Editorial: Malignant nerve sheath tumors

Abstract

Dunn et al.1 have provided a retrospective review of their institutional experience over an 18-year period during which time they treated 23 patients for malignant peripheral nerve sheath tumors in the setting of neurofibromatosis Type 1 (NF1). The authors analyzed their outcomes with respect to survival and local and distant recurrence. They were particularly interested in the role of a complete resection on survival and looked at what they term “gross-total resection [GTR]” as well as whether the surgical margins were free of tumor. They found that the surgeon’s estimate of resection was significant with respect to overall survival. They provide a relatively extensive review of the literature on this topic, including adjuvant therapies, such as radiation therapy and chemotherapy. Their study does not attempt to compare the presentation or outcomes of patients with NF1 with patients without NF1. While this is not the largest series of malignant nerve sheath tumors in the literature, it provides useful data and underscores many of the relevant issues with respect to the treatment of these rare lesions. The fact that the author group included several specialty areas (neurosurgery, neurology, orthopedic surgery, medical oncology, and radiation oncology) indicates that a multidisciplinary approach has become the standard for approaching these lesions. As pointed out in the report, there is no standard therapy for these lesions that has proven effective. The authors are somewhat alone in using the term gross-total resection in relationship to surgery for this lesion. Neurosurgeons frequently use this term in describing brain tumor resections, while surgical oncologists more often use the “margin” status when referring to malignant peripheral nerve sheath tumors.2–4 In most, but not all, studies, the presence of tumor cells on the pathological evaluation of the resected margins is negatively correlated with recurrence and survival. In this report, there were 4 cases in which tumor cells were seen by the pathologist, even though the surgeon thought that the entire tumor was resected. Although the authors describe this as occurring in 4 of their 23 patients, in actual fact, there were only 15 patients in whom the surgeon thought that a complete resection had been attained. Thus, this “error” occurred more than 25% of the time. In addition, the fact that 33% of patients who underwent “GTR” died within 5 years (43% for negative margins) indicates that there is no good indicator of surgical cure for this lesion, and that adjuvant therapy should probably be given in all cases. As discussed in the report, radiation therapy has been shown in some studies to be effective in reducing recurrence in these lesions. Recent data would suggest that a relatively high radiation dose is required for this to be true. Wong et al.5 found that the effective dose had to be greater than 60 Gy, which is not surprising given the relative resistance to radiation for this type of lesion. In this review, the mean dose was 56 Gy, indicating that many cases were treated with a dose that might not be expected to provide adequate control. Such high doses are probably safer when given as intraoperative radiation therapy in order to spare skin and other, more radiation-sensitive tissues from injury. As noted by the authors, the benefits of preoperative versus intraor postoperative radiation therapy have not been proven, but many centers use preoperative radiation therapy when there has been a biopsy that proves the malignant nature of the lesion prior to the larger resection. All of this indicates the need for data sharing and for multiinstitutional protocols to be developed to optimize outcomes for patients with these rare but deadly lesions. Algorithms that take the entire evidence base into account are needed, and areas in which the algorithm fails should be studied in a multicenter fashion. Although patients with NF1 are more likely to harbor malignant nerve sheath tumors than patients without NF1, there is nothing in the literature to indicate a difference in biological response to therapy between these patient groups. Neurosurgeons should continue to be involved in the surgical treatment of these lesions, as they provide a unique skill set with respect to nerve sparing and nerve repair. Orthopedic oncologists should be involved early in the diagnostic process, as some cases can only be adequately treated with aggressive procedures, including large amputations. (http://thejns.org/doi/abs/10.3171/2012.4.JNS11148)