DOI QR코드

DOI QR Code

Neoadjuvant Treatment with Preoperative Radiotherapy for Extremity Soft Tissue Sarcomas: Long-Term Results from a Single Institution in Turkey

  • Dincbas, Fazilet Oner (Department of Radiation Oncology, Cerrahpasa Medical Faculty, Istanbul University) ;
  • Oksuz, Didem Colpan (Department of Radiation Oncology, Cerrahpasa Medical Faculty, Istanbul University) ;
  • Yetmen, Ozlem (Department of Radiation Oncology, Lutfi Kirdar Kartal Training and Research Hospital) ;
  • Hiz, Murat (Department of Orthopedic Surgery, Cerrahpasa Medical Faculty, Istanbul University) ;
  • Dervisoglu, Sergulen (Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University) ;
  • Turna, Hande (Department of Medical Oncology, Cerrahpasa Medical Faculty, Istanbul University) ;
  • Kantarci, Fatih (Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University) ;
  • Mandel, Nil Molinas (Department of Medical Oncology, VKV American Hospital) ;
  • Koca, Sedat (Department of Radiation Oncology, Faculty of Medicine Bahcesehir University)
  • Published : 2014.02.28

Abstract

Background: To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Materials and Methods: Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses. Results: Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7%, 47%, 69.8%, and 80%, 60%, 60% in the chemoradiotherapy and radiotherapy groups, respectively. On univariate analysis, patients who were treated with hypofractionation experienced significantly superior LC, DFS and CSS rates with similar rates of late toxicity when compared with patients who were treated with conventional fractionation and statistical significance was retained on multivariate analysis. Conclusions: Treatment results are consistent with the literature. As neoadjuvant chemoradiotherapy provides effective LC and CSS with acceptable morbidity, it should be preferred for patients with large and borderline resectable STS.

Keywords

Soft-tissue sarcomas;preoperative radiotherapy/chemotherapy;limb-sparing surgery

References

  1. Zagars GK, Ballo MT, Pisters PW, et al (2003). Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer, 97, 2530-43. https://doi.org/10.1002/cncr.11365
  2. Suit HD, Mankin HJ, Wood WC, Proppe KH (1985). Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma. Cancer, 55, 2659-67. https://doi.org/10.1002/1097-0142(19850601)55:11<2659::AID-CNCR2820551122>3.0.CO;2-Q
  3. Wanebo HJ, Temple WJ, Popp MB, et al (1995). Preoperative regional therapy for extremity sarcoma, a tricenter update. Cancer, 75, 2299-306. https://doi.org/10.1002/1097-0142(19950501)75:9<2299::AID-CNCR2820750919>3.0.CO;2-Y
  4. Yang JC, Chang AE, Baker AR, et al (1998). Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol, 16, 197-203. https://doi.org/10.1200/JCO.1998.16.1.197
  5. Pervaiz N (2008). A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer, 113, 573-81. https://doi.org/10.1002/cncr.23592
  6. Nielsen OS, Cummings B, O'Sullivan B, et al (1991). Preoperative and postoperative irradiation of soft tissue sarcomas: Effect of radiation field size. Int J Radiat Oncol Biol Phys, 21, 1595-9. https://doi.org/10.1016/0360-3016(91)90337-4
  7. O'Sullivan B, Davis AM, Turcotte R, et al (2002). Preoperative versus postoperative radiotherapy in soft tissue sarcoma of the limbs: A randomised trial. Lancet, 359, 2235-41. https://doi.org/10.1016/S0140-6736(02)09292-9
  8. O'Sullivan B, Davis AM, Turcotte R, et al (2004) Five-years results of a randomized phase III trial of pre-operative vs post-operative radiotherapy in extremity soft tissue sarcoma [abstract]. Proc Am Soc Clin Oncol, 23, 815.
  9. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF (1996). Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol, 14, 1679-89. https://doi.org/10.1200/JCO.1996.14.5.1679
  10. Rosenberg SA, Tepper J, Glatstein E, et al (1982). 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 Oncol, 196, 305-15. https://doi.org/10.1097/00000658-198209000-00009
  11. Sadoski C, Suit HD, Rosenberg A, Mankin H, Efird J (1993). Preoperative radiation, surgical margins and local control of extremity sarcomas of soft tissues. J Surg Oncol, 52, 223-30. https://doi.org/10.1002/jso.2930520405
  12. Sampath S, Schultheiss TE, Hitchcock YJ, et al (2011). Preoperative versus postoperative radiotherapy in soft-tissue sarcoma:multi-institutional analysis of 821 patients. Int J Radiat Oncol Biol Phys, 81, 498-505. https://doi.org/10.1016/j.ijrobp.2010.06.034
  13. Schuetze SM, Patel S (2009). Should patients with high-risk soft tissue sarcoma receive adjuvant chemotherapy? Oncologist, 14, 1003-12. https://doi.org/10.1634/theoncologist.2009-0007
  14. Kraybill WG, Harris J, Spiro IJ, et al (2010). Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. Cancer, 116, 4613-21. https://doi.org/10.1002/cncr.25350
  15. Gortzak E, Azzarelli A, Buesa J, et al (2001). EORTC soft tissue bone sarcoma group and the national cancer institute of canada clinical trials group/canadian sarcoma group: A randomised phase II study on neoadjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma. Eur J Cancer, 37, 1096-103. https://doi.org/10.1016/S0959-8049(01)00083-1
  16. Grobmyer SR, Maki RG, Demetri GD, et al (2004). Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol, 15, 1667-72. https://doi.org/10.1093/annonc/mdh431
  17. Koshy M, Rich SE, Mohiuddin MM (2010). Improved survival with radiation therapy in high-grade soft tissue sarcomas of the extremities: A SEER analysis. Int J Radiat Oncol Biol Phys, 77, 203-9. https://doi.org/10.1016/j.ijrobp.2009.04.051
  18. Kunisada T, Ngan SY, Powell G, Choong PF (2002). Wound complications following preoperative radiotherapy for soft tissue sarcoma. Eur J Surg Oncol, 28, 75-9. https://doi.org/10.1053/ejso.2001.1213
  19. Le Cesne A, Judson I, Crowther D, et al (2000). Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colonystimulating factor in advanced soft tissue sarcomas: A trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol, 18, 2676-84. https://doi.org/10.1200/JCO.2000.18.14.2676
  20. Mack LA, Crowe PJ, Yang JL, et al (2005). Preoperative chemoradiotherapy (modified Eilber protocol) provides maximum local control and minimal morbidity in patients with soft tissue sarcoma. Ann Surg Oncol, 12, 646-53. https://doi.org/10.1245/ASO.2005.03.064
  21. Al-Absi E (2010). A systematic review and meta-analysis of oncologic outcomes of pre- versus postoperative radiation in localized resectable soft-tissue sarcoma. Ann Surg Oncol, 17, 1367-74. https://doi.org/10.1245/s10434-009-0885-7
  22. Dagan R, Indelicato DJ, McGee L, et al (2012). The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity. Cancer, 118, 3199-207. https://doi.org/10.1002/cncr.26489
  23. Davis AM, O'Sullivan B, Turcotte R, et al (2005). Canadian Sarcoma Group; NCI Canada Clinical Trial Group Randomized Trial: Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol, 75, 48-53. https://doi.org/10.1016/j.radonc.2004.12.020
  24. Delaney TF (2004). Optimizing radiation therapy and posttreatment function in the management of extremity soft tissue sarcoma. Curr Treat Options Oncol, 5,463-76. https://doi.org/10.1007/s11864-004-0035-1
  25. Eilber FR, Morton DL, Eckardt J, Grant T, Weisenburger T (1984). Limb salvage for skeletal and soft tissue sarcomas: Multidisciplinary preoperative therapy. Cancer, 53, 2579-84. https://doi.org/10.1002/1097-0142(19840615)53:12<2579::AID-CNCR2820531202>3.0.CO;2-V