Clinical investigation: brain
Radiation therapy for intracranial germ cell tumors

Presented as an oral presentation at the American Society for Therapeutic Radiology and Oncology, San Francisco, CA, November 4–8, 2001.
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Abstract

Purpose

To review the combined experiences of University of California, San Francisco, and Stanford University Medical Center in the treatment of intracranial germ cell tumors (GCT) and to assess the impact of craniospinal radiation (CSI) on patterns of relapse, progression-free survival (PFS), and overall survival (OS).

Patients and methods

Ninety-three patients received radiation for newly diagnosed intracranial GCTs, including 49 germinomas, 16 nongerminomatous GCTs (NGGCT), and 28 with no biopsy. Median follow-up for surviving patients was 4.5 years (range 0.25–34). Tests for variables correlating with OS and PFS were conducted using Cox proportional hazards model.

Results

Five-year PFS and OS rates were 60% ± 15% and 68% ± 14% for patients with NGGCT and 88% ± 5% and 93% ± 4% for those with germinoma. Of 6 patients with localized NGGCT who did not receive CSI, 1 experienced an isolated spinal recurrence but was salvaged. Of 41 patients with localized germinoma, 6 who received CSI and 35 who did not, no isolated spinal cord relapses occurred. Twenty-one patients with localized germinoma received neither CSI nor whole brain radiation. Of these, none of 18 with ventricular radiation relapsed. One of 3 patients with primary tumor radiation relapsed intracranially but had only received 11 Gy at initial treatment. On multivariate analysis, germinoma histology but not CSI correlated with improved PFS and OS.

Conclusion

CSI is not indicated in the treatment of localized germinomas. For patients with localized germinomas treated with radiation alone, we recommend ventricular irradiation followed by primary tumor boost to a total of 45–50 Gy.

Introduction

Intracranial germ cell tumors (GCT) represent 3–11% of pediatric and 1% of adult brain tumors (1). Intracranial GCTs comprise two distinct histologic groupings: germinomas are the most common histologic subtype, whereas nongerminomatous germ cell tumors (NGGCT) represent one-third of intracranial GCTs and consist of embryonal carcinoma, endodermal sinus (yolk sac) tumor, choriocarcinoma, teratoma, and GCT of mixed cellular origin 1, 2. Historically, radiation alone, frequently encompassing a large treatment volume, has constituted the gold standard of treatment for intracranial GCTs 1, 3, 4, 5. However, the morbidity of radiation therapy in children 6, 7, 8, 9, 10, 11, particularly craniospinal irradiation (CSI), has prompted many investigators to explore approaches that reduce the volume and dose of radiotherapy while preserving high cure rates.

The development of strategies to reduce the morbidity of radiotherapy has been hampered by an absence of randomized trials comparing treatment approaches. As pediatric consortia and cooperative groups prepare to design a randomized, phase III trial for children with intracranial GCTs, we sought to use the combined experiences of the University of California, San Francisco (UCSF), and Stanford University Medical Center (SUMC) to shed light on key treatment issues. In particular, historical differences in the radiation volumes prescribed in the two institutions provide a cohort of patients that allow assessment of the utility of CSI, because a greater proportion of patients treated at SUMC received CSI. Furthermore, we sought to elucidate the role of chemotherapy and the appropriate volume and dose of radiation in the treatment of intracranial GCTs.

Section snippets

Patients and methods

We conducted an historical cohort study of 93 patients with confirmed or suspected intracranial GCTs treated in the departments of radiation oncology at either SUMC or UCSF, between 1968 and 2001. Excluded patients had received prior radiation, did not receive radiation as part of their initial treatment regimen, or had extracranial metastases at the time of diagnosis.

Histologic confirmations of GCT were obtained in 65 of 93 cases (70%). Forty-nine patients (53%) had germinomas confirmed by

Pfs and OS by histology

Five-year PFS rates were 60% ± 15% for patients with biopsy-proven NGGCTs compared with 88% ± 5% for those with biopsy-proven germinomas (Fig. 1a). Five-year OS rates were 68% ± 14% and 93% ± 4% for patients with NGGCTs and germinomas, respectively (Fig. 1b). Patients treated without a biopsy had 5-year PFS and OS rates of 61% ± 11% and 85% ± 8%, respectively (Figs. 1a and 1b). Within each histologic subtype, PFS and OS rates were not substantially different for the subgroup of patients

Discussion

Controversy remains in the treatment of intracranial GCTs, due largely to the complexity and rarity of these tumors, coupled with a dearth of prospective randomized trials. Our data, in conjunction with the current literature, support distinct therapeutic approaches for germinomas and NGGCTs. The only factor predictive of superior clinical outcome in this study was the diagnosis of germinoma, as compared with NGGCT. Although many published studies group germinoma with NGGCT, their distinct

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    Supported in part by North American Brain Tumor Consortium grant NCI U01-CA62399 (D.A.H-K.), NIH grant M01 RR01271, Pediatric Clinical Research Center (D.A.H-K.), and CA 82103 (K.R.L. and M.S.B.).

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