Dario Callegaro

Background: In the EORTC 62961–ESHO 95 randomized trial (European Organization for Research and Treatment 62961–European Society of Hyperthermia Oncology 95; ClinicalTrials.gov identifier NCT00003052), neoadjuvant chemotherapy (NAC) combined with regional hyperthermia (RHT) improved survival in patients with soft tissue sarcoma (tumor size >5 cm, grade 2 or 3, deep location). This study investigated the survival benefit of NAC + RHT in a subgroup of patients who had extremity soft tissue sarcoma (ESTS) according to risk predictions using the Sarculator nomogram. Methods: Overall survival (OS) was predicted with the Sarculator nomogram using baseline prognostic parameters. Kaplan–Meier analysis was used to estimate observed OS. A bivariable Cox model including the Sarculator score, treatment, and their interaction was fitted. Hazard ratios for OS were calculated for each decile of the Sarculator risk distribution. Results: Of 143 patients with ESTS, 135 were analyzed (NAC, n = 70; NAC + RHT, n = 65) with a median follow‐up of 136 months (interquartile range, 110–183 months). Survival in the NAC + RHT group exceeded Sarculator predictions and improved compared with the group that received NAC alone (hazard ratio, 0.67; 95% confidence interval, 0.39–1.17; p = .081), with an absolute 5‐year OS difference of 15.6% (95% confidence interval, 0.0%–31.4%). Risk stratification suggested greater benefit of NAC + RHT as predicted OS decreased. However, the interaction between Sarculator score and treatment was not significant ( p = .495). Conclusions: This analysis of ESTS from a randomized trial confirmed the previously reported OS benefit by adding RHT to NAC. Although patients with higher predicted risk seemed to benefit more from the combined treatment, these findings do not suggest that treatment decisions should be based on risk estimates alone, supporting the use of RHT combined with chemotherapy in patients who have primary ESTS.

Supplemental Table 2. Prognostic Index of Inflammatory Biomarkers for primary Retroperitoneal Sarcoma (IBPI)

Supplemental Table 1. NLR changes after neoadjuvant treatments*

Supplemental Figure 2. Association of IBPI with postoperative serious complications Clavien-Dindo grade 3 or higher.

Supplemental Figure 1. Relationship between the risk of death, expressed as log-relative hazard from multivariable Cox model, and inflammation-related serum biomarkers.

Soft tissue sarcomas (STS) are a heterogeneous group of rare malignant tumors arising from mesenchymal tissues, with extremity and superficial trunk STS (e

ROC curves: Time-dependent ROC curves at 5 and 10 years for OS (A and B) and DFS (C and D) in the pooled cohort, comparing different prognostic models. The Sarculator model (black), Sarculator + CINSARC (yellow), and CINSARC alone (blue) are shown. The diagonal reference line represents a nondiscriminatory model. AUC values quantify the discriminative performance of each model.

Purpose:The Complexity INdex in SARComas (CINSARC) predicts the metastatic risk in patients with soft-tissue sarcoma. The aims of this study were to provide the first independent validation of CINSARC in patients with retroperitoneal sarcoma (RPS) and evaluate whether CINSARC could enhance the performance of Sarculator.Experimental Design:A retrospective cohort included patients with primary localized RPS resected with curative intent (2011–2015) at a single institution. The STRASS cohort comprised patients from the surgery-only arm of the EORTC-STBSG-62092 (STRASS) trial who had undergone CINSARC categorization. Patients were classified as CINSARC low-risk (C1) versus high-risk (C2). Primary study endpoints were overall survival (OS) and disease-free survival (DFS). Sarculator performance was assessed in terms of discrimination (the Harrell C-index) and calibration (calibration plots and the Brier score) before and after adding CINSARC.Results:The study cohorts included 104 and 69 patients, respectively, with similar OS. In a pooled cohort, in multivariable analysis for OS considering Sarculator and CINSARC, only Sarculator was significantly associated with OS [HR, 1.93; 95% confidence interval (CI), 1.35–2.74; P < 0.001]. In multivariable analysis for DFS, both Sarculator (HR, 1.51; 95% CI, 1.09–2.09; P = 0.013) and CINSARC (HR, 2.01; 95% CI, 1.26–3.23; P = 0.004) were significantly associated with DFS. However, the addition of CINSARC did not improve Sarculator’s discrimination or calibration for either OS or DFS.Conclusions:This study validates CINSARC as a prognostic predictor for OS and DFS in patients with primary RPS. CINSARC did not improve the performance of Sarculator, suggesting that its addition to the Sarculator may not provide added clinical benefit.

Supplementary Table 1: distribution of histology and grading by CINSARC for DDLPS and LMS

Supplemental Figure 3: boxplot showing the distribution of Sarculator predicted overall survival (A, C) and Sarculator predicted disease free survival (B, D) at 5 years (A, B) and at 10 years (C, D) stratified by CINSARC risk category (blue, C1; yellow, C2). The median predicted OS/DFS is marked by the central horizontal line in each box with the box edges representing the interquartile range.