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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 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.

Purpose In 2014 the American Society for Radiation Oncology's Accreditation Program for Excellence (APEx) was created in response to the Target Safely campaign. APEx is a powerful tool to measure and drive quality improvement in radiation oncology practices. Methods and Materials A task group from the American Society for Radiation Oncology's Practice Accreditation Committee was formed to provide an overview of the APEx accreditation program including analysis from specific program data. Results Through initiatives encouraged by the APEx program, participants are able to evaluate teamwork and effectiveness, implement documented procedures aimed at improving quality and safety, and establish quality management at the practice. The program's Self-Assessment measures performance with program requirements and indicates where compliance lacks standardization. Methods to address these deficiencies form part of on-going quality improvement. These quality outcomes promote the delivery of safe, high-quality care. Conclusion The accreditation process through APEx is a commitment to an ongoing safety culture. Any worthwhile accreditation program should provide a meaningful assessment of practice operations, supply the tools to identify deficiencies and provide the opportunity to showcase growth and development. A commitment to completing APEx is a commitment to excellence for patients and all those who care for them.

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.

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.

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.

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

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.

e20525 Background: Treatment for inoperable stage II-III non-small cell lung cancer (NSCLC) involves aggressive chemo-radiotherapy (CRT). While outcomes have improved with immunotherapy, some patients transition to hospice or die early in their treatment course. To help identify these patients, we developed a predictive model for early poor outcomes in NSCLC patients treated with curative intent. Methods: In a statewide consortium involving 27 sites, information was collected prospectively on stage II-III NSCLC patients who received curative CRT from April 2012 to November 2019. We defined an early poor outcome as termination of treatment due to hospice enrollment or death within 5 months of initiating radiation therapy. Potential predictors included clinical characteristics and patient reported outcomes (PROs) from validated questionnaires. Logistic regression models were used to assess potential predictors and build predictive models. Multiple imputation was used to handle missing data. We used Lasso regularized logistic regression to build a predictive model with multiple predictor variables. Results: Of the total of 2267 included patients, 128 patients discontinued treatment early due to hospice enrollment or death. The mean age of the 128 patients was 71 years old (range 48-91) and 59% received concurrent chemotherapy. Significant uni-variable predictors of early hospice or death were advanced age, worse ECOG performance status, high PTV volume, short distance to normal tissue critical structures, high mean heart dose, uninsured status, lower scores on the Functional and Physical Well-Being scale and the Lung Cancer Symptoms sub-scale of the FACT-L quality of life instrument, as well as higher levels of patient-reported lack of energy, cough, and shortness of breath. The best predictive model included age, ECOG performance status, PTV volume, mean heart dose, patient insurance status, and patient-reported lack of energy and cough. The pooled estimate of area under the curve (AUC) for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%. Conclusions: Our models identified a combination of clinical variables and PROs that may help identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at a high risk of early hospice enrollment or death. These preliminary results are encouraging and warrant further evaluation in a larger cohort of patients.

8523 Background: In the landmark PACIFIC trial, adjuvant durvalumab after definitive chemoradiation for unresectable stage III non-small-cell lung cancer (NSCLC) produced a 11% absolute overall survival benefit at two years compared to placebo, and the US Food and Drug Administration approved durvalumab for this indication in February 2018. We investigated the real-world use of adjuvant durvalumab and other immune checkpoint inhibitors (ICI) in a contemporary cohort of patients. Methods: We identified patients with unresectable stage III (AJCC 8th edition) NSCLC treated with definitive chemoradiation from February 2018 to March 2020 from a statewide radiation oncology quality consortium, representing a mix of community (n=22 centers, 336 patients) and academic practice settings (n=5 centers, 64 patients) across the state of Michigan. Use of adjuvant durvalumab or other ICI (atezolizumab, nivolumab, or pembrolizumab) was ascertained at the time of routine three- or six-month follow-up after completion of chemoradiation. Baseline characteristics of patients treated with or without adjuvant ICI were compared with the Chi-squared test for categorical variables and a two-sided t-test for continuous variables. Results: Of 400 patients with unresectable stage III NSCLC treated with definitive chemoradiation, 268 (67%) received adjuvant ICI. Of these, the majority received durvalumab (86%) followed by pembrolizumab (7.5%) and nivolumab (6.0%). The proportion of patients receiving ICI remained stable throughout the study period with no discernable time trends. Eight-five percent of white patients received ICI compared with 77% of black patients (p=0.04), but there were no differences in gender (54.5% male in ICI vs 52.3% no ICI), current smoking (42.2% ICI vs 37.9% no ICI, p=0.68), number of comorbidities (29.5% with 3 or more comorbidities in ICI vs. 26.5% in no ICI, p=0.86), baseline oxygen use (8.9% ICI vs 10.6% no ICI, p=0.59), age (median 66.4 years [IQR 60.3-73.4] for ICI vs. 66.9 years [IQR 61.1-72.2] no ICI, p=0.89), treatment at an academic center (16.0% ICI vs 15.9% no ICI, p=0.97), or ECOG performance status (59.3% ECOG 0 in ICI vs 62.8% no ICI). Conclusions: In a broad range of academic and community-based practices across a state including 27 sites, only two-thirds of potentially eligible stage III NSCLC patients received adjuvant durvalumab or other ICI agents despite a proven overall survival benefit. Receipt of ICI was not strongly associated with baseline demographic or comorbidity variables. Further work will seek to clarify the patient-level reasons behind non-initiation of adjuvant ICI.

Importance Randomized trials have established the long-term safety and efficacy of hypofractionated whole-breast radiotherapy, but little is known about the acute toxic effects experienced by patients treated with hypofractionation as compared with conventional fractionation, particularly in real-world settings and from the patient’s own perspective. Objective To evaluate prospectively collected data on acute toxic effects and patient-reported outcomes in a cohort treated with varying radiation fractionation schemes in practices collaborating in the Michigan Radiation Oncology Quality Consortium (MROQC). Design, Setting, and Participants We compared toxic effects in patients receiving hypofractionation (HF) vs conventional fractionation (CF) during treatment (through 7 days after treatment) and in follow-up (posttreatment days 8-210), after adjustment for sociodemographic, clinical, and treatment characteristics. The MROQC includes academic and community radiation oncology practices across Michigan. All 2604 patients who received adjuvant whole-breast radiotherapy after lumpectomy for unilateral breast cancer at MROQC participating sites from October 2011 through June 2014 were registered; we analyzed 2309 for whom there was a comprehensive physician toxicity evaluation within 1 week of completion of radiotherapy and at least 1 weekly toxicity evaluation during treatment. Exposures Hypofractionation vs CF. Main Outcomes and Measures Physicians reported dermatitis, pain, fatigue, and other common toxic effects associated with breast radiotherapy at baseline, weekly during radiotherapy, and in follow-up. Patients who consented also rated their own experiences, including breast pain, fatigue, and being bothered by symptoms. Results Of the 2309 evaluable patients, 578 received HF. During treatment, after adjustment for sociodemographic, clinical, and treatment factors, patients receiving CF had significantly higher maximum physician-assessed skin reaction (moist desquamation, 28.5% vs 6.6%, P P P = .003), burning/stinging bother (often/always, 38.7% vs 15.7%, P = .002), hurting bother (33.5% vs 16.0%, P = .001), swelling bother (29.6% vs 15.7%, P = .03), and fatigue (29.7% vs 18.9%, P = .02) but slightly greater absence of skin induration in follow-up (84.5% vs 81.2%, P = .02). No significant differences were observed in any other measured outcomes during follow-up extending through 6 months. Conclusions and Relevance Hypofractionation not only improves convenience but also may reduce acute pain, fatigue, and the extent to which patients are bothered by dermatitis in patients with breast cancer undergoing whole-breast radiotherapy.

Objective: To evaluate outcomes of intermediate- and high-risk prostate cancer patients on a prospective dose-escalation study of pelvic external-beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost. Methods: From November 1991 to April 2003, 197 patients were treated for intermediate- and high-risk disease features. All patients had prostate-specific antigen >10 ng/ml, Gleason score ≥7, or clinical stage ≥T2b, and all received pelvic EBRT (46 Gy) while receiving either two or three HDR boost treatments. HDR dose fractionation increased progressively and was divided into two dose levels. The mean prostate biologic equivalency dose was 88.2 Gy for the low-dose group and 116.8 Gy for the high-dose group (α/β = 1.2). Clinical failure was either local failure or distant metastasis; clinical event-free survival (cEFS) was defined as patients who lived free of clinical failure. Results: Median follow-up was 4.9 years. The 5-year rates were as follows: biologic failure (BF), 18.6%, clinical failure (CF), 9.8%, cEFS 84.8%, cause-specific survival (CSS), 98.3%, and overall survival (OS), 92.9%. Five-year biochemical failure (68.7% vs. 86%, p p = 0.04), cEFS (75.5% vs. 91.7%, p = 0.003), CSS (95.4% vs. 100%, p = 0.02), and OS (86.2% vs. 97.8%, p = 0.002) were significantly better for the high-dose group. Multivariate analysis showed that high-dose group ( p = 0.01, HR 0.35) and Gleason score ( p = 0.01, HR 1.84) were significant variables for cEFS. Multivariate analysis showed that high-dose group ( p = 0.01, HR 0.14) and age ( p = 0.03, HR 1.09 per year) were significant variables for overall survival. Conclusion: There is a strong dose–response relationship for intermediate- to high-risk prostate cancer patients. Improved locoregional control with higher radiation doses alone can significantly decrease biochemical and clinical failures.

Given evidence from randomized trials that have established the non-inferiority of more convenient and less costly courses of hypofractionated radiotherapy to the whole breast in selected breast cancer patients who receive lumpectomy, we sought to investigate the use of hypofractionated radiation therapy and factors associated with its use in a consortium of radiation oncology practices in Michigan. We sought to determine the extent to which variation in use occurs at the physician or practice level versus the extent to which use reflects individualization based on potentially relevant patient characteristics (such as habitus, age, chemotherapy receipt, or laterality).We evaluated associations between receipt of hypofractionated radiation therapy and various patient, provider, and practice characteristics in a multilevel model.Of 1477 patients who received lumpectomy and whole-breast radiation therapy and were registered by the Michigan Radiation Oncology Quality Consortium (MROQC) from October 2011 to December 2013, 913 had T1-2, N0 breast cancer. Of these 913, 283 (31%) received hypofractionated radiation therapy. Among the 13 practices, hypofractionated radiation therapy use ranged from 2% to 80%. On multilevel analysis, 51% of the variation in the rate of hypofractionation was attributable to the practice level, 21% to the provider level, and 28% to the patient level. On multivariable analysis, hypofractionation was more likely in patients who were older (odds ratio [OR] 2.16 for age ≥50 years, P=.007), less likely in those with larger body habitus (OR 0.52 if separation between tangent entry and exit ≥25 cm, P=.002), and more likely without chemotherapy receipt (OR 3.82, P.001). Hypofractionation use was not higher in the last 6 months analyzed: 79 of 252 (31%) from June 2013 to December 2013 and 204 of 661 (31%) from October 2011 to May 2013 (P=.9).Hypofractionated regimens of whole-breast radiation therapy have been variably administered in the adjuvant setting in Michigan after the publication of long-term trial results and consensus guidelines. Most of this variability is explained at the practice and provider level rather than by patient-level features, although care is being individualized to some degree.

Objective: Adding pelvic radiation to high-dose prostate radiation for prostate cancer patients with a >15% risk of positive lymph nodes (LN) is controversial. We performed a matched-pair analysis of patients treated at 2 institutions to assess the impact of pelvic radiotherapy (P-RT). Methods: From January 1993 to March 2003, 2 institutions treated 1432 prostate cancer patients with combined external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy. Those receiving EBRT were treated either to the prostate and seminal vesicles alone or to the entire pelvis (46 Gy). In all cases, prostate dose (EBRT and HDR) resulted in an average BED >100 Gy (α/β = 1.2). There were 755 cases identified as having a pelvic LN risk >15% using the Roach formula. Of these, 255 cases were treated without pelvic RT and randomly matched by Gleason score, T stage, and pretreatment PSA to 500 cases treated with pelvic RT, resulting in 250 pairs (1:1). Results: Median follow-up was 4.0 years (P = 0.7). The 4-year prostate biochemical failure (22% versus 14%, P = 0.12), distant metastasis (9% versus 4%, P = 0.6), event-free survival (72% versus 78%, P = 0.3), prostate cancer death rate (4% versus 2%, P = 0.9), and overall survival (89% versus 88%, P = 0.7) were not significantly different for patients treated with and without P-RT. Analysis with and without androgen deprivation therapy showed similar results. Conclusion: Improved biochemical, clinical, or survival outcomes were not observed for prostate cancer patients at risk for positive pelvic LN >15% when treated with high-dose EBRT and HDR brachytherapy to the prostate with or without pelvic radiation.

Purpose: To determine the long-term efficacy and cosmetic results of accelerated partial breast irradiation (APBI) by reviewing our institution's experience. Methods and Materials: A total of 199 patients with early-stage breast cancer were treated prospectively with adjuvant APBI after lumpectomy using interstitial brachytherapy. All patients had negative margins, 82% had Stage I disease, median tumor size was 1.1 cm, and 12% had positive lymph nodes. The median follow-up for surviving patients was 8.6 years. Fifty-three patients (27%) have been followed for ≥10 years. Results: Six ipsilateral breast tumor recurrences (IBTRs) were observed, for a 5-year and 10-year actuarial rate of 1.6% and 3.8%, respectively. A total of three regional nodal failures were observed, for a 10-year actuarial rate of 1.6%. Five contralateral breast cancers developed, for a 5- and 10-year actuarial rate of 2.2% and 5.2%, respectively. The type of IBTR (clonally related vs. clonally distinct) was analyzed using a polymerase chain reaction–based loss of heterozygosity assay. Eighty-three percent of IBTRs ( n = 5) were classified as clonally related. Multiple clinical, pathologic, and treatment-related factors were analyzed for an association with the development of an IBTR, regional nodal failure, or contralateral breast cancer. On multivariate analysis, no variable was associated with any of these events. Cosmetic results were rated as excellent/good in 99% of patients. Conclusions: Long-term results with APBI using interstitial brachytherapy continue to demonstrate excellent long-term local and regional control rates and cosmetic results. According to a polymerase chain reaction–based loss of heterozygosity assay, 83% of recurrences were classified as clonally related.