Multi-Institutional Data Collection and Analysis via the Pediatric Proton/Photon Consortium Registry

Care of patients with proton therapy has increased in the past decade. It is important to report on outcomes and disease specific utilization of particle therapy. In this chapter, we review our experience in developing a registry for pediatric patients treated with radiation to assess outcomes and provide a platform for shared research interests

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

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

An Update From the Pediatric Proton Consortium Registry

Background/objectives The Pediatric Proton Consortium Registry (PPCR) was established to expedite proton outcomes research in the pediatric population requiring radiotherapy. Here, we introduce the PPCR as a resource to the oncology community and provide an overview of the data available for further study and collaboration. Design/methods A multi-institutional registry of integrated clinical, dosimetric, radiographic, and patient-reported data for patients undergoing proton radiation therapy was conceived in May 2010. Massachusetts General Hospital began enrollment in July of 2012. Subsequently, 12 other institutions joined the PPCR and activated patient accrual, with the latest joining in 2017. An optional patient-reported quality of life (QoL) survey is currently implemented at six institutions. Baseline health status, symptoms, medications, neurocognitive status, audiogram findings, and neuroendocrine testing are collected. Treatment details of surgery, chemotherapy, and radiation therapy are documented and radiation plans are archived. Follow-up is collected annually. Data were analyzed 25 September, 2017. Results: A total of 1,854 patients have consented and enrolled in the PPCR from October 2012 until September 2017. The cohort is 55% male, 70% Caucasian, and comprised of 79% United States residents. Central nervous system (CNS) tumors comprise 61% of the cohort. The most common CNS histologies are as follows: medulloblastoma (n = 276), ependymoma (n = 214), glioma/astrocytoma (n = 195), craniopharyngioma (n = 153), and germ cell tumors (n = 108). The most common non-CNS tumors diagnoses are as follows: rhabdomyosarcoma (n = 191), Ewing sarcoma (n = 105), Hodgkin lymphoma (n = 66), and neuroblastoma (n = 55). The median follow-up is 1.5 years with a range of 0.14 to 4.6 years. Conclusion: A large prospective population of children irradiated with proton therapy has reached a critical milestone to facilitate long-awaited clinical outcomes research in the modern era. This is an important resource for investigators both in the consortium and for those who wish to access the data for academic research pursuits

Evolution of Proton Radiotherapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry.

INTRODUCTION Increasing concern that brainstem toxicity incidence after proton radiotherapy (PRT) might be higher than with photons led to a 2014 XXXX (XX) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the XXXX (XXXX). METHODS This prospective multicenter cohort study gathered data from patients under age 22 enrolled on the XXXX, treated between 2002-2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint guidelines by treatment era, histology, and extent of surgical resection. RESULTS A total of 467 patients with evaluable PRT plans were reviewed. Median age was 7.1 years (range: <1-21.9), 63.0% (n=296) were male, 76.0% (n=357) were white, and predominant histologies were medulloblastoma (55.0%, n=256) followed by ependymoma (27.0%, n=125). Extent of resection was mainly gross total resection (GTR) (67.0%, n=312), followed by subtotal resection (STR) or biopsy (20.0%, n=92). The XX brainstem constraint metrics most often exceeded were the goal D50% of 52.4 GyRBE (43.3%, n=202) and maximal D50% of 54 GyRBE (12.6%, n=59). The compliance rate increased after the new guidelines (2002-2014: 64.0% vs. 2015-2019: 74.6%, p=0.02), except for ependymoma (46.3% pre vs. 50.0% post guidelines, p=0.86), presenting lower compliance (48.8%) in comparison to medulloblastoma/PNET/pineoblastoma (77.7%), glioma (89.1%), and ATRT (90.9%) (p<0.001). Degree of surgical resection did not affect compliance rates (GTR/NTR 71.0% vs. STR/biopsy 72.8%, p=0.45), even within the ependymoma subset (GTR/NTR 50.5% vs. STR/biopsy 38.1%, p=0.82). CONCLUSION Since the publication of the XX guidelines, the pediatric proton community has implemented more conservative brainstem constraints in all patients except those with ependymoma, irrespective of residual disease after surgery. Future work will evaluate if this change in practice is associated with decreased rates of brainstem toxicity