Molecular residual disease (MRD) detection using bespoke circulating tumor DNA (ctDNA) assays in localized soft tissue sarcoma (STS): A multicenter study.
Bibliographic record
Abstract
11537 Background: Surgery and (neo)adjuvant radiotherapy (RT) are the mainstay curative treatments for localized STS. Despite treatment, up to 50% of STS patients experience metastatic relapse, and routine use of adjuvant systemic therapy (AST) remains controversial. The presence of ctDNA following curative-intent treatment of STS is a potential biomarker for MRD and may identify patients who are likely to benefit from AST. Given the genomic heterogeneity of STS, a histology-agnostic approach to ctDNA detection in this population is desirable. Methods: This multicentre prospective study enrolled patients with localized, high-risk (grade ≥ 2, size ≥ 5 cm) STS. Blood samples were collected at diagnosis, post- radiotherapy, post-surgery, and at serial longitudinal time points for up to 2 years. Standard radiologic follow-up was performed concurrently. Whole exome sequencing of tumor tissue was carried out to identify patient-specific, single nucleotide variants. Personalized, and tumor-informed multiplex PCR next-generation sequencing-based ctDNA (Signatera) assays were used to track ctDNA in serial plasma samples. The primary endpoint was ctDNA detection rate of >70% at diagnosis. Secondary endpoints were MRD detection after local therapy and correlation of ctDNA detection with disease relapse. Results: A total of 76 subjects (female n = 43; median age [range]: 58 [21- 84] years) were included in this study from Princess Margaret Cancer Center, Stanford University, and Emory University. The most common STS types observed were leiomyosarcoma (LMS, n = 28), liposarcoma (n = 14), (predominantly dedifferentiated [n = 6]), and myxofibrosarcoma (n = 11). Among 38 pts who had blood samples collected at baseline (time of surgery), ctDNA was positive in 30/38 (79%). A baseline sample prior to radiotherapy was collected in 24 pts. Following neoadjuvant radiotherapy, 8/24 pts (33%) who were ctDNA positive at baseline became ctDNA negative, while 29/30 became ctDNA-negative after surgical resection. Median follow-up was 19 months, and 19/76 pts (25%) experienced disease recurrence Among these 19 pts, ctDNA was detected in all pts with baseline studies. ctDNA was detected at or before radiologic recurrence in 9/19 pts (47%), predominantly LMS 4/9, with a median lead time of 64.8 days (range: 0-197 days). ctDNA was detected in 14/38 patients at baseline with no radiological recurrence during follow-up period. Conclusions: Personalized, tumor-informed ctDNA assays can detect MRD and has prognostic value after definitive therapy, surgery and (neo)adjuvant radiotherapy, in localized STS patients. Additional studies are ongoing to evaluate ctDNA as a predictive biomarker for benefit from AST in STS. Clinical trial information: NCT03818412 .
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".