Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival

Panagiotis Tsagozis, Otte Brosjö, Mikael Skorpil, Panagiotis Tsagozis, Otte Brosjö, Mikael Skorpil

Abstract

Background: Preoperative radiotherapy is often used to facilitate excision of soft-tissue sarcomas. We aimed define factors that affect local tumour control and patient survival.

Methods: A single institution registry study of 89 patients with non-metastatic soft-tissue sarcomas having preoperative radiotherapy between 1994 and 2014. Radiologic (presence of peritumoural oedema and volume change following radiotherapy) and histopathologic (tumour volume, grade and surgical margin) parameters were recorded. Outcomes were the events of local recurrence, amputation, metastasis and death.

Results: Local recurrence rate was low (12%) and marginal excision gave equal local control to wide excision. Pelvic localization was associated with a higher risk for amputation. The absence of peritumoural oedema on MRI defined a subgroup of tumours with more favourable oncologic outcome. Reduction of tumour volume following radiotherapy was also associated with better patient survival. Both these radiologic parameters were associated with lower tumour grade. Tumour necrosis was not significant for patient survival. The local complication rate, mainly wound healing problems and infection, was high (40%), but did not lead to any amputation.

Conclusion: Preoperative radiotherapy of high-risk soft-tissue sarcomas allows for good local control rate at the expense of local wound complications, which are however manageable. Marginal excision is sufficient for local control. Absence of peritumoural oedema on MRI, as well as tumour size reduction following radiotherapy are associated to superior patient survival and can be used ass early prognostic factors.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curve of local control rate depending on the surgical margin, of patients with non-metastatic soft-tissue sarcoma of the trunk and extremities, treated with preoperative radiotherapy. Excision with clear margin provides superior local control (p = 0.014), but there is no difference between wide excisions and marginal ones
Fig. 2
Fig. 2
Kaplan-Meier curve of limb salvage rate regarding the upper and lower extremity, of patients with non-metastatic soft-tissue sarcoma of the extremities, treated with preoperative radiotherapy. Pelvic localization is associated with a higher risk for amputation (p = 0.029)
Fig. 3
Fig. 3
Kaplan-Meier curve of overall survival depending on tumour size (a) and grade (b), of patients with non-metastatic soft-tissue sarcoma of the extremities, treated with preoperative radiotherapy. Patients with large tumours (dichotomized around the median volume) have inferior survival to the ones having smaller tumours (p = 0.003). Higher grade is also correlated to inferior overall survival (p = 0.004)
Fig. 4
Fig. 4
Kaplan-Meier curve of overall survival depending on the presence or absence of peri-tumoural oedema on MRI (a), as well as on the reduction or not of tumour size (b), of patients with non-metastatic soft-tissue sarcoma of the extremities, treated with preoperative radiotherapy. Absence of peri-tumoural oedema after radiotherapy (p = 0.040) and reduction of tumour volume (p = 0.015) are associated with superior overall survival

References

    1. Jebsen NL, Trovik CS, Bauer HCF, Rydholm A, Monge OR, Hall KS, et al. 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 Biol Phys. 2008;71(4):1196–1203. doi: 10.1016/j.ijrobp.2007.11.023.
    1. Albertsmeier M, Rauch A, Roeder F, Hasenhütl S, Pratschke S, Kirschneck M, et al. External beam radiation therapy for resectable soft tissue sarcoma: a systematic review and meta-analysis. Ann Surg Oncol. 2018;25:754–767. doi: 10.1245/s10434-017-6081-2.
    1. Al-Absi E, Farrokhyar F, Sharma R, Whelan K, Corbett T, Patel M, et al. A systematic review and meta-analysis of oncologic outcomes of pre- versus postoperative radiation in localized resectable soft-tissue sarcoma. Ann Surg Oncol. 2010;17(5):1367–1374. doi: 10.1245/s10434-009-0885-7.
    1. Schaefer I-M, Hornick JL, Barysauskas CM, Raut CP, Patel SA, Royce TJ, et al. Histologic appearance after preoperative radiation therapy for soft tissue sarcoma: assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score. Int J Radiat Oncol Biol Phys. 2017;98(2):375–383. doi: 10.1016/j.ijrobp.2017.02.087.
    1. Delisca GO, Alamanda VK, Archer KR, Song Y, Schwartz HS, Holt GE. Tumor size increase following preoperative radiation of soft tissue sarcomas does not affect prognosis. J Surg Oncol. 2013;107(7):723–727. doi: 10.1002/jso.23322.
    1. Miki Y, Ngan S, Clark JCM, Akiyama T, Choong PFM. The significance of size change of soft tissue sarcoma during preoperative radiotherapy. Eur J Surg Oncol. 2010;36(7):678–683. doi: 10.1016/j.ejso.2010.05.021.
    1. Einarsdottir H, Wejde J, Bauer HC. Pre-operative radiotherapy in soft tissue tumors. Assessment of response by static post-contrast MR imaging compared to histopathology. Acta Radiol. 2001;42(1):1–5.
    1. ESMO/European Sarcoma Network Working Group Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):102–112. doi: 10.1093/annonc/mdu254.
    1. Coindre JM, Terrier P, Bui NB, Bonichon F, Collin F, Le Doussal V, et al. 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. 1996;14(3):869–877. doi: 10.1200/JCO.1996.14.3.869.
    1. Strander H, Turesson I, Cavallin-Ståhl E. A systematic overview of radiation therapy effects in soft tissue sarcomas. Acta Oncol. 2003;42(5–6):516–531. doi: 10.1080/02841860310014732.
    1. Gingrich AA, Bateni SB, Monjazeb AM, Darrow MA, Thorpe SW, Kirane AR, et al. Neoadjuvant radiotherapy is associated with R0 resection and improved survival for patients with extremity soft tissue sarcoma undergoing surgery: a National Cancer Database Analysis. Ann Surg Oncol. 2017;24(11):3252–3263. doi: 10.1245/s10434-017-6019-8.
    1. Dagan R, Indelicato DJ, McGee L, Morris CG, Kirwan JM, Knapik J, et al. The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity. Cancer. 2012;118(12):3199–3207. doi: 10.1002/cncr.26489.
    1. Hoefkens F, Dehandschutter C, Somville J, Meijnders P, Van Gestel D. Soft tissue sarcoma of the extremities: pending questions on surgery and radiotherapy. Radiat Oncol. 2016;11(1):136. doi: 10.1186/s13014-016-0668-9.
    1. Kandel R, Coakley N, Werier J, Engel J, Ghert M, Verma S, et al. Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline. Curr Oncol. 2013;20(3):e247–e254. doi: 10.3747/co.20.1308.
    1. Harati K, Goertz O, Pieper A, Daigeler A, Joneidi-Jafari H, Niggemann H, et al. Soft tissue sarcomas of the extremities: surgical margins can be close as long as the resected tumor has no ink on it. Oncologist. 2017;22(11):1400–1410. doi: 10.1634/theoncologist.2016-0498.
    1. Gundle KR, Kafchinski L, Gupta S, Griffin AM, Dickson BC, Chung PW, et al. Analysis of margin classification systems for assessing the risk of local recurrence after soft tissue sarcoma resection. J Clin Oncol. 2018;JCO2017746941.
    1. Griffin AM, Dickie CI, Catton CN, Chung PWM, Ferguson PC, Wunder JS, et al. The influence of time interval between preoperative radiation and surgical resection on the development of wound healing complications in extremity soft tissue sarcoma. Ann Surg Oncol. 2015;22(9):2824–2830. doi: 10.1245/s10434-015-4631-z.
    1. Baldini EH, Lapidus MR, Wang Q, Manola J, Orgill DP, Pomahac B, et al. Predictors for major wound complications following preoperative radiotherapy and surgery for soft-tissue sarcoma of the extremities and trunk: importance of tumor proximity to skin surface. Ann Surg Oncol. 2013;20(5):1494–1499. doi: 10.1245/s10434-012-2797-1.
    1. Rosenberg LA, Esther RJ, Erfanian K, Green R, Kim HJ, Sweeting R, et al. Wound complications in preoperatively irradiated soft-tissue sarcomas of the extremities. Int J Radiat Oncol Biol Phys. 2013;85(2):432–437. doi: 10.1016/j.ijrobp.2012.04.037.
    1. Tseng JF, Ballo MT, Langstein HN, Wayne JD, Cormier JN, Hunt KK, et al. The effect of preoperative radiotherapy and reconstructive surgery on wound complications after resection of extremity soft-tissue sarcomas. Ann Surg Oncol. 2006;13(9):1209–1215. doi: 10.1245/s10434-006-9028-6.
    1. Shah C, Verma V, Takiar R, Vajapey R, Amarnath S, Murphy E, et al. Radiation therapy in the management of soft tissue sarcoma: a Clinician’s guide to timing, techniques, and targets. Am J Clin Oncol. 2016;39(6):630–635. doi: 10.1097/COC.0000000000000319.
    1. Haas RLM, Miah AB, LePechoux C, DeLaney TF, Baldini EH, Alektiar K, et al. Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies. Radiother Oncol J. 2016;119(1):14–21. doi: 10.1016/j.radonc.2015.12.002.
    1. Kubicek GJ, LaCouture T, Kaden M, Kim TW, Lerman N, Khrizman P, et al. Preoperative radiosurgery for soft tissue sarcoma. Am J Clin Oncol. 2018;41(1):86–89.
    1. Sampath S, Schultheiss TE, Hitchcock YJ, Randall RL, Shrieve DC, Wong JYC. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma: multi-institutional analysis of 821 patients. Int J Radiat Oncol Biol Phys. 2011;81(2):498–505. doi: 10.1016/j.ijrobp.2010.06.034.
    1. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359(9325):2235–2241. doi: 10.1016/S0140-6736(02)09292-9.

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