Phase II study of preirradiation chemotherapy for CNS germ cell malignancies: Long-term complications.

Abstract

2005 Background: This prospective multicenter phase II study was designed to assess the response rate and survival of patients with CNS germ cell malignancies treated with etoposide and cisplatin chemotherapy followed by limited dose and field radiation, as well as to document the long term complications including endocrine and cognitive complications associated with this approach to treatment. Methods: Thirty-four patients aged 6 to 24 who met eligibility criteria including histologically confirmed CNS germ cell tumors were enrolled and received four cycles at three- weekly intervals of cisplatin 20 mg/m2/day followed by etoposide 100 mg/m2/day over days 1-5 followed by radiation therapy. 59% (or 20/34) were germinomas. 5 of 20 patients with germinomas had disseminated disease, and all the non-germinomas were localized. Results: 20 of 20 patients (100%) with germinomas achieved complete response vs. 12 of 14 (86%) with nongerminomas. After median follow up time of 10.2 years, 19 of 20 (95%) and 12 of 14 (86%) of patients with germinomas and nongerminomas are alive, respectively. Interestingly all the patients who required hormone replacement at the time of last follow-up had evidence of one or more deficiencies at initial enrollment. Of these deficiencies, hypothyroidism and diabetes insipidus were the most common, 17/20 and 18/20 respectively. Similarly the majority of patients who presented with extra- ocular muscle impairment continued to have evidence of dysfunction at long term follow-up 12/15. Neurovascular complications were seen in 3/34 (8%), one with transient ischemic attacks secondary to radiation induced vasculitis, one with massive stroke and one with incidentally discovered intracranial aneurysm. Neurocognitive effects were minimal with 2/34 (5%) having documented cognitive difficulties and residing in a nursing home, and 5/34 (15%) patients noted to have memory issues, of which one had normalization at the time of last follow-up. Conclusions: Chemotherapy followed by radiation is highly effective with low incidence of neurovascular and subjective neurocognitive complications in patients with CNS germ cell malignancies. No significant financial relationships to disclose.