Patterns of treatment failure in infants with primitive neuroectodermal tumors who were treated on CCG-921: A phase III combined modality study

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Abstract
To analyze patterns of treatment failure in infants with primitive neuroectodermal tumors (PNETs) who were treated primarily with chemotherapy in a large multi-institutional study. Sixty-five prospectively staged patients with PNET confirmed by central pathology review, who were 18 months or younger were treated on Children's Cancer Group Study 921 (CCG-921) primarily with chemotherapy. Forty-six patients had posterior fossa (PF) primary tumors and 19 patients had supratentorial (ST) primaries. Patterns of sites of initial treatment failure were analyzed and compared to failure patterns of 180 older children who had PF-PNETs, and 44 older children with ST-PNETs who were treated on the same protocol. The entire cohort of younger patients fared much worse than those older than 18 months. Cumulative 5-year relapse incidence (+/-SE) for younger patients with PF-PNETs was 64.5 +/- 8.9% for patients without metastases (M0) compared to 71.4 +/- 13.4% for patients with metastases (M+). The cumulative 5-year relapse incidences for younger patients with ST-PNETs were 64.3 +/- 13.7% for M0 patients compared to 100 +/- 33.3% for M+ patients. Relapses in these patients occurred within 2 years. The overall treatment failure rate was significantly higher for younger compared to older patients with PF-PNET and ST-PNET. There was no statistically significant difference in relapse patterns between patients with PF primary tumors and ST primaries when stratified by stage. There was no statistically significant difference in relapse patterns between M0 and M+ patients. All patients had a high risk of recurrence at primary tumor site. Younger patients who had PF primary tumors without metastasis at presentation were significantly more likely to relapse in PF than older patients. Younger patients were at significant risk of relapse in the spine, but none had it as the sole site of first relapse. Despite aggressive chemotherapy, younger children with PNETs have high rates of treatment failure and fare worse than high-risk, older patients with PF-PNETs, indicating the need to maximize local, regional, and systemic therapies.