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

Purpose Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. Methods and Materials Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. Results The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P = .89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P = .95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P = .28). Conclusions Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.

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

Purpose 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 / Objectives: In patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) for the treatment of breast cancer may be associated with a different complication profile than those without macromastia. General complications of BCS followed by RT includes seroma, infection, wound complications, cosmetic deformity, asymmetry, acute versus long term arm and/or breast lymphedema. Oncoplastic reduction mammoplasty (ORM) aims to reduce breast volume while excising the tumor bed and its margins. Since breast volume was found to be a risk factor for chronic breast lymphedema, this study was performed to determine the impact of ORM on chronic breast lymphedema as well as other complications compared to BCS without ORM. Materials / Methods: We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2018. Chronic breast lymphedema (CBL) was defined as swelling that persisted >1 year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate various patient factors and treatment outcomes in women with BV ≥1300 cc compared to 1300 cc are at increased risk for developing several complications regardless of the presence of ORM. Those who had ORM experienced an increase in wound complications but having undergone ORM appeared to eliminate the increased risk of CBL associated with macromastia. This suggests that ORM should be considered at the time of BCS to reduce their future risk of CBL as there is no cure for this disease. Citation Format: Jenna Nicole Luker, Cara Canella, Sanjay Rama, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Maristella Evangelista, Dunya Atisha. The effect of oncoplastic reduction on the incidence of post-operative breast lymphedema in breast cancer patients undergoing lumpectomy [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 PS1-49.

Purpose/Objective(s):Unlike temporary breast edema caused by post-lumpectomy radiation therapy (RT), the edema that persists beyond one year is not well defined and difficult to treat. The aim of this study is to define the incidence and risk factors for the development of chronic breast lymphedema in women undergoing lumpectomy with RT at a large metropolitan cancer center. Materials/Methods:A retrospective chart review was performed on all patients who underwent lumpectomy from 2014 to 2018. Women who did not undergo RT at our institution and those with stage IV disease were excluded from the analysis. Patient demographics, comorbidities, operative data, RT data and postoperative complications were obtained. Chronic breast lymphedema (CBL) was defined as edema that persisted beyond one year post completion of radiation therapy. Breast volumes were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Using a density curve, the distribution of breast volumes was plotted for patients with and patients without CBL. Univariate analysis was used to evaluate factors associated with CBL. Multivariate regression analysis was used to evaluate factors associated with the risk of CBL while accounting for potential confounding variables as defined by the univariate analysis. Results:A total of 1173 patients were included for analysis. Seventy-four (6.3%) patients developed breast lymphedema beyond one year. For the entire cohort, mean age was 63 years old (SD=11.17), mean BMI was 31.15 kg/m2 (SD=7.17), mean breast volume was 1198.54 cm3 (SD=645.82 cm3), mean total radiation was 59.18 Gy (SD=16.76), and 139 (11.8%) patients underwent ALND. Compared to the cohort that did not develop CBL (n=1099), the CBL cohort (n=74) had a higher median BMI (33.23 kg/m2 vs. 29.81 kg/m2, P Conclusion:Chronic breast lymphedema presents a clinical concern for women undergoing lumpectomy with postoperative radiation, particularly in women with larger breasts. Further studies should focus on preventative strategies, as well as the psychosocial and economic impact of this morbidity. Citation Format: Sanjay Rama, Cara Canella, Jenna Luker, Kelley Park, Renee Barry, Saheli Ghosh, Simeng Zhu, Yalei Chen, Jessica Bensenhaver, Eleanor Walker, Kenneth Levin, Dunya Atisha, Maristella Evangelista. Factors associated with chronic breast lymphedema after adjuvant radiation in women undergoing breast conservation therapy [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 PS1-12.

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.

A growing number of cancer patients use complementary and alternative therapies during and after conventional cancer treatment. Patients are often reluctant to discuss these therapies with their oncologist, and oncologists may have limited knowledge and confidence on how to advise patients on the appropriate use. Integrative oncology is a patient-centered, evidence-informed field that utilizes mind–body practices, lifestyle modifications and/or natural products interwoven with conventional cancer treatment. It prioritizes safety and best available evidence to offer appropriate interventions alongside conventional care. There are few opportunities for oncologists to learn about integrative oncology. In this commentary, we highlight the Integrative Oncology Scholars (IOS) program as a means to increase competency in this growing field. We provide an overview of several integrative oncology modalities that are taught through this program, including lifestyle modifications, physical activity, and mind–body interventions. We conclude that as more evidence is generated in this field, it will be essential that oncology healthcare providers are aware of the prevalent use of these modalities by their patients and cancer centers include Integrative Oncology trained physicians and other healthcare professionals in their team to discuss and recommend evidence-based integrative oncology therapies alongside conventional cancer treatments to their patients.

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: Radiation dose to cardiac substructures is related to radiation-induced heart disease. However, substructures are not considered in radiation therapy planning (RTP) due to poor visualization on CT. Therefore, we developed a novel deep learning (DL) pipeline leveraging MRI’s soft tissue contrast coupled with CT for state-of-the-art cardiac substructure segmentation requiring a single, non-contrast CT input. MATERIALS/METHODS: Thirty-two left-sided whole-breast cancer patients underwent cardiac T2 MRI and CT-simulation. A rigid cardiac-confined MR/CT registration enabled ground truth delineations of 12 substructures (chambers, great vessels (GVs), coronary arteries (CAs), etc.). Paired MRI/CT data (25 patients) were placed into separate image channels to train a three-dimensional (3D) neural network using the entire 3D image. Deep supervision and a Dice-weighted multi-class loss function were applied. Results were assessed pre/post augmentation and post-processing (3D conditional random field (CRF)). Results for 11 test CTs (seven unique patients) were compared to ground truth and a multi-atlas method (MA) via Dice similarity coefficient (DSC), mean distance to agreement (MDA), and Wilcoxon signed-ranks tests. Three physicians evaluated clinical acceptance via consensus scoring (5-point scale). RESULTS: The model stabilized in ~19 h (200 epochs, training error 0.05) to ground truth. In four cases, DL yielded left main CA contours, whereas MA segmentation failed, and provided improved consensus scores in 44/60 comparisons to MA. DL provided clinically acceptable segmentations for all graded patients for 3/4 chambers. DL contour generation took ~14 s per patient. CONCLUSIONS: These promising results suggest DL poses major efficiency and accuracy gains for cardiac substructure segmentation offering high potential for rapid implementation into RTP for improved cardiac sparing.

PURPOSE To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here. PATIENTS AND METHODS Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs). RESULTS A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS ( P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS ( P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS ( P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR. CONCLUSION RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

The AeroForm chest wall tissue expander (TE) is a silicon shell containing a metallic CO2 reservoir, placed surgically after mastectomy. The patient uses a remote control to release compressed CO2 from the reservoir to inflate the expander. AeroForm poses challenges in a radiation therapy setting: The high density of the metallic reservoir causes imaging artifacts on the planning CT, which encumber structure definition and cause misrepresentation of density information, in turn affecting dose calculation. Additionally, convolution‐based dose calculation algorithms may not be well‐suited to calculate dose in and around high‐density materials. In this study, a model of the AeroForm TE was created in Eclipse treatment planning system (TPS). The TPS model was validated by comparing measured to calculated transmission through the AeroForm. Transmission was measured with various geometries using radiochromic film. Dose was calculated with both Varian’s Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB) algorithms. AAA and AXB were compared using dose profile and gamma analyses. While both algorithms modeled direct transmission well, AXB better modeled lateral scatter from the AeroForm TE. Clinical significance was evaluated using clinical data from four patients with AeroForm TEs. The AeroForm TPS model was applied, and RT plans were optimized using AAA, then re‐calculated with AXB. Structures of clinical significance were defined and dose volume histogram analysis was performed. Compared to AXB, AAA overestimates dose in the AeroForm device. Changes in clinically significant regions were patient‐ and plan‐specific. This study proposes a clinical procedure for modeling the AeroForm in a commercial TPS, and discusses the limitations of dose calculation in and around the device. An understanding of dose calculation accuracy in the vicinity of the AeroForm is critical for assessing individual plan quality, appropriateness of different planning techniques and dose calculation algorithms, and even the decision to use the AeroForm in a postmastectomy radiation therapy setting.

INTRODUCTION: The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS: We used the Institute for Healthcare Improvement’s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute’s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P < .01). CONCLUSION: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted.

Radiation dose to the heart and cardiac substructures has been linked to cardiotoxicities. Because cardiac substructures are poorly visualized on treatment-planning computed tomography (CT) scans, we used the superior soft-tissue contrast of magnetic resonance (MR) imaging to optimize a hybrid MR/CT atlas for substructure dose assessment using CT.Thirty-one patients with left-sided breast cancer underwent a T2-weighted MR imaging scan and noncontrast simulation CT scans. A radiation oncologist delineated 13 substructures (chambers, great vessels, coronary arteries, etc) using MR/CT information via cardiac-confined rigid registration. Ground-truth contours for 20 patients were inputted into an intensity-based deformable registration atlas and applied to 11 validation patients. Automatic segmentations involved using majority vote and Simultaneous Truth and Performance Level Estimation (STAPLE) strategies with 1 to 15 atlas matches. Performance was evaluated via Dice similarity coefficient (DSC), mean distance to agreement, and centroid displacement. Three physicians evaluated segmentation performance via consensus scoring by using a 5-point scale. Dosimetric assessment included measurements of mean heart dose, left ventricular volume receiving 5 Gy, and left anterior descending artery mean and maximum doses.Atlas approaches performed similarly well, with 7 of 13 substructures (heart, chambers, ascending aorta, and pulmonary artery) having DSC0.75 when averaged over 11 validation patients. Coronary artery segmentations were not successful with the atlas-based approach (mean DSC0.3). The STAPLE method with 10 matches yielded the highest DSC and the lowest mean distance to agreement for all high-performing substructures (omitting coronary arteries). For the STAPLE method with 10 matches,50% of all validation contours had centroid displacements3.0 mm, with the largest shifts in the coronary arteries. Atlas-generated contours had no statistical difference from ground truth for left anterior descending artery maximum dose, mean heart dose, and left ventricular volume receiving 5 Gy (P .05). Qualitative contour grading showed that 8 substructures required minor modifications.The hybrid MR/CT atlas provided reliable segmentations of chambers, heart, and great vessels for patients undergoing noncontrast CT, suggesting potential widespread applicability for routine treatment planning.

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

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.

10591 Background: TNBC is disproportionately prevalent in African American (AA) populations and in women with BRCA-1 germline mutations. BRCA mutation carriers are candidates for targeted therapy with PARP-inhibitors, and testing results may influence risk-reducing surgery choice. Methods: We evaluated genetic testing patterns and outcomes for TNBC patients treated in the prospectively maintained databases of academic cancer programs in two metropolitan cities in the Northeast (New York City, NYC) and Midwest (Detroit, Det), 1998-2018. Median follow up was 3.73 years. Testing patterns were also analyzed by time, comparing pts diagnosed before versus after the mid-2013 Supreme Court ruling that expanded testing availability by banning gene patenting. Results: Of 810 pts, 600 were from NYC and 200 from Det; 202 were AA and 488 WA. Pts undergoing genetic testing were younger (median age 50 vs 62; p < 0.0001). Compared to WA, AA pts were less likely to undergo genetic testing overall (23.8% vs 42.0%; p < 0.0001) and within site (NYC: 25.6% vs 42.8%, p = 0.008; Det: 22.3% vs 38.6%, p = 0.025). No significant differences were seen in frequency of pathogenic BRCA mutations (AA-14.6%; WA-29.3%) or VUSs (AA-6.3%; WA- 4.9%); p = 0.20. Genetic testing disparities were reduced among pts diagnosed after mid-2013 (AA-31.4% vs WA-44.0%; p = 0.01) compared to pre-mid-2013 (AA-18.3% vs WA-40.7%; p < 0.0001). No differences were seen in local or distant recurrence free survival between patients with BRCA, BRCA variants of uncertain significance, non-BRCA mutations, and patients without genetic mutations (local recurrence p = 0.827; distant recurrence p = 0.574). This outcome equivalence was consistent when stratified by WA vs AA identity. Conclusions: Genetic testing has increased for TNBC pts following the mid-2013 Supreme Court ban on gene patenting, but race-associated disparities persist. Pts undergoing genetic testing are more likely to undergo risk-reducing mastectomy, but testing results do not affect survival outcomes, regardless of race. Addressing genetic testing disparities will become increasingly important as mutation-associated targeted therapies are identified through advances in precision medicine.

Introduction In sub-Saharan Africa, breast cancer (BC) is the leading cancer in women and the second cause of cancer mortality. In order to reduce the burden of BC in women with African ancestry there is a need for a structured, coordinated effort to address gaps in our understanding of the factors associated with the disease that influence tumor initiation, progression, and outcomes. To address this need ‘Precision Medicine for African Breast Cancer (PMABC)’ a comprehensive partnership housed at the Henry Ford Cancer Institute was created with the aim of bringing together African researchers to study African BC. We are currently composed of nine leading institutions spanning West and East Africa and two institutions in the United States. Objectives The broad aim of PMABC is to bring together researchers and institutions across sub-Saharan Africa to partner with foreign institutions and funding agencies to study and identify new and improved methods of screening, diagnosing, and treating BC in Africans to improve the overall outcome. Among the aims of PMABC are: • Registry: Create a national BC registry building on data from participating institutions which comprise at least 80% of all BC cases seen in the respective country • Standardization of pathology protocol and reporting: harmonize the pathology reporting scheme and ensure its conformity to international standards Standardization of treatment protocols: Study and compare treatment protocols with international standards and make recommendations • Biorepository: Create a national repository of patient samples to be used in genetic and biological studies • Study African tumor biology: Build the capacity to be able to study African tumors locally and participate in clinical trials • Patient follow up and survival studies: study and obtain data on patient outcomes Achievements We currently have ethical approval and have begun work in nine institutions across West and East Africa. • Creation of a national database in Ghana that currently consists of over 7000 patients. The data is being analyzed to determine risk factors and the distribution of BC by subtypes • We are setting up two research labs in Ghana to train local researchers for basic and translational research • We have a biorepository of over 2000 patient samples that is available for collaborative studies • We have developed tumor models from continental African breast tumors • Building partnership with international organizations, pharmaceutical companies, and funding agencies to study African BC Conclusion PMABC serves as an umbrella institution to coordinate the work between these researchers and to provide resources for the institutions to provide a high level of BC research and treatment. We are aiming to partner with countries across Africa to translate the model created by PMABC in order fulfill the need for further BC research and standardization of data collection and treatment. PMABC is made possible because of the dedication and passion of our collaborating researchers. Citation Format: Sabrina I. Fossi, Sylvester Antwi, Kwabena Agbedinu, Kafui Akakpo, Samuel Mensah, Nelson Affram, Mohammed Sheriff, Foster Amponsah, Jacqueline Asibey, Osei Collins, Alex Mremi, Livingstone Aduse-Poku, Kurt Fernando, Haythem Ali, Eleanor Walker, Jessica Bensenhaver, Evelyn M. Jiagge. Precision medicine for African breast cancer: Bringing African researchers together to study African breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-189.

Introduction One major limitation to cancer prevention and control in Africa has been lack of accurate and reliable epidemiological data. To date, there is no publicly available systematic review and meta-analysis on the prevalence of breast cancer in Africa. This data is important to understand the burden of the disease in Africa and identify areas lacking reliable studies. Objective The objective of this review was to examine the prevalence of breast cancer in Africa based on region, subtype, and screening. Methods A systematic search of MEDLINE, EMBASE, PUBMED, ISI Web of Science, BIOSIS, African Journal Online, and Global Health was conducted. We included population-based or hospital-based cancer registry studies on breast cancer conducted on African populations and providing estimates of breast cancer cases or prevalence over a period. A random effect meta-analysis was done to determine the pooled prevalence of breast cancer in Africa based on region, subtype and screening, using Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC. Results Our search of databases yielded 2030 references that were imported into Covidence. A total of 44 studies were included in the review. The overall pooled prevalence of breast cancer in Africa was 0.48% (95% CI: 0.05-0.92). With regards to regional prevalence, the estimated prevalence of breast cancer among women in Sub-Saharan Africa (SSA), 0.68% (-0.03 - 0.1.39) was remarkably higher than that of women in North Africa (NA) 0.16% (95% CI: -0.11-0.42). Also, the overall prevalence of triple negative breast cancer (TNBC) among female breast cancer patients was 29.51% (CI: 23.94-35.08). A sub-group analysis revealed, TNBC was more prevalent in women from SSA 29.51 (CI: 23.94- 35.08, 18 studies) than women from NA 20.17(14.63-25.71, 8 studies). Meta-analysis of African women participation in Breast Self-Examination (BSE) produced a prevalence of 29.57 (CI: 7.90-51.25). This was higher than the prevalence of African women participation in Clinical Breast Examination and mammography, 12.22 (7.58-16.86). Conclusions Though the incidence of breast cancer in Africa is relatively low, the same cannot be said of its prevalence. Also, within Africa, there are clear regional and sub-regional differences in both breast cancer prevalence and the prevalence of TNBC among breast cancer patients. This may be attributed to limited infrastructure needed for breast cancer control and prevention especially within SSA regions. Establishment of robust hospital-based cancer registries in Africa will boost the collection of accurate and complete cancer data that can be used in epidemiological research, patient care improvement, and cancer control which will ultimately lead to the reduction of breast cancer burden in Africa. Citation Format: Livingstone Aduse-Poku, Kurt Fernando, Sabrina I. Fossi, Sylvester Antwi, Haythem Ali, Eleanor Walker, Evelyn M. Jiagge. A systematic review and meta-analysis of the prevalence of breast cancer in Africa: Identifying unanswered questions [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-152.

Racial and ethnic diversity has historically been difficult to achieve in National Cancer Institute-sponsored clinical trials, even while as many as 80% of those trials have faced difficulty in meeting overall recruitment targets. In an attempt to address these issues, NRG Oncology recently convened a comprehensive workshop titled "Clinical Trials Enrollment: Challenges and Opportunities." Discussants at the workshop included representatives of the three legacy groups of the NRG (ie, Gynecologic Oncology Group, National Surgical Adjuvant Breast and Bowel Program, and Radiation Therapy Oncology Group), a minority-based community clinical oncology program, a large integrated health care system, the leadership of the National Cancer Institute, and a large patient advocacy group. This article summarizes the concepts discussed at the workshop, which included: needs assessments, infrastructural support, training of investigators and research staff, specific clinical trial recruitment strategies (both system and community based), and development and mentoring of young investigators. Many new, more specific tactics, including use of diverse cancer care settings, direct-to-consumer communication, and the need for centralized information technology such as the use of software to match trials to special populations, are presented. It was concluded that new, innovative trial designs and the realities of limited funding would require the adoption of effective and efficient recruiting strategies, specialized training, and stakeholder engagement. US clinical research programs must generate and embrace new ideas and pilot test novel recruitment strategies if they are to maintain their historic role as world leaders in cancer care innovation and delivery.

The Duffy Antigen Receptor for Chemokines (DARC/ACKR1) is an atypical chemokine receptor which promiscuously binds chemokines of both CC and CXC chemokine families. DARC/ACKR1 maintains homeostatic levels of chemokines in circulation through its expression on erythrocytes, and in tissues participates in chemokine transport, where chemokines are transported across the cell layer to help establish chemokine gradients. Establishment of these chemokine gradients is essential for proper immune cell trafficking. In our recent study, we have shown that DARC/ACKR1 is expressed on the tumor epithelium, and through in silico analysis of data from the Cancer Genome Atlas (TCGA), that higher DARC/ACKR1 expression is positively and significantly correlated with tumor-associated leukocyte abundance when using CIBERSORT deconvolution methods. Specifically, higher DARC/ACKR1 expression was linked with increases in B cell, T cell, monocyte and macrophage populations. Higher DARC/ACKR1 expression is also significantly associated with better survival outcomes, across all breast cancer molecular subtypes. To further evaluate DARC/ACKR1 expression and influences on the breast TME, we have employed multiple approaches to characterize how DARC/ACKR1 impacts immune cell recruitment and subsequent infiltration into the tumor. In our patient cohort, we have recently completed Hyperion imaging mass cytometry staining of tumors that have been scored by IHC as DARC/ACKR1 high or low expressing. We used a panel of approximately 30 markers, including structural, immune, and other markers of interest. Following imaging, we have used cell segmentation software to quantify marker expression on a cell-by-cell basis. Using this method, we are able to conduct single-cell analyses of our markers of interest, while also retaining the spatial composition of the cells. We have used the tSNE algorithm to identify cell populations that cluster uniquely within DARC/ACKR1 high or low tumor expressing groups, specifically identifying different clusters of immune cell populations, which show different spatial expression patterns in our comparison groups. In addition to investigations of immune cell recruitment to the TME, we have also developed a novel DARC/ACKR1 breast cancer transgenic mouse model to study how disease progression may differ with differing DARC/ACKR1 phenotypes. Briefly, DARC -/- female mice were crossed with the male C3(1)Tag +/0 breast cancer transgenic mouse to generate DARC +/-, C3(1)Tag +/0 male mice. These males were subsequently backcrossed to DARC -/- females, to generate the target DARC/ACKR1 +/- or -/-, C3(1)Tag+ mice. These mice show evidence of early disease beginning at 3.5 months of age, and progress to advanced disease by 5 months of age. We have collected tumor tissue and blood specimens from mice ranging from 3.5 to 7 months of age, to characterize disease progression over time between our DARC/ACKR1 expressing and non-expressing groups. We have observed differences in tumors characteristics between our DARC/ACKR1 expressing groups, and upon histological and immunofluorescent evaluation, we have begun to observe differences in immune cell recruitment, following similar patterns to what we observed in our in silico and patient cohort analyses. Citation Format: Rachel Martini, Brittany Jenkins, Dorrah Deeb, Hiranmayi Ravichandran, Paula Ginter, Esther Cheng, Syed Hoda, Dhananjay Chitale, Haythem Ali, Eleanor Walker, Jessica Bensenhaver, Olivier Elemento, Nancy Manley, Lisa Newman, Melissa Davis. Breast tumor expression of DARC/ACKR1 and impacts on disease progression and immune cell recruitment in the tumor microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4975.

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.

Purpose Scales for rating acute radiation dermatitis (ARD) are inconsistent and have not been validated despite decades of clinical use, making ARD difficult to report reliably. We sought to design a photonumeric scale to consistently describe ARD in breast cancer patients undergoing radiation (RT). Methods Patients undergoing RT for breast cancer were enrolled on a prospective study that included photographs and reporting of physician-rated erythema, hyperpigmentation, and CTCAE toxicity score at baseline and 2, 4, and 6 weeks after initiating RT. Erythema and hyperpigmentation were also quantified using a hand-held colorimetric device. Photographs were taken using a standardized protocol that included 3 views to fully assess the breast/chest wall, axilla, and inframammary fold. 209 photographs from 35 patients with white skin (Fitzpatrick skin types I-IV) and 369 photographs from 50 patients with skin of color (Fitzpatrick skin types V-VI) were clustered according to the apparent severity of ARD. Due to the prevalence of hyperpigmentation that obscured erythema in patients with skin of color, separate images were used to illustrate ARD in this population. Two photonumeric scales (for white skin and skin of color) were developed via an iterative process until group consensus was achieved. Four raters with experience in the evaluation of ARD in breast cancer patients used the photonumeric scale to independently score the entire collection of photographs, sequenced in random order. Intra- and inter-rater agreements were assessed using weighted kappa scores. Results Of the 35 patients with white skin, 20% experienced severe erythema, and 40% experienced dry or moist desquamation. Of the 50 patients with skin of color, 34% experience severe hyperpigmentation, and 48% experienced dry or moist desquamation. Using the photonumeric scales, we observed high intra-rater agreement for independent ratings of erythema or hyperpigmentation (70 to 89% agreement fraction, kappa 0.55 to 0.81) and desquamation (79 to 87% agreement fraction, kappa 0.52 to 0.64). Similarly, we observed moderate to high inter-rater agreement for independent ratings of erythema or hyperpigmentation (61 to 76% agreement fraction, kappa 0.40 to 0.62) and desquamation (69 to 84% agreement fraction, kappa 0.36 to 0.58). Quantitative measurements of erythema in white patients using colorimetry correlated strongly with photonumeric grade (correlation coefficient 0.76, p Conclusions We report a new photonumeric scale with high intra- and inter-rater reliability for acute radiation dermatitis in breast cancer patients. To our knowledge, this is the first rigorously evaluated scale that is applicable to patients across the spectrum of skin pigmentation, including white skin and skin of color. The photonumeric scale will facilitate consistent reporting of acute radiation dermatitis in research and clinical settings using a simple, standardized instrument. Future work will include prospective real-time clinical validation with multiple raters and correlation with patient-reported outcomes. Funded by a Munn Idea Grant (G011480). Citation Format: Dean Shumway, Eleanor M Walker, Nirav Kapadia, Thy Thy Do, Kent Griffith, Mary Feng, Bonnie DePalma, Reshma Jagsi, Yolanda Helfrich, Erin Gillespie, Alexandria Miller, Adam Liss, Lori J Pierce. Development of a photonumeric scale for acute radiation dermatitis in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-12.

Purpose The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation. Patients and Methods This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method. Results Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients. Conclusion In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.

Purpose To evaluate intrafraction variability and deformation of the lumpectomy cavity (LC), breast, and nearby organs. Methods and Materials Sixteen left-sided postlumpectomy and 1 bilateral breast cancer cases underwent free-breathing CT (FBCT) and 10-phase 4-dimensional CT (4DCT). Deformable image registration was used for deformation analysis and contour propagation of breast, heart, lungs, and LC between end-exhale and end-inhale 4DCT phases. Respiration-induced motion was calculated via centroid analysis. Two planning target volumes (PTVs) were compared: PTV FBCT from the FBCT volume with an isotropic 10 mm expansion (5 mm excursion and 5 mm setup error) and PTV 4DCT generated from the union of 4DCT contours with isotropic 5 mm margin for setup error. Volume and geometry were evaluated via percent difference and bounding box analysis, respectively. Deformation correlations between breast/cavity, breast/lung, and breast/heart were evaluated. Associations were tested between cavity deformation and proximity to chest wall and breast surface. Results Population-based 3-dimensional vector excursions were 2.5 ± 1.0 mm (range, 0.8-3.8 mm) for the cavity and 2.0 ± 0.8 mm (range, 0.7-3.0 mm) for the ipsilateral breast. Cavity excursion was predominantly in the anterior and superior directions (1.0 ± 0.8 mm and −1.8 ± 1.2 mm, respectively). Similarly, for all cases, LCs and ipsilateral breasts yielded median deformation values in the superior direction. For 14 of 17 patients, the LCs and breast interquartile ranges tended toward the anterior direction. The PTV FBCT was 51.5% ± 10.8% larger ( P 4DCT . Bounding box analysis revealed that PTV FBCT was 9.8 ± 1.2 (lateral), 9.0 ± 2.2 (anterior–posterior), and 3.9 ± 1.8 (superior–inferior) mm larger than PTV 4DCT . Significant associations between breast and cavity deformation were found for 6 of 9 axes. No dependency was found between cavity deformation and proximity to chest wall or breast surface. Conclusions Lumpectomy cavity and breast deformation and motion demonstrated large variability. A PTV 4DCT approach showed value in patient-specific margins, particularly if robust interfraction setup analysis can be performed.

141 Background: Concerns about racial disparities in the adoption of medical advances motivate investigation of the use of hypofractionated radiotherapy, a less burdensome and less costly approach that is efficacious for most patients with early-stage breast cancer. Methods: A prospectively collected statewide quality consortium database from 25 institutions was queried for breast cancer patients who completed hypofractionated (HF) or conventionally fractionated whole breast radiotherapy (RT) from 1/2012-12/2018. We used patient-level multivariable modeling to evaluate associations between HF use and race, controlling for patient and facility factors, and multilevel modeling to account for patient clustering within facilities. Results: Of 10,318 patients analyzed, 80% self-reported their race as White, 18% as Black, and 2% as Asian, similar to statewide and national distributions. 31% of Whites were treated at academic centers compared to 65% of Blacks and 65% of Asians. In 2018, HF was utilized in 75% of Whites versus 60% of Blacks and 68% of Asians. On patient-level multivariable analysis (see Table), Black and Asian race were significantly associated with a lower likelihood of HF receipt, despite accounting for treatment year, age, laterality, BMI, breast volume, comorbidities, stage, triple-negative status, IMRT use, academic center treatment, and 2011 ASTRO Hypofractionation Guideline eligibility. On multilevel analysis, race was no longer significantly associated with HF receipt. Conclusions: We observed thatBlack and Asian patients receive hypofractionated RT less often, despite more frequent treatment at academic centers. Multilevel modeling eliminated this disparity, suggesting that differences in facility-specific HF use may contribute. Further inquiry is needed to determine if reduction of facility-level variation may reduce disparities in accessing HF treatment.[Table: see text]

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.

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.

AimsRadiation Therapy Oncology Group 98-04 sought to identify women with ‘good risk’ ductal carcinoma in situ (DCIS) who receive no significant benefit from radiation. Enrolment criteria excluded close or positive margins and grade 3 disease. To ensure reproducibility in identifying good risk pathology, an optional web based teaching tool was developed and a random sampling of 10% of submitted slides were reviewed by a central pathologist.MethodsSubmitting pathologists were asked to use the web based teaching tool and submit an assessment of the tool along with the pathology specimen form and DCIS H&E stained slide. Per protocol pathology was centrally reviewed for 10% of the cases.ResultsOf the 55 DCIS cases reviewed, three had close or positive margins and three were assessed to include grade 3 DCIS, therefore 95% of DCIS cases reviewed were correctly graded, and 89% reviewed were pathologically appropriate for enrolment. Regarding the teaching tool, 13% of DCIS cases included forms that indicated the website was used. One of these seven who used the website submitted DCIS of grade 3.ConclusionsCentral review demonstrates high pathological concordance with enrolment eligibility, particularly with regard to accurate grading. The teaching tool appeared to be underused.

OBJECTIVES The purpose of this study was to analyze the prognostic significance of sociodemographic factors on biochemical control (bNED) and overall survival (OS) in patients with prostate cancer. METHODS Prostate cancer patients treated with definitive external beam radiation therapy (EBRT)±hormone therapy from 1997 to 2006 were analyzed in this IRB-approved study. Patient demographics, treatment (Tx), and clinical outcome were obtained from electronic medical records. Median household income (mHHI) at the census block group level was obtained from the 2000 census data. Data on disease and Tx parameters included Gleason score, pre-Tx prostate-specific antigen (PSA), T stage, year of Tx, EBRT dose, and use of hormone therapy. Patients were categorized as having low-risk, intermediate-risk, or high-risk disease. Sociodemographic factors included age, race, marital status, and mHHI. Biochemical failure was defined as nadir PSA+2 ng/mL. OS was based on death from any cause. RESULTS A total of 788 consecutive patients were studied with a median follow-up of 7 years (range, 0.4 to 15 y). African Americans comprised 48% of the patients, whereas 46% of patients were white and 6% were other races. Whites had an average mHHI of $60,190 compared with $36,917 for African Americans (P