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Evaluation of two modalities of perioperative treatment in the management of extremity and truncal soft tissue sarcomas: neoadjuvant concurrent chemoradiotherapy and sequential treatment

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Abstract

Purpose

Patients with locally advanced grade 2–3 extremity/truncal soft tissue sarcomas (STS) are at high risk of recurrence. The objective of this study was to assess the efficacy and feasibility of neoadjuvant concurrent chemoradiotherapy (cCRT) in selected grade 2–3 patients with limb or trunk wall STS, and to compare this schedule to a sequential approach combining neoadjuvant chemotherapy and adjuvant radiotherapy.

Methods

We retrospectively included patients who underwent neoadjuvant cCRT at two comprehensive cancer centers from 1992–2016. We then compared these results to those of patients treated with preoperative chemotherapy and postoperative radiotherapy from a third comprehensive cancer center with a propensity score matched analysis.

Results

A total of 53 patients were treated by neoadjuvant cCRT; 58 patients could be matched with 29 patients in each treatment group after propensity score matching. Disease-free survival and overall survival at 5 years were 54.9 and 63.5%, respectively with neoadjuvant cCRT, with no significant difference when compared to the sequential treatment group. R0 resection rate was higher (90.9 vs 44.8%, p < 0.01) in the cCRT group than in the sequential treatment group during a shorter therapeutic sequence (118 vs 210.5 days, p < 0.01), with no impact on the surgical procedure or postoperative complications.

Conclusion

cCRT is feasible with acceptable immediate and late toxicities. It could facilitate surgery by increasing the R0 resection rate and improve patient compliance by shortening the therapeutic sequence.

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References

  1. Ducimetière F, Lurkin A, Ranchère-Vince D et al (2011) Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 6:e20294. https://doi.org/10.1371/journal.pone.0020294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ray-Coquard I, Thiesse P, Ranchère-Vince D et al (2004) Conformity to clinical practice guidelines, multidisciplinary management and outcome of treatment for soft tissue sarcomas. Ann Oncol 15:307–315

    Article  CAS  Google Scholar 

  3. Casali PG, Abecassis N, Bauer S et al (2018) Soft tissue and visceral sarcomas: ESMO–EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 29:iv51–iv67. https://doi.org/10.1093/annonc/mdy096

    Article  CAS  PubMed  Google Scholar 

  4. Zagars GK, Ballo MT, Pisters PWT 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 97:2530–2543. https://doi.org/10.1002/cncr.11365

    Article  PubMed  Google Scholar 

  5. Gronchi A, Vullo LS, Colombo C et al (2010) Extremity soft tissue sarcoma in a series of patients treated at a single institution: local control directly impacts survival. Ann Surg 251:506–511. https://doi.org/10.1097/SLA.0b013e3181cf87fa

    Article  PubMed  Google Scholar 

  6. Bramwell V, Rouesse J, Steward W et al (1994) Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma—reduced local recurrence but no improvement in survival: a study of the European organization for research and treatment of cancer soft tissue and bone sarcoma group. J Clin Oncol 12:1137–1149. https://doi.org/10.1200/JCO.1994.12.6.1137

    Article  CAS  PubMed  Google Scholar 

  7. 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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  9. Gronchi A, Ferrari S, Quagliuolo V et al (2017) Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol 18:812–822. https://doi.org/10.1016/S1470-2045(17)30334-0

    Article  CAS  PubMed  Google Scholar 

  10. Joiner M, van der Kogel A (2009) Basic clinical radiobiology. Hodder Arnold,

    Book  Google Scholar 

  11. Aupérin A, Le Péchoux C, Rolland E et al (2010) Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 28:2181–2190. https://doi.org/10.1200/JCO.2009.26.2543

    Article  CAS  PubMed  Google Scholar 

  12. Palassini E, Ferrari S, Verderio P et al (2015) Feasibility of preoperative chemotherapy with or without radiation therapy in localized soft tissue sarcomas of limbs and superficial trunk in the Italian sarcoma group/Grupo Español de Investigación en sarcomas randomized clinical trial: three versus five. J Clin Oncol 33:3628–3634. https://doi.org/10.1200/JCO.2015.62.9394

    Article  CAS  PubMed  Google Scholar 

  13. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  Google Scholar 

  14. Wang D, Zhang Q, Eisenberg BL et al (2015) 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 33:2231–2238. https://doi.org/10.1200/JCO.2014.58.5828

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rouëssé JG, Friedman S, Sevin DM et al (1987) Preoperative induction chemotherapy in the treatment of locally advanced soft tissue sarcomas. Cancer 60:296–300

    Article  Google Scholar 

  16. Gortzak E, Azzarelli A, Buesa J et al (2001) A randomised phase II study on neo-adjuvant chemotherapy for “high-risk” adult soft-tissue sarcoma. Eur J Cancer 37:1096–1103

    Article  CAS  Google Scholar 

  17. Grobmyer SR, Maki RG, Demetri GD et al (2004) Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol 15:1667–1672. https://doi.org/10.1093/annonc/mdh431

    Article  CAS  PubMed  Google Scholar 

  18. Bedi M, King DM, Shivakoti M et al (2013) Prognostic variables in patients with primary soft tissue sarcoma of the extremity and trunk treated with neoadjuvant radiotherapy or neoadjuvant sequential chemoradiotherapy. Radiat Oncol 8:60. https://doi.org/10.1186/1748-717X-8-60

    Article  PubMed  PubMed Central  Google Scholar 

  19. Issels R, Linder L, Verweij J et al (2018) Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol 4:483–492. https://doi.org/10.1001/JAMAONCOL.2017.4996

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pisters PWT, Ballo MT, Fenstermacher MJ et al (2003) Phase I trial of preoperative concurrent doxorubicin and radiation therapy, surgical resection, and intraoperative electron-beam radiation therapy for patients with localized retroperitoneal sarcoma. J Clin Oncol 21:3092–3097. https://doi.org/10.1200/JCO.2003.01.143

    Article  CAS  PubMed  Google Scholar 

  21. Pisters PWT, Patel SR, Prieto VG et al (2004) Phase I trial of preoperative doxorubicin-based concurrent chemoradiation and surgical resection for localized extremity and body wall soft tissue sarcomas. J Clin Oncol 22:3375–3380. https://doi.org/10.1200/JCO.2004.01.040

    Article  CAS  PubMed  Google Scholar 

  22. 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 116:4613–4621. https://doi.org/10.1002/cncr.25350

    Article  CAS  PubMed  Google Scholar 

  23. Mullen JT, Kobayashi W, Wang JJ et al (2012) Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas. Cancer 118:3758–3765. https://doi.org/10.1002/cncr.26696

    Article  PubMed  Google Scholar 

  24. Look Hong NJ, Hornicek FJ, Harmon DC et al (2013) Neoadjuvant chemoradiotherapy for patients with high-risk extremity and truncal sarcomas: a 10-year single institution retrospective study. Eur J Cancer 49:875–883. https://doi.org/10.1016/j.ejca.2012.10.002

    Article  CAS  PubMed  Google Scholar 

  25. Mahmoud O, Tunceroglu A, Chokshi R et al (2017) Overall survival advantage of chemotherapy and radiotherapy in the perioperative management of large extremity and trunk soft tissue sarcoma; a large database analysis. Radiother Oncol 124:277–284. https://doi.org/10.1016/j.radonc.2017.07.021

    Article  PubMed  Google Scholar 

  26. Gronchi A, Casali PG, Mariani L et al (2005) Status of surgical margins and prognosis in adult soft tissue sarcomas of the extremities: a series of patients treated at a single institution. J Clin Oncol 23:96–104. https://doi.org/10.1200/JCO.2005.04.160

    Article  CAS  PubMed  Google Scholar 

  27. Stoeckle E, Gardet H, Coindre J‑M et al (2006) Prospective evaluation of quality of surgery in soft tissue sarcoma. Eur J Surg Oncol 32:1242–1248. https://doi.org/10.1016/j.ejso.2006.05.005

    Article  CAS  PubMed  Google Scholar 

  28. Gronchi A, Verderio P, De Paoli A et al (2013) Quality of surgery and neoadjuvant combined therapy in the ISG-GEIS trial on soft tissue sarcomas of limbs and trunk wall. Ann Oncol 24:817–823. https://doi.org/10.1093/annonc/mds501

    Article  CAS  PubMed  Google Scholar 

  29. 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 77:203–209. https://doi.org/10.1016/j.ijrobp.2009.04.051

    Article  PubMed  Google Scholar 

  30. Coindre JM, Terrier P, Bui NB et al (1996) Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French federation of cancer centers sarcoma group. J Clin Oncol 14:869–877. https://doi.org/10.1200/JCO.1996.14.3.869

    Article  CAS  PubMed  Google Scholar 

  31. Guillou L, Coindre JM, Bonichon F et al (1997) Comparative study of the national cancer institute and French federation of cancer centers sarcoma group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 15:350–362

    Article  CAS  Google Scholar 

  32. Chibon F, Lagarde P, Salas S et al (2010) Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat Med 16:781–787. https://doi.org/10.1038/nm.2174

    Article  CAS  PubMed  Google Scholar 

  33. Neuville A, Chibon F, Coindre J‑M (2014) Grading of soft tissue sarcomas: from histological to molecular assessment. Pathology 46:113–120. https://doi.org/10.1097/PAT.0000000000000048

    Article  CAS  PubMed  Google Scholar 

  34. Lesluyes T, Pérot G, Largeau MR et al (2016) RNA sequencing validation of the complexity INdex in SARcomas prognostic signature. Eur J Cancer 57:104–111. https://doi.org/10.1016/j.ejca.2015.12.027

    Article  CAS  PubMed  Google Scholar 

  35. Chibon F, Lesluyes T, Valentin T, Le Guellec S (2019) CINSARC signature as a prognostic marker for clinical outcome in sarcomas and beyond. Genes Chromosomes Cancer 58:124–129. https://doi.org/10.1002/gcc.22703

    Article  CAS  PubMed  Google Scholar 

  36. Le Guellec S, Lesluyes T, Sarot E et al (2018) Validation of the complexity INdex in SARcomas prognostic signature on formalin-fixed, paraffin-embedded, soft-tissue sarcomas. Ann Oncol 29:1828–1835. https://doi.org/10.1093/annonc/mdy194

    Article  CAS  PubMed  Google Scholar 

  37. Peeken JC, Spraker MB, Knebel C et al (2019) Tumor grading of soft tissue sarcomas using MRI-based radiomics. EBioMedicine 48:332–340. https://doi.org/10.1016/j.ebiom.2019.08.059

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wang H, Chen H, Duan S et al (2019) Radiomics and machine learning with multiparametric preoperative MRI May accurately predict the histopathological grades of soft tissue sarcomas. J Magn Reson Imaging. https://doi.org/10.1002/jmri.26901

    Article  PubMed  PubMed Central  Google Scholar 

  39. Spraker MB, Wootton LS, Hippe DS et al (2019) MRI radiomic features are independently associated with overall survival in soft tissue sarcoma. Adv Radiat Oncol 4:413–421. https://doi.org/10.1016/j.adro.2019.02.003

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Institut Universitaire du Cancer de Toulouse-Oncopôle, 1 Avenue Irène Joliot-Curie, 31059, Toulouse, France

    J. Attal, A. Ducassou, E. Cohen-Jonathan Moyal & M. Delannes

  2. Department of Biostatistics, Institut Universitaire du Cancer de Toulouse-Oncopôle, 1 Avenue Irène Joliot-Curie, 31059, Toulouse, France

    B. Cabarrou & T. Filleron

  3. Department of Medical Oncology, Institut Universitaire du Cancer de Toulouse-Oncopôle, 1 Avenue Irène Joliot-Curie, 31059, Toulouse, France

    T. Valentin & C. Chevreau

  4. Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    J. P. Nesseler

  5. Department of Surgery, Institut Bergonié, 229 Cours de l’Argonne, 33000, Bordeaux, France

    E. Stoeckle

  6. Department of Pathology, Institut Universitaire du Cancer de Toulouse-Oncopôle, 1 Avenue Irène Joliot-Curie, 31059, Toulouse, France

    S. Le Guellec

  7. Department of Radiology, Institut Universitaire du Cancer de Toulouse-Oncopôle, 1 Avenue Irène Joliot-Curie, 31059, Toulouse, France

    B. Boulet

  8. Department of Radiation Oncology, institut de cancérologie de Lorraine, 6 avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France

    G. Vogin

  9. UMR 7365 CNRS-Université de Lorraine, IMoPA, Vandoeuvre-les-Nancy, France

    G. Vogin

  10. Department of Surgery, Institut Universitaire du Cancer de Toulouse-Oncopôle, 1 Avenue Irène Joliot-Curie, 31059, Toulouse, France

    G. Ferron

  11. INSERM U1037, Cancer Research Center of Toulouse (CRCT), 31000, Toulouse, France

    E. Cohen-Jonathan Moyal

  12. Université Toulouse III Paul Sabatier, 31000, Toulouse, France

    E. Cohen-Jonathan Moyal

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  1. J. Attal
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  2. B. Cabarrou
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  3. T. Valentin
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  4. J. P. Nesseler
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Corresponding author

Correspondence to J. Attal.

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Conflict of interest

J. Attal, B. Cabarrou, T. Valentin, J.P. Nesseler, E. Stoeckle, A. Ducassou, T. Filleron, S. Le Guellec, B. Boulet, G. Vogin, G. Ferron, E. C.-J. Moyal, M. Delannes and C. Chevreau declare that they have no competing interests.

Ethical standards

The study was approved by our Institutional Review Board. Each participant/participant’s guardian provided written informed consent. Consent for publication: yes.

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Data and material are available from the author upon request.

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Attal, J., Cabarrou, B., Valentin, T. et al. Evaluation of two modalities of perioperative treatment in the management of extremity and truncal soft tissue sarcomas: neoadjuvant concurrent chemoradiotherapy and sequential treatment. Strahlenther Onkol 197, 1051–1062 (2021). https://doi.org/10.1007/s00066-021-01847-5

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  • DOI: https://doi.org/10.1007/s00066-021-01847-5

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