Skip to main content

Advertisement

SpringerLink
Log in

Perioperative high-dose-rate brachytherapy (PoHDR) in the multidisciplinary management of adult soft tissue sarcomas: a realistic alternative for a moderate radiotherapy dose escalation

  • Original Research
  • Published:
Journal of Radiation Oncology

Abstract

Objective

Conservative surgery in combination with local radiation therapy is considered a standard approach for soft tissue sarcomas (STS) leading to high local control rates and widely replacing the need for amputations. A close relationship exists between total radiation dose and local control probability. Combination of external beam radiotherapy and perioperative brachytherapy represents a moderate dose escalation that could contribute to improve local control.

Material and methods

From May 2015 to October 2018, 23 patients with histologically proven STS of various locations were prospectively entered into a data registry of perioperative HDR brachytherapy (PoBT) combined with external beam radiotherapy (EBRT). Multidisciplinary treatment comprised wide surgical excision, PoBT (16.5 Gy delivered in 3 fractions of 5.5 Gy twice daily with a gap time of at least 6 h between fractions), and EBRT delivered either pre- or postoperatively (median dose 47 Gy, range 40–57.5 Gy) up to a total accumulated radiotherapy equivalent dose for tumor of 69.5 to 86.5 Gy (median, 76.1 Gy), representing a moderate total dose escalation over the 66 Gy traditionally used.

Results

With a median follow-up of 13.4 months (range, 1–35.4 months), 22 patients (96%) remain alive without evidence of local or distant recurrence, 1 patient (4%) is alive with local relapse, and no patient has died because of tumor progression. Treatment-related adverse effects were mild or moderate. No cases of grades 4–5 late toxicity have been observed during the follow-up period.

Conclusions

HDR PoBT is safe, feasible, and well tolerated and allows for a moderate radiation dose escalation with acceptable rates of tumor control. Further follow-up is necessary to confirm impact on final outcomes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, Casali PG, RARECARE Working Group (2013) Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer [Internet] 49(3):684–695

    Article  CAS  Google Scholar 

  2. Yang JC, Chang AE, Baker AR, Sindelar WF, Danforth DN, Topalian SL, DeLaney T, Glatstein E, Steinberg SM, Merino MJ, Rosenberg SA (1998 Jan) Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 16(1):197–203

    Article  CAS  Google Scholar 

  3. Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF (1996 Mar) Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 14(3):859–868

    Article  CAS  Google Scholar 

  4. Rosenberg SA, Tepper J, Glatstein E, Costa J, Baker A, Brennan M 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 196(3):305–315

    Article  CAS  Google Scholar 

  5. Fein DA, Lee WR, Lanciano RM, Corn BW, Herbert SH, Hanlon AL, Hoffman JP, Eisenberg BL, Coia LR (1995) Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control? Int J Radiat Oncol Biol Phys 32(4):969–976

    Article  CAS  Google Scholar 

  6. Kretzler A, Molls M, Gradinger R, Lukas P, Steinau H-U, Würschmidt F (2004 Jun) Intraoperative radiotherapy of soft tissue sarcoma of the extremity. Strahlentherapie und Onkol 180(6):365–370

    Article  Google Scholar 

  7. Jebsen NL, Trovik CS, Bauer HCF, Rydholm A, Monge OR, Hall KS, Alvegård T, Bruland ØS (2008) Radiotherapy to improve local control regardless of surgical margin and malignancy grade in extremity and trunk wall soft tissue sarcoma: a Scandinavian sarcoma group study. Int J Radiat Oncol 71(4):1196–1203

    Article  Google Scholar 

  8. Khanfir K, Alzieu L, Terrier P, Le Péchoux C, Bonvalot S, Vanel D et al (2003) Does adjuvant radiation therapy increase loco-regional control after optimal resection of soft-tissue sarcoma of the extremities? Eur J Cancer 39(13):1872–1880

    Article  CAS  Google Scholar 

  9. Pisters PWT, O’Sullivan B, Maki RG (2007) Evidence-based recommendations for local therapy for soft tissue sarcomas. J Clin Oncol 25(8):1003–1008

    Article  Google Scholar 

  10. 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 77(1):203–209

    Article  Google Scholar 

  11. Jacobs AJ, Michels R, Stein J, Levin AS (2015 Mar 3) Improvement in overall survival from extremity soft tissue sarcoma over twenty years. Sarcoma 2015:1–9

    Article  Google Scholar 

  12. Amin MB, Edge SB (2017) American Joint Committee on Cancer. AJCC cancer staging manual:1024 p

  13. Naghavi AO, Fernandez DC, Mesko N, Juloori A, Martinez A, Scott JG, Shah C, Harrison LB (2017) American Brachytherapy Society consensus statement for soft tissue sarcoma brachytherapy. Brachytherapy 16(3):466–489

    Article  CAS  Google Scholar 

  14. Haas RLM, Miah AB, LePechoux C, DeLaney TF, Baldini EH, Alektiar K et al (2016 Apr) Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies. Radiother Oncol 119(1):14–21

    Article  Google Scholar 

  15. van Leeuwen CM, Oei AL, Crezee J, Bel A, Franken NAP, Stalpers LJA, et al. The alfa and beta of tumours: a review of parameters of the linear-quadrAvailable from: http://www.ncbi.nlm.nih.gov/pubmed/29769103

  16. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53(282):457–481

    Article  Google Scholar 

  17. Cancer Institute N. Common terminology criteria for adverse events (CTCAE) Version 4.0 2009

  18. Davis AM, O’Sullivan B, Bell RS, Turcotte R, Catton CN, Wunder JS, Chabot P, Hammond A, Benk V, Isler M, Freeman C, Goddard K, Bezjak A, Kandel RA, Sadura A, Day A, James K, Tu D, Pater J, Zee B (2002) Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma. J Clin Oncol 20(22):4472–4477

    Article  CAS  Google Scholar 

  19. Pohar S, Haq R, Liu L, Koniarczyk M, Hahn S, Damron T, Aronowitz JN (2007) Adjuvant high-dose-rate and low-dose-rate brachytherapy with external beam radiation in soft tissue sarcoma: a comparison of outcomes. Brachytherapy 6(1):53–57

    Article  Google Scholar 

  20. Laskar S, Bahl G, Puri A, Agarwal MG, Muckaden M, Patil N, Jambhekar N, Gupta S, Deshpande DD, Shrivastava SK, Dinshaw KA (2007) Perioperative interstitial brachytherapy for soft tissue sarcomas: prognostic factors and long-term results of 155 patients. Ann Surg Oncol 14(2):560–567

    Article  Google Scholar 

  21. Pisters PW, Pollock RE (1999) Staging and prognostic factors in soft tissue sarcoma. Semin Radiat Oncol 9(4):307–314

    Article  CAS  Google Scholar 

  22. Zagars GK, Ballo MT, Pisters PWT, Pollock RE, Patel SR, Benjamin RS, Evans HL (2003) Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy. Cancer 97(10):2530–2543

    Article  Google Scholar 

  23. Munro TR, Gilbert CW (1961) The relation between tumour lethal doses and the radiosensitivity of tumour cells. Br J Radiol 34(400):246–251

    Article  CAS  Google Scholar 

  24. Fein DA, Corn BW, Lanciano RM, Herbert SH, Hoffman JP, Coia LR (1995) Management of retroperitoneal sarcomas: does dose escalation impact on locoregional control? Int J Radiat Oncol 31(1):129–134

    Article  CAS  Google Scholar 

  25. San Miguel I, San Julián M, Cambeiro M, Sanmamed MF, Vázquez-García B, Pagola M et al (2011) Determinants of toxicity, patterns of failure, and outcome among adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with greater than conventional doses of perioperative high-dose-rate brachytherapy and external beam radiotherapy. Int J Radiat Oncol 81(4):e529–e539

    Article  Google Scholar 

  26. Andrews SF, Anderson PR, Eisenberg BL, Hanlon AL, Pollack A (2004) Soft tissue sarcomas treated with postoperative external beam radiotherapy with and without low-dose-rate brachytherapy. Int J Radiat Oncol 59(2):475–480

    Article  Google Scholar 

  27. Davis AM, O’Sullivan B, Turcotte R, Bell R, Catton C, Chabot P et al (2005) Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol 75(1):48–53

    Article  Google Scholar 

  28. Martínez-Monge R, Cambeiro M, Ramos LI, Olarte A, Valtueña G, San-Julián M, Alcalde J, Naval-Gías L, Jurado M (2014) Volume of high-dose regions and likelihood of locoregional control after perioperative high-dose-rate brachytherapy: do hotter implants work better? Brachytherapy 13(6):591–596

    Article  Google Scholar 

  29. Hoefkens F, Dehandschutter C, Somville J, Meijnders P, Van Gestel D (2016) Soft tissue sarcoma of the extremities: pending questions on surgery and radiotherapy. Radiat Oncol 11(1):136

    Article  Google Scholar 

  30. Kandel R, Coakley N, Werier J, Engel J, Ghert M, Verma S, Sarcoma Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care (2013) Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline. Curr Oncol 20(3):247–e254

    Article  Google Scholar 

  31. Hasley I, Gao Y, Blevins AE, Miller BJ (2018) The significance of a "close" margin in extremity sarcoma: a systematic review. Iowa Orthop J 38:123–130

    PubMed  PubMed Central  Google Scholar 

  32. Petera J, Soumarová R, Růžičková J, Neumanová R, Dušek L, Sirák I, Mačingová Z, Paluska P, Kašaová L, Hodek M, Vošmik M (2010) Perioperative hyperfractionated high-dose rate brachytherapy for the treatment of soft tissue sarcomas: multicentric experience. Ann Surg Oncol 17(1):206–210

    Article  Google Scholar 

  33. Pellizzon ACA, Nadalin W, Salvajoli JV, Ribeiro dos Santos Novaes PE, Fogaroli RC, Conte Maia MA, Ferrigno R. High dose rate brachytherapy as a boost in management of adult soft-tissue sarcomas: results and complications. J Brachytherapy Int 2000;17:43–50

  34. Chun M, Kang S, Kim BS, Oh YT (2001) High dose rate interstitial brachytherapy in soft tissue sarcoma: technical aspects and results. Jpn J Clin Oncol 31(6):279–283

    Article  CAS  Google Scholar 

  35. Aronowitz JN, Pohar SS, Liu L, Haq R, Damron TA (2006) Adjuvant high dose rate brachytherapy in the management of soft tissue sarcoma. Am J Clin Oncol 29(5):508–513

    Article  Google Scholar 

  36. Emory CL, Montgomery CO, Potter BK, Keisch ME, Conway SA (2012) Early complications of high-dose-rate brachytherapy in soft tissue sarcoma: a comparison with traditional external-beam radiotherapy. Clin Orthop Relat Res 470(3):751–758

    Article  Google Scholar 

  37. Sharma DN, Deo SVS, Rath GK, Shukla NK, Bakhshi S, Gandhi AK et al (2015) Perioperative high-dose-rate interstitial brachytherapy combined with external beam radiation therapy for soft tissue sarcoma. Brachytherapy 14(4):571–577

    Article  Google Scholar 

  38. Zelefsky MJ, Nori D, Shiu MH, Brennan MF (1990) Limb salvage in soft tissue sarcomas involving neurovascular structures using combined surgical resection and brachytherapy. Int J Radiat Oncol Biol Phys 19(4):913–918

    Article  CAS  Google Scholar 

  39. Kubo T, Sugita T, Shimose S, Matsuo T, Hirao K, Kimura H, Kenjo M, Ochi M (2005) Nerve tolerance to high-dose-rate brachytherapy in patients with soft tissue sarcoma: a retrospective study. BMC Cancer 5:79

    Article  Google Scholar 

  40. Lin PP, Schupak KD, Boland PJ, Brennan MF, Healey JH (1998) Pathologic femoral fracture after periosteal excision and radiation for the treatment of soft tissue sarcoma. Cancer 82(12):2356–2365

    Article  CAS  Google Scholar 

  41. Alektiar KM, Zelefsky MJ, Brennan MF (2000) Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity and superficial trunk. Int J Radiat Oncol Biol Phys 47(5):1273–1279

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Xin Chen-Zhao and Angel Montero contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital HM Sanchinarro, c/Oña 10, 28050, Madrid, Spain

    Xin Chen-Zhao, Angel Montero, Emilio Sanchez, Ovidio Hernando, Mercedes Lopez, Raquel Ciervide, Mariola Garcia-Aranda, Jeannette Valero, Rosa Alonso & Carmen Rubio

  2. Department of Orthopaedic Surgery, University Hospital HM Sanchinarro, Madrid, Spain

    Jorge De las Heras

  3. Department of Medical Physics, University Hospital HM Sanchinarro, Madrid, Spain

    Miguel Angel De la Casa, Juan Garcia, Daniel Zucca & Pedro Fernandez-Leton

Authors
  1. Xin Chen-Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angel Montero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jorge De las Heras
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miguel Angel De la Casa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emilio Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ovidio Hernando
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mercedes Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Raquel Ciervide
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mariola Garcia-Aranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jeannette Valero
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rosa Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Daniel Zucca
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Pedro Fernandez-Leton
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Carmen Rubio
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Xin Chen and Angel Montero. The first draft of the manuscript was written by Xin Chen and Angel Montero and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Angel Montero.

Ethics declarations

Ethical approval

All human studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

Conflict of interest

The authors declare they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen-Zhao, X., Montero, A., De las Heras, J. et al. Perioperative high-dose-rate brachytherapy (PoHDR) in the multidisciplinary management of adult soft tissue sarcomas: a realistic alternative for a moderate radiotherapy dose escalation. J Radiat Oncol 9, 15–24 (2020). https://doi.org/10.1007/s13566-020-00421-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13566-020-00421-3

Keywords

Search

Navigation