Comparison of treatment effect and long-term outcomes for pediatric and adult Ewing sarcoma patients in British Columbia, Canada.
Bibliographic record
Abstract
11531 Background: Treatment of Ewing Sarcoma (EWS) is challenging. While it is known to be sensitive to chemotherapy and radiation, the number of lines of therapy available are limited. This disease affects pediatric patients (PP) more often than adults (AP), and reported outcomes are worse for AP onset EWS in the literature. It is unclear if this is due to difference in the biology of disease in AP compared to PP, or if this is due to differences in treatment approach. Furthermore, optimal treatments and real world impact of treatment is unclear in both the PP and AP populations. This study identifies the features of therapy received by AP and PP with EWS in a large, mutli-institutional cohort, and provides real world evidence for the expected outcomes in both AP and PP with EWS. Methods: A cohort study analysis of the Sarcoma Outcomes Unit database at BC Cancer was conducted to identify patients diagnosed with EWS in British Columbia from January 1, 2000 to December 31, 2018. Data on the frequency, amount, and regimen of chemotherapy were collected. Baseline Charlson comorbidity index, age at diagnosis, progression free survival and overall survival were collected. Results: 108 patients with EWS were identified, 66 AP and 42 PP Median age at diagnosis for adults was 37 (19-86) and median age for diagnosis of pediatric patients was 14 (1-18). Real world median PFS and OS for AP were 23 mos and 79 mos, and for the PP were 32 mos and NE. Five year overall survival was 54% in AP and 77% in PP. Overall, there was no difference in the number of lines of therapy received between PP and AP, but the type of therapy was more dose-dense in the PP than in the AP, (85% vs 28% for dose dense chemo). 5 year overall survival was longer for PP who received dose dense regimens compared to non-dose dense regimens (HR 0.87), but was not different in the AP receiving dose dense regimens (HR 0.95), even when controlling for comorbidities. The most common chemotherapy regimen for AP was Vincristine, Adriamycin, cyclophosphamide alternating with Ifosfamide and Etoposide q3weeks, whereas in the pediatric population the most common chemotherapy regimen was the same but alternating q2weeks. Conclusions: The treatment plans for PP with EWS were more often dose dense compared to the AP. Outcomes for PP were vastly better than for APs, despite overall similarities in the number of lines of therapy and types of agents used. Given the lack of difference between dose dense and non-dose dense regimens for APs, this is not the likely cause of difference in survival between PPs and APs. Extrapolating pediatric protocols to the adult setting may not be appropriate given the differences in outcomes. Further work to identify effective therapies and predictive biomarkers in this disease are needed, and my further identify reasons for discrepant outcomes in pediatric and adult populations.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".