Skip to main content
SpringerLink
Log in

Concurrent Chemoradiation Therapy for Soft Tissue Sarcoma

  • Chapter
  • First Online:
Radiation Therapy for Sarcomas and Skin Cancers

Part of the book series: Practical Guides in Radiation Oncology ((PGRO))

Abstract

Soft tissue sarcoma (STS) represents a heterogeneous group of malignancies. Many patients are treated with wide local excision with or without radiation therapy and/or chemotherapy. Patients with large and/or high-grade tumors have a particularly high risk of disease recurrence. Concurrent chemoradiation therapy dually seeks to reduce the risk of local recurrence through radiosensitization and to reduce the risk of distant recurrence through eradication of micrometastatic disease. The following chapter reviews classic anthracycline-based CRT (concurrent chemoradiotherapy) paradigms and describes more modern data that demonstrates improved tolerability of these regimens using modern radiotherapy and supportive care techniques. New CRT regimens using immunotherapy and targeted systemic therapy agents that are currently being tested in multicenter prospective trials will also be explored.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pisters PW, Leung DH, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996;14(5):1679–89.

    Article  Google Scholar 

  2. Zagars GK, Ballo MT, Pisters PW, Pollock RE, Patel SR, Benjamin RS. Preoperative vs. postoperative radiation therapy for soft tissue sarcoma: a retrospective comparative evaluation of disease outcome. Int J Radiat Oncol Biol Phys. 2003a;56(2):482–8.

    Article  Google Scholar 

  3. Zagars GK, Ballo MT, Pisters PW, Pollock RE, Patel SR, Benjamin RS. Prognostic factors for disease-specific survival after first relapse of soft-tissue sarcoma: analysis of 402 patients with disease relapse after initial conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys. 2003b;57(3):739–47.

    Article  Google Scholar 

  4. Zagars GK, Ballo MT, Pisters PW, Pollock RE, Patel SR, Benjamin RS. Surgical margins and reresection in the management of patients with soft tissue sarcoma using conservative surgery and radiation therapy. Cancer. 2003c;97(10):2544–53.

    Article  Google Scholar 

  5. Martin E, Coert JH, Flucke UE, Slooff WM, Ho VKY, van der Graaf WT, van Dalen T, van de Sande MAJ, van Houdt WJ, Grunhagen DJ, Verhoef C. A nationwide cohort study on treatment and survival in patients with malignant peripheral nerve sheath tumours. Eur J Cancer. 2020;124:77–87.

    Article  Google Scholar 

  6. Pisters PW, Ballo MT, Patel SR. Preoperative chemoradiation treatment strategies for localized sarcoma. Ann Surg Oncol. 2002;9(6):535–42.

    Article  Google Scholar 

  7. DeLaney TF, Liebsch NJ, Pedlow FX, Adams J, Weyman EA, Yeap BY, Depauw N, Nielsen GP, Harmon DC, Yoon SS, Chen YL, Schwab JH, Hornicek FJ. Long-term results of phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol. 2014;110(2):115–22.

    Article  Google Scholar 

  8. Mullen JT, Kobayashi W, Wang JJ, Harmon DC, Choy E, Hornicek FJ, Rosenberg AE, Chen YL, Spiro IJ, DeLaney TF. Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas. Cancer. 2012;118(15):3758–65.

    Article  Google Scholar 

  9. Kraybill WG, Harris J, Spiro IJ, Ettinger DS, DeLaney TF, Blum RH, Lucas DR, Harmon DC, Letson GD, Eisenberg B, T. Radiation Therapy Oncology Group. 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(4):619–25.

    Article  Google Scholar 

  10. Kraybill WG, Harris J, Spiro IJ, Ettinger DS, DeLaney TF, Blum RH, Lucas DR, Harmon DC, Letson GD, Eisenberg B. 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. 2010;116(19):4613–21.

    Article  Google Scholar 

  11. Pisters PW. Preoperative chemotherapy and split-course radiation therapy for patients with localized soft tissue sarcomas: home run, base hit, or strike out? J Clin Oncol. 2006;24(4):549–51.

    Article  Google Scholar 

  12. Wang D, Zhang Q, Eisenberg BL, Kane JM, Li XA, Lucas D, Petersen IA, DeLaney TF, Freeman CR, Finkelstein SE, Hitchcock YJ, Bedi M, Singh AK, Dundas G, Kirsch DG. 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.

    Article  Google Scholar 

  13. Chowdhary M, Sen N, Jeans EB, Miller L, Batus M, Gitelis S, Wang D, Abrams RA. Neoadjuvant interdigitated chemoradiotherapy using mesna, doxorubicin, and ifosfamide for large, high-grade, soft tissue sarcomas of the extremity: improved efficacy and reduced toxicity. Am J Clin Oncol. 2019;42(1):1–5.

    Article  Google Scholar 

  14. Lu E, Perlewitz KS, Hayden JB, Hung AY, Doung YC, Davis LE, Mansoor A, Vetto JT, Billingsley KG, Kaempf A, Park B, Ryan CW. Epirubicin and Ifosfamide with preoperative radiation for high-risk soft tissue sarcomas. Ann Surg Oncol. 2018;25(4):920–7.

    Article  Google Scholar 

  15. Kim JR, Moon YJ, Kwon KS, Bae JS, Wagle S, Kim KM, Park HS, Lee H, Moon WS, Chung MJ, Kang MJ, Jang KY. Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. PLoS One. 2013;8(12):e82870.

    Article  ADS  Google Scholar 

  16. Stower H. A new generation of immunotherapy. Nat Med. 2019;25:1798–9. https://doi.org/10.1038/s41591-019-0684-z.

    Article  Google Scholar 

  17. Keung EZ, Burgess M, Salazar R, et al. Correlative analyses of the SARC028 trial reveal an association between sarcoma-associated immune infiltrate and response to pembrolizumab. Clin Cancer Res. 2020;26:1258–66.

    Article  Google Scholar 

  18. Pollack SM, He Q, Yearley JH, Emerson R, Vignali M, Zhang Y, Redman MW, Baker KK, Cooper S, Donahue B, Loggers ET, Cranmer LD, Spraker MB, Seo YD, Pillarisetty VG, Ricciotti RW, Hoch BL, McClanahan TK, Murphy E, Blumenschein WM, Townson SM, Benzeno S, Riddell SR, Jones RL. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer. 2017;123(17):3291–304.

    Article  Google Scholar 

  19. Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D’Angelo S, Attia S, Riedel RF, Priebat DA, Movva S, Davis LE, Okuno SH, Reed DR, Crowley J, Butterfield LH, Salazar R, Rodriguez-Canales J, Lazar AJ, Wistuba LH II, Baker RG, Maki DR, Patel S. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017;18(11):1493–501.

    Article  Google Scholar 

  20. D’Angelo SP, Mahoney MR, Van Tine BA, Atkins J, Milhem MM, Jahagirdar BN, Antonescu CR, Horvath E, Tap WD, Schwartz GK, Streicher H. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol. 2018;19(3):416–26.

    Article  Google Scholar 

  21. Formenti SC, Demaria S. Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013;105(4):256–65.

    Article  Google Scholar 

  22. Casper ES, Waltzman RJ, Schwartz GK, Sugarman A, Pfister D, Ilson D, Woodruff J, Leung D, Bertino JR. Phase II trial of paclitaxel in patients with soft-tissue sarcoma. Cancer Investig. 1998;16(7):442–6.

    Article  Google Scholar 

  23. Schlemmer M, Reichardt P, Verweij J, Hartmann JT, Judson I, Thyss A, Hogendoorn PC, Marreaud S, Van Glabbeke M, Blay JY. Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group. Eur J Cancer. 2008;44(16):2433–6.

    Article  Google Scholar 

  24. Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, Isambert N, Peyrade F, Chevreau C, Bompas E, Brain EG, Blay JY. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol. 2008;26(32):5269–74.

    Article  Google Scholar 

  25. Fata F, O'Reilly E, Ilson D, Pfister D, Leffel D, Kelsen DP, Schwartz GK, Casper ES. Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer. 1999;86(10):2034–7.

    Article  Google Scholar 

  26. Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24(24):3953–8.

    Article  Google Scholar 

  27. Schwartz GK, Winter K, Minsky BD, Crane C, Thomson PJ, Anne P, Gross H, Willett C, Kelsen D. Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114). J Clin Oncol. 2009;27(12):1956–62.

    Article  Google Scholar 

  28. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Bilgen EJS, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A, C. Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.

    Article  Google Scholar 

  29. Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, Chen M, Kim DW, Kim HK, Min YJ, Kang JH, Choi JH, Kim SW, Zhu G, Wu YL, Kim SR, Lee KH, Song HS, Choi YL, Sun JM, Jung SH, Ahn MJ, Park K. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung Cancer: KCSG-LU05-04. J Clin Oncol. 2015;33(24):2660–6.

    Article  Google Scholar 

  30. Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16(2):187–99.

    Article  Google Scholar 

  31. Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017;28(4):777–83.

    Article  Google Scholar 

  32. Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR, Cancer and B. Leukemia Group. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007;25(13):1698–704.

    Article  Google Scholar 

  33. Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, Brockstein BE, Agulnik MB, Mittal BB, Yunus F, Samant S, Raez LE, Mehra R, Kumar P, Ondrey F, Marchand P, Braegas B, Seiwert TY, Villaflor VM, Haraf DJ, Vokes EE. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014;32(25):2735–43.

    Article  Google Scholar 

  34. Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler JJ, Limaye S, Riley S, Posner M. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14(3):257–64.

    Article  Google Scholar 

  35. Fujisawa Y, Yoshino K, Kadono T, Miyagawa T, Nakamura Y, Fujimoto M. Chemoradiotherapy with taxane is superior to conventional surgery and radiotherapy in the management of cutaneous angiosarcoma: a multicentre, retrospective study. Br J Dermatol. 2014;171(6):1493–500.

    Article  Google Scholar 

  36. Watson D. Soft-tissue sarcoma of the extremity. Experience with limb-sparing surgery. Med J Aust. 1994;160(7):412–6.

    Article  Google Scholar 

  37. Cormier J. Cohort analysis of patients with localized, high-risk, extremity soft tissue sarcoma treated at two cancer centers: chemotherapy-associated outcomes. J Clin Oncol. 2004;22:4567–74.

    Article  Google Scholar 

  38. O’Byrne K. The role of adjuvant chemotherapy in the treatment of adult soft tissue sarcomas. Crit Rev Oncol Hematol. 1998;27(3):221–7.

    Article  Google Scholar 

  39. Collaboration SM-A. Adjuvant chemotherapy for localized resectable soft tissue sarcoma of adults: meta-analysis of individual data. Lancet. 1997;350(9092):1647–54.

    Article  Google Scholar 

  40. Brodowicz T. Intensified adjuvant IFADIC chemotherapy for adult soft tissue sarcoma: a prospective randomized feasibility trial. Sarcoma. 2000;4(4):151–60.

    Article  Google Scholar 

  41. Schenone A. Risk-stratified patients with resectable soft tissue sarcoma benefit from epirubicin-based adjuvant chemotherapy. Cancer Med. 2014;3(3):603–12.

    Article  Google Scholar 

  42. Pasquali S. Prognostic stratification using the nomogram sarculator and its impact on study results in a randomized controlled trial (RCT) for localized soft tissue sarcomas (STS): a secondary analysis of the EORTC-STBSG 62931. ASCO; 2018.

    Google Scholar 

  43. Abdalla E. Metastatectomy for limited metastases from soft tissue sarcoma. Curr Treat Options in Oncol. 2002;3(6):497–505.

    Article  Google Scholar 

  44. Bramwell V. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma. Cochrane Database Syst Rev. 2003;(3):CD003293.

    Google Scholar 

  45. Verma S. Meta-analysis of ifosfamide-based combination chemotherapy in advanced soft tissue sarcoma. Cancer Treat Rev. 2008;34(4):339–47.

    Article  MathSciNet  Google Scholar 

  46. O’Bryan R. Dose response evaluation of Adriamycin in human neoplasia. Cancer. 1977;39:1940–8.

    Article  Google Scholar 

  47. Judson I. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415–23.

    Article  Google Scholar 

  48. Grenader T. Long-term response to pegylated liposomal doxorubicin in patients with metastatic soft tissue sarcomas. Anti-Cancer Drugs. 2009;20(1):15–20.

    Article  Google Scholar 

  49. Judson I. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001;37(7):870–7.

    Article  Google Scholar 

  50. Van der Graaf W. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879–86.

    Article  Google Scholar 

  51. Demetri G. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016;34(8):786–93.

    Article  Google Scholar 

  52. Schoffski P. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016;387(10028):1629–37.

    Article  Google Scholar 

  53. Stacchiotti S. Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network. Ann Oncol. 2012;23:501–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, USA

    Matthew B. Spraker

  2. Department of Internal Medicine, Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA

    S. Haarberg, H. Ellis & B. A. Van Tine

Authors
  1. Matthew B. Spraker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Haarberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Ellis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. A. Van Tine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew B. Spraker .

Editor information

Editors and Affiliations

  1. Department of Radiation Oncology, University of Washington, Seattle, WA, USA

    Edward Kim

  2. Department of Radiation Oncology, University of Washington, Seattle, WA, USA

    Upendra Parvathaneni

  3. Department of Radiation Oncology, The Ohio State University James Cancer Center, Columbus, OH, USA

    Meng Xu Welliver

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Spraker, M.B., Haarberg, S., Ellis, H., Van Tine, B.A. (2022). Concurrent Chemoradiation Therapy for Soft Tissue Sarcoma. In: Kim, E., Parvathaneni, U., Welliver, M.X. (eds) Radiation Therapy for Sarcomas and Skin Cancers. Practical Guides in Radiation Oncology. Springer, Cham. https://doi.org/10.1007/978-3-031-06706-8_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-06706-8_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-06705-1

  • Online ISBN: 978-3-031-06706-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation