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Purpose: The purpose of the study was to evaluate the toxicity, local control, overall and disease-free survival of elderly breast cancer (BC) patients treated with adjuvant once-weekly ultra-hypofractionated radiotherapy (RT) either with intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT). Methods: From July 2011 to July 2018, BC patients receiving 5.7 Gy once a week for 5 weeks to the whole breast after breast-conserving surgery were considered for the study. Inclusion criteria were: T1–T3 invasive BC, no or limited axillary involvement, age ≥ 65 years or women with commuting difficulties or disabling diseases. Results: A total of 271 patients were included in the study. Median age was 76 (46–86) years. Most of BC were T1 (77%), while the remaining were T2 (22.2%) and T3 (0.4%). Axillary status was negative in 68.3% of the patients. The only severe acute toxicity (G3) at the end of RT was erythema (0.4%), registered in the 3DCRT group; no G3 edema or epitheliolysis was recorded. With 18 months of median follow-up, severe early–late toxicity (G3) was reported in terms of fibrosis and breast retraction, both with an incidence of 1.4%, mostly in the 3DCRT group. Oncological outcomes at a median follow-up of 2.9 years reported 249/271 (91.9%) patients alive and free from any event and 5 (1.8%) isolated locoregional recurrences. At 3 years, disease-free survival and overall survival were 94.9% and 97.8%, respectively. Breast volume > 500 cm3 was reported as predictive for moderate–severe (≥ G2) acute toxicity. Conclusions: Weekly ultra-hypofractionated whole breast RT seems feasible and effective. Toxicity was mild, local control was acceptable, and overall survival was 97.8% at 3 years. Rates of severe toxicity were reduced with the IMRT technique.

Aim: To evaluate outcome of intraoperative electron boost (IOERT) and hypofractionated whole breast irradiation (HWBI) for breast cancer (BC) in young women. Methods and Materials: Women aged ≤ 48 with pT1-2 N0-1 BC received 12 Gy IOERT boost during conservative surgery followed by 3-dimensional conformal HWBI in 13 fractions (2.85 Gy/die). Local relapses (LR) and survival (disease-free, DFS; specific, BCSS; overall, OS) were analyzed. Results: 481 consecutive BC patients, mostly node negative, with median age of 42 were treated between 2004 and 2014. Median tumor size was 1.48 cm and median IOERT collimator was 4 cm. After 25-day mean interval, HWBI was delivered. At a median follow-up of 9.6 years, there were 23 LRs (4.8 %, 9 of which were in the boost region). Ten-year LR cumulative incidence was 4.1 % (95 %CI, 2.5–6.3). Over time, local control rate decreased for Luminal A and HER2 positive with negative hormonal receptors, while remained steady for triple negative. At multivariate analysis, LR predictors included age < 40, extensive intraductal component and the use of 4-cm IOERT collimator size. Ten-year survival outcomes were as follows: DFS 80.0 % (95 % CI, 75.8–83.5), BCSS 97.5 % (95 % CI, 95.5–98.6 %), OS 96.5 % (95 % CI, 94.3–97.9). Luminal B HER2 negative had the worse survival outcomes. Perioperative complications were uncommon (16.4 %), acute toxicity was mild (<2% Grade 3), but moderate/severe fibrosis was described in 40.8 % of the cases. Cosmesis was scored as excellent/good in 86 % of the cases. Conclusions: ELIOT boost and HWBI achieved an excellent local control at the cost of tumor bed fibrosis. IOERT boost dose lower than 12 Gy is advisable.

Aims: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients. Conclusions: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reporte

Background: Postmastectomy radiotherapy (PMRT) with TomoHelicalTM (TH) or TomoDirectTM (TD) allows a uniform target coverage. In this study, we compare treatment plans using TD and TH in the setting of hypofractionated PMRT and immediate breast reconstruction. Material and methods: The TD-treatment plans of breast cancer patients treated between May 2016 and August 2019 were retrospectively selected. All the TD plans were re-planned on TH with the same prescription dose (40.05 Gy/15 fractions) and according to our dose/volume constraints. Data about the 2 treatment plans were compared with a focus on PTV coverage and all the organs at risk (OARs) constraints. Results: Fifty patients for a total number of 100 treatment plans (50 with TD and 50 re-planned with TH) were analyzed. All the median value in the TD PTV CHEST WALL plans fulfilled the predefined planning objectives, even though TH emerged as best for target coverage with statistically significant difference for V90%. TD provided the lowest V95% for the PTV SVC, but the median value was near to the recommended value of 90% (89.8 % vs 98.6% for TD and TH, respectively). Overall, TD reached the best OARs sparing. The main statistically significant differences with TH were for contralateral breast, ipsilateral and contralateral lung. All the other dose values for TH were higher than TD, but they fulfilled the recommended/acceptable predefined planning objectives. Conclusions: In the setting of PMRT, TD compared to TH reached an acceptable target volume coverage, with an optimal sparing of OARs.

Aim: To evaluate reconstruction failure (RF) rate in patients receiving implant-based immediate breast reconstruction (IBR) and hypofractionated (HF) postmastectomy radiation therapy (PMRT). Materials and methods: Stage II–III breast cancer patients, treated with HF-PMRT using intensity modulated radiotherapy were stratified in two groups according to IBR: single-stage direct-to-implant (DTI-group) and two-stage expander and implant (TE/I-group). Irradiated patients were matched with non-irradiated ones who underwent the same IBR during the same period. Prescription dose was 40.05 Gy/15 fractions to chest wall and infra/supraclavicular nodal region. Primary endpoint was RF defined as the need of major revisional surgery (MaRS) for implant removal or conversion to autologous reconstruction. Secondary endpoint was the rate of minor revisional surgeries (MiRS) including implant repositioning or substitution with another implant. Results: One hundred and seven irradiated patients (62 in TE/I-group, 45 in DTI-group) were matched with 107 non-irradiated subjects. Median follow-up was 4.2 years (0.1–6.1) In the TE/I setting, MaRS was performed in 8/62 irradiated patients (12.9%) of the irradiated TE/I group compared to 1/62 (1.6%) non-irradiated subjects (p = 0.015). In the DTI setting, MaRs occurred in 3/45 irradiated patients (6.7%) compared to 1/45 non-irradiated ones (2.2%) (p = 0.35). Overall MaRS rate was 10.3% in the irradiated group. MiRS was performed in 35.6% and 31.1% of the irradiated and non-irradiated DTI-groups (p = 0.65), respectively, and in 12.9% and 8.1% of the irradiated and non-irradiated TE/I groups (p = 0.38), respectively. Conclusions: Compared to the non-irradiated counterparts, the TE/I group showed higher rate of RF, while no statistically significant difference was observed for the DTI group. The use of hypofractionation and IMRT to implant-based IBR did not seem to increase the risk of RF which appeared to be in line with the literature.

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Background: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a “less intensive” or personalized approach. Patients and methods: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1–3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. Results: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33–76), with mostly pre-and peri-menopausal (65%) and stage I–II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5–100%; interquartile range, IQR: 87.5–100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73–92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77–94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3–4.7) two distant events were observed, and all patients were alive at the date of last visit. Conclusions: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated

We report on the second Assisi Think Tank Meeting (ATTM) on breast cancer which was held under the auspices of the European Society for RadioTherapy & Oncology (ESTRO). In discussing in-depth current evidence and practice it was designed to identify grey areas in diverse forms of the disease. It aimed at addressing uncertainties and proposing future trials to improve patient care. Before the meeting, three key topics were selected: 1) primary systemic therapy, mastectomy, breast reconstruction and post-mastectomy radiation therapy, 2) therapeutic options in ductal carcinoma in situ, and 3) therapy de-escalation in early stage breast cancer. Clinical practice in these areas was investigated by means of an online questionnaire. The time lapse period between the survey and the meeting was used to review the literature and on-going clinical trials. At the ATTM both were discussed in depth and research protocols were proposed.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.

Background: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. Patients and Methods: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. Results: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6–6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. Conclusions: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Aims: To report the long-term outcome of a single institution series of pure ductal carcinoma in situ (DCIS) treated with accelerated partial irradiation using intraoperative electrons (IOERT). Methods: From 2000 to 2010, 180 DCIS patients, treated with quadrantectomy and 21 Gy IOERT, were analyzed in terms of ipsilateral breast recurrences (IBRs) and survival outcomes by stratification in two subgroups. The low-risk group included patients who fulfilled the suitable definition according to American Society of Radiation Oncology (ASTRO) Guidelines (size ≤2.5 cm, grade 1–2 and surgical margins ≥3 mm) (Suitable), while the remaining ones formed the high-risk group (Non-Suitable). Results: Eighty-four and 96 patients formed the Suitable and Non-Suitable groups, respectively. In the whole population, the cumulative incidence of IBR at 5, 7 and 10 years was 19%, 21%, and 25%, respectively. In the Suitable group, the cumulative incidence of IBR remained constant at 11% throughout the years, while in the Non-Suitable group increased from 26% at 5 years to 36% at 10 years (p < 0.0001). When hormonal positivity and HER2 absence of expression were added to the selection of the Suitable group, the cumulative incidence of IBR dropped and stabilized at 4% at 10 years. None died of breast cancer. In the whole population, 5-year and 10-year overall survival rate was 98% and 96.5%, respectively, without any difference between the two groups. Conclusions: The overall and by group IBR rates were high and stricter criteria are required for acceptable local control for Suitable DCIS. Because of the concerns raised, IOERT should not be used in clinical practice.

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