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. 2023 Mar 31;15(7):2109.
doi: 10.3390/cancers15072109.

Evaluating Focal Areas of Signal Intensity (FASI) in Children with Neurofibromatosis Type-1 (NF1) Treated with Selumetinib on Pediatric Brain Tumor Consortium (PBTC)-029B

Natasha Pillay-Smiley  1   2 , James Leach  1   3 , Adam Lane  1   2 , Trent Hummel  1   2 , Jason Fangusaro  4   5 , Peter de Blank  1   2
Affiliations

Evaluating Focal Areas of Signal Intensity (FASI) in Children with Neurofibromatosis Type-1 (NF1) Treated with Selumetinib on Pediatric Brain Tumor Consortium (PBTC)-029B

Natasha Pillay-Smiley et al. Cancers (Basel). .

Abstract

Background: Understanding the effect of selumetinib on FASI may help elucidate the biology, proliferative potential, and role in neurocognitive changes for these NF1-associated lesions.

Methods: Patients with NF1-associated LGG and FASI treated with selumetinib on PBTC-029B were age-matched to untreated patients with NF1-associated FASI at Cincinnati Children's Hospital Medical Center. Paired bidirectional measurements were compared over time using nonparametric tests.

Results: Sixteen age-matched pairs were assessed (age range: 2.8-16.9 years, 60% male). Initial FASI burden was not different between groups (median range 138.7 cm2 [88.4-182.0] for the treated subjects vs. 121.6 cm2 [79.6-181.9] for the untreated subjects; p = 0.98). Over a mean follow-up of 18.9 (±5.9) months, the LGG size consistently decreased with treatment while no consistent change among the treated or untreated FASI size was seen. At the paired time points, the median treated LGG decreased significantly more than the treated FASI (-41.3% (LGG) versus -10.7% (FASI), p = 0.006). However, there was no difference in the median size change in the treated versus untreated FASI (-10.7% (treated FASI) versus -17.9% (untreated FASI), p = 0.08). Among the treated subjects, there was no correlation between the change in LGG and FASI (r = -0.04, p = 0.88).

Conclusions: Treatment with selumetinib did not affect the overall FASI size in children with NF1 treated for progressive low-grade glioma.

Keywords: FASI; MEK inhibitor; NF1; low grade glioma; selumetinib.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Spider plots demonstrating the percent change in the cross product of lesions from the baseline. Change in FASI from the chosen anatomic locations are shown on treatment with selumetinib (a) and without treatment (b) with variable responses. Treatment of LGG with selumetinib showed a consistent decrease over time (c).
Figure 1
Figure 1
Spider plots demonstrating the percent change in the cross product of lesions from the baseline. Change in FASI from the chosen anatomic locations are shown on treatment with selumetinib (a) and without treatment (b) with variable responses. Treatment of LGG with selumetinib showed a consistent decrease over time (c).
Figure 2
Figure 2
Longitudinal analysis of 15 treated/untreated subjects analyzed at paired time points over an average follow-up time of 18.5 (±6.5) months, with each bar representing individual patients. Decrease in the FASI size with treatment (a) compared to without treatment (b) did not reach statistical significance. In the treated patients, there was a significant difference between the treated LGG (c) and treated FASI (a).
Figure 3
Figure 3
Comparison of the change in FASI to the change in the LGG size at paired time points did not show any correlation.
Figure 4
Figure 4
T2 weighted MR imaging of a typical LGG and FASI at four time points during treatment. (A) The measured FASI in the right medial cerebellum (arrow) stayed relatively stable during the treatment course. (B) The presumed low-grade glioma involving the splenium of the corpus collosum (arrowhead) decreased substantially from the baseline over the treatment course.
Figure 5
Figure 5
Change from the baseline in the size of the thalamic and lentiform FASI. Spider plot demonstrates the decrease in most untreated FASI with a substantial increase in two treated FASI.
See this image and copyright information in PMC

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