Optimising Radium 223 Therapy for Metastatic Castration-Resistant Prostate Cancer -5-year Real-World Outcome: Focusing on Treatment Sequence and Quality of Life.

AIMS: Real-world evidence of radium 223 (Ra-223) for the treatment of men with metastatic castration-resistant prostate cancer is emerging. In this prospective single-centre service evaluation, we report for the first time in the UK, real-world quality of life (QoL) and survival outcomes, including the sequencing impact, in 228 treated patients. We aim to share our 5-year experience on how to optimise Ra-223 treatment. MATERIALS AND METHODS: Patients who received Ra-223 therapy between 2014 and 2018 at the Northern Centre for Cancer Care, Newcastle upon Tyne, UK were included in this evaluation. Demographics, clinical characteristics, blood parameters, treatment sequencing and QoL data using abbreviated Functional Assessment of Cancer Therapy-Prostate questionnaires were prospectively collected and analysed. RESULTS: In total, 228 patients were included; median age 72 years (51-87). The medium overall survival was 11.1 months. Overall survival in post-chemotherapy and chemotherapy-naïve patients was 8.1 and 12.3 months, respectively (P = 0.02, hazard ratio 1.52, 95% confidence interval 1.06-2.17); in pre-enzalutamide and post-enzalutamide patients was 11.3 and 10.4 months, respectively (P = 0.65, hazard ratio 0.92, 95% confidence interval 0.63-1.33); in pre-abiraterone and prednisolone and post-abiraterone and prednisolone patients was 11.8 and 10.5 months, respectively (P = 0.08, hazard ratio 0.74, 95% confidence interval 0.51-1.06); in this latter group, the fracture rate was 24% (15/63). QoL post Ra-223 (n = 101 evaluated) showed that pain scores improved in 54%, there was no change in 17% and pain scores worsened in 30% of treated patients. Overall QoL scores showed a similar trend. QoL was not significantly associated with overall survival. CONCLUSIONS: Ra-223 palliates pain and improves disease-related QoL in most patients in the real-world setting. Our survival outcome is comparable with other real-world studies. Chemotherapy-naïve patients seemed to have better survival than those who received prior chemotherapy. No significant survival differences were observed between pre- and post-abiraterone and prednisolone or enzalutamide patients. The fracture rate in the post-abiraterone and prednisolone group seemed to be high. Bone health evaluation and protection should be incorporated as standard of care.

Systemic chemotherapy and its implications for resection of colorectal liver metastasis.

BACKGROUND: Liver resection remains the only chance of cure for patients with colorectal liver metastasis. Modern chemotherapy can play a role in the management of these patients but is not without risk. METHODS: The online databases Medline and Pubmed were searched to identify relevant articles. Keywords used in these searches were "colorectal cancer", "liver metastasis", "chemotherapy", "liver resection", "monoclonal antibody", "steatohepatitis", "sinusoidal obstruction" and "liver regeneration". Databases were searched for the period January 1970 to September 2009 inclusively. In addition hand referencing of retrieved articles was performed. RESULTS: Modern chemotherapy regimens can effectively downstage initially unresectable disease such that surgical resection can be performed with the prospect of long term cure. There is insufficient evidence however to recommend its use in either the neoadjuvant or adjuvant setting in those with resectable disease from the outset. CONCLUSION: Chemotherapy can be associated with significant changes to the hepatic parenchyma with subsequent increased risk of morbidity and mortality in the perioperative period. Much work needs to be done to understand the molecular mechanisms underlying these changes to make extended resections safer in patients who are at risk.

The development of a protocol for the use of 5-HT3 antagonists in chemotherapy-induced nausea and vomiting.

The purpose of this study was to evaluate the effectiveness of three 5-HT3 antagonists in routine clinical practice. The ultimate aim was to develop an antiemetic protocol, selecting a single 5-HT3 antagonist. Each of the drugs was studied for a 4-month period and data was collected from patients on nausea, vomiting (both acute and delayed) and side-effects by means of a diary card. A total of 274 patients were enrolled into the study. Success rates for acute emesis seen over the study period were in excess of 90%. There were no statistically significant differences between any of the three drugs investigated with respect to both acute and delayed nausea and vomiting. Similarly, there was no difference between the three groups for the incidence of constipation, diarrhoea and headache. Granisetron demonstrated a lesser deviation from the protocol in respect of the number of intravenous doses given to patients. The study allowed an effective 5-HT3 antagonist protocol to be developed for use in the management of nausea and vomiting in cancer patients.

Survival from cancer: local control and radiotherapy.

Adjuvant radiotherapy is considered to be highly effective in maintaining local control but is widely perceived to confer no survival advantage in the management of solid tumours. However, recent adjuvant radiotherapy studies are beginning to show survival improvements in parallel with improvements in loco-regional disease control.