SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease

TLDR

The study compared chemotherapy plus focal radiotherapy versus reduced‑dose craniospinal irradiation alone in intracranial germinoma to assess equivalent outcomes and limit irradiation beyond the primary site. Localized germinoma patients were treated with either reduced‑dose CSI or two courses of carboplatin‑etoposide alternating with etoposide‑ifosfamide followed by local radiotherapy; metastatic patients received CSI with focal boosts, optionally preceded by chemotherapy. In localized germinoma, 5‑year event‑free and overall survival were similar between reduced‑dose CSI alone and combined chemotherapy‑radiotherapy, but progression‑free survival favored CSI alone (0.97 vs 0.88); relapse patterns showed ventricular recurrences with combined therapy and primary‑site recurrences with CSI alone, while metastatic patients achieved 0.98 event‑free and overall survival, indicating that reduced‑dose CSI alone is effective for both localized and metastatic disease.

Abstract

We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s). Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy. Patients with localized germinoma (n = 190) received either CSI alone (n = 125) or combined therapy (n = 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 ± 0.02 vs 0.88 ± 0.04; P = .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n = 45) had 0.98 ± 0.023 event-free and overall survival. Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. Reduced-dose craniospinal radiation alone is effective in metastatic disease.