Limitations and benefits of FDG-PET/CT in NF1 patients with nerve sheath tumors: A cross-sectional/longitudinal study.

The purposes of this study were to re-confirm the usefulness of PET/CT in the differentiation of benignity/malignancy of neurogenic tumors in NF1 patients, and to analyze the natural course of plexiform neurofibroma (pNF) and clarify whether PET/CT is also useful for detecting tumors other than neurogenic tumors. PET/CT was prospectively imaged in 36 NF1 patients. There were 14 malignant peripheral nerve sheath tumors (MPNSTs) in 14 patients, and 54 pNFs in 30 patients. Nine patients had both MPNST and pNF. Maximal standardized uptake value (SUVmax) was significantly higher in MPNST (median 7.6: range 4.1-10.4) (P < .001) compared with that of pNF (median 3.7: range 1.6-9.3). The cut-off value of 5.8 resulted in a sensitivity of 78.6% and specificity of 88.9%. Median age was 29 y, and median maximum tumor diameter was 82 mm in 14 MPNST patients. The 5-y overall survival rate was 46.8%. Three patients with low-grade MPNST were alive without disease at the time of this report. In 9 patients in which pNF and MPNST co-existed, 2 showed a higher SUVmax of pNF than that of MPNST. Natural history analysis of pNF (n = 43) revealed that no factors significantly correlated with increased tumor size. Nine lesions other than neurogenic tumors were detected by PET/CT including 5 thyroid lesions and 3 malignant neoplasms. This study revealed the usefulness and limitation of PET/CT for NF1 patients. In the future, it will be necessary to study how to detect over time the malignant transformation of pNF to MPNST, via an intermediate tumor.

Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas.

BACKGROUND: Pirfenidone, an oral anti-inflammatory, antifibrotic agent with activity in idiopathic pulmonary fibrosis, may mediate anti-tumor activity in neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) by inhibition of fibroblast proliferation and collagen synthesis. The primary objective of this open label, single arm phase II trial was to evaluate the activity of pirfenidone in children and young adults with inoperable PN. PROCEDURE: Patients (3-21 years) with NF1-related progressive PN received pirfenidone at the previously determined optimal dose (500 mg/m(2) orally, q8h) on a continuous dosing schedule (one cycle = 28 days). Volumetric MRI analysis was used to assess response. Progression was defined as ≥ 20% PN volume increase compared to baseline. Pirfenidone would be considered active if it doubled the median time to progression (TTP) compared to the TTP on the placebo arm of a phase II trial with the farnesyltransferase inhibitor tipifarnib, which used near identical eligibility criteria. Toxicities, objective response rate, and quality of life (QOL) also were evaluated. RESULTS: Thirty-six patients were enrolled and tolerated pirfenidone well with intermittent nausea and vomiting as the most frequent toxicities. A dose reduction was required in only three patients. The median TTP for pirfenidone was 13.2 months compared to 10.6 months for the placebo control group from the tipifarnib trial (two-tailed P = 0.92; one-tailed P = 0.46). No objective responses were observed. CONCLUSIONS: Pirfenidone was well tolerated, but did not demonstrate activity as defined in this trial and does not warrant further evaluation in children with NF1 and progressive PN.

Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1.

OBJECTIVE: To characterize morbidity, mortality, and surgical outcomes in pediatric patients with symptomatic plexiform neurofibromas (PNFs). STUDY DESIGN: We conducted retrospective analysis of data from clinical records of surgical history and other neurofibromatosis type 1 (NF1)-related complications in children with PNFs seen at Cincinnati Children's Hospital Medical Center between 1997 and 2007. RESULTS: A total of 154 children with NF1 and PNFs were identified. Children with symptomatic PNFs had increased incidence of other NF1-related tumors (P < .05). Patients with NF1 and PNFs had a higher mortality rate (5/154, 3.2%) when compared with patients without or with asymptomatic PNFs (2/366, 0.5%; P = .024). The most common morbidities leading to surgeries were neurologic, disfigurement, orthopedic, and airway complaints. Less extensive resection predicted a shorter interval to second surgery (P < .0019). The highest recurrence was seen in tumors located in the head, neck, and thorax (P < .001). CONCLUSIONS: These findings quantify the increased risk for additional tumors and mortality associated with symptomatic PNFs. Surgical interventions were required in many cases and resulted in added morbidity in some cases. Patients with PNFs were more likely to benefit from surgery when the indications were airway compression or disfigurement.