ISOLS/MSTS 2015 Abstract 11288 11288: Histologic Response of Infiltrative Myxofibrosarcomas and Undifferentiated Pleomorphic Sarcomas to Pre-Operative Radiotherapy Authors:

740 words) Background: Infiltrative growth pattern is often observed in superficial myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). According to the past literatures, radiographic infiltration of superficial MFS and UPS on magnetic resonance (MR) images indicates a high possibility of histologic infiltration. In recent years, this growth pattern has become widely recognized as a primary risk factor for local recurrence and possibly distant metastases. However, the role of radiotherapy (RT) as adjuvant therapy remains uncertain. Questions/Purposes: The aims of this study are to clarify the efficacy of preoperative RT strategy for infiltrative MFS and UPS by examining pathologic findings and patients’ clinical outcomes, and to reveal current issues concerning pre-operative RT on infiltrative MFS and UPS. Patients and Methods: From 1996 to 2014, 252 soft tissue sarcomas diagnosed as malignant fibrous histiocytoma (MFH), MFS, or UPS were surgically treated at our institution. Ninety-six patients initially excised outside were excluded. Among the remaining 156 cases, MR images were available for review in 101 cases. Of the 101 cases, 19 cases had a subcutaneous or on-fascia tumor, but one case amputated without RT was excluded. The total of 18 cases were included in this study. These cases were pathologically reviewed and re-labeled as MFS or UPS according to the World Health Organization (WHO) classification published in 2013. All the 18 cases fit either of MFS or UPS. MR images before RT were reviewed in terms of the maximum diameter and peripheral growth pattern of the tumors. If a tumor extends on a fascial plane or into subcutaneous fat tissue for 2 mm or more from the edge of the main mass on gadolinium-enhanced, fat-saturated T1-weighted MR imaging, then the tumor is considered ‘infiltrative’. Specimens of all the cases were microscopically reviewed. Firstly, overall histologic response to RT was measured on the 4-grade scale proposed by Willett CG et al. in 1987, by the ratio of necrosis or severe ISOLS/MSTS 2015 Abstract 11288 cellular alteration; the ratios of less than 50%, 50–80%, more than 80% but not 100%, and 100% were classified as +1, +2, +3, and +4, respectively. In this evaluation, grades +3 and +4 were considered as good response (GR), and the rest as poor response (PR). Then, the peripheral area, where an infiltrative growth pattern was observed on pre-RT MR images with contrast, was graded regarding the degree of viable tumor cells remaining in the area. We classified a case with no viable tumor cells in the infiltrative area as grade A, while a case with some but fewer viable tumor cells than initial biopsy as grade B, and that with similar tumor viability to initial biopsy as grade C. For cases with viable tumor cells remaining in the infiltrative area, how far viable tumor cells extended from the edge of main mass was also measured on glass slides. These two pathologic results (GR vs. PR, and grade A vs. grade B or C) were compared between MFS and UPS using Fisher’s exact test. Clinical outcomes were reported in terms of patient survival, local recurrence, and distant metastasis. Results: Eighteen cases included six MFSs and 12 UPSs. All the cases were non-metastatic at the first presentation. Radiographically, all cases except for three UPSs were infiltrative. Histologic GR was observed in ten (83%) UPS but only one (17%) MFS case. Among the 15 radiographically infiltrative cases, viable tumor cells remained in the infiltration after RT in seven (47%) cases (MFS: 5/6, UPS: 2/9). In these seven cases, the distance from the edge of the main tumor mass to the furthest extension of viable tumor cells was almost the same as that of pre-RT radiographic infiltration (Table 1, 2). There was a statistically significant correlation between myxofibrosarcoma and both of histologic PR and residual viable tumor cells in the infiltration according to Fisher’s exact test (p = 0.01 and 0.04, respectively). Two cases (11%) had local recurrence; one recurred in the field of RT (case 4), while the other did outside (case 5). Both of them had histologic PR and viable tumor cells in the radiographic infiltration (Table 1). Conclusions: (1) Pre-operative radiotherapy can improve local control for infiltrative UPS. (2) In contrast, MFS cells in the infiltration are more likely to remain viable even after pre-operative RT. (3) Some infiltration can exceed 3cm, which is currently a standard extra-length of RT field from the edge of main mass. Therefore pre-operative RT planning for infiltrative UPS and MFS should be strictly based on MRI rather than CT. ISOLS/MSTS 2015 Abstract 11288 Table 1. Summary of 18 cases in this study Case No. Age, sex Dx T location T depth IGP Initial T size Willet grading HIP LR/Met FU (month) Status 1 88, M UPS Forearm OF + 30 mm +3 B – 88 CDF 2 78, F UPS Lower leg OF + 70 mm +2 A – 86 CDF 3 66, M MFS Scapula SC + 50 mm +2 B – 69 CDF 4 83, M MFS Forearm OF + 53 mm +1 B LR (32) 75 AWD 5 76, F UPS Lower leg OF + 43 mm +1 B LR (31) 72 NED 6 81, F UPS Thigh SC – 82 mm +4 N/A – 60 CDF 7 54, F UPS Lower leg SC – 60 mm +4 N/A – 63 CDF 8 73, F MFS Lower leg SC + 57 mm +2 B – 58 CDF 9 82, M UPS Pelvis OF + 40 mm +4 A – 59 CDF 10 47, F UPS Lower leg OF + 38 mm +3 A Met (28) 57 AWD 11 68, M MFS Lower leg SC + 24 mm +2 A Met (3) 47 NED 12 63, M UPS Lower leg OF + 42 mm +4 A – 34 CDF 13 66, F UPS Thigh OF + 43 mm +4 A – 17 CDF 14 41, F UPS Shoulder SC – 55 mm +3 N/A Met (18) 23 AWD 15 66, F MFS Shoulder OF + 41 mm +3 B – 16 CDF 16 68, F UPS Lower leg OF + 48 mm +4 A – 14 CDF 17 84, F MFS Lower leg OF + 31 mm +1 C – 13 CDF 18 51, M UPS Thigh OF + 20 mm +3 A – 7 CDF Dx diagnosis, MFS myxofibrosarcoma, UPS undifferentiated pleomorphic sarcoma, T tumour, OF on-fascia, SC mainly subcutaneous, IGP infiltrative growth pattern, N necrosis, HIP histologic infiltration pattern, N/A not applicable, LR local recurrence, Met metastasis, FU follow-up, CDF continuous disease free, AWD alive with disease, NED no evidence of disease ISOLS/MSTS 2015 Abstract 11288 Table 2. The maximum length of viable tumor cell extension from the edge of the main mass on specimen for the 7 cases with tumor viability in the radiographic infiltrated area Infiltration on MRI a (before RT) Infiltration on MRI a (after RT) Histologic infiltration (after RT) Margin Case 1 (UPS) 10 mm ND 10 mm Wide Case 3 (MFS) 7 mm 78 mm 4 mm Wide Case 4 (MFS) 29 mm 28 mm 25 mm Positive Case 5 (UPS) 25 mm ND 30 mm Wide Case 8 (MFS) 7 mm 51mm 12 mm Wide Case 15 (MFS) 27 mm 17 mm 20 mm Wide Case 17 (MFS) 33 mm 43 mm 24 mm Wide ND no data available for evaluation a Radiographic infiltration was measured on gadolinium-enhanced, fat-saturated T1-weighted MRI.