What is an adequate margin for inﬁltrative soft-tissue sarcomas? Tomohiro Fujiwara a, b, * , Jonathan Stevenson a , Michael Parry a , Yusuke Tsuda a , Kim Tsoi a , Lee Jeys a a Department of Oncology, The Royal Orthopaedic Hospital, Birmingham, United Kingdom b Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan article info Article history: Received 21 June 2019 Received in revised form 24 September 2019 Accepted 5 October 2019 Available online 8 October 2019 Keywords: Soft-tissue sarcoma Myxoﬁbrosarcoma Undifferentiated pleomorphic sarcoma Margin Prognosis abstract Objectives: What constitutes an adequate margin of resection for inﬁltrative subtypes of soft-tissue sarcomas remains unclear. We aimed to determine the prognostic signiﬁcance of the margin in milli- metres for myxoﬁbrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). Methods: 305 patients diagnosed with either a high-grade, localised MFS (n ¼ 98) or UPS (n ¼ 207) were included. The relationship of closest margin in millimetres to viable tumour and oncological outcomes was analysed. Results: The overall local recurrence (LR) rate for all patients were 12%: 19% with positive margin and 10% with negative margin (p ¼ 0.051). The LR rate was similar in patients with negative but <10 mm margin; 13%, 6%, 15%, 17% with 0.1e0.9 mm, 1.0e1.9 mm, 2.0e4.9 mm, and 5.0e9.9 mm margin, respectively. However, the LR rate decreased to 3% if the margin was 10 mm. By the R- or Rþ1-classiﬁcation, the 10- year cumulative probability of LR was 9%,15%, 48% for R0, R1, R2 resections, respectively, which was not sensitive enough to stratify the LR risk in patients with negative margins. However, the cumulative probability of LR was signiﬁcantly stratiﬁed by metric distance; the 10-year cumulative LR probability was 3%, 14%, 25% with 10.0 mm, 0.1e9.9 mm, and 0 mm, respectively (p ¼ 0.026). A trend towards improved local control by adjuvant radiotherapy was seen in patients with 0e9.9 mm margin (p ¼ 0.078). Conclusion: The resection margin, when measured as a metric distance, correlates with a reduction in LR, and appears to be more signiﬁcant on local control than radiotherapy. To minimise the risk of LR, a margin distance of at least 10 mm is advocated for MFS and UPS. © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Introduction The signiﬁcance of a wide resection margin in local control of soft tissue sarcomas (STSs) has been emphasized for decades [1e8]. While several authors have demonstrated that tumours resected with positive margins have a signiﬁcantly higher rate of local recurrence [2,3,5,6,9e13], there is no consensus on what is an adequate margin distance for minimizing the risk of local recur- rence. To date, several investigations have attempted to quantify the distance associated with a reduced risk of LR. Dickinson et al. stratiﬁed patients into ﬁve groups (contaminated, < 1 mm but clear, 1e4 mm, 5e9 mm, and 10e19 mm) and concluded that a margin greater than 1 mm was satisfactory for local control of STSs [5]. Sampo et al. reported that the incidence of LR correlated with increasing surgical margin, from 0 to 4 cm, and concluded that a surgical margin of 2e3 cm is ‘reasonable’ [6]. However, these pre- vious investigations were performed using patient cohorts con- sisting of a variety of STSs including tumour types with an inﬁltrative margin, which are associated with higher rates of local recurrence [14]. Myxoﬁbrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) frequently present with an inﬁltrative growth pattern [15e18]. This inﬁltrative growth pattern was ﬁrst reported in 1999 by Fanburg-Smith et al., where pathological inﬁltration was observed in patients with 83% of superﬁcial and 24% of deep MFH (now termed UPS) [15]. In a retrospective review of 89 patients diagnosed with MFS or UPS, Iwata et al. observed inﬁltrative growth in 36% of MFS and 22% of UPS on preoperative MRI, which was deﬁned as a tail-like extensive lesion along the normal fascial plane [17]. Although their surgical protocol was to excise 2e3 cm * Corresponding author. The Royal Orthopaedic Hospital, Bristol Road South, Birmingham, B31 2AP, UK. E-mail address: tomomedvn@gmail.com (T. Fujiwara). Contents lists available at ScienceDirect European Journal of Surgical Oncology journal homepage: www.ejso.com https://doi.org/10.1016/j.ejso.2019.10.005 0748-7983/© 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. European Journal of Surgical Oncology 46 (2020) 277e281