Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer - Real-World Outcomes From UK Centres.

AIMS: Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. MATERIALS AND METHODS: We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. RESULTS: Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3-43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months - upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4-7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. CONCLUSIONS: This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer.

Challenges to Treating Older Glioblastoma Patients: the Influence of Clinical and Tumour Characteristics on Survival Outcomes.

AIMS: There is now evidence to support giving single-agent chemotherapy, radiotherapy or hypofractionated concurrent chemoradiotherapy to older patients with glioblastoma (GBM). However, the clinical basis on which treatment decisions are made is under-researched and not standardised. This retrospective, multicentre study assessed whether pre-morbid characteristics or tumour imaging features could predict for overall survival in a cohort of older patients with GBM. MATERIALS AND METHODS: Patients aged > 70 years, diagnosed with GBM at three neuro-oncology centres from 2010 to 2015 were retrospectively analysed. Demographic, clinical, radiological and treatment details were included in a multivariate model to examine for predictors of overall survival. RESULTS: In total, 339 patients were included with a median overall survival of 3.8 months. One and 2 year overall survival rates were 13% and 4%, respectively. The median age at diagnosis was 75 years. Pre-treatment characteristics predicting for overall survival included Eastern Cooperative Oncology Group performance status over 0 (performance status 1, hazard ratio 1.66, P = 0.042; performance status 2, hazard ratio 1.78, P = 0.031; performance status 3, hazard ratio 2.20, P = 0.008; performance status 4, hazard ratio 2.40, P = 0.021), radiological evidence of mass effect (hazard ratio 1.31, P = 0.049), multifocal tumours (hazard ratio 3.419, P = 0.013), presenting with seizures (hazard ratio 0.63, P = 0.008) and tumours confined to the cerebral hemisphere (hazard ratio 0.59, P = 0.048). Subtotal resection decreased risk of death by 37% (P = 0.019) and total tumour resection by 44% (P = 0.019). Palliative radiotherapy decreased risk of death by 41% (P = 0.005), temozolomide alone by 60% (P = 0.004) and radical chemoradiotherapy by 81% (P < 0.001). CONCLUSION: Clinical presentation, performance status and imaging characteristics are independent prognostic indicators of overall survival in older GBM patients, irrespective of age or treatment received.

Comprehensive Geriatric Assessment in Men Aged 70 Years or Older with Localised Prostate Cancer Undergoing Radical Radiotherapy.

AIMS: Treatment decisions for men aged 70 years or over with localised prostate cancer need to take into account the risk of death from competing causes and fitness for the proposed treatment. Objective assessments such as those included in a comprehensive geriatric assessment (CGA) might help to inform the decision-making process. The aim of this study was to describe the CGA scores of a cohort of older men with prostate cancer, evaluate potential screening tools in this population and assess whether any CGA component predicts significant acute radiotherapy toxicity. MATERIALS AND METHODS: This was a prospective cohort study undertaking pretreatment CGA, Vulnerable Elders Survey (VES-13) and G8 assessment in patients aged 70 years and over with localised prostate cancer planned to undergo radical external beam radiotherapy. RESULTS: In total, 178 participants were recruited over a 3 year period and underwent a CGA. Fifty-five (30.1%) participants were defined as having health needs identified by their CGA. Both VES-13 and G8 screening tools showed a statistically significant association with CGA needs (P < 0.001 and X2 = 15.02, P < 0.001, respectively), but their sensitivity was disappointing. There was no association between a CGA (or its components) and significant acute radiotherapy toxicity. CONCLUSIONS: Many older men with localised prostate cancer are vulnerable according to a CGA. The screening tools evaluated were not sufficiently sensitive to identify this group. CGA outcome does not predict for significant acute radiotherapy toxicity.

Advantage of a one-stop referral and management service for ruptured abdominal aortic aneurysms.

BACKGROUND: In 2005, 4003 deaths in England and Wales were attributed to ruptured abdominal aortic aneurysm (RAAA). This study examined the referral and management patterns of this condition within one English county. METHODS: West Sussex has a population of 811 000 and is served by five hospitals with two main vascular networks. Between January 2005 and December 2007, data for community and in-hospital RAAA interventions and deaths were obtained. Probability of intervention and outcome for each network were calculated. RESULTS: Of 341 RAAA, 228 (66.9 per cent) presented to hospital. The mean distance travelled to hospitals with a full on-site vascular service was 17.6 (95 per cent confidence interval 15.5 to 19.7) km (124 patients) compared with 11.0 (9.5 to 12.7) km (104 patients) to hospitals with a partial or no vascular service (P < 0.001). Patients managed by the network with a one-stop RAAA management policy had an odds ratio of 2.4 for undergoing surgery and 2.5 for surviving the operation (P = 0.001 and P = 0.017 respectively). CONCLUSION: Patients with RAAA should be offered a one-stop emergency vascular service even if this involves further travel. Such a strategy offers significantly higher chance of intervention and survival from ruptured AAA.