A Phase 2 Trial of Response-Based Radiation Therapy for Localized Central Nervous System Germ Cell Tumors: Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors

Abstract

Purpose: Children's Oncology Group study ACNS1123 tested the efficacy of reduced dose and field of radiation therapy (RT) for patients with localized nongerminomatous germ cell tumors (NGGCT) who achieved a complete (CR) or partial response (PR) to chemotherapy. Here, we evaluate the quality of RT and patterns of failure for patients eligible for reduced RT in this phase 2 trial.

Methods and materials: Patients with localized NGGCT with CR/PR after induction chemotherapy received reduced RT to 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed total dose. An atlas was provided to assist with complex RT volumes. Early interventional review was performed for the initial RT plan. Complete RT plans for all patients and images of relapsed patients were centrally reviewed at completion of therapy.

Results: Between May 2012 and September 2016, 107 eligible patients were enrolled and 66 achieved a CR/PR after induction chemotherapy (± second-look surgery) and were eligible for reduced RT. Median follow-up was 4.4 years. Median age was 11.0 years (3.7-21.6), and 75% were male. Progression-free survival and overall survival at 4 years were 87.9% ± 4.0% and 92.4% ± 3.3% for 66 evaluable patients, respectively. Eight patients relapsed: 6 with isolated spinal relapse and 2 with disease in the brain and spine. After central review, 62 (94%) patients had RT targets contoured and dose delivered per protocol. None of the patients with deviations (n = 4) have progressed.

Conclusions: Patterns of failure suggest the spine is at risk for recurrence for patients with localized NGGCT who receive reduced RT after a CR/PR to induction chemotherapy. Although survival data are encouraging, the pattern of failure has influenced the next prospective trial design. RT compliance was excellent despite complexity of radiation volumes, suggesting that providing visual guidance in the form of an online atlas contributes to higher quality RT plans.

Fig. 1.

Patient 5 with pineal primary tumor location progressed in the spine. Representative sagittal contrast enhanced thoracolumbar spine magnetic resonance imaging (MRI) demonstrating progression with a lumbar mass.

Fig. 2.

Patient 2 with bifocal suprasellar and pineal location primaries with locoregional and distant progression. Axial fluid-attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) of patient 2 demonstrating (a) intraventricular progression, (b) hypothalamic progression, and (c) prepontine space progression. (d) Sagittal computed tomography (CT) of the head demonstrating area of progression (dark blue contour) with radiation therapy (RT) dose coregistered (green color wash = 30.6 Gy whole ventricular irradiation [WVI], red color wash = 54 Gy primary site boost, red contour line: primary site boost volume)

Fig. 3.

Patient 6 with pineal primary location with multifocal leptomeningeal progression. Axial contrast-enhanced brain magnetic resonance imaging (MRI) demonstrating areas of progression (a) in the right temporal area (light blue contour), midfrontal area (light green contour) with radiation therapy (RT) dose coregistered (mint blue color wash = 18 Gy, purple color wash = 30.6 Gy, yellow color wash = 54 Gy primary site boost), and (b) bilateral cerebellar recurrence = light blue contour. (c) Contrast-enhanced sagittal thoracolumbar spine MRI demonstrating thecal sac leptomeningeal disease.