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

Annals of Surgical Oncology volume 24, pages 3252–3263 (2017)Cite this article

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.

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References

  1. Siegel RI, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5.

    Article  PubMed  Google Scholar 

  2. Leachman BK, Galloway TJ. The role for radiation therapy in the management of sarcoma. Surg Clin North Am. 2016;96:1127–39.

    Article  PubMed  Google Scholar 

  3. Crago AM, Lee AY. Multimodality management of soft tissue tumors in the extremity. Surg Clin North Am. 2016;96:977–92.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  9. Brennan MF, et al. Local recurrence in adult soft tissue sarcoma: a randomized trial of brachytherapy. Arch Surg. 1987;122:1289–93.

    CAS  Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  11. Ueda T, et al. Multivariate analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma. Cancer. 1988;62:1444–50.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  30. Cheng EY, et al. Soft tissue sarcomas: preoperative versus postoperative radiotherapy. J Surg Oncol. 1996;61:90–9.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  40. Ballo MT, Zagars GK. Radiation therapy for soft tissue sarcoma. Surg Oncol Clin North Am. 2003;12:449–67.

    Article  Google Scholar 

  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.

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Acknowledgement

This work was supported in part by the Dr. Mark Starr Family Fund. It also was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) through grant no. UL1TR001860 and by the Agency for Health Care Research and Quality through grant no. T32HS 022236. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, UC Davis Medical Center, Sacramento, CA, USA

    Alicia A. Gingrich MD, Sarah B. Bateni MD, Amanda R. Kirane MD, Richard J. Bold MD & Robert J. Canter MD

  2. Department of Radiation Oncology, UC Davis Medical Center, Sacramento, CA, USA

    Arta M. Monjazeb MD

  3. Department of Pathology, UC Davis Medical Center, Sacramento, CA, USA

    Morgan A. Darrow MD

  4. Department of Orthopedic Surgery, UC Davis Medical Center, Sacramento, CA, USA

    Steven W. Thorpe MD

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  1. Alicia A. Gingrich MD
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Correspondence to Robert J. Canter MD.

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Gingrich, A.A., Bateni, S.B., Monjazeb, A.M. et al. Neoadjuvant Radiotherapy is Associated with R0 Resection and Improved Survival for Patients with Extremity Soft Tissue Sarcoma Undergoing Surgery: A National Cancer Database Analysis. Ann Surg Oncol 24, 3252–3263 (2017). https://doi.org/10.1245/s10434-017-6019-8

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Keywords

  • National Cancer Database (NCDB)
  • Neoadjuvant RT
  • Soft Tissue Sarcomas (STS)
  • Surgical Margin Status
  • Facility Type