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We present the case of a 56-year-old female with a diagnosis of acute T-cell lymphoblastic leukemia who received myeloablative conditioning for bone marrow transplant with total body irradiation (TBI) using volumetric modulated arc therapy (VMAT) to the upper body and anterior-posterior/posterior-anterior (AP/PA) open fields to the lower body followed by hematopoietic stem cell transplant. Her clinical course was complicated by high-grade pulmonary toxic effects 55 days after treatment that resulted in death. We discuss the case, planning considerations by radiation oncologists and radiation physicists, and the multidisciplinary medical management of this patient.

Randomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes.Patients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50%60% and V100%35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with6 months follow-up (FU).Of 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy.We report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.

The omission of radiation therapy (RT) in older women with stage 1 estrogen-receptor-positive (ER+) breast cancer receiving endocrine therapy (ET) is an acceptable strategy based on randomized trial data. Less is known about the omission of ET with or without RT.We analyzed surveillance, epidemiology, and end results (SEER)-Medicare data for 13,321 women age 66 years or older with stage I ER+ breast cancer from 2007 to 2012 who underwent breast-conserving surgery. Patients were classified into 4 groups: (1) ET + RT (reference); (2) ET alone; (3) RT alone; and (4) neither RT nor ET (NT). Second breast cancer events (SBCEs) were captured using the Chubak high-specificity algorithm. We used χMost women underwent both treatments, with 44% undergoing ET + RT, 41% RT alone, 6.6% ET alone, and 8.6% NT, but practice patterns varied over time. From 2007 to 2012, RT decreased from 49% to 30%, whereas ET alone and ET + RT increased (ET alone, 5.4%-9.6%; ET + RT, 38%-51%). Compared with patients age 66 to 69 years, patients age 80 to 85 years were more likely to receive NT (odds ratio [OR], 8.9), RT (OR, 1.9), or ET (OR, 8.8) versus ET + RT (P.01). Three percent of subjects had an SBCE (2.2% ET + RT, 3.0% RT alone, 3.2% ET alone, 7.0% NT). Relative to ET + RT, NT and ET alone were associated with higher SBCE (NT: SHR, 3.7, P.001; ET alone: SHR, 2.2, P = .008), whereas RT was not associated with a higher SBCE (SHR 1.21; P = .137). Clinical factors associated with higher SBCE were HER2 positivity and pT1c (SHR, 1.7; P = .006).Treatment with RT alone in older women with stage I ER+ disease is decreasing. RT alone is not associated with an increased risk for SBCE. By contrast, NT and ET are both associated with higher SBCE in multivariable analysis with propensity weighting. Further study of the omission of endocrine therapy in this patient population is warranted.

The optimal management of residual micrometastases and isolated tumor cells (ITC) in patients with invasive breast cancer who undergo neoadjuvant chemotherapy (NAC) followed by definitive surgery is not well-studied. We evaluated the role of regional nodal irradiation (RNI) in clinically node-positive (cN1) breast cancer patients with residual low-volume nodal disease following NAC.We queried the National Cancer Database (NCDB) and included patients with cN1 invasive breast cancer diagnosed from 2004 to 2016 who were treated with NAC and definitive surgery and had residual micrometastases (ypN1mi) or ITC (ypN0i+). We used univariable (UVA) and multivariable (MVA) Cox regression analyses to determine prognostic factors and Kaplan-Meier (KM) methods to evaluate overall survival (OS). We used inverse probability treatment weighting (IPTW) to reweight data to account for confounding factors.Our final cohort included 1980 patients, including 527 patients with ypN0i + disease and 1453 patients with ypN1mi disease. 1101 patients (45.0%) received RNI in the overall cohort with a higher proportion of ypN1mi patients receiving RNI (56.5%) compared to 53.1% of ypN0i + patients. There was no significant difference in OS between ypN0i + and ypN1mi patients. RNI had no significant effect on OS in the overall cohort using Cox MVA and KM methods. With separate subset analysis of ypN0i + and ypN1mi patients, there was no significant effect of RNI on OS. This was confirmed with IPTW.In a national hospital-based study of cN1 invasive breast cancer patients with residual ITC or micrometastases after NAC, RNI did not have a significant effect on OS.

Purpose Autoimmune connective tissue disease (CTD) has historically represented a relative contraindication to breast conservation (BC) among patients with early-stage breast cancer. Controversy exists regarding the use of hypofractionated radiation therapy (RT) among patients with CTDs. We evaluated acute and late toxicity in patients with breast cancer and CTD treated with BC. Methods and Materials Of 1983 patients treated with BC from 2012 to 2016, we identified 91 patients with an autoimmune disease (AD). Each patient was matched to a control without AD based on age, RT field, and fractionation. RT toxicity and clinician-rated cosmesis were compared between cases and controls. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method. Results The median follow-up was 49.9 months for cases and 53.0 months for controls, and 67% of cases and controls were treated with hypofractionated RT. There was no difference in grade 2/3 acute toxicity between cases and controls (26.4% vs. 16.5%, respectively; P = .148). There was a significantly higher rate of grade 2/3 late toxicity among cases (25.8% vs 12.1% among controls; P = .049). Active AD at the time of RT increased the rate of grade 2/3 late toxicity compared with controls (41.7% in cases vs. 11.4% in controls; P = .018). Among patients treated with hypofractionated RT, there was no difference in acute or late grade 2/3 toxicity between cases and controls (acute: 13.1% in cases vs. 11.5% in controls [P > 0.9]; late: 11.9% in cases vs. 13.1% in controls [P > 0.9]). The rates of good/excellent clinician-rated cosmesis were similar between groups (92.9% in cases vs. 98.9% in controls; P = .142). Conclusions In the largest matched case-control study of patients with CTD treated with conventional and hypofractionated RT, we demonstrate low rates of radiation toxicity, with good to excellent clinician-rated cosmesis. There was increased late toxicity in cases, especially in patients with active AD at time of RT. There was no increase in acute or late toxicity in the patients treated with hypofractionation.

Background The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT®) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians’ recommendations for adjuvant RT. Methods The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. Results Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors. Conclusions DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.

We describe a model case of unplanned pregnancy during radiation therapy to the chest wall and peripheral lymphatics for breast cancer. We use the Morbidity and Mortality Conference format to demonstrate how radiation oncology departments should evaluate and manage this situation.

Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients who cannot tolerate chemotherapy, there is no randomized data regarding the role of anti-HER2 therapy without chemotherapy. The National Cancer Database (NCDB) was queried for non-metastatic breast cancer patients with estrogen receptor-positive (ER+) and HER2+ breast cancer who received surgery and endocrine therapy, without chemotherapy from 2013 to 2016. Outcomes were compared between endocrine therapy alone (ET) or endocrine therapy with anti-HER2 therapy (ET + aHER2). Univariate and multivariate Cox-proportional hazards models were used to analyze the association between clinical characteristics and survival outcomes between groups. Propensity score matching (PSM) was performed to account for differences between the two groups. Of all patients with non-metastatic ER+/HER2+ breast cancer, we identified 9458 (20.5%) who did not receive chemotherapy. Of the 6741 patients who received ET, 17.2% also received aHER2 therapy. Median follow-up was 31.7 months (IQR 21.1–42.1). In the aHER2 group (vs. ET), there were more patients with older age, higher stage, node positivity, poorly or undifferentiated disease, lymphovascular invasion, lobular cancer, and Medicare insurance. Compared to the ET cohort, ET + aHER2 was not significantly associated with improved OS on multivariate analysis (HR 0.88 95% CI 0.68–1.15) or after propensity score matching (HR 0.80 95% CI 0.57–1.11). There is no significant difference in survival with the addition of HER2 therapy to endocrine therapy in ER+/HER2+ non-metastatic breast cancer patients who do not receive chemotherapy. To our knowledge, this is the largest series investigating this question.

The purpose of this study is to systematically review data pertaining to breast cancer and radiation-induced skin reactions in patients with skin of color (SOC), as well as data pertaining to objective measurements of skin pigmentation in the assessment of radiation dermatitis (RD).We conducted a systematic review utilizing MEDLINE electronic databases to identify published studies until August 2022. Key inclusion criteria included studies that described RD in breast cancer with data pertaining to skin of color and/or characterization of pigmentation changes after radiation.We identified 17 prospective cohort studies, 7 cross-sectional studies, 5 retrospective studies and 4 randomized controlled trials. Prospective cohort and retrospective series demonstrate worse RD in African American (AA) patients using subjective physician-graded scales. There is more limited data in patients representing other non-White racial subgroups with SOC. 2 studies utilize patient reported outcomes and 15 studies utilize objective methods to characterize pigmentation change after radiation. There are no prospective and randomized studies that objectively describe pigmentation changes with radiotherapy in SOC.AA patients appear to have worse RD outcomes, though this is not uniformly observed across all studies. There are no studies that describe objective measures of RD and include baseline skin pigmentation as a variable, limiting the ability to draw uniform conclusions on the rate and impact of RD in SOC. We highlight the importance of objectively characterizing SOC and pigmentation changes before, during and after radiotherapy to understand the incidence and severity of RD in SOC.

Extending the superior border of the breast tangent fields to include the low axilla is a technique employed to target the axillary lymph node (LN) without adding additional fields. This technique, commonly referred to as high tangents, is typically done in the supine position. The feasibility of delivering high tangents in the prone position has never been reported. Patients from 2012 to 2018 at a single institution who were prescribed treatment with high tangents using two tangentially opposed beams in the prone position were identified. The levels I–III axillary LNs were retrospectively contoured. The dose delivered to the LN, breast, and organs at risk was calculated using the original treatment plan. For LN, coverage was defined as > 90% of the prescribed dose. Forty-one patients treated with high tangents were identified. The median age was 62. Most patients underwent sentinel LN biopsy (88%), of which 59% had macroscopic disease and 30% had micrometastatic disease. Four patients had no axillary staging. Most patients (76%) were treated with hypofractionated radiation. The median distance from the superior border of the anterior oblique field to the humeral head was 0.6 cm (range: 0–1.5 cm). The mean coverage of the level I and level II axilla was 88.7% and 40.0% respectively. Axillary level I coverage for distance from the humeral head 1 cm was 76.4% (p = 0.017). This series demonstrates the feasibility of high tangents in the prone position, offering good coverage of level I LN, particularly with

Internal mammary lymph nodes (IMLNs) account for approximately 10%–40% of the lymphatic drainage of the breast. Internal mammary lymph nodes measuring up to 10 mm are commonly seen on high-risk screening breast MRI examinations in patients without breast cancer and are considered benign if no other suspicious findings are present. Benign IMLNs demonstrate a fatty hilum, lobular or oval shape, and circumscribed margins without evidence of central necrosis, cortical thickening, or loss of fatty hilum. In patients with breast cancer, IMLN involvement can alter clinical stage and treatment planning. The incidence of IMLN metastases detected on US, CT, MRI, and PET-CT ranges from 10%–16%, with MRI and PET-CT demonstrating the highest sensitivities. Although there are no well-defined imaging criteria in the eighth edition of the American Joint Committee on Cancer Staging Manual for Breast Cancer, a long-axis measurement of ≥ 5 mm is suggested as a guideline to differentiate benign versus malignant IMLNs in patients with newly diagnosed breast cancer. Abnormal morphology such as loss of fatty hilum, irregular shape, and rounded appearance (which can be quantified by a short-axis/long-axis length ratio greater than 0.5) also raises suspicion for IMLN metastases. MRI and PET-CT have good sensitivity and specificity for the detection of IMLN metastases, but fluorodeoxyglucose avidity can be seen in both benign conditions and metastatic disease. US is helpful for staging, and US-guided fine-needle aspiration can be performed in cases of suspected IMLN metastasis. Management of suspicious IMLNs identified on imaging is typically with chemotherapy and radiation, as surgical excision does not provide survival benefit and is performed only in rare cases.

ObjectiveTo evaluate the effect of definitive radiotherapy dose on survival in patients with human papillomavirus positive oropharyngeal carcinoma.MethodsHuman papillomavirus positive oropharyngeal carcinoma patients staged T1–3 and N0–2c, who received definitive radiotherapy (fraction sizes of 180 cGy to less than 220 cGy), were identified from the National Cancer Database 2010–2014 and stratified by radiation dose (50 Gy to less than 66 Gy, or 66 Gy or more).ResultsA total of 2173 patients were included, of whom 124 (6 per cent) received a radiation dose of 50 Gy to less than 66 Gy. With a median follow up of 33.8 months, patients had a 3-year overall survival rate of 88.6 per cent (95 per cent confidence interval = 87.1–90.1 per cent). On multivariate Cox analysis, a radiotherapy dose of 50 Gy to less than 66 Gy (hazard ratio = 0.95, 95 per cent confidence interval = 0.52–1.74, p = 0.86) was not a predictor of increased mortality risk.ConclusionHuman papillomavirus positive oropharyngeal carcinoma patients had excellent outcomes with definitive radiotherapy doses of 50 Gy to less than 66 Gy. These results further support patients enrolling into clinical trials for radiation dose de-escalation.

Purpose: The development of trastuzumab has significantly improved prognosis and treatment of Her2 positive breast cancer. The efficacy of trastuzumab monotherapy is limited and thus standard of care is to combine trastuzumab with chemotherapy. Yet for those who cannot tolerate chemotherapy, there is no randomized data comparing no trastuzumab with trastuzumab monotherapy in the non-metastatic setting. We therefore examined the outcomes of non-metastatic patients treated with trastuzumab without chemotherapy in the National Cancer Database (NCDB). Methods: We included female patients from 2013-2016 with clinical stage I-III breast cancer who received surgery with ER+/HER+ disease. Patients treated with Her2 therapy after 2013 had their treatment classified under immunotherapy, whereas those treated before 2013 had Her2 therapy classified under chemotherapy. Exclusion criteria included male sex, prior cancer history, and clinical stage IV disease. We also excluded patients with pathologic stage 0 (DCIS), stage IV, or unknown pathologic stage. Treatments compared included chemotherapy (CT), adjuvant hormone therapy alone (HT), combination HT + trastuzumab (HT+T), and no adjuvant treatment (NT). Pearson chi square analysis, one-way ANOVA, and the Kaplan Meier method was used to evaluate the differences in clinical characteristics for the treatment groups and effects of treatment on overall survival. Results: We identified 46,025 patients who met eligibility criteria. The median follow-up was 31 months (SD 13.16) for CT, 30 months (SD 14.07) for HT, 30 months (SD 12.87) for HT + T, and 27 months (SD 14.61) for NT. Most patients received standard of care with CT (78%, n=36008), 12% (n=5632) received adjuvant HT without T (HT), 3% (n=1157) were treated with HT+T, and 12% (n=2669) with NT. There was a higher representation of elderly patients >70 years old in the HT (41%) and HT +T (51%) and NT arm (38%) compared to the CT arm (13%). There was a higher representation of lobular histology specifically in the HT + T arm (52%) compared to CT (11%), HT (11%), or NT arm (11%). There was a higher representation of patients with Charlson Deyo Comorbidity Scores of 1-2 (vs. 0) in the HT (21%) and HT +T arms (21%) compared to the CT (15%) or NT (18%) arms. There was a higher representation of node positive patients (N1-3 vs. N0) in the CT (38%) and HT+T (27%) groups vs. the HT (13%) and NT (16%) arms. Similarly, there were more patients with high grade disease (G3) and lymphovascular invasion (+LVI) in the CT (48% G3, 25% +LVI) and HT+T (45% G3, 20% +LVI) arms vs. in the HT (30% G3, 12% +LVI) and NT (39% G3, 15% +LVI) arms. Medicare patients were more likely to be treated with HT +T (58%) or HT (50%) than CT (24%) or NT (45%) which likely reflects the overlap of Medicare and older age. As compared to the standard of care CT arm, the patients treated without CT, had significantly worse overall survival. There was no improvement in OS for HT+T vs. HT without T. Hazard ratios for treatment regimens without CT were significantly worse with a HR 2.26 (95% CI 0.4-1.9) for HT without T, 3.01 (95% CI 0.3-2.3) for HT + T, and 4.37 (95% CI 3.7-5.1) for NT (p Citation Format: Susanna Nguy, S. Peter Wu, Cheongeun Oh, Naamit K Gerber. Outcomes of patients with ER+/HER2+ non-metastatic breast cancer treated with trastuzumab without chemotherapy [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 P1-18-02.

BACKGROUND Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes. METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated. RESULTS We identified 2164 patients who met the eligibility criteria. The median follow-up for all patients was 3.73 [interquartile range (IQR) 2.27-6.07] years. Five-year OS was 97.7% (95%CI: 96.8%-98.6%) with 28 deaths; 5-year LRFS was 98.0% (97.2-98.8) with 31 IBTRs. We identified 37 patients with isolated IBTR, 19 (51.4%) as ductal carcinoma in situ and 18 (48.6%) as invasive disease, of whom 83.3% had an in situ component. Median time from initial diagnosis to IBTR was 1.97 (IQR: 1.03-3.5) years. Radiotherapy information was available for 30 of 37 patients. Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed. Twenty-five of thirty-two (78.1%) patients had concordant hormone receptor status, HER-2 receptor status, and estrogen receptor (ER) (P = 0.006) and progesterone receptor (PR) (P = 0.001) status from primary to IBTR were significantly associated. There were no observed changes in HER-2 status from primary to IBTR. The concordance between quadrant of primary to IBTR was 10/19 [(62.2%), P = 0.008]. Tumor size greater than 1.5 cm (HR = 0.44, 95%CI: 0.22-0.90, P = 0.02) and use of endocrine therapy upfront (HR = 0.36, 95%CI: 0.18-0.73, P = 0.004) decreased the risk of IBTR. CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Hypofractionation has historically been underused among breast cancer patients with connective tissue diseases given a theoretical risk of increased toxicity and their overall underrepresentation in clinical trials that established hypofractionation as standard of care. We aim to compare the rates of toxicity in patients with autoimmune connective tissue diseases treated with conventionally fractioned radiation therapy (CF-RT) and hypofractionated radiation therapy (HF-RT) including accelerated partial breast irradiation.A total of 1983 patients treated with breast conservation between 2012 and 2016 were reviewed for diagnosis of autoimmune disease. Univariate analysis using binary logistic regression was performed to evaluate the effect of disease and treatment variables on acute and late toxicity. Multivariate analyses using Cox regression models were used to evaluate the independent associations between covariates and the primary end points. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for reach risk group.Ninety-two patients with autoimmune disease were identified. Median follow-up was 59 months. Of the patients 35% received CF-RT and 65% received HF-RT, of whom 70% received whole breast radiation (WBI) without regional nodal irradiation, 12% received WBI with regional nodal irradiation, and 18% received accelerated partial breast radiation. Patients who received CF-RT were significantly more likely to have autoimmune disease (AD) symptoms (78% vs 37%, P.001), to be managed on disease-modifying antirheumatic drugs (DMARDs; 41% vs 15%, P = .013), and to have active autoimmune disease (84% vs 43%, P.001). On multivariate analysis, HF-RT was associated with a significantly decreased odds of acute and late grade 2/3 toxicity compared with CF-RT fractionation (acute: OR 0.200, 95% CI 0.064-0.622, P = .005; late: OR 0.127, 95% CI 0.031-0.546, P = .005).Hypofractionation including accelerated partial-breast irradiation is associated with less acute or late grade 2/3 toxicity in this population.

PURPOSE/OBJECTIVE(S) Definitive radiation therapy (RT) is a curative treatment modality for gastric MALT. Reducing radiation dose to organs at risk (OAR) is imperative for patients with curative disease and excellent long-term prognosis. Advanced RT planning with DIBH and/or IMRT is available to improve the therapeutic ratio of RT by minimizing dose to normal tissues while maintaining adequate target coverage. We aimed to compare dosimetric parameters when using different radiation planning and delivery techniques in patients with gastric MALT. MATERIALS/METHODS After institutional review board approval, we identified adult patients (age ≥ 18 years) with biopsy-proven gastric MALT who were treated at our institution from 2010 to 2020. Each patient underwent two simulation CT scans: free breathing (FB) and DIBH. Four plans were generated for each patient including DIBH-IMRT, DIBH-3DCRT, FB-IMRT, and FB-3DCRT with a prescribed dose of 30 Gy in 20 fractions. The CTV was defined as the entire stomach including the gastroesophageal junction to the pylorus. The PTV included a 1 to 1.5 cm expansion from the CTV. Paired t-tests were used to compare mean calculated dose values for each OAR based on treatment technique. RESULTS Our cohort consisted of 8 patients (6 male, 2 female) with a median age 62.5 years (39 to 83 years). Compared to 3D-CRT, IMRT was associated with significantly decreased heart dose for both DIBH (Dmean 354.7 vs 440.5 cGY, P = 0.029) and FB (Dmean 521.2 vs 699.6 cGY, P = 0.006). IMRT was also associated with decreased dose to the left ventricle (LV), left anterior descending artery (LAD), liver, and lungs compared to 3D in both FB and DIBH. For IMRT plans, DIBH was associated with significantly lower heart V30 and V20 and a trend towards significance for lower heart Dmean (354.7 vs 521.2 cGY, P = 0.059) in comparison to FB. For 3D plans, DIBH was associated with a lower heart V30 and V20, and a higher lung V20, V10, and V5 in comparison to FB. CONCLUSION Both IMRT and DIBH represent modalities for reducing heart dose in gastric MALT patients receiving definitive RT. IMRT also reduces LV, LAD, liver and lung dose regardless of technique used to account for respiratory motion whereas DIBH was not associated with reduced doses to the LAD, kidney, or liver.

PURPOSE/OBJECTIVE(S) TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. MATERIALS/METHODS Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% ≥ 90%, D98% ≥ 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant. RESULTS Patients were treated to 12 Gy in 8 BID fractions (n = 6) or 13.2 Gy in 8 BID fractions (n = 3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2). CONCLUSION Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.

Purpose/Objective(s) The supraclavicular (SCV), medial axillary and internal mammary nodes (IMNs) are not typically resected in breast cancer patients (pts). The optimal local therapy of pts with nodal disease in these regions is not well-studied. We aim to evaluate outcomes of breast cancer patients with unresected nodal disease. Materials/Methods We identified 79 pts at our institution from 2016- 2021 with unresected nodal disease in the axilla, SCV and/or IMNs defined as grossly enlarged nodes on CT, MRI or PET scan +/- biopsy confirmation. Pts were treated with breast/chest wall and regional nodal irradiation with an additional boost to the unresected nodal region. Distant failure (DF) and local-regional failure (LRF) were assessed. Kaplan-Meier was used to calculate disease-free survival (DFS), overall survival (OS) and local recurrence-free survival (LRFS). Logistic regression was used to identify variables associated with worse DFS. Acute and late toxicity of RT were evaluated. Results 33% of pts were treated with breast-conserving surgery, 65% with mastectomy and all had axillary surgery (81% ALND, 19% SLNB). 47% of pts received IMN boost (IMN), 40% axillary/SCV boost (axSCV) and 15% both IMN and axSCV boost (IMN/axSCV). Most had cT2-3 (72%), hormone receptor positive (75%), and HER-2 negative disease (84%). 57% of axSCV had cN3A disease; 84% of IMN and 83% of IMN/axSCV had cN3b disease. 7% of axSCV and 17% of IMN/axSCV had cN3c disease. Most pts received chemotherapy (97%). Median nodal boost dose was 10 Gy (range 10-20 Gy), with 17% axSCV, 22% IMN, and 17% IMN/axSCV receiving 14-20 Gy. Rates of acute and late grade 3 toxicity did not differ by boost location (acute: IMN: 20%, axSCV: 11% and IMN/axSCV 20%, P = 0.559; late: IMN: 40%, axSCV: 25%, IMN/axSCV: 40%, P = 0.630) nor by boost dose (10 Gy vs 14-20 Gy). There were no grade 4+ toxicities. With a median follow up of 30 months, the 3-year LRR, DFS, and OS was 94.5%, 86.3% and 93.8% respectively. Crude rates of failure for the entire group were 13.9% (10.1% DF; 3.8% DF+LRF). Rates of failure by boost group were axSCV: 13.3% (10% DF; 3.3% DF+LRF), IMN: 5.4% (2.7% DF, 2.7% DF+LRF), IMN/axSCV 41.7% (33.3% DF, 8.3% DF+LRF). There were no LRFs without DFs. Median time to failure was 23 months (IQR 18-34). On univariate analysis clinical tumor size (cT) and IMN/axSCV vs. IMN or axSCV alone was associated with worse DFS (HR: 9.78 95% CI 2.07-46.2, P = 0.004 and HR: 9.49 95% CI 2.67-33.7, P = 0.001). On multivariate analysis, cT approached significance (HR 6.15; 95% CI 0.95-39.8, P = 0.05). IMN/axSCV vs. IMN or axSCV alone retained significance (HR 4.80; 95% CI 1.27-18.13, P = 0.02). The difference between the axSCV vs. IMN group was not significant. Conclusion In this population of pts with unresected nodal disease, boost RT to radiographically positive LN regions can be safely delivered with low rates of grade 3+ toxicity. The majority of failures were distant with no isolated LRFs. Failures were highest in the IMN/axSCV group (∼40%). Further treatment escalation is necessary for these pts.

Problem Physician-scientists are individuals trained in both clinical practice and scientific research. Often, the goal of physician-scientist training is to address pressing questions in biomedical research. The established pathways to formally train such individuals are, mainly, MD-PhD programs and physician-scientist track residencies. Although graduates of these pathways are well equipped to be physician-scientists, numerous factors, including funding and length of training, discourage application to such programs and impede success rates. Approach To address some of the pressing challenges in training and retaining burgeoning physician-scientists, New York University Grossman School of Medicine formed the Accelerated MD-PhD-Residency Pathway in 2016. This pathway builds on the previously established accelerated three-year MD pathway to residency at the same institution. The Accelerated MD-PhD-Residency Pathway conditionally accepts MD-PhD trainees to a residency position at the same institution through the National Resident Matching Program. Outcomes Since its inception, 2 students have joined the Accelerated MD-PhD-Residency Pathway, which provides protected research time in their chosen residency. The pathway reduces the time to earn an MD and PhD by one year and reduces the MD training phase to three years, reducing the cost and lowering socioeconomic barriers. Remaining at the same institution for residency allows for the growth of strong research collaborations and mentoring opportunities, which foster success. Next steps The authors and institutional leaders plan to increase the number of trainees that are accepted into the Accelerated MD-PhD-Residency Pathway and track the success of these students through residency and into practice to determine if the pathway is meeting its goal of increasing the number of practicing physician-scientists. The authors hope this model can serve as an example to leaders at other institutions who may wish to adopt this pathway for the training of their MD-PhD students.

Background: Radiation therapy has immune-modulating effects resulting from apoptosis of tumor cells and DNA damage. The downstream generation of cytosolic DNA activates the cyclic GMP-AMP Synthase (cGAS)-STimulator of INterferon Gene (STING) signaling axis in both tumor and nearby immune cells, leading to increased induction of type I interferon (IFN-I) and other immune stimulating molecules. TAK-676 is a novel synthetic STING agonist being investigated (+/- pembrolizumab) in an ongoing first-in-human phase 1 study (NCT04420884). TAK-676 is a potent modulator of the innate immune system and leads to downstream activation of the adaptive immune system to produce antitumor responses in preclinical studies. In contrast to intratumorally injected STING agonists, TAK-676 is optimally designed for reduced serum degradation and enhanced permeability, allowing systemic IV delivery and access to tumor sites and lymphatics. The addition of TAK-676 following radiation therapy may enhance the immune response by increasing the STING-mediated IFN-I release and further stimulate T cell-mediated antitumor immunity, particularly in combination with anti-PD-1/PD-L1 therapies. Impaired IFN signaling has been linked to checkpoint inhibitor (CPI) resistance. Preclinical studies show that addition of a STING agonist may reverse the mechanisms of resistance in tumors with prior exposure to CPIs. This phase 1 trial was designed to investigate the safety and preliminary antitumor activity of TAK-676 + pembrolizumab following radiation therapy (NCT04879849). Methods: Patients aged ≥18 years with advanced NSCLC, TNBC, or SCCHN who have progressed on CPIs with ≥2 lesions, one of which can be targeted with radiation, are being enrolled. Patients receive 8 Gy x 3 fractions of image-guided radiation therapy followed by (after a minimum of 40 hours) IV pembrolizumab 200 mg on day 1 plus escalating doses of IV TAK-676 on days 1, 8, and 15 of a 21-day cycle. TAK-676 dose escalation is guided by the Bayesian Optimal Interval design. Patients receive TAK-676 + pembrolizumab until disease progression, intolerance, or withdrawal of consent. Once pharmacologically active dose levels of TAK-676 have been observed, paired biopsies will be collected in patients with a safely accessible lesion outside the radiation field at screening and between days 15 and 21 of cycle 1. The primary objective is to determine the safety and tolerability of TAK-676 + pembrolizumab following radiation therapy; secondary objectives are to determine the recommended phase 2 dose of TAK-676 + pembrolizumab following radiation therapy, and to assess preliminary antitumor activity both locally (in the radiation field) and systemically (non-radiated lesions). As of January 2022, nearly 10% of the planned patients have been enrolled. Citation Format: Benjamin Cooper, Steven J. Chmura, Jason J. Luke, Stephen L. Shiao, Reva K. Basho, Wade T. Iams, David B. Page, Cong Li, Richard C. Gregory, Michael H. Shaw, Kristin H. Horn, John P. Gibbs, Vicky A. Appleman, Allison J. Berger, Adnan O. Abu-Yousif, Neil B. Lineberry, Kate F. Stumpo, Aymen Elfiky, Naamit K. Gerber. Phase 1 study of TAK-676 + pembrolizumab following radiation therapy in patients with advanced non-small-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or squamous-cell carcinoma of the head and neck (SCCHN) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT243.

Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients who cannot tolerate chemotherapy, there is no randomized data regarding the role of anti-HER2 therapy without chemotherapy.The National Cancer Database (NCDB) was queried for non-metastatic breast cancer patients with estrogen receptor-positive (ER+) and HER2+ breast cancer who received surgery and endocrine therapy, without chemotherapy from 2013 to 2016. Outcomes were compared between endocrine therapy alone (ET) or endocrine therapy with anti-HER2 therapy (ET + aHER2). Univariate and multivariate Cox-proportional hazards models were used to analyze the association between clinical characteristics and survival outcomes between groups. Propensity score matching (PSM) was performed to account for differences between the two groups.Of all patients with non-metastatic ER+/HER2+ breast cancer, we identified 9458 (20.5%) who did not receive chemotherapy. Of the 6741 patients who received ET, 17.2% also received aHER2 therapy. Median follow-up was 31.7 months (IQR 21.1-42.1). In the aHER2 group (vs. ET), there were more patients with older age, higher stage, node positivity, poorly or undifferentiated disease, lymphovascular invasion, lobular cancer, and Medicare insurance. Compared to the ET cohort, ET + aHER2 was not significantly associated with improved OS on multivariate analysis (HR 0.88 95% CI 0.68-1.15) or after propensity score matching (HR 0.80 95% CI 0.57-1.11).There is no significant difference in survival with the addition of HER2 therapy to endocrine therapy in ER+/HER2+ non-metastatic breast cancer patients who do not receive chemotherapy. To our knowledge, this is the largest series investigating this question.

Young women with ductal carcinoma in situ (DCIS) represent a unique cohort given considerations for future risk reduction and treatment effects on fertility and quality of life. We evaluated national patterns of care in the treatment of young women and the impact of those treatments on overall survival (OS).Women younger than 50 years of age diagnosed with pure DCIS from 2004 to 2016 in the National Cancer Database (NCDB) were identified. Clinical, demographic, and choice of local therapy are summarized and trended over time. OS was analyzed using Cox proportional hazard models.A total of 52,150 women were identified, and the most common surgical treatment was breast-conservation surgery (BCS; 59%). Bilateral mastectomy (BM) increased in frequency from 2004 to 2016 (11-27%; p 0.001). In women 40 years of age, BM (39%) surpassed BCS (35%) in 2010 with a continued upward trend. On multivariable analysis, no OS benefit of BM (hazard ratio [HR] 0.99, p = 0.90) or unilateral mastectomy (UM; HR 0.98, p = 0.80) was observed when compared with BCS + radiation therapy (RT). Inferior OS was seen with BCS, Black race, estrogen receptor (ER)-negative, and tumor ≥ 2.5 cm (p ≤ 0.006). In ER+ patients, there was a significant difference in endocrine therapy (ET) use between BM (11%), UM (33%), and BCS (28%) compared with BCS + RT (64%, p 0.001).The use of BM for DCIS is increasing in younger patients and now exceeds breast-conservation approaches in women 40 years of age with no evidence of improved OS. Among ER+ patients, the rates of ET are lower in the BM, UM, and BCS-alone groups compared with BCS + RT.

Treatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010.The National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease.Of 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P .001). The use of doses36 Gy decreased over a corresponding time period (OR 0.44, P .001).Analysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses36 Gy.

Objectives/hypothesis To assess patterns of care and outcomes with the use of neoadjuvant chemotherapy followed by definitive radiation in local-regionally advanced nasopharyngeal carcinoma. Study design Retrospective database analysis. Methods We queried the National Cancer Database for patients with T3-4N2 or T1-4N3 nasopharyngeal carcinoma who received concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method, propensity-score matching, and a Cox proportional hazards model adjusting for demographic and disease-specific prognostic factors. Results From 2004 to 2014, a total of 1,731 patients were identified, including 504 patients (27%) who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy was used more frequently in years 2008 to 2010 (34%) and 2011 to 2014 (30%) compared with 2004 to 2007 (22%) (χ2 P = .001). At a median follow-up of 36.6 months, patients had 3-year OS of 66% in the neoadjuvant group compared with 70% in those who received concurrent chemoradiotherapy (log rank P = .29). On subgroup analysis by histology, T stage, and N stage, there remained no differences in OS between the two groups. On multivariable analysis, there was no significant survival difference associated with neoadjuvant chemotherapy (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 0.89-1.25, P = .54). In a propensity score-matched population of 1,008 patients (504 with neoadjuvant therapy and 504 without), there was no significant survival difference associated with neoadjuvant chemotherapy (H: 1.13, 95% CI: 0.93-1.38, P = .22). Conclusions Neoadjuvant chemotherapy was used in over 25% of patients, and its use is increasing. However, neoadjuvant chemotherapy was not associated with any differences in survival compared to concurrent chemoradiotherapy. Level of evidence 4 Laryngoscope, 128:2770-2777, 2018.

Hypofractionated whole-breast radiation therapy (RT) has proved to be equivalent to conventionally fractionated RT in multiple randomized trials. There is controversy regarding its use in younger women because of their underrepresentation in trials and the concern for late toxicity. We evaluated disease control and cosmetic outcomes in patients aged50 years treated with hypofractionated RT in 4 prospective single-institutional trials.From 2003 to 2015, 1313 patients were enrolled in 4 prospective protocols investigating the use of adjuvant hypofractionated RT after breast-conserving surgery with a daily or weekly concomitant boost. We identified the records of 348 patients aged50 years at consultation for this analysis. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method by study and across studies using meta-analytic methods. The late effects of RT, clinician-rated cosmesis, and patient-rated cosmesis were also evaluated.With a median follow-up period of 66.9 months, the overall survival rate was 99.6%, the disease-free survival rate was 96.3%, and the local recurrence-free survival rate was 97.7% at 3 years. Clinician-rated cosmesis (n = 242) was excellent or good in 93.4% of cases and fair or poor in 6.6%. Patient-rated cosmesis (n = 259) was excellent or good in 86.1% and fair or poor in 13.9%. When patients rated themselves differently than their physicians, patients more often rated themselves poorly compared with their physicians (P = .0044, Cochran-Mantel-Haenszel test).At a median follow-up of 5 years, an analysis of patients aged 50 years demonstrated that hypofractionated RT was safe and effective, with good to excellent cosmesis as assessed by both clinicians and patients.

BACKGROUND The treatment of ductal carcinoma in situ (DCIS) remains controversial and may be particularly difficult for patients with minimal disease. There is a dearth of information regarding patients who have been diagnosed with DCIS on core needle biopsy (CNB), who have no residual disease in the lumpectomy specimen. The purpose of this study was to explore the frequency of this presentation and short-term outcomes in these patients. METHODS Our institutional Breast Cancer Database was queried for all women who were diagnosed with pure DCIS from 2010 to 2016 and treated with lumpectomy. Variables included patient and tumor characteristics, adjuvant treatment, and ipsilateral breast tumor recurrence (IBTR). Statistical analyses included Pearson's chi-square, Fisher's exact tests, and Kaplan-Meier analysis. RESULTS Of 547 patients with pure DCIS, 50 (14%) had DCIS on CNB only. Of the patients with DCIS on CNB only, 15 were treated with lumpectomy and radiation therapy (RT), while 35 underwent lumpectomy without RT. At a median follow-up of 4 years, there were 3 (6%) IBTR all within the same quadrant as the original lumpectomy site. None of the patients who recurred received adjuvant RT or hormonal therapy. CONCLUSIONS Despite the minimal extent of disease exhibited in these cases, 6% of patients with DCIS on CNB only had IBTR at a median follow-up of 4 years. These data suggest that even minimal DCIS represents a significant risk of recurrence to the patient. Size and margins are not sufficient criteria to stratify risk and guide decisions for adjuvant therapies.

BACKGROUND Delays in postoperative head and neck (HN) radiotherapy have been associated with decreased overall survival; however, the impact of delays in postoperative HN chemoradiotherapy remains undefined. METHODS All patients with nonmetastatic HN cancer (oral cavity, oropharynx, larynx, hypopharynx) who underwent curative intent surgery and received adjuvant chemoradiotherapy were identified from the National Cancer Database (2005-2012). Overall treatment time (OTT) was defined as the time from surgery to the end of radiation therapy. Statistical methods included Cox proportional hazards modeling, which adjusted for clinicopathologic, demographic, and socioeconomic factors. Recursive partitioning analysis (RPA) identified the optimal threshold of OTT via conditional inference trees to estimate the greatest differences in overall survival (OS) on the basis of randomly selected training and validation sets. RESULTS A total of 16,733 patients were included, with a median follow-up of 37 months. Median OS for OTT in a predefined threshold of ≤ 13 weeks was 10.1 years (95% confidence interval [CI], 9.8 years; not reached) compared with 8.7 years (95% CI, 8.2-9.2 years) in > 13 weeks. On multivariate analysis, OTT of > 13 weeks versus ≤ 13 weeks independently increased mortality risk (hazard ratio, 1.10; 95% CI, 1.04-1.17; P =

We present the case of a 55-year old postmenopausal female with bilateral early stage clinically node negative breast cancer who was treated with bilateral lumpectomy with axillary lymph node dissection revealing N1a nodal disease in her right breast with extra-nodal extension and micrometastatic disease in her left breast. Given the controversy in management for low nodal burden for macroscopic and microscopic nodal disease, we review the key trials in regional nodal management that have included patients with low nodal burden to explain our reasoning for treatment decisions. Our patient was treated with both hypofractionation and conventional treatment. She is an excellent teaching case to demonstrate how much of an impact the decision regarding fractionation can have on long term breast cosmesis and toxicity.

Purpose/Objective(s) The prognostic and treatment implications of isolated tumor cells (ypN0i+) and micrometastatic (ypN1mi) nodal disease after neoadjuvant chemotherapy (NACT) is not well-studied. These patients are excluded from the ongoing NSABP B-51 trial which only includes patients with macroscopic nodal disease after NACT. We evaluate the long-term outcomes and the role of post-mastectomy radiation therapy (PMRT) in breast cancer patients with ypN0i+ and ypN1mi disease after NACT and mastectomy (MX). Materials/Methods Using the National Cancer Database (NCDB), we identified patients (≥ 18 year old) with breast cancer who were treated with NACT and MX diagnosed between 2004 and 2016. Patients with cT4 or metastatic disease were excluded. Chi-square testing was used to evaluate clinicopathological parameters of those treated with and without PMRT. Kaplan-Meier analysis was used to evaluate the effect of PMRT on overall survival (OS). Univariate and multivariate Cox proportional hazard models with and without inverse probability treatment weighting (IPTW) were used to identify prognostic factors associated with OS. Results Our final cohort consisted of 3,253 patients (34.0% ypN0i+, 66.0% ypN1mi) with a median age at diagnosis of 49 years (29 – 74 years). PMRT was utilized in 60.4% of the entire cohort, 51.8% of ypN0i+ patients and in 64.9% of ypN1mi patients. There was an increase in use of PMRT throughout the study period (56.2% in 2004-2011 vs. 61.9% in 2012-2016). With a median follow up of 36.8 months, the 5-year OS was 84.3% and 79.9% for ypN0i+ and ypN1mi patients, respectively (HR 1.23 [0.97-1.55], P = 0.092). Without accounting for covariates, there was no significant effect of PMRT on OS in ypN0i+ patients, ypN1mi patients, or in the entire cohort. In IPTW-MVA, PMRT had no significant effect on OS (HR 0.93 [0.74-1.18], P = 0.565]. Factors that were significant for worse OS on IPTW-MVA were higher comorbidity score, higher grade, hormone-receptor negative subtype, higher ypT stage, presence of lymphovascular invasion, Asian/Pacific Islander race, and more recent year of diagnosis. HER-2 positive subtype, receipt of hormone therapy, and private insurance were associated with improved OS. Conclusion Patients with ypN1mi disease had a trend towards worse OS in comparison to patients with ypN0i+ disease. The majority of patients with ypN0i+ and ypN1mi are receiving PMRT with higher rates of PMRT in ypN1mi vs. ypN0i+. PMRT rates are increasing with time. There is no association of PMRT with improved OS. Prospective randomized controlled data is needed to further evaluate the role of PMRT in these patients who were excluded from the ongoing NSABP B-51.

Purpose To investigate cardiac toxicity associated with breast radiation therapy (RT) at 10-year follow-up in BCIRG-001, a phase 3 trial comparing adjuvant anthracycline chemotherapy (fluorouracil, doxorubicin, and cyclophosphamide) with anthracycline–taxane chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) in women with lymph node–positive early breast cancer. Methods and Materials Prospective data from all 746 patients in the control arm (fluorouracil, doxorubicin, and cyclophosphamide) of BCIRG-001 at 10-year follow-up were obtained from Project Data Sphere. Cardiac toxicities examined included myocardial infarction (MI), heart failure (HF), arrhythmias, and relative and absolute left ventricular ejection fraction decrease of >20% from baseline. Toxicities were compared between patients who received RT versus no RT, left-sided RT versus no RT, and internal mammary nodal RT versus no RT. Results Of the 746 patients, 559 (75%) received RT to a median dose of 50 Gy. Myocardial infarction occurred in 3 RT patients (0.5%) versus 6 no-RT patients (3%) ( P =.01). Heart failure was seen in 15 RT patients (2.7%) versus 3 no-RT patients (1.6%) ( P =.6). Among these, 35 RT patients (18%) had a left ventricular ejection fraction relative decrease of >20% baseline versus 7 (10%) who did not receive RT ( P =.1). Arrhythmias were more common in RT patients (3.2%) versus no-RT patients (0%) ( P =.01). On univariable and multivariable analysis HF was not significantly associated with RT, and MI was negatively associated with RT. Conclusions In this retrospective analysis of prospective toxicity outcomes, there is an increased risk of arrhythmias but no clear evidence of significantly increased risk of MI or HF at 10 years in lymph node–positive women treated with breast RT and uniform adjuvant doxorubicin-based chemotherapy. Given the low incidence of these outcomes, studies with larger numbers are needed to confirm our findings.

Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non–small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

Background and purpose We evaluated the effect of post-mastectomy radiation (PMRT) in 1–3 positive lymph nodes (LN) in patients who received uniform modern systemic therapy. Materials and methods Cohort study using individual data collected for 1,649 node-positive women who received doxorubicin/cyclophosphamide with sequential docetaxel in 2000–2003 on the control arm of BCIRG-005. All women underwent mastectomy or lumpectomy and axillary LN dissection. PMRT was given at investigator's discretion. Results A total of 523 women with 1–3 positive LN underwent mastectomy and 39% (206/523) received PMRT. With a median follow-up of 10years, PMRT improved loco-regional control (LRC) from 91% to 98% ( p =0.001) but had no effect on overall survival (OS) (84% vs. 86%, p =0.9). On multivariate analysis, PMRT improved local control (LC) (hazard ratio, 0.14; 95% CI, 0.03–0.62; p =0.01) and LRC (hazard ratio, 0.15; 95% CI, 0.04–0.50; p =0.002). PMRT did not significantly impact OS on multivariate analysis (hazard ratio, 0.91; 95% CI, 0.55–1.51; p =0.7). Results remained consistent with the use of propensity score analysis. Conclusions In this cohort of patients with N1 disease treated with modern systemic therapy, PMRT improves LRC but has no effect on OS. The rates of OS were excellent, irrespective of adjuvant radiation.

Purpose: Resident physicians use social media (SM) for many reasons. We sought to characterize current SM use by radiation oncology (RO) trainees for education and professional development. Methods and Materials: An anonymous 40-question survey was sent by e-mail to RO residents in the 2018 to 2019 academic year. SM platform use, time spent on SM, professional use, and opinions regarding SM use were assessed. Descriptive statistics and a univariate logistic regression analysis were performed to identify factors associated with perceptions of SM and spending >25% of SM time for academic or professional purposes. Results: Of the 615 residents surveyed, 149 responded (24% response rate). Facebook (73%), theMednet (62%), Instagram (59%), Twitter (57%), and Doximity (50%) were the top SM platforms used. Most respondents (53%) reported 60 minutes per day over the past week. Residents with an RO mentor on SM (n = 35; 24%; odds ratio [OR]: 2.79; 95% confidence interval [CI], 1.29-6.08; P = .010), those participating in RO discussions on SM (n = 71; 48%; OR: 2.85; 95% CI, 1.42-5.72; P = .003), and those interacting with professional societies (n = 69; 46%; OR: 7.11; 95% CI, 3.32-15.24; P < .001) were more likely to spend >25% of their SM time on professional/academic purposes. The vast majority of respondents agreed that SM exposed them to novel educational content (82%) and was helpful for career development (65%). In addition, 69% agreed that SM can improve clinical skills and knowledge. A substantial minority agreed that SM distracts them from studying (38%) or they felt pressure to have a SM presence (29%). Conclusions: Most RO residents reported that SM provides novel educational content and can help with career development. Potential disadvantages of SM for trainees may include distraction and pressure to maintain a SM presence. SM use by RO trainees merits further research to optimize its potential for education and professional development.

To compare heart and lung doses for adjuvant whole breast irradiation (WBI) between radiation plans generated supine with deep inspiratory breath hold (S-DIBH) and prone with free-breathing (P-FB) and examine the effect of breast volume (BV) on dosimetric parameters.Patients with left breast ductal carcinoma in situ or invasive cancer receiving adjuvant WBI were enrolled on a single-institutional prospective protocol. Patients were simulated S-DIBH and P-FB; plans were generated using both scans. Wilcoxon signed-rank and rank-sum tests were used to compare intrapatient differences between plans for the entire cohort and within BV groups defined by tertiles.Forty patients were enrolled. Thirty-four patients are included in the analysis owing to patient withdrawal or inability to hold breath. With WBI dose of 4005 to 4256 cGy, mean heart dose (MHD) was 80 cGy in S-DIBH and 77 cGy in P-FB (P = .08). Mean ipsilateral lung dose (MLD) was 453 cGy in S-DIBH and 45 cGy in P-FB (P.0001). Mean and max left anterior descending artery doses were 251 cGy and 551 cGy in S-DIBH, respectively (P = .1), and 324 cGy and 993 cGy in P-FB, respectively (P = .3). Hot spot and separation were 109% and 22 cm in S-DIBH, respectively, and 107% and 16 cm in P-FB, respectively (P.0001). For patients with smallest BV, S-DIBH improved MHD and left anterior descending artery doses; for those with largest BV, P-FB improved cardiac dosimetry. With increasing BV, there was an increasing advantage of P-FB for MHD (P = .05), and max (P = .03) and mean (P = .02) left anterior descending artery doses, and the reduction in MLD, hot spot, and separation with P-FB increased (P .05).MHD did not differ between P-FB and S-DIBH, whereas MLD was significantly lower with P-FB. Analysis according to breast volume revealed improved cardiac dosimetry with S-DIBH for women with smallest BV and improved cardiac dosimetry with P-FB for women with larger BV, thereby providing a dosimetric rationale for using breast size to help determine the optimal positioning for WBI.

Two commonly used whole breast irradiation (WBI) techniques, deep inspiration breath hold (DIBH) and prone positioning, are compared with regard to dosimetry and estimated late cardiac morbidity and secondary lung cancer mortality using published models. Forty patients with left-sided DCIS or breast cancer who underwent lumpectomy and required adjuvant WBI were enrolled on a prospective trial comparing supine DIBH (S-DIBH) with prone free breathing (P-FB) planning. Patients underwent CT simulation in both positions; two plans were generated for each patient. Comparative dosimetry was available for 34 patients. Mean cardiac and lung doses were calculated. Risk of death from ischemic heart disease (IHD), risk of at least one acute coronary event (ACE), and lung cancer mortality were estimated from published data. Difference between S-DIBH and P-FB plans was compared using paired two-tailed t test. Estimated mean risk of death from IHD by age 80 was 0.1% (range 0.0%-0.2%) for both plans (P = 1.0). Mean risk of at least one ACE was 0.3% (range 0.1%-0.6%) for both plans (P = .6). Mean lung cancer mortality risk was 1.4% (range 0.5%-15.4%) for S-DIBH and 1.0% (range 0.4%-9.8%) for P-FB (P = .008). Excess lung cancer mortality due to radiation was 0.5% (range 0.1%-6.0%) with S-DIBH and 0.0% (range 0.0%-0.4%) with P-FB (P = .008). Both S-DIBH and P-FB provide excellent cardiac sparing. Prone positioning results in lower lung dose than S-DIBH and leads to an absolute decrease of 0.5% in excess lung cancer mortality for patients receiving WBI.

The advent of affordable and rapid next-generation DNA sequencing technology, along with the US Supreme Court ruling invalidating gene patents, has led to a deluge of germline and tumor genetic variant tests that are being rapidly incorporated into clinical cancer decision-making. A major concern for clinicians is whether the presence of germline mutations may increase the risk of radiation toxicity or secondary malignancies. Because scarce clinical data exist to inform decisions at this time, the American Society for Radiation Oncology convened a group of radiation science experts and clinicians to summarize potential issues, review relevant data, and provide guidance for adult patients and their care teams regarding the impact, if any, that genetic testing should have on radiation therapy recommendations. During the American Society for Radiation Oncology workshop, several main points emerged, which are discussed in this manuscript: (1) variants of uncertain significance should be considered nondeleterious until functional genomic data emerge to demonstrate otherwise; (2) possession of germline alterations in a single copy of a gene critical for radiation damage responses does not necessarily equate to increased risk of radiation-induced toxicity; (3) deleterious ataxia-telangiesctasia gene mutations may modestly increase second cancer risk after radiation therapy, and thus follow-up for these patients after indicated radiation therapy should include second cancer screening; (4) conveying to patients the difference between relative and absolute risk is critical to decision-making; and (5) more work is needed to assess the impact of tumor somatic alterations on the probability of response to radiation therapy and the potential for individualization of radiation doses. Data on radiosensitivity related to specific genetic mutations is also briefly discussed.

The therapeutic management of regional lymph nodes in breast cancer has seen a remarkable change in the past 2 decades. Clinical trials have refined our knowledge regarding the biology of the disease including the prognostic significance of disease in the regional lymph nodes. The contemporary management of lymph nodes is also influenced by advances in surgical technique, radiation oncology delivery systems, and effective systemic therapy regimens. This paper describes the role of regional nodal irradiation in the context of the de-escalation of axillary surgery, improved understanding of the molecular and pathologic features, and increasing use of neoadjuvant chemotherapy.