Survival and prognostic factors of patients with Ewing sarcoma at first recurrence following modern era multimodal therapy: A report from the Children’s Oncology Group (COG).
Bibliographic record
Abstract
10035 Background: Ewing sarcoma (EwS) is a rare malignancy of children, adolescents and young adults for which outcomes have progressively improved through intensification of conventional chemotherapy, including interval compression of cycles. Prior cooperative group reports of relapsed EwS included patients treated less intensively and with fewer treatment options at relapse. Here, we report overall survival (OS) and prognostic factors post-first recurrence in patients with EwS treated with frontline interval-compressed chemotherapy. Methods: We included patients treated on the last three phase 3 COG EwS studies treated with interval compressed chemotherapy, which accrued from 2001-2019. Patients with initially localized disease (L-EwS) were treated on AEWS0031 arm B and AEWS1031. Patients with initially metastatic disease (M-EwS) were treated on AEWS1221. The primary outcome was OS from first relapse. Demographic and clinical data from original diagnosis and from relapse were analyzed as potential prognostic factors. Kaplan-Meier survival curves were constructed and groups compared with log-rank tests. Results: 366 patients experienced disease recurrence as first event and were included in this analysis (AEWS0031 arm B, n = 69, AEWS1031, n = 115, for a total of 184 with L-EwS; AEWS1221, n = 182, all with M-EwS). Median age at relapse was 16 years. Median time from initial enrollment to first relapse was 1.52 years and was shorter for patients with M-EwS (Kruskall-Wallis, p < 0.001). First relapses were isolated local, isolated distant, and combined in 24%, 70%, and 6.4% of patients, respectively. Metastatic stage at initial diagnosis was associated with increased risk of post-first recurrence OS event (p < 0.0001). Two-year OS post-first recurrence (OS 2y ) was 25.6% for patients with M-EwS and 48.5% for patients with L-EwS. Time to first recurrence was also a predictor of post-recurrence survival (p < 0.0001): patients with initial L-EwS and relapse < 2 years from diagnosis had OS 2y of 31.4% vs. 70.8% for later relapses. Patients with initial M-EwS and relapse < 2 years from diagnosis had OS 2y of 18.9% vs. 71.2%. Patients with combined relapses had higher risk of post-relapse death compared to other patterns of failure (p = 0.003), an effect that was largely driven by the one seen in patients with initial L-EwS. Conclusions: Overall survival of patients with first recurrent EwS after having received modern era therapy with interval compressed chemotherapy on recent COG trials remains poor, particularly for M-EwS, early relapse and combined relapses. These data will inform the design of trials for this relapsed population and provide critical data to help counsel patients about goals of care at first relapse.
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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 | 0.001 |
| 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) | 0.001 | 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".