No benefit from TMZ treatment in GB with truly unmethylated MGMT promoter: Reanalysis of the CE.6 and the pooled Nordic/NOA-08 trials in elderly GB patients.

BACKGROUND: The treatment of elderly/ frail patients with glioblastoma is a balance between avoiding undue toxicity, while not withholding effective treatment. It remains debated, whether these patients should receive combined chemo-radiotherapy with temozolomide (RT/TMZ➜TMZ) regardless of the O6-methylguanine DNA methyltransferase gene promoter (MGMTp) methylation status. MGMT is a well-known resistance factor blunting the treatment effect of TMZ, by repairing the most genotoxic lesion. Epigenetic silencing of the MGMTp sensitizes glioblastoma to TMZ. For risk adapted treatment, it is of utmost importance to accurately identify patients, who will not benefit from TMZ treatment. METHODS: Here, we present a reanalysis of the clinical trials CE.6 and the pooled NOA-08 and Nordic trials in elderly glioblastoma patients that compared RT to RT/TMZ➜TMZ, or RT to TMZ, respectively. For 687 patients with available MGMTp methylation data, we applied a cutoff discerning truly unmethylated glioblastoma, established in a pooled analysis of four clinical trials for glioblastoma, with RT/TMZ➜TMZ treatment, using the same quantitative methylation specific MGMTp PCR assay. RESULTS: When applying this restricted cutoff to the elderly patient population, we confirmed that glioblastoma with truly unmethylated MGMTp derived no benefit from TMZ treatment. In the Nordic/NOA-08 trials RT was better than TMZ, suggesting little or no benefit from TMZ. CONCLUSION: For evidence-based treatment of glioblastoma patients validated MGMTp methylation assays should be used that accurately identify truly unmethylated patients. Respective stratified management of patients will reduce toxicity without compromising outcome and allow testing of more promising treatment options.

Time to dismiss boost? Outcomes of children with localized and metastatic germinoma.

PURPOSE: To determine long-term outcomes of a cohort of children with germinoma treated with chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy METHODS: This retrospective study analyzed the outcome of patients with germinoma consecutively diagnosed and treated at a tertiary care center from January 2000 to December 2021. MRIs were reviewed by two radiologists, blinded to patient data. Tumor location at diagnosis, tumor response to chemotherapy and at completion of radiation therapy and site of relapse were assessed. Tumor response was assessed radiologically by determining the tumor size and response on diffusion-weighted imaging, in addition to biochemical, cytological parameters and neurological status. RESULTS: Of 46 pediatric germinoma patients, 29 children (14 male; median age 12.8 years) received no primary tumor boost. Median follow-up was 63 months (range 9-187 months). Twenty-five children had localized disease and tumor location was suprasellar (n = 11), pineal (n = 10), bifocal (n = 3) and basal ganglia (n = 1) while 4 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either ventricular irradiation (VI) (23.4 Gy) (n = 23), whole brain (WBI) (23.4 Gy) (n = 5) or craniospinal radiation (CSI) (23.4 Gy) (n = 1). Two children, who had localized disease at presentation and received VI after chemotherapy, relapsed 9 months and 32 months after completion of treatment respectively. No patient had a local relapse. Location of relapse was distant, outside (n = 1) and out- and inside (n = 1) the irradiation field. Five-year progression free survival (PFS) was 91% and overall survival (OS) was 100%. CONCLUSIONS: In this case series, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy of 23.4 Gy delivered without primary tumor boost. No local relapse was observed despite omitting primary tumor boost in patients with localized and metastatic germinoma.

Trigeminal nerve integrated dose and pain outcome after gamma knife radiosurgery for trigeminal neuralgia.

BACKGROUND: Gamma knife radiosurgery (GKRS) is an established treatment for trigeminal neuralgia. Identifying factors that influence outcome will help improve patients' results. METHODS: We conducted a retrospective review of all patients treated with GKRS for trigeminal neuralgia at our institution from 2005 to 2010. Patients' clinical features and treatment details were reviewed. Analysis was performed to identify predictors of response and recurrence. RESULTS: A hundred and forty five patients were treated. Mean follow up period was 24 months. At last follow up, 48 patients (33%) were pain free with no medications, and 48 patients (33%) were pain free maintained on medications. Twenty-eight patients (19%) had pain after the treatment but had significant reduction in their pain severity. Twenty-one patients (15%) did not have any significant pain reduction. Forty-four patients (30%) developed facial numbness. Recurrence occurred in 51 patients (35%). Post-treatment numbness was a predictor of good treatment response (OR 2.720, CI 1.193-6.200, p 0.0173). Higher integrated dose was a predictor of poor pain response to radiosurgery (OR 0.729, CI 0.566-0.940, p 0.0146). At an integrated dose value of 5.3 mJ or less, there was more than 50% chance of pain free outcome. Longer pain duration prior to treatment was the only independent predictor of increased recurrence risk (HR 1.038, 95%CI 1.001-1.075; p=0.0412). CONCLUSIONS: Radiosurgery is an effective treatment modality for trigeminal neuralgia. Post treatment numbness is associated with good treatment response and higher integrated dose predicts poor outcome after radiosurgery for trigeminal neuralgia.

Prolonged survival in a patient with choroidal metastases from urothelial bladder cancer.

Choroidal metastases secondary to urothelial carcinoma are extremely rare and are usually associated with an extremely poor prognosis. We present a case of an 88-year-old man with newly diagnosed urothelial carcinoma of the bladder who presented with acute loss of vision before commencing definitive concurrent chemoradiotherapy to the bladder. Ophthalmological examination demonstrated bilateral choroidal metastases. He received palliative radiotherapy to the orbits and completed his planned radiotherapy to the bladder. He remained disease-free at last follow-up 4 years after the completion of treatment. We review the literature particularly with regard to diagnosis and management of choroidal metastases. Choroidal metastases should be considered in a patient with a history of urothelial cancer presenting with new onset of eye symptoms.

Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: 2-year follow-up.

OBJECTIVE: To evaluate the efficacy and complications of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma. DESIGN: Retrospective review. PARTICIPANTS: 64 patients with juxtapapillary choroidal melanoma. METHODS: Consecutive patients with juxtapapillary choroidal melanomas located within 2 mm of the optic nerve, treated with stereotactic radiotherapy at Princess Margaret Hospital from October 1998 to January 2006, were reviewed for treatment effect and complication rates. RESULTS: Median age was 63 years. Median tumor height was 4.2 mm, and median maximum tumor diameter was 9.8 mm. The prescribed radiation dose was 70 Gy in 5 fractions over 10 days, and the median follow-up was 26 months. After treatment, there was local tumor recurrence in 3 patients, and in 8 patients there was systemic progression. Actuarial rates of local tumor control, metastases, and survival at 26 months were 94%, 12%, and 94%, respectively. Rates of radiation-induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 26 months were 28%, 45%, 80%, and 52%, respectively. Enucleation was necessary for 7 patients. CONCLUSIONS: Stereotactic radiotherapy offers a noninvasive alternative with acceptable ocular toxicity rates to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma.