Anaplastic astrocytoma cells not detectable on autopsy following long-term temozolomide treatment: A case report

Abstract

We herein present an autopsy case of a glioma patient who received long-term treatment with temozolomide (TMZ). The patient, a 35-year-old man with a hypointense tumor of the left frontal lobe, without contrast enhancement following gadolinium (Gd) administration on T1-weighted images, underwent tumor removal surgery, after which the tumor was diagnosed as anaplastic astrocytoma. By the third round of surgery, the tumor had progressed to anaplastic astrocytoma with contrast enhancement following Gd administration, and the patient received 60 Gy of external beam radiotherapy and nimustine hydrochloride (ACNU)-based chemotherapy. After the fifth tumor removal surgery, TMZ was substituted with ACNU chemotherapy, which suppressed tumor progression. Following the 41st TMZ treatment, hemorrhage was observed in the residual tumor, and the hematoma had been replaced by a hemangioma. The hemangioma and surrounding brain tissue was removed during the sixth surgery. The patient survived for 14 years and 9 months after the initial surgery, but succumbed to hydrocephalus due to bleeding from hemangiomas. The histopathological specimens of the first to the sixth surgeries revealed mutant isocitrate dehydrogenase 1 (IDH1; R132H point mutation) and p53-positive tumor cells, but cells positive for the R132H mutation or p53 could not be detected by immunohistochemistry in the autopsy specimens of the brain after 108 courses of TMZ treatment. Mutant IDH1 (R132H) cells were also not detected in the autopsy specimens of the brain by polymerase chain reaction analysis.

Triple-drug Therapy With Bevacizumab, Irinotecan, and Temozolomide Plus Tumor Treating Fields for Recurrent Glioblastoma: A Retrospective Study

“…Thus, not treating rGBM patients with TMZ may not be justified, or at least the tumor MGMT promoter methylation status requires re-evaluation before making a therapeutic decision. Individual cases of as many as 101 (44) and 108 (45) cycles of TMZ including its use for recurrent glioma, did not report unexpected toxicities and treatment was effective in controlling tumor regrowth. Perry et al demonstrated that re-challenging rGBM patients with continuous, dose-intense TMZ at 50 mg/M 2 /d was effective, especially among patients whose tumor progressed during the first six cycles of conventional adjuvant TMZ therapy or after a treatment-free interval (46).…”