Intensity-modulated ventricular irradiation for intracranial germ-cell tumors: Survival analysis and impact of salvage re-irradiation.

BACKGROUND AND PURPOSE: The roles of surgery, chemotherapy, and parameters of radiation therapy for treating very rare central nervous system germ cell tumors (CNS-GCT) are still under discussion. We aimed to evaluate the survival and recurrence patterns of patients with CNS-GCT treated with chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy. MATERIALS AND METHODS: We reviewed the clinical outcomes of 20 consecutive patients with CNS-GCT treated with chemotherapy and intensity-modulated radiation therapy from 2004 to 2014 in two partner institutions. RESULTS: Twenty children with a median age of 12 years were included (16 males). Sixteen tumors were pure germinomas, and 4 were non-germinomatous germ cell tumors (NGGCT). All patients were treated with intensity-modulated radiation therapy guided by daily images, and 70% with volumetric intensity-modulated arc radiotherapy additionally. The median dose for the whole-ventricle was 25.2 Gy (range: 18-30.6 Gy) and 36 Gy (range: 30-54 Gy) for the tumor bed boost. The median post-radiation therapy follow-up was 57.5 months. There were 3 recurrences (2 NGGCT and 1 germinoma that recurred as a NGGCT), with 1 death from the disease and the other 2 cases each successfully rescued with chemotherapy and craniospinal irradiation. The overall survival at 5 years was 95% and disease-free survival was 85%. CONCLUSIONS: The results of this study suggest that the combined use of chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy is effective for CNS-GCTs, especially pure germinomas. Even being rescued with craniospinal irradiation, the NGGCT cases have markedly worse prognoses and should be more rigorously selected for localized treatment.

Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study.

BACKGROUND: The treatment of central nervous system (CNS) germ cell tumors (GCT) remains controversial. The purpose of this study was to demonstrate efficacy of a chemotherapy only strategy, with less morbidity, when compared to regimens with irradiation. METHODS: Between January 2001 and December 2004 newly diagnosed patients with CNS GCT were treated with one of two risk-tailored chemotherapy regimens. Twenty-five patients aged 4 months to 24.5 years were stratified: Regimen A consisted of 4-6 cycles of carboplatin/etoposide alternating with cyclophosphamide/etoposide for low risk (LR) localized germinoma with normal cerebrospinal fluid (CSF) and serum tumor markers. Regimen B consisted of 4-6 cycles of carboplatin/cyclophosphamide/etoposide for intermediate-risk (IR) germinoma with positive human chorionic gonadotrophin-beta (HCGbeta) and/or CSF HCGbeta <50 mIU/ml and high-risk (HR) biopsy-proven non-germinomatous malignant elements (MMGCT) or elevated serum/CSF alpha-fetoprotein and/or HCGbeta serum/CSF >50 mIU/ml. RESULTS: Eleven patients were classified as LR, 2 IR, and 12 HR. Seventeen (68%) patients achieved complete radiographic and marker responses after two courses and 19 (76%) after four courses of chemotherapy. Eleven patients relapsed at a mean of 30.8 months; eight of them subsequently received irradiation. The 6-year event free and overall survival for the 25 patients was 45.6% and 75.3%, respectively. CONCLUSION: These intensive chemotherapy regimens proved less effective than irradiation containing regimens. Our results indicate that, at the present time, standard treatment for CNS GCT continues to include irradiation either alone or combined with chemotherapy for pure germinomas and with chemotherapy for those with MMGCT.

Intensity-modulated and 3D-conformal radiotherapy for whole-ventricular irradiation as compared with conventional whole-brain irradiation in the management of localized central nervous system germ cell tumors.

PURPOSE: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). METHODS AND MATERIALS: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a "boost" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. RESULTS: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. CONCLUSIONS: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.

Improvement in the outcome of children with germ cell tumors.

PURPOSE: To describe the clinical characteristics and estimate the survival of children and adolescents with germ cell tumors treated with cisplatin-based combination chemotherapy according to three different protocols in Brazil. METHODS: From 1983 to 1997, 106 patients were treated at the Hospital do Cancer, Sao Paulo for a diagnosis of germ cell tumor. We performed a retrospective review of the clinical and histopathological data to identify prognostic factors and evaluate their outcome. RESULTS: Patients were treated with only surgery (n = 32), surgery and radiotherapy (n = 1) and chemotherapy (n = 73). From 1983 to 1986 (period I), there were 30 patients and 21 received chemotherapy according to the modified VAB-6 protocol. Twenty-two of 35 patients registered between 1987 and 1991 (period II) were treated with EPO/VAC combination chemotherapy. From 1991 to 1997 (period III), there were 41 patients and 31 received chemotherapy according to the Brazilian TCG-91 protocol. Important prognostic factors included stage (P < 0.001), metastatic status (P < 0.001) and surgical procedure at diagnosis (P < 0.001). An incremental improvement in outcomes was noted across the periods of treatment (P = 0.070). Five-year OS was respectively 42.9 +/- 10.8%, 53.9 +/- 11.4% and 80.6 +/- 7.1% for periods I, II, and III for the patients who received chemotherapy. CONCLUSION: An improvement in the survival of children with germ cell tumors was achieved in the most recent trial (TCG-91) with a risk adapted approach incorporating only cisplatin and etoposide. These results indicate that in selected patients complex three-agent regimens may not be necessary to achieve long term survival.