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.

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.

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.

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.

Modeling tumor and treated lung volume influences in the irradiation of non-small-cell lung cancer patients.

PURPOSE: The proposal of a hypothetical model in patients treated by irradiation for non-small-cell lung cancer show the dependence of local tumor control and patient cure rates on the volume of tumor and irradiated lung tissue. RESULTS: The local tumor control rates from conventional doses of irradiation decreases and the metastases rate increases with the tumor volume. Dose escalation will increase the potential cure rates (product of the local control and the freedom from metastases rates). Any potential gain will, however, be modified by the effect of irradiation on normal lung. Studies indicate that this is dependent on the volume of lung irradiated above a threshold dose. CONCLUSION: A clinically significant and measurable increase in cure rates from dose escalation may be seen in smaller tumors. This is unlikely to occur in larger tumors, although dose escalation to a restricted volume combined with effective systemic chemotherapy is one of the options that may be explored. The relevance of modeling and future studies of tumor and normal tissue volume effects, will increase from the widespread usage of the dose-volume histogram.

Radical cystectomy for invasive bladder cancer--a local experience.

OBJECTIVES: The aim of this study of patients undergoing cystectomy for invasive transitional cell carcinoma of the bladder was to compare clinical and pathological staging and to review factors that predict survival. PATIENTS: Sixty-three patients (73% male) underwent radical cystectomy between January 1988 and February 1994. The mean age was 61 years (range 33-77 years). RESULTS: Of the patients 14% had clinical and 24% pathological stage T1 disease; figures for T2 disease were 24% and 6%, respectively, for T3 disease 46% and 45%, and for T4 disease 16% and 25%. For T1 and T4 disease the clinical stage predicted the pathological stage in over 80% of cases, and for patients with T3 disease the predictive value of clinical staging was 68%; in no patient with clinical stage T2 disease was this confirmed at cystectomy. The prevalence of tumour infiltration of the lymph glands on histological examination of the cystectomy specimen correlated more closely with pathological stage than with clinical stage. For clinical and pathological staging, respectively, the prevalences were 0% and 0%, for T1, 27% and 0% for T2, 20% and 29% for T3, and 40% and 38% for T4. The overall survival rate (life-table method) was 33% at a median follow-up of 42 months in the surviving patients. No patient with tumour infiltration of the lymph glands survived. Survival also correlated more closely with pathological than with histological stage. For clinical and pathological stage T1 disease the 5-year survival rates were 73% and 91%, respectively; for T2 the rates were 27% and 75%, for T3 32% and 31%, and for T4 28% and 29%. The operative mortality rate was 2% and the rate of recurrence of local disease 10%. CONCLUSIONS: Survival after cystectomy correlates more closely with pathological than with clinical stage of disease. The accuracy of clinical staging in T2 disease is poor. Cystectomy is the standard against which other treatments for bladder cancer must be measured.

Combined cisplatin and gemcitabine for non-small cell lung cancer: influence of scheduling on toxicity and drug delivery.

The scheduling of cytotoxic chemotherapy has important bearing on the toxicity and ability to deliver chemotherapy at or close to full dose. We report new data on the influence of different schedules of cisplatin and gemcitabine on toxicity and drug delivery in phase II studies of non-small cell lung cancer. Patients in six phase II studies had standard entry criteria for advanced non-small cell lung cancer. Whereas gemcitabine was given on days 1, 8, and 15 of a 28-day cycle in all these studies, the scheduling of cisplatin varied and was given either on day 1, day 2, day 15 (in two studies), or days 1, 8, and 15 (in two studies). The protocol dose per infusion for gemcitabine was 1,000 mg/m2 (five studies) and 1,500 mg/m2 (one study); for cisplatin, it was 100 mg/m2 when given once per cycle and 30 mg/m2 when given on days 1, 8, and 15. Similar dose reduction schedules were implemented in the event of grade 3 or higher drug toxicity for all studies except for the day 1 cisplatin study, in which the dose was omitted for grade 2 thrombocytopenia. Nonhematologic toxicity was very low. Hematologic toxicity was moderate, and in patients who developed grade 3 or 4 toxicity, there was no hemorrhage from thrombocytopenia and neutropenic sepsis was rare. The incidence of grade 3 or 4 thrombocytopenia with the day 1, day 2, day 15 (two studies combined), and days 1, 8, and 15 (two studies combined) cisplatin regimens was 50%, 52%, 26%, and 38%. The incidence of grade 3 or 4 neutropenia with these four regimens was 51%, 37%, 56%, and 49%, respectively. Although the hematologic toxicity might appear relatively similar, it represents the toxicity at the administered rather than the intended (protocol) dose, because drug delivery was reduced or omitted in the event of grade 3 or 4 toxicity. Differences between the schedules are revealed by analysis of the actual dosages delivered. The median dosage of gemcitabine per scheduled infusion was statistically higher with the day 15 cisplatin regimens (combined) compared with any of the other regimens treating at 1,000 mg/m2 (P < .003, z-score). The dose with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 664, 829, 889, and 774 mg/m2, respectively. Both the percentages of cycles in which gemcitabine infusions were given at full dose and in which there were no omissions of gemcitabine infusions (including infusions with dose reductions) were statistically higher in the day 15 cisplatin regimen than with any of the other regimens (P < .0001, chi-square test). The percentage of cycles containing full-dose gemcitabine with the day 1, day 2, day 15, and days 1, 8, and 15 cisplatin regimens was 24%, 44%, 75%, and 46%, respectively. The percentage of cycles in which there were no omissions of gemcitabine infusions for the four regimens above was 32%, 55%, 83%, and 72%, respectively. Apart from the once-weekly regimen (days 1, 8, and 15) in which the protocol gemcitabine dose was 1,250 mg/m2, the day 15 cisplatin schedule allowed for the highest median concentration of gemcitabine. More importantly, the day 15 cisplatin schedule provided the longest duration of gemcitabine exposure, which is particularly important for its activity as gemcitabine is a phase-specific agent. The day 15 cisplatin schedule is associated with the best dose intensity and the longest median duration of exposure to gemcitabine, and best meets the goal of administering both agents at full doses in combination.