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      The Impact of Surgical Margins and Adjuvant Radiotherapy in Patients with Undifferentiated Pleomorphic Sarcomas of the Extremities: A Single-Institutional Analysis of 192 Patients

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          Abstract

          Background: Undifferentiated pleomorphic sarcomas are a frequent subtype within the heterogeneous group of soft tissue sarcomas. As the attainment of negative margins can be complicated at the extremities, we determined the prognostic significance of surgical margins in our patient population. Methods: We retrospectively determined the relationship between local recurrence-free survival (LRFS), overall survival (OS), and potential prognostic factors in 192 patients with UPS of the extremities who were suitable for surgical treatment in curative intent. The median follow-up time was 5.1 years. Results: The rates of LRFS and OS after 2 years were 75.7% and 87.2% in patients with R0-resected primary tumors and 49.1% and 81.8% in patients with R1/R2-status (LRFS: p = 0.013; OS: p = 0.001). Adjuvant radiotherapy significantly improved LRFS (5-year: 67.6% vs. 48.4%; p < 0.001) and OS (5-year: 82.8 vs. 61.8; p = 0.016). Both, negative margins and adjuvant radiotherapy were found to be independent prognostic factors in multivariate analysis. Conclusions: The data from this study could underscore the beneficial prognostic impact of negative margins on LRFS and OS. However, the width of negative margins seemed to be not relevant. Notably, adjuvant radiotherapy was not only able to decrease the risk of local failure but also improved OS in a significant manner.

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          Most cited references23

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          Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities.

          To identify specific independent adverse clinicopathologic factors for event-free survival in a cohort of consecutively treated patients with extremity soft tissue sarcomas. Prospectively collected data from a population of 1,041 adult patients with localized (American Joint Committee on Cancer [AJCC] stage IA to IIIB) extremity soft tissue sarcomas were analyzed. Patients were treated at a single institution between 1982 and 1994. Patient, tumor, and pathologic factors were analyzed by univariate and multivariate techniques to identify independent prognostic factors for the end points of local recurrence, distant recurrence, disease-specific survival, and post-metastasis survival. The 5-year survival rate for this cohort of patients was 76%, with a median follow-up time of 3.95 years. Significant independent adverse prognostic factors for local recurrence were age greater than 50 years, recurrent disease at presentation, microscopically positive surgical margins, and the histologic subtypes fibrosarcoma and malignant peripheral-nerve tumor. For distant recurrence, intermediate tumor size, high histologic grade, deep location, recurrent disease at presentation, leiomyosarcoma, and nonliposarcoma histology were independent adverse prognostic factors. For disease-specific survival, large tumor size, high grade, deep location, recurrent disease at presentation, the histologic subtypes leiomyosarcoma and malignant peripheral-nerve tumor, microscopically positive surgical margins, and lower extremity site were adverse factors. For post-metastasis survival, only large tumor size ( > 10 cm) was an adverse prognostic factor. The independent adverse prognostic factors for distant recurrence and disease specific survival differ from those identified for subsequent local recurrence. Patients with microscopically positive surgical margins or patients who present with locally recurrent disease are at increased risk for subsequent local recurrence and tumor-related mortality. Specific histopathologic subtypes are associated with increased risks for local failure and tumor-related mortality.
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            Advances in sarcoma genomics and new therapeutic targets.

            Increasingly, human mesenchymal malignancies are being classified by the abnormalities that drive their pathogenesis. Although many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities, and in many cases sarcomas are resistant to adjuvant therapies. In this Review, we discuss the core molecular determinants of sarcomagenesis and emphasize the emerging genomic and functional genetic approaches that, coupled with novel therapeutic strategies, have the potential to transform the care of patients with sarcoma.
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              Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients.

              Prognostic factors for patients with soft-tissue sarcoma who are treated with conservative surgery and radiation are documented poorly. The clinicopathologic features and disease outcome for 1225 patients with localized sarcoma who were treated with conservative surgery and radiation were reviewed retrospectively. Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for local control, metastatic recurrence, and disease specific survival. The median follow-up of surviving patients was 9.5 years. The respective local control rates at 5 years, 10 years, and 15 years were 83%, 80%, and 79%. Factors predictive of local recurrence were positive or uncertain resection margins; tumors located in the head and neck and the deep trunk; presentation with local recurrence; patient age > 64 years; malignant fibrous histiocytoma, neurogenic sarcoma. or epithelioid sarcoma histopathology; tumor measuring > 10 cm in greatest dimension; and high pathologic grade. Freedom from metastasis at 5 years, 10 years, and 15 years was 71%, 68%, and 66%, respectively. Factors that were predictive of metastatic recurrence were high tumor grade; large tumor size (> 5 cm); and leiomyosarcoma, rhabdomyosarcoma, synovial sarcoma, or epithelioid sarcoma. The respective disease specific survival rates at 5 years, 10 years, and 15 years were 73%, 68%, and 65%. Adverse factors for disease specific survival were high tumor grade; large tumor size (> 5 cm); tumors located in the head and neck and deep trunk; rhabdomyosarcoma, epithelioid sarcoma, or clear cell sarcoma; patient age > 64 years; and positive or uncertain resection margins. Soft-tissue sarcoma comprises a heterogeneous group of diseases. Prognostic factors for local recurrence, metastatic recurrence, lymph node recurrence, disease free survival, and disease specific survival are different, and optimal treatment strategies need to take this complexity into account. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11365
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                05 February 2020
                February 2020
                : 12
                : 2
                : 362
                Affiliations
                [1 ]Department of Plastic Surgery, BG-University Hospital Bergmannsheil, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany
                [2 ]Department of Plastic Surgery, Martin-Luther Hospital, Caspar-Theyss-Strasse 27-29, D-14193 Berlin, Germany
                [3 ]Institute of Pathology, Ruhr-University Bochum, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany
                Author notes
                [* ]Correspondence: kamran.harati@ 123456t-online.de ; Tel.: +49-234-302-3445; Fax: +49-234-6379
                Author information
                https://orcid.org/0000-0003-1283-2982
                Article
                cancers-12-00362
                10.3390/cancers12020362
                7072160
                32033261
                c6388b23-ea8d-4294-a38b-2711072a33b5
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 January 2020
                : 03 February 2020
                Categories
                Article

                pleomorphic sarcoma,margins,survival,surgery,extremity
                pleomorphic sarcoma, margins, survival, surgery, extremity

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