Selumetinib for NF1-Related Plexiform Neurofibromas: Time to Response and Response Assessment

　　In children with NF1-related inoperable plexiform neurofibromas,tumor shrinkage with selumetinib is gradual and typically measured in months.In the SPRINT phase II trial of 50 pediatric patients,74%achieved a partial response and 70%a confirmed partial response.With 28-day treatment cycles,the median time to first partial response was 8 cycles(about 8 months),and the median time to best tumor reduction was 16 cycles(about 16 months).Responses varied:some patients showed earlier volume changes,while others took longer.

　　Selumetinib inhibits MEK1/2 signaling to control tumor growth,so volumetric change is rarely visible in the first weeks.Across the trial,first partial response occurred anywhere between 4 and 20 cycles.An MRI showing no obvious shrinkage after one month of treatment therefore does not indicate treatment failure and should not be used as an early verdict on efficacy.

　　Response is generally assessed with REiNS imaging criteria:a decrease of at least 20%in tumor volume from baseline is the key threshold for partial response,and it should be confirmed on subsequent scans.A single measurement or a change in diameter alone is not sufficient.

　　For monitoring,SPRINT performed baseline MRI and then volume assessments every 4 cycles(roughly every 4 months)for the first 2 years,and every 6 cycles(about every 6 months)thereafter.