Excellent survival outcomes and high response rates were associated with a regimen of neoadjuvant chemotherapy with or without second-look surgery before cranial irradiation in children with newly diagnosed nongerminomatous germ cell tumors.

The regimen should be included as a backbone for further studies, according to results from a phase 2 trial released online ahead of print in the Journal of Clinical Oncology.

In this trial, patients were treated with induction chemotherapy, which consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Those who demonstrated less than complete response were encouraged to undergo second-look surgery.


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Those who did not demonstrate complete or partial response with or without second-look surgery were administered high-dose chemotherapy, which consisted of thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation.

There were 102 patients in the study, treated between January 2004 and July 2008. The median age was 12 years; 76% were male; 53.9% had pineal region masses and 23.5% had suprasellar lesions.

Of those who received neoadjuvant therapy, 69% achieved complete or partial response; 5-year event-free survival was 84% ± 4% (SE); and overall survival was 93% ± 3%.

At a median follow-up of 5.1 years, 16 patients recurred or progressed, and seven died after relapse. None of the deaths were related to treatment.

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Ten patients experienced relapse at the site of primary disease and three at a distant site. One patient experienced relapse at both.

Progression was detected by marker increase in two patients. Increased serum alpha-fetoprotein was a negative prognostic value, whereas histologic subtype and increased beta-human chorionic gonadotropin were not signifinantly linked with negative outcomes. 

Reference

  1. Goldman S, Bouffet E, Fisher PG, et al. Phase II trial assessing the ability of neoadjuvant chemotherapy with or without second-look surgery to eliminate measurable disease for nongerminomatous germ cell tumors: a Children’s Oncology Group study. J Clin Oncol. 2015. [epub ahead of print]. doi: 10.1200/JCO.2014.59.5132.