Phase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.

TitlePhase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.
Publication TypeJournal Article
Year of Publication2019
AuthorsFangusaro 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
JournalJ Clin Oncol
Date Published2019 12 01
KeywordsAdolescent, Age Factors, Antineoplastic Combined Chemotherapy Protocols, Central Nervous System Neoplasms, Chemoradiotherapy, Child, Child, Preschool, Cranial Irradiation, Disease Progression, Female, Humans, Male, Neoplasm Recurrence, Local, Neoplasms, Germ Cell and Embryonal, Progression-Free Survival, Radiation Dosage, Risk Factors, Time Factors, United States, Young Adult

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% ± 4.04% and 92.4% ± 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 α-fetoprotein and β-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.

Alternate JournalJ Clin Oncol
PubMed ID31545689
PubMed Central IDPMC6900864
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
U10 CA180886 / CA / NCI NIH HHS / United States
U10 CA180899 / CA / NCI NIH HHS / United States
UL1 TR003167 / TR / NCATS NIH HHS / United States