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Peer-reviewedCC BY 4.0Cancers

Preoperative Radiotherapy and Local Recurrence in Grade 3 Soft Tissue Sarcoma: A Causal Bayesian Network Analysis

5 affiliations
  1. 1Lucerne School of Business, Lucerne University of Applied Sciences and Arts, 6002 Lucerne, Switzerland
  2. 2Swiss Sarcoma Network, LUKS Sarcoma-IPU, University Teaching Hospital of Lucerne, 6000 Lucerne, Switzerland
  3. 3Faculty of Health Sciences and Medicine, University of Lucerne, 6002 Lucerne, Switzerland
  4. 4Kantonsspital Winterthur Sarcoma Center, 8401 Winterthur, Switzerland
  5. 5Faculty of Medicine, University of Zurich, 8006 Zurich, Switzerland

Abstract

Background: Estimating the effect of preoperative radiotherapy in grade 3 (G3) soft tissue sarcoma (STS) is difficult because treatment reflects clinical risk. We estimated whether local recurrence risk among treated patients would differ under surgery alone. Methods: We retrospectively analyzed a multicentre registry of 151 surgically treated G3 patients without chemotherapy; 99 received preoperative radiotherapy and 52 underwent surgery alone. Propensity score weighting targeted the average treatment effect among treated patients (ATT). The primary weighted interventional Bayesian network (BN) adjusted for age, metastasis, tumor size, depth, body location, and whoops surgery. Logistic regression and BN conditioning and intervention were reference analyses. Differential follow-up was assessed using a weighted Aalen–Johansen analysis. Results: Local recurrence occurred in 31 patients (20.5%). Weighting reduced the maximum absolute standardized mean difference from 0.866 to 0.139. Median bootstrap ATT estimates were +3.3 percentage points for conventional logistic regression, +5.2 for weighted logistic regression, and +1.37 for the weighted interventional BN. At 1 year, the weighted Aalen–Johansen risk difference was +0.83 percentage points, with a wide 95% confidence interval spanning benefit and harm. Conclusions: The weighted interventional BN produced a near-null estimate, but modest benefit or harm remained plausible. Treatment effect estimates were sensitive to the assumed causal structure, limiting definitive conclusions about radiotherapy benefit. Given the modest sample, limited treatment overlap, differential follow-up, and residual confounding, causal interpretation should remain cautious. These findings do not support changing established indications for preoperative radiotherapy, but this framework provides a transparent approach to evaluating treatment strategies in rare cancers.

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BibTeX
@article{valle2026preoperative,
  title = {{Preoperative Radiotherapy and Local Recurrence in Grade 3 Soft Tissue Sarcoma: A Causal Bayesian Network Analysis}},
  author = {Andrea Valle and Bruno Fuchs and Mirko Birbaumer and Philip Heesen},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18203269},
  url = {https://www.mdpi.com/2072-6694/18/20/3269},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Preoperative Radiotherapy and Local Recurrence in Grade 3 Soft Tissue Sarcoma: A Causal Bayesian Network Analysis
AU  - Andrea Valle
AU  - Bruno Fuchs
AU  - Mirko Birbaumer
AU  - Philip Heesen
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18203269
UR  - https://www.mdpi.com/2072-6694/18/20/3269
AB  - Background: Estimating the effect of preoperative radiotherapy in grade 3 (G3) soft tissue sarcoma (STS) is difficult because treatment reflects clinical risk. We estimated whether local recurrence risk among treated patients would differ under surgery alone. Methods: We retrospectively analyzed a multicentre registry of 151 surgically treated G3 patients without chemotherapy; 99 received preoperative radiotherapy and 52 underwent surgery alone. Propensity score weighting targeted the average treatment effect among treated patients (ATT). The primary weighted interventional Bayesian network (BN) adjusted for age, metastasis, tumor size, depth, body location, and whoops surgery. Logistic regression and BN conditioning and intervention were reference analyses. Differential follow-up was assessed using a weighted Aalen–Johansen analysis. Results: Local recurrence occurred in 31 patients (20.5%). Weighting reduced the maximum absolute standardized mean difference from 0.866 to 0.139. Median bootstrap ATT estimates were +3.3 percentage points for conventional logistic regression, +5.2 for weighted logistic regression, and +1.37 for the weighted interventional BN. At 1 year, the weighted Aalen–Johansen risk difference was +0.83 percentage points, with a wide 95% confidence interval spanning benefit and harm. Conclusions: The weighted interventional BN produced a near-null estimate, but modest benefit or harm remained plausible. Treatment effect estimates were sensitive to the assumed causal structure, limiting definitive conclusions about radiotherapy benefit. Given the modest sample, limited treatment overlap, differential follow-up, and residual confounding, causal interpretation should remain cautious. These findings do not support changing established indications for preoperative radiotherapy, but this framework provides a transparent approach to evaluating treatment strategies in rare cancers.
SN  - 2072-6694
ER  -