Analysis of the Rate of Re-planning in Spot-Scanning Proton Therapy.

Purpose: Finite proton range affords improved dose conformality of radiation therapy when patient regions-of-interest geometries are well characterized. Substantial changes in patient anatomy necessitate re-planning (RP) to maintain effective, safe treatment. Regularly planned verification scanning (VS) is performed to ensure consistent treatment quality. Substantial resources, however, are required to conduct an effective proton plan verification program, which includes but is not limited to, additional computed tomography (CT) scanner time and dedicated personnel: radiation therapists, medical physicists, physicians, and medical dosimetrists. Materials and Methods: Verification scans (VSs) and re-plans (RPs) of 711 patients treated with proton therapy between June 2015 and June 2018 were studied. All treatment RP was performed with the intent to maintain original plan integrity and coverage. The treatments were classified by anatomic site: brain, craniospinal, bone, spine, head and neck (H&N), lung or chest, breast, prostate, rectum, anus, pelvis, esophagus, liver, abdomen, and extremity. Within each group, the dates of initial simulation scan, number of VSs, number of fractions completed at the time of VS, and the frequency of RP were collected. Data were analyzed in terms of rate of RP and individual likelihood of RP. Results: A total of 2196 VSs and 201 RPs were performed across all treatment sites. H&N and lung or chest disease sites represented the largest proportion of plan modifications in terms of rate of re-plan (RoR: 54% and 58%, respectively) and individual likelihood of RP on a per patient basis (likelihood of RP [RP%]: 46% and 39%, respectively). These sites required RP beyond 4 weeks of treatment, suggesting continued benefit for frequent, periodic VS. Disease sites in the lower pelvis demonstrated a low yield for RP per VS (0.01-0.02), suggesting that decreasing VS frequency, particularly late in treatment, may be reasonable. Conclusions: A large degree of variation in RoR and individual RP% was observed between anatomic treatment sites. The present retrospective analysis provides data to help develop anatomic site-based VS protocols.

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

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). P < .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, P = .04; MVA: HR, 3.64, P = .03), advanced stage disease (UVA: HR, 4.68, P < .01; MVA: HR, 3.10, P < .05), dose > 60 Gy equivalent (GyE; relative biologic effectiveness, 1.1) (UVA: HR, 1.99, P < .01; MVA: HR, 2.20, P < .01), primary disease (UVA: HR, 2.00 versus recurrent, P = .01; MVA: HR, 2.46, P = .01), concurrent chemotherapy (UVA: HR, 2.05, P < .01; MVA: not statistically significant [NS]), definitive intent treatment (UVA: HR, 1.70 versus adjuvant, P < .02; MVA: NS), bilateral neck treatment (UVA: HR, 2.07, P = .03; MVA: NS), and greater number of beams (5 beam UVA: HR, 5.55 versus 1 or 2 beams, P < .02; MVA: NS). Maximal weight change from baseline was associated with higher odds of a replan (≥3 kg: OR, 1.97, P = .04; ≥ 5 kg: OR, 2.13, P = .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.

Low-Dose Hypofractionated Total Skin Electron Beam Therapy for Adult Cutaneous T-Cell Lymphoma.

PURPOSE: Historically, the standard of care for total skin electron beam therapy (TSEBT) delivered 30 to 36 Gy over 5 to 10 weeks. Given the high risk of relapse, a majority of patients require additional treatments. Therefore, attempts to use a shortened course of TSEBT have been investigated. METHODS AND MATERIALS: We conducted a single-institution retrospective review to evaluate disease response, control, and toxicity using a low-dose, hypofractionated course of TSEBT (HTSEBT) in patients with mycosis fungoides. RESULTS: Forty patients received 57 courses of HTSEBT. Median dose (Gy)/fractionation was 12/3, spanning a median time of 2.4 weeks. Overall response rate of patients assessed (n = 54) was 100%. Thirty-one courses (57.4%) resulted in a complete response and 23 courses (42.6%) resulted in a partial response. Cumulative incidence of progressive skin disease at 3 months was 37.2%, at 6 months, 56.9%, and at 1 year, 81.5%. Of the 40 patients treated with a first course of HTSEBT, 31 received subsequent courses of radiotherapy. Cumulative incidence of subsequent treatment was 28.0% at 3 months, 46.8% at 6 months, and 70.0% at 1 year. Patients who underwent repeat courses of HTSEBT continued to have similar treatment responses to repeat courses without increased toxicities. Toxicities from all courses were acceptable with the exception of 1 patient, who experienced grade 4 skin toxicity (moist desquamation requiring hospitalization). CONCLUSIONS: Low-dose HTSEBT provides good palliation in patients with cutaneous T-cell lymphoma with a satisfactory response and toxicity profile. HTSEBT allows therapy to be completed in far fewer treatments. Low-dose HTSEBT is an appropriate treatment option for patients unable to come for daily treatment. HTSEBT provides a way to decrease exposure to other patients and staff during public health emergencies such as the coronavirus disease 2019 (COVID-19) pandemic.

11C-Choline PET Guided Salvage Radiation Therapy for Isolated Pelvic and Paraortic Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Rationale and Early Genitourinary or Gastrointestinal Toxicities.

PURPOSE: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of 11C-choline-positron emission tomography (CholPET) guided lymph node (LN) radiation therapy (RT) in patients who experience biochemical failure after radical prostatectomy. METHODS AND MATERIALS: From 2013 to 2016, 107 patients experienced biochemical failure of prostate cancer, had CholPET-detected pelvic and/or paraortic LN recurrence, and were referred for RT. Patients received androgen suppression and CholPET guided LN RT (median dose, 45 Gy) with a simultaneous integrated boost to CholPET-avid sites (median dose, 56.25 Gy), all in 25 fractions. RT-naïve patients had the prostatic fossa included in the initial treatment volumes followed by a sequential boost (median dose, 68 Gy). GI and GU AEs were reported per Common Terminology Criteria for Adverse Events (version 4.0) with data gathered retrospectively. Differences in maximum GI and GU AEs at baseline, immediately post-RT, and at early (median, 4 months) and late (median, 14 months) follow-up were assessed. RESULTS: Median follow-up was 16 months (interquartile range [IQR], 11-25). Median prostate-specific antigen at time of positive CholPET was 2.3 ng/mL (IQR, 1.3-4.8), with a median of 2 (IQR, 1-4) choline-avid LNs per patient. Most recurrences were within the pelvis (53%) or pelvis + paraortic (40%). Baseline rates of grade 1 to 2 GI AEs were 8.4% compared with 51.9% (4.7% grade 2) of patients post-RT (P < .01). These differences resolved by 4-month (12.2%, P = .65) and 14-month AE assessments (9.1%, P = .87). There was no significant change in grade 1 to 2 GU AEs post-RT (64.1%) relative to baseline (56.0%, P = .21), although differences did arise at 4-month (72.2%, P = .01) and 14-month (74.3%, P = .01) AE assessments. CONCLUSIONS: Salvage CholPET guided nodal RT has acceptably low rates of acute GI and GU AEs and no significant detriment in 14-month GI AEs. These data are of value in counseling patients and designing prospective trials evaluating the oncologic efficacy of this treatment strategy.

The Implications of Genetic Testing on Radiation Therapy Decisions: A Guide for Radiation Oncologists.

The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision-making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Because scarce clinical data exist to inform decisions at this time, the American Society for Radiation Oncology convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. During the American Society for Radiation Oncology workshop, several main points emerged, which are discussed in this manuscript: (1) variants of uncertain significance should be considered nondeleterious until functional genomic data emerge to demonstrate otherwise; (2) possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; (3) deleterious ataxia-telangiesctasia gene mutations may modestly increase second cancer risk after radiation therapy, and thus follow-up for these patients after indicated radiation therapy should include second cancer screening; (4) conveying to patients the difference between relative and absolute risk is critical to decision-making; and (5) more work is needed to assess the impact of tumor somatic alterations on the probability of response to radiation therapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

Percutaneous Image-Guided Nodal Biopsy After 11C-Choline PET/CT for Biochemically Recurrent Prostate Cancer: Imaging Predictors of Disease and Clinical Implications.

PURPOSE: Management of recurrent prostate cancer necessitates timely diagnosis and accurate localization of the sites of recurrent disease. The purpose of this study was to assess predictors of histologic outcomes after 11C-choline positron emission tomography/computed tomography (CholPET) to increase the positive predictive value and specificity of CholPET in identifying imaging predictors of malignant and benign nodal disease to better inform clinical decision making regarding local therapy planning. MATERIALS AND METHODS: Retrospective review of patients undergoing CholPET followed by percutaneous core needle biopsy between January 1, 2010 and January 1, 2016. A total of 153 patients were identified who underwent 166 biopsy procedures. Patient, CholPET, procedural, and pathologic characteristics were recorded. RESULTS: A total of 157 biopsies were technically successful, and 110 (70.1%; 95% confidence interval, 62.2-77.1) yielded histologic results abnormal for metastatic prostate cancer. Lesion location, lesion maximum standardized uptake value (SUVmax), SUV ratio (calculated as the ratio of SUVmax to SUV mean in the right atrium), prostate-specific antigen, lesion short axis length, total Gleason score, and castration resistance were all associated with abnormal biopsy results (P values <.001, <.001, <.001, .02, .02, .02, and .015, respectively). External iliac, common iliac, and inguinal sites were associated with much lower rates of histologic positivity (mean [95% confidence interval], 51.2% [35.1-67.1], 46.2% [19.2-74.9], and 33.3% [7.5-70.1]), respectively. CONCLUSIONS: In a cohort of patients in whom core needle biopsy was performed after CholPET, characteristics of choline localization including node location, SUVmax, lesion-to-blood pool SUV ratio, prostate-specific antigen, total Gleason score, and castration resistance were significantly associated with abnormal biopsy results for metastatic disease on CholPET. Relatively high false positive rates were found in common iliac, external iliac, and inguinal lymph node locations. Histologic confirmation of these sites should be strongly considered in the appropriate clinical scenario before designing additional local therapy plans.

Prospective Immunophenotyping of CD8+ T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT.

PURPOSE: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8+ T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa). METHODS AND MATERIALS: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8+ T-cell subpopulations, including tumor-reactive (TTR), effector memory, central memory (TCM), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk. RESULTS: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the TTR cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032). CONCLUSIONS: An increase in the TTR cell subpopulation was protective against the risk of disease progression, and an increase in the TCM cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8+ T-cell subpopulations and by enhancing their antitumor effect.

Prostate cancer-specific PET radiotracers: A review on the clinical utility in recurrent disease.

Prostate cancer-specific positron emission tomography (pcPET) has been shown to detect sites of disease recurrence at serum prostate-specific antigen (PSA) levels that are lower than those levels detected by conventional imaging. Commonly used pcPET radiotracers in the setting of biochemical recurrence are reviewed including carbon 11/fludeoxyglucose 18 (F-18) choline, gallium 68/F-18 prostate-specific membrane antigen (PSMA), and F-18 fluciclovine. Review of the literature generally favors PSMA-based agents for the detection of recurrence as a function of low PSA levels. Positive gallium 68/F-18 PSMA positron emission tomography/computed tomography scans detected potential sites of recurrence in a median 51.5% of patients when PSA level is <1.0 ng/mL, 74% of patients when PSA level is 1.0 to 2.0 ng/mL, and 90.5% of patients when PSA level is >2.0 ng/mL. Review of carbon 11/fludeoxyglucose 18 (F-18) choline and F-18 fluciclovine data commonly demonstrated lower detection rates for each respective PSA cohort, although with some important caveats, despite having similar operational characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new insight into the early patterns of disease spread, which has prompted judicious reconsideration of additional local therapy after either prostatectomy, definitive radiation therapy, or postprostatectomy radiation therapy. This review discusses the literature, clinical utility, availability, and fundamental understanding of pcPET imaging needed to improve clinical practice.

A Multi-institutional Analysis of Trimodality Therapy for Esophageal Cancer in Elderly Patients.

PURPOSE: The therapeutic gains of neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy may be offset by increased incidences of morbidity and mortality in elderly patients. This study aimed to determine the impact of age on the risks and benefits of trimodality therapy for esophageal cancer. METHODS AND MATERIALS: We evaluated 571 patients treated with trimodality therapy at 3 high-volume tertiary cancer centers in the United States from 2007 to 2013. Two hundred two of 571 (35%) patients were 65 years or older at diagnosis and were classified as elderly. Toxicity and treatment parameters for the elderly cohort were compared with the younger cohort (ages 22-64) by the use of univariate (UVA) and multivariable (MVA) logistic analyses. Age was analyzed as a continuous hazard for cardiac and pulmonary toxicities. Survival was assessed by the Kaplan-Meier method. RESULTS: Elderly patients had a higher risk for postoperative cardiac toxicities (UVA: odds ratio [OR] 2.2, P<.001; MVA: OR 2.07, P=.004) and pulmonary toxicities (UVA: OR 2.0, P<.001; MVA: OR 2.03, P<.001) and a higher 90-day postoperative mortality (5.4% vs 2.2%, P=.049). Of the elderly patients, 6.9% experienced acute respiratory distress syndrome compared with 3.8% of younger patients (P=.11). Cardiac toxicity was linearly associated with age, and the relative risk increased by 61% for every additional decade of age. There was no difference in postoperative gastrointestinal or wound adverse events or in length of hospital stay. Grade 3+ acute toxicities from nCRT were infrequent and were clinically similar regardless of age. Freedom from esophageal cancer and disease-free survival were similar, but overall survival was significantly shorter in the elderly cohort. CONCLUSIONS: Elderly patients experienced more postoperative cardiopulmonary toxicities and mortality than did younger patients after nCRT. Compared with contemporary outcomes for trimodality therapy, both cohorts had acceptable rates for adverse events and disease control. For appropriately selected elderly patients, trimodality therapy for esophageal cancer is a reasonable treatment option.

Patterns of Recurrence After Postprostatectomy Fossa Radiation Therapy Identified by C-11 Choline Positron Emission Tomography/Computed Tomography.

PURPOSE: To evaluate C-11 choline positron emission tomography/computed tomography (CholPET) in staging and determining patterns of recurrence in prostate cancer patients with rising prostate-specific antigen levels after prostatectomy radiation therapy (RT). METHODS AND MATERIALS: The study includes patients with biochemical failure after postprostatectomy RT who underwent CholPET between 2008 and 2015. Patient and disease characteristics were examined in relation to sites of recurrence. All RT dosimetry records were reviewed, and recurrences were mapped on a representative computed tomography dataset with their relationship relative to the irradiated fossa field as out of field (OOF), edge of field (EOF; recurrence within <45-Gy isodose lines), or in field (IF; recurrence within ≥45-Gy isodose lines). RESULTS: Forty-one patients were identified with 121 sites of recurrence (median 2 sites; interquartile range [IQR], 1-4). The median prostate-specific antigen level at CholPET was 3.1 (IQR, 1.9-5.6) ng/mL. Median interval from RT to biochemical failure was 24 (IQR, 10-46) months, with recurrence identified on CholPET at a median of 15 (IQR, 7-28) months from biochemical failure. Histologic confirmation of recurrence was obtained in 20 patients (49%), with the remainder confirmed by treatment response. Five patients (12%) had IF recurrences, 10 patients (24%) had EOF recurrences (median dose 10 Gy; IQR, 5-30 Gy), and 36 patients (88%) had OOF recurrences. Ten patients had combination failures: 6 (15%) EOF/OOF and 4 (10%) IF/OOF. Fifty-seven recurrences (47%) were pelvic nodal sites inferior to the L5-S1 interspace, of which 52 (43%) were within a pelvic RT field. Eighty-one recurrences (67%) were nodal and inferior to the aortic bifurcation. CONCLUSIONS: Using CholPET, we found that the majority of patients evaluated for biochemical failure recurred outside of the postprostatectomy RT field. Furthermore, most recurrence sites were nodal and inferior to the aortic bifurcation. These results provide data that may be useful for examining strategies that include elective lymph node irradiation in postprostatectomy patients.

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease.

BACKGROUND: Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE: To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION: C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS: Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS: CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY: We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

Cardiac ¹8F-fluorodeoxyglucose uptake on positron emission tomography after thoracic stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: Previous studies have shown that increased cardiac uptake of (18)F-fluorodeoxyglucose (FDG) on positron emission tomography (PET) may be an indicator of myocardial injury after radiotherapy. We reviewed patients treated with thoracic stereotactic body radiation therapy (SBRT) and established correlations between SBRT dose and observed changes in cardiac FDG-PET uptake. MATERIAL AND METHODS: Retrospective analysis identified 39 patients that were treated with SBRT for lung tumors close to the heart. Patients were grouped according to whether or not they had changes in cardiac FDG-PET uptake within the planned SBRT field. RESULTS: At a median follow-up interval of 39 months (range, 6-81 months), nine patients (23%) showed increased cardiac FDG uptake associated with the heart V20. Of the 19 patients who received 20 Gy to ≥5 cm(3) of the heart, nine (47%) developed increased FDG uptake (vs. 0% for the 20 patients who received 20 Gy to <5 cm(3)) (P=0.0004), all within the 20-Gy isodose line. Patients with hypercholesterolemia prior to SBRT were also more likely to show increased cardiac FDG uptake (P=0.0190). CONCLUSION: Increased FDG uptake in the heart after SBRT was observed when the 20 Gy isodose line exceeded 5 cm(3) of the heart.

Aortic dose constraints when reirradiating thoracic tumors.

BACKGROUND AND PURPOSE: Improved radiation delivery and planning has allowed, in some instances, for the retreatment of thoracic tumors. We investigated the dose limits of the aorta wherein grade 5 aortic toxicity was observed after reirradiation of lung tumors. MATERIAL AND METHODS: In a retrospective analysis, 35 patients were identified, between 1993 and 2008, who received two rounds of external beam irradiation that included the aorta in the radiation fields of both the initial and retreatment plans. We determined the maximum cumulative dose to 1 cm(3) of the aorta (the composite dose) for each patient, normalized these doses to 1.8 Gy/fraction, and corrected them for long-term tissue recovery between treatments (NIDR). RESULTS: The median time interval between treatments was 30 months (range, 1-185 months). The median follow-up of patients alive at analysis was 42 months (range, 14-70 months). Two of the 35 patients (6%) were identified as having grade 5 aortic toxicities. There was a 25% rate of grade 5 aortic toxicity for patients receiving composite doses ≥120.0 Gy (vs. 0% for patients receiving <120.0 Gy) (P=0.047). CONCLUSIONS: Grade 5 aortic toxicities were observed with composite doses ≥120.0 Gy (NIDR ≥90.0 Gy) to 1cm(3) of the aorta.