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IMPORTANCE: Understanding whether physicians accurately detect symptoms in patients with breast cancer is important because recognition of symptoms facilitates supportive care, and clinical trials often rely on physician assessments using Common Toxicity Criteria for Adverse Events (CTCAE). OBJECTIVE: To compare the patient-reported outcomes (PROs) of patients with breast cancer who received radiotherapy from January 1, 2012, to March 31, 2020, with physicians’ CTCAE assessments to assess underrecognition of symptoms. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included a total of 29 practices enrolled in the Michigan Radiation Oncology Quality Consortium quality initiative. Of 13 725 patients with breast cancer who received treatment with radiotherapy after undergoing lumpectomy, 9941 patients (72.4%) completed at least 1 PRO questionnaire during treatment with radiotherapy and were evaluated for the study. Of these, 9868 patients (99.3%) were matched to physician CTCAE assessments that were completed within 3 days of the PRO questionnaires. EXPOSURES: Patient and physician ratings of 4 symptoms (pain, pruritus, edema, and fatigue) were compared. MAIN OUTCOMES AND MEASURES: We used multilevel multivariable logistic regression to evaluate factors associated with symptom underrecognition, hypothesizing that it would be more common in racial and ethnic minority groups. RESULTS: Of 9941 patients, all were female, 1655 (16.6%) were Black, 7925 (79.7%) were White, and 361 (3.6%) had Other race and ethnicity (including American Indian/Alaska Native, Arab/Middle Eastern, and Asian), either as self-reported or as indicated in the electronic medical record. A total of 1595 (16.0%) were younger than 50 years, 2874 (28.9%) were age 50 to 59 years, 3353 (33.7%) were age 60 to 69 years, and 2119 (21.3%) were 70 years or older. Underrecognition of symptoms existed in 2094 of 6781 (30.9%) observations of patient-reported moderate/severe pain, 748 of 2039 observations (36.7%) of patient-reported frequent pruritus, 2309 of 4492 observations (51.4%) of patient-reported frequent edema, and 390 of 2079 observations (18.8%) of patient-reported substantial fatigue. Underrecognition of at least 1 symptom occurred at least once for 2933 of 5510 (53.2%) of those who reported at least 1 substantial symptom. Factors independently associated with underrecognition were younger age (younger than 50 years compared with 60-69 years: odds ratio [OR], 1.35; 95% CI, 1.14-1.59; P

Simple intensity modulation of radiation therapy reduces acute toxicity compared with 2-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiation therapy (IMRT) offers an advantage over forward-planned, 3-dimensional conformal radiation therapy (3DCRT).Using prospective data regarding patients receiving adjuvant whole breast radiation therapy without nodal irradiation at 23 institutions from 2011 to 2018, we compared the incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle). We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting, adjusting for treatment facility as a random effect.Of 1185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly segmented forward-planned IMRT, 458 (59.2%) did; and of 580 treated with inverse-planned IMRT, 245 (42.2%) did. Of 1296 patients treated with hypofractionation and 3DCRT, 432 (33.3%) experienced acute toxicity; of 709 treated with highly segmented forward-planned IMRT, 227 (32.0%) did; and of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with inverse-probability-of-treatment weighting, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% confidence interval, 0.45-0.91) with conventional fractionation and 0.41 (95% confidence interval, 0.26-0.65) with hypofractionation.This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared with 3DCRT in reducing acute toxicity of breast radiation therapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness.

Introduction: Little data have been reported about the patient experience during curative radiotherapy for lung cancer in routine clinical practice, or how this relates to treatment toxicity reported by clinicians. The purpose of this study was to compare clinician-reported adverse events (AEs) with patient-reported outcomes (PROs) including both specific symptoms/side effects as well as overall quality of life (QOL) during and after definitive radiotherapy (RT) for locally advanced lung cancer (LALC) in a large statewide cohort. Methods and Materials: Patient-reported outcomes (PROs) were prospectively collected from patients treated with definitive radiotherapy for LALC at 24 institutions within the XXXX Radiation Oncology Quality Consortium between 2012-2018 using the Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI). Physicians prospectively recorded adverse events (AEs) using CTCAE version 4.0. Patient-reported quality of life (QOL) changes from baseline were assessed during and after radiotherapy using the FACT-TOI. Spearman correlation coefficients were calculated for AEs and similar PROs, and multivariable analysis was used to assess associations with QOL. Results: 1361 patients were included and 53% of respondents reported clinically meaningful declines in QOL at the end of RT. Correlation between clinician-reported esophagitis and patient-reported trouble swallowing was moderate (R=0.67) while correlations between clinician-reported pneumonitis and patient-reported shortness of breath (R=0.13) and cough (R=0.09) were weak. Clinician-reported AEs were significantly associated with clinically meaningful declines inpatient-reported QOL, with R=-0.46 for a summary AE-score. QOL was more strongly associated with fatigue (R=-0.41) than lung-specific AEs. Conclusions: AEs are associated with clinically meaningful declines in QOL during and after RT for LALC, but associations between AEs and QOL are only modest. This highlights the importance of PRO data, and future research should assess whether earlier detection of PRO changes could allow for interventions that reduce the frequency of treatment-related clinically meaningful declines in QOL.

Purpose Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. Methods Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)–approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. Results Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. Conclusions In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation.

PURPOSE: Adjuvant therapy in patients with ductal carcinoma in situ who undergo partial mastectomy remains controversial, particularly for low-risk patients (60 years or older, estrogen-positive, tumor extent < 2.5 cm, grade 1 or 2, and margins ≥ 3 mm). We performed a cost-effectiveness analysis comparing three strategies: no adjuvant treatment after surgery, a five-fraction course of accelerated partial breast irradiation using intensity-modulated radiation therapy (accelerated partial breast irradiation [APBI]–alone), or APBI plus an aromatase inhibitor for 5 years. MATERIALS AND METHODS: Outcomes including local recurrence, distant metastases, and survival as well as toxicity data were modeled by a patient-level Markov microsimulation model, which were validated against trial data. Costs of treatment and possible adverse events were included from the societal perspective over a lifetime horizon, adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALYs) were calculated based on utilities extracted from the literature. RESULTS: No adjuvant therapy was the least costly approach ($5,744), followed by APBI-alone ($11,070); combined therapy was costliest ($16,052). Adjuvant therapy resulted in slightly higher QALYs (no adjuvant, 11.320; APBI-alone, 11.343; and combination, 11.381). In the base case, no treatment was the cost-effective strategy, with an incremental cost-effectiveness ratio of $239,109/QALY for APBI-alone and $171,718/QALY for combined therapy. The incremental cost-effectiveness ratio for combined therapy compared with APBI-alone was $131,949. Probabilistic sensitivity analyses found that no therapy was cost effective (defined as $100,000/QALY of lower) in 63% of trials, APBI-alone in 19%, and the combination in 18%. CONCLUSION: No adjuvant therapy represents the most cost-effective approach for postmenopausal women 60 years or older who receive partial mastectomy for low-risk ductal carcinoma in situ.

Cannabis use rates are increasing in the United States. Patients with cancer use cannabis for many reasons, even without high-quality supporting data. This study sought to characterize cannabis use among patients seen in radiation oncology in a state that has legalized adult non-medical use cannabis and to identify key cannabis-related educational topics.Cannabis history was documented by providers using a structured template at patient visits in an academic radiation oncology practice 10/2020-11/2021. Cannabis use data, including recency/frequency of use, reason, and mode of administration, were summarized, and logistic regression was used to explore associations between patient and disease characteristics and recent cannabis use. A multivariable model employed stepwise variable selection using the Akaike Information Criterion (AIC).Of 3143 patients total, 91 (2.9%) declined to answer cannabis use questions, while 343 (10.9%) endorsed recent use (≤1 month ago), 235 (7.5%) noted non-recent use (1 month ago), and 2474 (78.7%) denied history of cannabis use. In multivariable analyses, those ≥50 years old [OR 0.409 (95%CI 0.294, 0.568), p0.001] or with history of prior courses of radiation [OR 0.748 (95%CI: 0.572, 0.979), p=0.034] were less likely, while those with a mental health diagnosis not related to substance use [OR 1.533 (95%CI: 1.171, 2.005), p=0.002] or who smoked tobacco [OR 3.003 (95%CI 2.098,4.299) p0.001] were more likely to endorse recent cannabis use. Patients reported pain, insomnia, and anxiety as the most common reasons for use. Smoking was the most common mode of administration.Patients are willing to discuss cannabis use with providers and reported recent cannabis use for a variety of reasons. Younger patients new to oncologic care and those with a history of mental illness or tobacco smoking may benefit most from discussions about cannabis given higher rates of cannabis use in these groups.

Purpose Scales for rating acute radiation dermatitis (ARD) have not been validated despite decades of clinical use, and little is known regarding the relationship between toxicity scores and patient-reported symptoms. Skin tone also complicates assessment of ARD, and as such we sought to design an illustrated scale to consistently describe ARD across several skin tone types in breast cancer patients undergoing radiation (RT). Methods and Materials Patients undergoing RT for breast cancer were enrolled on a prospective study with photographs obtained at 2-week intervals. Photographs were clustered according to the apparent severity of acute radiation dermatitis and a descriptive photonumeric scale was developed. Four clinically experienced raters used both the illustrated photonumeric scale and the Common Terminology Criteria for Adverse Events to independently score the collection of photographs in 2 independent sessions. Results Among 80 unique patients with 192 photographs, 47 patients (59%) completed questionnaires about their symptoms during RT. Physicians completed toxicity forms at the point-of-care for 52 patients (65%). Photonumeric ratings compared against patient reports of dry and moist desquamation demonstrated high specificity (95% and 93%, respectively) and negative predictive value (84% and 92%), indicating correct identification of patients who did not report dry or moist desquamation. The sensitivity and positive predictive value for separate measures of dry and moist desquamation were considerably lower. A combined measure of any desquamation (dry or moist) portrayed higher diagnostic accuracy, resulting in 72% sensitivity, 93% specificity, 75% positive predictive value, and 92% negative predictive value. Photonumeric ratings of dry or moist desquamation were significantly associated with patient reports of itching, burning or stinging, hurting, and swelling. Conclusions The Michigan scale for acute radiation dermatitis is a simple grading rubric that is distinguished by characterization of its intra- and interrater reliability and diagnostic accuracy, correlation with patient-reported symptoms of bother and pain, and applicability across the spectrum of skin pigmentation.

BACKGROUND: Current national guidelines encourage consideration for treating the at-risk regional nodes (axillary, supraclavicular, and/or internal mammary) with directed regional nodal irradiation (RNI) during post-lumpectomy radiotherapy for high risk N0 (node negative) and N1 (1-3 nodes positive) breast cancer patients. This recommendation is based on the results of several randomized trials published over the last decade. Evidence regarding translation of these trials into clinical practice in the United States has been limited to date. In this study, we sought to characterize the temporal changes in and clinical factors associated with the utilization of RNI during post-lumpectomy radiotherapy for N0-N1 breast cancer across a contemporary, statewide consortium of radiation oncology practices. METHODS: Within a statewide radiation oncology quality consortium, 12,170 breast cancer patients were consecutively enrolled between 1/1/2013 and 10/31/2019 in both academic (teaching) and community (non-teaching) facilities. Data on receptor status, adjuvant systemic therapy, age, TNM stage, extent of axillary surgery, race, body mass index (BMI), type of treating facility, and year completing radiotherapy (RT) were collected. Eligibility for the present analysis was limited to patients with N0 and N1 disease not receiving neoadjuvant systemic therapy and receiving adjuvant radiotherapy after lumpectomy for non-metastatic breast cancer. Multiple variable logistic regression models were separately fit to explain the use of directed RNI (to the axilla, supraclavicular region, and/or internal mammary region) for the N0 and N1 populations separately and described using odds ratios (OR), with significant ORs (p RESULTS: A total of 8,468 patients from 29 treating facilities met the inclusion criteria: 6,929 (81.8%) with N0 and 1,539 (18.2%) N1 disease. RNI was performed in addition to whole breast radiation in 95 (1.4%) and 908 (59%) patients in the N0 and N1 cohorts respectively. For the N0 cohort, significant correlates of RNI on multivariable analysis (MVA) were receipt of adjuvant chemotherapy (OR 2.7), higher T-stage (OR 1.9 for T2 vs T1 and 27.3 for T3/T4 vs T1), axillary surgery [compared to sentinel node biopsy (SLN) alone : no axillary surgery (OR 14.5), axillary lymph node dissection (ALND) with 10+ nodes removed (OR 15.1) ALND after SLN (OR 2.7)], and underweight BMI (OR 4.9 compared to overweight, which was the reference as the largest BMI category). For the N1 cohort, MVA suggested adjuvant chemotherapy (OR 1.8) and larger tumors (OR 1.6 [T2 vs T1]) were significantly associated with use of RNI. The year completing RT was also significantly associated with RNI use, with 22% and 15% increases per year from 2013 to 2019 in the N0 and N1 cohorts, respectively. Lastly, receiving treatment in an academic facility compared to a community facility was significantly associated with receipt of RNI in both the N0 (OR 1.8) and N1 (OR 2.2) cohorts. CONCLUSION: In this large cohort, selective use of RNI added to post-lumpectomy whole breast radiotherapy is estimated to have increased over time, suggesting growing implementation of recent trial data and current clinical practice guidelines. Patient, treatment, and tumor characteristics appear to factor into the decision to treat with RNI, but differences in use between academic and community practices suggest opportunities for improving the consistency of care across care delivery settings. Ongoing trials seeking to identify subgroups of N1 patients in whom RNI can safely be omitted may be especially important to inform decisions, given the almost even split (59% receiving, 41% not) in practice observed in this large American cohort. Citation Format: Derek Bergsma, Kent Griffith, Reshma Jagsi, Michael Dominello, Thomas Boike, Joshua Dilworth, Amit Bhatt, Frank Vicini, Maggie Grubb, Jean Moran, James Hayman, Lori Pierce, on behalf of MROQC, the Michigan Radiation Oncology Quality Consortium. Contemporary practice patterns for the use of regional nodal irradiation during post-lumpectomy radiotherapy for patients with N0/N1 breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-07.

BACKGROUND: Evaluating whether physicians (MDs) accurately detect symptoms in patients (pts) is important because recognition of symptoms facilitates supportive care and because clinical trials often rely on MD assessments using the Common Toxicity Criteria for Adverse Events (CTCAE). METHODS: Breast cancer pts who received radiotherapy (RT) after lumpectomy at 29 practices were enrolled in a quality initiative, MROQC. Of 13,725 pts who completed RT between 1/1/2012 and 3/31/2020, 9,941 completed at least one pt-reported outcomes (PRO) questionnaire during RT. Where MD CTCAE assessments were available within 3 days of PRO evaluation, pt and MD ratings of 4 symptoms were compared. Pts reported breast pain via an approved modification of the Brief Pain Inventory, asking for ratings in the last 24 hours of pain at its worst, least, average, and “right now.” MDs were deemed to under-recognize pain when pts reported moderate pain (score 4-6) but MDs graded pain as 0 (absent) on the CTCAE, or when pts reported severe pain (score 7-10) but MDs’ CTCAE grade was ≤1. Bother from pruritis and edema were measured by modified scaled measures adapted from the Skindex. MDs were deemed to under-recognize pruritus and edema if they graded these as absent (grade 0) when pts reported bother often or all of the time from itching or swelling, respectively. MDs were deemed to under-recognize fatigue if they graded fatigue as absent (grade 0) when pts reported having significant fatigue most of the time or always.We describe the proportion of pts for whom under-recognition of at least 1 of these 4 symptoms occurred at least once during the treatment course and use multivariable logistic regression to evaluate predictors of this under-recognition, hypothesizing that it would be more common in racial minorities. RESULTS: 3,434/9,940 pts (34.5%) reported substantial breast pain, 3,039/9,923 (30.6%) frequent bother from pruritus, 2,363/9,906 (23.9%) frequent bother from edema, and 2,209/8,860 (24.9%) severe fatigue. We could evaluate under-recognition in 9,868 pts, with 37,593 independent paired observations of pt and MD reports (35,797 on the same date and 1,796 within 3 days). Under-recognition existed in 2,094/6,781 (30.9%) observations of pt-reported moderate/severe pain, 748/2,039 (36.7%) of pt-reported frequent pruritis, 2,309/4,492 (51.4%) of pt-reported frequent edema, and 390/2,079 (18.8%) of pt-reported severe fatigue. Under-recognition of at least 1 of these 4 symptoms occurred at least once during the pt’s treatment course for 2,933/5,510 (53.2%) of the pts who reported at least 1 substantial symptom during RT.Factors independently associated with under-recognition were (Table): younger age (OR=1.4 and 1.2 for CONCLUSIONS: PRO collection appears essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since MDs systematically miss substantial symptoms in certain patients, including pts who are younger or of black or other race, improving symptom detection may be a targetable mechanism to reduce disparities in RT experiences and outcomes. Multivariable model of symptom under-recognitionOR95% CIpAge--0.001 Citation Format: Reshma Jagsi, Kent A. Griffith, Frank Vicini, Thomas Boike, Michael Dominello, Gregory Gustafson, James A. Hayman, Jean M. Moran, Jeffrey Radawski, Eleanor Walker, Lori J. Pierce, on behalf of MROQC, the Michigan Radiation Oncology Quality Consortium. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-07.

PURPOSE Understanding acute toxicities after whole-breast radiotherapy is important to inform patients, guide treatment decisions, and target supportive care. We evaluated patient-reported outcomes prospectively collected from a cohort of patients with breast cancer. METHODS We describe the maximal toxicity reported by 8,711 patients treated between 2012 and 2019 at 27 practices. Multivariable models identified characteristics associated with (1) breast pain, (2) bother from itching, stinging/burning, swelling, or hurting of the treated breast, and (3) fatigue within 7 days of completing whole-breast radiotherapy. RESULTS Moderate or severe breast pain was reported by 3,233 (37.1%): 1,282 (28.9%) of those receiving hypofractionation and 1,951 (45.7%) of those receiving conventional fractionation. Frequent bother from at least one breast symptom was reported by 4,424 (50.8%): 1,833 (41.3%) after hypofractionation and 2,591 (60.7%) after conventional fractionation. Severe fatigue was reported by 2,008 (23.1%): 843 (19.0%) after hypofractionation and 1,165 (27.3%) after conventional fractionation. Among patients receiving hypofractionated radiotherapy, younger age ( P < .001), higher body mass index (BMI; P < .001), Black ( P < .001) or other race ( P = .002), smoking status ( P < .001), larger breast volume ( P = .002), lack of chemotherapy receipt ( P = .004), receipt of boost treatment ( P < .001), and treatment at a nonteaching center predicted breast pain. Among patients receiving conventionally fractionated radiotherapy, younger age ( P < .001), higher BMI ( P = .003), Black ( P < .001) or other race ( P = .002), diabetes ( P = .001), smoking status ( P < .001), and larger breast volume ( P < .001) predicted breast pain. CONCLUSION In this large observational data set, substantial differences existed according to radiotherapy dose fractionation. Race-related differences in pain existed despite controlling for multiple other factors; additional research is needed to understand what drives these differences to target potentially modifiable factors. Intensifying supportive care may be appropriate for subgroups identified as being vulnerable to greater toxicity.

The addition of adjuvant durvalumab improves overall survival in locally advanced nonsmall-cell lung cancer (NSCLC) patients treated with definitive chemoradiation, but the real-world uptake of adjuvant durvalumab is unknown.We identified patients with stage III NSCLC treated with definitive concurrent chemoradiation from January 2018 to October 2020 from a statewide radiation oncology quality consortium, representing a mix of community (n=22 centers) and academic (n=5) across the state of Michigan. Use of adjuvant durvalumab was ascertained at the time of routine 3-month or 6-month follow-up after completion of chemoradiation.Of 421 patients with stage III NSCLC who completed chemoradiation, 322 (76.5%) initiated adjuvant durvalumab. The percentage of patients initiating adjuvant durvalumab increased over time from 66% early in the study period to 92% at the end of the study period. There was substantial heterogeneity by treatment center, ranging from 53% to 90%. In multivariable logistic regression, independent predictors of durvalumab initiation included more recent month (odds ratio [OR]: 1.05 per month, 95% confidence interval [CI]: 1.02-1.08, P=0.003), lower Eastern Cooperative Oncology Group score (OR: 4.02 for ECOG 0 vs. 2+, 95% CI: 1.67-9.64, P=0.002), and a trend toward significance for female sex (OR: 1.66, 95% CI: 0.98-2.82, P=0.06).Adjuvant durvalumab for stage III NSCLC treated with definitive chemoradiation was rapidly and successfully incorporated into clinical care across a range of community and academic settings in the state of Michigan, with over 90% of potentially eligible patients starting durvalumab in more recent months.

Purpose Therapeutic misconception is the tendency for a clinical trial participant to overlook the scientific objective of a clinical trial and instead believe that an experimental intervention is intended for personal therapeutic benefit. We sought to evaluate this tendency in the setting of a clinical trial of a new radiation therapy technology. Methods Patients with left-sided, node positive breast cancer enrolled in a randomized clinical trial evaluating intensity modulated radiation therapy with deep inspiration breath hold (IMRT-DIBH) versus 3-dimensional conformal radiation therapy (3DCRT). Patients who enrolled completed surveys at baseline, after randomization, and upon completion of radiation therapy to evaluate expectations, satisfaction, and experiences. Results Forty women participated in the survey study, with 20 in each arm. Most participants endorsed the perception that participation in the trial might result in better treatment than the current standard treatment (77%) and more medical attention than being off trial (54%). At baseline, most women (74%) believed that a new treatment technology is superior than an established one. Before randomization, 43% of participants believed IMRT-DIBH would be more effective than standard treatment with 3DCRT, none believed that 3DCRT would be more effective, 23% believed that they would be the same, and 34% did not know. None believed that IMRT-DIBH would cause worse long-term side effects, whereas 37% thought that 3DCRT would. Most (71%) reported that they would choose to be treated with IMRT-DIBH; none would have elected 3DCRT if given a choice. Nearly half (44%) in the 3DCRT arm wished that they had been assigned to the IMRT-DIBH arm; none in the IMRT-DIBH arm expressed a wish for crossover. Conclusions Most participants reported the perception that trial participation would result in better treatment and more medical attention than off trial, hallmarks of therapeutic misconception. Our observations provide empirical evidence of a fixed belief in the superiority of new technology and highlight the importance of adjusting expectations through informed consent to mitigate therapeutic misconception.

Purpose Preclinical data and subset analyses from immunotherapy clinical trials indicate that prior radiation therapy was associated with better progression-free survival and overall survival when combined with immune checkpoint inhibitors in patients with non-small cell lung cancer. We present a prospective study of hypofractionated image guided radiation therapy (HIGRT) to a single site of metastatic disease concurrently with atezolizumab in patients with metastatic non-small cell lung cancer. Methods and Materials Patients meeting eligibility criteria received 1200 mg of atezolizumab intravenously every 3 weeks with concurrent 3- or 5-fraction HIGRT starting no later than the second cycle. The 3-fraction regimen employed a minimum of 8 Gy per fraction compared with 6 Gy for the 5-fraction regimen. Imaging was obtained every 12 weeks to assess response. Results From October 2015 to February 2017, 12 patients were enrolled in the study (median age 64; range, 55-77 years). The best response by the Response Evaluation in Solid Tumors criteria was partial response in 3 and stable disease in 3, for a disease control rate of 50%. Five patients had a grade 3 immune-related adverse event, including choreoretinitis (n = 1), pneumonitis (n = 1), transaminitis (n = 1), fatigue (n = 1), and peripheral neuropathy (n = 1). The median progression-free survival was 2.3 months, and the median overall survival was 6.9 months (range, 0.4-not reached). There was no clear association between peripheral blood T cell repertoire characteristics at baseline, PD-L1, or tumor mutations and response or outcome. One long-term survivor exhibited oligoclonal T cell populations in a baseline tumor biopsy that were consistently detected in peripheral blood over the entire course of the study. Conclusions HIGRT plus atezolizumab resulted in an overall response rate of 25% and disease control rate of 50% in this pilot study. The incidence of grade 3 adverse events was similar to that of atezolizumab alone. Alhough it was a pilot study with limited sample size, the results generated hypotheses worthy of further investigation.

Purpose To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response. Methods and Materials Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m2, 8.4 mg/m2, 16.5 mg/m2, 27.5 mg/m2). Dose escalation was managed by the time-to-event continual reassessment method algorithm. Linear mixed models were used to correlate change in 24-hour T1, Ktrans (capillary permeability), and fractional plasma volume with change in tumor volume. Results Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The most common tumor types were melanoma (59%) and non-small cell lung cancer (18%). No dose limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia (6.9%, 2 of 29). The median intracranial response rate was 46% (95% confidence interval, 24-68) and median overall survival was 5.2 months (95% confidence interval, 4.5-9.4). No neurologic deaths occurred. Among 10 patients undergoing dynamic contrast-enhanced MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 and 4 months (P ≤ .01). Conclusions The addition of RRx-001 to WBRT is well tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, the recommended phase 2 dose is 10 mg twice weekly. A reduction in fractional plasma volume on dynamic contrast-enhanced MRI 24 hours after RRx-001 suggests antiangiogenic activity associated with longer-term tumor response.

Background: Treatment planning for I-125 plaque therapy for uveal melanoma has advanced significantly since the Collaborative Ocular Melanoma Study trial, with more widely available image-guided planning and improved dosimetry. Objective: We evaluated real-world practice patterns for I-125 plaque brachytherapy in the United States by studying practice patterns at centers that comprise the Ocular Oncology Study Consortium (OOSC). Methods: The OOSC database and responses to a treatment practice survey were evaluated. The database contains treatment information from 9 institutions. Patients included in the database were treated between 2010 and 2014. The survey was conducted in 2018 and current treatment planning methods and prescriptions were queried. Results: Examination of the OOSC database revealed that average doses to critical structures were highly consistent, with the exception of one institution. Survey responses indicated that most centers followed published guidelines regarding dose and prescription point. Dose rate ranged from 51 to 118 cGy/h. As of 2018, most institutions use pre-loaded plaques and fundus photographs and/or computed tomography or magnetic resonance imaging in planning. Conclusions: While there were differences in dosimetric practices, overall agreement in plaque brachytherapy practices was high among OOSC institutions. Clinical margins and planning systems were similar among institutions, while prescription dose, dose rates, and dosimetry varied.

We investigated whether the use of chemotherapy before whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxic effects or worse cosmetic outcome compared with WBI alone.We identified 6754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a statewide consortium. We reported rates of 4 toxic effects: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxic effect measure (including moist desquamation and either patient- or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at 1 year after WBI. Successive multivariable models were constructed to estimate the effect of chemotherapy on these outcomes.Rates of moist desquamation, patient-reported pain, composite acute toxic effects, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3895 patients receiving HWBI. Receipt of chemotherapy before CWBI was not associated with higher rates of patient-reported pain, composite acute toxic effects, or impaired cosmetic outcome compared with CWBI without chemotherapy but was associated with more moist desquamation (odds ratio, 1.32 [1.07-1.63]; P = .01). Receipt of chemotherapy before HWBI was not associated with higher rates of any of the 4 toxic effects compared with HWBI alone.In this cohort, use of chemotherapy before WBI was generally well tolerated. CWBI with chemotherapy but not HWBI with chemotherapy was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at 1 year were comparable in patients receiving chemotherapy before either CWBI or HWBI. These data support the use of HWBI after chemotherapy.

Cardiac radiation exposure is associated with an increased rate of adverse cardiac events in patients receiving radiation therapy for locally advanced non-small cell lung carcinoma (NSCLC). Previous analysis of practice patterns within the Michigan Radiation Oncology Quality Consortium (MROQC) revealed 1 in 4 patients received a mean heart dose20 Gy and significant heterogeneity existed among treatment centers in using cardiac dose constraints. The purpose of this study is to analyze the effect of education and initiation of standardized cardiac dose constraints on heart dose across a statewide consortium.From 2012 to 2020, 1681 patients from 27 academic and community centers who received radiation therapy for locally advanced NSCLC were included in this analysis. Dosimetric endpoints including mean heart dose (MHD), mean lung dose, and mean esophagus dose were calculated using data from dose-volume histograms. These dose metrics were grouped by year of treatment initiation for all patients. Education regarding data for cardiac dose constraints first occurred in small lung cancer working group meetings and then consortium-wide starting in 2016. In 2018, a quality metric requiring mean heart dose20 Gy while maintaining dose coverage (D95) to the target was implemented. Dose metrics were compared before (2012-2016) versus after (2017-2020) initiation of interventions targeting cardiac constraints. Statistical analysis was performed using the Wilcoxon rank sum test.After education and implementation of the heart dose performance metric, mean MHD declined from an average of 12.2 Gy preintervention to 10.4 Gy postintervention (P.0001), and the percentage of patients receiving MHD20 Gy was reduced from 21.1% to 10.3% (P.0001). Mean lung dose and mean esophagus dose did not increase, and target coverage remained unchanged.Education and implementation of a standardized cardiac dose quality measure across a statewide consortium was associated with a reduction of mean heart dose in patients receiving radiation therapy for locally advanced NSCLC. These dose reductions were achieved without sacrificing target coverage, increasing mean lung dose, or increasing mean esophagus dose. Analysis of the clinical ramifications of the reduction in cardiac doses is ongoing.

Single-fraction (SF) radiation therapy is effective and convenient for patients with painful noncomplex bone metastases. Prior survey results reported a low recommendation of SF radiation therapy in the US. We sought to assess contemporary treatment recommendations for the management of bone metastases among diverse physicians participating in a statewide quality consortium.Members of the Michigan Radiation Oncology Quality Consortium were surveyed between April and May 2017. Physicians rated the importance of 31 variables on their choice of dose fractionation. The survey also covered 7 patient scenarios.Fifty-six physicians responded who were practicing at 18 of 20 centers surveyed. Respondents recommended 23 dose-fractionation schedules across the 7 scenarios. Highest-rated factors considered when choosing a dose fractionation regimen were performance status, prognosis, spinal cord compression, and prior radiation therapy. Recommendations for SF overall were uncommon (16.1%). On multivariable analysis, factors associated with SF use included academic employment (odds ratio [OR] 2.04; 95% CI, 1.02-4.08; P = .044) and higher palliative case volume (OR 2.59; 95% CI, 1.45-4.63; P = .001). Stereotactic body radiation therapy (SBRT) was recommended in 16.4% of scenarios overall, and on multivariable analysis, significant predictors for SBRT use were academic employment (OR 2.99; 95% CI, 1.39-6.44; P = .005), more recent residency completion (OR 4.37; 95% CI, 1.26-15.17; P = .02), spine location (OR 12.54; 95% CI, 3.96-39.68; P .001), and prior radiation therapy (OR 26.67; 95% CI, 7.86-90.57; P .001). SF rates were higher than in a survey reported in 2009 (16.1% vs 9.4%, P = .0004).SF radiation therapy remains uncommonly recommended, although it may be recommended more now than it was 10 years ago despite the increased utilization of SBRT. We identify multiple key drivers in physician decision making affecting SF recommendations that have not been addressed by prior level one evidence. Further research with evidence-based recommendations to clarify the role of SF and SBRT in management of patients with bony metastases are needed.

PURPOSE: In recent years, the American Society for Radiation Oncology (ASTRO) has received requests for a standard list of data elements from other societies, database architects, Electronic Health Record vendors and, most recently, the pharmaceutical industry. These requests point to a growing interest in capturing radiation oncology data within registries and for quality measurement, interoperability initiatives, and research. Identifying a short and consistent list will lead to improved care coordination, a reduction in data entry by practice staff, and a more complete view of the holistic approach required for cancer treatment.METHODS AND MATERIALS: The task force formulated recommendations based on analysis from radiation specific data elements currently in use in registries, accreditation programs, incident learning systems, and electronic health records. The draft manuscript was peer reviewed by 8 reviewers and ASTRO legal counsel and was revised accordingly and posted on the ASTRO website for public comment in April 2019 for 2 weeks. The final document was approved by the ASTRO Board of Directors in June 2019.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

Background: Breast conserving surgery (BCS) and radiotherapy (RT) reduce the risk of breast cancer recurrence, but can cause various functional deficits in breast cancer survivors. Side effects to the shoulder can include pain, stiffness, and restricted mobility, which are difficult to objectively assess in the clinic. Methods: The mechanical integrity of the shoulder and the pectoralis major (PM) was assessed in patients at least 1 year post-treatment with BCS and RT. Nine patients with node-negative breast cancer were treated with 2 RT fields to the breast alone after BCS and sentinel node biopsy (Group 1). Nine patients with node-positive breast cancer were treated with ≥3 RT fields to the breast and draining lymphatics after BCS and axillary lymph node dissection (ALND) (Group 2). Nodal RT was delivered to the supraclavicular and infraclavicular (level III axillary) nodes in 9/9 patients, the internal mammary nodes in 6/9 patients, and the full axilla (levels I, II, and III) in 1/9 patient. Nine age-matched healthy controls (mean age 54) with no history of breast cancer or shoulder injury were also examined. The mechanical integrity of the shoulder was objectively quantified using robot-assisted biomechanical measures of shoulder stiffness. The shear elastic modulus, or 'stiffness', of the clavicular and sternocostal fiber regions of PM was assessed using ultrasound shear wave elastography. Participants were examined while they were relaxed or actively contracting force with their shoulder muscles. Linear mixed effect models with Bonferroni-corrected multiple comparisons were used to determine if shoulder stiffness or PM shear elastic modulus differed between the two breast cancer groups and controls. Results: Patients in Groups 1 (mean age 54) and 2 (mean age 57) were an average (SD) 754(111) and 988(163) days since initiating RT (p=0.003). Shoulder stiffness did not differ between the 2 groups and healthy controls (F2,27=0.76, p=0.48), There was a significant group difference in PM shear elastic modulus (F2,27=8.33, p=0.0015), with Group 2 patients exhibiting an average greater stiffness of 14-21% in the sternocostal and 12-28% in the clavicular regions of the PM versus Group 1 patients (p Conclusions: Although power is limited due to small sample size, this study provides the first evidence that the mechanical integrity of the shoulder remains intact in patients who receive ALND combined with a supraclavicular field (generally without full axillary radiotherapy). The observation of altered PM function without subsequent changes to shoulder stiffness in patients treated with ALND and ≥3 RT fields suggests these patients likely develop new neuromuscular strategies to stabilize the shoulder joint to compensate for the PM. Future work is needed to appreciate whether certain muscle strategies are associated with poorer quality of life in breast cancer survivors, and to prospectively monitor the impact of breast cancer treatments on PM mechanical properties. Citation Format: Lipps DB, Leonardis JM, Lehmann S, Dess RT, McGinnis G, Strauss JB, Hayman JA, Pierce LJ, Jagsi R. Mechanical properties of the shoulder and pectoralis major in women undergoing breast conserving therapy with axillary dissection and regional nodal radiotherapy versus sentinel node biopsy and radiotherapy to the breast alone [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-18.

Objective: Elderly patients with low-risk hormone-positive breast cancer are at risk of over treatment. Avoidance of radiation therapy (RT) in favor of endocrine therapy alone was first heralded as the optimal conservative strategy due to logistical simplicity, low acute sequelae and a reduction of contralateral cancers not seen with RT. However, long-term use of aromatase inhibitors (AI) is not without costs and morbidity, often leading to low compliance and notable late effects. We therefore performed a cost-effectiveness analysis to compare the outcomes and costs between AI for five years without RT versus hypofractionated RT alone without endocrine therapy. Materials and Methods: Using data from available phase III trials and meta-analyses, we constructed a patient-level microsimulation Markov decision model to replicate the comparative outcomes between the strategies above from the societal perspective among 200,000 simulated patients. Five years of anastrozole was compared to a 15-fraction hypofractionated whole breast RT course without boost in a cohort of patients with low-risk disease as defined by CALGB 9343 entry criteria. Noncompliance with AI was modeled from recent population-based data. Relative effectiveness on ipsilateral breast tumor recurrence and contralateral breast cancers were based off the NSABP B-21 trial, adjusted to match the modern outcomes demonstrated in CALGB 9343 and PRIME II with further adjustment for AI over tamoxifen (ATAC, EBCTCG meta-analysis). Indirect costs of travel were accounted for, as were the costs of common and serious side-effects from RT (dermatitis, fibrosis, second malignancy, heart disease) and AI (arthralgia, hot flashes, osteopenia, fracture, thrombosis). A 1-year cycle time and lifetime horizon were used, with all costs adjusted to 2018 US dollars and extracted primarily from Medicare reimbursement data. The primary measure of efficacy was the quality-adjusted life-year (QALY) with age-adjusted utilities extracted from the literature. Half-cycle correction and a 3% discount rate were applied. Probabilistic sensitivity analysis was used to vary all parameters simultaneously. Results: On average, RT was approximately $3,981 more expensive than endocrine therapy over the lifetime horizon. Under a number of assumptions, RT appeared similar in long-term effectiveness to AI therapy, with a difference of less than 0.03 quality-adjusted life years. Given the low value of the denominator in the incremental cost-effectiveness ratio (ICER), RT did not meet the formally defined $100,000/QALY threshold. On one-way sensitivity analysis, the ICER was particularly sensitive to the incidence and impact of salvage strategies for recurrence, treatment of contralateral breast cancers, cardiac events and fracture rates. Conclusions: Modeling with the available evidence suggests it is likely that quality-of-life after RT-alone is nearly identical to an AI-alone strategy but associated with a small increase in cost. These results suggest select patients at risk of noncompliance can safely be treated with RT-alone rather than AI alone. Given the relative pros and cons of each strategy, RT-alone should be considered for select elderly low-risk breast patients. Citation Format: Ward MC, Vicini F, Chadha M, Pierce L, Recht A, Hayman J, Thaker N, Khan A, Keisch M, Shah C. Evaluating the cost of endocrine therapy vs. radiation therapy alone for low risk hormone positive early stage breast cancer in elderly patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-15-02.

For sentinel lymph node (SLN) metastasis from Merkel cell carcinoma (MCC), the benefit of completion lymph node dissection (CLND) versus radiation therapy (RT) is unclear. This study compares outcomes for patients with SLN metastasis undergoing CLND or RT. We also evaluated positive non-SLNs as a prognostic factor. Using a prospective database, we identified MCC patients with SLN metastasis who underwent CLND or RT. At our institution, CLND was recommended for patients with acceptable perioperative risk, while therapeutic RT was offered to those with high perioperative risk. Primary outcomes were MCC-specific survival (MCCSS), disease-free survival (DFS), nodal recurrence-free survival (NRFS), and distant recurrence-free survival (DRFS). From 2006 to 2017, 163 patients underwent CLND (n = 137) or RT (n = 26). Median follow-up was 1.9 years. CLND had no significant differences for MCCSS (5-year survival 71% vs. 64%, p = 1.0), DFS (52% vs. 61%, p = 0.8), NRFS (76% vs. 91%, p = 0.3), or DRFS (65% vs. 75%, p = 0.3) compared with RT. Patients with positive non-SLNs (n = 44) had significantly worse MCCSS (5-year survival 39% vs. 87%, p

PURPOSE/OBJECTIVE(S) Early concerns were raised about higher rates of radionecrosis (RN) with concurrent use of immune checkpoint inhibition (ICI) and stereotactic radiotherapy (SRT) for brain metastases (BM). We sought to clarify if this same concern translated to linear accelerator-based SRT for BM. MATERIALS/METHODS We retrospectively reviewed cases of SRT delivered at a single institution for BM (2004-2019). In total, 251 patients and 723 courses of treatment were analyzed on a per-treatment basis for any grade RN. RN was graded by CTCAE v5 and defined as an enlarging lesion after SRT that resolved spontaneously, resolved with steroids, or was surgically resected and found to have no viable tumor. Differences were assessed with Chi-squared, Kaplan-Meier, and univariable/multivariable Cox regression analyses with candidate variables including timing of ICI with SRT (neoadjuvant, concurrent defined as within 3 months, or adjuvant), primary histology, and symptomatic vs not at time of BM diagnosis, among others. RESULTS In total, 251 patients received SRT for BM: 53 without ICI, 58 neoadjuvant ICI, 102 concurrent ICI, and 38 adjuvant ICI. Median follow up for the surviving patients who received any ICI was 24.0 months (IQR 7.6-41.4) and not different from those without ICI at 26.8 months (IQR 8.8-45.6) (P = 0.22) with 38% of patients alive at last follow up. Analyzed by timing of ICI at the patient level, those not receiving ICI were more likely to have a diagnosis of breast or other cancers as compared to melanoma, lung, and kidney primaries that were more common with ICI (P < 0.01). This is likely due to the longer historical use of ICI in these malignancies. The overall rates of Grade 1-3 RN were 4.0%, 4.6%, and 2.2% (no Grade 4+ events). Median time to RN was 11.4 months (IQR 6.0-22.5). Analyzed by timing of ICI on a per-treatment basis, there was no difference among rates of any grade RN for no (13.5%), neoadjuvant (9.8%), concurrent (8.5%), and adjuvant ICI (14.1%) (P = 0.052). On univariable analysis, primary histology, performance status, SRT fractionation, and metastasis diameter were significantly associated with time to RN (all P < 0.05). Time to RN did not vary among treatment courses with neoadjuvant, concurrent, adjuvant, or no ICI (P = 0.72). On multivariable analysis, once histology and SRT fractionation were included, only a performance status of ECOG 0 (HR 0.43 CI 0.23-0.81) and increasing diameter (HR 1.58 CI 1.24-2.03) remained significant (both P < 0.01). CONCLUSION In this large single-institution study of linear accelerator-based SRT, consistent with previous reports, we found that lesion diameter positively correlated with risk of RN. However, there was not an increased risk of RN in patients who received ICI. On subset analysis, there was no association of RN with ICI timing - including with concurrent administration. These data suggest that linear accelerator-based SRT is safe to combine with ICI. AUTHOR DISCLOSURE S.G. Allen: Employee; University of Michigan Mott Children's Hospital. J.J. Waninger: None. S.R. Birer: None. S. Journey: None. J. Skvarce: None. D.R. Wahl: Research Grant; Agios Inc, Innocrin Inc, American Cancer Society, NIH. Stock Options; Lycera Inc. Advisory Board Member; Agios Inc. T.S. Lawrence: None. J.A. Hayman: Research Grant; Blue Cross Blue Shield of Michigan. M.M. Kim: Research Grant; Blue Earth Diagnostics.; Red Journal. Site PI of ongoing CCTG CE.7, N0577, A071801, and NCI 9979 trials; NCTN (Alliance, NRG, CCTG) and ETCTN.M. Green: None.

PURPOSE/OBJECTIVE(S) Cannabis use rates are increasing throughout the United States along with shifts in state-level policy. Patients with cancer use cannabis for a broad range of indications, but there is limited quality data to support many of these uses. To date, few studies have sought to understand cannabis use in populations of patients served by radiation oncology departments. MATERIALS/METHODS Standardized electronic medical record prompts were used by clinicians for cannabis history documentation for 1050 adult patients seen for initial consultation or follow-up between 10/2020 and 2/2021 at an academic radiation oncology department. Cannabis use data, including recency/frequency of use, indication, and mode of administration, were later gathered using the Michigan Radiation Oncology Analytics Resource (M-ROAR) under an IRB-approved protocol. Cannabis use characteristics were summarized, and logistic regression was used to explore associations between age and gender and recent cannabis use. RESULTS In total, 54 (5.1%) of 1050 unique patients declined to answer questions about cannabis use. Of the remaining 996 patients, 106 (10.6%) endorsed recent cannabis use (≤1 month ago), 71 (7.1%) noted remote use (> 1 month ago), and 819 (82.2%) denied history of cannabis use. The median age of those with recent cannabis use was 59.5 (IQR: 49.7-66.4) vs. 65.4 (IQR: 57.1-73.5) in all others. A multivariable logistic regression analysis revealed an association between age (OR 0.96; 95% CI: 0.95-0.97; P < 0.001) but not gender (male OR 1.24; 95% CI: 0.82-1.88; P = 0.310) and recent cannabis use. Patients noted pain (46.2%), anxiety (23.6%), insomnia (17.9%), "for the high" (17.0%), nausea (15.1%), poor appetite (14.2%), "to fight cancer" (4.7%), and depression (1.9%) as indications for use. The most common mode of administration was inhalation via smoking (47.2%), followed by oral (edibles, 36.8%), topical (15.1%), oral (drinks, 4.7%), vaping (3.8%), sublingual (1.0%), and rectal (1.0%). Most patients used cannabis daily (58.5%). Only 4 individuals (3.8%) noted use multiple times daily, while the remainder endorsed weekly (20.8%) or less than weekly (17.0%) use. CONCLUSION Approximately 10% of patients seen in a radiation oncology department reported recent cannabis use for a variety of reasons. These findings suggest a need for: 1) collection of cannabis use history in radiation oncology departments, 2) efforts to destigmatize cannabis use to facilitate frank discussions between patients and providers, 3) patient education about the fact that cannabis is not an evidence-based cancer treatment, 4) recommendation against inhaled forms of cannabis, which may carry risk of pulmonary toxicity, and 5) careful application of proven therapies to address symptoms when appropriate to provide alternatives to cannabis. Further research is needed to assess changes in cannabis use patterns over the course of cancer treatment and to evaluate risks and benefits of cannabis use in patients with cancer.

Multiple factors influence the risk of developing pneumonitis after radiation therapy (RT) for lung cancer, but few resources exist to guide clinicians in predicting risk in an individual patient treated with modern techniques. We analyzed toxicity data from a state-wide consortium to develop an integrated pneumonitis risk model.All patients (N = 1302) received conventionally fractionated RT for stage II-III non-small cell lung cancer between April 2012 and July 2019. Pneumonitis occurring within 6 months of treatment was graded by local practitioners and collected prospectively from 27 academic and community clinics participating in a state-wide quality consortium. Pneumonitis was modeled as either grade ≥2 (G2+) or grade ≥3 (G3+). Logistic regression models were fit to quantify univariable associations with dose and clinical factors, and stepwise Akaike information criterion-based modeling was used to build multivariable prediction models.The overall rate of pneumonitis of any grade in the 6 months following RT was 16% (208 cases). Seven percent of cases (n = 94) were G2+ and1% (n = 11) were G3+. Adjusting for incomplete follow-up, estimated rates for G2+ and G3+ were 14% and 2%, respectively. In univariate analyses, gEUD, V5, V10, V20, V30, and mean lung dose (MLD) were positively associated with G2+ pneumonitis risk, whereas current smoking status was associated with lower odds of pneumonitis. G2+ pneumonitis risk of ≥22% was independently predicted by MLD of ≥20 Gy, V20 of ≥35%, and V5 of ≥75%. In multivariate analyses, the lung V5 metric remained a significant predictor of G2+ pneumonitis, even when controlling for MLD, despite their close correlation. For G3+ pneumonitis, MLD and V20 were statistically significant predictors. Number of patient comorbidities was an independent predictor of G3+, but not G2+ pneumonitis.We present an analysis of pneumonitis risk after definitive RT for lung cancer using a large, prospective dataset. We incorporate comorbidity burden, smoking status, and dosimetric parameters in an integrated risk model. These data may guide clinicians in assessing pneumonitis risk in individual patients.

BACKGROUND AND PURPOSE: T2 signal and FLAIR changes in patients undergoing stereotactic radiosurgery for brain AVMs may occur posttreatment and could result in adverse radiation effects. We aimed to evaluate outcomes in patients with these imaging changes, the frequency and degree of this response, and factors associated with it. MATERIALS AND METHODS: Through this retrospective cohort study, consecutive patients treated with stereotactic radiosurgery for brain AVMs who had at least 1 year of follow-up MR imaging were identified. Logistic regression analysis was used to evaluate predictors of outcomes. RESULTS: One-hundred-sixty AVMs were treated in 148 patients (mean, 35.6 years of age), including 42 (26.2%) pediatric AVMs. The mean MR imaging follow-up was 56.5 months. The median Spetzler-Martin grade was III. The mean maximal AVM diameter was 2.8 cm, and the mean AVM target volume was 7.4 mL. The median radiation dose was 16.5 Gy. New T2 signal and FLAIR hyperintensity were noted in 40% of AVMs. T2 FLAIR volumes at 3, 6, 12, 18, and 24 months were, respectively, 4.04, 55.47, 56.42, 48.06, and 29.38 mL Radiation-induced neurologic symptoms were encountered in 34.4%. In patients with radiation-induced imaging changes, 69.2% had new neurologic symptoms versus 9.5% of patients with no imaging changes (P = .0001). Imaging changes were significantly associated with new neurologic findings (P

We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.

Hypofractionated radiation therapy is a less burdensome and less costly approach that is efficacious for most patients with early-stage breast cancer. Concerns about racial disparities in adoption of medical advances motivate investigation of the use of hypofractionated radiation in diverse populations. The goal of our study was to determine whether hypofractionated whole breast radiation therapy after breast-conserving surgery was being similarly used across racial groups in the state of Michigan.A prospectively collected statewide quality consortium database from 25 institutions was queried for patients with breast cancer who completed hypofractionated (HF) or conventionally fractionated whole breast radiation therapy from January 2012 to December 2018. We used patient-level multivariable modeling to evaluate associations between HF use and race, controlling for patient and facility factors, and multilevel modeling to account for patient clustering within facilities.Of 9634 patients analyzed, 81% self-reported race as white, 17% as black, and 2% as Asian, similar to statewide and national distributions. In addition, 31.7% of whites were treated at teaching centers compared with 66.7% of blacks and 64.8% of Asians. In 2018, HF was used in 72.7% of whites versus 56.7% of blacks and 67.6% of Asians (P = .0411). On patient-level multivariable analysis, black and Asian races were significantly associated with a lower likelihood of HF receipt (P.001), despite accounting for treatment year, age, laterality, body mass index, breast volume, comorbidities, stage, triple-negative status, intensity modulated radiation therapy use, teaching center treatment, and 2011 American Society for Radiation Oncology Hypofractionation Guideline eligibility. On multilevel analysis, race was no longer significantly associated with HF receipt.We observed that black and Asian patients receive hypofractionated whole breast radiation therapy less often than whites, despite more frequent treatment at teaching centers. Multilevel modeling eliminated this disparity, suggesting that differences in facility-specific HF use appear to have contributed. Further inquiry is needed to determine whether reduction of facility-level variation may reduce disparities in accessing HF treatment.

The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on "Signs and Symptoms of SCLC" and "Principles of Pathologic Review."

Purpose Palliative radiation therapy for bone metastases is often viewed as a single entity, despite national guidelines providing input principally only for painful uncomplicated bone metastases. Data surrounding the treatment of bone metastases are often gleaned from questionnaires of what providers would theoretically do in practice or from population-based data lacking critical granular information. We investigated the real-world treatment of bone metastases with radiation therapy. Methods and Materials Twenty diverse institutions across the state of Michigan had data extracted for their 10 most recent cases of radiation therapy delivered for the treatment of bone metastases at their institution between January and February 2017. Uni- and multivariable binary logistic regression was used to assess the use of single fraction (8 Gy × 1) radiation therapy. Results A total of 196 cases were eligible for inclusion. Twenty-eight different fractionation schedules were identified. The most common schedule was 3 Gy × 10 fractions (n = 100; 51.0%), 4 Gy × 5 fractions (n = 32; 16.3%), and 8 Gy × 1 (n = 15; 7.7%). The significant predictors for the use of single fraction radiation therapy were the presence of oligometastatic disease (P = .008), previous overlapping radiation therapy (P = .050), and academic practice type (P = .039). Twenty-nine cases (14.8%) received >10 fractions (median 15, range 11-20). Intensity modulated radiation therapy was used in 14 cases (7.1%), stereotactic body radiation therapy in 11 (5.6%), and image guidance with cone beam computed tomography in 11 (5.6%). Of the cases of simple painful bone metastases (no previous surgery, spinal cord compression, fracture, soft tissue extension, or overlapping previous radiation therapy; n = 70), only 12.9% were treated with 8 Gy × 1. Conclusions Bone metastases represent a heterogeneous disease, and radiation therapy for bone metastases is similarly diverse. Future work is needed to understand the barriers to single fraction use, and clinical trials are necessary to establish appropriate guidelines for the breadth of this complex disease.

PURPOSE: The purpose of this study is to identify dosimetric variables that best predict for acute esophagitis in patients treated for locally advanced non–small cell lung cancer in a prospectively accrued statewide consortium. METHODS AND MATERIALS: Patients receiving definitive radiation therapy for stage II-III non–small cell lung cancer within the Michigan Radiation Oncology Quality Consortium were included in the analysis. Dose-volume histogram data were analyzed to determine absolute volumes (cc) receiving doses from 10 to 60 Gy (V10, V20, V30, V40, V50, and V60), as well as maximum dose to 2 cc (D2cc), mean dose (MD), and generalized equivalent uniform dose (gEUD). Logistic regression models were used to characterize the risk of toxicity as a function of dose and other covariatcs. The ability of each variable to predict esophagitis, individually or in a multivariate model, was quantified by receiver operating characteristic analysis. RESULTS: There were 533 patients who met study criteria and were included; 437 (81.9%) developed any grade of esophagitis. Significant variables on univariate analysis for grade ≥2 esophagitis were concurrent chemotherapy, V20, V30, V40, V50, V60, MD, D2cc, and gEUD. For grade ≥3 esophagitis, the predictive variables were: V30, V40, V50, V60, MD, D2cc, and gEUD. In multivariable modeling, gEUD was the most significant predictor of both grade ≥2 and grade ≥3 esophagitis. When gEUD was excluded from the model, D2cc was selected as the most predictive variable for grade ≥3 esophagitis. For an estimated risk of grade ≥3 esophagitis of 5%, the threshold values for gEUD and D2cc were 59.3 Gy and 68 Gy, respectively. CONCLUSIONS: In this study, we report the novel finding that gEUD and D2cc, rather than MD, were the most predictive dose metrics for severe esophagitis. To limit the estimated risk of grade ≥3 esophagitis to

Radiation esophagitis (RE) is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC). While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc) and generalized equivalent uniform dose (gEUD)], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC) and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc) and 0.727 (gEUD). Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs) of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.

Purpose Limited data exist regarding the range of heart doses received in routine practice with radiation therapy (RT) for breast cancer in the United States today and the potential effect of the continual assessment of the cardiac dose on practice patterns. Methods and Materials From 2012 to 2015, 4688 patients with breast cancer treated with whole breast RT at 20 sites participating in a state-wide consortium were enrolled into a registry. The importance of limiting the cardiac dose has been emphasized in the consortium since 2012, and the mean heart dose (MHD) has been reported by each institution since 2014. The effects on the MHD were estimated for both conventional and accelerated fractionation using regression models, with technique (intensity modulated RT [IMRT] vs 3-dimensional conformal RT), deep inspiration breath hold use, patient position (supine vs prone), nodal RT (if delivered), and boost (yes vs no) as covariates. Results For left-sided breast cancer treated with conventional fractionation, the median MHD in 2012 was 2.19 Gy versus 1.65 Gy in 2015 ( P P Conclusions The MHD for left-sided breast cancer decreased during a recent 4-year period, coincident with an increased focus on cardiac sparing in the radiation oncology community in general and a state-wide consortium specifically. These data suggest a positive effect of systematically monitoring the heart dose delivered.

Purpose Regional nodal irradiation, including radiation therapy (RT) to the internal mammary node (IMN) region, improves oncologic outcomes in patients with node-positive breast cancer. Concern remains, however, given the proximity of the IMNs to the heart and the association between cardiac RT exposure and toxicity. The objective of the study was to evaluate rates of ischemic cardiac events (ICEs) and associated risk with treatment of the IMN region. Methods and Materials The cardiac outcomes of 2126 patients treated with adjuvant breast RT or breast and nodal RT from 1984 to 2007 at a single institution were reviewed. The primary endpoint was an ICE following RT initiation. The association between IMN RT and ICEs was assessed using Cox proportional hazards models. Treatment with both IMN RT and 3-dimensional (3D) conformal radiation therapy (CRT) began in 1997; therefore, subset analyses of patients with only 3D CRT were performed to minimize bias associated with improved treatment technique. Results The median follow-up period was 9.3 years. An ICE occurred in 87 patients (4.1%). No increased 10-year rate of ICEs was observed with IMN RT compared with no IMN RT in the total cohort (3.2% [95% confidence interval (CI), 2.4%-4.3%] vs 3.4% [95% CI, 1.5%-7.5%]; hazard ratio [HR], 0.88; P=.73). Similarly, no statistically significant difference was noted in the 3D CRT–planned, left-sided disease subset (5.1% [95% CI, 1.8%-14.1%] vs 4.0% [95% CI, 2.0%-8.0%]; HR, 1.18, P=.76). On multivariate analysis, adjusting for cardiac risk factor imbalances, no significantly increased hazard was noted with IMN RT (HR, 1.84; P=.28) in the 3D CRT–planned, left-sided disease subset. Conclusions No statistically significant association between IMN RT and ICEs was demonstrated in a review of patients treated at a single institution from 1984 to 2007. Given the long natural history and low overall rate of ICEs, continued follow-up of this study, as well as additional studies in the 3D CRT era, is warranted to confirm these results. Minimizing cardiac exposure, when treating a limited IMN field, is critical to limit excess risk of ICEs.

Purpose/objective(s) Cardiac radiation exposure is associated with an increased rate of adverse cardiac events in patients receiving radiation therapy for locally advanced non-small cell lung carcinoma (NSCLC). Previous analysis of practice patterns within the statewide Michigan Radiation Oncology Quality Consortium (MROQC) revealed 1 in 4 patients received a mean heart dose > 20 Gy and significant heterogeneity existed among treatment centers in using cardiac dose constraints. The purpose of this study is to analyze the effect of education and initiation of standardized cardiac dose constraints on heart dose across a statewide consortium. Materials/methods From 2012 to 2020, 1604 patients from 27 academic and community centers who received radiation therapy for locally advanced NSCLC were included in this analysis. Dosimetric endpoints including mean heart dose (MHD), mean lung dose, and mean esophagus dose were calculated using data from dose-volume histograms. These dose metrics were grouped by year of treatment initiation for all patients. Education regarding data for cardiac dose constraints was discussed in small lung cancer working group meetings and consortium-wide starting in 2016. This was followed in 2018 by implementation of a quality metric requiring mean heart dose Results Following education and implementation of the heart dose performance metric, mean MHD declined from an average of 12.2 Gy pre-intervention to 10.4 Gy post-intervention, and the percentage of patients receiving MHD > 20 Gy reduced by half. (Table). Mean lung dose and mean esophagus dose did not increase, and tumor coverage remained unchanged. Conclusion Education and implementation of a standardized cardiac dose quality measure across a statewide consortium was associated with a reduction of mean heart dose in patients receiving radiation therapy for locally advanced NSCLC. These dose reductions were achieved without sacrificing tumor coverage, increasing mean lung dose or mean esophagus dose. Analysis of the clinical ramifications of the reduction in cardiac doses is ongoing.

PURPOSE/OBJECTIVE(S) Regional collaborative quality initiatives that incent participation through direct payment and streamlined reimbursement for high-performing sites have been shown to drive improvements in surgical outcomes. Numerous quality measures have been proposed in radiation oncology, and research has identified readily measurable indicators like dose to critical structures that predict for subsequent toxicity in patients. A decade ago, we initiated a voluntary statewide collaboration for quality improvement in radiation oncology and now describe its impact on care delivery. MATERIALS/METHODS Following SQUIRE guidelines, we describe the approach and measures that the program has implemented. To evaluate impact, we describe compliance at baseline and now with active measures among participating practices. RESULTS Since beginning data collection in 2012, radiation oncologists, physicists, data abstractors, and practice administrators from sites in one state (currently numbering 27) have convened thrice yearly. At these meetings, experts have spoken regarding trends within the field and inspired discussions regarding potential targets for quality improvement within the consortium. Blinded data on practices at various sites have also been regularly presented, and the group has iteratively developed new initiatives and consensus-based benchmarks to improve radiation oncology care delivery, patient experiences, and outcomes. An observational dataset with detailed information from over 20,000 patients has been assembled to evaluate quality. Compliance with select measures is described in the table, including use of guideline-concordant hypofractionated radiotherapy, motion management, doses to targets/normal tissues, and consistency in delineating and naming contoured structures (a precondition for quality evaluation). CONCLUSION Although observational analysis cannot fully exclude secular trends, contextual data revealing slow uptake of best practices elsewhere in the US suggests that this initiative has improved the consistency, efficiency, and quality of radiation oncology care in its member practices and may be a model for other regions.

Purpose/objective(s) The benefit of radiotherapy (RT) in poor-prognosis patients with leptomeningeal disease (LMD) is not well characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT. Materials/methods Patients with breast cancer and classic radiographic LMD (36% cytology-confirmed) treated with palliative whole brain and/or partial spine RT between 2000-2020 at a single academic institution were included in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method, and differences in subgroups were determined using the log-rank test. Multivariate Cox proportional hazards models adjusting for estrogen receptor (ER), progesterone receptor (PR), HER2, ECOG performance status (ECOG), and systemic disease status assessed factors associated with OS. Domain-specific and any symptom improvement were ascertained by chart review of patient- and physician-report, and a multivariate logistic regression model developed incorporating ER/PR status, HER2 status, ECOG and steroid use to identify factors associated with symptom benefit. Results Among 64 patients of median age 50 years (IQR 31-69), the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had concurrent brain metastases, and 57% of patients had ER+ and/or PR+ tumors, 22% HER2+, and 38% triple-negative disease. Among 92% of symptomatic patients whose primary symptom domains were cranial nerve deficit (34%), sensory/motor deficits due to intracranial disease (25%) sensory/motor deficits due to spine disease (27%), and headaches/nausea (14%), 42% had > 1 reported symptom domain. Two-thirds of patients were on steroids prior to RT, and only 13% of patients received intrathecal therapy. Following a median dose of 30 Gy in 10 fractions, symptom improvement in any domain was noted in 59% of patients with symptoms pre-RT, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in > 1 symptom domain. Overall survival was only 2.1 months (95% CI 1.8-3.3) in the triple-negative subgroup, and higher among patients with HER2+ disease (5.2 months, 95% CI 3.8-NR, P = 0.003). On multivariate analysis, ER+ (HR 0.4, 95% CI 0.2-0.8, P = 0.009) and HER2+ (HR 0.4, 95% CI 0.2-0.9, P = 0.018) disease were associated with improved OS. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2-11, P = 0.029). Conclusion Even in this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yields symptomatic improvement, and may especially be of benefit among better-prognosis patients with hormone receptor-positive or HER2-positive disease. Author disclosure J. Takayesu: None. E. Sapir: Research Grant; LipoMedix, BioProtect. Consultant; AstraZeneca, MSD, Belong.Life. J. Xie: None. Y. Sun: None. A. Morikawa: Institutional research; Novartis, Lilly, Takeda, Eisai/H3b, Pfizer/National Comprehensive Cancer Network. L. Junck: Advisory Board; Orbus Therapeutics. D. Leung: None. Y. Umemura: None. J. Heth: None. W. Al-Holou: None. D.R. Wahl: Research Grant; Agios Inc, Innocrin Inc, American Cancer Society, NIH. Stock Options; Lycera Inc. Advisory Board Member; Agios Inc. T.S. Lawrence: None. C. Mayo: None. J.A. Hayman: Research Grant; Blue Cross Blue Shield of Michigan. M.M. Kim: Research Grant; Blue Earth Diagnostics.

Purpose/Objective(s) Recent landmark studies in radiation oncology suggest hypofractionation is appropriate for treatment of many cancers. The COVID-19 pandemic may have increased pressure to adopt hypofractionation because of concerns about disease spread at treatment centers. We know of no recent U.S. study of trends in radiation fractionation that includes comparisons of multiple disease sites and data post-COVID. Therefore, we sought to describe trends in treatment fractionation at a single academic center from 2014-2020. Materials/Methods From our institutional database, for the years 2014-2020, we extracted the total number of patients treated, total number of fractions delivered, and mean number of fractions per treatment course for all cancers and specifically for treatment of breast cancer, prostate cancer, and bone metastases. For breast and prostate, we included only radiation courses delivered to the primary site. Results The dataset included 16,224 courses of radiation treatment and 257,352 treatment fractions. The mean number of fractions per treatment course overall declined steadily throughout the study period, from 18.3 in 2014 to 14.9 in 2020. For breast cancer, the mean number of fractions per treatment course was steady from 2014-2016 but began to decline more rapidly from 2017-2020. Fractionation for prostate cancer followed a similar time trend, but there was a more substantial decline from 2014 (mean 36.6 fractions per treatment course) to 2020 (mean 16.7 fractions per treatment course). For bone metastases, fractionation was relatively consistent throughout the study period. For breast patients, during the onset of COVID-19 in 2020, the monthly rate of decrease in number of fractions increased to 0.19 from a historical mean of 0.05, as the mean number of sessions dropped from 22 to 19. For bone metastases, in 2020, the mean number of sessions dropped from 6.3 to 5.3, with a monthly rate of decrease of 0.13 compared to historical mean of 0.03. COVID-19 did not spike the monthly rate of change in number of fractions for prostate which began a steady decline in 2017 with increased use of SBRT. Conclusion We observed increased adoption of hypofractionation at our institution during the study period for both breast and prostate cancer. For bone metastases, hypofractionation had largely been adopted before the study period. There was evidence of an accelerated trend toward hypofractionation for some cancers during the COVID-19 pandemic.

Objective The benefit of radiotherapy (RT) in patients with leptomeningeal disease (LMD) is poorly characterized. This study assessed the overall survival (OS) and clinical improvement of a largely symptomatic cohort of breast cancer patients with LMD, to identify patient subsets most likely to benefit from palliative RT. Methods Patients with breast cancer-related classic radiographic LMD (36% cytology-confirmed) were treated with palliative whole brain and/or partial spine RT between 2000–2020 at a single academic institution in this retrospective analysis. OS was calculated from date of LMD diagnosis using the Kaplan-Meier method. A multivariate logistic regression model incorporating ER/PR status, HER2 status, ECOG and steroid use was developed to identify factors associated with symptom benefit, which was ascertained retrospectively by chart review. Results Among 64 patients, the radiographic distribution of LMD was in the brain (58%), spine (22%), or both (20%). A total of 63% had brain metastases, and 57% of patients had ER+ and/or PR+, 22% HER2+, and 38% triple-negative disease. Of the symptomatic patients (94%), primary symptom domains included cranial nerve deficits (34%), sensory/motor deficits from intracranial disease (25%) or spinal disease (27%), and headaches/nausea (14%), with 42% of patients reporting >1 symptom domain. Two-thirds of patients were on steroids prior to RT, and 13% of patients received intrathecal therapy. OS was 3.75 months. Following a median dose of 30Gy in 10 fractions, 59% of symptomatic patients experienced symptom improvement, with similar improvement rate across domains (12%, 15%, 19%, 14%, respectively); 21% of patients had improvement in >1 symptom domain. Hormone receptor positivity was independently associated with symptom improvement following RT (OR 3.5, 95% CI 1.2–11, p=0.029). Conclusions In this poor-prognosis cohort of breast cancer patients with LMD, palliative RT yielded symptomatic improvement, and may be particularly beneficial among better-prognosis patients with hormone receptor-positive disease.

Background and purpose Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. Materials and methods Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4 weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. Results In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were −28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to −27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. Conclusions Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity.