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Grazia Lazzari,1 Ilaria Benevento,1 Antonietta Montagna,1 Barbara D’Andrea,1 Giuseppina De Marco,2 Giovanni Castaldo,1 Antonella Bianculli,3 Raffaele Tucciariello,3 Vito Metallo,1 Angela Pia Solazzo1 1Radiation Oncology Unit, IRCCS, CROB, Rionero in Vulture, PZ, Italy; 2Radiation Oncology Unit, University Vanvitelli, Napoli, NA, Italy; 3Physic Unit, Radiation Oncology Unit, IRCCS, CROB, Rionero in Vulture, PZ, ItalyCorrespondence: Grazia Lazzari, Radiation Oncology Unit, IRCCS, CROB, Rionero in Vulture, PZ, 85028, Italy, Email lazzarigrazia@gmail.comPurpose: We administered a new breast cancer (BC) adjuvant therapy sequence that delivered postoperative radiotherapy (PORT) before chemotherapy (CT). Our aim was to assess the gain in time to start PORT and the G2–G3 acute–subacute toxicity rate of whole breast adjuvant hypofractionated radiotherapy (AH-RT) administered up-front to the third-generation adjuvant CT (A-CT) in high-risk nodal positive BC in a preliminary report at 2 years.Methods: This retrospective study analysed the duration of treatment and safety of AH-RT administered up-front to A-CT in high-risk nodal positive BC patients (pts). Data on 45 pts treated between 2022– 2023 were collected. All pts underwent the third-generation A-CT after AH-RT 15– 5 fractions with or without a boost. Acute toxicity was scored according to CTCAE v5.0 for skin, pulmonary, and cardiac adverse events. Univariate and multivariate analyses were conducted to assess significant prognosticators for skin/lung/heart acute toxicities in the AH-RT 5– 15 fractions arms and CT (p < 0.005).Results: A reduction in the time to PORT initiation and overall adjuvant treatment time was recorded. RT was initiated 5 median weeks after surgery, and A-CT was performed 9 median weeks after surgery. The median duration of the entire adjuvant treatment was 35 weeks after surgery. At 6 months mean follow-up, no significant differences in G2–G3 toxicity were noted between the different hypofractionated RT arms, irrespective of the CT schedules, irradiated volumes, or boost (SIB or sequential) in univariate and multivariate analyses. In the multivariate analysis, no significant effects in CT schedules and AH-RT 5– 15 arms for skin/lung acute toxicities (p = 0.077 and p = 0.68; 0.67 and 0.87, respectively) were recorded.Conclusion: As a new PORT approach in BC, AH-RT up-front to the third-generation A-CT appeared safe with a low acute toxicity profile, providing an advantage in shortening the time from surgery to PORT initiation and the overall adjuvant treatment time.Keywords: PORT, third-generation chemotherapy, hypofractionated radiotherapy |