Xrt-07. late-onset lymphopenia during craniospinal radiation is associated with an increased risk of tumor recurrence in newly-diagnosed pediatric medulloblastoma

Abstract A recent publication (PMID 33556478) demonstrated an increased risk of tumor recurrence in patients with newly-diagnosed pediatric medulloblastoma who have decreased lymphocyte counts early in their course of craniospinal radiation (CSI) (weeks 1 and 2). We set out to confirm this data in an independent population of pediatric patients with newly-diagnosed medulloblastoma. We analyzed 54 patients treated from 1997-2013. All patients that received radiation in or after 2007 received protons. Per standard of care, patients with clinically high-risk disease were treated with 36-39.6 Gy CSI while patients with standard-risk disease received 23.4 Gy. Total dose to the primary site of disease ranged from 54-55.8 Gy. The mean patient age at diagnosis was 8 years. 16/54 (30%) patients developed a recurrence at an average of 30.2 months after diagnosis. Lymphocyte counts were analyzed both as a continuous variable and as CTCAE v5.0 grades (grades 0-2 lymphopenia (ALC >/=500) compared to grade 3 and 4 (ALC<500/mm3)) using Cox regression. As expected, patients with M+ disease had increased risk of tumor recurrence (p=0.001). There was no correlation between risk of tumor recurrence and early lymphopenia (weeks 0-3 radiation). However, in both weeks 4 and 5 of radiation, decreases in ALC closely correlated with an increased risk of tumor recurrence (week 4 p=0.038, week 5 p=0.042). Similarly, patients with grade 3/4 lymphopenia at weeks 4 and 5 of radiation had an increased risk of tumor recurrence (week 4 p=0.040, week 5 p=0.008) compared to those with grade 0-2 lymphopenia. In summary, both M+ disease and lymphopenia during weeks 4 and 5 of radiation correlated with an increased risk of tumor recurrence in pediatric medulloblastoma.