Radiation Oncology/MPNST

Malignant Peripheral Nerve Sheath Tumor Epidemiology Account for 5-10% of soft tissue tumors Majority arise de novo or from neurofibromas; prior RT (median 15 years ago) a risk factor Pathology Normal nerve sheath: Schwann cells, perineural cells, fibroblasts, endothelial cells, pericytes, epineural lipocytes MPNSTs - Malignant tumors arising from or differentiating toward cells of peripheral nerve sheath; resemble fibrosarcomas in their basic organization Criteria (one of the following): arise from peripheral nerve arise from pre-existing benign nerve sheath tumor (e.g., neurofibroma) displays a constellation of histologic features seen above, and reflecting Schwann cell differentiation Cytogenetics Loss of NF1 gene (neurofibromin) and high levels of RAS activity; necessary but not sufficient In addition, p27-Kip1, p53, or p16 Treatment Overview Literature mostly consists of small series or case reports Primary treatment is surgery RT appears beneficial in local control, but has no impact on long-term survival. Dose >60 Gy preferred Chemotherapy does not appear very effective Outcomes MGH 1991-2001 12963767 -- "Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment." (Baehring JM, Neurology. 2003 Sep 9;61(5):696-8.) Retrospective. 54 patients. Median f/u 54 months Median survival: 66 months Local recurrence: 26% after median 22 months; Distant recurrence: 20% Univariate factors: tumor diameter <5 cm (HR 0.4), total resection, lower age Multivariate factors: extent of surgery, RT (HR 0.22), age, chemo (but caution: small sample size) Mayo 1975-1993 9788415 -- "Malignant peripheral nerve sheath tumor: analysis of treatment outcome. (Wong WW, Int J Radiat Oncol Biol Phys. 1998 Sep 1;42(2):351-60.) Retrospective. 134 patients, 27% extremities, 73% non-extremities. Median f/u 53 months Path: 10% Grade I, 32% Grade II, 32% Grade III, 24% Grade IV RT (54%): 3-5 cm margins, no attempt to include LNs; 10% BT prescribed median 15 Gy to target volume 5-year OS (10-year OS): 52% (34%). Median survival 61 months. RT did not affect 5-year survival (58% RT vs. 43% no RT) Survival predictors: prior XRT, surgical margins Local control: surgical margins, RT dose, use of IOERT/BT Distant control: tumor size, grade, histologic subtype Conclusion: Goal resection with negative margins. Adjuvant RT >=60 Gy, and inclusion of IOERT/BT provides improved local control St. Jude 1995 8591083 -- "Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience." (DeCou JM, Ann Surg Oncol. 1995 Nov;2(6):524-9.) Retrospective. 28 patients treated over 30 years. 45% extremity, 34% trunk, 21% head/neck 5-year OS: 39% (resectable 65%, nonresectable 0% and median 12 months) Survival predictors: surgical margins, sarcoma IRS group Role for RT: authors recommend only for +margins Review Zurich (Switzerland) 2005 -- 16442014 "Malignant peripheral nerve sheath tumors: an update." (Fuchs B, J Surg Orthop Adv. 2005 Winter;14(4):168-74.) Malignant Intracranial Nerve Sheath Tumor Historically also called malignant Schwannoma, but Malignant Intracranial Nerve Sheath Tumor preferred, since it is not yet clear whether these tumors truly arise from Schwann cells Only 5 cases reported in literature: 2/5 patients were disease-free 17 and 19 months after surgery 3/5 patients recurred (5 months (death 9 months), 10 months (death 18 monts), and last had 3rd recurrence 5 years after surgery) Saint-Etienne (France) 2004 14744297 -- "Malignant nerve sheath tumor of the right cerebral peduncle: case report." (Beauchesne P, Neurosurgery. 2004 Feb;54(2):500-3; discussion 503-4.) Case report. 35 yo man with right cerebral peduncle tumor Treated with stereotactic biopsy and cranial RT to 56.25 Gy in 24 fractions After recurrence, treated with doxorubicin with mild benefit OS: 29 months (recurred 24 months after initial treatment) NYU 1998 9452273 -- "Malignant intracerebral nerve sheath tumor: a case report and review of the literature." (Sharma S, Cancer. 1998 Feb 1;82(3):545-52.) Case report. 8 yo girl with right posterior temporal lobe tumor Treated with surgery. RT appears to have been used, but no information provided OS: healthy recurrence-free 17 months after surgery Abstract -- "Immunocytochemistry of recurring intracerebral nerve sheath tumour." (Bruner JM, J Neuropathol Exp Neurol 43: 296, 1984 (abstr).)