Radiation-Induced Lymphopenia in Patients with Breast Cancer after Mastectomy: Results from Chinese POTENTIAL Trial

Abstract

<h3>Purpose/Objective(s)</h3> POTENTIAL is an ongoing prospective, multicenter, phase III, randomized trial investigating whether internal mammary nodal irradiation (IMNI) improves prognosis in high-risk breast cancer with positive axillary nodes after mastectomy. This study aimed to assess the incidence and risk factors of radiation-induced lymphopenia (RIL) in patients from the POTENTIAL trial, and the trends of lymphocyte recovery from RIL were also evaluated. <h3>Materials/Methods</h3> Eligible patients were randomly assigned to receive IMNI (IMNI group) or not (no IMNI group). The prescribed dose is either 50 Gy in 25 fractions (conventional fractionated radiation therapy, CFRT) or 43.5 Gy in 15 fractions (hypofractionated radiation therapy, HFRT). Peripheral lymphocyte count (PLC) tests were performed before radiation therapy (RT), weekly during RT, at 1, 2 weeks, 3, 6 months and 1 year after RT. The lowest PLC (nadir-PLC) during RT or within two weeks after RT was graded according to CTCAE version 5.0. PLCs were summarized as means ± standard deviation and compared by the t test. <h3>Results</h3> A total of 431 patients treated in 15 Chinese institutions were prospectively evaluated, including 214 (49.7%) patients in IMNI group and 217 (50.3%) in no IMNI group. 291 (67.5%) patients received HFRT and 140 (32.5%) received CFRT. Chest wall ± IMN was irradiated with intensity-modulated RT (IMRT) in 397 (92.1%) patients and electrons in 34 (7.9%) patients. Supra/infraclavicular axillary nodal region was irradiated with IMRT technique in 431 (100%) patients. All patients received a median of 8 cycles of chemotherapy, including neoadjuvant chemotherapy in 153 (35.5%) patients. 52 (12.1%) patients had ≥ Grade 1 lymphopenia before RT. A total of 417 (96.8%) patients developed RIL during RT or within two weeks after RT, grade 1 in 37 (8.6%) patients, grade 2 in 190 (44.1%) patients, grade 3 in 187 (43.4%) patients, and grade 4 in 3 (0.7%) patients. Mean PLC at 1 year after RT was still significantly lower than mean baseline PLC (1.35±0.32 vs. 1.58±0.46, P=0.001). Among 187 patients who had grade ≥ 3 RIL, most (118/122, 96.7%) of them recovered with grade ≤ 2 lymphopenia at 3 months after RT. The mean nadir-PLC was significantly higher in the no IMNI group than in the IMNI group (0.58±0.23 vs. 0.52±0.19, p=0.005). The incidence of grade ≥ 3 RIL was similar in the IMNI and no IMNI group (48.6% vs. 45.3%, p=0.061). In both HFRT and CFRT groups, the PLC declined steadily during RT but started to recover at 1 week after RT. The mean nadir-PLC was significantly higher in the HFRT group than in the CFRT group (0.57±0.22 vs. 0.51±0.18, p=0.011), and the incidence of grade ≥ 3 RIL was significantly higher in the CFRT than in the HFRT group (53.6% vs. 39.50%, p=0.006). Left-sided tumors, low baseline PLC, CFRT and IMRT techniques were risk factors for developing grade ≥ 3 RIL. <h3>Conclusion</h3> The incidence of RIL was high in breast cancer patients receiving IMRT after mastectomy. The risk of grade ≥ 3 RIL is lower with HFRT than with CFRT. IMNI may not increase the risk of grade ≥ 3 RIL.