Pediatric Cancer

SS 14 - Pediatrics 2

99 - A Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT): A Children's Oncology Group (COG) Study. Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors

Monday, October 22
10:45 AM - 10:55 AM
Location: Room 008

A Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT): A Children’s Oncology Group (COG) Study. Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors
E. S. Murphy1, J. Fangusaro2, G. Dhall3, U. Bartels4, M. Fouladi5, D. Shaw6, S. Khatua7, C. Williams Hughes8, A. Panigraphy9, M. Souweidane10, D. Morris11, H. M. Lu12, A. Gajjar13, A. Onar14, S. Wu13, D. A. Haas-Kogan15, and S. MacDonald12; 1Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 2Lurie Children’s Hospital of Chicago, Chicago, IL, 3Children's Hospital Los Angeles, Los Angeles, CA, 4The Hospital for Sick Children, Toronto, ON, Canada, 5Cincinnati Children's Hospital Medical Center, Cincinatti, OH, 6Seattle Childrens Hospital, seattle, OR, 7The University of Texas MD Anderson Cancer Center, Houston, TX, 8Childrens Oncology Group, Littleton, CO, 9Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, 10Memorial Sloan Kettering Cancer Center, New York, NY, 11University of North Carolina at Chapel Hill, Chapel Hill, NC, 12Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 13St. Jude Children's Research Hospital, Memphis, TN, 14St. Jude Childrens Research Hospital, Memphis, TN, 15Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA

Purpose/Objective(s): Results from COG ACNS0122 utilizing a combination of chemotherapy and craniospinal irradiation (CSI) demonstrated excellent 5-year outcomes for non-germinomatous germ cell tumors (NGGCTs). The majority of failures for non-metastatic NGGCTs were local on that trial. COG ACNS 1123 tested the efficacy of reduced dose and field radiation therapy (RT) for non-metastatic patients who achieved a complete (CR) or partial response (PR) to chemotherapy. Here, we evaluate the quality of RT and patterns of failure for NGGCT patients eligible for reduced dose and field radiation therapy on this prospective phase II trial.

Materials/Methods: Patients with localized NGGCT received alternating cycles of carboplatin/etoposide and ifosfamide/etoposide (6 total) followed by response evaluation. Those who became tumor marker negative and achieved radiological CR or PR were eligible for reduced RT to 30.6 Gy whole ventricular field (WVI) and 54 Gy tumor-bed total dose as compared to 36 Gy CSI and 54 Gy total dose on ACNS0122. An online expert consensus contouring atlas was made available. All RT treatment plans were centrally reviewed for target and normal tissue contours and radiation therapy dose. Brain and spine MRIs of relapsed patients were centrally reviewed. RT doses to areas of recurrence were calculated.

Results: Between 5/2012-9/2016, 107 eligible patients were accrued and 66 patients met criteria to proceed to reduced dose and volume RT. Median age was 11 years (range: 4- 22) and 75% were male. 8 of 66 patients progressed. Median follow up for patients without progression was 25 months from RT completion. The 2-year progression-free survival (PFS) was 89% (95% CI: 81%-97%) and overall survival was 92% (95% CI: 86%- 99%). After central review, 62 (94%) patients had RT targets and normal structures contoured and dose delivered per protocol; there were 2 major and 2 minor deviations. None of the patients with deviations have progressed. Four (50%) patients had recurrence at end of treatment and median time to progression was 3.5 months (range: 1.7-19.1) from RT start. Importantly, all failures had a distal component, completely out of the RT field. Six patients had spine only progression and 2 had progression in brain and spine. Of those with intracranial relapse, one recurred locally and dose to the area of the recurrence was: V54 = 53%, V30.6 = 100%, mean 52 Gy, maximum 56 Gy, and minimum 31 Gy. The second patient had leptomeningeal relapse and all areas of recurrent disease had received a mean dose of 10 Gy or less.

Conclusion: Providing an online contouring atlas can lead to high quality RT targeting and dose delivery on prospective trials. Patterns of failure suggest the spine/thecal sac is at risk for recurrence for localized NGGCT patients who receive WVI plus primary site boost RT after achieving a CR/PR to induction chemotherapy. The early survival data are encouraging, although the distant failure rate remains concerning. Longer follow-up of the ACNS1123 cohort may better inform future recommendations.

Author Disclosure: E.S. Murphy: None. J. Fangusaro: Pediatric Advisory Board; Celgene Corporation. G. Dhall: None. U. Bartels: None. D. Shaw: None. S. Khatua: None. C. Williams Hughes: None. A. Panigraphy: None. H. Lu: Employee; Massachusetts General Hospital. S. Wu: None. D. Haas-Kogan: Research Grant; Novartis. Clinical Advisory Board; Cellworks. S. MacDonald: None.

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99 - A Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT): A Children's Oncology Group (COG) Study. Patterns of Failure and Radiation Dosimetry for Nongerminomatous Germ Cell Tumors



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