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[Display omitted] • PBI is valid alternative to WBI in patients at low-risk of local relapse. • PBI is delivered by means of various techniques, one of which is IOeRT. • After IOeRT, an unexpectedly high LR rate was observed in the only phase III RCT. • Patient selection impacts on LR rates after IOeRT. • With appropriate patient selection IOeRT outcomes overlap with other RT techniques. [ABSTRACT FROM AUTHOR]

This review is aimed at evaluating whether radiation therapy (RT) can be omitted in older adult early-stage low-risk breast cancer (BC) patients. The published data are particularly relevant at present, during the COVID-19 pandemic emergency, to define a treatment strategy and to prioritize essential therapy. Cochrane Database of Systematic Reviews and PubMED were systematically researched from outset through April 2020 using Mesh terms. Only randomized controlled trials (RCT), with one arm without adjuvant whole-breast irradiation (WBI), were included in the analysis. Recent literature regarding the COVID pandemic and BC RT was assessed. The reported RCTs identified a group of BC patients (pT1-2N0M0 R0, grade 1–2, estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative tumours) in which the absolute risk of local recurrence (LR) was considered low enough to omit RT. The most common risk factors were tumor diameter, nodal and receptor status. Adjuvant RT had a significant impact on LR but not on distant metastasis (DM) or death. During the COVID 19 pandemic, results from RTCs were re-considered to define treatment recommendations for BC patients. International scientific societies and radiation oncology experts suggested RT omission, whenever possible, in older adult early-stage BC patients. Adjuvant RT might be omitted in a highly selected group of older adult early-stage BC patients with favourable prognostic factors. Hypofractionated regimens should be the standard. RT omission, partial breast irradiation (PBI), and ultra- hypofractionated regimens could be considered in selected cases due to the pandemic. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether a boost to the tumor bed after breast-conserving surgery (BCS) and radiotherapy (RT) to the whole breast affects local control and disease-free survival. Methods and Materials: A total of 1,138 patients with pT1 to pT2 breast cancer underwent adjuvant RT at the University of Florence. We analyzed only patients with a minimum follow-up of 1 year (range, 1–20 years), with negative surgical margins. The median age of the patient population was 52.0 years (±7.9 years). The breast cancer relapse incidence probability was estimated by the Kaplan-Meier method, and differences between patient subgroups were compared by the log rank test. Cox regression models were used to evaluate the risk of breast cancer relapse. Results: On univariate survival analysis, boost to the tumor bed reduced breast cancer recurrence (p < 0.0001). Age and tamoxifen also significantly reduced breast cancer relapse (p = 0.01 and p = 0.014, respectively). On multivariate analysis, the boost and the medium age (45–60 years) were found to be inversely related to breast cancer relapse (hazard ratio [HR], 0.27; 95% confidence interval [95% CI], 0.14–0.52, and HR 0.61; 95% CI, 0.37–0.99, respectively). The effect of the boost was more evident in younger patients (HR, 0.15 and 95% CI, 0.03–0.66 for patients <45 years of age; and HR, 0.31 and 95% CI, 0.13–0.71 for patients 45–60 years) on multivariate analyses stratified by age, although it was not a significant predictor in women older than 60 years. Conclusion: Our results suggest that boost to the tumor bed reduces breast cancer relapse and is more effective in younger patients. [Copyright &y& Elsevier]

Purpose: To analyze the relationship between a delay in radiotherapy (RT) after breast-conserving surgery and ipsilateral breast recurrence (BR). Methods and Materials: We included in our analysis 4,820 breast cancer patients who had undergone postoperative RT at the University of Florence. The patients were categorized into four groups according to the interval between surgery and RT (T1, <60 days; T2, 61–120 days; T3, 121–180 days; and T4, >180 days). Results: On multivariate analysis, the timing of RT did not reach statistical significance in patients who received only postoperative RT (n = 1,935) or RT and hormonal therapy (HT) (n = 1,684) or RT, chemotherapy (CHT), and HT (n = 529). In the postoperative RT-only group, age at presentation, surgical margin status, and a boost to the tumor bed were independent prognostic factors for BR. In the RT plus HT group, age at presentation and boost emerged as independent prognostic factors for BR (p = 0.006 and p = 0.049, respectively). Finally, in the RT, CHT, and HT group, only multifocality was an independent BR predictor (p = 0.01). Only in the group of patients treated with RT and CHT (n = 672) did multivariate analysis with stepwise selection show RT timing as an independent prognostic factor (hazard ratio, 1.59; 95% confidence interval, 1.01–2.52; p = 0.045). Analyzing this group of patients, we found that most patients included had worse prognostic factors and had received CHT consisting of cyclophosphamide, methotrexate, and 5-fluorouracil before undergoing RT. Conclusion: The results of our study have shown that the timing of RT itself does not affect local recurrence, which is mainly related to prognostic factors. Thus, the “waiting list” should be thought of as a “programming list,” with patients scheduled for RT according to their prognostic factors. [Copyright &y& Elsevier]

Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and 5-fluorouracil 600 mg/m2) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46–52 Gy) with standard fractionation. The boost dose was 6–16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of the present analysis is to determine the long-term results in terms of breast relapse and specific survival in patients treated with conserving surgery and adjuvant treatment for early breast cancer. Methods: From January 1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated consecutively at the University of Florence. The median age of the patient population was 55 years (range 30–80). All patients were followed for a median of 7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or local recurrence) was estimated by using Kaplan–Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. Results: The Cox regression model by stepwise selection showed some parameters, such as chemotherapy (HR 1.53; CI 1.19–1.95), pT status (HR 1.62, CI 1.31–2.01), positive axillary lymph nodes (HR 1.92, CI 1.66–2.22), and local recurrence (HR 4.58; CI 3.66–5.73), as independent prognostic factors for breast cancer death. Moreover, we found lower rate survival among patients treated before 1991 in comparison to women treated after 1991 (p =0.0001) probably due to inadequate treatment. For local disease free survival, age at presentation (HR 0.47; CI 0.35–0.63), use of tamoxifen (HR 0.42; CI 0.25–0.71), surgical margins (HR 2.00; CI 1.21–3.30), and chemotherapy (HR 0.53; CI 0.31–0.91) emerged by multivariate analyses as significant breast relapse predictors. Conclusion: In our experience breast conserving surgery followed by adjuvant radiotherapy treatment gives high rates of local control in women with early breast cancer. The use of routinely adjuvant chemotherapy and hormone therapy lowered the local recurrence and probably the modification of therapeutic approach in the last decades also improved the specific survival. [Copyright &y& Elsevier]