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ACNS1123 was a Children’s Oncology Group Phase 2 study that was undertaken to determine whether irradiation could be safely reduced without impacting survival in a subgroup of NGGCT patients. Between May 2012-Jan 2017, 107 eligible patients were accrued to Stratum 1 (NGGCT stratum). Sixty-six (61.7%) patients achieved a complete/partial response (CR/PR) to induction chemotherapy and received 30.6Gy whole ventricular field irradiation followed by 54Gy tumor-bed boost achieving a 2-year progression-free survival rate of 89% (95% CI:81%-97%) and overall survival rate of 92% (95% CI:86%- 99%). Eight patients progressed; 6 had a spinal relapse and 2 patients had a local plus spinal relapse. Seven of eight patients had marker elevation at relapse and data was not available in one patient. At diagnosis, location was pineal in six cases, suprasellar in one, and bifocal in one case. Four patients had beta HCGβ and AFP elevation and two each had HCGβ and AFP elevation alone at diagnosis. Only two patients had HCGβ or AFP >1000 (HCGβ 3550 in one patient and AFP of 1340 in another). All eight patients were CR by markers; four had radiographic CR and four had a PR. Five patients had surgery at diagnosis: two had embryonal carcinoma, one germinoma, and two mixed germ cell tumor with malignant elements on histology. A consistent significant risk factor could not be identified to explain excess of spinal failures seen in our cohort.

ACNS0334, a Phase 3 trial, compared outcomes of children

BACKGROUND COG ACNS 1123 tested reduced radiotherapy (RT) for non-metastatic, non-germinomatous germ cell tumor (NGGCT) patients. The impact of central review on quality of RT and pattern of failure for NGGCT patients is evaluated. METHODS Patients who achieved a complete response (CR) or partial response (PR) to induction chemotherapy were eligible for reduced dose and field RT of 30.6 Gy whole ventricular field (WVI) and 54 Gy tumor-bed total dose. An online contouring atlas was available. Within three days of RT start, WVI plans were submitted for rapid central review. Within one week of RT completion, the complete RT record was submitted. Brain and spine MRIs of relapsed patients were centrally reviewed. RESULTS Between 5/2012–9/2016, 107 eligible patients were accrued and 70 met reduced RT criteria. Rapid RT review was performed for 49 (70%) of 70 patients. Forty-four (89.8%) required no modification. All modifications were completed and plans became compliant. Final central review was performed for 66 evaluable patients: 62 (94%) were per protocol; there were 2 major (1 dose and 1 target) and 2 minor deviations. Eight patients progressed; none had deviations. Median time to progression was 3.54 months (range: 1.7–19.1) from RT start. All failures had a spine component; two also had cranial component: one local progression (within the RT boost volume) and one leptomeningeal disease. CONCLUSION Providing an online contouring atlas and performing a rapid central review lead to high quality radiotherapy on this prospective trial. The deviations did not contribute to the pattern of failure.

BACKGROUND The objective of stratum 2 of COG ACNS1123 was to evaluate children and young adults (3–21 years) with localized central nervous system (CNS) germinoma and investigate whether simplified pre-irradiation chemotherapy followed by response based dose-reduced whole ventricular irradiation (WVI) would maintain a high progression-free survival (PFS) while reducing long term treatment burden. METHODS Pre-irradiation chemotherapy consisted of 4 cycles of carboplatin and etoposide every 21 days followed by response-based irradiation (XRT). Patients with a complete response (CR) to pre-XRT chemotherapy received 18Gy WVI + 12Gy boost to the tumor bed. Patients with partial response (PR) but less than 1.5 cm residual proceeded to 24Gy WVI + 12Gy boost. All patients were also enrolled on COG ALTE07C1 to prospectively evaluate and longitudinally model the cognitive, social and behavioral functioning. RESULTS During a total accrual time of 45.5 months from 05/2012 to 06/2018, 137 eligible patients were enrolled. Median age was 14.09 years (4.95–21.46), 73% were male, and 45.26% had elevated βhCG in serum and/or cerebrospinal fluid. Twenty-nine patients (21.17%) did not have tissue biopsy. Eleven patients underwent second-look surgery; 7 had mature teratoma and 4 had non-viable tumor. Eighty-one patients (59.13%) had a CR. There were 4 relapses in patients receiving 18Gy WVI + boost, but no deaths. No unexpected treatment-related events were observed. The estimated 3-year PFS was 94.4 ±2.7% among 74 evaluable subjects. CONCLUSION This study shows promise in XRT reduction for patients with localized CNS germinoma and CR. Long-term survival outcomes and ALTE07C1 data are being evaluated.