Enrico Martin

174 Chapter 7 be difficult and should ultimately be assessed in clinical trials. Second, the preclinical data have to be robust before performing a clinical trial. For example, Albritton et al. based their trial on evidence found from one in vitro study. 91 It is reasonable to consider in vitro studies by themselves as weaker evidence compared to in vivo studies, and it is therefore unsurprising that such studies might not effectively translate to the clinical setting. 92 Third, most studies include all types of STS since it is challenging to perform a trial in a disease as rare as MPNST. In this review, four out of the six identified studies were performed in all types of soft tissue sarcomas, for which preclinical evidence was not necessarily found in MPNSTs specifically. The investigators should however be applauded for their efforts in performing histotype subanalyses, although likely underpowered, as certain histological subtypes might well be more sensitive to a particular drug therapy than others. Finally, as suggested by the present review that is based on in vivo evidence, a combination of different drugs is likely to be more potent in MPNST patients compared to monotherapy. However, many of the published trials only investigated single targeted therapy. Strengths and limitations Unfortunately, quantitative comparison between different studies investigating different treatments in vivo was not fully feasible. To date, no tool has been established that shows high reliability of translating preclinical outcomes into clinical evidence, limiting the ability to make direct comparisons between preclinical studies. Despite the challenges in drawing quantitative comparisons across studies, assessing treatment effect by stratifying outcomes into low, intermediate, and high effect has been successfully done previously. 23 Overall, despite these limitations, to our knowledge, the current article represents the largest review to date to pool the available literature on in vivo therapies for MPSNT. By assessing various animal models and treatment regimens through a descriptive systematic review, we aimed to facilitate treatment-related decisions in patients with MPNST. 93 For now, such animal studies serve as the cornerstone to the advancement of therapeutics for MPNST in humans and are therefore necessary to carefully review and assess prior to initiation of human trials. 92 Identification of multiple potential MPNST drugs in this review underscore fundamental principles that will guide optimization of treatment regimens in the future. For example, novel therapies should focus on improving survival while simultaneously limiting toxicity and maintaining quality of life. The utility of ultimately discovering a systemic treatment specifically targeting MPNSTs may drastically alter the course of the MPNST management, allowing for preoperative tumor reduction and potentially minimizing the need for higher doses of radiation as well as more intensive surgeries.