|Title||Phase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|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|
|Journal||J Clin Oncol|
|Date Published||2019 12 01|
|Keywords||Adolescent, 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 (ClinicalTrials.gov 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; ClinicalTrials.gov 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 Journal||J Clin Oncol|
|PubMed Central ID||PMC6900864|
|Grant List||P30 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