Abstract

The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy. We then examined associations between timing of multi-agent chemotherapy (neoadjuvant or adjuvant) and OS. We used a Cox proportional hazards model and propensity score matching (PSM) to account for covariates including demographic, patient, clinical, treatment, and facility factors. In the overall cohort, we observed no association between multi-agent chemotherapy or its timing and improved OS. Multi-agent chemotherapy was associated with improved OS in several subgroups, including patients with larger tumors (>5 cm), those treated at high-volume centers, or those who received radiation. We also identified an OS benefit to multi-agent chemotherapy among the elderly (>70 years) and African American patients. Multi-agent chemotherapy was associated with improved survival for patients with tumors >5 cm, who receive radiation, or who receive care at high-volume centers. Neither younger age nor chemotherapy timing was associated with better outcomes. These ‘real-world’ findings align with recent randomized trial data supporting the use of multi-agent chemotherapy in high-risk patients with localized STS.

Highlights

  • Surgery, with or without radiation, remains the mainstay of treatment for adult patients with primarily localized extremity and trunk soft tissue sarcoma (STS)

  • The subgroup analysis identified a subset of patients with large (>5 cm) tumors treated with radiation at high-volume facilities for whom multi-agent chemotherapy was associated with improved survival

  • While our study found no association between multi-agent chemotherapy and overall survival (OS) in the overall study cohort, subgroup analysis highlighted its potential benefit for patients with larger tumors (>5 cm), those that received radiation, and those treated at high-volume facilities

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Summary

Introduction

With or without radiation, remains the mainstay of treatment for adult patients with primarily localized extremity and trunk soft tissue sarcoma (STS). There is conflicting evidence regarding the impact of chemotherapy on survival for these patients [1,2,3,4,5,6,7,8,9,10,11]. Clinical practice guidelines reflect the equivocal nature of the data and present chemotherapy as a treatment option for high-grade disease [12,13]. A treating physician must decide whether to offer chemotherapy, and whether to use single- or multi-agent chemotherapy and whether to use a neoadjuvant or adjuvant approach. This is reflected in the wide variation in practice patterns [14]. While there are data to support a survival benefit associated with the use of multi-agent rather than single-agent chemotherapy regimens [6,9,11], neoadjuvant and adjuvant chemotherapy have not been directly compared

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