Recommendations for imaging tumor response in neurofibromatosis clinical trials

Abstract

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.

Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas

“…The consensus guidelines of REiNS (Response Evaluation in Neurofibromatosis and Schwannomatosis) state that volumetric analysis of MRI should be used to assess tumor response in NF1-related PN clinical trials. 20 Additionally, the phase II placebo-controlled trial of R11577 has provided an historical control group for single-arm trials of new agents in progressive PNs using TTP as the primary endpoint. With these tools in hand, and based on the results from the phase Pelvis ± extremity n=7…”

Current whole-body MRI applications in the neurofibromatoses

“…[29][30][31] Tumor volumetry is preferred for quantifying complex PNST such as plexiform neurofibromas that can be large and infiltrative whereas 2D or linear measurement is more likely to misrepresent the true tumor dimensions by overestimating or underestimating PNST size and can be fraught with interobserver and intraobserver variations. [32][33][34] Tumor volumetry, particularly in infiltrative plexiform neoplasms such as the ones identified in patients with NF syndromes, has become the optimal approach for assessing tumor burden.…”

Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

“…Response was defined as C20 % reduction in tumor volume from baseline. Progression was defined as C20 % increase in volume, and tumors that showed \20 % reduction and [20 % increase in volume were categorized as stable [17]. In case of stable disease, everolimus was stopped and patients were subsequently monitored every 3 months for 1 year, and treatment was resumed in case of VS growth [20 %.…”