Radium-223 therapy for metastatic castration-resistant prostate cancer: survival benefit when used earlier in the treatment pathway.

BACKGROUND: Radium-223 dichloride (Ra-223) therapy improves overall survival in bony metastatic castration-resistant prostate cancer (mCRPC) patients. Recent guidance change recommends Ra-223 following at least two prior therapies for mCRPC. We evaluated how this change affects overall survival and the optimal timing of Ra-223 in the mCRPC treatment pathway. METHODS: Retrospective analysis of all mCRPC patients receiving Ra-223 therapy at a single UK centre over a 70-month period. Overall survival, number of prior lines of therapy commenced before Ra-223 initiation and number of Ra-223 therapy cycles completed were identified. RESULTS: One hundred ninety-one mCRPC patients received Ra-223 therapy during the study period. One hundred twenty-one (63%) received one prior therapy (group 1) and 70 (37%) received two prior therapies (group 2). Median survival in group 1 was significantly improved, compared to group 2 (448 days vs. 341 days (P = 0.03). Subgroup analysis of 111/191 (58%) patients that completed the recommended six Ra-223 therapy cycles showed additional improved survival. Median survival in group 1 was incrementally significantly improved, compared to group 2 within these patients (665 days vs. 552 days; P = 0.05). There was no difference in the number of patients completing the recommenced six cycles of therapy between the groups [72/121 (59%) vs. 39/70 (56%); P = 0.61]. CONCLUSION: We found a significant survival benefit when Ra-223 was used earlier in the mCRPC treatment pathway, with additional survival advantage seen in those patients completing all six Ra-223 cycles. Our results support the use of Ra-223 earlier in the treatment pathway.

Selective internal radiation therapy for liver tumours.

Primary and secondary liver malignancies are common and associated with a poor prognosis. Surgical resection is the treatment of choice; however, many patients have unresectable disease. In these cases, several liver directed therapies are available, including selective internal radiation therapy (SIRT). SIRT is a multidisciplinary treatment involving nuclear medicine, interventional radiology and oncology. High doses of localised internal radiation are selectively delivered to liver tumour tissues, with relative sparing of adjacent normal liver parenchyma. Side effects are minimal and radiation protection measures following treatment are straightforward. In patients who have progressed following chemotherapy, clinical trials demonstrate prolonged liver progression-free survival. SIRT is offered at 10 centres in England via the NHS England Commissioning through Evaluation programme and is approved by the National Institute for Health and Care Excellence for certain liver malignancies. SIRT holds unique promise for personalised treatment of liver tumours.

Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer.

PURPOSE: Radium Ra 223 dichloride (radium-223, Xofigo®) is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision. METHODS: An independent research consultancy agency observed radium-223 procedures and conducted interviews with all key staff members involved in radium-223 treatment delivery in 11 nuclear medicine centres across six countries (Germany, Italy, the Netherlands, Spain, Switzerland and the UK) experienced in administering radium-223. The findings were collated and discussed at a meeting of experts from these centres, during which key consensus recommendations were defined. RESULTS: The recommendations cover centre organization and preparation; patient referral; radium-223 ordering, preparation and disposal; radium-223 treatment delivery/administration; and patient experience. Guidance includes structured coordination and communication within centres and multidisciplinary teams, focusing on sharing best practice to provide high-quality, patient-centred care throughout the treatment pathway. CONCLUSIONS: These expert recommendations are intended to complement existing management guidelines. Sharing best practice and experience will help nuclear medicine centres to optimize radium-223 service provision and improve patient care.

Pharmacological stress myocardial perfusion scintigraphy: use of a modified adenosine protocol in patients with asthma.

BACKGROUND: Stress radionuclide myocardial perfusion scintigraphy (MPS) using adenosine pharmacological vasodilatation is the preferred method in many centres because of its convenience, safety and speed. It can, however, cause bronchospasm and hence its use is avoided in patients with known or suspected bronchospasm. Owing to service pressures, we use technologist-led adenosine stressing for patients referred for MPS studies. We use a modified adenosine infusion protocol under medical supervision for patients with asthma to prevent and minimize adenosine-induced bronchospasm. In this study, we audited our use of this modified protocol in asthmatic patients and compared the side-effect profile with the standard adenosine protocol used in nonasthmatic patients. METHODS: We audited 50 consecutive patients with asthma attending our department for stress MPS. All patients were taking regular inhalers+/-oral steroids. Patients who had exacerbation of asthma requiring hospital admission during the preceding 6 months were excluded. Before commencing the infusion, two inhaled puffs of salbutamol were administered. A modified adenosine infusion protocol was used, starting initially at a rate of 70 microg/kg/min and increasing to the standard 140 microg/kg/min within 1 min and then maintained for a further 5 min. Technetium-99m tetrofosmin was injected at 3 min. Blood pressure (BP), pulse rate (PR), oxygen saturation and ECG were monitored before, during and at the end of the infusion. All side effects were recorded. Fifty-eight consecutive patients without asthma were included as controls and received the standard 140 microg/kg/min infusion over 6 min. RESULTS: One hundred and eight patients, 50 with asthma and 58 without asthma, were entered into the study. The test was stopped early in two patients (4%) with asthma and 11 patients (19%) without asthma (chi=5.679; P=0.017). Proportionally, more nonasthmatics developed shortness of breath (SOB) (47 of 58, 81% without asthma vs. 35 of 50, 70% with asthma); however, this did not reach statistical significance (chi=1.788, P=NS). Three out of 50 (6%) patients in the asthma group experienced severe SOB but only one of those 50 patients (2%) developed bronchospasm, manifesting as wheeze. In the nonasthma group, five of 58 patients (8.6%) experienced severe SOB but none developed a wheeze. Less flushing (16 of 50, 32% vs. 36 of 58, 62%; P=0.002), dizziness (12 of 50, 24% vs. 26 of 58, 45%; P=0.023) and neck/throat pain (5 of 50, 10% vs. 16 of 58, 28%; P=0.021) was observed in the modified infusion group with asthma compared with the standard infusion group without asthma. Statistical significance was observed in these three side effects. No significant difference in other side effects was noted. A similar decrease in mean diastolic BP, and an increase in mean PR were observed during the infusion in both asthmatic and nonasthmatic groups. The mean systolic BP decreased significantly in nonasthmatic patients (P<0.001) but not in the asthmatic group. No significant change in oxygen saturation was seen during infusion in the asthmatic group. CONCLUSION: The modified adenosine infusion protocol with salbutamol premedication can be used in patients with asthma. This protocol resulted in fewer side effects and changes in BP and PR in asthmatic patients compared with nonasthmatic patients who received the standard adenosine infusion.