Phase II trial of response-based radiation therapy for patients with localized CNS nongerminomatous germ cell tumors: A Children's Oncology Group Study Journal Article

Authors: Fangusaro, J.; Wu, S.; MacDonald, S.; Murphy, E.; Shaw, D.; Bartels, U.; Khatua, S.; Souweidane, M.; Lu, H. M.; Morris, D.; Panigrahy, A.; Onar-Thomas, A.; Fouladi, M.; Gajjar, A.; Dhall, G.
Article Title: Phase II trial of response-based radiation therapy for patients with localized CNS nongerminomatous germ cell tumors: A Children's Oncology Group Study
Abstract: PURPOSE Stratum 1 of ACNS1123 ( identifier: NCT01602666), a Children's Oncology Group phase II trial, evaluated efficacy of reduced-dose and volume of radiotherapy (RT) in children and adolescents with localized nongerminomatous germ cell tumors (NGGCTs). The primary objective was to evaluate the impact of reduced RT on progression-free survival (PFS) with a goal of preserving neurocognitive function. PATIENTS AND METHODS Patients received six cycles of chemotherapy with carboplatin and etoposide alternating with ifosfamide and etoposide, as used in the Children's Oncology Group predecessor study (ACNS0122; identifier: NCT00047320). Patients who achieved a complete response (CR) or partial response (PR) with or without second-look surgery were eligible for reduced RT, defined as 30.6 Gy whole ventricular field and 54 Gy tumor-bed boost, compared with 36 Gy craniospinal irradiation plus 54 Gy tumor-bed boost used in ACNS0122. RESULTS A total of 107 eligible patients were enrolled. Median age was 10.98 years (range, 3.68 to 21.63) and 75% were male. Sixty-six of 107 (61.7%) achieved a CR or PR and proceeded to reduced RT. The 3-year PFS and overall survival and standard error values were 87.8% 6 4.04% and 92.4% 6 3.3% compared with 92% and 94.1%, respectively, in ACNS0122. There were 10 recurrences, prompting early study closure; however, after a retrospective central review, only disease in eight of 66 (12.1%) patients eligible for reduced RT subsequently progressed; six patients had distant spinal relapse alone and two had disease with combined local plus distant relapse. Serum and CSF a-fetoprotein and b-human chorionic gonadotropin levels were not associated with PFS. CONCLUSION Patients with localized NGGCT who achieved a CR or PR to chemotherapy and received reduced RT had encouraging PFS similar to patients in ACNS0122 who received full-dose craniospinal irradiation. However, the patterns of failure were distinct, with all patients having treatment failure in the spine. © 2019 by American Society of Clinical Oncology.
Keywords: adolescent; adult; cancer survival; child; controlled study; preschool child; school child; treatment response; treatment failure; major clinical study; overall survival; neutropenia; cancer recurrence; cancer combination chemotherapy; drug efficacy; cancer radiotherapy; comparative study; radiation dose; prospective study; carboplatin; progression free survival; multiple cycle treatment; phase 2 clinical trial; anemia; etoposide; leukopenia; thrombocytopenia; relapse; ifosfamide; central nervous system tumor; febrile neutropenia; lymphocytopenia; hyponatremia; cerebrospinal fluid; clinical evaluation; cognition; second look surgery; non seminomatous germinoma; alpha fetoprotein; chorionic gonadotropin; hypernatremia; craniospinal irradiation; human; male; female; priority journal; article; central nervous system nongerminomatous germ cell tumor
Journal Title: Journal of Clinical Oncology
Volume: 37
Issue: 34
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2019-12-01
Start Page: 3283
End Page: 3290
Language: English
DOI: 10.1200/jco.19.00701
PUBMED: 31545689
PROVIDER: scopus
PMCID: PMC6900864
Notes: Source: Scopus
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