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Background and purpose: Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methods: Nineteen patients who received 30–34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. Results: Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9–76.8 %) and a median MDA of 5.1 mm (IQR 3.4–7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0–4.8 %). DSC was 0.97 (IQR 0.94–0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8–100 %) to 99.6 % (IQR 93.9–100 %). Conclusion: Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.

Abstract Background The aim of this study was to compare patient perceptions of radiotherapy (RT) before and after treatment to better inform future patients and providers. Methods Seventy‐eight consecutive patients with rectal adenocarcinoma treated with neo‐ or adjuvant chemoradiation, surgical resection, and adjuvant chemotherapy from 2009 to 2018 and who were without recurrence were included. Patients were surveyed ≥6 months after ileostomy reversal or ≥3 months after adjuvant chemotherapy. The survey assessed patients' baseline knowledge and fears of RT, how their short‐ and long‐term side effects compared with initial expectations, and how their experiences compared for each modality (RT, surgery, and chemotherapy). Results Forty patient‐responses were received. Before treatment, 70% of patients indicated little to no knowledge of RT, though 43% reported hearing frightening stories about RT. The most commonly top‐ranked fears included organ damage (26%), skin burns (14%), and inability to carry out normal daily activities (10%). Eighty percent reported short‐term effects of RT to be less than or as expected, with urinary changes (93%), abdominal discomfort (90%), and anxiety (88%) most commonly rated as less than or as expected. 85% reported long‐term effects to be less than or as expected, with pain (95%), changes to the appearance of the treated area (85%), and dissatisfaction with body image (80%) most commonly rated as less than or as expected. Surgery was most commonly rated as the most difficult treatment (50%) and most responsible for long‐term effects (55%). RT was least commonly rated as the most difficult treatment (13%), and chemotherapy was least commonly rated as most responsible for long‐term effects (13%). Conclusions The majority of patients indicated short‐ and long‐term side effects of RT for rectal cancer to be better than initial expectations. In the context of trimodality therapy, patients reported RT to be the least difficult of the treatments.

Abstract Background Little is known regarding anal cancer patients' perspectives on undergoing radiation therapy. Additionally, the stigma surrounding anal cancer diagnosis warrants a better understanding of the barriers to complete disclosure in patient‐healthcare team interactions. Methods Included patients had squamous cell carcinoma of the anus treated with definitive chemoradiation (CRT) from 2009 to 2018. Survey questions were adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Discrimination and Stigma Scale. Results A total of 46 anal cancer patients who underwent CRT were surveyed, of which 72% responded. 73% of respondents indicated little to no pre‐treatment knowledge of CRT. 70% reported overall short‐term effects as worse than expected, most commonly with bowel habits (82%), energy (73%), and interest in sexual activity (64%). 39% reported overall long‐term effects to be worse than expected, most commonly with changes to bowel habits (73%), sexual function (67%), and interest in sexual activity (58%). However, 94% agreed they were better off after treatment. Regarding stigma, a subset reported hiding their diagnosis (12%, 24%) and side effects (24%, 30%) from friends/family or work colleagues, respectively, and 15% indicating they stopped having close relationships due to concerns over stigma. Conclusions Although patients' perceptions of the severity of short‐term CRT side effects were worse than expectations, the vast majority agreed they were better off after treatment. Targeted counseling on common concerns may improve the anal cancer treatment experience. A notable subset reported stigma associated with treatment, warranting further evaluation to understand the impact on the patient experience.

Predictors of genitourinary toxicity after post-prostatectomy radiotherapy remain elusive. A previously defined germline DNA signature (PROSTOX) has shown predictive ability for late grade ≥ 2 GU toxicity after intact prostate stereotactic body radiotherapy. We explore whether PROSTOX would predict toxicity among patients receiving post-prostatectomy SBRT on a phase II clinical trial.

Purpose: Both the superstructures of virtual discourse in radiation oncology and the entities occupying influential positions in the social media landscape of radiation oncology remain poorly characterized. Methods and Materials: NodeXL Pro was used to prospectively sample all tweets with the hashtag #radonc every 8 to 10 days during the course of 1 year (December 4, 2018, to November 29, 2019). Twitter handles were grouped into conversational clusters using the Clauset-Newman-Moore community detection algorithm. For each sample period, the top 10 #radonc Twitter influencers, defined using betweenness centrality, were categorized. Influencers were scored in each sample period according to their top 10 influence rank and summarized with descriptive statistics. Linear regression assessed for characteristics that predicted higher influence scores among top influencers. Results: In the study, 684,000 tweets were sampled over 38 periods. #radonc tweets took on the crowd superstructure of a hub-and-spoke broadcast network formed when prominent individuals are widely repeated by many audience members. Professional societies were the most influential category of Twitter handles with an average influence score of 7.63 out of 10 (standard deviation [SD] = 1.94). When industry handles were present among top 10 influencers, they exhibited the second highest average influence scores (6.75, SD = 1.06), followed by individuals with scores of 5.28 (SD = 0.43). The categories of influencers were stable during the course of 1 year. The role of attending physician, radiation oncology specialty, male sex, academic practice, and US-based handles in North America were predictors of higher influence score. Conclusions: Twitter influencers in radiation oncology represent a diverse group of people and organizations, but male academic radiation oncologists based in North America occupy particularly influential positions in virtual communities broadly characterized as “hub and spoke” broadcast networks. Periodic network-based analyses of the social media discourse in radiation oncology are warranted to maintain an awareness of the handles that are influencing discussions on Twitter and ensure that social media utilization continues to contribute to the field of radiation oncology in a meaningful way.

Abstract Purpose Stereotactic body radiotherapy (SBRT) delivers ablative doses with excellent local control. However, implementing SBRT for abdominal and pelvic tumors has been limited by the risk for treatment‐related gastrointestinal toxicity. MRI‐guided radiotherapy may ameliorate these risks and increase the therapeutic ratio. We report the clinical outcomes of stereotactic MRI‐guided adaptive radiotherapy (SMART) for primary and metastatic tumors in the abdomen and pelvis. Methods From November 2014 to August 2017, the first 106 consecutive patients with 121 tumors in the abdomen and pelvis were treated with SMART at a single institution. Of the cohort, 41.5%, 15.1%, and 43.4% had primary, locally recurrent, and oligometastatic tumors, respectively. SMART was delivered using a tri‐cobalt‐60 gantry with on‐board 0.35 Tesla MRI with respiratory breath‐hold and daily adaptive re‐planning when anatomically necessary. A median of 40Gy in five fractions was prescribed. The Common Terminology Criteria for Adverse Events v.4.03 was used to score treatment‐related toxicities. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Results Of the 510 treatments, seventy‐one (13.9%) were adapted. Fatigue, nausea, and pain were the most common acute toxicities. 0.9 and 0% of patients experienced acute grade three and four toxicities, respectively. 5.2 and 2.1% of patients experienced late grade three and four toxicities, respectively. After a median follow‐up of 20.4 months, the 2‐year LC rate was 74% on a per‐lesion basis. Two‐year LC was 96% for lesions that were treated with BED10≥100 versus 69% for BED10

Abstract Purpose Though utilization of medical procedures has been shown to vary considerably across the United States, similar efforts to characterize variation in the delivery of radiation therapy (RT) procedures have not been forthcoming. Our aim was to characterize variation in the delivery of common RT procedures in the Medicare population. We hypothesized that delivery would vary significantly based on provider characteristics. Methods The Centers for Medicare and Medicaid Services (CMS) Physician and Other Supplier Public Use File was linked to the CMS Physician Compare (PC) database by physician NPI to identify and sum all treatment delivery charges submitted by individual radiation oncologists in the non‐facility‐based (NFB) setting in 2016. Multivariable logistic regression analysis was carried out to determine provider characteristics (gender, practice rurality, practice region, and years since graduation) that predicted for the delivery of 3D conformal RT (3DCRT), intensity modulated RT (IMRT), stereotactic body RT (SBRT), stereotactic radiosurgery (SRS), low dose rate (LDR) brachytherapy, and high dose rate (HDR) brachytherapy delivery in the Medicare patient population. The overall significance of categorical variables in the multivariable logistic regression model was assessed by the likelihood ratio test (LRT). Results In total, 1,802 physicians from the NFB practice setting were analyzed. Male gender predicted for greater LDR brachytherapy delivery (OR 8.19, 95% CI 2.58–26.05, p

Abstract Background Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT. Methods Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator’s discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used. Discussion The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies. Trial registration Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020. https://clinicaltrials.gov/ct2/show/NCT04384770 Protocol version Version 2.1, Aug 28, 2020.

Purpose: To determine the effect of daily shifts based on rigid registration to intraprostatic markers on coverage of boost doses delivered to gross nodal disease for prostate cancer. Methods and Materials: Seventy-five cone beam computed tomographies (CBCTs) from 15 patients treated with definitive radiation for clinically node-positive prostate cancer underwent fiducial-based and pelvic bony-based registration to the initial planning scans. Gross tumor volumes of nodal boost targets were contoured directly on each CBCT registration. The nodal displacement (3-dimensional translation from the node centroid on planning CT to node centroid on registered CBCT) and dose coverage (minimum dose [Dmin], mean dose [Dmean], dose delivered to 95% of the gross tumor volumes [D95]) were calculated for each registration on all nodal targets. All doses for each node were normalized to its intended prescription dose (dose covering 95% of a 3 mm planning target volume [PTV] expansion). Results: Forty-one gross nodal targets were analyzed. Most boosted nodes (80.5%, 33/41) were treated with conventional fractionation using volumetric-arc radiation therapy, and 19.5% (8/41) underwent stereotactic body radiation therapy (SBRT). Dmin, Dmean, and D95 were all significantly lower with fiducial-based registration compared with bony-based registration (P < .0001). Nodal displacement was significantly higher for fiducial-based registrations (P < .0001). The 3-dimensional translation between the fiducial-based and bony-based registrations (bony-to-fiducial vector) was the most significant predictor of nodal displacement (P < .0001). On fiducial-based registrations, a 3 to 5 mm gross nodal PTV margin is sufficient in most directions; however, superior and posterior margins of 8 to 9 mm are required as a result of asymmetrical prostatic motion. Conclusions: Large and anisotropic PTV margins are likely needed to adequately dose gross nodal targets when patient setup is based on rigid registration to intraprostatic markers. Alternative approaches such as adaptive replanning may be required to overcome these limitations.

BackgroundPatients with prostate cancer treated with stereotactic body radiation therapy (SBRT) may experience gastrointestinal (GI) toxicity. The hydrogel may mitigate this toxicity by reducing the rectal radiation dose. The purpose of this study is to compare rectal radiation dose and GI toxicity in patients receiving prostate SBRT with and without hydrogel.MethodsConsecutive patients treated with SBRT between February 2017 and January 2020 with and without hydrogel were retrospectively identified. Baseline characteristics including prostate volume, rectal diameter, body mass index (BMI), age, pretreatment prostate-specific antigen (PSA), Gleason score, T-stage, and androgen deprivation therapy (ADT) usage were compared. Dosimetric outcomes (V40Gy, V36Gy, V32Gy, V38Gy, and V20Gy), rates of acute (≤90 days) and late (>90 days) GI toxicity, and PSA outcomes were evaluated for patients with and without hydrogel.ResultsA total of 92 patients were identified (51 hydrogel and 41 non-hydrogel). There were no significant differences in baseline characteristics. Rectal V38(cc) was significantly less in the hydrogel group (mean 0.44 vs. mean 1.41 cc, p = 0.0002), and the proportion of patients with V38(cc) < 2 cc was greater in the hydrogel group (92% vs. 72%, p = 0.01). Rectal dose was significantly lower for all institutional dose constraints in the hydrogel group (p < 0.001). The hydrogel group experienced significantly less acute overall GI toxicity (16% hydrogel vs. 28% non-hydrogel, p = 0.006), while the difference in late GI toxicity trended lower with hydrogel but was not statistically significant (4% hydrogel vs. 10% non-hydrogel, p = 0.219). At a median follow-up of 14.8 months, there were no biochemical recurrences in either group.ConclusionHydrogel reduces rectal radiation dose in patients receiving prostate SBRT and is associated with a decreased rate of acute GI toxicity.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

Purpose: Previous studies have shown that stereotactic ablative radiation therapy (SABR) increases local control for cholangiocarcinoma, but gastrointestinal toxicity resulting from this treatment approach remains a concern. SABR using magnetic resonance–guided radiation therapy (MRgRT) may improve the therapeutic ratio of treatment for cholangiocarcinoma patients given the radiosensitivity of neighboring gastrointestinal organs. Methods: Seventeen consecutive patients with unresectable locally advanced cholangiocarcinoma were treated with SABR using MRgRT between May 2015 and August 2017, subsequent to our previously reported series of patients treated using a standard Linac with cone beam computed tomography. Twelve patients presented with extrahepatic cholangiocarcinoma and 5 patients with intrahepatic tumors. MRgRT-based SABR was administered at a median dose of 40 Gy in 5 fractions. Results: The median overall survival (OS) was 18.5 months, with a 1-year OS of 76% and 2-year OS of 46.1%. Three of the 17 patients progressed locally, yielding a 1-year local control of 85.6% and a 2-year local control of 73.3%. Although 12 of 17 patients experienced an acute grade 1 toxicity, none experienced acute grade 2 toxicities. One patient had an acute grade 3 duodenal ulcer with perforation (6%), and one patient had a late radiation-related toxicity grade 2 gastritis/colitis. Conclusions: Our findings demonstrate diminished toxicity and excellent overall survival and local control. The clinical outcomes and safety profile of SABR delivered with MRgRT suggest that MRgRT is a promising treatment approach for treating cholangiocarcinoma.

Purpose: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). Methods and Materials: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. Results: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P

Purpose: The clinical efficacy of radiation therapy is mechanistically linked to ionization-induced free radicals that cause cell and tissue injury through direct and indirect mechanisms. Free radical reaction dynamics are influenced by many factors and can be manipulated by static weak magnetic fields (WMF) that perturb singlet-triplet state interconversion. Our study exploits this phenomenon to directly increase ionizing radiation (IR) dose absorption in tumors by combining WMF with radiation therapy as a new and effective method to improve treatment. Methods and Materials: Coils were custom made to produce both homogeneous and gradient magnetic fields. The gradient coil enabled simultaneous in vitro assessment of free radical/reactive oxygen species reactivity across multiple field strengths from 6 to 66 G. First, increases in IR-induced free radical concentrations using oxidant-sensitive fluorescent dyes in a cell-free system were measured and verified. Next, human and murine cancer cell lines were evaluated in in vitro and in vivo models after exposure to clinically relevant doses of IR in combination with WMF. Results: Cellular responses to IR and WMF were field strength and cell line dependent. WMF was able to enhance IR effects on reactive oxygen species formation, DNA double-strand break formation, cell death, and tumor growth. Conclusions: We demonstrate that the external presence of a magnetic field enhances radiation-induced cancer cell injury and death in vitro and in vivo. The effect extends beyond the timeframe when free radicals are induced in the presence of radiation into the window when endogenous free radicals are produced and therefore extends the applicability of this novel adjunct to cancer therapy in the context of radiation treatment.

Purpose: Second malignancies (SMs) after radiation therapy are rare but serious sequelae of treatment. This study investigates whether radiation therapy use is associated with changes in baseline SM risk. Methods and Materials: We extracted all patients with cancer, with or without SM, in the Surveillance, Epidemiology, and End Results database from 1973 to 2014. Cumulative incidence of SM for patients stratified by radiation therapy status was calculated using a competing risk model, both for the entire cohort and for subgroups based on the primary tumor's anatomic location. Results: We identified 2,872,063 patients with cancer, including 761,289 patients who received radiation therapy and 2,110,774 who did not. The SM rate at 20 years for patients receiving radiation therapy versus no radiation therapy was 21.4% versus 18.8%. The relative risk for SM associated with radiation therapy for the overall group was 1.138 at 20 years. The relative risks for SM associated with radiation therapy to malignancies arising from central nervous system and orbits, head and neck, thorax, abdomen, and pelvis at 20 years were 0.704, 1.011, 0.559, 0.646, and 1.106 for men and 0.792, 1.298, 1.265, 0.780, and 0.988 for women, respectively. Conclusions: The association between SM and radiation therapy varies with both sex and disease anatomic location, with the largest increase in SM seen in females irradiated to the head and neck region. Overall, the absolute change in SM rates associated with radiation therapy remains small, with differences in various clinical contexts.

Purpose: The purpose of our study was to better understand and identify concerns that may be responsible for the declining radiation oncology (RO) residency applicant pool. Methods and Materials: All RO residency programs affiliated with a US medical school were asked to participate in the study survey. An optional and anonymous survey consisting of 12 questions was emailed to all graduating medical students in 2020 at the 12 allopathic medical schools that agreed to survey administration. Survey responses were collected from March to May 2020. Results: The study consisted of 265 survey responses out of 1766 distributed to eligible medical students, resulting in a response rate of 15.0%. The majority of students reported no exposure to RO (60.8%) and never considered it as a career option (63.8%). Neutral perceptions of the field were more common (54.3%) than positive (39.6%) and negative (6.0%). The top factors attracting medical students to RO were perceptions of high salary, favorable lifestyle and workload, and technological focus. The top negative factors were the field’s interplay with physics, competitive United States Medical Licensing Examination board scores for matched applicants, and the focus placed on research during medical school. In the subgroup of students who were interested in RO but ultimately applied to another specialty, the job market was the most salient concern. Conclusions: Finding a place for RO in medical school curricula remains a challenge, with most surveyed students reporting no exposure during their education. Concern over the job market was the primary deterrent for medical students interested in pursuing RO. For disinterested students who had not considered RO as a career option, the required physics knowledge was the main deterrent.

Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials.Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network.Results: Median follow-up time was 32.3 months (range 3–98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses.Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

Purpose: To assess the optimal planning target volume (PTV) margins for stereotactic body radiotherapy (SBRT) of prostate cancer based on inter- and intra-fractional prostate motion determined from daily image guidance.Methods and Materials: Two hundred and five patients who were enrolled on two prospective studies of SBRT (8 Gy × 5 fractions) for localized prostate cancer treated at a single institution between 2012 and 2017 had complete inter- and intra-fractional shift data available. All patients had scheduled kilovoltage planar imaging during SBRT with rigid registration to intraprostatic fiducials prior to each of four half-arcs delivered per fraction, as well as cone beam CT verification of anatomy prior to each fraction. Inter- and intra- fractional shift data were obtained to estimate the required PTV margins based on the classic van Herk formula. Inter- and intra-fractional motion were compared between patients with and without severe toxicities using the independent two-sample Wilcoxon test.Results: The margins required to account for inter-fractional motion were estimated to be 0.99, 1.52, and 1.45 cm in lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. The margins required to account for intra-fractional motion were estimated to be 0.19, 0.27, and 0.31 cm in LR, SI and AP directions, respectively. Large intra-fractional shifts were mostly observed in the SI and AP directions, with 2.0 and 5.4% of patients experiencing average intra-fractional motion >3 mm in the SI and AP directions, respectively, compared with none experiencing mean shifts >3 mm in the LR direction. Six patients experienced grade 3 gastrointestinal or genitourinary toxicity. There were no significant differences in mean inter- or intra-fractional motion in any of the cardinal directions compared to patients without severe toxicity (inter-fractional p = 0.46–0.99, intra-fractional p = 0.10–0.84).Conclusion: The inter- and intra-fractional margins estimated from this study are in line with prior reported values. Intra-fractional prostate motion was generally small with larger margins required for the SI and AP directions, notably just slightly exceeding the commonly used 3 mm posterior PTV margin even with realignment between half-arcs. Development of severe toxicity was not significantly associated with the degree of inter- or intra-fractional motion.

Purpose: To report a single-institutional experience using magnetic resonance imaging (MRI) guided radiation therapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and materials: Between October 2014 and August 2016, 13 consecutive patients with recurrent or new primary cancers of the head and neck that occurred in a previously irradiated field were prospectively enrolled in an institutional registry trial to investigate the feasibility and efficacy of MRI guided radiation therapy using a 0.35-T MRI scanner with a cobalt-60 radiation therapy source called the ViewRay system (ViewRay Inc., Cleveland, OH). Eligibility criteria included biopsy-proven evidence of recurrent or new primary squamous cell carcinoma of the head and neck, measurable disease, and previous radiation to >60 Gy. MRI guided reirradiation was delivered either using intensity modulated radiation therapy with conventional fractionation to a median dose of 66 Gy or stereotactic body radiation therapy (SBRT) using 7 to 8 Gy fractions on nonconsecutive days to a median dose of 40 Gy. Two patients (17%) received concurrent chemotherapy. Results: The 1- and 2-year estimates of in-field control were 72% and 72%, respectively. A total of 227 daily MRI scans were obtained to guide reirradiation. The 2-year estimates of overall survival and progression-free survival were 53% and 59%, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis and/or conjunctivitis, and 1 case of aspiration pneumonia. Conclusions: Our preliminary findings show that reirradiation with MRI guided radiation therapy results in effective disease control with relatively low morbidity for patients with recurrent and second primary cancers of the head and neck. The superior soft tissue resolution of the MRI scans that were used for planning and delivery has the potential to improve the therapeutic ratio.