95% CI 0.50-0.94) significant protection from disease progression. Higher pretreatment BMI was associated with a lower risk of death (HR 0.94, 95% CI 0.90-0.99) and disease progression (HR 0.96, 95% CI 0.93-0.99).Conclusion: Laryngeal and oropharyngeal cancer patients treated with definitive RT who are compliant with regular dietetic counseling and contact appear to have improved outcomes.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Purpose: Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC.Methods and Materials: A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method.Results: Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding.Conclusions: Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose Within a multifraction high-dose-rate vaginal cuff brachytherapy course, we determined if individual variations in organ at risk (OAR) volume and cylinder insertion geometry (CIG) impacted dose and whether planned minus fractional (P − F) differences led to a discrepancy between planned dose and delivered dose. Methods and Materials We analyzed vaginal cuff brachytherapy applications from consecutive patients treated with three fractions of 5 Gy after each undergoing a planning CT and three repeat fractional CTs (fCTs). Rectal and bladder D 2ccs and volumes were recorded in addition to the x (in relationship to midplane) and y (in relationship to the table) angles of CIG. Paired t-tests and multiple regression analyses were performed. Results Twenty-seven patients were identified. In comparing the planning CT vs. mean fCT rectal volumes, bladder volumes, x angles, and y angles, only bladder volume was significantly different (planned volume higher, t = 2.433, p = 0.017). The cumulative mean planned OAR D 2cc vs. delivered D 2cc was only significantly different for the bladder (planned dose lower, t = −2.025, p = 0.053). Regression analysis revealed planned rectal D 2cc ( p < 0.0003) and a positive (posterior) y insertion angle ( p = 0.015) to significantly impact delivered rectal D 2cc . Additionally, P − F rectal volume ( p = 0.037) was significant in determining rectal delivered dose. Conclusions A more posterior y angle of insertion was found to increase rectal D 2cc leading us to believe that angling the vaginal cylinder anteriorly may reduce rectal dose without significantly increasing bladder dose. Although attention should be paid to OAR volume and CIG to minimize OAR dose, the clinical significance of P − F changes remains yet to be shown. [ABSTRACT FROM AUTHOR]

Context.--Radiation is a key arm in the multidisciplinary treatment of patients with head and neck squamous cell carcinoma. During the past 2 decades, significant changes in the way radiation therapy is planned and delivered have improved efficacy and decreased toxicity. Refined approaches in the application of radiation and chemoradiation have led to organ-sparing treatment regimens for laryngeal and pharyngeal cancers and have improved local and regional control rates in the postoperative, adjuvant setting. The molecular and genetic determinants of tumor cell response to radiation have been studied, and several potential biomarkers are emerging that could further improve application and efficacy of radiation treatment in head and neck squamous cell carcinoma. Objective.--To discuss the current understanding of potential biomarkers related to radiation response in head and neck squamous cell carcinoma. Data Sources.--Existing published literature. Conclusions.--Several potential biomarkers are actively being studied as predictors and targets to improve the use and efficacy of radiation therapy to treat head and neck squamous cell carcinoma. Several promising candidates have been defined, and new markers are on the horizon. [ABSTRACT FROM AUTHOR]

An efficient and simple class solution is proposed for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) planning using the Volumetric Arc Therapy (VMAT) delivery technique following the NRG Oncology protocol NRG-CC001 treatment planning guidelines. The whole-brain planning target volume (PTV) was subdivided into subplanning volumes that lie in plane and out of plane with the hippocampal-avoidance volume. To further improve VMAT treatment plans, a partial-field dual-arc technique was developed. Both the arcs were allowed to overlap on the in-plane subtarget volume, and in addition, one arc covered the superior out-of-plane sub-PTV, while the other covered the inferior out-of-plane subtarget volume. For all plans ( n = 20), the NRG-CC001 protocol dose-volume criteria were met. Mean values of volumes for the hippocampus and the hippocampal-avoidance volume were 4.1 cm 3 ± 1.0 cm 3 and 28.52 cm 3 ± 3.22 cm 3 , respectively. For the PTV, the average values of D 2% and D 98% were 36.1 Gy ± 0.8 Gy and 26.2 Gy ± 0.6 Gy, respectively. The hippocampus D 100% mean value was 8.5 Gy ± 0.2 Gy and the maximum dose was 15.7 Gy ± 0.3 Gy. The corresponding plan quality indices were 0.30 ± 0.01 (homogeneity index), 0.94 ± 0.01 (target conformality), and 0.75 ± 0.02 (confirmation number). The median total monitor unit (MU) per fraction was 806 MU (interquartile range [IQR]: 792 to 818 MU) and the average beam total delivery time was 121.2 seconds (IQR: 120.6 to 121.35 seconds). All plans passed the gamma evaluation using the 5-mm, 4% criteria, with γ > 1 of not more than 9.1% data points for all fields. An efficient and simple planning class solution for HA-WBRT using VMAT has been developed that allows all protocol constraints of NRG-CC001 to be met. [ABSTRACT FROM AUTHOR]

Purpose To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined. Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results Average (±SD) planned bladder volume was 299.7 ± 68.5 cm 3 . Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm 3 (range, 74.3-251.4 cm 3 ). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm 3 ; P =.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV_Bowel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX–XII, which would help in establishing RT limiting doses for organs at risk (OAR). Methods: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX–XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. Results: We successfully developed a contouring atlas for CNs IX–XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66–70Gy). The median CN (IX–XI) and (XII) volumes were 10c.c (range: 8–12c.c) and 8c.c (range: 7–10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX–XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX–XI) and (XII) were 72Gy (range: 66–77) and 71Gy (range: 64–78), respectively. Conclusions: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. [ABSTRACT FROM AUTHOR]

Purpose. Transoral robotic surgery (TORS) has increased in popularity in the management of squamous cell carcinoma of the head and neck. However, TORS does not address the neck or retropharyngeal nodes (RPN). In the current report, we highlight the impact of the lack of adjuvant radiotherapy on RPN recurrence after TORS. Materials and Methods. A 58-year-old Caucasian male presented with squamous cell carcinoma of the head and neck of unknown primary. He was offered radiotherapy as a definitive management for clinical stage T0N2aM0, stage IVA, but he opted to left neck dissection. Follow-up PET-CT scan revealed recurrence in the left base of tongue and right level II lymph node. He was offered radiotherapy which he declined and opted to TORS and right neck dissection. Follow-up PET-CT scan showed recurrence in left RPN for which he underwent salvage concurrent chemoradiotherapy to 70 Gy. Results. After a followup of 9 months from the date of salvage chemoradiotherapy completion, the patient is with no evidence of disease. Conclusions. TORS followed by adjuvant radiotherapy seems reasonable in the context of squamous cell carcinoma of the head and neck due to the odds of RPN involvement. Further reports are warranted to optimize post-TORS adjuvant treatment. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To study the influence of timing of postseed implant imaging on rectal dose–volume parameters for cesium-131 (131Cs) seed prostate implants. Methods and Materials: Fifteen patients were treated in our institution with combination 131Cs brachytherapy followed by pelvic external beam radiation therapy for intermediate to high-risk prostate cancers. For all patients, CT scans were scheduled at 7 days (CT7) and again at 2 months for external beam radiation therapy simulation purpose (CT60) postseed implantation. Comprehensive postseed implant dosimetry was performed for both CT7 and CT60 scans. In each case, dose–volume histogram parameters, rectal separation (the distance between the center of posterior most seed and most anterior rectal wall), and posterior row activity (the total activity implanted within 2–4mm anterior to the posterior wall of the prostate) data were collected. The absolute rectal volumes receiving 100% and 110% prescription dose were also collected. Results: Rectal dose correlated strongly with rectal separation (p <0.001). The mean change in rectal separation between CT7 and CT60 scans was 1.1 (±1.7) mm, and the corresponding change in 0.1-cc rectal dose was 18 (±26.5) Gy. Posterior row activity did not correlate with rectal dose (p =0.51). The mean volume of rectum that receives between 100% and 110% of the prescription dose (RV100 and RV110) increased twofold, between CT7 and CT60 evaluations (0.03 [±0.06] cc vs. 0.07 (±0.05) cc, respectively, p =0.06). Conclusions: Our study has demonstrated that rectal doses after 131Cs seed implants are influenced by the timing of postseed imaging. This may be a consequence of prostatic and periprostatic edema resolution. [Copyright &y& Elsevier]

Purpose: Anatomic changes and positional variability during intensity-modulated radiation therapy (IMRT) for head and neck cancer can lead to clinically significant dosimetric changes. We report our single-institution experience using an adaptive protocol and correlate these changes with anatomic and positional changes during treatment. Methods and Materials: Twenty-three sequential head and neck IMRT patients underwent serial computed tomography (CT) scans during their radiation course. After undergoing the planning CT scan, patients underwent planned rescans at 11, 22, and 33 fractions; a total of 89 scans with 129 unique CT plan combinations were thus analyzed. Positional variability and anatomic changes during treatment were correlated with changes in dosimetric parameters to target and avoidance structures between planning CT and subsequent scans. Results: A total of 15/23 patients (65%) benefited from adaptive planning, either due to inadequate dose to gross disease or to increased dose to organs at risk. Significant differences in primary and nodal targets (planning target volume, gross tumor volume, and clinical tumor volume), parotid, and spinal cord dosimetric parameters were noted throughout the treatment. Correlations were established between these dosimetric changes and weight loss, fraction number, multiple skin separations, and change in position of the skull, mandible, and cervical spine. Conclusions: Variations in patient positioning and anatomy changes during IMRT for head and neck cancer can affect dosimetric parameters and have wide-ranging clinical implications. The interplay between random positional variability and gradual anatomic changes requires careful clinical monitoring and frequent use of CT- based image-guided radiation therapy, which should determine variations necessitating new plans. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study. [Copyright &y& Elsevier]

Purpose: After breast-conserving surgery, a seroma often forms in the surgical cavity. If not drained, it may affect the volume of tumor bed requiring a boost after whole-breast radiation therapy (WBRT). Our objective was to evaluate the change in seroma volume that occurs during WBRT, before boost planning. Methods and Materials: A retrospective review was performed of women receiving breast-conserving therapy with evidence of seroma at the time of WBRT planning. Computed tomography (CT) simulation was performed before WBRT and before the tumor bed boost. All patients received either a hypofractionated (42.4 Gy/16 fraction + 9.6 Gy/4 fraction boost) or standard fractionated (50.4 Gy/28 fraction + 10 Gy/5 fraction boost) regimen. Seroma volumes were contoured and compared on CT at the time of WBRT simulation and tumor bed boost planning. Results: Twenty-four patients with evidence of seroma were identified and all patients received WBRT without drainage of the seroma. Mean seroma volume before WBRT and at boost planning were significantly different at 65.7 cm3 (SD, 50.5 cm3) and 35.6 cm3 (SD, 24.8 cm3), respectively (p < 0.001). Mean and median reduction in seroma volume during radiation were 39.6% (SD, 23.8%) and 46.2% (range, 10.7–76.7%), respectively. Fractionation schedule was not correlated with change in seroma volume. Length of time from surgery to start of radiation therapy showed an inverse correlation with change in seroma volume (Pearson correlation r = –0.53, p < 0.01). Conclusions: The volume of seroma changes significantly during WBRT. Consequently, the accuracy of breast boost planning is likely affected, as is the volume of normal breast tissue irradiated. CT-based boost planning before boost irradiation is suggested to ensure appropriate coverage. [Copyright &y& Elsevier]

Purpose: With 54° of freedom from the skull to mandible to C7, ensuring adequate immobilization for head-and-neck radiotherapy (RT) is complex. We quantify variations in skull, mandible, and cervical spine movement between RT sessions. Methods and Materials: Twenty-three sequential head-and-neck RT patients underwent serial computed tomography. Patients underwent planned rescanning at 11, 22, and 33 fractions for a total of 93 scans. Coordinates of multiple bony elements of the skull, mandible, and cervical spine were used to calculate rotational and translational changes of bony anatomy compared with the original planning scan. Results: Mean translational and rotational variations on rescanning were negligible, but showed a wide range. Changes in scoliosis and lordosis of the cervical spine between fractions showed similar variability. There was no correlation between positional variation and fraction number and no strong correlation with weight loss or skin separation. Semi-independent rotational and translation movement of the skull in relation to the lower cervical spine was shown. Positioning variability measured by means of vector displacement was largest in the mandible and lower cervical spine. Conclusions: Although only small overall variations in position between head-and-neck RT sessions exist on average, there is significant random variation in patient positioning of the skull, mandible, and cervical spine elements. Such variation is accentuated in the mandible and lower cervical spine. These random semirigid variations in positioning of the skull and spine point to a need for improved immobilization and/or confirmation of patient positioning in RT of the head and neck. [Copyright &y& Elsevier]

Abstract: Purpose: We correlated rectal and bladder point and volumetric dose data in patients treated for advanced cervix cancers with combined intracavitary-interstitial high-dose-rate (HDR) brachytherapy (BT). The results are compared with published Vienna applicator data. Methods and Materials: We retrospectively analyzed 30 individual combined intracavitary plus interstitial implants from 10 patients treated with external beam radiation therapy (EBRT) followed by HDR BT for locally advanced cervix carcinoma. EBRT consisted of 45Gy to the pelvis followed by 9–14.4Gy boost to involved parametria. BT consisted of a total dose of 21Gy delivered in 7Gy fraction. For each implant, CT-image-based simulation and image-guided BT treatment planning was performed. Bladder and rectal doses were evaluated and analyzed using both International commission on Radiation Units and Measurements (ICRU) reference points and dose–volume histograms. The cumulative doses to the rectum and bladder were calculated by combining contributions from external beam therapy and BT. To facilitate comparison with published literature, the total doses were normalized to equivalent dose in 2-Gy fractions (EQD2) using the equation EQD2total =EQD2EBRT +EQD2BT. Results: For the patient population considered, the mean ICRU bladder dose was 75 (±4) Gy3 compared to bladder D 0.1 cc and D 2 cc doses of 84 (±4) and 78 (±3) Gy3, respectively. The mean ICRU rectal dose was 73 (±4) Gy3 compared to rectal D 0.1 cc and D 2 cc doses of 79 (±5) and 74 (±4) Gy3, respectively. For rectum, the mean dose ratios (D 0.1 cc/D ICRU) and (D 2 cc/D ICRU) were 1.08 and 1.01, respectively, compared to Vienna applicator study mean dose ratios of 1.08 and 0.93, respectively. ICRU rectal dose correlated with volumetric rectal doses and best with volumetric D 2 cc dose (r S =0.91, p =0.0003); however, ICRU bladder dose did not correlate with volumetric bladder dose. Conclusions: Our study findings reveal a strong correlation between ICRU rectal reference dose and volumetric rectal D 2 cc dose in combined intracavitary-interstitial HDR brachytherapy. This surrogate rectal–dose relationship is valuable in establishing rectal tolerance dose levels in transitioning from traditional two-dimensional to image-based three-dimensional dose planning. [Copyright &y& Elsevier]

Simple Summary: The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma. Patients with locoregional, pathologically high-risk disease recur frequently despite adjuvant cisplatin–radiation therapy. Targeting PD1 may reverse immunosuppression induced by cancer, chemotherapy, or radiation therapy. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule for adding fixed-dose pembrolizumab to standard adjuvant cisplatin–radiation therapy. Eligible patients had resected, human papillomavirus-negative, stage III–IV oral cavity, pharynx, or larynx cancer with extracapsular nodal extension or positive margin. A total of four dose-limiting toxicities were observed in 34 patients (fever, wound infection, diverticulitis, nausea). Three of four were successfully rechallenged with pembrolizumab. The recommended phase II schedule was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before adjuvant CRT. The regimen was safe and feasible in the cooperative group setting. Further development is warranted. The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin–radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III–IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG institutions. During the first cohort, only one DLT was observed (fever), thus RP2S was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before CRT. During expansion, three additional DLTs were observed (wound infection, diverticulitis, nausea). Of the 34 patients, 28 (82%) received five or more doses of pembrolizumab. This regimen was safe and feasible in a cooperative group setting. Further development is warranted. [ABSTRACT FROM AUTHOR]

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of target coverage, target conformality, and OAR sparing when range and HU uncertainties are neglected. However, when accounting for these uncertainties during robust optimization, VMAT outperforms IMPT in terms of achievable target conformity and OAR sparing. Comparison between achievable dose distributions using modern, robust optimization of IMPT for high dose per fraction SBRT regimens for the prostate has not been previously investigated. [ABSTRACT FROM AUTHOR]