Abstract 3552: Subgroup-specific pattern of recurrence in medulloblastoma.
Bibliographic record
Abstract
Abstract Background: Medulloblastoma constitutes the most common malignant brain tumor of childhood. Although multimodel treatment strategies, encompassing surgery, chemotherapy, and radiation, results in up to 80% five-year overall survival, recurrent medulloblastoma is almost always uniformly fatal. Recent integrated genomic studies have shown that medulloblastoma comprises 4 clinical and biologically distinct variants. We sought to delineate subgroup-specific differences in recurrent medulloblastoma. Methods: We identified a discovery cohort of all recurrent medulloblastomas at the Hospital for Sick Children between 1994-2012, and subgrouped cases using nanoString. Clinical details were ascertained via retrospective chart review. Our findings were confirmed through analysis of an independent validation cohort of 85 recurrences. Primary and recurrent matched pairs were evaluated where possible. Results: Twenty-nine recurrent cases were identified, ten with a local recurrence within the tumor bed only, and 19 recurred with metastases. Notably, SHH tumors recurred more frequently in the tumor bed (8/11, 73%) whereas Group 3 and Group 4 developed with metastatic relapses more frequently (16/18, 89%; p<0.01). Late recurrences were observed more commonly in Group 4 cases with a mean time to recurrence of 3.2 years compared to under two years for both SHH and Group 3 (p<0.004), with a tendency to a prolonged interval to death post-recurrence in Group 4 cases (p=0.07). Spinal metastases in the absence of supratentorial metastases were observed in three non-SHH recurrences. The presence of metastases at diagnosis and histology were not predictive factors of recurrence site. In an independent validation cohort of 85 recurrences, 13 recurrences appeared in the tumor bed only of which nine were SHH and 72 recurred with metastases. Of these metastatic relapses, only three SHH tumors were observed, while 36 and 33 belonged to Group 3 or Group4 (p<0.001), respectively. Strikingly, in all instances where matched primary and recurrent pairs were available, the subgroup affiliation remained stable at recurrence. Conclusions: Significant differences in the pattern of recurrence exist across medulloblastoma subgroups. Longer surveillance periods across the entire neuro-axis may be required for Group 4 patients even in the absence of local tumor bed or supratentorial recurrence. Intensified local therapy should be considered upon initial treatment for SHH patients. Citation Format: Vijay Ramaswamy, Marc Remke, Eric Bouffet, David Shih, Claudia Faria, Ulrich Schüller, Sri Gururangan, Roger McLendon, Nada Jabado, Adam Fontebasso, Sandra Dunn, Joanna Triscott, Cynthia Hawkins, Uri Tabori, Kari Codispoti, Roger Packer, Stefan M. Pfister, Andrey Korshunov, Michael D. Taylor. Subgroup-specific pattern of recurrence in medulloblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3552. doi:10.1158/1538-7445.AM2013-3552
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".