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Published in: Clinical Sarcoma Research 1/2020

01-12-2020 | Soft Tissue Sarcoma | Research

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

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

Published in: Clinical Sarcoma Research | Issue 1/2020

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Abstract

Background

Soft 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.

Methods

A 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).

Results

In 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).

Conclusion

In 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.
Literature
1.
go back to reference Fletcher CDM, WH Organization. WHO Classification of Tumours of Soft Tissue and Bone. New York: IARC Press; 2013. Fletcher CDM, WH Organization. WHO Classification of Tumours of Soft Tissue and Bone. New York: IARC Press; 2013.
2.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRef
3.
go back to reference Rouhani P, et al. Cutaneous soft tissue sarcoma incidence patterns in the US: an analysis of 12,114 cases. Cancer. 2008;113(3):616–27.CrossRef Rouhani P, et al. Cutaneous soft tissue sarcoma incidence patterns in the US: an analysis of 12,114 cases. Cancer. 2008;113(3):616–27.CrossRef
4.
go back to reference Willeumier JJ, et al. Individualised risk assessment for local recurrence and distant metastases in a retrospective transatlantic cohort of 687 patients with high-grade soft tissue sarcomas of the extremities: a multistate model. BMJ Open. 2017;7:2.CrossRef Willeumier JJ, et al. Individualised risk assessment for local recurrence and distant metastases in a retrospective transatlantic cohort of 687 patients with high-grade soft tissue sarcomas of the extremities: a multistate model. BMJ Open. 2017;7:2.CrossRef
5.
go back to reference Daigeler A, et al. Long-term outcome after local recurrence of soft tissue sarcoma: a retrospective analysis of factors predictive of survival in 135 patients with locally recurrent soft tissue sarcoma. Br J Cancer. 2014;110(6):1456–64.CrossRef Daigeler A, et al. Long-term outcome after local recurrence of soft tissue sarcoma: a retrospective analysis of factors predictive of survival in 135 patients with locally recurrent soft tissue sarcoma. Br J Cancer. 2014;110(6):1456–64.CrossRef
6.
go back to reference Kraybill WG, et al. Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: radiation Therapy Oncology Group Trial 9514. J Clin Oncol. 2006;24(4):619–25.CrossRef Kraybill WG, et al. Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: radiation Therapy Oncology Group Trial 9514. J Clin Oncol. 2006;24(4):619–25.CrossRef
7.
go back to reference Brennan MF. Staging of soft tissue sarcomas. Ann Surg Oncol. 1999;6(1):8–9.CrossRef Brennan MF. Staging of soft tissue sarcomas. Ann Surg Oncol. 1999;6(1):8–9.CrossRef
8.
go back to reference Cheng EY. Surgical management of sarcomas. Hematol Oncol Clin North Am. 2005;19(3):451–70.CrossRef Cheng EY. Surgical management of sarcomas. Hematol Oncol Clin North Am. 2005;19(3):451–70.CrossRef
9.
go back to reference von Mehren M, et al. Soft Tissue Sarcoma, Version 22018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(5):536–63.CrossRef von Mehren M, et al. Soft Tissue Sarcoma, Version 22018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(5):536–63.CrossRef
10.
go back to reference Sarcoma Meta-analysis Collaboration. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Lancet. 1997;350(9092):1647–54.CrossRef Sarcoma Meta-analysis Collaboration. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Lancet. 1997;350(9092):1647–54.CrossRef
11.
go back to reference Woll PJ, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol. 2012;13(10):1045–54.CrossRef Woll PJ, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol. 2012;13(10):1045–54.CrossRef
12.
go back to reference Pervaiz N, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113(3):573–81.CrossRef Pervaiz N, et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008;113(3):573–81.CrossRef
13.
go back to reference Pasquali S, et al. Neoadjuvant treatment: a novel standard? Curr Opin Oncol. 2017;29(4):253–9.CrossRef Pasquali S, et al. Neoadjuvant treatment: a novel standard? Curr Opin Oncol. 2017;29(4):253–9.CrossRef
14.
go back to reference Sabolch A, et al. Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity. Am J Clin Oncol. 2012;35(2):151–7.CrossRef Sabolch A, et al. Risk factors for local recurrence and metastasis in soft tissue sarcomas of the extremity. Am J Clin Oncol. 2012;35(2):151–7.CrossRef
15.
go back to reference Grimer RJ. Size matters for sarcomas! Ann R Coll Surg Engl. 2006;88(6):519–24.CrossRef Grimer RJ. Size matters for sarcomas! Ann R Coll Surg Engl. 2006;88(6):519–24.CrossRef
16.
go back to reference DeLaney TF, et al. Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas. Int J Radiat Oncol Biol Phys. 2003;56(4):1117–27.CrossRef DeLaney TF, et al. Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas. Int J Radiat Oncol Biol Phys. 2003;56(4):1117–27.CrossRef
17.
go back to reference Loong HH, Wong KH, Tse T. Controversies and consensus of neoadjuvant chemotherapy in soft-tissue sarcomas. ESMO Open. 2018;3(Suppl 1):e000293.CrossRef Loong HH, Wong KH, Tse T. Controversies and consensus of neoadjuvant chemotherapy in soft-tissue sarcomas. ESMO Open. 2018;3(Suppl 1):e000293.CrossRef
18.
go back to reference Ratan R, Patel SR. Chemotherapy for soft tissue sarcoma. Cancer. 2016;122(19):2952–60.CrossRef Ratan R, Patel SR. Chemotherapy for soft tissue sarcoma. Cancer. 2016;122(19):2952–60.CrossRef
19.
go back to reference Tanaka K, et al. Perioperative chemotherapy with ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities (JCOG0304). Jpn J Clin Oncol. 2015;45(6):555–61.PubMed Tanaka K, et al. Perioperative chemotherapy with ifosfamide and doxorubicin for high-grade soft tissue sarcomas in the extremities (JCOG0304). Jpn J Clin Oncol. 2015;45(6):555–61.PubMed
20.
go back to reference Movva S, et al. Patterns of chemotherapy administration in high-risk soft tissue sarcoma and impact on overall survival. J Natl Compr Canc Netw. 2015;13(11):1366–74.CrossRef Movva S, et al. Patterns of chemotherapy administration in high-risk soft tissue sarcoma and impact on overall survival. J Natl Compr Canc Netw. 2015;13(11):1366–74.CrossRef
21.
go back to reference Gronchi A, Jones RL. The value of neoadjuvant chemotherapy in localized high-risk soft-tissue sarcoma of the extremities and trunk. JAMA Oncol. 2018;4:1167–8.CrossRef Gronchi A, Jones RL. The value of neoadjuvant chemotherapy in localized high-risk soft-tissue sarcoma of the extremities and trunk. JAMA Oncol. 2018;4:1167–8.CrossRef
22.
go back to reference Maretty-Kongstad K, et al. A validated prognostic biomarker score for adult patients with nonmetastatic soft tissue sarcomas of the trunk and extremities. Translational Oncology. 2017;10(6):942–8.CrossRef Maretty-Kongstad K, et al. A validated prognostic biomarker score for adult patients with nonmetastatic soft tissue sarcomas of the trunk and extremities. Translational Oncology. 2017;10(6):942–8.CrossRef
23.
go back to reference Schenone AD, et al. Risk-stratified patients with resectable soft tissue sarcoma benefit from epirubicin-based adjuvant chemotherapy. Cancer Med. 2014;3(3):603–12.CrossRef Schenone AD, et al. Risk-stratified patients with resectable soft tissue sarcoma benefit from epirubicin-based adjuvant chemotherapy. Cancer Med. 2014;3(3):603–12.CrossRef
24.
go back to reference Greto D, et al. Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma. Tumori. 2018. p. 300891618765565. Greto D, et al. Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma. Tumori. 2018. p. 300891618765565.
Metadata
Title
Chemotherapy improves distant control in localized high-grade soft tissue sarcoma of the extremity/trunk
Authors
Victoria T. Rizk
Arash O. Naghavi
Andrew S. Brohl
David M. Joyce
Odion Binitie
Youngchul Kim
John P. Hanna
Jennifer Swank
Ricardo J. Gonzalez
Damon R. Reed
Mihaela Druta
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Clinical Sarcoma Research / Issue 1/2020
Electronic ISSN: 2045-3329
DOI
https://doi.org/10.1186/s13569-020-00132-w

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