METHODS
This retrospective study was approved by our Institutional Review Board
(IRB) prior to data abstraction or analysis. A waiver of informed
consent was granted by the IRB as the study was entirely retrospective.
The study population included patients 2 to 21 years old at tumor
diagnosis treated for newly-diagnosed medulloblastoma at our tertiary
children’s hospital between 1997-2013 with therapy that included CSI.
Patients treated on clinical research studies SJMB96 (NCT00003211) or
SJMB03 (NCT00085202)11,12, and those treated for
medulloblastoma outside of the context of a clinical trial were eligible
for inclusion in our analyses. All patients treated prior to 2007
received photon beam RT while those treated in or after 2007 received
proton beam RT.
Patients were classified as having high-risk disease, prior to the
advent of molecular risk stratification, if they had metastatic disease
(M stage) or post-operative residual disease >1.5
cm2; patients not meeting these criteria were
classified as having clinically standard-risk disease.
The following data were abstracted from the medical record for each
eligible patient: name, date of birth, gender, date of tumor diagnosis,
age at diagnosis, tumor pathology, date and extent of surgical
resection, M stage, start and end dates of RT, dose and modality (photon
or proton beam) of RT, complete blood count (CBC) results at the start
of/during/immediately after RT, post-RT chemotherapy regimen used, date
of first recurrence (to allow calculation of recurrence-free survival
(RFS), and survival status (alive or dead).
Weekly lymphocyte counts were analyzed both as a continuous variable and
graded per the National Cancer Institute’s Common Terminology Criteria
for Adverse Events (CTCAE) version 5.0: grade 1—absolute lymphocyte
count (ALC) < lower limit of normal -
0.8x109/L, grade 2—ALC < 0.8 -
0.5x109/L, grade 3—ALC < 0. 5-
0.2x109/L, and grade 4—ALC <
0.2x109/L.
Descriptive statistics were used to characterize the study population.
Kaplan-Meier survival curves were constructed, and the log-rank test was
used to determine differences in survival curves by key clinical
variables. Cox proportional hazards regression was used to assess the
associations (hazards ratio and 95% confidence intervals) between
patient characteristics and lymphopenia during RT with risk of disease
recurrence, unadjusted and adjusted for risk group. A p-value of 0.05
was used as the cut-off for statistical significance. All analyses were
conducted in Stata (SE version 17; Stata Corp, College Station, TX).