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24-07-2017 | Soft-tissue sarcoma | Article

Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National Cancer Database Analysis

Journal: Annals of Surgical Oncology

Authors: Alicia A. Gingrich, MD, Sarah B. Bateni, MD, Arta M. Monjazeb, MD, Morgan A. Darrow, MD, Steven W. Thorpe, MD, Amanda R. Kirane, MD, Richard J. Bold, MD, Robert J. Canter, MD

Publisher: Springer International Publishing

Abstract

Background

Neoadjuvant radiotherapy (RT) is increasingly advocated for the management of soft tissue sarcoma (STS). Therefore, this study sought to characterize the impact of neoadjuvant RT on rates of R0 resection and overall survival (OS) in extremity STS patients undergoing surgery.

Methods

From January 2003 to December 2012, the study identified patients with a diagnosis of extremity STS from the National Cancer Database. After exclusion of patients younger than 18 years, not treated by surgery, who had metastases at diagnosis, intraoperative RT, and missing or unknown data, 27,969 patients were identified. Logistic regression and Cox-proportional hazard analysis were used to compare rates of R0 resection among preoperative, postoperative, and no-RT cohorts and to determine predictors of R0 resection and OS.

Results

The mean age of the patients was 59.5 ± 17.1 years, and 45.9% were female. The median tumor size was 10.5 cm. The data showed that 51% of the patients did not receive RT, 11.8% received preoperative RT, and 37.2% received postoperative RT. The rates of R0 resection were 90.1% for the preoperative RT cohort, 74.9% for the postoperative RT cohort, and 79.9% for the no-RT cohort (P < 0.001). The independent predictors for achievement of R0 resection included academic facility type (odds ratio [OR] 1.36; 95% confidence interval [CI] 1.20–1.55), histologic subtype, tumor size (OR 0.99; 95% CI 0.99–0.99), Charlson score (OR 0.92; 95% CI 0.84–0.99), and preoperative RT (OR 1.83; 95% CI 1.61–2.07). Both R0 resection and RT (pre- or post-operative) were associated with increased OS.

Conclusions

Preoperative RT independently predicts higher rates of R0 resection for patients with extremity STS undergoing surgical resection. Negative surgical margins and pre- or postoperative RT are associated with improved OS.
Literature
1.
Siegel RI, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5.CrossRefPubMed
2.
Leachman BK, Galloway TJ. The role for radiation therapy in the management of sarcoma. Surg Clin North Am. 2016;96:1127–39.CrossRefPubMed
3.
Crago AM, Lee AY. Multimodality management of soft tissue tumors in the extremity. Surg Clin North Am. 2016;96:977–92.CrossRefPubMed
4.
Sherman KI, Wayne JD, Chung J, et al. Assessment of the multimodality therapy use for extremity sarcoma in the United States. J Surg Oncol. 2014;109:395–404.
5.
Leachman BK, Galloway TJ. The role for radiation therapy in the management of sarcoma. Surg Clin North Am. 2016;96:1127–139.CrossRefPubMed
6.
Rosenberg SA, et al. The treatment of soft-tissue sarcomas of the extremities: prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. 1982;196:305–15.CrossRefPubMedPubMedCentral
7.
Yang JC, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol. 1998;16197–203.
8.
Beane JD, et al. Efficacy of adjuvant radiation therapy in the treatment of soft tissue sarcoma of the extremity: 20-year follow up of a randomized prospective trial. Ann Surg Oncol. 2014;21:2484–9.CrossRefPubMed
9.
Brennan MF, et al. Local recurrence in adult soft tissue sarcoma: a randomized trial of brachytherapy. Arch Surg. 1987;122:1289–93.CrossRefPubMed
10.
Pisters PW. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14:859–68.CrossRefPubMed
11.
Ueda T, et al. Multivariate analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma. Cancer. 1988;62:1444–50.CrossRefPubMed
12.
Koshy M, Rich SE, Mohiuddin MM. Improved survival with radiation therapy in high-grade soft tissue sarcoma of the extremities: a SEER analysis. Int J Radiat Oncol Biol Phys. 2010;77:203–09.
13.
Hou CH, Lazarides AL, Speicher PJ, et al. The use of radiation therapy in localized high-grade STS and potential impact on survival. Ann Surg Oncol. 2015;22:2831–8.CrossRefPubMed
14.
Kachare SD, Brinkly J, Vohra NA, et al. Radiotherapy associated with improved survival for high-grade sarcoma of the extremity. J Surg Oncol. 2015;112:338–43.CrossRefPubMed
15.
Gutierrez JC, et al. Outcomes for soft-tissue sarcoma in 8249 cases from a large state cancer registry. J Surg Res. 2007;141:105–14.CrossRefPubMed
16.
O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft tissue sarcoma of the limbs: a randomized trial. Lancet. 2002;359:2235–41.CrossRefPubMed
17.
Davis AM, O’Sullivan B, Turcotte R, et al. Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol. 2005;75:48–53.CrossRefPubMed
18.
NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma (2014). National comprehensive cancer network. Retrieved at http://​www.​nccn.​org/​professionals/​physician_​gls/​pdf/​sarcoma.​pdf. Accessed 30 Apr 2017.
19.
Davis LE, Ryan CW. Preoperative therapy for extremity soft tissue sarcomas. Curr Treat Options Oconcol. 2015;16:25
20.
Nathenson MJ, Sausville E. Looking for answers: the current status of neoadjuvant treatment in localized soft tissue sarcomas. Cancer Chemother Pharmacol. 2016. doi:10.​1007/​s00280-016-3055-1.
21.
Fairweather M, Keung E, Raut CP. Neoadjuvant therapy for soft-tissue sarcomas. Oncology. 2016;30:99–106.PubMed
22.
Canter RJ, Martinez SR, Tamurian RM, et al. Radiographic and histologic response to neoadjuvant therapy in patients with soft tissue sarcoma. Ann Surg Oncol. 2010;17:2578–84.CrossRefPubMedPubMedCentral
23.
Messiou C, Bonvalot S, Gronchi A, et al. Evaluation of response after preoperative radiotherapy in soft tissue sarcomas: the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group recommendations for radiological examination and reporting with an emphasis on magnetic resonance imaging. Eur J Cancer. 2016;56:37–44.CrossRefPubMed
24.
Roberge D, Skamene T, Nahal A, et al. Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma. Radiother Oncol. 2010;97:404–7.CrossRef
25.
Pisters PW, Leung DH, Woodruff J, et al. Analysis of prognostic factors in 1041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996;14:1679–89.CrossRefPubMed
26.
Zagars GK, Ballo MT, Pisters PW, et al. Surgical margins and resection in the management of patients with soft tissue sarcoma using conservative surgery and radiation therapy. Cancer. 2003;97:2544–53.CrossRefPubMed
27.
Tanabe K, Pollock R, Ellis L, et al. Influence of surgical margins on outcomes in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer. 1994;73:1652–9.CrossRefPubMed
28.
McKee MD, Liu DF, Brooks JJ, et al. The prognostic significance of margin width for extremity and trunk sarcoma. J Surg Oncol. 2004;85:68–76.CrossRefPubMed
29.
Willeumier JJ, Fiocco M, Nout R, et al. High-grade soft tissue sarcomas of the extremities: surgical margins influence only local recurrence not overall survival. Int Orthop. 2015;39:935–41.CrossRefPubMed
30.
Cheng EY, et al. Soft tissue sarcomas: preoperative versus postoperative radiotherapy. J Surg Oncol. 1996;61:90–9.CrossRefPubMed
31.
Biau DJ, Ferguson PC, Chung P, et al. Local recurrence of localized soft tissue sarcoma: a new look at old predictors. Cancer. 2012;118:5867–77.CrossRefPubMed
32.
Atean I, Pointreau Y, Rosset P, et al. Prognostic factors of extremity soft tissue sarcoma in adults: a single-institution analysis. Cancer Radiother. 2012;16:661–6.CrossRefPubMed
33.
Grochi A, Lo Vullo S, Colombo C, et al. Extremity soft tissue sarcoma in a series of patients treated at a single institution: local control directly impacts survival. Ann Surg. 2012;251:506–11.CrossRef
34.
O’Donnell PW, Griffin AM, Eward WC, et al. The effect of the setting of a positive surgical margin in soft tissue sarcoma. Cancer. 2014;120:2866–75.CrossRefPubMed
35.
Alamanda VK, Crosby SN, Archer KR, et al. Predictors and clinical significance of local recurrence in soft tissue sarcoma of the extremity. Acta Oncol. 2013;52:793–802.CrossRefPubMed
36.
Blumenfeld P, Sen N, Abrams R, et al. Advances in radiation therapy for primary and metastatic adult soft tissue sarcomas. Curr Oncol Rep. 2016;18:36.CrossRefPubMed
37.
Kuklo TR, Temple HT, Owens BD, et al: Preoperative versus postoperative radiation therapy for soft tissue sarcomas. Am J Orthop. 2005;34:75–80.PubMed
38.
Zagars GK, Ballo MT, Pisters P, et al. Preoperative vs postoperative radiation therapy for soft tissue sarcoma: a retrospective comparative evaluation of disease outcome. Int J Radiat Oncol. 2003;56:482–8.CrossRef
39.
Sampath S, Shcultheiss TE, Hitchock YJ, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma: multi-institutional analysis of 821 patients. Int J Radiat Oncol Biol Phys. 2011;81:496–505.CrossRef
40.
Ballo MT, Zagars GK. Radiation therapy for soft tissue sarcoma. Surg Oncol Clin North Am. 2003;12:449–67.CrossRef
41.
Willeumier JJ, Rueten-Budde AJ, Jeys LM, 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:e012930.