Finlay, Jonathan L.

Abstract Background Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx). Methods A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. Results A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease. Conclusions GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

Purpose Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor. Materials and Methods A standardized data sheet was provided to treating physicians listing the reports that were to be sent to the registry for abstraction. Follow-up information was sought twice yearly. Results Information was complete for 42 patients. Median age at diagnosis was 24 months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors were infratentorial; 26 were supratentorial. Twenty patients (48%) received a primary complete resection. Primary therapy included chemotherapy in all patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or progressive disease was reported in nine and 19 patients, respectively. Twenty-seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one patient died of toxicity. Fourteen patients (33%) show no evidence of disease (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the median event-free survival is 10 months. Conclusion Aggressive therapy has prolonged the natural history in a subset of children. Prospective multi-institutional and national clinical trials designed specifically for AT/RT are needed. Enrollment onto the AT/RT registry should be continued.