Main Session
Sep 27
PQA 02 - Pediatric Cancer, Sarcoma and Cutaneous Tumors, Medical Education & Professional Development, and Health Services Research

2343 - Lymphopenia and Neutropenia During Radiotherapy Independently Predict Overall Survival in Chemotherapy-Naïve Patients with Molecularly-characterized Medulloblastoma

04:00pm - 05:00pm ET
Poster Hall - Exhibit Hall A
Screen: 10
POSTER

Presenter(s)

Isaac Lasko, MD Headshot
Isaac Lasko, MD - Loyola University Medical Center, Maywood, IL

I. Lasko1,2, T. Lin3, G. W. Robinson4, A. Gajjar4, A. Onar3, and C. L. Tinkle1; 1Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, TN, 2Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, 3Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN, 4Division of Neuro-Oncology, St. Jude Children’s Research Hospital, Memphis, TN

Purpose/Objective(s):

Medulloblastoma is risk-stratified by using clinical and molecular features to individualize treatment.(1) Lymphocyte counts during radiotherapy (RT) may also predict survival, however no such study has analyzed patients treated uniformly on a prospective trial, with molecularly-characterized disease, who are chemotherapy naïve, incorporating additional cell species such as neutrophils and monocytes.(2)

Materials/Methods:

This is an IRB-approved post-hoc analysis of patients treated on the phase III trial SJMB03. All patients underwent maximal safe resection, photon RT with craniospinal irradiation to either 23.4 Gy or 36-39.6 Gy and primary site boost to 55.8 Gy (with no concurrent chemotherapy), then chemotherapy.(1) Immunologic cell counts were retrospectively collected from weekly labs during RT, then log-transformed due to positive skew. Nadir was defined as the lowest count during RT. CTCAE 4.0 cytopenia grades were assessed. Cox proportional hazards models were performed for PFS and OS, incorporating methylation group and clinical risk group as covariates.

Results:

155 patients included had mean age 9.4 years, 36.1% female. Clinical risk groups were 64.5% average and 35.5% high. 76.1% underwent gross total resection, 18.7% near total resection, and 5.2% subtotal resection. 34.8% of patients had M+ disease. Methylation groups were 14.2% WNT, 17.4% SHH, 20.6% Group 3, 40.6% Group 4, and 7.1% unknown. In multivariable Cox models, independent predictors of OS in the overall cohort were ANC nadir (HR 0.39, p=0.005) and grade =4 lymphopenia at week 2 (HR 2.12, p=0.02), both of which also predicted for PFS. Models within each subgroup showed that in SHH, ANC nadir (HR 0.34, p=0.01) and grade =3 neutropenia (HR 11.95, p=0.005) predicted PFS while grade =4 lymphopenia at week 2 (HR 6.32, p=0.01) predicted OS. In Group 3, ANC nadir (PFS: HR 0.16, p=0.001; OS: HR 0.13, p=0.001) and grade =3 neutropenia (PFS: HR 11.95, p=0.005; OS: HR 4.34, p=0.02) predicted survival. In Group 4, grade =4 lymphopenia at week 2 (PFS: HR 4.59, p=0.03; OS: HR 4.59, p=0.01) and monocyte nadir (PFS: HR 0.34, p=0.01; OS: HR 0.38, p=0.04) predicted survival.

Conclusion:

Low nadirs and high-grade cytopenias of both neutrophils and lymphocytes during RT are independently associated with survival outcomes in MB. Prospective validation may facilitate incorporation of these variables into current risk-stratification strategies.

References:

  1. Gajjar A, Robinson GW, Smith KS, et al. Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). J. Clin. Oncol. 2021;39:822–835.
  2. Grassberger C, Shinnick D, Yeap BY, et al. Circulating Lymphocyte Counts Early During Radiation Therapy Are Associated With Recurrence in Pediatric Medulloblastoma. Int. J. Radiat. Oncol. Biol. Phys. 2021;110:1044–1052.