Background: Recent data found a correlation between lymphopenia occurring early during craniospinal irradiation (CSI) and risk of disease recurrence in newly-diagnosed childhood medulloblastoma. 1 However, the population included patients that received myelosuppressive chemotherapy prior to or during RT. Here we investigate the effect of lymphopenia during RT in patients with newly-diagnosed pediatric medulloblastoma who did not receive myelosuppressive chemotherapy with RT. Procedure: We analyzed 54 patients with newly-diagnosed medulloblastoma (ages 2-21 years) treated between 1997-2013 with CSI. Log-rank tests were used to determine survival differences, and Cox proportional hazards regression was used to assess associations between patient characteristics and lymphopenia with disease recurrence risk. Results: 78% of patients (40/51) had grade ≥3 lymphopenia by RT week 3; 49% (23/47) improved to grade ≤2 lymphopenia by week 5. Similarly, the lowest median absolute lymphocyte count (ALC) occurred during RT week 3. Sixteen of 54 (30%) patients recurred an average of 30.2 months post-diagnosis. There was higher risk of disease recurrence in patients with grade ≥3 lymphopenia during weeks 4 (log-rank p=0.015; Cox p=0.03) and 5 (log-rank p=0.0009; Cox p=0.004) of RT. Recurrence-free survival was lower in patients with ALC Conclusions: Lymphopenia during RT weeks 4 and 5 correlates with increased risk of tumor recurrence in pediatric patients with newly-diagnosed medulloblastoma. Future studies should correlate baseline numbers of tumor-infiltrating lymphocytes with risks of lymphopenia during RT and tumor recurrence.

Purpose: Pediatric patients with medulloblastoma in LMICs are most treated with 3D conformal photon craniospinal irradiation (CSI), a time-consuming, complex treatment to plan, especially in resource-constrained settings. Therefore, we developed and tested a 3D conformal CSI autoplanning tool for varying patient lengths. Methods and Materials: Autocontours were generated with a deep learning model trained:tested (80:20 ratio) on 143 pediatric medulloblastoma CT scans (patient ages, 2-19 years, median=7 years). Using the verified autocontours, the autoplanning tool generated 2 lateral brain fields matched to a single spine field, an extended single spine field, or 2 matched spine fields. Additional spine sub-fields were added to optimize the corresponding dose distribution. Feathering was implemented (yielding 9-12 fields) to give a composite plan. Each planning approach was tested on 6 patients (ages, 3-10 years). A pediatric radiation oncologist assessed clinical acceptability of each autoplan. Results: The autocontoured structures’ average Dice similarity coefficient ranged from 0.65-0.98. The average V95 for the brain/spinal canal for single, extended, and multi-field spine configurations was 99.9±0.06%/99.9±0.10%, 99.9±0.07%/99.4±0.30%, and 99.9±0.06%/99.4±0.40%, respectively. The average maximum dose across all field configurations to the brainstem, eyes (L/R), lenses (L/R) and spinal cord were 23.7±0.08 Gy, 24.1±0.28 Gy, 13.3±5.27 Gy, 25.5±0.34 Gy, respectively (prescription=23.4 Gy/13 fractions). Of the 18 plans tested, all were scored as clinically acceptable as-is or clinically acceptable with minor, time-efficient edits preferred or required. No plans were scored as clinically unacceptable. Conclusion: The autoplanning tool successfully generated pediatric CSI plans for varying patient lengths in 3.50 ± 0.4 minutes on average, indicating potential for an efficient planning aid in resource-constrained settings.

Background: Pediatric brain tumor survivors are at risk for poor social outcomes. It remains unknown whether cognitive sparing with proton radiotherapy (PRT) supports better social outcomes relative to photon radiotherapy (XRT). We hypothesized that survivors treated with PRT would outperform those treated with XRT on measures of cognitive and social outcomes. Further, we hypothesized that cognitive performance would predict survivor social outcomes. Procedure: Survivors who underwent PRT (n=38) or XRT (n=20) participated in a neurocognitive evaluation >1 year post-radiotherapy. Group differences in cognitive and social functioning were assessed using ANCOVA. Regression analyses examined predictors of peer relations and social skills. Results: Age at evaluation, radiation dose, tumor diameter, and sex did not differ between groups (all p>0.05). However, XRT participants were younger at diagnosis (XRT M=5.0 years, PRT M=7.6 years) and further out from radiotherapy (XRT M=8.7 years, PRT M=4.6 years). The XRT group performed worse than the PRT group on measures of processing speed (p=0.01) and verbal memory (p<0.01); however, social outcomes did not differ by radiation type. The proportion of survivors with impairment in peer relations and social skills exceeded expectation (2(1)=38.67, p<0.001; 2(1)=5.63, p<0.05), and verbal memory approached significance as a unique predictor of peer relations (t=-2.01, p=0.05). Total tumor RT dose significantly predicted social skills (t=-2.23, p<0.05). Conclusions: Regardless of radiation modality, survivors are at risk for social challenges, with one-quarter being socially excluded or undervalued. Deficits in verbal memory may place survivors at particular risk. Results support monitoring of cognitive and social functioning throughout survivorship.