Stewart Goldman1, Eric Bouffet2, Paul G Fisher2, Jeffrey C Allen2, Patricia L Robertson2, Paul J Chuba2, Bernadine Donahue2, Cynthia S Kretschmar2, Tianni Zhou2, Allen B Buxton2, Ian F Pollack2. 1. Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA. sgoldman@luriechildrens.org. 2. Stewart Goldman, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Eric Bouffet, The Hospital for Sick Children, Toronto, ON, Canada; Paul G. Fisher, Lucile Packard Children's Hospital Stanford, Palo Alto; Cynthia S. Kretschmar, Children's Hospital Los Angeles, Los Angeles; Tianni Zhou, California State University, Long Beach; Allen B. Buxton, Children's Oncology Group, Monrovia, CA; Jeffrey C. Allen and Bernadine Donahue, New York University Langone Medical Center, New York, NY; Patricia L. Robertson, University of Michigan C.S. Mott Children's Hospital, Ann Arbor; Paul J. Chuba, St. John Hospital and Medical Center, Grosse Pointe, MI; and Ian F. Pollack, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.
Abstract
PURPOSE: This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. PATIENTS AND METHODS: Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. RESULTS: The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. CONCLUSION: Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies.
PURPOSE: This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. PATIENTS AND METHODS: Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. RESULTS: The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. CONCLUSION: Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies.
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