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Purpose: Patients with breast cancer who are unsuitable for surgical resection are typically managed with palliative systemic therapy alone. We report outcomes of 5-fraction ablative radiation therapy for nonresected breast cancers., Methods and Materials: This is a retrospective analysis of an institutional registry of patients with breast cancer who were unsuitable for resection and underwent 35 to 40 Gy/5 fractions to the primary breast tumor or regional lymph nodes from 2014 to 2021. Primary outcomes were cumulative incidence of local failure and grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0)., Results: We reviewed 57 patients who received 61 treatment courses (median age of 81 years; range, 38-99). Unresectable tumor (10%), patient refusal (18%), medical inoperability (35%), and metastatic disease (37%) were the causes of not having surgery. Five patients (8%) had previously undergone adjuvant locoregional radiation therapy. Fifty-four percent (n = 33/61) of treatment courses targeted the breast only, 31% (n = 19/61) both the breast and lymph nodes, and 15% (n = 9/61) the lymph nodes only. Sixty-seven percent (n = 35/52) of the courses that targeted the breast were delivered with partial breast irradiation and 33% (n = 17/52) with whole breast radiation therapy (median dose of 25 Gy in 5 fractions) ± simultaneous integrated boost to the primary tumor. Most primary tumors (65%, n = 34/52) and target lymph nodes (61%, n = 17/28) were treated with a dose of 35 Gy in 5 fractions. Most treatments (52%) were delivered with intensity modulated radiation therapy (IMRT). Radiation therapy was delivered daily (20%), every other day (18%), twice weekly (36%), or weekly (26%). The 2-year cumulative incidence of local failure was 11.4% and grade≥3 toxicity was 15.1%. The grade ≥3 toxicity was 6.5% for IMRT treatments, versus 7.7% for non-IMRT treatments targeting partial breast or lymph nodes (hazard ratio, 1.13, P = .92), versus 38.9% for non-IMRT treatments targeting the entire breast (hazard ratio, 6.91, P = .023). All grade ≥3 toxicity cases were radiation dermatitis. No cases of brachial plexopathy were observed., Conclusions: Thirty-five to 40 Gy in 5 fractions is a safe and effective breast stereotactic body radiation therapy (SBRT) regimen and may be an attractive option for patients who are not surgical candidates. Highly conformal techniques (ie, IMRT or partial breast irradiation) were associated with a reduced risk of toxicity and should be the preferred treatment approaches., Competing Interests: Disclosures HS reports honoraria from Elekta for educational activities., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation., Methods: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test., Results: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77)., Conclusions: The risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer., Competing Interests: Declaration of competing interest Dr. Whelan has received in-kind funding from Exact Sciences for work not related to this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Radiation pneumonitis (RP) is a potentially severe inflammatory reaction that occurs in approximately 1-16% of breast cancer patients treated with radiation (RT)., Methods: Case histories and patient demographics were collected from 4 patients who received either hypofractionated (42.56 Gy in 16 fractions) or conventionally fractionated (50 Gy in 25 fractions) RT for breast cancer at a cancer centre from 2018-2020 and experienced clinically symptomatic RP. Lung dose parameters including mean lung dose, V5, and V20 were collected from institutional planning software and compared to institutional guidelines., Results: The 4 cases were all female, aged 42-73 years old and received 2- or 4-field RT with wide or high tangent techniques. The most common symptoms in patients who developed RP were exertional dyspnea and dry cough. Corticosteroid doses in the daily range of 40-60 mg were the primary treatment followed by a highly variable tapering schedule. Two patients experienced a recurrence of symptoms after initial treatment and were restarted on corticosteroids. Patients had several predisposing risk factors including administration of wide tangents, chemotherapy with cyclophosphamide and/or taxanes, age>65 years, and comorbidities such as diabetes., Discussion: Identification of RP is difficult as evidenced by the large gap in time between the appearance of RP symptoms to treatment with corticosteroids in several patients. Irregular tapering schedules may contribute to symptom recurrence. Three of the four patients treated with 4-field wide tangents exceeded the 35% dose constraint for ipsilateral lung V20 or V17.5., Conclusion: Careful radiation planning and review of lung dose constraints is essential to reduce risk of RP. Greater standardization of steroid tapering practices is recommended., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Severe radiation dermatitis (RD) is distressing and may have adverse long-term effects including fibrosis and telangiectasia. Treatment interruptions due to severe RD may increase the risk of recurrence. Two randomized trials of Mepitel film demonstrated efficacy in preventing severe RD in breast cancer, but this product has not been widely adopted in North America. We aimed to assess the feasibility and efficacy of Mepitel film for prevention of breast RD at a Canadian center., Methods and Materials: Patients were stratified based on breast size and receipt of postmastectomy radiation therapy. The primary outcome was RD grade using the Common Terminology Criteria for Adverse Events. Secondary outcomes included moist desquamation, patient- and clinician-reported symptoms of skin toxicity, and cosmetic outcomes., Results: Thirty patients receiving external beam radiation therapy to the breast or chest wall were enrolled. Two patients (6.7%) discontinued use of the Mepitel film before completing radiation therapy. No patients developed grade 3 RD or higher. Five patients (17.9%) developed grade 2 RD: 3 (10.7%) had moist desquamation, and 2 (7.1%) had brisk erythema without moist desquamation., Conclusions: Mepitel film completely prevented grade 3 RD. Rates of moist desquamation and grade 2 RD were lower with Mepitel film than in studies using aqueous cream, but unlike previous trials of Mepitel film we did not achieve complete prevention of moist desquamation. Further research is needed to confirm the efficacy of Mepitel film versus standard prophylaxis for RD and identify the patients who will benefit the most from the film., (Copyright © 2020 American Society for Radiation Oncology. All rights reserved.)

Background: The adoption of hypofractionated radiotherapy (HFRT) into clinical practice varies widely despite randomized trials and guidelines supporting its equivalence to conventional fractionated radiotherapy (CFRT) for certain patient populations. We assessed the use of HFRT at a single institution from 2011 to 2018, as well as time-savings calculations., Patients and Methods: A retrospective cohort study was conducted for patients with breast cancer receiving adjuvant radiotherapy by HFRT or CFRT. Trends in HFRT use (≤ 16 fractions) were stratified according to 4 subgroups: tangential breast RT, locoregional breast RT, tangential chest wall RT, and locoregional chest wall RT. Treatment time savings were approximated using the institutional median treatment time., Results: A total of 5190 patients were included. HFRT use in all subgroups increased from 2011 to 2018. Tangential breast HFRT alone increased from 62.2% in 2011 to 96.9% in 2018. Locoregional breast HFRT and tangential chest wall HFRT use increased from less than 10% in 2011 to 76.2% and 76.9% in 2018. In locoregional chest wall RT, HFRT use of 44.9% was observed in 2018. Increased use of locoregional HFRT was mainly due to institutional policy changes. Time-savings calculations showed that 4002 hours of treatment or an additional 1402 HFRT courses could have been administered if all patients received HFRT., Conclusion: The use of HFRT at our center increased in all patient subgroups. More evidence and guidelines for patients receiving chest wall or locoregional HFRT are required because the use of HFRT remains low in these patient cohorts., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Breast cancer radiotherapy (RT) can increase the risk of cardiac disease with increasing dose; as such, reducing excessive dosage to the heart is a concern for clinicians. The purpose of the present study was to assess mean heart dose (MHD) in patients with breast cancer receiving RT, where it was hypothesized that MHD decreased over time., Methods: Patients planned for adjuvant unilateral whole breast/chest wall RT from 2011 to 2018 were included for a retrospective chart-review at a single-institution, academic center. MHD (Gy) was summarized by laterality, fractionation, and heart-sparing techniques., Results: A total of 4,687 patients were included. The median MHD for left-sided conventional RT (50 Gy in 25 fractions) was 2.16 Gy across all years, decreasing until 2015 and increasing after. Median MHD for left-sided hypofractionated RT (42.6 Gy in 16 fractions) was 1.47 Gy, also decreasing until 2015 and increasing after. The increase in MHD after 2015 was attributed to a significant increase in the use of wide tangents (including internal mammary chain) after 2015 (P < .0001). Several treatment factors were associated with higher MHD in both right- and left-sided cancers, including locoregional RT, high tangents, wide tangents, bolus, heart shielding, treatment to the chest wall, higher volume of tissue irradiated by tangential fields, higher baseline breast separation values, and smaller heart volume. After adjusting for laterality and fractionation in the multivariate analysis, locoregional RT, wide tangents, heart shielding, boost, treatment to the chest wall, higher volume of tissue irradiated by tangential fields, higher baseline breast separation, and lower heart volume were significantly associated with higher MHD (P < .0001)., Discussion/conclusions: MHD should be considered when determining the most appropriate RT techniques for both right- and left-sided cancers as higher MHD was significantly associated with various treatment techniques and patient factors., (Copyright © 2020. Published by Elsevier Inc.)

A subset of patients with ductal carcinoma in situ (DCIS) of the breast develop ipsilateral invasive breast cancer after breast-conserving surgery with or without adjuvant radiotherapy. Risk assessment and prediction of adverse outcomes for individual patients based on traditional clinical and pathological parameters are limited. The Oncotype DCIS Score is a commercially available multigene assay that has been independently validated in a prospective clinical trial and a population-based cohort. The score helps to identify a subset of women >50 years old with unifocal disease that carries <10% risk of any local recurrence after breast-conserving surgery alone. In this population, individual patients and physicians may consider omitting adjuvant radiotherapy. In this article, we review the literature and summarize the evidence regarding the role of the Oncotype DCIS Score in estimating the risk of ipsilateral local recurrence and ipsilateral invasive breast cancer recurrence. The available data on clinical utility and cost-effective analysis for optimizing decisions on adjuvant treatments are discussed., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Individual prediction of local recurrence (LR) risk after breast-conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS) is needed to identify women at low risk, for whom radiotherapy may be omitted. PATIENTS AND METHODS: Three predictive models of LR-clinicopathologic factors (CPF) alone; CPF + estrogen receptor (ER) + human epidermal growth factor receptor 2 (HER2); and CPF + DCIS score (DS)-were developed among 1102 cases of DCIS in patients with complete covariate and outcome data. Categorizations of discrete variables and transformations of continuous variables were examined in Cox models; 2-way interactions and interactions with time were assessed. Internal validation was performed by bootstrapping. Individual predicted 10-year LR risks were computed from covariate values, estimated regression parameters, and estimated baseline survival function. Accuracy was assessed by c statistics and calibration plots., Results: The strongest prediction model incorporated CPF + DS. The c statistics for CPF + DS, CPF + ER + HER2, or CPF-alone models were 0.7025, 0.6879, and 0.6825, respectively. The CPF + DS model was better calibrated at predicting low (≤ 10%) individual 10-year LR risks after BCS alone than those incorporating CPF + ER + HER2 or CPF alone, evidenced by c statistics and plots of observed by predicted risks. Among women aged ≥ 50 with no adverse CPF, the CPF + DS model identified the greatest proportion of women (62.3%) with predicted individual 10-year LR ≤ 10% without radiotherapy compared to the CPF + ER + HER2 (50.9%) or CPF alone (46.5%) models., Conclusion: Individual prediction of LR incorporating DS is more accurate and identifies a higher proportion of women with low predicted risk of LR after BCS alone, for whom radiotherapy may be omitted., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite clear benefits of radiotherapy (RT) for breast cancer, there are numerous side effects. Radiation dermatitis has a significant impact on quality of life and can result in treatment interruptions or cessation. The purpose of this study was to prospectively follow breast radiation dermatitis and determine trends including peak toxicity., Patients and Methods: Upon initiation of RT treatment, to assess skin reaction, each patient was seen weekly by the healthcare team, or contacted via telephone to assess patient-reported symptoms. Weekly progression of radiation dermatitis was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Patients were stratified for analysis of radiation dermatitis based on RT technique and dosage., Results: A total of 148 patients with 2 or more skin assessments were analyzed. The majority of patients received 2-field tangential RT (64.2%) with a dose of 5000 cGy in 25 fractions. Overall, patients experienced the most Grade 2 CTCAE toxicity (61.9%) 2 weeks after completion of RT; Grade 3 toxicity also peaked at this time (8.3%). Regardless of stratification by RT technique or by dosage of RT, Grade 2 and 3 toxicities consistently peaked at 1 or 2 weeks after RT., Conclusions: Breast radiation dermatitis appears to peak approximately 2 weeks after RT. Treatment factors such as technique or dosing regimen do not appear to have a substantial effect on radiation dermatitis, but our study was limited by small sample size. This study provides additional evidence that radiation dermatitis should continue to be followed closely, especially in the 2 weeks following RT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Phyllodes tumours are rare and histologically diverse, posing challenges in prognosis and treatment. Due to their rarity, they have seldom been studied., Purpose: The purpose was to investigate clinical practices in the management of phyllodes tumours, as well as patient outcomes to contribute to the limited body of knowledge surrounding these tumours., Methods: A retrospective review was conducted on all patients with phyllodes tumours at a single institution. Descriptive analyses were conducted on demographic, disease and treatment (breast-conserving surgery, mastectomy, surgical re-excision, adjuvant/palliative radiation, palliative chemotherapy) information. Overall and disease-free survivals were analyzed, and the cumulative incidence of recurrence and metastases was compared., Results: 79 patients with phyllodes tumours of the breast were included in the study. Tumours were classified as malignant, borderline, or benign in 67.1%, 21.5%, and 11.4% of patients, respectively. There were no statistically significant differences in overall or disease-free survival between patients with benign, borderline or malignant disease. Only patients with malignant disease developed recurrence or metastases. Those with malignant disease who received mastectomies had a lower 10-year cumulative incidence of recurrence; however this was not statistically significant (p = 0.69). All patients had negative surgical margins due to a re-excision or mastectomy following margin-positive breast conserving surgery. Of all risk factors assessed, necrosis was significantly associated with increased incidence of recurrence (local or distant) in patients with malignant disease (p = 0.03)., Conclusion: The presence of tumour necrosis is a significant negative prognostic factor. Breast-conserving surgery may be adequate in providing local control, given negative surgical margins., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Radiation therapy (RT) after breast-conserving surgery (BCS) for Ductal Carcinoma in Situ (DCIS) halves the risk of local recurrence (LR). The omission of RT is often supported by the paradigm that patients who develop LR can be salvaged with further breast-conserving therapy leading to higher rates of breast preservation and improved quality of life. However, population-based, long-term rates of breast preservation in women treated by upfront BCS ± RT are unknown., Methods and Materials: Women diagnosed with pure DCIS from 1994 to 2003 treated with BCS ± RT in Ontario were identified. Median follow-up is 12 years. The development and treatment of LR and contralateral breast cancers were determined by administrative databases with validation. The 10-year mastectomy-free survival was calculated using the Kaplan-Meier method. The impact of RT on breast preservation was determined by propensity-adjusted cox proportional hazards model., Results: The cohort includes 3303 women with DCIS; 1649 (50%) underwent BCS alone, 1654 (50%) underwent BCS + RT. Women treated by BCS alone were more likely to develop a LR compared to those treated by upfront BCS + RT (20.8% versus 15.5%, p < 0.001). Mastectomy was used to treat LR in 57.4% (197/343) of women who recurred after BCS alone and 67.6% (174/257) of those who recurred after BCS + RT. Women treated with upfront BCS + RT had higher rates of bilateral breast preservation at 10 years compared to those treated by BCS alone (87.3% vs.82.7%, p = 0.0096)., Conclusion: Local Recurrence after BCS alone does not favor breast preservation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness., Methods: A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity., Results: Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive., Conclusion: For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.