Abstract Background A 13-year-old female presented in March 2021 with one month of headaches and diplopia. MRI of her brain showed a 5.9x5.4x4.8cm left frontal mass, and pathology confirmed a grade IV astrocytoma, IDH mutant, as well as MSH2 germline mutation consistent with Lynch Syndrome and high tumor mutational burden. Patients with Lynch Syndrome with the MSH2 variant have an increased risk for numerous types of cancer, including high-grade astrocytoma, which tends to have a shorter survival time than non-MSH2-associated astrocytomas due to increased mutational burden. She also had PIK3CA, TP53, ATRX, APC, and NF1 mutations. She was started on pembrolizumab 2mg/kg IV every 3 weeks, and bevacizumab 10mg/kg was added IV every 3 weeks for a total of 23 months until her mother decided to transition to hospice care. Two doses of ipilimumab were given until discontinuation due to severe colitis. Olaparib, a PARP inhibitor, was given for 11 months during the pembrolizumab and bevacizumab infusions before being stopped due to adverse effects. Alpelisib, a PI3K inhibitor, was then started and had to be discontinued due to hypotensive shock after one week. Intermittent courses of high-dose dexamethasone were given during treatment to aid with edema secondary to her tumor. She completed two courses of cranial radiation and two resections during treatment. She survived 29 months after her diagnosis. Conclusion High-grade pediatric gliomas are highly aggressive tumors with a median survival of approximately 12 months from diagnosis. We present a pediatric case of grade IV astrocytoma with Lynch Syndrome who survived 29 months after the time of diagnosis with a combination of pembrolizumab, bevacizumab, and Olaparib. Further research is needed to advance high-grade glioma treatment in pediatric patients, particularly those with concurrent Lynch syndrome.
Casey et al. (Fri,) studied this question.