Elsevier

Journal of Surgical Research

Volume 255, November 2020, Pages 378-387
Journal of Surgical Research

Oncology
Radiotherapy is Associated With Improved Survival in Patients With Synovial Sarcoma Undergoing Surgery: A National Cancer Database Analysis

https://doi.org/10.1016/j.jss.2020.05.075Get rights and content

Abstract

Background

Previous studies have demonstrated an association of perioperative radiotherapy (RT) with improved survival in patients with synovial sarcoma (SS) undergoing surgery, but the mechanism for this is unknown. In this study, we sought to further analyze this association using a hospital-based data set where data on chemotherapy administration and surgical margin status are available.

Methods

Using the National Cancer Database, we identified 1216 patients with SS (aged ≥18 y) from 2004-2012 undergoing surgery. Cox proportional hazards analysis was used to study the effect of clinicopathologic variables on overall survival (OS).

Results

Mean age at diagnosis was 41.5 y (range 18-90), and 71.3% of tumors were high grade; 22.9% underwent surgery alone, 59.6% received RT with surgery, 44.2% received chemotherapy with surgery, and 26.3% received trimodality therapy. Age, sex, grade, Charlson-Deyo score, and RT (hazard ratio, 0.676; 95% confidence interval, 0.519-0.880; P = 0.004) were associated with improved OS, whereas chemotherapy (hazard ratio, 1.20; 95% confidence interval, 0.899-1.60; P = 0.217) and surgical margin status were not. Trimodality therapy with surgery, RT, and chemotherapy was associated with improved OS when compared with therapy with surgery and chemotherapy alone.

Conclusions

In patients with SS undergoing surgery, we observed a significant improved association of OS with the addition of RT when adjusting for comorbidity score, margin status, and receipt of chemotherapy. These data further support routine implementation of RT in the treatment of patients with SS, including those receiving aggressive multimodality and trimodality care.

Introduction

Soft tissue sarcomas (STSs) constitute a rare heterogeneous group of mesenchymal neoplasms, with an incidence of approximately 12,000 new cases per year in the United States.1 Because of the heterogeneity of histologic subtypes, the behavior and biology of the tumors can vary widely.2,3 As a result, recent efforts have focused on optimizing the care of patients with STS based on histology-specific paradigms.4,5 However, these efforts can prove challenging as extensive data on rare subtypes are lacking, with data typically emanating from single-institution studies compared with a paucity of clinical trials.1

Synovial sarcomas (SSs) are an example of a rare STS subtype, which comprise 6%-9% of all STS.2 In general, SS is considered a high-grade STS with distinguishing histologic characteristics and unique clinical behavior compared with other types of adult STS.3 Morphologically, it resembles some pediatric sarcomas, such as Ewing sarcoma and desmoplastic small round cell sarcoma2,3 and has been observed to respond well to ifosfamide-based chemotherapy in some studies.6,7 As such, chemotherapy in the management of localized disease is frequently endorsed by some experts, often in conjunction with intensive, multiagent protocols.6,7 However, it is important to note that the age of onset for SS is typically older than for other pediatric sarcomas,8 raising questions about the ability of these patients to tolerate aggressive cytotoxic chemotherapy regimens.

Overall, although surgery is the mainstay of treatment for localized STS, there is an appreciation for the use of multimodality therapy, including radiotherapy (RT) and chemotherapy. Small retrospective and prospective studies have shown improvement in local control and recurrence-free survival with perioperative RT, but have not shown improvement in overall survival (OS).2,9, 10, 11, 12, 13 However, larger retrospective studies using registry databases depict a different impact of RT on survival outcomes. For example, a National Cancer Database (NCDB) analysis demonstrated an association of neoadjuvant and adjuvant RT with improved OS among patients with STS undergoing surgical resection.14 Using the Surveillance, Epidemiology, and End Results (SEER) database, Naing et al.15 observed improved survival specifically in patients with SS after surgery and RT. However, this study was limited by a lack of information on chemotherapy administration and surgical margins, as these data points are not available in the SEER database. Because other studies have shown a survival benefit with the use of perioperative chemotherapy in SS16 (and other studies have shown that margin status can impact the association of RT with cancer recurrence and survival), we sought to assess the impact of these variables on the association of RT and SS survival in a data set where this relevant clinical and pathologic information is available. We specifically hypothesized that perioperative RT would remain associated with improved survival in patients with SS even after controlling for chemotherapy administration, margin status, and comorbidity score.

Section snippets

Methods

NCDB is a large national database that collects tumor and treatment information from more than 1500 Commission on Cancer accredited facilities and accounts for 70% of cancer cases within the United States.17 Information contained within the NCDB includes receipt of chemotherapy and surgical margin status, not previously available in other large-scale data sets, such as SEER. Using the NCDB, we retrospectively identified patients who were diagnosed with SS according to the International

Results

The clinicopathologic characteristics of the 1216 patients with SS are depicted in Table 1. The mean age at diagnosis was 41.5 y. There was a slight male predominance at 51.6%, most patients were Caucasian (81.9%), and most patients had a comorbidity score of 0 (88.9%). Tumors were located in the lower extremity for 47.5% of patients, whereas it was located in the upper extremity for 20.2%. In 35.9% of patients, the tumor was 5-10 cm and in 23.2% of patients the tumor was 10 cm or larger. Among

Discussion

In this study, we analyzed a large national data set of patients with SS to identify predictors of OS in patients undergoing surgery. Importantly, similar to prior studies, we found that the use of RT in surgical patients was associated with improved OS, and this association of RT with superior survival persisted after controlling for chemotherapy administration, surgical margin status, and comorbidity score. Despite this, our trends in treatment analysis revealed that more than 40% of patients

Conclusions

In this study of surgically managed patients with SS, we observed a significant association of RT with improved OS when adjusting for comorbidity score, margin status, and receipt of chemotherapy. Chemotherapy was not associated with improved OS. However, patients receiving trimodality therapy had similar 5-y survival compared with surgery and surgery plus RT cohorts. These data further support routine implementation of RT in the multimodality treatment of patients with SS, including those

Acknowledgment

This work was funded by a seed grant from the Outcomes Research Group at the University of California Davis Medical Center.

Author contribution: A.A.G. and R.J.C. contributed to study design and acquisition of data from the National Cancer Database. A.A.G., Y.L., and C.-S.L. performed the data analysis. A.A.G., A.S.M., and R.J.C. interpreted the data. A.A.G. and A.S.M. drafted the manuscript and performed the literature review. S.W.T., M.A.D., A.M.M., and R.J.C. revised the work and provided

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    These authors contributed equally to this study.

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