PMC6196276_01
(A) T1+contrast MRI images: Upper panels are right temporal lobe; lower panels are corresponding right parietal images. Baseline (Aug. 2016) demonstrates the first appearance a temporal lobe lesion ~2 months post radiation/temozolomide; the lower panel demonstrates the primary GB. Middle section ~11 months later (June 2017) demonstrates slightly less enhancement of the temporal lobe lesion, and a dramatic reduction in enhancement and size of the parietal lobe lesion with decreased edema and treatment related cerebral atrophy. At ~12 months (Aug. 2017) the temporal lobe lesion has increased to 18 x 13 mm; the parietal lobe remains stable and in remission. (B) StrataNGS cancer hotspot sequencing was performed on the resection of the primary parietal lobe lesion, which possessed mutations in BRAF (V600E), PTEN (319fs), and the TERT promoter (C228T). Following progression on TTFields, the separate anterior temporal lesion was resected and demonstrated BRAF, PTEN, and TERT alterations, and the acquisition of a deep deletion of CDK2NA and an activating mutation in mTOR (V2006I). No other pathologic alterations were identified in the remaining 47 genes of the 88 genes assessed.
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August 2017. A post-radiation MRI was done in August 2016, showing increased thickness of the residual enhancing region in the right parietal lobe in addition to a new lesion in the right middle temporal gyrus (Figure 1). August 2016 to November 2016 (Figure 1), and stayed stable on bi-monthly follow up MRIs until August 2017. At this time the temporal lobe lesion was at 17.9 mm in diameter (on T1+contrast); the parietal lobe lesion was essentially resolved, confirming pseudo-progression of this tumor (Figure 1). T2/FLAIR images showed abnormality with an area of restricted diffusion and peripheral rim enhancement in the region of the right temporal lobe lesion.
(A) H&E stained section of right parietal tumor at original magnification of 40x, reveals a densely cellular astrocytic neoplasm with nuclear atypia, mitosis, and vascular endothelial proliferation. Palisaded necrosis was also present but not shown in this field. (B) H&E stained section of right temporal mass at original magnification of 40x, also reveals a densely cellular astrocytic neoplasm with slightly more gemistocytic features, nuclear atypia, mitosis, and vascular endothelial proliferation that was similar to the previously resected tumor. This material lacked necrosis.
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A gross total resection of the temporal lesion was achieved in August 2017, confirming a grade 4 astrocytoma, with wild type IDH1/2, unmethylated MGMT, and negative 1p19q co-deletion (Figure 2).
Demonstration of isodose cloud for temporal lobe lesion (see arrow). Purple denotes 5Gy isodose; green denotes 8.57 Gy isodose.
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An isodose cloud is depicted (Figure 3).
Demonstration of the field intensity distribution in axial slices through the centers of the (A) primary right parietal lobe lesion and (B) the right temporal lobe secondary lesion. The median field intensity in the region of the primary lesion was 1.7 V/cm (mean of 1.66 V/cm). In the region of the secondary lesion the median intensity was 1.48 V/cm (mean of 1.56 V/cm). This suggests that TTFields intensities around both lesions exceeded the therapeutic threshold of 1 V/cm.
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