Ute Bartels1, Arzu Onar-Thomas2, Sunita K Patel3, Dennis Shaw4, Jason Fangusaro5, Girish Dhall6, Mark Souweidane7, Aashim Bhatia8, Leanne Embry9, Christine L Trask10, Erin S Murphy11, Shannon MacDonald12, Shengjie Wu2, James M Boyett2, Sarah Leary11, Maryam Fouladi13, Amar Gajjar14, Soumen Khatua15. 1. Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada. 2. Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 3. City of Hope National Medical Center, Departments of Population Sciences and Supportive Care Medicine, Duarte, California, USA. 4. Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio, USA. 5. Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, USA. 6. Children's of Alabama, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA. 7. Department of Neurological Surgery, Weill Cornell Medicine and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 8. Department of Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, New York, USA. 9. Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. 10. Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. 11. Department of Pediatrics, Children's Hospital and Regional Medical Center, Seattle, Washington, USA. 12. Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. 13. Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA. 14. Department of Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee, USA. 15. Department of Pediatric Hematology-Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
BACKGROUND: The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. METHODS: Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. RESULTS: One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. CONCLUSIONS: While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.
BACKGROUND: The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. METHODS: Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. RESULTS: One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. CONCLUSIONS: While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.
Authors: Donald J Mabbott; Brenda J Spiegler; Mark L Greenberg; James T Rutka; Douglas J Hyder; Eric Bouffet Journal: J Clin Oncol Date: 2005-04-01 Impact factor: 44.544