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Purpose: To assess the acute toxicity and quality of life (QOL) of hypofractionation compared with conventional fractionation for whole breast irradiation (WBI) after breast-conserving surgery., Methods and Materials: Women with node-negative breast cancer who had undergone breast-conserving surgery with clear margins were randomly assigned to conventional WBI of 5000 cGy in 25 fractions over 35 days or hypofractionated WBI of 4256 cGy in 16 fractions over 22 days. Acute skin toxicity and QOL were assessed at baseline and 2, 4, 6, and 8 weeks from the start of treatment for a subgroup of patients. QOL was assessed at baseline and 4 weeks posttreatment for all patients. In the acute toxicity substudy, repeated measures modeling was used to investigate treatment by time interactions over the 8-week period for acute toxicity and QOL mean change score. QOL mean change score from baseline to 4 weeks posttreatment was compared for all patients., Results: In the acute toxicity substudy, 161 patients participated. In the main trial, 1152 patients participated. Acute skin toxicity was initially similar between groups but was less with hypofractionation compared with conventional fractionation toward the end of the 8-week period (P < .001). QOL at 6 weeks from the start of treatment was improved with hypofractionation for the skin side effects, breast side effects, fatigue, attractiveness, and convenience domains (all P < .05). In the main trial, hypofractionation resulted in improved overall QOL and QOL attributed to skin side effects, breast side effects, and attractiveness (all P < .01)., Conclusions: Hypofractionated WBI compared with conventional WBI resulted in less acute toxicity and improved QOL. This further supports the benefits of hypofractionation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background It is controversial whether ductal carcinoma in situ (DCIS) is a preinvasive marker of breast cancer or if it is part of a spectrum of small cancers with malignant potential. Comparing clinical outcomes in women with invasive and noninvasive breast lesions might help to resolve the issue. Methods From a database of 2641 patients with breast cancer, we selected women who had been treated with breastconserving surgery for a cancer that was 2.0 cm or less in size, node-negative, and nonpalpable. No subject received chemotherapy. Cancers were categorized as noninvasive (stage 0, n = 172) or invasive (stage 1, n = 401) based on a review of the pathology records. We compared the actuarial risks of in-breast recurrence after invasive and noninvasive breast lesions before and after adjusting for tamoxifen and radiotherapy. Results The 18-year cumulative risk of in-breast recurrence was 35.2% for patients with dcis and 12.8% for patients with small invasive cancers (hazard ratio: 2.4; 95% confidence interval: 1.5 to 3.8; p < 0.0003). After adjustment for radiotherapy and tamoxifen treatment, the difference was small and nonsignificant (hazard ratio: 1.4; 95% confidence interval: 0.9 to 2.4; p = 0.22). Conclusions For women with small, nonpalpable, node-negative breast cancers, the likelihood of experiencing an inbreast recurrence was associated with radiotherapy and with tamoxifen, but not with the presence of cancer cells invading beyond the basement membrane. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Accelerated partial breast irradiation (APBI) is an alternative to whole breast irradiation that is delivered over a shorter period of time with less toxicity. Appropriate patient selection is critical to its success and the American Society for Radiation Oncology (ASTRO) has published detailed selection criteria for ‘suitable’ patients. This study evaluated the effect of those selection criteria on APBI eligibility based on pathology reports. Materials and methods: From March 2004 to March 2007 all patients referred to a single cancer centre for breast radiotherapy were screened for participation in a phase I/II trial of permanent breast seed implant brachytherapy. Eligible patients underwent a computed tomography simulation and those referred from an outside institution had a secondary expert breast pathology assessment. Initial and expert pathology reports were compared regarding completeness and accuracy. Results: In total, 143 patients were eligible for the trial; 79 patients had surgery carried out outside our institution. In the initial pathology report, the most frequently missing critical information was the resection margin width (29.1%) and the presence of extensive in situ carcinoma (11.4%). Comparing initial and reviewed pathology, the agreement was higher than 90% for most features. The main source of disagreement was the width of the negative resection margin, with 34.4% disagreement (P =0.016), although it changed eligibility in only 3.6%. There was major disagreement in the evaluation of lymphovascular invasion. Overall, pathology review changed the eligibility for a patient from ‘suitable’ for APBI to ‘cautionary’ in 18.6% of the cases. Conclusion: Using stringent eligibility criteria has a direct effect on patient screening for APBI. The use of synoptic pathology reporting and a quality assurance programme with secondary expert assessments are recommended. [Copyright &y& Elsevier]

Background:Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that may progress to invasive cancer. Identification of factors that predict recurrence and distinguish DCIS from invasive recurrence would facilitate treatment recommendations. We examined the prognostic value of nine molecular markers on the risks of local recurrence (DCIS and invasive) among women treated with breast-conserving therapy.Methods:A total of 213 women who were treated with breast-conserving therapy between 1982 and 2000 were included; 141 received breast-conserving surgery alone and 72 cases received radiotherapy. We performed immunohistochemical staining on the DCIS specimen for nine markers: oestrogen receptor, progesterone receptor, Ki-67, p53, p21, cyclinD1, HER2/neu, calgranulin and psoriasin. We performed univariable and multivariable survival analyses to identify markers associated with the recurrence.Results:The rate of recurrence at 10 years was 36% for patients treated with breast-conserving surgery alone and 18% for women who received breast-conserving surgery and radiotherapy. HER2/neu+/Ki-67+ expression was associated with an increased risk of DCIS recurrence, independent of grade and age (HR=3.22; 95% CI: 1.47-7.03; P=0.003). None of the nine markers were predictive of invasive recurrence.Conclusion:Women with a HER2/neu/neu+/Ki67+ DCIS have a higher risk of developing DCIS local recurrence after breast-conserving surgery. [ABSTRACT FROM AUTHOR]

BACKGROUND Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A--subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.) [ABSTRACT FROM AUTHOR]

Abstract: Aims: Post-mastectomy radiotherapy (PMRT) decreases locoregional recurrence and increases survival for women with large tumours and/or node-positive disease. The American Society of Clinical Oncology has published treatment guidelines, but has also indicated that the optimal technique for PMRT remains unknown. The objective of this study was to evaluate the variability in which a bolus is currently used in PMRT and to identify the clinical situations in which a bolus is used. Materials and methods: In 2004, an e-mail survey was sent to all active physician members of the American Society for Therapeutic Radiology and Oncology, the Canadian Association of Radiation Oncologists and the European Society for Therapeutic Radiology and Oncology. The survey focused on the technical details regarding the use of a bolus in PMRT. Results: In total, 1035 responses were obtained: 642 from the Americas (568 from the USA), 327 from Europe and 66 from Australasia. Respondents from the Americas were significantly more likely to always use a bolus (82%) than the Europeans (31%), as were the Australasians (65%) (P <0.0001). Europeans were significantly more likely to use a bolus for specific indications (P <0.0001). The results also showed wide variation in the schedule of application (every day [33%] and alternate days [46%]) and thickness used (<1cm [35%] and ≥1cm [48%]). Conclusions: There is a wide variation in the use of a bolus in PMRT with significant regional differences. This probably translates into a variation in the dose delivered to the skin and may have an effect on local recurrence and/or toxicity. A randomised clinical trial is needed to evaluate the benefit and toxicity associated with the use of a bolus in PMRT. [Copyright &y& Elsevier]

Higher mean lung dose (MLD) in breast cancer patients has been associated with pneumonitis, pulmonary fibrosis and secondary lung cancer primaries. This study examined MLD in a single institution from 2014 to 18 to assess trends in median MLD (Gy) over time and factors associated with higher MLD to determine best practices for limiting lung toxicity. General linear regressions were analysed to determine significant change in median MLD over time in patients receiving conventional or hypofractionated schedules for whole breast/chest wall (WB) radiotherapy with or without sequential boost or simultaneous integrated boost, WB tangential radiotherapy only and WB locoregional radiotherapy. Univariate and multivariable linear regression analysed identified factors associated with MLD. In total, 3894 patients were included in the analysis. The total median MLD across all years was 6.8 Gy in patients treated with conventional fractionation and 3.4 Gy in patients treated with hypofractionation. A significant increase in MLD was observed between 2014 and 2018 in patients receiving conventional or hypofractionation, conventional WB treatment with locoregional radiotherapy, conventional WB radiotherapy with simultaneous integrated boost and hypofractionated WB radiotherapy with sequential boost. Increased MLD was significantly correlated with lower lung volume and larger treatment volume due to locoregional radiotherapy, inclusion of a boost, chest wall treatment and reverse decubitus or supine positioning (P < 0.0001). A significant increase in MLD was observed over the years in patients receiving conventional and hypofractionated radiotherapy. Techniques such as prone positioning should be considered to lower MLD, particularly for patients with predisposing pulmonary risk. • Median mean lung dose (MLD) from 2014–2018 was 6.8 Gy for conventional and 3.4 Gy for hypofractionated radiotherapy (RT). • There was a significant increase in median MLD from 2014 to 2018 in both conventional and hypofractionated RT (p < 0.0001). • Wide tangents, lower lung volume, boost, chest wall, conventional or locoregional RT were associated with higher median MLD. • Prone positioning was significantly associated with lower median MLD than reverse decubitus and supine positioning. [ABSTRACT FROM AUTHOR]