Search

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

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.

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 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.

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.

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.

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

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/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.

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.

Objective Because of the short potential doubling time of esophageal cancer, there is a theoretical benefit to using an accelerated radiation treatment schedule. This study evaluates outcomes and treatment-related mortality and morbidity of patients treated with neoadjuvant hyperfractionated accelerated chemoradiation for resectable esophageal cancer. Methods and materials Outcomes from 250 consecutive patients with resectable esophageal cancer treated with preoperative hyperfractionated accelerated chemoradiotherapy (45 Gy in 30 twice-daily fractions over 3 weeks) followed by planned transhiatal esophagectomy were analyzed. Grade 3 or greater treatment related toxicity, surgical complications, and treatment-related mortality were determined. Additionally, available surgical specimens were graded for pathological response to chemoradiation. Overall survival (OS) and locoregional control were calculated using the Kaplan-Meier method. The log rank test was used to determine statistical significance. Results Median follow-up was 59 months for surviving patients; 87% of patients had adenocarcinoma and 13% had squamous cell carcinoma. Eleven percent of patients did not have surgery because of the development of metastases, declining performance status, or refusal. Twenty-seven patients were found to have unresectable and/or metastatic disease at the time of surgery. Overall, 10 of 223 operated patients died within 3 months, resulting in a perioperative mortality rate of 4%. Median OS was 28.4 months (95% confidence interval, 22.3-35.6 months) for all patients and 35.1 months (95% confidence interval, 27.4-47 months) for patients who underwent esophagectomy. There were 32 isolated locoregional failures with a 3-year locoregional control rate of 83%. Of 129 patients who had independent pathology review, 29% had complete response to treatment. This group had a median OS of 98.9 months and 3-year OS of 74%. Conclusion Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

Introduction Most patients with lung cancer are elderly and poorly represented in randomized clinical trials. They are often undertreated because of concerns about their ability to tolerate aggressive treatment. We tested the hypothesis that elderly patients undergoing definitive lung radiation might tolerate treatment differently than younger patients. Methods A total of 125 patients who underwent definitive lung radiotherapy were identified from a prospective institutional database (University of Michigan cohort). Logistic regression modeling was performed to assess the impact of age on esophagitis grade 2 or higher or grade 2 or higher and pneumonitis grade 3 or higher or grade 2 or higher, with adjustment for esophageal and lung dose, respectively, as well as for chemotherapy utilization, smoking status, and performance status. The analysis was validated in a large cohort of 691 patients from the Michigan Radiation Oncology Quality Consortium registry, an independent statewide prospective database. Results In the University of Michigan cohort, multivariable regression models revealed a significant inverse correlation between age and rate of esophagitis for both toxicity levels, (adjusted OR = 0.93 for both models and 95% confidence intervals of 0.88–0.98 and 0.87–0.99), with areas under the curve of 0.747 and 0.721, respectively, demonstrating good fit. This same association was noted in the Michigan Radiation Oncology Quality Consortium cohort. There was no significant association between age and pneumonitis. Conclusions There is a lower incidence of esophagitis with increasing age even after adjustment for use of chemotherapy. This is a novel finding in thoracic oncology. No age dependence was noted for pulmonary toxicity. The elderly are able to tolerate definitive thoracic radiation well and should be offered this option when clinically warranted.

Breast-conserving surgery (BCS) and radiotherapy reduce breast cancer recurrence but can cause functional deficits in breast cancer survivors. A cross-sectional study quantified the long-term pathophysiological impact of these treatments on biomechanical measures of shoulder stiffness and ultrasound shear wave elastography measures of the shear elastic modulus of the pectoralis major (PM). Nine node-positive patients treated with radiotherapy to the breast and regional nodes after BCS and axillary lymph node dissection (Group 1) were compared to nine node-negative patients treated with radiotherapy to the breast alone after BCS and sentinel node biopsy (Group 2) and nine healthy age-matched controls. The mean follow-up for Group 1 and Group 2 patients was 988 days and 754 days, respectively. Shoulder stiffness did not differ between the treatment groups and healthy controls (p = 0.23). The PM shear elastic modulus differed between groups (p = 0.002), with Group 1 patients exhibiting a stiffer PM than Group 2 patients (p

PURPOSE: Radiation-induced cardiac toxicity (RICT) is an increasingly well-appreciated source of morbidity and mortality in patients receiving thoracic radiotherapy (RT). Currently available methods to predict RICT are suboptimal. We investigated circulating microRNAs (c-miRNAs) as potential biomarkers of RICT in patients undergoing definitive RT for non-small cell lung cancer (NSCLC). METHODS: Data from 63 patients treated on institutional trials were analyzed. Prognostic models of grade 3 or greater (G3+) RICT based on pre-treatment c-miRNA levels (‘c-miRNA’), mean heart dose (MHD) and pre-existing cardiac disease (PCD) (‘clinical’), and a combination of these (‘c-miRNA + clinical’) were developed. Elastic net Cox regression and full cross-validation were used for variable selection, model building, and model evaluation. Concordance statistic (c-index) and integrated Brier score (IBS) were used to evaluate model performance. RESULTS: MHD, PCD, and serum levels of 14 c-miRNA species were identified as jointly prognostic for G3+ RICT. The ‘c-miRNA and ‘clinical’ models yielded similar cross-validated c-indices (0.70 and 0.72, respectively) and IBSs (0.26 and 0.28, respectively). However, prognostication was not improved by combining c-miRNA and clinical factors (c-index 0.70, IBS 0.28). The ‘c-miRNA’ and ‘clinical’ models were able to significantly stratify patients into high- and low-risk groups of developing G3+ RICT. Chi-square testing demonstrated a marginally significantly higher prevalence of PCD in patients with high- compared to low-risk c-miRNA profile (p=0.09), suggesting an association between some c-miRNAs and PCD. CONCLUSIONS: We identified a pre-treatment c-miRNA signature prognostic for G3+ RICT. With further development, pre- and mid-treatment c-miRNA profiling could contribute to multiparametric, patient-specific dose-selection and treatment-adaptation.

Although large volumes of information are entered into our electronic health care records, radiation oncology information systems and treatment planning systems on a daily basis, the goal of extracting and using this big data has been slow to emerge. Development of strategies to meet this goal is aided by examining issues with a data farming instead of a data mining conceptualization. Using this model, a vision of key data elements, clinical process changes, technology issues and solutions, and role for professional societies is presented. With a better view of technology, process and standardization factors, definition and prioritization of efforts can be more effectively directed.

BACKGROUND The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. METHODS This study examined the overall survival of patients treated with radiation therapy for brain metastases from non–small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. RESULTS Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. CONCLUSIONS Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091–100. © 2016 American Cancer Society.

BACKGROUND: Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. SIGNIFICANCE: Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial.

Objective: Patient-reported toxicities after breast radiotherapy merit understanding in order to inform decisions and target supportive care interventions. Methods: As part of a collaborative quality improvement initiative, the Michigan Radiation Oncology Quality Consortium prospectively collects patient-reported outcomes data from women treated for breast cancer at 26 practices across the state. Of all 11,107 patients treated with lumpectomy and whole breast radiation therapy between 1/1/2012 and 12/31/2018, 2817 refused patient surveys. We describe here the maximal toxicity reported by the 7689 patients who provided survey responses within 7 days of end of treatment and for whom we had sufficient data to determine dose-fractionation and treatment fields. Multivariable logistic regression models separately identified the individual and treatment characteristics associated with 1) breast pain, 2) a bother scale (related to itching, stinging/burning, swelling, or hurting of the treated breast), and 3) fatigue. Breast pain was considered moderate or severe when score ≥4 on modified 10-point Brief Pain Inventory measure. Bother from multiple breast symptoms was considered frequent when score ≥3 on a scaled measure (range 0-4) averaging responses on four items derived from the Skindex. Fatigue was considered severe when rated as present “always” or “most of the time” over past four weeks. Results: Moderate or severe breast pain was reported by 2882 (37.5%) overall: 1022 (28.3%) of those receiving hypofractionation (HF) and 1860 (45.7%) of those receiving conventional fractionation (CF). Frequent bother from multiple breast symptoms was reported by 1029 (13.4%) overall: 288 (8.0%) after HF and 741 (18.2%) after CF. Severe fatigue was reported by 1795 (23.4%) overall: 681 (18.8%) after HF and 1114 (27.4%) after CF. In addition to treatment fractionation (p Conclusions: In this large observational dataset of patient-reported toxicities after whole breast radiotherapy, substantial differences existed by radiotherapy dose-fractionation. Race differences in breast pain and bother existed despite controlling for multiple other factors, including age, body habitus, comorbidities, and treatment characteristics; further research is needed to understand what drives these differences in order to target potentially modifiable factors. Intensification of supportive care may be appropriate for subgroups identified as being vulnerable to greater toxicity. Multivariable Models of Patient-Reported Toxicity OutcomesIndependent VariableOdds Ratio (CI) [p value] in Model with Dependent Variable=Moderate or Severe Breast PainOdds Ratio (CI) [p value] in Model with Dependent Variable=Frequent Bother from Multiple Breast SymptomsOdds Ratio (CI) [p value] in Model with Dependent Variable=Severe FatigueAge 70+ vs 60-690.77 (0.67 - 0.89) [p40 vs Overweight 25- Citation Format: Reshma Jagsi, Kent Griffith, Frank Vicini, Jay Burmeister, Michael Dominello, Inga Grills, James Hayman, Jean Moran, Peter Paximadis, Jeffrey Radawski, Eleanor Walker, Lori Pierce. Identifying patients at higher risk of toxicity after breast radiotherapy: Analysis of patient-reported outcomes in the Michigan Radiation Oncology Quality Consortium cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD6-6.

It is an exciting time for big data efforts in radiation oncology. The use of big data to help aid both outcomes and decision making research is becoming a reality. However, there are true challenges that exist in the space of gathering and utilizing performance and outcomes data. Here, we summarize the current state of big data in radiation oncology with respect to outcomes and discuss some of the efforts and challenges in radiation oncology big data.

The management of Merkel cell carcinoma (MCC) requires multidisciplinary care for optimal patient outcomes. Radiotherapy (RT) is most commonly used as adjuvant therapy to improve locoregional control in patients with MCC who undergo surgery. Additionally, it can sometimes be used as definitive monotherapy for patients who decline or are not candidates for surgery and as palliative treatment in those with metastatic MCC. This article discusses the indications, treatment considerations, and recommended dose prescriptions for RT in the management of early- and advanced-stage disease. Considerable hope exists that immunotherapy advances will synergize with RT to further enhance clinical outcomes.

INTRODUCTION: To determine the recommended Phase II 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 MRI after RRx-001 correlate with response. METHODS AND MATERIALS: Five centers participated in this phase I/II trial of RRx-001 given once pre-WBRT then twice weekly during WBRT (30 Gy/10 fractions). 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 Model (TITE-CRM). Correlative DCE-MRI was performed in a subset of patients and linear mixed models used to correlate change in 24-hour T1, Ktrans (capillary permeability) and Vp (plasma volume) with change in tumor volume. RESULTS: Between 2015–2017, 31 patients were enrolled. Two patients dropped out prior to any therapy and 7 were treated with concurrent temozolomide following a study amendment. Median age was 60 years (range, 30–76) and 17 were male. The most common tumor types were melanoma (58%) and non-small cell lung cancer (20%). No dose-limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia in 6.9% (2/29). The median intracranial response rate was 46% (95%CI 24–68) and median overall survival was 5.2 months (95%CI 4.5–9.4). No neurologic deaths occurred. Among 10 evaluable patients undergoing DCE-MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 month and 4 months (p≤0.01). CONCLUSION: The addition of RRx-001 to WBRT is safe and well-tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, and in the absence of a dose response, the recommended Phase 2 dose is 10 mg administered twice weekly. A reduction in Vp by DCE-MRI 24 hours after RRx-001 suggests anti-angiogenic activity that is associated with longer-term tumor response.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

A formal communication process was established and evaluated for the management of patients with cardiac implantable electronic devices (CIEDs) receiving radiation therapy (RT). Methods to estimate dose to the CIED were evaluated for their appropriateness in the management of these patients. A retrospective, institutional review board (IRB) approved study of 69 patients with CIEDs treated with RT between 2005 and 2011 was performed. The treatment sites, techniques, and the estimated doses to the CIEDs were analyzed and compared to estimates from published peripheral dose (PD) data and three treatment planning systems(TPSs) - UMPlan, Eclipse's AAA and Acuros algorithms. When measurements were indicated, radiation doses to the CIEDs ranged from 0.01-5.06 Gy. Total peripheral dose estimates based on publications differed from TLD measurements by an average of 0.94 Gy (0.05-4.49 Gy) and 0.51 Gy (0-2.74 Gy) for CIEDs within 2.5 cm and between 2.5 and 10 cm of the treatment field edge, respectively. Total peripheral dose estimates based on three TPSs differed from measurements by an average of 0.69 Gy (0.02-3.72 Gy) for CIEDs within 2.5 cm of the field edge. Of the 69 patients evaluated in this study, only two with defibrillators experienced a partial reset of their device during treatment. Based on this study, few CIED-related events were observed during RT. The only noted correlation with treatment parameters for these two events was beam energy, as both patients were treated with high-energy photon beams (16 MV). Differences in estimated and measured CIED doses were observed when using published PD data and TPS calculations. As such, we continue to follow conservative guidelines and measure CIED doses when the device is within 10 cm of the field or the estimated dose is greater than 2 Gy for pacemakers or 1 Gy for defibrillators.

BACKGROUND/PURPOSE: Although inverse-planned intensity-modulated radiotherapy (IMRT) and deep inspiration breath hold (DIBH) may allow for more conformal dose distributions, it is unknown whether using these technologies reduces cardiac or pulmonary toxicity of breast radiotherapy. METHODS: A randomized controlled trial compared IMRT-DIBH versus standard, free-breathing, forward-planned, three-dimensional conformal radiotherapy in patients with left-sided, node-positive breast cancer in whom the internal mammary nodal region was targeted. Endpoints included dosimetric parameters and changes in pulmonary and cardiac perfusion and function, measured by single photon emission computed tomography (SPECT) scans and pulmonary function testing performed at baseline and one-year post-treatment. RESULTS: Of 62 patients randomized, 54 who completed all follow-up procedures were analyzed. Mean doses to the ipsilateral lung, left ventricle, whole heart, and left anterior descending coronary artery (LAD) were lower with IMRT-DIBH; the percent of left ventricle receiving ≥5 Gy (V5) averaged 15.8% with standard radiotherapy and 5.6% with IMRT-DIBH (p