PMC7264170_01
Clinical progression of the index case.. A timeline of the patient's clinical course is shown with representative imaging at the top and corresponding medical and radiation treatments below.
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Fig1
Magnetic resonance imaging (MRI) with MR angiography showed a 2.2 cm enhancing predominantly cystic lesion adjacent to the hematoma and within the left anterior temporal pole, concerning for an underlying neoplasm (Supplementary Fig. 1a, b). Nine months after surgery and four cycles of maintenance chemotherapy, repeat imaging demonstrated new nodular enhancement within the inferior aspect of the resection bed with mild surrounding FLAIR abnormalities (Supplementary Fig. 1c, d). Repeat MRI showed an increased size of the rim-enhancing mass measuring up to 5.3 cm with a prominent cystic component (Supplementary Fig. 1e, f). However, on repeat imaging 2 months after starting bevacizumab therapy, there was evidence of a recurrent enhancement within the resection bed, as well as a new focus of enhancement within the occipital lobe with signs of internal hemorrhage, prompting cessation of bevacizumab therapy (Supplementary Fig. 1g, h). Within days of stopping treatment, the patient became acutely obtunded and was found to have significant intratumoral hemorrhages within the temporal and occipital lobes (Supplementary Fig. 1i, j), requiring emergent decompressive hemicraniectomy and hematoma evacuation. This was managed conservatively with lumbar drainage, but his hospital course was significant for repeat surveillance imaging demonstrating significant growth of the tumor from the temporal focus, crossing over the corpus callosum into the contralateral hemisphere (Supplementary Fig. 1k, l).
Genomic analysis.. a CNV of the tumor from the first and second surgeries, in the upper and lower panel respectively, depict the loss of amplification on chromosome 7, beside other events. b Representation of clonal evolution of tumors from three distinct surgeries using fishplot, where the width of each different colored clone represents clonal fraction at the given timepoint, in relationship to the patient's surgeries and treatments. c Mutation signatures of three specimens represent the most aberrant COSMIC signatures. d Distribution of 96 mutation signatures of all specimens.
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Fig2
Final pathology was consistent with WHO grade IV glioblastoma (Supplementary Fig. 2a) with a Ki67% index over 20%. Pathology re-demonstrated recurrent glioblastoma (Supplementary Fig. 2b) with marked absence of any immune inflammatory response (Supplementary Fig. 3). Pathology showed areas of viable tumor within largely hemorrhagic material (Supplementary Fig. 2c). Repeat imaging one month after completing RT showed a growing left temporal tumor-related cyst, and due to the severity of his symptoms, he underwent a fourth surgery for left temporal lobectomy and tumor cyst fenestration into the basal cisterns with histopathological confirmation of progressive tumor (Supplementary Fig. 2d).