دورية أكاديمية
MBCL-16. EFFICACY OF CARBOPLATIN GIVEN CONCOMITANTLY WITH RADIATION AND ISOTRETINOIN AS A PRO-APOPTOTIC AGENT IN MAINTENANCE THERAPY IN HIGH-RISK MEDULLOBLASTOMA: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP
| العنوان: | MBCL-16. EFFICACY OF CARBOPLATIN GIVEN CONCOMITANTLY WITH RADIATION AND ISOTRETINOIN AS A PRO-APOPTOTIC AGENT IN MAINTENANCE THERAPY IN HIGH-RISK MEDULLOBLASTOMA: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP |
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| المؤلفون: | Leary, Sarah, Packer, Roger, Jaju, Alok, Heier, Linda, Burger, Peter, Smith, Kyle, Michalski, Jeff, Li, Yimei, Billups, Catherine, Hwang, Eugene, Gajjar, Amar, Pollack, Ian, Fouladi, Maryam, Northcott, Paul, Olson, James |
| المصدر: | Neuro-Oncology ; volume 22, issue Supplement_3, page iii391-iii391 ; ISSN 1522-8517 1523-5866 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Neurology (clinical), Oncology |
| الوصف: | BACKGROUND Metastasis, residual disease, and diffuse anaplasia are high-risk features in medulloblastoma. METHODS This was a randomized phase 3 study. Patients age 3–21 years with high-risk medulloblastoma received (+/-) daily carboplatin with 36Gy craniospinal radiation and weekly Vincristine followed by six cycles of maintenance chemotherapy with Cisplatin, Cyclophosphamide and Vincristine (+/) 12 cycles of isotretinoin during and following maintenance. The primary endpoint was event-free survival, with exact log-rank test to compare arms. Retrospective molecular analysis included DNA methylation and exome sequencing. RESULTS Of 294 medulloblastoma patients enrolled, 261 were eligible by central review of radiology and pathology, median age 8.6 years (range 3.3–21.2), 70% male, 189 (72%) with metastatic disease, 58 (22%) with diffuse anaplasia, 14 (5%) with >1.5cm2 residual disease. The 5-year EFS and OS for all subjects was 63%+4 and 73%+3, respectively. Isotretinoin randomization was closed due to futility. 5-year EFS was 66 + 5 with carboplatin versus 59 + 5 without (p=0.11), with effect exclusively observed in Group 3 subtype: 73%+8 with carboplatin versus 54%+9 without (p<0.05). Overall survival differed by molecular subgroup (p=0.006): WNT 100%, SHH 54%+11, Group 3 74%+6, Group 4 77%+5 at 5 years. MYC amplification or isochromosome 17 were unfavorable in Group 3 (p=0.029). Chromosome 11 loss or chromosome 17 gain were favorable in group 4 (p<0.001). No survival difference was observed with TP53 mutation in SHH subtype in this high-risk cohort. CONCLUSIONS Therapy intensification with carboplatin improved survival for high-risk group 3 medulloblastoma. These findings further support an integrated clinical and molecular risk stratification for medulloblastoma. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/neuonc/noaa222.492 |
| الإتاحة: | https://doi.org/10.1093/neuonc/noaa222.492Test http://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_3/iii391/34687643/noaa222.492.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.CE3010F4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/neuonc/noaa222.492 |
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