Proton and Carbon Ion Therapy for MPNST

Malignant peripheral nerve sheath tumors (MPNSTs) are recognized as aggressive malignancies with a poor prognosis, often resulting in high rates of local recurrence and distant metastasis. Surgery with adequate oncologic margins remains the mainstay therapy for nonmetastatic disease. Nevertheless, complete resection with negative margins is often complicated by the necessity to sacrifice the involved peripheral nerves. The local recurrence rate increases in case of positive margins, and even when aggressive surgery obtains negative margins, the outcomes are not satisfactory. Due to their aggressive behavior, a multimodality approach is recommended for MPNST treatment. Both chemotherapy and radiotherapy are widely used for the clinical management of MPNST. Radiotherapy is mainly considered as part of the local treatment of these tumors due to their predominant pattern of local recurrence, especially for patients with positive margins where the local recurrence rate is demonstrated to be higher than with negative margin resection. In the case of macroscopic residual disease or a voluminous tumor not suitable for surgery or local recurrence, radiotherapy also has a role. It is largely demonstrated that high doses of radiotherapy are required to control tumor growth. The possibility to deliver high doses is often limited by the critical structures involved in the target of radiotherapy. More recently, advances in RT techniques have allowed for the safe delivery of higher doses. The major interest aroused in the last decades for proton and carbon ion radiotherapy is due to their intrinsic physical selectivity, which allows for the release of a high dose to the tumor while sparing critical tissues, even if they are closely adjacent to the tumor, as typically found in MPNST. Furthermore, carbon ion has superior radiobiological efficacy, which is theoretically more effective on radioresistant tumors.