The mitotic rate as a prognostic biomarker after preoperative radiotherapy for high-grade limb/trunk soft tissue sarcoma

Zhengxiao Ouyang; Tianyu Wang; Jennifer Brown; Zsolt Orosz; Sally Trent; Thomas Cosker; Harriet Branford White; Duncan Whitwell; Xiaoning Guo; Christopher Leonard Maxime Gibbons

doi:10.1016/j.radonc.2024.110482

The mitotic rate as a prognostic biomarker after preoperative radiotherapy for high-grade limb/trunk soft tissue sarcoma

Radiother Oncol. 2024 Nov:200:110482. doi: 10.1016/j.radonc.2024.110482. Epub 2024 Aug 17.

Affiliations

¹ Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Nuffield Orthopaedic Centre, Oxford University Hospitals Foundation Trust, Oxford, UK.
² Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
³ Nuffield Orthopaedic Centre, Oxford University Hospitals Foundation Trust, Oxford, UK.
⁴ Department of Oncology, Churchill Hospital, Oxford University Hospitals Foundation Trust, Oxford, UK.
⁵ Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China. Electronic address: [email protected].
⁶ Nuffield Orthopaedic Centre, Oxford University Hospitals Foundation Trust, Oxford, UK. Electronic address: [email protected].

PMID: 39159680
DOI: 10.1016/j.radonc.2024.110482

Abstract

Purpose: Currently there is no generally accepted standardized approach for the pathological evaluation of soft tissue sarcoma (STS) histology appearance after preoperative radiotherapy (PORT). This study aimed to investigate the prognostic value of pathological appearance after PORT for patients with high-grade limb/trunk STS.

Methods: A cohort of 116 patients with high-grade STS of the limb/trunk treated with PORT followed by resection were evaluated. Patient characteristics, imaging tumor morphology (size, volume), and histopathology (mitotic and necrosis rate, viable cell, hyalinization/fibrosis cytopathic effect) were reviewed and reassessed. Disease free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the hazard ratio was derived from Cox proportional hazard models. Two predictive nomograms were calculated based on significant predictors identified.

Results: The 5-year DFS and OS were 52.9% and 70.3%, respectively. Tumor size before (HR:1.07, 95%CI: 1.01-1.14) and after PORT (HR:1.08, 95%CI: 1.01-1.14), tumor volume (HR:1.06, 95%CI: 1.01-1.12), mitotic rate after PORT (HR: 1.06, 95%CI: 1.02-1.11), mitotic rate change after PORT (HR:1.04, 95%CI:1.00-1.09) were independent risk factors for DFS. Tumor size before (HR:1.08, 95%CI: 1.03-1.14) and after PORT (HR:1.09, 95%CI: 1.04-1.15), tumor volume (HR:1.05, 95%CI: 1.01-1.09), mitotic rate after PORT (HR: 1.09, 95%CI: 1.04-1.13), mitotic rate change after PORT (HR:1.05, 95%CI:1.01-1.09) were independent risk factors for OS. The C-index of pathologic predictive nomogram based on mitotic rate for DFS and OS were 0.67 and 0.73, respectively. The C-index of morphology-pathology predictive nomogram for OS was 0.79.

Conclusion: Tumor size before and after PORT, tumor volume, mitotic rate after PORT, mitotic rate change after PORT were independent risk factors for DFS and OS in high-grade STS patients treated with PORT. The mitotic rate, independent of tumor morphology, showed its potential as a prognostic biomarker for pathologic evaluation in patients treated with PORT.

Keywords: Mitotic rate; Preoperative radiotherapy; Risk factors; Soft tissue sarcoma; Survival analysis.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Extremities*
Female
Humans
Male
Middle Aged
Mitotic Index
Neoplasm Grading
Nomograms
Prognosis
Retrospective Studies
Sarcoma* / mortality
Sarcoma* / pathology
Sarcoma* / radiotherapy
Sarcoma* / surgery
Soft Tissue Neoplasms / mortality
Soft Tissue Neoplasms / pathology
Soft Tissue Neoplasms / radiotherapy
Soft Tissue Neoplasms / surgery
Torso
Young Adult