Ahmet SALDUZ, Buğra ALPAN, Natig VALIYEV, Emre OZMEN, Ayça IRİBAS, Fulya AĞAOĞLU, Aysel BAYRAM, Bilge BİLGİÇ, Harzem ÖZGER

Neoadjuvant radiotherapy for myxoid liposarcomas: Oncologic outcomes and histopathologic correlations

Objective: The aim of this study was to evaluate the histopathological features of primary extremitymyxoid liposarcoma before and after neoadjuvant radiation therapy, and to evaluate the oncologicaloutcomes of the patients.Methods: The study included 23 patients (16 men and 7 women with a mean age of 43 (24e69) years)with primary myxoid liposarcoma of the extremities, who were treated between January 1998 andDecember 2015. Inclusion criteria were histopathological conŞrmation of the diagnosis with both theinitial biopsy and the resection specimen, and having undergone neoadjuvant radiotherapy. Demographic, clinical and histopathological data were evaluated.Results: Over a mean follow-up time of 55.2 (8e139) months, 5 patients (21.7%) died secondary todisease progression, leaving 18 patients (78.3%) still alive at the time of last follow-up. Only one patient(4%) experienced local recurrence and six (26%) patients developed distant metastases. Disease-freesurvival at 5 and 10 years were 66%; whereas, overall patient survival at 5 and 10 years were 78.1%and 71.0%, respectively. Tumor size (>15 cm) and presence of metastasis were signiŞcantly associatedwith increased overall mortality. On histopathology, necrosis was present in 12/23 resection specimens.Hyalinization/Şbrosis and residual viable tumor was present in all specimens. Adipocytic maturation/cytodifferentiation was seen in 8/23 patients.Conclusion: Neoadjuvant radiotherapy was effective for myxoid liposarcomas histopathologically,although these histopathological features did not affect the patients' oncological outcomes. Favorableoncological outcomes were obtained with neoadjuvant radiotherapy, surgical resection and chemotherapy.Level of evidence: Level IV, therapeutic study.© 2017 Turkish Association of Orthopaedics and Traumatology. Publishing services by Elsevier B.V. This isan open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

___

1. Goldblum JR, Weiss SW, Folpe AL. Enzinger and Weiss's soft tissue tumors. Elsevier Health Sciences; 2013.

2. Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2002.

3. Peterson JJ, Kransdorf MJ, Bancroft LW, O'Connor MI. Malignant fatty tumors: classification, clinical course, imaging appearance and treatment. Skeletal Radiol. 2003;32(9):493e503.

4. DeLaney TF. Radiation therapy: neoadjuvant, adjuvant, or not at all. Surgical Oncol Clin N Am. 2012;21(2):215e241.

5. Haas RLM, DeLaney TF, O'Sullivan B, et al. Radiotherapy for management of extremity soft tissue sarcomas: why, when, and where? Int J of Radiat Oncol Biol Phys. 2012;84(3):572e580.

6. DeLaney TF, Spiro IJ, Suit HD, et al. Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas. Int J of Radiat Oncol Biol Phys. 2003;56(4):1117e1127.

7. Olsullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomized trial. Lancet. 2002;359(9325):2235e2241.

8. Davis AM, O'Sullivan B, Turcotte R, et al. Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiotherapy Oncol. 2005;75(1):48e53.

9. Pitson G, Robinson P, Wilke D, et al. Radiation response: an additional unique signature of myxoid liposarcoma. Int J of Radiat Oncol Biol Phys. 2004;60(2): 522e526.

10. Chung PWM, Deheshi BM, Ferguson PC, et al. Radiosensitivity translates into excellent local control in extremity myxoid liposarcoma. Cancer. 2009;115(14): 3254e3261.

11. Guadagnolo BA, Zagars GK, Ballo MT, et al. Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy. Int J of Radiat Oncol Biol Phys. 2008;70(3): 760e765.

12. de Vreeze RSA, de Jong D, Haas RL, Stewart F, van Coevorden F. Effectiveness of radiotherapy in myxoid sarcomas is associated with a dense vascular pattern. Int J of Radiat Oncol Biol Phys. 2008;72(5):1480e1487.

13. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92(3):205e216.

14. Engstrom K, Bergh P, Cederlund C-G, et al. Irradiation of myxoid/round cell EUR liposarcoma induces volume reduction and lipoma-like morphology. Acta Oncol. 2007;46(6):838e845.

15. Roberge D, Skamene T, Nahal A, Turcotte RE, Powell T, Freeman C. Radiological and pathological response following pre-operative radiotherapy for soft-tissue sarcoma. Radiotherapy Oncol. 2010;97(3):404e407.

16. Wortman JR, Tirumani SH, Tirumani H, et al. Neoadjuvant radiation in primary extremity liposarcoma: correlation of MRI features with histopathology. Eur Radiol. 2016;26(5):1226e1234.

17. Stacchiotti S, Collini P, Messina A, et al. High-grade soft-tissue sarcomas: tumor response assessmentdpilot study to assess the correlation between radiologic and pathologic response by using RECIST and choi criteria 1. Radiology. 2009;251(2):447e456.

18. Stacchiotti S, Verderio P, Messina A, et al. Tumor response assessment by modified Choi criteria in localized high-risk soft tissue sarcoma treated with chemotherapy. Cancer. 2012;118(23):5857e5866.

19. Miki Y, Ngan S, Clark JCM, Akiyama T, Choong PFM. The significance of size change of soft tissue sarcoma during preoperative radiotherapy. Eur J of Surg Oncol. 2010;36(7):678e683.

20. Baxter KJ, Govsyeyev N, Namm JP, Gonzalez RJ, Roggin KK, Cardona K. Is multimodality therapy necessary for the management of pure myxoid liposarcomas? A multi-institutional series of pure myxoid liposarcomas of the extremities and torso. J Surg Oncol. 2015;111(2):146e151.

21. Suzan E, Hoekstra HJ, van Ginkel RJ, Bastiaannet E, Suurmeijer AJH. Clinicopathologic prognostic factors in myxoid liposarcoma: a retrospective study of 49 patients with long-term follow-up. Ann of Surg Oncol. 2007;14(1):222e229.

22. Wardelmann E, Haas R, Bovee J, et al. Evaluation of response after neoadjuvant treatment in soft tissue sarcomas; the European Organization for Research and Treatment of CancereSoft Tissue and Bone Sarcoma Group (EORTCeSTBSG) recommendations for pathological examination and reporting. Eur J Cancer. 2016;53:84e95.

23. Antonescu CR, Tschernyavsky SJ, Decuseara R, et al. Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma a molecular and clinicopathologic study of 82 cases. Clin Cancer Res. 2001;7(12):3977e3987.

24. Kilpatrick SE, Doyon J, Choong PFM, Sim FH, Nascimento AG. The clinicopathologic spectrum of myxoid and round cell liposarcoma. Cancer. 1996;77(8):1450e1458.

25. Nishida Y, Tsukushi S, Nakashima H, Ishiguro N. Clinicopathologic prognostic factors of pure myxoid liposarcoma of the extremities and trunk wall. Clin Orthop Relat Res. 2010;468(11):3041e3046.

26. Smith TA, Easley KA, Goldblum JR. Myxoid/round cell liposarcoma of the extremities: a clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma. Am J Surg Pathol. 1996;20(2):171e180.

27. Eilber FC, Rosen G, Eckardt J, et al. Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas. J Clin Oncol. 2001;19(13):3203e3209.

28. Oh YJ, Yi SY, Kim KH, et al. Prognostic model to predict survival outcome for curatively resected liposarcoma: a multi-institutional experience. J Cancer. 2016;7(9):1174e1180.

29. Kim HS, Lee J, Yi SY, et al. Liposarcoma: exploration of clinical prognostic factors for risk based stratification of therapy. BMC Cancer. 2009;9(1):1.