Phase II Trial of Primary Chemotherapy Followed by Reduced-Dose Radiation for CNS Germ Cell Tumors

Abstract

Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.

Pre‐radiation chemotherapy with response‐based radiation therapy in children with central nervous system germ cell tumors: A report from the Children's Oncology Group

“…Ten of 11 evaluable patients with low-risk germinoma achieved CR or PR on central review, which compares favorably to other series [3,12,13,15,16,19,35,38,[40][41][42]. In the most recent series 10 of 11 patients with pure germinomas were disease-free, whereas 5 of 11 patients with elevated CSF HCG relapsed, including 2 with HCG 101-233 mIU/ml, after chemotherapy plus local RTof 24 Gy [15].…”

“…While 5% of germinomas may contain syncytiotrophoblastic giant cells that secrete HCG [34], controversy exists regarding the prognostic significance of modest elevations of HCG [35]. Buckner et al noted excellent response and survival in three patients with CSF HCG 79.6-147 mIU/ml [16], whereas Balmaceda et al noted a trend toward increased PD (P 0.06) in 29 patients [23]. It remains unclear whether patients¼with pure germinoma and HCG 50-2,000 mIU/ml (e.g., Patient 24) should be classified as high-risk patients, but our intent was to follow the guidelines of previous European series [5,14,25,33,[35][36][37].…”

“…It is possible that patients with high HCG are more likely to relapse if local control is minimized. However, modest reductions in RT have not had a significant effect on event-free survival (EFS) [12][13][14][15][16]35,38]. Lowering radiation dose by 5 Gy (45 Gy + 30 Gy neuraxis) was reported in the German ′89 study to have a negligible effect (EFS 87% for 49 patients) [35].…”

“…Lowering radiation dose by 5 Gy (45 Gy + 30 Gy neuraxis) was reported in the German ′89 study to have a negligible effect (EFS 87% for 49 patients) [35]. Several other studies have reported decreased radiation dose or field after neoadjuvant chemotherapy [12][13][14]16,38]. The largest recent French trial noted response to pre-radiation chemotherapy in all 38 evaluable patients with a 3-year EFS of 96.4% for 57 patients [33,36].…”

“…The biologic disparity between pure germinomas and nongerminomatous tumors is also supported by the difference in mean age at diagnosis (adolescent versus middle school years), with nongerminomatous tumors having a more heterogeneous appearance with spread to distant structures [1][2][3][4][5]. With the goal of reducing potential late sequelae of cranial radiation [6][7][8][9][10][11], platinum-based regimens have sought to decrease radiation dose by administering chemotherapy before reduced radiation [12][13][14][15][16]. It is not yet known whether this approach will lead to similar cure rates with decreased toxicity.…”