IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres.

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.

Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study.

BACKGROUND: Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. METHODS: In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. FINDINGS: 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9-18·5) for patients on denosumab and 11·2 months (IQR 5·6-17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8-24·9) with denosumab compared with 17·1 months (15·0-19·4) with zoledronic acid (hazard ratio 0·82, 95% CI 0·71-0·95; p = 0·0002 for non-inferiority; p = 0·008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0·0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p = 0·09). INTERPRETATION: Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer. FUNDING: Amgen.