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Published in: Current Oncology Reports 6/2016

01-06-2016 | Sarcomas (SR Patel, Section Editor)

Advances in Radiation Therapy for Primary and Metastatic Adult Soft Tissue Sarcomas

Authors: Philip Blumenfeld, Neilayan Sen, Ross Abrams, Dian Wang

Published in: Current Oncology Reports | Issue 6/2016

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Abstract

Soft tissue sarcomas (STS) consist of a heterogeneous group of rare malignancies arising from mesenchymal origin. While surgical resection is the primary treatment for STS, the use of radiotherapy (RT) as an adjunctive modality has been shown to improve oncologic outcomes. Technologic improvements, such as image guidance and intensity-modulated radiotherapy that significantly improve both the precision and delivery of RT, have led to the reduction of long-term RT toxicities without compromising outcomes. This review addresses these technologic advancements as well as discussing the most current updates regarding the use of brachytherapy, charged particles, and novel agents with RT.
Literature
2.
go back to reference Fletcher CDM, Unni KK, Mertens F, editors. World Health Organization classification of tumors: pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press; 2002. Fletcher CDM, Unni KK, Mertens F, editors. World Health Organization classification of tumors: pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press; 2002.
3.
go back to reference Lawrence Jr W, Donegan WL, Natarajan N, et al. Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons. Ann Surg. 1987;205(4):349–59.CrossRefPubMedPubMedCentral Lawrence Jr W, Donegan WL, Natarajan N, et al. Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons. Ann Surg. 1987;205(4):349–59.CrossRefPubMedPubMedCentral
4.
go back to reference Enneking WF, Spanier SS, Malawar MM. The effect of the anatomic setting on the results of surgical procedure for soft parts sarcoma of the thigh. Cancer. 1981;47(5):1005–22.CrossRefPubMed Enneking WF, Spanier SS, Malawar MM. The effect of the anatomic setting on the results of surgical procedure for soft parts sarcoma of the thigh. Cancer. 1981;47(5):1005–22.CrossRefPubMed
5.
go back to reference Riad S, Griffin AM, Liberman B, et al. Lymph node metastasis in soft tissue sarcoma in an extremity. Clin Orthop Relat Res. 2004;426:129–34.CrossRefPubMed Riad S, Griffin AM, Liberman B, et al. Lymph node metastasis in soft tissue sarcoma in an extremity. Clin Orthop Relat Res. 2004;426:129–34.CrossRefPubMed
6.
go back to reference Rosenberg SA, Tepper J, Glatstein E, 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(3):305–15.CrossRefPubMedPubMedCentral Rosenberg SA, Tepper J, Glatstein E, 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(3):305–15.CrossRefPubMedPubMedCentral
7.
go back to reference Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14(3):859–68.PubMed Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14(3):859–68.PubMed
8.
go back to reference Yang JC, Chang AE, Baker AR, 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;16(1):197–203.PubMed Yang JC, Chang AE, Baker AR, 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;16(1):197–203.PubMed
9.
go back to reference Gitelis S, Thomas R, Templeton A, Schajowicz F. Characterization of the pseudocapsule of soft-tissue sarcomas. An experimental study in rats. Clin Orthop Relat Res. 1989;246:285–92.PubMed Gitelis S, Thomas R, Templeton A, Schajowicz F. Characterization of the pseudocapsule of soft-tissue sarcomas. An experimental study in rats. Clin Orthop Relat Res. 1989;246:285–92.PubMed
10.
go back to reference 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 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
11.
go back to reference O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359:2235–41.CrossRefPubMed O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359:2235–41.CrossRefPubMed
12.•
go back to reference Wang D, Bosch W, Roberge D, et al. RTOG sarcoma radiation oncologists reach consensus on gross tumor volume and clinical target volume on computed tomographic images for preoperative radiotherapy of primary soft tissue sarcoma of extremity in Radiation Therapy Oncology Group studies. Int J Radiat Oncol Biol Phys. 2011;81(4):e525–8. In this article, a group of RTOG sarcoma radiation oncology experts have reached a consensus on how to contour gross tumor volume and clinical target volume for preoperative radiation treatment of primary extremity soft tissue sarcoma. Detailed description and images were also published in the RTOG website Core Lab Contouring Atlas https://www.rtog.org/LinkClick.aspx?fileticket=AThtvc6dabE%3d&tabid=356. Wang D, Bosch W, Roberge D, et al. RTOG sarcoma radiation oncologists reach consensus on gross tumor volume and clinical target volume on computed tomographic images for preoperative radiotherapy of primary soft tissue sarcoma of extremity in Radiation Therapy Oncology Group studies. Int J Radiat Oncol Biol Phys. 2011;81(4):e525–8. In this article, a group of RTOG sarcoma radiation oncology experts have reached a consensus on how to contour gross tumor volume and clinical target volume for preoperative radiation treatment of primary extremity soft tissue sarcoma. Detailed description and images were also published in the RTOG website Core Lab Contouring Atlas https://​www.​rtog.​org/​LinkClick.​aspx?​fileticket=​AThtvc6dabE%3d&​tabid=​356.
13.
go back to reference Halperin EC. Intensity-modulated radiation treatment techniques and clinical applications. In: Perez and Brady’s principles and practice of radiation oncology. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008. Print. Halperin EC. Intensity-modulated radiation treatment techniques and clinical applications. In: Perez and Brady’s principles and practice of radiation oncology. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008. Print.
14.
go back to reference Alektiar KM, Brennan MF, Healey JH, Singer S. Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity. J Clin Oncol. 2008;26(20):3440–4.CrossRefPubMed Alektiar KM, Brennan MF, Healey JH, Singer S. Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity. J Clin Oncol. 2008;26(20):3440–4.CrossRefPubMed
15.
go back to reference O’Sullivan B, Griffin AM, Dickie CI, et al. Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma. Cancer. 2013;119(10):1878–84.CrossRefPubMed O’Sullivan B, Griffin AM, Dickie CI, et al. Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma. Cancer. 2013;119(10):1878–84.CrossRefPubMed
16.••
go back to reference 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 radiation therapy oncology group RTOG-0630 trial. J Clin Oncol. 2015;33(20):2231–8. Results of a multi-institutional phase II trial of image-guided preoperative radiation treatment for primary extremity soft tissue sarcoma (RTOG 0630) have demonstrated a significant reduction in late toxicity in extremity STS patients treated with preoperative IG-RT to a reduced target volume when compared to the NCIC SR2 trial. Excellent local control, the absence of marginal-field recurrences, and the favorable late toxicity profile suggest that the parameters used in this protocol are appropriate for preoperative IG-IMRT for extremity STS. This is a sarcoma research milestone publication.CrossRefPubMed 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 radiation therapy oncology group RTOG-0630 trial. J Clin Oncol. 2015;33(20):2231–8. Results of a multi-institutional phase II trial of image-guided preoperative radiation treatment for primary extremity soft tissue sarcoma (RTOG 0630) have demonstrated a significant reduction in late toxicity in extremity STS patients treated with preoperative IG-RT to a reduced target volume when compared to the NCIC SR2 trial. Excellent local control, the absence of marginal-field recurrences, and the favorable late toxicity profile suggest that the parameters used in this protocol are appropriate for preoperative IG-IMRT for extremity STS. This is a sarcoma research milestone publication.CrossRefPubMed
17.
go back to reference Alektiar KM, Leung D, Zelefsky MJ, Healey JH, Brennan MF. Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity. Ann Surg Oncol. 2002;9(1):48–56.CrossRefPubMed Alektiar KM, Leung D, Zelefsky MJ, Healey JH, Brennan MF. Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity. Ann Surg Oncol. 2002;9(1):48–56.CrossRefPubMed
18.
go back to reference Alektiar KM, Brennan MF, Singer S. Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity. Cancer. 2011;117(14):3229–34.CrossRefPubMed Alektiar KM, Brennan MF, Singer S. Local control comparison of adjuvant brachytherapy to intensity-modulated radiotherapy in primary high-grade sarcoma of the extremity. Cancer. 2011;117(14):3229–34.CrossRefPubMed
19.
go back to reference Mendenhall WM, Indelicato DJ, Scarborough MT, et al. The management of adult soft tissue sarcomas. Am J Clin Oncol. 2009;32(4):436–42.CrossRefPubMed Mendenhall WM, Indelicato DJ, Scarborough MT, et al. The management of adult soft tissue sarcomas. Am J Clin Oncol. 2009;32(4):436–42.CrossRefPubMed
20.
go back to reference Lewis JJ, Leung D, Woodruff JM, Brennan MF. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg. 1998;228(3):355–65.CrossRefPubMedPubMedCentral Lewis JJ, Leung D, Woodruff JM, Brennan MF. Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg. 1998;228(3):355–65.CrossRefPubMedPubMedCentral
21.
go back to reference Feng M, Murphy J, Griffith KA, et al. Long-term outcomes after radiotherapy for retroperitoneal and deep truncal sarcoma. Int J Radiat Oncol Biol Phys. 2007;69(1):103–10.CrossRefPubMed Feng M, Murphy J, Griffith KA, et al. Long-term outcomes after radiotherapy for retroperitoneal and deep truncal sarcoma. Int J Radiat Oncol Biol Phys. 2007;69(1):103–10.CrossRefPubMed
22.
go back to reference Gieschen HL, Spiro IJ, Suit HD, et al. Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma. Int J Radiat Oncol Biol Phys. 2001;50(1):127–31.CrossRefPubMed Gieschen HL, Spiro IJ, Suit HD, et al. Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma. Int J Radiat Oncol Biol Phys. 2001;50(1):127–31.CrossRefPubMed
23.
go back to reference Ballo MT, Zagars GK, Pollock RE, Benjamin RS, Feig BW, Cormier JN, et al. Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment. Int J Radiat Oncol Biol Phys. 2007;67(1):158–63.CrossRefPubMed Ballo MT, Zagars GK, Pollock RE, Benjamin RS, Feig BW, Cormier JN, et al. Retroperitoneal soft tissue sarcoma: an analysis of radiation and surgical treatment. Int J Radiat Oncol Biol Phys. 2007;67(1):158–63.CrossRefPubMed
24.
go back to reference Tzeng CW, Fiveash JB, Popple RA, et al. Preoperative radiation therapy with selective dose escalation to the margin at risk for retroperitoneal sarcoma. Cancer. 2006;107(2):371–9.CrossRefPubMed Tzeng CW, Fiveash JB, Popple RA, et al. Preoperative radiation therapy with selective dose escalation to the margin at risk for retroperitoneal sarcoma. Cancer. 2006;107(2):371–9.CrossRefPubMed
25.
26.
go back to reference Baldini BH, Bosch W, Kane III JM, et al. Retroperitoneal sarcoma (RPS) High risk gross tumor volume boost (HR GTV Boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists. Ann Surg Oncol. 2015. doi:10.1245/s10434-015-4633-x.PubMedCentral Baldini BH, Bosch W, Kane III JM, et al. Retroperitoneal sarcoma (RPS) High risk gross tumor volume boost (HR GTV Boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists. Ann Surg Oncol. 2015. doi:10.​1245/​s10434-015-4633-x.PubMedCentral
27.
go back to reference Baldini EH, Abrams RA, Bosch W, et al. Retroperitoneal sarcoma target volume and organ at risk contour delineation agreement among NRG sarcoma radiation oncologists. IJROBP. 2015;92(5):1053–9. doi:10.1016/j.ijrobp.2015.04.039. Epub 2015 May 1.PMID:26194680. Baldini EH, Abrams RA, Bosch W, et al. Retroperitoneal sarcoma target volume and organ at risk contour delineation agreement among NRG sarcoma radiation oncologists. IJROBP. 2015;92(5):1053–9. doi:10.​1016/​j.​ijrobp.​2015.​04.​039. Epub 2015 May 1.PMID:26194680.
28.
go back to reference Yoon SS, Chen YL, Kirsch DG, et al. Proton-beam, intensity-modulated, and/or intraoperative electron radiation therapy combined with aggressive anterior surgical resection for retroperitoneal sarcomas. Ann Surg Oncol. 2010;17(6):1515–29.CrossRefPubMedPubMedCentral Yoon SS, Chen YL, Kirsch DG, et al. Proton-beam, intensity-modulated, and/or intraoperative electron radiation therapy combined with aggressive anterior surgical resection for retroperitoneal sarcomas. Ann Surg Oncol. 2010;17(6):1515–29.CrossRefPubMedPubMedCentral
29.
go back to reference Yoon SS, Duda DG, Karl DL, et al. Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2011;81(4):1081–90.CrossRefPubMedPubMedCentral Yoon SS, Duda DG, Karl DL, et al. Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2011;81(4):1081–90.CrossRefPubMedPubMedCentral
30.
go back to reference Sleijfer S, Ray-coquard I, Papai Z, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009;27(19):3126–32.CrossRefPubMed Sleijfer S, Ray-coquard I, Papai Z, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009;27(19):3126–32.CrossRefPubMed
31.•
go back to reference Wong P, Houghton P, Kirsch DG, et al. Combining targeted agents with modern radiotherapy in soft tissue sarcomas. J Natl Cancer Inst. 2014;106(11). In this article, a group of NRG Oncology sarcoma experts focused on translational research has worked with the NCI Radiation Research Program and Molecular Pharmacology Branch to establish positional statements on investigation of targeted agents in combination with radiation treatment of sarcoma. Wong P, Houghton P, Kirsch DG, et al. Combining targeted agents with modern radiotherapy in soft tissue sarcomas. J Natl Cancer Inst. 2014;106(11). In this article, a group of NRG Oncology sarcoma experts focused on translational research has worked with the NCI Radiation Research Program and Molecular Pharmacology Branch to establish positional statements on investigation of targeted agents in combination with radiation treatment of sarcoma.
32.
go back to reference Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg. 1999;229(5):602–10.CrossRefPubMedPubMedCentral Billingsley KG, Burt ME, Jara E, et al. Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg. 1999;229(5):602–10.CrossRefPubMedPubMedCentral
33.
go back to reference Burt BM, Ocejo S, Mery CM, et al. Repeated and aggressive pulmonary resections for leiomyosarcoma metastases extends survival. Ann Thorac Surg. 2011;92(4):1202–7.CrossRefPubMed Burt BM, Ocejo S, Mery CM, et al. Repeated and aggressive pulmonary resections for leiomyosarcoma metastases extends survival. Ann Thorac Surg. 2011;92(4):1202–7.CrossRefPubMed
34.
go back to reference Miyamoto C. (Chairperson & Professor, Department of Radiation Oncology, Temple University School of Medicine) Personal communication. 2010;23:51. Miyamoto C. (Chairperson & Professor, Department of Radiation Oncology, Temple University School of Medicine) Personal communication. 2010;23:51.
35.
go back to reference Dhakal S, Corbin KS, Milano MT, et al. Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys. 2012;82(2):940–5.CrossRefPubMed Dhakal S, Corbin KS, Milano MT, et al. Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys. 2012;82(2):940–5.CrossRefPubMed
36.
go back to reference Mehta N, Selch M, Wang PC, et al. Safety and efficacy of stereotactic body radiation therapy in the treatment of pulmonary metastases from high grade sarcoma. Sarcoma. 2013;2013:360214.CrossRefPubMedPubMedCentral Mehta N, Selch M, Wang PC, et al. Safety and efficacy of stereotactic body radiation therapy in the treatment of pulmonary metastases from high grade sarcoma. Sarcoma. 2013;2013:360214.CrossRefPubMedPubMedCentral
37.
go back to reference Soyfer V, Corn BW, Shtraus N, et al. Single-institution Experience of SBRT for lung metastases in sarcoma patients. Am J Clin Oncol. 2014. [Epub ahead of print]. Soyfer V, Corn BW, Shtraus N, et al. Single-institution Experience of SBRT for lung metastases in sarcoma patients. Am J Clin Oncol. 2014. [Epub ahead of print].
38.
go back to reference Navarria P, Ascolese AM, Cozzi L, et al. Stereotactic body radiation therapy for lung metastases from soft tissue sarcoma. Eur J Cancer. 2015;51(5):668–74.CrossRefPubMed Navarria P, Ascolese AM, Cozzi L, et al. Stereotactic body radiation therapy for lung metastases from soft tissue sarcoma. Eur J Cancer. 2015;51(5):668–74.CrossRefPubMed
Metadata
Title
Advances in Radiation Therapy for Primary and Metastatic Adult Soft Tissue Sarcomas
Authors
Philip Blumenfeld
Neilayan Sen
Ross Abrams
Dian Wang
Publication date
01-06-2016
Publisher
Springer US
Published in
Current Oncology Reports / Issue 6/2016
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-016-0523-z

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