Intraoperative Electron Radiation Therapy Combined with External Beam Radiation Therapy after Gross Total Resection in Extremity Soft Tissue Sarcoma: A European Pooled Analysis
We report a pooled analysis evaluating the combination of gross complete limb-sparing surgery, intraoperative electron radiation therapy (IOERT), and external beam radiation therapy (EBRT) in patients with extremity soft tissue sarcoma (STS).
Individual data of 259 patients (median follow-up 63 months) with extremity STS from three European expert centers were pooled. Median age was 55 years and median tumor size was 8 cm. Eighty percent of patients presented with primary disease, mainly located in the lower limb (81%). Union for International Cancer Control 7th edition stage at presentation was as follows: stage I: 9%; stage II: 47%; stage III: 39%; stage IV: 5%. Most patients showed high-grade lesions (91%), predominantly liposarcoma (31%). Median IOERT dose was 12 Gy, preceeded (17%) or followed (83%) by EBRT, with a median dose of 45 Gy.
Surgery resulted in R0 resections in 71% of patients and R1 resections in 29% of patients. The 5-year local control (LC) rate was 86%, and significant factors in univariate analysis were disease status and resection margin. Only margin remained significant in multivariate analysis. The 5-year distant control rate was 69%, and significant factors in univariate analysis were histology, grading, resection margin, and metastases prior to/at IOERT. Only grading and metastases remained significant in multivariate analysis. Actuarial 5-year rates of freedom from treatment failure and OS were 61% and 78%, respectively. Significant factors for OS were grading and metastases prior to/at IOERT (univariate, multivariate). Limb preservation and good functional outcome were achieved in 95% and 81% of patients.
Our pooled analysis confirmed prior reports of encouraging LC and survival, with excellent rates of preserved limb function with this treatment approach. Resection margin remained the most important factor for LC, while grading and metastases prior to/at IOERT mainly predicted survival.
The authors thank Alexandra Diwo and Christiane Boos for their assistance in data handling and database management. No writing assistance was involved.
Conflict of interest
Falk Roeder, Antonino de Paoli, Ladan Saleh-Ebrahimi, Ingo Alldinger, Giulio Bertola, Giovanni Boz, Federico Navarria, Miguel Cuervo, Matthias Uhl, Ana Alvarez, Markus Buechler, Burkhard Lehner, Juergen Debus, Felipe A. Calvo, and Robert Krempien declare no conflicts of interest.
- 2.National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology—Soft Tissue Sarcoma V2.2017. http://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed 10 Feb 2017.
- 13.Roeder FF, Schulz-Ertner D, Nikoghosyan AV, et al. A clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma. BMC Cancer. 2012;12:287.CrossRefGoogle Scholar
- 14.Roeder FF, Timke C, Saleh-Ebrahimi L, et al. Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 Gy) and intraoperative radiation therapy (15 gy) in patients with primarily resectable pancreatic cancer—NEOPANC. BMC Cancer. 2012;12:112.CrossRefGoogle Scholar
- 15.Roeder F, Ulrich A, Habl G, et al. Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis. BMC Cancer. 2014;14:617.CrossRefGoogle Scholar
- 20.Calvo FA, Sole CV, Polo A, et al. Limb-sparing management with surgical resection, external-beam and intraoperative electron-beam radiation therapy for boost for patients with primary soft tissue sarcoma of the extremity: a multicentric pooled analysis of long-term outcomes. Strahlenther Onkol. 2014;190:891–8.CrossRefGoogle Scholar
- 24.Alvarez A, Calvo FA, Gonzales C, et al. IORT in soft tissue sarcomas involving extremities: toxicities and long-term functional results [abstract]. Revisiones en cancer. 2008;22:s55.Google Scholar
- 28.Kraybill WG, Harris J, Spiro IJ, 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;24:619–25.CrossRefGoogle Scholar
- 45.Dickie CI, Parent AL, Chung PW, et al. Measuring interfractional and intrafractional motion with cone beam computed tomography and an optical localization sytem for lower extremity soft tissue sarcoma patients treated with intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2010;78:1437–44.CrossRefGoogle Scholar
- 46.Wang D, Zhang Q, Eisenberg BL, et al. Significant reduction of late toxicities in patients with extremity sarcoma treated with image-guided radiation therapy to a reduced target volume: results of a radiation therapy oncology group RTOG-0630 trial. J Clin Oncol. 2015;33:2231–38.CrossRefGoogle Scholar
- 50.Callister MD, Beauchamp CP, Fitch TR, Gunderson LL. Preoperative radiation and IOERT for soft-tissue sarcomas of the extremities and trunk [abstract]. Revisiones en Cancer. 2008;22:54.Google Scholar