Cerebral Ketones Detected by 3T MR Spectroscopy in Patients with High-Grade Glioma on an Atkins-Based Diet.

BACKGROUND AND PURPOSE: Ketogenic diets are being explored as a possible treatment for several neurological diseases, but the physiologic impact on the brain is unknown. The objective of this study was to evaluate the feasibility of 3T MR spectroscopy to monitor brain ketone levels in patients with high-grade gliomas who were on a ketogenic diet (a modified Atkins diet) for 8 weeks. MATERIALS AND METHODS: Paired pre- and post-ketogenic diet MR spectroscopy data from both the lesion and contralateral hemisphere were analyzed using LCModel software in 10 patients. RESULTS: At baseline, the ketone bodies acetone and ß-hydroxybutyrate were nearly undetectable, but by week 8, they increased in the lesion for both acetone (0.06 ± 0.03 ≥ 0.27 ± 0.06 IU, P = .005) and ß-hydroxybutyrate (0.07 ± 0.07 ≥ 0.79 ± 0.32 IU, P = .046). In the contralateral brain, acetone was also significantly increased (0.041 ± 0.01 ≥ 0.16 ± 0.04 IU, P = .004), but not ß-hydroxybutyrate. Acetone was detected in 9/10 patients at week 8, and ß-hydroxybutyrate, in 5/10. Acetone concentrations in the contralateral brain correlated strongly with higher urine ketones (r = 0.87, P = .001) and lower fasting glucose (r = -0.67, P = .03). Acetoacetate was largely undetectable. Small-but-statistically significant decreases in NAA were also observed in the contralateral hemisphere at 8 weeks. CONCLUSIONS: This study suggests that 3T MR spectroscopy is feasible for detecting small cerebral metabolic changes associated with a ketogenic diet, provided that appropriate methodology is used.

Temozolomide retreatment in a recurrent prolactin-secreting pituitary adenoma: Hormonal and radiographic response.

BACKGROUND: Temozolomide is an oral alkylating agent with schedule-dependent antitumor activity against high-grade malignancies including high-grade glioma. Increasingly, reports have suggested that temozolomide may have activity as a salvage therapy for aggressive, recurrent pituitary adenomas or carcinomas that fail surgery, radiation and other pharmacotherapy. To our knowledge, temozolomide retreatment following initial responsiveness has not previously been demonstrated. CASE REPORT: A woman was diagnosed with a prolactin-secreting pituitary adenoma in 1995 (age 44). Despite bromocriptine therapy, transphenoidal resection, radiotherapy, and cabergoline treatment she experienced continued clinico-radiographic progression, and temozolomide was initiated in 2011. She received three treatment cycles with rapid, dramatic clinico-radiographic response, and 99.3% reduction in serum prolactin. After three years of close observation, she developed recurrent radiographic progression and prolactin elevation. She was re-initiated on temozolomide, and after four cycles, clinical, radiographic and hormonal response was observed with a 92.2% reduction in serum prolactin. CONCLUSIONS/SUMMARY: Temozolomide is an increasingly described treatment option for refractory pituitary adenomas and carcinomas. In the current report, we document rapid biochemical response following retreatment with temozolomide in aggressive pituitary adenoma. When "off label" salvage therapy with temozolomide is offered for patients with recurrent prolactinomas, retreatment at the time of recurrence can be considered.

Impact of temozolomide on gonadal function in patients with primary malignant brain tumors.

BACKGROUND: Cumulative exposure to alkylating agents may produce impaired reproductive function. Temozolomide is an alkylating agent approved for treating malignant gliomas. OBJECTIVE: A pilot study was undertaken to investigate the effects of temozolomide on semen integrity in men with newly diagnosed or recurrent malignant gliomas. METHODS: Eligible patients had no known fertility problems or impotence. Comprehensive semen analysis and serum sex hormones were obtained at baseline and following 3 and at least 6 months of temozolomide. RESULTS: Thirteen men were recruited. Mean age was 42 years (28-58). Three had recurrent and 10 newly diagnosed malignant glioma. Four were unable to ejaculate or were azoospermic at baseline. Four provided samples at baseline and after at least 6 months of temozolomide. Five were unable to complete the study. Two of four patients with paired baseline and 6-month samples received 6 months of standard monthly temozolomide. Two patients received standard radiation and concurrent temozolomide followed by adjuvant temozolomide. At 6 months, three of these four patients demonstrated low sperm motility (two low at baseline); three had abnormally low percent normal forms (one abnormal at baseline); two developed abnormally low sperm density. Sex hormone values were normal in all four patients at all time points. CONCLUSION: Changes in semen analysis parameters following 6 months of temozolomide were observed. The small sample size precludes any firm conclusions regarding the importance and duration of these findings and their relation to temozolomide exposure. With validation in a larger study, these results may have important implications for counseling prior to initiation of temozolomide therapy in these patients.