Survival after chemotherapy and stem cell transplant followed by delayed craniospinal irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients

Abstract

Pediatric embryonal brain tumor patients treated with craniospinal irradiation (CSI) are at risk for adverse effects, with greater severity in younger patients. Here we compare outcomes of CSI vs. high-dose chemotherapy (HD), stem cell transplant (SCT) and delayed CSI in newly diagnosed patients. Two hundred one consecutive patients treated for medulloblastoma (72 %), supratentorial primitive neuroectodermal tumor (sPNET; 18 %) or pineoblastoma (10 %) at two institutions between 1988 and 2014 were retrospectively identified. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by log-rank tests. Adjuvant CSI regimens were used for 56 % of patients (upfront-CSI), and HD/SCT regimens were used in 32 % of patients. HD/SCT patients were significantly younger than those receiving upfront-CSI (2.9 vs. 7.8 years; P < 0.0001). There were no differences in metastases, extent of resection, or CSI dose between upfront-CSI and HD/SCT patients, but median follow-up was shorter in the HD/SCT group (6.2 vs. 3.9 years; P = 0.007). There were no significant outcome differences between upfront-CSI and HD/SCT patients who received CSI as a prophylaxis or following relapse (OS 66 % vs. 61 %, P = 0.13; PFS 67 % vs. 62 %, P = 0.12). Outcomes were equivalent when restricting analyses to HD/SCT patients who received prophylactic CSI prior to relapse (OS 66 % vs. 65 %, P = 0.5; PFS 67 % vs. 74 %, P = 0.8). At last follow-up, 48 % of HD/SCT patients had received neither definitive nor salvage radiotherapy. In this retrospective cohort, outcomes with adjuvant HD/SCT followed by delayed CSI are comparable to upfront-CSI for carefully surveyed pediatric embryonal brain tumor patients. Future prospective studies are required to validate this finding, and also to assess the impact of delayed CSI on neurocognitive outcomes.

Misactivation of Hedgehog signaling causes inherited and sporadic cancers

“…Moreover, survivors are debilitated by significant therapy-associated toxicity, chief among which are neurocognitive deficits, endocrine and growth abnormalities, and an increased risk of secondary malignancy (82)(83)(84). To reduce the burden of treatment-associated toxicity of radiotherapy, high-dose chemotherapy with hematopoietic stem cell rescue and other risk-adapted therapeutic strategies have been used, particularly in young patients (85)(86)(87)(88). However, outcomes remain suboptimal and patients are frequently afflicted with significant therapy-associated sequelae.…”

Post-Surgical Prognosis of Patients with Pineoblastoma: A Systematic Review and Individual Patient Data Analysis with Trends over Time

“…Recent studies by Mynarek et al, and Handsford et al similarly found an age of three years to be critically predictive of worse prognosis [ 7 , 64 ]. A 2017 study by Raleigh et al in very young pediatric embryonal brain tumor patients found that post-surgical RT delivered before disease recurrence resulted in better outcomes than did RT at the time of recurrence [ 65 ]. Thus, it is possible that the poor outcomes are driven, at least in part, by the omission or delay of RT in this patient population due to concern for its deleterious toxicities in the very young.…”

Embryonal Tumors

“…Forty-eight percent of high-dose CTx patients received neither definitive nor salvage radiotherapy. This cohort, however, included various diagnoses as medulloblastoma, pineoblastoma, and stPNET (Raleigh et al 2017). By contrast, for pineoblastoma use of HD-CTx showed limited impact on survival (Mynarek et al 2017).…”