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To assess the efficacy, and the acute and late toxicity of hypofractionated radiotherapy (Hypo‐RT), and the impact of age and comorbidities on disease progression and death in elderly breast cancer (BC) patients. Women aged ≥65 years who received Hypo‐RT (42.4 Gy in 16 fractions, plus a boost for high‐risk patients) were considered for the present analysis. Competing risk analysis was used to estimate the 5‐year cumulative incidence of BC progression and BC‐related death, calculating the adjusted subhazard ratios (SHR) with 95% confidence intervals (95%CI) in relation to age, hypertension‐augmented Charlson Comorbidity Index (hCCI), tumor characteristics, and chemotherapy. The sample included 794 patients with a median age of 74 years (range 65‐91 years). At the baseline, 70% of these patients had at least one comorbidity. With a median follow‐up of 48.3 months, the 5‐year cumulative incidence of BC progression and BC‐related death was 6.7% (95%CI 4.8%‐9.2%) and 2.3% (95%CI 1.2%‐3.9%), respectively. Old age (≥80 years) and a high burden of comorbidity (hCCI ≥ 2) were independently associated with BC progression. Hypo‐RT is safe in elderly BC patients, but age and comorbidities influence BC progression. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Objective: After breast conservative surgery (BCS) and whole-breast radiotherapy (WBRT), the use of boost irradiation is recommended especially in patients at high risk. However, the standard technique and the definition of the boost volume have not been well defined. Methods: We retrospectively compared an anticipated pre-operative photon boost on the tumour, administered with low-dose fractionated radiotherapy, and neoadjuvant chemotherapy with two different sequential boost techniques, administered after BCS and standard adjuvant WBRT: (1) a standard photon beam (2) and an electron beam technique on the tumour bed of the same patients. The plans were analyzed for the dosimetric coverage of the CT-delineated irradiated volume. The minimal dose received by 95% of the target volume (D95), the minimal dose received by 90% of the target volume (D90) and geographic misses were evaluated. Results: 15 patients were evaluated. The sequential photon and electron boost techniques resulted in inferior target volume coverage compared with the anticipated boost technique, with a median D95 of 96.3% (range 94.7–99.6%) and 0.8% (range 0–30%) and a median D90 of 99.1% (range 90.2–100%) and 54.7% (range 0–84.8%), respectively. We observed a geographic miss in 26.6% of sequential electron plans. The results of the anticipated boost technique were better: 99.4% (range 96.5–100%) and 97.1% (range 86.2–99%) for median D90 and median D95, respectively, and no geographic miss was observed. We observed a dose reduction to the heart, with left-sided breast irradiation, using the anticipated pre-operative boost technique, when analyzed for all dose–volume parameters. When compared with the sequential electron plans, the pre-operative photon technique showed a higher median ipsilateral lung Dmax. Conclusion: Our data show that an anticipated pre-operative photon boost results in a better coverage with respect to the standard sequential boost while also saving the organs at risk and consequently fewer side effects. Advances in knowledge: This is the first dosimetric study that evaluated the association between an anticipated boost and neoadjuvant chemotherapy treatment. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is clinically the most aggressive breast cancer (BC) subtype. There is an urgent need for effective therapies for patients with TNBC. Recent findings confirm the important role of factors related to the immune system in the clinical outcome and response to treatment of TNBC patients. Avelumab selectively binds to PDL1, and competitively blocks its interaction with anti-programmed death 1 (anti-PD-1) antibodies. Unlike anti-PD-1 antibodies, which target T-cells, avelumab targets tumor cells, and is therefore expected to have fewer side effects, including a lower risk of Immune-Related Adverse Events (irAEs). Uncertainties remain regarding a potential synergy resulting in increased toxicities by combining radiotherapy and immune-checkpoint inhibitors (ICIs). Effects of concomitant ICIs with thoracic radiotherapy on pulmonary toxicities is not currently known. There are no published data available on the effects of combining anti-PD-L1 with adjuvant radiotherapy (RT) for BC in a clinical setting. We reported a preliminary experience on the first patient treated at the National Cancer Institute of Milan with the association of avelumab and concomitantly RT for TNBC. [ABSTRACT FROM AUTHOR]

Purpose: To examine interobserver variability between the radiation oncologist (RTO) and the radiation therapist (RTT) in delineating the tumor bed (TB) in early breast cancer (BC)., Methods: We retrospectively analyzed patients who received a radiotherapy boost to the TB. In a first group, the clinical target volume (CTV) for the boost was the surgical bed, defined by using surgical clips. In a second group, the CTV was defined by identifying a seroma cavity or a metallic find on the scar. These contours were compared in terms of volume, number of slices, and Dice similarity coefficient (DSC)., Results: Forty patients were assessed: 20 had surgical clips (group 1) while the other 20 had none (group 2). There was no difference in the number of slices contoured by the 2 operators for group 1, but a statistically significant difference emerged in the volumes: the RTT identified a TB that was a mean 45% smaller than the one identified by the RTO. Random differences were found between the 2 operators for group 2. The TBs delineated for this group were significantly larger ( P <0.05) than those identified by the RTT for group 1. The mean Dice value between the RTO's and the RTT's TBs was 0.69±0.07 (range 0.53-0.81) for group 1 and 0.37±0.18 (range 0-0.58) for group 2 ( P <0.05)., Conclusions: This study showed that the use of clips coincided with less interoperator variability. With appropriate training, the RTT may play an important part in the multidisciplinary radiotherapy team.

Triple-negative breast cancer (TNBC) is clinically the most aggressive breast cancer (BC) subtype. There is an urgent need for effective therapies for patients with TNBC. Recent findings confirm the important role of factors related to the immune system in the clinical outcome and response to treatment of TNBC patients. Avelumab selectively binds to PDL1, and competitively blocks its interaction with anti-programmed death 1 (anti-PD-1) antibodies. Unlike anti-PD-1 antibodies, which target T-cells, avelumab targets tumor cells, and is therefore expected to have fewer side effects, including a lower risk of Immune-Related Adverse Events (irAEs). Uncertainties remain regarding a potential synergy resulting in increased toxicities by combining radiotherapy and immune-checkpoint inhibitors (ICIs). Effects of concomitant ICIs with thoracic radiotherapy on pulmonary toxicities is not currently known. There are no published data available on the effects of combining anti-PD-L1 with adjuvant radiotherapy (RT) for BC in a clinical setting. We reported a preliminary experience on the first patient treated at the National Cancer Institute of Milan with the association of avelumab and concomitantly RT for TNBC.

Aim: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer., Material and Methods: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method., Results: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs., Conclusions: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Purpose: To evaluate the dosimetric coverage of axillary levels I, II, and III obtained with standard whole breast irradiation in 1 to 2 positive sentinel lymph nodes (SLNs) patients not submitted to axillary lymph nodes dissection (ALND), and to compare the lymph nodes areas coverage obtained with 3D conformal radiation therapy, intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT)., Methods: Patients with 1 to 2 positive SLNs undergoing breast-conserving therapy, without ALND, were included in the analysis. For each patient, 3 treatment plans were performed: a 3D conventional tangential plan, a static IMRT plan, and a volumetric IMRT, designed to encompass the entire breast parenchyma. The volumes of axillary levels I, II, and III receiving 90% and 95% (V90, V95) of the whole breast prescribed dose were evaluated. Dose-volume histograms were compared by means of the Friedman test., Results: Ten patients were enrolled. All defined breast volumes received &gt;95% of the prescribed dose with the 3 techniques. Median V95 for axillary level I was 26.4% (range 4.7%-61.3%) for 3D plans, 8.6% (range 0.64%-19.1%) for static IMRT plans, and 2.6% (range 0.4%-4.7%) for volumetric IMRT plans (p&lt;0.001). Median V95 for axillary level II was 5.4% (range 0%-14.6%), 1.9% (range 0%-15%), and 2.6% (range 0.4%-4.7%) for 3D, static IMRT, and volumetric IMRT, respectively (p&lt;0.001)., Conclusions: Results of our analysis showed that standard 3D tangential whole breast irradiation failed to deliver a therapeutic dose to axillary levels I and II. The coverage was even lower using static and volumetric IMRT techniques.