A quality improvement programme in radiotherapy using workflow audits.

BACKGROUND: Evaluation of the quality of healthcare depends on measures of structures, processes and outcomes. Progress in recording data allows for better measures of processes, such as the completeness of clinical data, the performance of professional tasks and the use of checklists. OBJECTIVES: To report the results of a radiotherapy (RT) workflow audit and a subsequent online survey of user experience. METHODS: The RT workflow audit was developed in 2016 and has been undertaken twice a year at 28 facilities or units, with a total of 32 linear accelerators. Electronic patient folders were reviewed to assess the documentation of 90 task items, of which 64 were scored. The auditor came from another facility. The online survey took place in July 2020. It contained questions on the audit's process, professional value and future use. Invitations were sent by email to the 151 radiotherapist staff at the 28 units where the audit had been implemented. Responses were anonymous. RESULTS: For the RT workflow audit, scores improved from 60% in some units in 2016 to >90% in all units for at least 2 years since 2018. The number of responders to the online survey was 58, giving a responder rate of 38%. The margin of error of the results was 10%. The audit's task items were considered appropriate by 77% of responders, and feedback was reported by 78% of them. The audit was considered very or extremely valuable to their unit's service delivery by 58% of responders. Changes in the unit as a result of the audit were reported by 77% of responders. The audit was very useful or extremely useful to 75% of responders in maintaining personal professional standards. The proportion of responders who were very or extremely supportive of continuing with the audit was 77%. The comments in the online survey will be helpful for ongoing review of the RT workflow audit. CONCLUSIONS: The RT workflow audit extends the scope of accreditation audits by including measures of processes. Users of the audit evaluate its processes favourably and report that it has value both in their unit's clinical service and for their personal professional standards. The audit is effective in developing quality improvement programmes.

How to publish your work in a peer-reviewed journal: A short guide.

The basis of a manuscript is the research question, which is reported within a standard publication structure. The 'Background' section clarifies the question. The 'Methods' section describes what was done in the study. The 'Results' section describes the data observed and the analysis of these data. The 'Discussion' section describes how findings of the study relate to current knowledge and the practical implications of the results, and suggests future studies. This structure differs from that of a thesis, the aims of which are broader than reporting on a specific research question.

Cost considerations in determining the affordability of adjuvant trastuzumab in breast cancer.

The drug cost of adjuvant trastuzumab to benefit one patient with localised human epidermal growth factor receptor 2 (HER2)-positive breast cancer depends on the baseline survival rate (BLSR) of the prognostic group of the patient. This varies from ZAR13 752 900 (BLSR 90%) to ZAR4 006 100 (BLSR 60%). All treated patients are exposed to potential toxicity. The value and affordability of treatments need to be considered, as there are finite resources available in our healthcare system. All patients must have access to cost-effective treatments. However, patient selection for expensive treatments is important, as expenditure on patients where the gains are relatively small will result in resources not being available for other patients. The state, healthcare institutions and the pharmaceutical industry need to work together to optimise the benefits of treatment to patients.

Treatment of carcinoma of the anal canal at Groote Schuur Hospital.

OBJECTIVES: Chemoradiation is the treatment of choice for squamous carcinoma of the anal canal, resulting in the same local control rates as surgery but with the advantage of organ function preservation. We aimed to review all cases of anal canal carcinoma treated at Groote Schuur Hospital between 2000 and 2004 and to assess treatement outcome. METHODS: The records for 31 patients presenting during this period were reviewed. Patient and tumour characteristics were recorded. Twenty-six patients were treated with chemoradiation. Local failure-free, colostomy-free and overall survival were calculated using the Kaplan-Meier method. RESULTS: Compared with the literature, the median patient age was younger and the stage was more advanced in this study. The complete response rate for all stages with chemoradiation was 80%. The local failure-free survival at 5 years was 60.7%. Colostomy-free and overall survival at 5 years were 59.2% and 65.6%, respectively. CONCLUSIONS: The patients presented with locally advanced disease. Chemoradiation is effective treatment for this group of patients and the majority avoid a permanent colostomy as they preserve anal sphincter function.

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL). METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 (arm A) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms. RESULTS: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0-4.2), 4.1 (3.4-4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4-5.9), 5.1 (4.3-6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4-11.6), 9.8 (8.8-11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3-4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms. CONCLUSIONS: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.

10-year update on chemotherapy for non-small cell lung cancer.

BACKGROUND: A 1995 meta analysis of chemotherapy in patients with advanced non-small cell carcinoma indicated clinical benefit from cisplatin based chemotherapy. Subsequent studies have aimed to increase the efficacy or decrease the toxicity of chemotherapy. PATIENT AND METHODS: Illustrative studies and meta analyses of different aspects of chemotherapy which have taken place over the last decade, are reviewed. RESULTS: The use of novel (third generation) chemotherapy agents has resulted in a further increase in patient survival. Gemcitabine was shown to be associated with an increase in progression free survival when compared to other third generation agents as well as a strong tendency to increased overall survival. An increase in survival was also shown with doublet chemotherapy regimes as compared to the use of single agents only. The use of triplet agent chemotherapy results in no further increased survival, but increased toxicity. Cisplatin is associated with increased survival over carboplatin based chemotherapy regimens when third generation agents are used, but increased nausea and vomiting. Non-platin third generation combinations give equivalent survival to platin-based regimens. CONCLUSIONS: First line chemotherapy given to patients with advanced NSCLC should be two-drug combination regimen. Non-platin containing regimens may be used as an alternative to platinum based regimens in the first line.

Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer.

PURPOSE: The objective of this trial was to compare two vinorelbine-based doublets with carboplatin (CBDCA-VC) or with gemcitabine (VG) in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 316 patients with advanced NSCLC previously untreated were randomized to either vinorelbine 30 mg/m(2) D1,8 with carboplatin AUC 5 D1 (VC) or vinorelbine 25mg/m(2) with gemcitabine (VG) 1000 mg/m(2) both given D1,8 every 3 weeks. The primary endpoint was response rate with secondary parameters being survival (OS), progression-free survival (PFS), tolerance and clinical benefit. RESULTS: The median number of cycles was four in each arm with a total of 1268 cycles. The objective response (OR) on intent-to-treat was 20.8% in VC and 28% in VG (p=0.15). Median PFS was 3.9 months in VC and 4.4 months (mo) in VG (p=0.18). Median survival was significantly longer (p=0.01) for VG with 11.5 mo compared to 8.6 mo in VC with 1 year survival at 48.9 and 34.4%, respectively. Tolerance was better in the VG arm as compared to the VC patients. Four toxic deaths were recorded in the VC group. Clinical benefit response rate was 32.4% compared to 40.9% in 111 and 110 evaluable patients in VC and VG, respectively. CONCLUSION: VG compared to VC resulted in a similar overall response rate, favourable median survival and a better toxicity profile. For non-cisplatin-based chemotherapy, VG is a useful alternative.

Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer.

BACKGROUND: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. PATIENTS AND METHODS: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. CONCLUSIONS: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.

Docetaxel as neoadjuvant therapy for radically treatable stage III non-small-cell lung cancer: a multinational randomised phase III study.

BACKGROUND: Docetaxel (Taxotere) is a potent anticancer agent, with proven efficacy as first-line therapy in non-small-cell lung cancer (NSCLC). The aim of this large randomised multicentre phase III study was to evaluate docetaxel in the neoadjuvant (pre-operative) setting. PATIENTS AND METHODS: Patients with stage IIIA or locally treatable IIIB NSCLC were randomly assigned to receive neoadjuvant docetaxel (n = 134) or no chemotherapy (n = 140) before surgery/curative-intention radiotherapy. Patients received up to three 3-weekly cycles of docetaxel (100 mg/m(2)) as 1-h intravenous infusions. RESULTS: Median survival was 14.8 months in the docetaxel group and 12.6 months in the control group. Median times to disease progression were 9.0 months (docetaxel arm) and 7.6 months (control arm). There were three complete responses and 25 partial responses in patients treated with docetaxel who were evaluable for response (n = 101). Docetaxel was well-tolerated: 103 patients (77%) received all three planned cycles. The major toxicity was grade 4 neutropenia (69 patients, 55%) and neutropenic fever (eight patients, 6%). Radiotherapy was well-tolerated after docetaxel administration. CONCLUSIONS: Neoadjuvant docetaxel is generally well-tolerated and shows a promising trend towards longer survival in patients with NSCLC.

Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naïve patients with advanced non-small-cell lung cancer.

BACKGROUND: To evaluate the efficacy and safety of pemetrexed therapy for chemotherapy-naïve patients with surgically incurable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients received pemetrexed 600 mg/m2 every 3 weeks. Restaging was performed after every two cycles of therapy and toxicity was assessed at each cycle of pemetrexed. In the absence of disease progression or undue toxicity, treatment was continued for a maximum of 12 cycles. RESULTS: Fifty-nine patients (median age 59 years; range 39-74 years) received a median of four cycles of pemetrexed. Nineteen patients (32%) had a ECOG performance status (PS) of two and 39 patients (66%) had stage IV disease. The most common histological sub-types were adenocarcinoma (20 patients, 34%) and large cell (18 patients, 31%). Sixteen patients (27%) had received prior radiotherapy. Nine patients achieved a partial response for an overall response rate of 15.8% (95% confidence interval CI 7% to 28%). The median duration of response was 4.9 months, and the median survival was 7.2 months. The principal toxicities were myelosuppression and rash. While grade 3 or 4 neutropenia was seen in 25 patients (42%), only two patients (3%) developed grade 3 infection. Eighteen patients (31%) developed grade 3 or 4 cutaneous toxicity, which improved with prophylactic oral dexamethasone administered for 3 days beginning the day before pemetrexed treatment. Asymptomatic elevations in hepatic biochemistry (especially alanine transaminase and aspartate transaminase) were seen in 47 patients (80%); however, these did not interfere with the dose or schedule of pemetrexed and returned to normal levels throughout the study. CONCLUSIONS: This is the largest study confirming the encouraging single-agent activity of pemetrexed in chemotherapy-naïve patients with NSCLC. In addition, this study demonstrates that a dose of 600 mg/m2 can be delivered safely; however, treatment should be restricted to patients with a PS of 0 or 1. The results of combination studies are awaited with interest.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.