Search

Background Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in elderly patients, there is limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of elderly breast cancer patients with BM (≥ 65 yo) treated at our institution and compared them to younger patients. Methods An IRB-approved single-institutional review of biopsy-proven breast cancer patients with BM treated with 1 to 5-fraction stereotactic radiation therapy (SRT) from 2015 to 2020 was performed. Primary endpoint was intracranial progression free survival (PFS) defined as time interval between end of SRT to date of first CNS progression. Secondary endpoints were overall survival (OS) from end of SRT, and radiation treatment patterns. Kaplan-Meier estimates, and Cox proportional hazard regression method were used for survival analyses. SPSS v26.0 was used for statistical analysis and p-value < 0.05 was considered significant. Results A total of 115 metastatic breast cancer patients with BMs were included of which N=29 were ≥65 yo and N=86 were < 65 yo. They received a total of 43 and 143 courses of stereotactic linac-based radiation therapy (RT) respectively to a mean number of 4.3 BM lesions (range 1-22). Median age at RT was 70 years (range 65-84) compared to 50.5 years (31-64) in younger patients. About 55.2% of elderly patients were ER/PR positive/Her2 negative (vs 24.4% in younger cohort), 31% were Her2 positive (vs 41.9%) and 13.8% were triple negative (vs 33.7%). Among patient characteristics, there was significant difference among elderly and young patients in hormone receptor status (p = 0.016); CNS only oligometastatic disease (0% vs 11.2%, p = 0.005); and the presence of extracranial disease at SRS (97.7% vs 79.7%, p < 0.001). There was no significant difference between the two age groups in Karnofsky performance score (KPS) (62.7% vs 45.5% with KPS ≤ 80, p = 0.131), number of brain lesions treated (23.2% vs 30.1% with ≥ 5 BMs, p = 0.445), number of patients receiving prior whole brain radiotherapy (WBRT) (10.3% vs 19.8%, p = 0.062), surgery (23.2% vs 30.1%, p = 0.592), systemic therapy (including chemotherapy, targeted therapy and endocrine therapy) after SRT (86% vs 86.7%, p = 0.543), and salvage WBRT (10.3% vs 19.8%, p = 0.134). Median OS after RT was poorer in patients ≥ 65 yo compared to younger patients (7.9 months vs 14.4 months, p = 0.020), while intracranial PFS from RT was similar (8.5m vs 6.5m, p =0.345). The rates of freedom from neurological death and leptomeningeal disease (LMD) at 1 year were similar between the two groups (83.3% vs 87%, p = 0.780 and 87.6% vs 73.3%, p = 0.627, respectively). On univariate analysis, significant predictors of survival were age ≥65 yo (hazard risk, HR = 1.56), KPS < 80 (HR = 1.69), extracranial progression at RT (HR = 2.44), systemic therapy after RT (HR = 0.28) and LMD (HR = 1.57). On multivariate analysis, age was not a significant factor for survival after adjusting for KPS, extracranial progression and systemic therapy. Conclusions Although elderly women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and outcomes for breast cancer patients with BMs and personalized decision making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in elderly patients. Citation Format: Rituraj Upadhyay, Haley K. Perlow, Nicole Williams, Brett Klamer, Julia White, Jose G. Bazan, Sachin R. Jhawar, Dukagjin M. Blakaj, John Grecula, Andrea Arnett, Evan Thomas, Arnab Chakravarti, Raju R. Raval, Maryam Lustberg, Joshua Palmer, Sasha Beyer. Radiation Treatment Patterns for Elderly Women with Breast Cancer Brain Metastases [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-10.

Background: Recent studies suggest racial and ethnic differences in tumor genomics and receipt of systemic treatment may be drivers of racial and ethnic disparities in clinical outcomes (e.g., mortality, recurrence) in patients with breast cancer (BC). For patients of Hispanic ethnicity, the relationship between ethnoracial categories (i.e., Hispanic Black, Hispanic White), tumor genomics, and receipt of systemic has not been well elucidated. The objective of this study is to examine implications of ethnoracial categories on Oncotype DX recurrence score (RS), receipt of chemotherapy for high risk RS and endocrine therapy (ET) use in the National Cancer Database (NCDB). Materials/Methods: Patients diagnosed from 2004-2017 with stage I or stage II HR+/HER2- BC with RS available in the NCDB were identified. The data was divided into Black and White patients then stratified by ethnicity. Study ethnoracial categories included non-Hispanic White (NHW), Hispanic White (HW), non-Hispanic Black (NHB) and Hispanic Black (HB). High-risk RS was defined using the original definition of RS>30. On univariable analysis, intra-racial differences in RS score (t-test) and the proportion of patients with high-risk RS (chi-square test) were examined by ethnicity. Systemic therapy (chemotherapy and ET) were assessed with univariable analysis within racial groups by ethnicity (chi-square test). Results: The ethnoracial composition of the cohort was 220,490 (87.5%) NHW, 20,690 (8.2%) HB, 10,477(4.2%) HW and 296 (< 1%) HB. Overall, Hispanic patients had higher mean RS relative to non-Hispanic patients (18.4 [11.8] vs. 18.0 [10.8], p=0.0004) and a higher proportion of RS>30 (10.4% vs. 9.6%, p=0.0028). Amongst White patients, Hispanic ethnicity was associated with higher mean RS (18.3 [11.7] HW vs. 17.8 [10.6] NHW) and higher rate of RS>30 (10.4% HW vs. 9.1% NHW, p< 0.0001). There was no significant difference in mean RS between NHB and HB patients (19.0 [13.5] HB vs. 20.0 [12.7], p=0.1855) but there was a trend towards a lower proportion of RS>30 in HB patients (10.8% HB vs. 14.6% NHB, p=0.0688. In patients with RS>30, the proportion that received chemotherapy was similar based on ethnicity within White (80.7% HW vs. 82.3% NHW, p=0.1843) and Black (78.1% HB vs. 81.2% NHB, p=0.6601) patients. ET use was slightly lower in HW vs. NHW patients (90.6% vs. 91.7%, p< 0.0001). There was no significant difference in ET use in NHB vs HB patients (89.9% vs. 89.9%, p=0.9651). Conclusions: In our examination of the early-stage breast cancer patients in the NCDB, Hispanic ethnicity was associated with higher RS amongst White patients with an opposite trend in Black women. Systemic therapy use was largely similar across ethnoracial categories. Future, studies should disaggregate Hispanic ethnicity by race to better understand tumor characteristics and clinical outcomes in this population. Citation Format: Jose G. Bazan, Sachin R. Jhawar, Daniel Stover, Sasha Beyer, Julia White, Samilia Obeng-Gyasi. Understanding Ethnoracial Differences in Oncotype DX Recurrence Scores in Patients with Early-Stage Breast Cancer: An Analysis Based on Hispanic Ethnicity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-60.

This cohort study characterizes the inclusion of Hispanic ethnicity or ethnoracial categories in breast cancer studies from the National Cancer Database.

Purpose: The TARGIT-A trial of kilovoltage intraoperative radiation therapy (IORT) versus external beam radiation therapy (EBRT) demonstrated a significant reduction in non-breast cancer mortality (nBCM) in women that received IORT, largely attributed to an increase in cardiac mortality in patients that received EBRT. Further, If EBRT does result in excess nBCM due to cardiac or other causes, then treatment with lumpectomy (Lump) alone or mastectomy (Mast) alone should result in lower rates of nBCM rates compared to Lump+EBRT. Our primary objective was to determine whether Lump+EBRT results in increased nBCM compared to Lump+IORT in women with early-stage breast cancer (BC) with a hypothesis that the two approaches should result in equivalent nBCM. We also tested the hypotheses that Lump+EBRT should have the same rates of nBCM as Lump alone or Mast alone. Materials/Methods: We used the Surveillance Epidemiology and End Results (SEER) database to identify women with early-stage BC treated with Lump alone, Lump+EBRT, Lump+IORT, or Mast alone from 2000-2016. SEER does not distinguish between kilovoltage IORT and electron IORT. We included patients with characteristics similar to the TARGIT-A study: age≥45 years; ductal carcinoma in situ (DCIS) or T1; lymph-node negative. We excluded patients that: received chemotherapy; received postmastectomy radiation therapy; had unknown cause of death; and had ≤1 month of follow-up. The primary endpoint was nBCM which is captured in the SEER database (patients were censored if they were alive or dead due to cancer at last follow-up). Cox-proportional hazards multivariate regression models were used to compare nBCM between Lump+EBRT and Lump+IORT adjusting for confounders that were statistically significant on univariate analysis. We secondarily compared nBCM in the Lump+EBRT vs. Lump population and Lump+EBRT vs. Mast population. Results: We identified 219,470 women that met the inclusion criteria: 121,776 Lump+EBRT; 1,735 Lump+IORT; 41,900 Lump; 54,059 Mast. Median follow-up time was 61 months for the entire cohort (IQR, 30-99 months) but was shorter for Lump+IORT patients (29 months) compared to the other groups (63 months Lump+EBRT; 62 months Mast; 57 months Lump). There were a total of 16,640 nBCM events: 6,210 Lump+EBRT; 5,708 Lump; 4,704 Mast; 18 Lump+IORT. The 5-year cumulative incidence of nBCM was 3.1% for Lump+EBRT vs. 1.6% for Lump+IORT (p=0.034). After adjustment for potential confounders (age, tumor location, marital status, race/ethnicity, DCIS vs. invasive, tumor grade, hormone receptor status, and receipt of axillary surgery), patients treated with Lump+IORT had a 38% relative reduction in the risk of nBCM compared to those treated with Lump+EBRT (HR=0.62, 95% CI 0.39-0.99, p=0.045). Other factors associated with increased nBCM included older age, divorced/single/widowed status (vs. married), Black race, high tumor grade, receipt of axillary lymph node dissection (vs. sentinel lymph node biopsy), no axillary surgery (vs. sentinel node biopsy), and ER-/PR- disease (vs. ER+ or PR+). In contrast, patients treated with Lulmp+EBRT had lower nBCM compared to those that received Lump alone (adjusted HR=0.55, 95% CI 0.53-0.57, p Citation Format: Jose G Bazan, Jay Fisher, Sachin Jhawar, Erin Healy, Sasha Beyer, Julia R. White. Impact of intraoperative radiation therapy and external beam radiation therapy on non-breast cancer mortality in early-stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-09.

Background: Adjuvant regional nodal irradiation (RNI) after breast conserving surgery or mastectomy is supported by clinical trials for patients with node-positive breast cancer. RNI results in increased radiation dose to organs-at-risk (OARs) such as the heart and lungs. While regular acquisition of both free breathing (FB) and deep inspiration breath hold (DIBH) scans has been widely adopted for left-sided breast cancers (LBCs) as a cardiac-sparing technique, DIBH scans are not routinely acquired for right-sided breast cancers (RBCs). Therefore, when OAR constraints cannot be met with 3D conformal radiation therapy (3DCRT) planning on the FB scan, the only option is intensity modulated radiation therapy (IMRT), with its inherent increased cost, resource utilization, and requirement for insurance authorization. Given these challenges, we have regularly acquired FB and DIBH scans for right-sided RNI since 2018. We hypothesized that acquisition of DIBH scans would result in a reduced need for IMRT and reduced dose to OARs. Methods: We retrospectively identified patients who were treated with right-sided RNI who had both FB and DIBH scans. All patients had target volumes (breast or chest wall and regional lymph nodes [undissected axillary, supraclavicular, and internal mammary nodes]) prospectively contoured on the FBCT scan based upon the RTOG Breast Atlas. This initiated a treatment planning algorithm that began with creating a FB 3DCRT plan and changed to DIBH 3DCRT then FB IMRT when OAR constraints could not be met while maintaining acceptable planning target volume (PTV) coverage. For patients who did not have contours available on the DIBH scan, the treating physician retrospectively completed the PTV contours. For each patient, three total plans were created for comparison using our institutional target coverage and OAR metrics: FB 3DCRT, FB IMRT, and DIBH 3DCRT. We compared PTV coverage and doses to multiple OARs including the contralateral breast, esophagus, heart, lungs (left, right, total lung dose), and liver. PTV coverage and OAR doses were evaluated by a one-way ANOVA followed by Bonferroni comparison. A p < 0.05 was considered statistically significant.Results: We identified 38 patients in whom FB and DIBH scans were acquired. Only 32% (N=12) were treated with the standard FB 3DCRT. Of the remaining 26 patients 73% (N=19) were treated DIBH 3DCRT, and only 27% (N=7) were treated with FB IMRT, resulting in a FB IMRT rate of 18% overall. Without DIBH scans, 68% (N=19) would have advanced to FB IMRT. Dosimetric comparison across these 38 patients (N=114 plans) demonstrated that DIBH 3DCRT had at least equivalent OAR metrics as compared to FB 3DCRT, with significant improvement in max heart dose (9.6 Gy vs. 14.9 Gy; p = 0.034), right lung V20 (32.1% vs 37.8%; p < 0.01), mean total lung dose (8.9 Gy vs. 10.5 Gy; p < 0.01), and mean liver dose (1.8 Gy vs. 4.0 Gy; p < 0.01). FB IMRT plans resulting in significantly lower right lung V20 (26.3% FB IMRT vs. 37.8% FB 3DCRT vs. 32.1% DIBH 3DCRT), but resulted in higher dose to the heart and contralateral breast: mean heart dose (2.2 Gy FB IMRT vs. 1.0 Gy FB 3DCRT vs. 0.9 Gy DIBH 3DCRT; p < 0.01), maximum heart dose (16.4 Gy FB IMRT vs. 14.9 Gy FB 3DCRT vs. 9.6 Gy DIBH 3DCRT; p < 0.01) and contralateral breast D5% (5.0 Gy FB IMRT vs. 2.9 Gy FB 3DCRT vs. 3.0 Gy DIBH 3DCRT; p < 0.01).Conclusions: We found that acquiring DIBH scans for RBC patients receiving RNI reduced the need for FB IMRT from 68% to 18%. As compared to FB 3DCRT, DIBH 3DCRT resulted in in equivalent target coverage with significantly lower lung and liver doses. FB IMRT is useful to keep the right lung V20 within acceptable limits at the expense of higher dose to other OARs. Our data support the routine acquisition of DIBH scans in RBC patients undergoing RNI in order to decrease the proportion of patients that require FB IMRT. Citation Format: Sachin R Jhawar, Kylee Lindsey, Karla Kuhn, Kayla Tedrick, Ian Zoller, William Taylor, Eric Cochran, Erin Healy, Sasha Beyer, Julia White, Jose G Bazan. Should deep inspiration breath hold scans be standardly acquired for right-sided breast/chestwall and regional nodal irradiation? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-02.

Background: Whole breast irradiation (WBI) after a positive sentinel lymph node biopsy (SNB) is recommended to be treated in the supine position to facilitate inclusion of the low axilla with “high tangents” when regional nodal irradiation is not planned. Treatment in the prone position has several advantages over supine positioning including minimizing heart and lung doses for many and decreased skin toxicity for larger breasted women. We hypothesized that, using three dimensional conformal radiation therapy (3DCRT), the low axilla can be safely and adequately treated in the prone position with minimal toxicity and good outcomes. Methods: We identified patients who underwent post lumpectomy whole breast and low axilla irradiation in the prone position using 3DCRT from 2014 to 2020. Standard 3DCRT treatment planning included delineation of surgical cavity, breast and low axillary clinical target volumes (CTV) with 5 mm expansion to planning target volumes (PTV). The “low axilla” CTV was generally defined as the level I axilla according to the RTOG Breast Cancer Atlas. Dosimetric data for both targets and organs at risk (OARs) was extracted from approved treatment plans’ dose-volume histograms (DVHs). Toxicity and cancer outcomes were collected from the electronic medical records. Descriptive statistical analysis was performed. Results: Seventy patients were identified. Median age was 61 years (range 34-87), median body mass index (BMI) was 30.4 kg/m2 (range 22.1-49.1), and 88.6% (N=62) had hormone sensitive, HER2 negative breast cancer. The median tumor size was 1.35 cm (range 0.07-4.5cm). For 56 patients (80.0%), a SNB was done with median of 2 (range 1-7) sentinel nodes removed - 19 (34%) with macro-metastasis (median size 4 mm, range 2.2-13mm), 21 (37.5%) with micrometastasis, and 16 (28.6%) with isolated tumor cells. Three patients had an additional node with isolated tumor cells. Thirteen (18.6%) were Nx (no nodal evaluation) and 1 had an unsuccessful SLNB with no lymph nodes obtained. Hypofractionation was used in 97.1% (N=68): 4256 cGy in 16 fractions (N=44, 62.8%) or 4000 cGy in 15 fractions (N=24, 34.3%). All targets were covered adequately. The median V95/V90 of the PTVbreast_eval, PTVlump_eval, and PTVAx were 96%/98.3% (range 76.2/91.9% - 99.6/101.4%), 100.1%/101.2% (range 87.6/94.9%-102.8/103.3%), and 95.3%/97.5% (range 82.4/91.6%-100.4/101.7%) respectively. The mean heart dose for all patients was 83.5 cGy; 82.7 cGy for right-sided tumors and 83.8 cGy for left-sided tumors. The median V16 of the ipsilateral lung was 4.25% (range 0.2 - 11.3%). Overall, toxicity was low with no grade 3 or higher events. For acute toxicity, most patients (N=54, 77.1%) reported grade 1 fatigue and had either grade 1 (N=52, 74.2%) or grade 2 (N=15, 21.4%) dermatitis. For late toxicity, 14 patients (20%) were referred to physical therapy after radiation, 7 (10%) for range of motion, 5 (7%) for arm lymphedema evaluation and 4 (6%) for other reasons. With a median follow-up of 18.5 months (range 0-63 months), 1 patient recurred both locally and regionally (1.4%) and one other patient recurred distantly. Conclusions: Patients with a positive SNB or are Nx who are recommended to have post-lumpectomy whole breast and low axilla irradiation can be safely and adequately treated in the prone position using 3DCRT with minimal toxicity and good outcomes. Citation Format: Victoria Doss, Erin Healy, Sasha Beyer, Sachin R. Jhawar, Jose G. Bazan, Julia White. Radiation of the low axilla in the prone position [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-17.

Background: Breast-cancer related lymphedema (BCRL) is a devastating treatment complication driven by the extent of axillary surgery (axillary lymph node dissection [ALND] versus sentinel lymph node biopsy [SLNB]). Regional nodal irradiation (RNI) may increase the risk of BCRL by up to 5%. Recently, investigators identified a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) as a potential organ-at-risk (OAR) demonstrating that increasing radiation dose to the ALTJ was associated with a higher risk of BCRL. Here, we set to validate whether radiation dose to the ALTJ is associated with BCRL. Materials/Methods: We identified patients with stage II-III breast cancer treated with adjuvant RNI after M or L from 2013-2018 excluding those with BCRL pre-radiation. RNI treatment planning included delineation of clinical target volumes (CTVs): breast or chest wall and regional lymph nodes per the RTOG Breast Cancer Atlas. The CTVs were expanded by 5mm to create the planning target volume (PTV). Dose delivered was 50 Gy/25 fractions with goal of 47.5 Gy (95%) to 95% of each PTV. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb >2.5 cm at any 1 visit or ≥2 cm on at least 2 visits. All patients suspected of having BCRL at routine follow-up visits were evaluated by physical therapy. The ALTJ was retrospectively contoured and the following metrics collected: maximum/minimum/mean dose; V10Gy-V50Gy. Follow-up time was defined as the time from surgery to the development of BCRL or last follow-up. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. All variables with p Citation Format: Erin Healy, Sachin Jhawar, Sasha Beyer, Julia R White, Jose G Bazan. Breast cancer related lymphedema in patients undergoing RNI: Is the axillary lateral vessel thoracic junction an organ-at-risk? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-08.

Delineation of treatment targets and organs-at-risk (OAR) for treatment planning is the standard of care across all disease sites for curative radiation therapy. However, this approach has been variably adopted for breast cancer with significant variation amongst experts regarding contouring breast cancer target volumes. In order to create a framework for the contouring of breast cancer cases, particularly within the context of clinical trials, the Radiation Therapy Oncology Group (RTOG) Breast Atlas was created in 2009. Since that time, numerous other atlases have been developed and several retrospective studies since 2015 have called into question the adequacy of clinical target volume delineation as defined by the RTOG atlas and other atlases based on patterns of failure. Here, we will review the existing atlases, highlighting the differences between them and potential opportunities for improvement based on these patterns of failure studies. Ultimately, the results of recently completed and ongoing prospective clinical trials, which included contouring guidelines based on current atlases, will provide important information regarding patterns of failure and toxicity in patients treated with modern radiotherapy using a systematic target volume delineation and OAR-driven approach to treatment planning.

Background: Hormone receptor (HR) low (1-10%) HER2-negative breast cancer (BC) is emerging as a distinct subtype with similarities in clinical outcomes to triple-negative BC. However, there is a lack of consensus on treatment recommendations for chemo-immunotherapy and endocrine therapy in this subset. Here, we present results from a US National Cancer Database (NCDB) analyses of patients with HER2-negative BC evaluating response to neoadjuvant chemotherapy (NAC) and patterns of care by HR expression. Methods: Patients with stage I-III HER2-negative BC diagnosed in 2018 were identified in NCDB, a nationwide oncology outcomes database in the US. Quantitative HR expression was unavailable prior to 2018. Data were categorized into four groups by estrogen receptor (ER) and progesterone receptor (PR) expression: ER< 1% & PR< 1% (HR-Neg), ER 1-10% and/or PR 1-10% (HR-Low), ER >11-30% and/or PR>11-30% (HR-Int), ER> 30% and/or PR > 30% (HR-High). Those with undocumented HR status (3%) or without curative intent surgery (5%) were excluded. The primary outcome was pathologic complete response (pCR) by HR expression in those undergoing neoadjuvant chemotherapy. Key secondary objectives included assessment of clinicopathologic characteristics and practice patterns. The categorical variables were compared between the four groups using a Chi-square test. Age was compared using a Kruskal-Wallis test. Results: Out of 104,205 incident cases, 2541 (2.4%) were HR-Low and 1241 (1.2%) were HR-Int. Significant differences were found between HR groups with higher grade, clinical stage, and Ki-67 in HR-Low vs. HR-Int or HR-High groups (Table 1). Patients with HR-Low and HR-Int BC were more likely to receive chemotherapy than HR-High (74%, 70% vs. 20%; p < 0.001) and the use of adjuvant endocrine therapy correlated with HR expression. Only half of patients in the HR-Low group received any endocrine therapy compared to higher rates in the HR-Int and HR-High groups (52% vs. 74%, 92%; p< 0.001). pCR rates in those receiving neoadjuvant chemotherapy were significantly different by HR status, with higher pCR rates in HR-Low vs. HR-High groups (p< 0.001) (Table 2). NAC utilization significantly differed between groups. A higher proportion of patients with HR-Low BC received NAC than other HR-positive groups (p < 0.001). Additionally, there was an increased use of NAC in patients with HR-Low BC treated at academic vs. community cancer centers (p< 0.001). Conclusions: This is one of the largest real-world analyses comparing key differences in biology and practice patterns of HR-Low, HER2-negative BC. Consistent with prior studies, we report HR-Low BC to be a rare and distinct subtype with higher pCR rates compared to HR-High BC. Practice patterns show wide variability in utilization of neoadjuvant chemotherapy and endocrine therapy for these patients. Future studies should address this disparity and enhance representation of patients with HR-Low BC in clinical trials to improve long-term outcomes. Table 1: Patient demographics Table 2: Neoadjuvant chemotherapy response amongst differing HR expression levels Citation Format: Dionisia Quiroga, Michael Grimm, Julie Stephens, Kai Johnson, Nicole Williams, Preeti K. Sudheendra, Mathew A. Cherian, Daniel Stover, Ashley C. Pariser, Margaret Gatti-Mays, Robert Wesolowski, Jose G. Bazan, Sasha Beyer, Ko Un Park, Bridget Oppong, Bhuvaneswari Ramaswamy, Julia White, Sachin R. Jhawar, Sagar Sardesai. Impact of low hormone receptor expression on neoadjuvant chemotherapy response and patterns of care in early-stage HER2-negative breast cancer: a US National Cancer Database analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-17.

IntroductionDuring the coronavirus 2019 (COVID-19) pandemic in USA, NET use has been recommended to allow safe deferral of surgical treatment in early stage, estrogen receptor positive breast cancer (ER+BC). In such circumstances, after NET use there is limited guidance on locoregional treatment, especially with management of the axilla. We aimed to evaluate patterns of care in early stage ER+BC during the first several months of the COVID-19 pandemic.MethodA cross-sectional, 30-item survey was developed using a standardized survey development framework. The survey was administered May 8 - June 12, 2020 to a convenience sample of medical oncologists (MO), radiation oncologists (RO), and surgeons (SO) - breast committee members of two national cooperative groups (Alliance and SWOG) with additional participation through chain referrals. Providers were presented with general questions on NET use before and during the pandemic. They were asked their propensity for omitting axillary lymph node dissection (ALND) after NET if 1 micrometastatic node is found on sentinel lymph node biopsy, based on duration of NET.Results114 providers from 29 US states completed the survey - 42 (37%) MO, 14 (12%) RO, and 58 (51%) SO, the majority (N=73/96, 76%) with practices dedicated ≥ 75% to BC, at NCI designated comprehensive cancer centers 52% (N=48/94) and in large cities (N=49/94, 52%). Prior to COVID-19, most rarely (N=49/107, 46%) or sometimes (N=36, 33%) used NET for early stage ER+BC. Nearly half were willing to delay surgery up to 2 months (46%) and 3 months (21%) without use of NET (Table 1, †p Table 1. Management of early stage, node negative, ER+BC during COVID-19 pandemicTotal (N, %)Med OncRad OncSurgeonHow long are you willing to delay surgery (without use of endocrine therapy)?Up to 1 month25 (23%)10 (24%)015 (26%)Up to 2 months51 (46%)17 (40%)7 (64%)27 (47%)Up to 3 months23 (21%)9 (21%)2 (18%)12 (21%)Up to 4 months3 (3%)2 (5%)1 (9%)0Up to 6 months8 (7%)4 (10%)1 (9%)3 (5%)Have you changed your practice during the current pandemic?Yes - institution mandated change to delay surgery8 (25%)4 (36%)04 (29%)Yes - based on multidisciplinary team discussion (no explicit institutional mandate to delay cancer surgery)21 (66%)6 (55%)7 (100%)8 (57%)No - was not allowed by institution to change0000No - was not necessary3 (9%)1 (9%)02 (14%)If using endocrine therapy before surgery, which regimen are you using?†Tamoxifen for all patients0000Tamoxifen for premenopausal patients; aromatase inhibitor for postmenopausal patients77 (81%)26 (63%)051 (94%)Ovarian suppression with aromatase inhibitor for premenopausal patients; aromatase inhibitor for postmenopausal patients18 (19%)15 (37%)03 (6%)How are you staging the axilla prior to starting endocrine therapy?Exam only28 (26%)8 (19%)2 (17%)18 (33%)Exam + US77 (71%)30 (71%)10 (83%)37 (67%)Exam + US + cross sectional image (CT scan)4 (4%)4 (10%)0 (0%)0 (0%)SLNB0000If using endocrine therapy first (before surgery), are you†Sending genomic assay on biopsy specimen on all patients28 (26%)18 (44%)1 (8%)9 (16%)Sending genomic assay on biopsy specimen on only select patients (ie. high grade, size on imaging/exam, high Ki-67)51 (48%)19 (46%)8 (67%)24 (44%)Not sending genomic assay. Using PEPI score instead.4 (4%)1 (2%)1 (8%)2 (4%)Not sending genomic assay. Using Magee Equations for Estimating Oncotype DX Recurrence Score instead.2 (2%)002 (4%)None of above21 (20%)3 (7%)2 (17%)18 (33%)If using endocrine therapy first, what duration do you plan to use it for the average patient?†Minimum 1 year for all patients0000Minimum 6 months for all patients7 (6%)4 (10%)0 (0%)3 (5%)Minimum 3 months for all patients19 (18%)7 (17%)1 (8%)11 (20%)As short as possible (less than 3 months), until it is safe to proceed with surgery in light of COVID-19 situation57 (53%)14 (34%)9 (75%)34 (62%)Duration of therapy depends on patient''s risk of cancer progression (ie. tumor grade, percent hormone positivity)25 (23%)16 (39%)2 (17%)7 (13%)If using endocrine therapy before surgery, do you plan to re-image the breast prior to surgery?†Yes, re-image all patients27 (25%)14 (34%)1 (8%)12 (22%)No8 (7%)0 (0%)2 (17%)6 (11%)Case by case basis72 (67%)27 (66%)9 (75%)36 (67%) Citation Format: Ko Un Park, Megan E Gregory, Maryam B Lustberg, Jose G Bazan, Chengli Shen, Shoshana M Rosenberg, Victoria S Blinder, Priyanka Sharma, Lajos Pusztai, Ann H Partridge, Alastair Thompson. Emerging from COVID-19 pandemic: Provider perspective on use of neoadjuvant endocrine therapy (NET) in early stage hormone receptor positive 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 SS2-05.

Using evidence-based radiation therapy to direct care for patients with breast cancer is critical to standardizing practice, improving safety, and optimizing outcomes. To address this need, the Veterans Affairs (VA) National Radiation Oncology Program (NROP) established the VA Radiation Oncology Quality Surveillance Program (VAROQS) to develop clinical quality measures (QM). The VA NROP contracted with the American Society for Radiation Oncology (ASTRO) to commission five Blue-Ribbon Panels for breast, lung, prostate, rectal, and headneck cancers.The Breast Cancer Blue-Ribbon Panel experts worked collaboratively with NROP to develop consensus QM for use throughout the VA system. establishing a set of quality measures for patients in several areas including: 1) consultation and work up, 2) simulation, treatment planning and treatment, and 3) follow up care. As part of this initiative, consensus dose volume histogram (DVH) constraints were outlined.In total, 36 quality measures were established. Herein we review the process utilized to develop QM and final consensus QM pertaining to all aspects of radiation patient care as well as DVH constraints.The QM and expert consensus DVH constraints are intended for ongoing quality surveillance within the VA system, centers providing community care for Veterans, and also available for use by the greater non-VA community measures of quality care for breast cancer patients receiving radiation.

Background: While most patients with metastatic breast cancer (MBC) experience widespread disease progression on systemic therapy (ST), some have more limited progression, termed oligoprogression (OP). Patients with OP may benefit from local ablative therapies, such as stereotactic body radiation therapy (SBRT)/stereotactic radiosurgery (SRS), in order to avoid changing to the next line of ST. Here, we aim to evaluate patterns of progression in patients with MBC by breast cancer subtype (hormone-receptor positive/HER2- [HR+/HER2-], HER2+, and tripe-negative [TN]) to determine if and how often OP occurs. We hypothesize that OP does occur, and that it is more likely to occur in the HR+/HER2- and HER2+ BC subtypes compared to the TN subtype. Materials/Methods: We identified patients seen at our breast center from 1/2013-12/2017 with an associated ICD9/ICD10 code for metastases. We excluded patients that: did not have MBC; did not receive at least part of their treatment course for MBC at our institution; did not have imaging available for review. For the remaining cases, we reviewed each point at which a change in management was made to determine if OP of diffuse progression (DP) occurred. We defined OP as progression of disease in 1-4 lesions, with the exception of brain metastases, in which up to 10 lesions were allowed (provided patients received SRS and not whole brain radiation therapy). Findings such as malignant effusions, ascites, leptomeningeal disease, and lymphangitic/peritoneal carcinomatosis were scored as DP, regardless of the stability of other lesions. In addition, we collected demographic, tumor and treatment information. We set to determine the overall rate of OP and to compare the rate of OP amongst the HR+/HER2-, HER2+, and TN subtypes using a chi-square test. We also set to compare the overall survival in patients with OP vs. DP using the Kaplan-Meier method. A p-value4 metastases (84%). The median lines of ST for all patients was 3 (IQR=1-4). The crude rate of OP was 30% (N=306) and was highest amongst the HER2+ subtype (46.5%, 87/187) followed by HR+/HER2- (27.5%, 178/647) and TN (22.4%, 41/183), p20% and the majority have disease potentially amenable to SBRT/SRS. These data serve to inform and support the development of prospective clinical trials evaluating the role of SBRT/SRS for oligoprogressive MBC. Citation Format: Jose G Bazan, Amber Holbrook, Sachin Jhawar, Julia R White. Patterns of progression in metastatic breast cancer: Does oligoprogression exist? [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 P4-12-03.

Background Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein metastatic disease invades the meninges of the central nervous system via contiguous spread from bone or brain metastases or hematogenous spread from systemic disease. Breast cancer is the most common solid tumor etiology of LMC. Approximately 5% of patients (pts) with breast cancer develop LMC. LMC has a median survival of 4 weeks when untreated and 8-16 weeks with treatment. The diagnosis of LMC remains challenging with only 60% of pts having cerebrospinal fluid (CSF) positive for malignant cells. There is no generally accepted standard of care for treatment of LMC but it may involve intrathecal or systemic chemotherapy, whole brain or spinal radiotherapy, or a combination of modalities. We aimed to assess detection and treatment strategies of LMC in pts with breast cancer treated at the Ohio State University Comprehensive Cancer Center-James (OSUCCC-James) to better characterize the disease and guide clinical care. Methods An IRB-approved single-institution retrospective protocol was developed. Medical records of 469 pts who had undergone a procedure related to LMC diagnosis or treatment were identified and reviewed to determine study eligibility. Comprehensive data was obtained through information warehouse and chart review was performed for the eligible 69 pts with breast cancer diagnosed with LMC and treated at the OSUCCC-James between January 1, 2005 and December 31, 2015. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan Meier methods. Comparisons in OS between groups were analyzed using Log-rank tests. Results Sixty-nine female pts were included in the analysis with the following characteristics: median age 55.7 years (range: 48-60.6 years), Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (86%; N=59), and Caucasian (78%; N=54). They had the following subtypes hormone receptor positive (HR +), and human epidermal growth factor receptor (HER2) negative (61%, N=42), triple negative (25%, N=17) and HER2 positive (10%, N=7). The most common sites of metastases included bone (42%), brain (28%), and lung (12%). The median time between the diagnosis of first metastasis and LMC was 0.9 years (range: 0-3.2 years). Of the 40 (58%) pts who underwent lumbar puncture, 21 (52%) pts had positive CSF cytology. Sixty-eight pts (99%) had MRI findings suggestive of LMC. The most common treatment modalities were systemic chemotherapy (N=14, 41%), radiotherapy (N=12, 35%), and intrathecal chemotherapy (N=14, 35%). Fifty-six pts (81%) had a change in systemic chemotherapy agent after diagnosis. The median OS of all pts was 2.4 months (95% confidence interval: 1.2-4.4). Pts with ER+/PR+/HER2- had a better OS (4.4 months, 95%CI 1.5, 6.1)) compared to those with HER2+ (1.3 months, 95%CI 0.2, 1.9) or ER-/PR-/HER2- (0.6 months, 95%CI 0.0, 15.8) subtypes (p-value=0.004). Pts with negative CSF cytology had a greater OS compared to those with positive CSF cytology (9.8 vs. 0.7 months, p=0.026) and pts who had a change in systemic treatment had a greater OS compared with patients who had no new treatment (2.5 months vs. 1.2 months, p =0.039). No significant difference was seen in OS between ECOG performance status groups. Conclusions LMC is a relatively rare yet devastating complication of breast cancer. Based on our institutional experience, LMC remains a clinical challenge and is associated with poor OS. Pts with triple negative and HER2 positive disease and those with high disease burden fare worse. Pts who had change in systemic therapy fare better. Dedicated clinical trials are urgently needed to improve outcomes. Citation Format: Hannah Rinehardt, Nicole Williams, Evan Morgan, Mahmooud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, Anupama Suresh, Vinay Puduvalli, Pierre Giglio, Maryam Lustberg, Robert Wesolowski, Sagar Sardesai, Daniel Stover, Jeffrey VanDeusen, Jose Bazan, Bhuvaneswari Ramswamy, Anne Noonan. Assessment of leptomeningeal carcinomatosis management and outcomes in patients with advanced breast cancer from 2005 to 2015: A single institution experience [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 P2-20-07.

BackgroundChest radiation therapy (RT) has been associated with increased cardiac morbidity and mortality in numerous studies including the landmark Darby study published in 2013 demonstrating a linear increase in cardiac mortality with increasing mean heart radiation dose. However, the extent to which cardiotoxicity has been incorporated as an endpoint in prospective RT studies remains unknown.MethodsWe queried clincaltrials.gov to identify phase II/III trials in lung, esophageal, lymphoma, mesothelioma, thymoma, or breast cancer from 1/1/2006-2/1/2021 enrolling greater than 100 patients wherein chest RT was delivered in at least one treatment arm. The primary endpoint was the rate of inclusion of cardiotoxicity as a specific primary or secondary endpoint in the pre- (enrollment started prior to 1/1/2014) versus post-Darby era using the Chi-square test (pResultsIn total, 1,822 trials were identified, of which 256 merited inclusion. 32% were for esophageal, 31% lung, 28% breast, and 7% lymphoma/thymoma/mesothelioma cancers, respectively. 5% (N=13) included cardiotoxicity as an endpoint: 6 breast cancer, 3 lung cancer, 3 esophageal cancer, and 1 lymphoma study. There was no difference in the inclusion of cardiotoxicity endpoints in the pre-Darby versus post-Darby era (3.9% vs. 5.9%, P=0.46). The greatest absolute increase in inclusion of cardiotoxicity as an endpoint was seen for lung cancer (0% vs. 6%, p=0.17) and breast cancer (5.7% vs. 10.8%, p=0.43) studies, though these increases remained statistically non-significant. We found no clinical trial factors associated with the inclusion of cardiotoxicity as an endpoint.ConclusionsAmong prospective trials involving chest RT, cardiotoxicity remains an uncommon endpoint despite its prevalence as a primary source of toxicity following treatment. In order to better characterize cardiac toxicities, future prospective studies involving chest RT should include cardiotoxicity endpoints.

Regional nodal irradiation (RNI) improves disease outcome in breast cancer patients, but the contribution of internal mammary node irradiation (IMNI) in the context of modern systemic treatment is still controversial. The aim of our study is to evaluate the effect of IMNI in patients with modern systemic treatment in real-world setting. We retrospectively analyzed patients with primary breast cancer treated with surgery followed by adjuvant chemotherapy and adjuvant chestwall/breast irradiation and RNI from 5/2007-12/2010. RNI was delivered to the ipsilateral supraclavicular region and infraclavicular region + / − IMNs. We separated two groups based on the presence and the absence of IMNI. The primary end point was disease-free survival (DFS). DFS and overall survival (OS) were evaluated with Kaplan–Meier method. Differences between two groups were compared with the log-rank test (p

Purpose Quantitative changes in positron emission tomography with computed tomography imaging metrics over serial scans may be predictive biomarkers. We evaluated the relationship of pretreatment metabolic tumor growth rate (MTGR) and standardized uptake value velocity (SUVV) with disease recurrence or death in patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy (SABR). Methods and Materials Under institutional review board approval, we retrospectively identified patients who underwent positron emission tomography with computed tomography at diagnosis and staging and simulation for SABR. Two cohorts underwent SABR between November 2005 to October 2012 (discovery) and January 2012 to April 2016 (validation). MTGR and SUVV were calculated as the daily change in metabolic tumor volume and maximum standardized uptake value, respectively. Cox proportional hazard models identified predictors of local, regional, and distant recurrence and death for the combined cohort. MTGR and SUVV thresholds dichotomizing risk of death in the discovery cohort were applied to the validation cohort. Results A total of 152 lesions were identified in 143 patients (92 lesions in 83 discovery cohort patients). In multivariable models, increasing MTGR trended toward increased hazard of distant recurrence (hazard ratio, 6.98; 95% confidence interval, 0.67-72.61; P = .10). In univariable models, SUVV trended toward risk of death (hazard ratio, 11.8, 95% confidence interval, 0.85-165.1, P = .07). MTGR greater than 0.04 mL/d was prognostic of decreased survival in discovery (P = .048) and validation cohorts (P Conclusions MTGR greater than 0.04 mL/d is prognostic of death in patients with non-small cell lung cancer treated with SABR. Increasing SUVV trends, nonsignificantly, toward increased risk of recurrence and death. MTGR and SUVV may be candidate imaging biomarkers to study in trials evaluating systemic therapy with SABR for patients at high risk of out-of-field recurrence.

Objectives: Upper extremity dysfunction (UED) is a known side effect of breast cancer treatment. It is unclear, however, to what degree radiation contributes to this morbidity. We aimed to characterize the level of UED using patient-reported outcomes (PROs) prior to, during, and after treatment with radiation for breast cancer. Our secondary aims were to evaluate the association of UED with pain scores. Methods: This is a single-institution, prospective, longitudinal cohort study of patients treated with radiation for breast cancer. The validated patient-reported outcome measure, Quick Disabilities of the Arm, Shoulder and Hand (QD) was used to capture UED prior to radiation, at the end of radiation, and 1 month following the completion of radiation. Pain scores were also collected at these intervals using the numeric pain reporting scale (NPRS) from 0 (no pain) to 10 (worst pain). Results: Forty-four patients were enrolled on this study and 43 (97.7%) had completed radiation at the time of analysis. Thirteen patients (29.5%) were treated with mastectomy, axillary lymph node dissection and regional nodal irradiation in the supine position. The other 31 (70.5%) patients underwent lumpectomy and sentinel lymph node biopsy. Of these patients, 26 (83.9%) were treated in the prone position and 30 (96.8%) received whole breast irradiation. Median time from surgery to radiation was 69 days (range 35 – 212 days), 76 days for mastectomy and 68 days for lumpectomy. Median time from start to end of radiation was 38 days for mastectomy and 28 days for lumpectomy. Pre-treatment median QD score prior to radiation was 12.5 (11.4 for lumpectomy, 15.9 for mastectomy), 9.1 at the end of radiation (9.1 for lumpectomy, 18.2 for mastectomy), and 2.4 at 1 month after radiation (2.3 for lumpectomy, 2.5 for mastectomy). Median NPRS scores at pre-treatment, post-treatment and 1 month follow-up were 1, 1, and 1 for lumpectomy and 0, 1, 0 for mastectomy patients, respectively. Conclusion: In this initial pilot study with 1 month of follow up, patient-reported UED as demonstrated by QD scores were higher pre-radiation and decreased by one month after. This likely reflects recuperation after surgical procedure. Median average pain scores were low at all time points. Further evaluation of UED over time to characterize the long-term effect of radiation and correlation with quality of life and other clinical factors is planned. Citation Format: Healy E, Pan X, Beyer S, Washington I, Bazan J, White J. Initial report of a prospective, pilot study of patient-reported upper extremity dysfunction in women undergoing radiation for breast cancer [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 P1-12-13.

Background: Shoulder/arm morbidity is a late complication of breast cancer treatment. Postmastectomy radiation therapy (PMRT)/regional nodal irradiation (RNI) increases dose to the muscles and soft tissues of the shoulder and upper neck and back. Most patients are treated with 3D conformal radiation therapy (3DCRT) or Intensity modulated radiation therapy (IMRT). Here, we set to analyze the impact of 3DCRT vs. IMRT on radiation dose to the shoulder, and to retrospectively explore the relationship of treatment technique on long term patient-reported outcomes in the subset of patient who had completed the quick Disabilities of the Arm, Shoulder, and Hand (q-DASH) questionnaire. Materials/Methods: We identified consecutive patients in our department treated with PMRT/RNI for curative intent from 2013-2016. We excluded patients treated for recurrent disease, those with metastatic disease, and those with unresected disease in the supraclavicular (SCV) fossa and/or axillary apex requiring a radiation boost to that area. We contoured the shoulder as all of the muscles/soft tissue/bone from 2 cm above the ipsilateral SCV planning target volume (PTV) to the cranial aspect of the breast or chestwall PTV. No planning constraints were set for the shoulder since this was retrospectively contoured. We used the dose volume histogram to determine the volume of shoulder receiving at least 5 Gy, 10 Gy,...,50 Gy (V5-V50, respectively). We identified patients that completed a q-DASH questionnaire ≥6 months from the end of PMRT/RNI. Descriptive statistics were used to summarize the shoulder dose and q-DASH values. Differences between groups were assessed by the t-test or chi-square test with p Results: We found 237 patients treated with PMRT/RNI with median age of 52 y (IQR 44-60 y), 75% treated with mastectomy, 85% had axillary lymph node dissection (ALND), median of 18 nodes removed (IQR 12-26). All patients received 50 Gy/25 fractions. A total of 68 patients (28.7%) were treated with IMRT. IMRT significantly reduced the V20-V50 to the shoulder vs. 3DCRT (e.g., V45Gy=21.7 mL vs. 208.4 mL, p Conclusion: In summary, we found that IMRT reduces radiation dose to the shoulder and is associated with a trend towards reduced q-DASH scores at least 6 months after PMRT/RNI in a subset of our cohort. These results support prospective evaluation of IMRT as a technique to reduce shoulder morbidity in breast cancer patients receiving PMRT/RNI. Citation Format: Bazan JG, Dicostanzo D, Hock K, Healy E, Beyer S, White JR. Analysis of radiation dose to the shoulder by treatment technique and correlation with patient reported outcomes in patients receiving regional nodal irradiation [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 P3-12-04.

Purpose: Consensus guidelines for regional nodal irradiation (RNI)/postmastectomy radiation (PMRT) clinical target volumes (CTV) have slight variations amongst leading national organizations. In the US, the Radiation Therapy Oncology Group (RTOG) defines the caudal edge of the supraclavicular (SCV) CTV as the junction of the brachiocephalic and axillary vessels while the internal mammary nodal (IMN) CTV starts at the superior aspect of the medial first rib. This leaves an anatomical gap between the two target volumes. The European Society of Radiation Oncology (ESTRO) does not recommend leaving a gap between the SCV CTV and IMN CTV. We set to analyze radiation dose and patterns of failure in this region. Materials and Methods: We identified consecutive patients treated with RNI/PMRT at our institution from 2013-2016. Patients with metastatic or recurrent disease were excluded. All patients received 50 Gy/25 fractions to the breast/chestwall+regional nodes (including IMN PTV) +/- boost to the lumpectomy cavity/mastectomy scar using 3D conformal radiotherapy (3DCRT) or intensity modulated radiation therapy (IMRT). We retrospectively contoured the vessels from one slice below the caudal border of the SCV PTV contour to one slice cranial to the first IMN PTV contour. We calculated the mean dose and the relative V40Gy, V45Gy, and V47.5Gy of the gap region.A gap failure was defined as a first recurrence in this region with or without simultaneous loco-regional recurrence (LRR) or distant metastases (DM). We used the cumulative incidence method to calculate the gap recurrence rate with DM, LRR, and death, as competing risks. Results: 230 patients were included with median age 52 years, predominantly stage III disease (60%), and most treated with preoperative (51%) or postoperative (41%) systemic therapy. Breast cancer subtype was ER+/HER2- in 138 patients, triple negative in 44 patients, and HER2+ in 48 patients. The median (IQR) mean dose, V40Gy, V45Gy, and V47.5 Gy in the gap region were: 20.3 Gy (14.8-26.2 Gy), 6% (1.3%-20.0%), 0.6% (0%-7.0%), and 0% (0%-1.3%). The mean dose to the gap region was slightly higher in patients treated with IMRT (N=68) compared to 3DCRT (N=162): 25.3 Gy (SD 7.5 Gy) vs. 19.5 Gy (SD 8.0 Gy), p Conclusion: In a clinical practice in which we routinely contour and treat the IMN PTV and SCV PTV with a gap region between those two volumes, we found that the mean radiation dose to this region is low, at about 50% or less compared to the prescription dose. Despite this, recurrences in this region are exceedingly uncommon and have not yet occurred in the absence of simultaneous DM. While the follow-up is limited, these data support the current guidelines of not routinely targeting this region. Citation Format: Bazan JG, Dicostanzo D, Healy E, Beyer S, White JR. Analysis of radiation dose in the gap region between the supraclavicular target volume to the internal mammary target volume in women receiving regional nodal irradiation [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 P3-12-03.

Background: The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly among the elderly (age ≥65 years). We sought to compare patterns of care for the treatment of SCCA in elderly versus nonelderly patients. Methods: Data for patients with stages I–III SCCA diagnosed from 2004 through 2015 were obtained from the National Cancer Database. Patients were categorized as having received standard-of-care (SOC) chemoradiation (CRT) with multiagent chemotherapy, non-SOC therapy, palliative therapy, or no treatment. Differences in treatment groups were tested using the chi-square test. We used logistic regression to identify predictors of SOC CRT and multiagent versus single-agent chemotherapy in patients receiving CRT. Propensity score matching was used to compare overall survival (OS) in elderly patients receiving multiagent versus single-agent chemotherapy for those receiving CRT. Results: We identified 9,156 elderly and 17,640 nonelderly patients. A lower proportion of elderly versus nonelderly patients (54.5% vs 65.0%; PPP1.5-fold increase in the likelihood of elderly patients receiving single-agent chemotherapy (odds ratio, 1.52; 95% CI, 1.39–1.66) in multivariate analysis. After propensity score matching, 3-year OS was higher in elderly patients who received CRT with multiagent versus single-agent chemotherapy (77.1% vs 67.5%; hazard ratio, 0.78; 95% CI, 0.68–0.89; P=.0002). Conclusions: In this comprehensive study of patients with stages I–III SCCA, elderly patients were less likely than nonelderly patients to receive SOC CRT. The low proportion of elderly patients receiving SOC CRT with multiagent chemotherapy for localized anal cancer suggests that the optimal treatment approach for this vulnerable population remains undefined.

1007 Background: Prospective and retrospective studies of patients (pts) with oligometastatic (OM) disease have supported that metastases (mets) directed treatment (MDT) with SBRT or SR in addition to standard of care systemic therapy (SOC ST) can improve progression-free (PFS) and overall survival (OS) compared with SOC ST alone. However, randomized evidence in oligometastatic breast cancer (OMBC) are lacking. NRG-BR002, a randomized Phase IIR/III trial, sought to determine the efficacy of SOC ST + MDT (SBRT or SR) as first line treatment of OMBC. Methods: OMBC pts with ≤ 4 extracranial mets on standard imaging with controlled primary disease were eligible if on first line SOC ST for ≤ 12 months without progression. Pts were randomized (1:1) to ARM 1 – SOC ST (mainly chemotherapy, endocrine therapy, anti-HER2) or ARM 2 – SOC ST with MDT of all mets. Stratification included mets number (1 vs > 1), ER/PR and Her2 status, and chemotherapy use. Phase IIR targeted sample size was 128 total/116 eligible pts, for 92% power and 1-sided significance level = 0.15 to determine if adding MDT shows a signal for improved PFS (hazard ratio [HR] = 0.55, corresponding to median PFS (mPFS) from 10.5 to 19 months), in order to continue to the full phase III trial for OS. PFS and OS were estimated by Kaplan-Meier and arms compared with log-rank. Results: 125 of the 129 pts randomized were eligible (ARM 1 = 65, ARM 2 = 60). Key characteristics included median age 54, 79% ER+ or PR+/HER2-, 13% HER2+, 8% triple negative. 60% had 1 metastasis and 20% presented synchronously with primary disease. Following randomization, systemic therapy was delivered to 95% in ARM 1 and 93% in ARM 2; ablation: SBRT 93%, SR 2%, and 5% none. The median follow-up was 30 mo. The mPFS (70% CI) in ARM 1 was 23 mo (18, 29) and 19.5 mo (17, 36) in ARM 2; 24 and 36-mo PFS (70% CI) for ARM 1 were 45.7% (38.9, 52.5) and 32.8% (26.0, 39.5) compared with 46.8 (39.2, 54.3) and 38.1 (29.7, 46.6) in ARM 2; HR (70% CI): 0.92 (0.71, 1.17); and 1-sided log-rank p = 0.36. As PFS did not show signal, OS reporting is included: median OS was not reached in either arm; 36-mo OS (95% CI) in ARM 1 71.8% (58.9, 84.7) and ARM 2 68.9% (55.1, 82.6; 2-sided log-rank p = 0.54). Analysis of first failure showed new mets outside index area (Arm 1) /RT field (Arm 2) developed similarly in both arms at 40%. There were fewer new mets inside treated/index area for Arm 2 6.7% vs ARM 1 29.2%, respectively. There were no grade 5 treatment-related adverse events (AEs), 1 grade 4 AE in ARM 1, and 9.7% and 5.3% grade 3 AEs in ARMS 1 and 2, respectively. Circulating tumor cell counts (0 vs ≥1) at baseline were similar in both arms and were not prognostic HR (95% CI): 1.04 (0.54, 2.02). Conclusions: The addition of MDT to SOC ST did not show signal for improved PFS, nor OS difference in patients with OMBC. The trial will not proceed to the Phase III component. Clinical trial information: NCT02364557.

Background/PurposeShoulder/arm morbidity is a late complication of breast cancer treatment with surgery and regional nodal irradiation (RNI). We set to analyze the impact of radiation technique [intensity modulated radiation therapy (IMRT) or 3D conformal radiation therapy (3DCRT)] on radiation dose to the shoulder with a hypothesis that IMRT use results in smaller volume of shoulder receiving radiation. We explored the relationship of treatment technique on long-term patient-reported outcomes using the quick disabilities of the arm, shoulder, and hand (q-DASH) questionnaire.Materials/MethodsWe identified patients treated with adjuvant RNI (50 Gy/25 fractions) from 2013 to 2018. We retrospectively contoured the shoulder organ-at-risk (OAR) from 2 cm above the ipsilateral supraclavicular (SCL) planning target volume (PTV) to the inferior SCL PTV slice and calculated the absolute volume of shoulder OAR receiving 5–50 Gy (V5–V50). We identified patients that completed a q-DASH questionnaire ≥6 months from the end of RNI.ResultsWe included 410 RNI patients: 54% stage III, 72% mastectomy, 35% treated with IMRT. IMRT resulted in significant reductions in the shoulder OAR volume receiving 20–50 Gy vs. 3DCRT. In total, 82 patients completed the q-DASH. The mean (SD) q-DASH=25.4 (19.1) and tended to be lower with IMRT vs. 3DCRT: 19.6 (16.4) vs. 27.8 (19.8), p=0.078.ConclusionWe found that IMRT reduces radiation dose to the shoulder and is associated with a trend toward reduced q-DASH scores ≥6 months post-RNI in a subset of our cohort. These results support prospective evaluation of IMRT as a technique to reduce shoulder morbidity in breast cancer patients receiving RNI.

PURPOSE/OBJECTIVE(S) The excellent survival and locoregional outcomes from the APT trial in predominantly stage I HER2+ breast cancer (BC) treated with upfront surgery (∼75% breast conservation surgery [BCS]) and adjuvant paclitaxel/trastuzumab has raised optimism that radiation (RT) may be de-escalated in this setting. Our initial analysis using the National Cancer Database (NCDB) instead demonstrated an association between RT omission and worse overall survival (OS) in these patients. Patients with HER2+ disease that receive neoadjuvant systemic therapy (NST) demonstrate great outcomes for patients with a pathologic complete response (pCR). This suggests that pCR may be used to de-escalate RT in early-stage HER2+ patients treated with NST+BCS. We used the NCDB to test the hypothesis that RT omission results in equivalent OS in cT1-2 (< 3 cm) N0 HER2+ patients treated with NST+BCS with pCR. MATERIALS/METHODS We identified patients with cT1-T2 (< 3 cm) N0 HER2+ BC treated with anti-HER2 based NST and BCS +/- RT from 2013-2015. We identified factors associated with RT omission using logistic regression analysis. We evaluated OS in the subset of patients with pCR stratified by receipt of RT. We used a propensity score matched (PSM) analysis to compare OS between the groups. Patients were matched on clinical and demographic factors. The effect of RT omission was evaluated with a Cox proportional hazards model with robust standard errors to account for clustering in matched pairs. RESULTS We identified 4,842 patients (4,505 RT; 337 no RT): 31.7% ER-/PR-; 48.5% with pCR. On multivariate analysis, age≥70 (OR = 2.88, P < 0.0001), Black race (OR = 1.43, P = 0.03), and use of single-agent cytotoxic chemotherapy (OR = 1.47, P = 0.02) were associated with RT omission. There was a trend towards RT omission in patients with pCR (OR = 1.21, P = 0.11). OS data was available in 1,581 (1,471 RT; 110 no RT) of the 2,348 patients with pCR. Median follow-up was 27.1 months (IQR = 19.7-37.0 months) with 14 deaths (3 RT; 11 RT omission). The 2-year OS was significantly worse for patients with RT omission (96.9% vs. 99.7%, P = 0.02). The PSM cohort consisted of 103 (of a possible 110) pairs of patients with 6 deaths (3 RT; 3 RT omission) and median follow-up 25.6 months (IQR, 17.9-35.9 months). In the PSM cohort, RT omission was not significantly associated with an increased risk of death (2-year OS 96.7% vs. 98.5%; HR = 1.12, 95% CI 0.23-5.41, P = 0.89). CONCLUSION We did not find an association between RT omission and increased risk of death in patients with cT1-T2 (< 3 cm) N0 HER2+ BC treated with NST+BCS with pCR. Patients that did not receive RT tended to be older, of Black race, and to have received single-agent cytotoxic chemotherapy. These data support prospective evaluation of RT omission in this patient population in a randomized controlled trial.

Objectives: Neutrophil-lymphocyte ratio (NLR) has been associated with mortality in non-small cell lung cancer (NSCLC), but its association with recurrence in locally advanced NSCLC (LA-NSCLC), specifically, is less established. We hypothesized pre- and post-treatment NLR would be associated with recurrence and mortality. Methods: We studied the association of pre-treatment NLR (pre-NLR) and post-treatment NLR at 1 (post-NLR1) and 3 months (post-NLR3) with outcomes in patients with LA-NSCLC treated with chemoradiation. Pre-NLR was dichotomized by 5, an a priori cutoff previously shown to be prognostic in LA-NSCLC. Post-NLR1 and post-NLR3 were dichotomized by their medians. Linear and logistic regression were used to correlate thoracic vertebral body dose with post-NLR. Results: We identified 135 patients treated with chemoradiation for LA-NSCLC between 2007 and 2016. Median follow-up for living patients was 61.1 months. On multivariable analysis, pre-NLR ≥ 5 was associated with worse overall survival (HR = 1.82; 95% CI 1.15 – 2.88; p = 0.011), but not with any recurrence, locoregional recurrence, or distant recurrence. Post-NLR1 ≥ 6.3 was not associated with recurrence or survival. Post-NLR3 ≥ 6.6 was associated with worse overall survival (HR = 3.27; 95% CI 2.01– 5.31; p < 0.001), any recurrence (HR = 2.50; 95% CI 1.53 – 4.08; p < 0.001), locoregional recurrence (HR = 2.50; 95% CI 1.40 – 4.46; p = 0.002), and distant recurrence (HR = 2.53; 95% CI 1.49 – 4.30; p < 0.001). Post-NLR3 ≥ 6.6 correlated with thoracic vertebral body volume receiving 5 Gy (p = 0.026), 10 Gy (p = 0.041), and 60 Gy (p = 0.044). Conclusion: Pre-treatment NLR is associated with worse overall survival and post-treatment NLR is associated with worse survival and recurrence. Additionally, post-treatment NLR at 3 months correlates with thoracic vertebral body dose. These findings should be validated independently and prospectively studied.

Rates of acute esophagitis in breast cancer patients undergoing regional nodal irradiation (RNI) are under-reported. We set to identify esophageal dose-volume constraints associated with grade 2 esophagitis (G2E). We hypothesized that the G2E rate was higher with intensity modulated radiation therapy (IMRT) vs. 3D conformal radiation therapy (3DCRT).We identified patients that received RNI (50 Gy/25 fractions) from 1/2013 to 6/2019. We retrospectively contoured the esophagus in a consistent manner and recorded esophageal mean dose, max dose, and V10-V50. Our primary endpoint was the G2E rate. Receiver operating characteristics curves analysis (e.g., Youden's J statistic) were used to determine the cutpoints for the dosimetric parameters which were then tested in logistic regression models.We identified 531 patients (50% left-sided; 41% IMRT; 16.2% G2E). G2E was significantly higher in IMRT vs. 3DCRT patients (23.6% vs. 10.9%, p 0.0001). All esophageal dosimetric parameters were significantly associated with G2E after adjusting for age and laterality. The cutpoints for esophageal mean dose, V10 and V20 were 11 Gy, 30%, and 15%, respectively. The associations between the dichotomized dose-volume parameters and G2E were OR = 3.82 (95% CI 2.28-6.40, p 0.0001) for esophageal mean dose, OR = 5.37 (95% CI 3.01-9.58, p 0.0001) for esophageal V10, and OR = 3.23 (95% CI 1.93-5.41, p 0.0001) for esophageal V20.In patients receiving RNI with modern techniques, we found that G2E occurs in15%, and more frequently with IMRT. These data strongly support the routine contouring of the esophagus in RNI planning, and our constraints should be incorporated in future prospective protocols of RNI.

Purpose Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node–positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns. Methods and Materials Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post). Results Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post). Conclusions An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints.

Introduction Elderly patients account for the majority of lung cancer diagnoses but are poorly represented in clinical trials. We evaluated the overall survival (OS) of elderly patients with stage III NSCLC treated with definitive radiation compared with that of patients treated with definitive chemoradiation. Methods We conducted a comparative effectiveness study of radiation therapy versus chemoradiation in elderly (≥70 years old) patients with stage III NSCLC not treated surgically diagnosed from 2003 to 2014; the patients were identified by using the National Cancer Database. Two cohorts were evaluated: patients (n = 5023) treated with definitive radiation (≥59.4 Gy) and patients (n = 18,206) treated with definitive chemoradiation. Chemoradiation was further defined as concurrent (radiation and chemotherapy started within 30 days of each other) or sequential (radiation started >30 days after chemotherapy). We compared OS between the treatment groups by using the Kaplan-Meier method and Cox proportional hazards regression before and after propensity score matching (PSM). Results Treatment with chemoradiation was associated with improved OS versus that with radiation both before PSM (hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.64-0.68, p Conclusions We found that definitive chemoradiation resulted in a survival advantage compared with definitive radiation in elderly patients. Sequential chemotherapy and radiation was superior to concurrent chemoradiation. Although prospective trials are needed, this analysis suggests that chemoradiation should be strongly considered for elderly patients and the optimal sequencing of chemotherapy and radiation remains an unanswered question for this patient population.

PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V(5)-V(60)) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points. RESULTS: We identified 201 patients, the majority having NSCLC (n = 162, 81%) and stage III to IV disease (n = 179, 89%). All patients received either cisplatin/etoposide (n = 107, 53%) or carboplatin/paclitaxel (n = 94, 47%). Median RT dose was 60 Gy (range, 60–70 Gy). The rate of HT3+ was 49% (n = 99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004–1.080, P = .032), as were increasing TVB V(5) to V(20).These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n = 1, m = 1.79, and TD(50) = 21.4 Gy. Optimal cut-points identified were V(5) = 65%, V(10) = 60%, V(20) = 50%, and mean dose = 23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. CONCLUSIONS: We found that mean TVB dose and low-dose parameters (V(5)-V(20)) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n = 1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.