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Breast cancer adjuvant hypofractionated radiotherapy (AH-RT) in 15 or 5 fractions (frs) has become a new standard of care with advantages like better treatment compliance, reduced costs and RT waiting list. Conventionally adjuvant chemotherapy (A-CT) is delivered before radiotherapy (RT). Nowadays its course has been lengthened due to customized novel drugs combination, leading to a prolonged time to start RT. We started a mono-institutional study on AH-RT in upfront to A- CT in high risk breast cancer to assess toxicity and survival outcomes. Here in an interim analysis on acute toxicity.

In 2022 a mono-institutional study started to assess feasibility of AH-RT given in upfront to A-CT in high risk breast cancer patients (pts). Up to now 45 patients have been enrolled. Mean age was 55 years (30-70). BCS occurred in 30 pts and mastectomy in 15 pts. All pts had A-CT; NACT was delivered in 10 pts.  AH-RT - 15 frs was given to 28 pts. Supraclavicular area (SVC) and internal mammary chain (IMC) in 10 pts , chest wall (CW) in 5 pts were included . AH-RT - 5 fr (8 SVC area and 5 CW ) was delivered to 17 pts. AH-RT-15 consisted of 2.67 Gy/fr/40.05 Gy (SIB 3,2 Gy/fr/48 Gy). AH-RT - 5 was 5.7 Gy/fr /28.5 Gy (SIB 6.4 Gy/fr/ 32 Gy ) and 5.4 Gy /fr /27 Gy on nodal areas. RT started after 45 mean days from surgery (30-55) soon after the pathological result. A-CT was defined on the basis of Oncotype, molecular phenotype and nodal involvement and started after 10 mean days (8-15) RT off. Long term A-CT consisted of 4-12 cycles of Taxane-antracicline-anti-Her2 -TDM-1 combination or long term capecitabine. Follow up was conducted after 2 weeks off RT, 1 month, 3-6-9 months during chemotherapy. Acute toxicity was scored according CTCAE v5 for skin, pulmonary and cardiac adverse events. Pearson’s covariance multivariate analysis was conducted to assess as significant prognosticators for skin / lung/heart  acute toxicities the AH-RT 5/15 frs  arms and chemotherapy ( p <0.005).

At 4 months mean follow up no patient experienced ≥G3 acute toxicity. No significant differences in toxicity were found between the different RT arms. G2 skin toxicity was experienced in 8 % of pts with SIB and 5 % without SIB. G1-G2 skin toxicity and dysphagia were recorded in pts treated on SVC(3%). Pneumonitis G2 occurred in ICM pts in the Taxane and TDM1 arms (3%). Multivariate analysis confirmed no significant effect for CT and AH-RT arm for skin /lung acute toxicities ( p= .077) and irradiated volumes ( p= .065).

AH-RT upfront to A-CT seems to be feasible with a low acute toxicity prophile during long course A-CT, showing no significant differences in toxicity for skin and lung between two AH-RT arms , chemotherapy and irradiated volumes. Longer follow-up is needed to evaluate late toxicity, local control and survival outcomes to create a new standard of care.