Chemotherapy improves distant control in localized high-grade soft tissue sarcoma of the extremity/trunk

John P Hanna,Mihaela Druta,Victoria T Rizk,Damon R Reed,Youngchul Kim,Andrew S Brohl,Arash O Naghavi,Jennifer Swank,David M Joyce,Ricardo J Gonzalez,Odion Binitie

doi:10.1186/s13569-020-00132-w

John P Hanna, Mihaela Druta + Show 9 more

Open Access

https://doi.org/10.1186/s13569-020-00132-w

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Abstract

BackgroundSoft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial. Our goal was to identify a subset of patients with primary STS that benefit with the addition of chemotherapy.MethodsA retrospective chart review included intermediate to high-grade localized primary STS of the extremity/trunk, and tumor size > 5 cm. The effect of chemotherapy was evaluated for local control (LC), distant control (DC), progression free survival (PFS), and overall survival (OS).ResultsIn this cohort (n = 273), patients were treated with surgery (98%), radiation (81%), and chemotherapy (24.5%). With a median follow-up of 51 months, the entire cohort’s 5-year LC, DC, PFS, and OS are 79.1%, 59.9%, 43.8%, and 68.7%, respectively. The addition of chemotherapy did not provide a DC benefit (p = 0.238) for the entire cohort. High-grade disease (n = 210) experienced a 5-year benefit in DC (68% vs. 54.4%, p = 0.04), which was more pronounced with MAI (Mesna, Adriamycin, Ifosfamide) based regimens (74.2%, p = 0.016), and a 5-year PFS (50.8% vs 45%, p = 0.025) and OS benefit (76.2% vs 70%, p = 0.067) vs. no chemotherapy. On multivariate analysis of the high-grade subset, chemotherapy independently predicted for a DC benefit (HR 0.48 95% CI 0.26–89, p = 0.019). The benefit of chemotherapy was more pronounced with MAI, showing a significant benefit in DC (HR 0.333 95% CI 0.145–0.767, p = 0.01) and PFS (HR 0.52 95% CI 0.28–0.99, p = 0.047).ConclusionIn patients with localized STS > 5 cm, the high-grade subset had a distant control benefit with the addition of chemotherapy, leading to improved progression free survival. This is more pronounced with the use of MAI and should be considered in patients eligible for this regimen.

Highlights

Soft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial
The cohort primarily consisted of Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 (n = 236, 86.4%), grade 3 (n = 210, 77%), ≥ 8 cm in size (n = 179, 66%), underwent surgery (n = 267, 98%), received radiation (n = 220, 81%), and received chemotherapy (n = 67, 25%) (Table 1)
Independent predictors of outcome in high‐grade subset On multivariate analysis of the high-grade cohort, chemotherapy independently predicted for a distant control (DC) benefit (HR 0.475 95% CI 0.236–.954, p = 0.037); there was no statistical benefit noted on progression free survival (PFS) (HR 0.629 95% CI 0.361–1.095, p = 0.101)

Summary

Introduction

Soft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial. Rizk et al Clin Sarcoma Res (2020) 10:11 the heterogeneity and rarity of the disease, clinical studies evaluating the role of chemotherapy for patients at a high-risk of distant metastasis (e.g., high grade, > 5 cm, and often tumor depth) have led to inconsistent results, and its use is not well defined in current guidelines [8, 9]. Given the ongoing controversy regarding the role of systemic therapy for high-risk localized soft tissue sarcoma, we performed a retrospective review of the experience of our large, high-volume sarcoma referral center. The goal of this study was to review and contrast the treatment response of patients seen at the Moffitt Cancer Center (MCC) with intermediate to high-grade, tumor size ≥ 5 cm, STS of the extremities and trunk that received surgery and/or radiation with the response of those that received surgery and/or radiation combined with chemotherapy

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