Enrico Martin

98 Chapter 5 presumed feasible. Function preservation was also not considered preoperatively by almost 30% of surgeons. However, considering it in an early stage of treatment may be beneficial, as long-term disabilities may be minimized since localized MPNSTs do have a median survival of 5-8 years. 5,10 Combining knowledge of reconstructive possibilities by reconstructive and nerve surgeons as an addition to oncological resection margins may improve the delicate balance between oncological and functional outcomes. Such a multidisciplinary approach by these surgical specialties may also optimize the preoperative surgical planning for the extent of the resection to preserve functional anatomy using planned positive margins, or going wider and resecting functional structures beyond the reconstruction tools of the plastic surgeons. Currently, functional reconstructions are uncommonly performed in STS patients, especially those requiring nerve reconstruction, even though outcomes can be very satisfactory. 31 Multimodal treatment in MPNST To date, no study has yet demonstrated that MPNSTs should be treated differently than other high-grade STS. 13,18 As such, MPNST treatment guidelines grossly follow general STS guidelines. 21,23 However, even in large dedicated sarcoma centers, the use of chemotherapy and radiotherapy differs significantly. 18 Radiotherapy was considered by most respondents in tumors sizes >10cm and positive surgical margins. This is concordance with findings in another survey on multimodal treatment in STS and STS guidelines. 21,32 Although surgical oncologists clearly preferred neoadjuvant administration of radiotherapy, others did not. Neoadjuvant administration did prove in one trial to require lower dosage of radiation, which eventually resulted in lower long-termmorbidity at the price of increased postoperative complications. 33,34 However, neoadjuvant radiotherapy may complicate possible nerve reconstruction and fibrous tissue will always have to be removed to create a vascularized wound bed for nerve regeneration. 35 As such, the differences in opinion on preferred timing may also be related to specialty bias. Indications for the use of chemotherapy in localized MPNSTs and STS in general is conflicting as reflected by responses to this survey. Thus far, trials and meta-analyses have not been able to provide definitive conclusions on the beneficial effect of perioperative chemotherapy in STS as observed effects are relatively small. 36–39 Preliminary results from a recent randomized trial did however show a positive effect for localized high-risk (high-grade, large, and deep-seated) extremity STS on both overall survival and disease-free survival. 13 For MPNSTs, chemotherapy regimens should ideally involve an anthracycline-based regimen, such as doxorubicin, in combination with ifosfamide. 13,14,40,41 Preferred timing of chemotherapy administration has not been studied thoroughly, but several hypotheses exist favoring neoadjuvant therapy translated from research in breast cancer. This includes earlier initiation of systemic therapy, possible downstaging of the tumor, and eliminating micro-metastases before exposure to wound-healing cytokines triggered by operation. 41–43 However, these theories have not yet been proven in STS. Unfortunately, studies show that MPNSTs are relatively chemoresistant, possibly more so in NF1 patients. 41,43 Some smaller studies