Circulating Lymphocyte Counts Early During Radiotherapy are Associated with Recurrence in Pediatric Medulloblastoma

Abstract

Background Decreased peripheral lymphocyte counts are associated with outcome after RT in several solid tumors, though appear late during or after the radiation course and often correlate with other clinical factors. Here we investigate if absolute lymphocyte counts (ALC) are independently associated with recurrence in pediatric medulloblastoma early during RT. Methods We assessed 202 medulloblastoma patients treated between 2000 and 2016 and analyzed ALC throughout therapy, focusing on both early markers (ALC during week 1 – ALC wk1; grade 3+ Lymphopenia during week 2 – Lymphopenia wk2) and late markers (ALC nadir). Uni- and multivariable regressions were used to assess association of clinical and treatment variables with ALC and of ALC with recurrence. Results Thirty-six recurrences were observed, with a median time to recurrence of 1.6 years (Range 0.2-10.3) and 7.1 years median follow-up. ALC during RT was associated with induction chemotherapy (p<0.001), concurrent carboplatin (p=0.009), age (p=0.01) and high-risk status (p=0.05). On univariable analysis, high-risk disease (HR 2.0[1.06–3.9],p=0.03) and M stage≥1 (HR 2.2[1.1–4.4]) were associated with recurrence risk, as was lower ALC early during RT (ALC wk1 HR 0.28[0.12–0.65],p=0.003; Lymphopenia wk2 HR 2.27[1.1-4.6],p=0.02). Neither baseline ALC nor nadir correlated with outcome. These associations persisted when excluding carboplatin and pre-RT chemotherapy patients, and in the multivariable analysis accounting for confounders lymphocyte counts remain significant (ALC wk1 HR 0.23[0.09–0.57],p=0.002; Lymphopenia wk2 HR 2.3[1.1–4.8],p=0.03). Conclusion ALC during weeks 1 and 2 of RT was associated with recurrence and low ALC is an independent prognostic factor in medulloblastoma. Strategies to mitigate the risk of radiation-induced lymphopenia should be considered.