Acute Toxicological Outcomes of Postmastectomy Radiotherapy in Node Positive Breast Cancer with or without Internal Mammary Nodal Irradiation: Preliminary Results of POTANTIAL Trial

Abstract

<h3>Purpose/Objective(s)</h3> To report acute toxicological outcomes of an ongoing prospective, multicenter, phase III, randomized controlled trial (NCT04320979) designed to evaluate the safety and efficacy of internal mammary node irradiation (IMNI) after mastectomy for high-risk node-positive breast cancer. <h3>Materials/Methods</h3> Eligible patients were randomly assigned (1:1) to receive IMNI (IMNI arm) or not (no IMNI arm). The prescribed dose was either 50 Gy in 25 fractions (conventional fractionated radiotherapy, CFRT) or 43.5 Gy in 15 fractions (hypofractionated radiotherapy, HFRT) Acute toxicities were evaluated weekly during radiotherapy (RT) and at 1 week, 2 weeks, 3 months, 6 months after RT according to Common Toxicity Criteria for Adverse Events v3.0. Clinically significant toxicities were defined as ³ grade 3 dermatitis, esophagitis, myelosuppression and ³ grade 2 pneumonitis. The mean dose, maximum dose, and V10–V50 of ipsilateral lung and neighboring esophagus were evaluated. Chi-square test was performed to compare the differences between IMNI and no IMNI arms. <h3>Results</h3> Between May 8, 2020, and June 8, 2021, 219 patients treated in 14 centers were analyzed with minimum follow-up of 6 months. There were 114 (52.1%) and 105 (47.9%) patients in no IMNI and IMNI arm. Chest wall ± IMN was irradiated with intensity-modulated RT (IMRT) in 196 (89.5%) patients and electrons in 23 (10.5%) patients. Supra/infraclavicular ± axillary nodal regions were irradiated with IMRT technique in all patients. There were 147 (67.1%) patients treated with HFRT and 72 (32.9%) patients treated with CFRT. Among patients treated with HFRT and CFRT, the differences were significant in mean lung dose (13.1 Gy vs 13.4 Gy, p=.048 and 14.4 Gy vs 15.2 Gy, p=.009), V10 of lung (37.0% vs 37.9%, p=.024 and 39.0% vs 41.0%, p=.011), but not significant in mean esophagus dose (14.7 Gy vs 15.3 Gy, p=.447 and 16.9 Gy vs 18.8 Gy, p=.257), V10 of esophagus (58.0% vs 62.1%, p=.260 and 59.0% vs 77.4%, p=.059) between no IMNI and IMNI arm. There were no statistically significant differences in ³ grade 3 dermatitis (1.8% vs 1.0%, p = 1.000), ³ grade 3 esophagitis (0.9% vs 0.0%, p=1.000), or ³ grade 2 pneumonitis (3.8% vs 2.0%, p=.684) between no IMNI and IMNI arm. 108 (49.3%) patients had ≥ grade 3 myelosuppression, including 107 (48.9%) lymphopenia, 6 (2.8%) leucopenia, and no thrombocytopenia. The incidence of ≥ grade 3 myelosuppression were significantly higher in IMNI arm than no IMNI arm (56.2% vs 42.1%, p=.037). <h3>Conclusion</h3> IMNI caused acceptable dermatitis, esophagitis and pneumonitis in breast cancer after mastectomy. Higher risk of myelosuppression, mainly lymphopenia, was found in IMNI arm.