NF1 plexiform neurofibroma growth rate by volumetric MRI

Dombi, Eva; Solomon, Jeffrey; Gillespie, Andrea; Fox, Elizabeth; Balis, Frank M.; Patronas, Nicholas J.; Korf, Bruce R.; Babovic‐Vuksanovic, Dusica; Packer, Roger J.; Belasco, Jean B.; Goldman, Stewart; Jakacki, Regina I.; Kieran, Mark W.; Steinberg, Seth M.; Widemann, Brigitte C.

doi:10.1212/01.wnl.0000250332.89420.e6

Cited by 169 publications

(152 citation statements)

References 12 publications

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“…Several studies have described more rapid growth rates of PN in younger children compared to older children or adults. [21][22][23] Therefore, stratification based on age or progression status could be considered for clinical trials evaluating TTP as the primary endpoint.…”

Section: -1315mentioning

confidence: 99%

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Recommendations for imaging tumor response in neurofibromatosis clinical trials

et al. 2013

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Methods: Currently used imaging endpoints, designs of NF clinical trials, and knowledge of the natural history of NF-related tumors, in particular PN and VS, were reviewed. Consensus recommendations for response evaluation for future studies were developed based on this review and the expertise of group members.Results: MRI with volumetric analysis is recommended to sensitively and reproducibly evaluate changes in tumor size in clinical trials. Volumetric analysis requires adherence to specific imaging recommendations. A 20% volume change was chosen to indicate a decrease or increase in tumor size. Use of these criteria in future trials will enable meaningful comparison of results across studies. Conclusions:The proposed imaging response evaluation guidelines, along with validated clinical outcome measures, will maximize the ability to identify potentially active agents for patients with NF and benign tumors. 1,2 Linear measurements are performed for their ease of use and are suitable for most malignant lesions that rapidly change in size. Disease-specific recommendations have been developed for some diseases in which linear measurements are not practical or meaningful, such as the Response Assessment in Neuro-Oncology (RANO) criteria for brain tumors.3,4 In addition, an international effort is under way to develop measurement guidelines for pediatric brain tumors, which will be applicable to neurofibromatosis type 1 (NF1)-related gliomas.

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Section: -1315mentioning

confidence: 99%

“…The inverse relationship between age and PN growth rate has been confirmed in other studies. [21][22][23] Spontaneous PN shrinkage was not observed in the placebo arm of the study and has only infrequently been observed in other studies. Comparison of measurement sensitivity to detect change in tumor size meningiomas, and ependymomas.…”

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Recommendations for imaging tumor response in neurofibromatosis clinical trials

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“…A longitudinal study evaluating PN growth rate showed a significant variability among patients, 23 making clinical trial design for treatment of these tumors challenging. No study to date has demonstrated Figure Plexiform neurofibroma (PN) growth before, during (in red), and after treatment with pegylated interferon-␣-2b (PI)…”

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Phase I trial of pegylated interferon-α-2b in young patients with plexiform neurofibromas

Jakacki¹,

Dombi²,

Potter³

et al. 2011

Neurology

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Objective: Interferon has antiproliferative and antiangiogenic properties. We sought to evaluate preliminary efficacy and determine the recommended phase II dose (RP2D) for pegylated interferon-␣-2b (PI) in patients with unresectable progressive or symptomatic plexiform neurofibromas (PN).Methods: PI was administered weekly in cohorts of 3-6 patients during the dose-finding phase and continued for up to 2 years. Twelve patients were treated at the RP2D to further evaluate toxicity and activity.Results: Thirty patients (median age 9.3 years, range 1.9-34.7 years) were enrolled. No doselimiting toxicity (DLT) was seen in patients treated at the 3 g/kg dose level (DL) during the first 4 weeks. All 5 patients treated at the 4.5 g/kg DL came off study or required dose reductions for behavioral toxicity or fatigue. Similar DLT on the 3 g/kg DL became apparent over time. There was 1 DLT (myoclonus) in 12 patients enrolled at the 1.0 g/kg DL. Eleven of 16 patients with pain showed improvement and 13 of 14 patients with a palpable mass had a decrease in size. Five of 17 patients (29%) who underwent volumetric analysis had a 15%-22% decrease in volume. Three of 4 patients with documented radiographic progression prior to enrollment showed stabilization or shrinkage. Conclusions:The RP2D of PI for pediatric patients with PN is 1 g/kg/wk. Clinical and radiographic improvement and cessation of growth can occur. Classification of evidence:This study provides Class III evidence that pegylated interferon-␣-2b in patients with unresectable, progressive, symptomatic, or life-threatening PNs results in radiographic reduction or stabilization of PN size. Neurology ® 2011;76:265-272 GLOSSARY AUC ϭ area under the curve; DL ϭ dose level; DLT ϭ dose-limiting toxicity; FDA ϭ Food and Drug Administration; IFN ϭ interferon; MTD ϭ maximum tolerated dose; NF1 ϭ neurofibromatosis type 1; NHT ϭ nonhematologic toxicity; PEG ϭ polyethylene glycol; PI ϭ pegylated interferon-␣-2b; PN ϭ plexiform neurofibroma; RP2D ϭ recommended phase II dose; STIR ϭ short T1-inversion recovery; TSH ϭ thyroid-stimulating hormone; VA ϭ volumetric analyses.Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurogenetic disorder characterized by a wide variety of progressive cutaneous, neurologic, skeletal, and neoplastic manifestations.1 PN are one of several types of neurofibromas that may occur in patients with NF1 and are characterized by a proliferation of Schwann cells, fibroblasts, and mast cells occurring along the length of a nerve. They occur in 25%-50% of adults and children with NF1, 2,3 and typically infiltrate adjacent normal tissue, making complete surgical resection usually impossible. As they grow, they frequently become disfiguring as well as disabling or even life-threatening. 4,5 Regrowth following subtotal resection is common.6 Standard chemotherapy is not effective and there is currently no standard medical treatment despite various clinical trials. [7][8][9] Interferons (IFNs) have both antiproliferative and antiangiogenic pr...

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“…The majority of these tumors are benign in nature and include cutaneous and subcutaneous neurofibromas as well as plexiform neurofibromas, which are histologically distinct from schwannomas. 15,26 Whereas conventional schwannomas are more commonly seen in patients with NF2, 4% of cases of the cellular schwannoma variant, as seen in Case 1, occur in patients with NF1. 55 Patients with NF1 are also at risk for the development of MPNST, a high-grade soft-tissue sarcoma that can be quite difficult to cure.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral schwannomas: a rare disease with varying natural history

Scott

Koral²,

Margraf

et al. 2013

PED

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Although intracerebral schwannomas are typically regarded as benign intracranial tumors, malignancy and recurrence have been reported among patients harboring such neoplasms. The available literature consists of case reports and small series that present variable characteristics distinguishing these unusual lesions. Little advancement has been made to further the understanding and management of these tumors. The authors present 3 cases from their institution that highlight the difference between typical benign intracerebral schwannomas and histopathological variants that may portend more aggressive behavior. Also provided is a review of the literature in the hope of gaining a better understanding of these rare tumors.

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NF1 plexiform neurofibroma growth rate by volumetric MRI

Cited by 169 publications

References 12 publications

Recommendations for imaging tumor response in neurofibromatosis clinical trials

Recommendations for imaging tumor response in neurofibromatosis clinical trials

Phase I trial of pegylated interferon-α-2b in young patients with plexiform neurofibromas

Intracerebral schwannomas: a rare disease with varying natural history

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