A radiation therapy contouring atlas for delineation of the level I-II axilla in the prone position: a single institution experience.

PURPOSE: With transition from supine to prone, tenting of the pectoralis major occurs displacing the muscle from the chest wall and shifting the level I-II axillary spaces. For patients whom we aim to treat the level I-II axilla using the prone technique, accurate delineation of these nodal regions is necessary. While different consensus guidelines exist for delineation of nodal anatomy supine, to our knowledge there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS: The level I-II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by two radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I-II axilla on non-contrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS: Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I-II axilla prone using bone, muscle and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior border of level II, and the anterior, posterior, medial and lateral border of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS: The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I-II axilla when the axilla is a target in addition to the breast.

Harnessing the cGAS-STING pathway to potentiate radiation therapy: current approaches and future directions.

In this review, we cover the current understanding of how radiation therapy, which uses ionizing radiation to kill cancer cells, mediates an anti-tumor immune response through the cGAS-STING pathway, and how STING agonists might potentiate this. We examine how cGAS-STING signaling mediates the release of inflammatory cytokines in response to nuclear and mitochondrial DNA entering the cytoplasm. The significance of this in the context of cancer is explored, such as in response to cell-damaging therapies and genomic instability. The contribution of the immune and non-immune cells in the tumor microenvironment is considered. This review also discusses the burgeoning understanding of STING signaling that is independent of inflammatory cytokine release and the various mechanisms by which cancer cells can evade STING signaling. We review the available data on how ionizing radiation stimulates cGAS-STING signaling as well as how STING agonists may potentiate the anti-tumor immune response induced by ionizing radiation. There is also discussion of how novel radiation modalities may affect cGAS-STING signaling. We conclude with a discussion of ongoing and planned clinical trials combining radiation therapy with STING agonists, and provide insights to consider when planning future clinical trials combining these treatments.

Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline

This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns.

Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation.

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns. CONCLUSIONS: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI.

Risk of Radiation Dermatitis in Patients With Skin of Color Who Undergo Radiation to the Breast or Chest Wall With and Without Regional Nodal Irradiation.

PURPOSE: Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS: We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS: A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS: Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Different Re-Irradiation Techniques after Breast-Conserving Surgery for Recurrent or New Primary Breast Cancer.

Breast re-irradiation (reRT) after breast-conserving surgery (BCS) using external beam radiation is an increasingly used salvage approach for women presenting with recurrent or new primary breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. There is also limited data on efficacy and safety of external beam hypofractionation and accelerated partial-breast irradiation (APBI) regimens. This paper reviews existing retrospective and prospective data for breast reRT after BCS, APBI reRT outcomes and delivery at our institution and the need for a randomized controlled trial using shorter courses of radiation to better define patient selection for different reRT fractionation regimens.

Early effectiveness and toxicity outcomes of reirradiation after breast conserving surgery for recurrent or new primary breast cancer.

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Definitive Radiation With Nodal Boost for Patients With Locally Advanced Breast Cancer.

PURPOSE: The optimal local therapy of patients with nodal disease in supraclavicular (SCV), internal mammary nodes (IMN) and level III axilla is not well studied. We aimed to evaluate the outcomes of patients with breast cancer and advanced nodal disease that received a nodal boost. METHODS AND MATERIALS: This retrospective study included 79 patients with advanced nodal disease who underwent adjuvant radiation with a nodal boost to the SCV, IMNs, and/or axilla. All patients had radiographic changes after systemic therapy concerning for gross nodal disease. Overall survival, disease-free survival (DFS), and local recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS: All patients received an initial 50 Gy to the breast/chest wall and regional nodes, of whom 46.8% received an IMN boost, 38.0% axillary (ax)/SCV boost, and 15.2% both IMN and ax/SCV boost (IMN + ax/SCV). Most patients had hormone receptor positive (74.7%) and human epidermal growth factor receptor 2 negative disease (83.5%). In addition, 12.7% of patients had clinical (c) N2 disease, 21.5% cN3A disease, 51.9% cN3B disease, and 5.1% cN3C disease. Most patients received chemotherapy (97.5%). The median nodal boost dose was 10 Gy (range, 10-20 Gy), with 21.6% of IMN, 16.7% of ax/SCV, and 16.7% of IMN + ax/SCV receiving 14 to 20 Gy. With a median follow up of 30 months, the 3-year local recurrence-free survival, DFS, and overall survival rates were 94.5%, 86.3%, and 93.8%, respectively. Crude rates of failure were 13.9% (10.1% distant failure [DF] alone; 3.8% DF + locoregional failure [LRF]). Rates of failure by boost group were 13.3% for ax/SCV (10.0% DF alone; 3.3% DF + LRF), 5.4% for IMN (2.7% DF alone, 2.7% DF + LRF), and 41.7% for IMN + ax/SCV (33.3% DF, 8.3% DF + LRF). There were no LRFs without DFs. The median time to failure was 22.8 months (interquartile range, 18-34 months). Clinical tumor size and IMN + ax/SCV versus IMN or ax/SCV alone was associated with worse DFS (hazard ratio [HR]: 9.78; 95% confidence interval [CI], 2.07-46.2; P = .004 and HR: 9.49; 95% CI, 2.67-33.7; P = .001, respectively). On multivariate analysis, IMN + ax/SCV versus IMN or ax/SCV alone retained significance (HR: 4.80; 95% CI, 1.27-18.13; P = .02). CONCLUSIONS: In this population of patients with locally advanced breast cancer, the majority of failures were distant with no isolated LRFs. Failures were the highest in the IMN + ax/SCV group (∼40%). Further treatment escalation is necessary for these patients.

Disparities in the Uptake of Telemedicine and Implications for Clinical Trial Enrollment in Patients With Breast Cancer.

PURPOSE: Since the COVID-19 pandemic, telemedicine has emerged as an alternative to office visits in routine radiation oncology practice. The purpose of this study was to identify factors associated with patient preference for an initial consult via telemedicine and correlation with clinical trial enrollment. METHODS AND MATERIALS: We evaluated patients with breast cancer seen during the open enrollment of a prospective randomized trial from June 1, 2020, to May 13, 2021. Univariate and multivariate logistic regression models were used to identify factors associated with virtual versus in-person initial consultation. All statistical tests were 2-sided, and the null hypothesis was rejected for P < .05. RESULTS: We identified 476 patient consultations with 259 office visits and 217 telemedicine visits. On multivariate analysis, increased age, unemployment, chemotherapy receipt, and radiation at our institution were associated with decreased usage of telemedicine for consultation visit. Out of 217 patients who underwent a telemedicine initial consultation, 10% were eligible to enroll on the trial, and of those eligible 76% enrolled. Out of 259 patients who underwent office visit initial consultation, 14% were eligible to enroll on the trial, and of those eligible 53% enrolled. Among eligible patients, there was no statistically significant difference in clinical trial enrollment between telemedicine and office visits. CONCLUSIONS: Older patients, unemployed patients, those receiving chemotherapy, and those who subsequently received radiation at our institution were less likely to use telemedicine for their initial consult. Despite these disparities in telemedicine usage, there was no difference in clinical trial enrollment. Telemedicine may be an effective platform for clinical trial enrollment though further strategies to improve its access are essential.

Radiation Recall Dermatitis after Donor Lymphocyte Infusion for Adult T-Cell Leukemia Lymphoma Post-Allogeneic Stem Cell Transplant.

To our knowledge, this is the first case report describing radiation recall dermatitis (RRD) after donor lymphocyte infusion post-allogeneic stem cell transplant in a patient with acute T-cell leukemia lymphoma. Given its rare occurrence, unclear clinical characterization, and etiology, RRD remains poorly understood. In the setting of novel immunotherapies and recent development of COVID-19 mRNA vaccines, we aimed to better characterize RRD and its most likely pathogenesis in our patient's case.

Radiation-induced skin changes after breast or chest wall irradiation in patients with breast cancer and skin of color: a systematic review.

INTRODUCTION: 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). METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Regional nodal irradiation (RNI) in breast cancer patients with residual isolated tumor cells or micrometastatic nodal disease after neoadjuvant chemotherapy.

Background/Purpose: 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. Methods/Materials: 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. Results: 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. Conclusions: 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.

Accelerated partial breast irradiation in early stage breast cancer.

Accelerated partial breast irradiation (APBI) is increasingly used to treat select patients with early stage breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. This has led to controversy surrounding appropriate patients for APBI and an assessment of the toxicity and cosmetic outcomes of APBI as compared to whole breast irradiation (WBI). This paper reviews existing data for APBI, APBI delivery at our institution, and ongoing research to better define patient selection, treatment delivery, dosimetric considerations and toxicity outcomes.

Pulmonary Toxic Effects After Myeloablative Conditioning With Total Body Irradiation Delivered via Volumetric Modulated Arc Therapy With Fludarabine.

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.

Radiation Without Endocrine Therapy in Older Women With Stage I Estrogen-Receptor-Positive Breast Cancer is Not Associated With a Higher Risk of Second Breast Cancer Events.

PURPOSE: 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. METHODS AND MATERIALS: 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 χ2 tests for descriptive statistics, multivariable multinomial logistic regression to estimate relative risk of undergoing a treatment, and multivariable, propensity-weighted competing-risks survival regression to estimate standardized hazard ratio (SHR) of SBCE. We set significance at P ≤ .01. RESULTS: Most 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). CONCLUSIONS: 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.

Five-Fraction Prone Accelerated Partial Breast Irradiation: Long-Term Oncologic, Dosimetric, and Cosmetic Outcome.

PURPOSE: 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. METHODS AND MATERIALS: 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 with >6 months follow-up (FU). RESULTS: 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. CONCLUSIONS: 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.

Toxicity and Cosmetic Outcome of Breast Irradiation in Women with Breast Cancer and Autoimmune Connective Tissue Disease: The Role of Fraction and Field Size.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Hypofractionation including accelerated partial-breast irradiation is associated with less acute or late grade 2/3 toxicity in this population.

Radiation in Early-Stage Breast Cancer: Moving beyond an All or Nothing Approach.

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens' decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions.