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Biomedical subjects

M R Stockler

Publications and source records attributed to M R Stockler.

15 recordsLinked to original sources

Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer.

People affected by cancer want information about their prognosis but clinicians have trouble estimating and talking about it. We sought to determine the nature and accuracy of medical oncologists' estimates of life expectancy in newly referred patients with incurable cancer. With reference to each patient, medical oncologists estimated how long they thought 90, 50, and 10% of similar patients would live. These proportions were chosen to reflect worst case, predicted, and best case scenarios suitable for discussions. After a median follow-up of 35 months, 86 of the 102 patients had died with an observed median survival of 12 months. Oncologists' estimates of each patient's worst case, predicted and best case scenarios were well-calibrated: 10% of patients lived for fewer months than estimated for the worst 10% of similar patients; 50% lived for at least as long as estimated for 50% of similar patients (predicted survival), and 17% lived for more months than estimated for the best 10% of similar patients. Oncologists' estimates of each patient's predicted survival were imprecise: 29% were within 0.67-1.33 times the patient's actual survival, 35% were too optimistic (>1.33 times the actual survival), and 39% were too pessimistic (<0.67 times the actual survival). The proportions of patients with actual survival times bounded by simple multiples of their predicted survival were as follows: 61% between half to double their predicted, 6% at least three to four times their predicted, and 4% no more than 1/6 of their predicted; similar to the proportions in an exponential distribution (about 50%, 10% and 10% respectively). Ranges based on simple multiples of the predicted survival time appropriately convey prognosis and its uncertainty in newly referred people with incurable cancer.

Adolescent↗

Patients' preferences for adjuvant endocrine therapy in early breast cancer: what makes it worthwhile?

Adjuvant endocrine therapy improves recurrence and survival rates, but has side effects and is inconvenient. The aim of this study was to determine the preferences of premenopausal women who had adjuvant endocrine therapy in a randomised trial. In all, 85 (or eighty-five) women completed semistructured interviews 6-30 months after finishing adjuvant endocrine therapy. Hypothetical scenarios based on known potential survival times (5 or 15 years) and rates (60% or 80% at 5 years) without adjuvant endocrine therapy were used to determine the smallest gains women judged necessary to make their adjuvant endocrine therapy worthwhile. Although a third of the women considered gains of 1% in survival rates or 6 months in survival times sufficient to make their adjuvant endocrine therapy worthwhile, more than half the women required gains of at least 5% in survival rates or 3 years in survival time as necessary to make adjuvant endocrine therapy worthwhile. Larger benefits were required by women who had longer treatment, worse side effects, and by those who were treated with goserelin alone. The route of administration (tablet vs injection) did not affect preferences and some women judged small benefits sufficient to make their adjuvant endocrine therapy worthwhile, but many women required larger benefits than their counterparts in similar studies of preferences for adjuvant chemotherapy.

Adult↗

Patients' preferences for adjuvant chemotherapy in early breast cancer: what makes AC and CMF worthwhile now?

BACKGROUND: Studies of women who had adjuvant chemotherapy for early breast cancer 10-20 years ago showed that many judged small benefits sufficient to make it worthwhile. Indications, regimens and supportive care have changed. We sought the preferences of contemporary women who received similar chemotherapy. PATIENTS AND METHODS: Ninety-seven consecutive consenting women who completed adjuvant chemotherapy for early breast cancer 3-34 months previously were interviewed. Preferences were elicited with a structured, scripted interview using the trade-off method. Women were presented with four hypothetical scenarios based on known life expectancies (5 and 15 years) and survival rates (65% and 85% at 5 years) without adjuvant chemotherapy. RESULTS: Improvements of an additional year in life expectancy or 3% in survival rates were judged sufficient to make adjuvant chemotherapy worthwhile by 68-84% of women. Half the women judged 1 day or 0.1% sufficient to make adjuvant chemotherapy worthwhile. Recollections of better well-being during adjuvant chemotherapy, having dependants and having a friend or relative who died from cancer were independently associated with judging smaller benefits sufficient to make adjuvant chemotherapy worthwhile (all P < 0.05). CONCLUSIONS: Preferences were highly variable, but the benefits judged sufficient to make adjuvant chemotherapy worthwhile were even smaller than those found in previous studies. Preferences were influenced by factors other than direct benefits and harms of chemotherapy.

Adult↗

Beauty is in the eye of the examiner: reaching agreement about physical signs and their value.

Despite advances in other areas, evidence-based medicine is yet to make substantial inroads on the standard medical physical examination. We have reviewed the evidence about the accuracy and reliability of the physical examination and common clinical signs. The physical examination includes many signs of marginal accuracy and reproducibility. These may not be appreciated by clinicians and could adversely affect decisions about treatment and investigations or the teaching and examination of students and doctors-in-training. We provide a selected summary of the reliability and accuracy as well as important messages of key findings in the physical examination.

Clinical Competence↗

Weekly docetaxel as second line treatment after mitozantrone for androgen-independent prostate cancer.

BACKGROUND: Two recent phase III trials have shown an improvement in survival with the use of docetaxel in metastatic androgen-independent prostate cancer (AIPC) compared to mitozantrone. However no phase II trials have clearly defined the level of activity of docetaxel after mitozantrone. AIMS: We sought to define the activity and toxicity of weekly docetaxel as second line chemotherapy after mitozantrone in men with AIPC. METHODS: Twenty men were treated with docetaxel 40 mg/m2 weekly for 3 of every 4 weeks until progression or prohibitive toxicity. End-points included prostate specific antigen response, common toxicity criteria, time to progression and overall survival. RESULTS: Nine patients (45%) had a 50% or greater reduction in PSA maintained for at least 1 month. Weekly docetaxel was well tolerated with few major toxicities: two patients had Grade 3 diarrhoea (10%) and six had grade 2-4 haematologic toxicities (30%). The median time to progression was 5 months (range 0-13) and median survival was 13 months (range 1-24) from starting docetaxel. The median survival from starting mitozantrone was 19 months. Men who had responded to mitozantrone were no more likely to respond to docetaxel (P = 0.2 Fischer's exact test). CONCLUSIONS: Weekly docetaxel is a safe and active second-line treatment after mitozantrone for androgen-resistant prostate cancer, with similar levels of activity to the first-line setting.

Adenocarcinoma↗

Systematic review of taxane-containing versus non-taxane-containing regimens for adjuvant and neoadjuvant treatment of early breast cancer.

The use of taxanes in early breast cancer is increasing. However, there are few mature studies of taxanes in this setting, and their role is uncertain. Our systematic review of randomised trials of adjuvant or neoadjuvant systemic therapy identified ten reported trials comparing a taxane-containing group with a non-taxane-containing control group in women with early breast cancer. Four of five neoadjuvant trials showed higher rates of complete response with taxanes, although differences were not significant. All five adjuvant trials showed improvements in disease-free survival with taxanes, and these improvements were significant in three trials and independent of oestrogen-receptor status. Two trials showed a significant improvement in overall survival. These results support the use of adjuvant taxanes in women with early breast cancer and involved lymph nodes. Longer follow-up of these trials and results from continuing trials are needed to clarify the best use of taxanes in early breast cancer.

Adult↗

Outcomes research: what is it and why does it matter?

Outcomes research is a broad umbrella term without a consistent definition. However it tends to describe research that is concerned with the effectiveness of public-health interventions and health services; that is, the outcomes of these services. Attention is frequently focused on the affected individual - with measures such as quality of life and preferences - but outcomes research may also refer to effectiveness of health-care delivery, with measures such as cost-effectiveness, health status and disease burden. The present review details the historical background of outcomes research to reveal the origins of its diversity. The value and relevance of outcomes research, commonly employed research techniques and examples of recent publications in the area are also discussed.

Australia↗

Hospitalised patients' views on doctors and white coats.

OBJECTIVES: To determine hospitalised patients' feelings, perceptions and attitudes towards doctors and how these are affected by whether or not doctors wear a white coat. DESIGN: Cross-sectional questionnaire survey. SETTING: The medical and surgical wards of two Sydney teaching hospitals, on one day in January 1999. PATIENTS: 154 of 200 consecutive patients (77%). MAIN OUTCOME MEASURES: The effects of white-coat-wearing on patients' feelings and ability to communicate and on their perceptions of the doctor; why patients think doctors wear white coats and their preferences for the wearing of white coats and doctors' attire in general; and patients' rating of the importance of these effects and preferences. RESULTS: Patients reported that white-coat-wearing improved all aspects of the patient-doctor interaction, and that when doctors wore white coats they seemed more hygienic, professional, authoritative and scientific. The more important that patients considered an aspect, the greater the positive effect associated with wearing a white coat. From a list of doctors' reasons for wearing white coats, patients thought that doctors wore white coats because it made them seem more professional, hygienic, authoritative, scientific, competent, knowledgeable and approachable. 36% of the patients preferred doctors to wear white coats, 19% preferred them not to wear white coats and 45% did not mind. CONCLUSIONS: Patients reported feeling more confident and better able to communicate with doctors who wore white coats. The recognition, symbolism and formality afforded by a white coat may enhance communication and facilitate the doctor-patient relationship.

Adult↗

Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Australian and New Zealand Germ Cell Trial Group.

BACKGROUND: Most patients with metastatic germ-cell tumours are cured with chemotherapy. However, the optimum chemotherapy regimen is uncertain, and there is variation in international practice. We did a multicentre randomised trial to compare two standard chemotherapy regimens for men with good-prognosis germ-cell tumours. METHODS: Good prognosis was defined by modified Memorial Sloan-Kettering criteria. The first regimen (regimen A) was based on treatment recommendations from Indiana University and comprised three cycles of 20 mg/m2 cisplatin on days 1-5, 100 mg/m2 etoposide on days 1-5, and 30 kU bleomycin on days 1, 8, and 15, repeated every 21 days. The second regimen (regimen B) was based on the control regimen of a published randomised clinical trial and comprised four cycles of 100 mg/m2 cisplatin on day 1, 120 mg/m2 etoposide on days 1-3, and 30 kU bleomycin on day 1, repeated every 21 days. The primary outcome measure was overall survival. Analysis was by intention to treat. FINDINGS: 166 patients were randomised, 83 to each regimen. The trial was stopped when the second planned interim analysis met predefined stopping rules. The median follow-up was 33 months. Overall survival was substantially better with regimen A (three vs 13 deaths, hazard ratio 0.22 [95% CI 0.06-0.77], p=0.008). This difference was due to deaths from cancer (one vs nine), and not deaths from treatment (two vs two) and remained significant after adjustment for other prognostic factors (0.25 [0.07-0.88], p=0.03). INTERPRETATION: In men with good-prognosis germ-cell tumours, the regimen developed at Indiana University is superior to the alternative regimen studied in this trial. The lower total dose and dose-intensity of bleomycin and the lower dose-intensity of etoposide in regimen B could be responsible for the worse outcome.

Adolescent↗

Evidence-based medicine: useful tools for decision making.

Evidence-based medicine (EBM) integrates clinical experience and patient values with the best available research information. There are four steps in incorporating the best available research evidence in decision making: asking answerable questions; accessing the best information; appraising the information for validity and relevance; and applying the information to patient care. Applying EBM to individual patients requires drawing up a balance sheet of benefits and harms based on research and individual patient data. The most realistic and efficient use of EBM by clinicians at the point of care involves accessing and applying valid and relevant summaries of research evidence (evidence-based guidelines and systematic reviews). The future holds promise for improved primary research, better EBM summaries, greater access to these summaries, and better implementation systems for evidence-based practice. Computer-assisted decision support tools for clinicians facilitate integration of individual patient data with the best available research data.

Australia↗

Convergent discriminitive, and predictive validity of the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) assessment and comparison with analogous scales from the EORTC QLQ-C30 and a trial-specific module. European Organisation for Research and Treatment of Cancer. Core Quality of Life Questionnaire.

The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) is a measure of health-related quality of life (HRQL) that was designed to be an outcome measure for clinical trials in advanced hormone-resistant prostate cancer. The cross-sectional validity of the PROSQOLI was assessed using baseline data from a randomized trial in which HRQL was also assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and a trial-specific quality of life module (QLM-P14). Convergent validity was assessed with the multitrait-multimethod matrix approach; discriminative validity was assessed according to conventional clinical criteria; and predictive validity was assessed by the ability to predict survival duration. These assessments provided strong support for the validity of all PROSQOLI scales except those for family/marriage relationships and passing urine; modifications of these two scales are under evaluation. The strength, consistency, and independence of the prognostic information provided by the HRQL scales were striking. Differences between the instruments were generally subtle. These data support validity of the PROSQOLI and the analogous scales from the QLQ-C30 and QLM-P14 in symptomatic men with advanced hormone resistant prostate cancer. The PROSQOLI is a short, simple, and valid measure of HRQL in this setting.

Analysis of Variance↗

Responsiveness to change in health-related quality of life in a randomized clinical trial: a comparison of the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) with analogous scales from the EORTC QLQ-C30 and a trial specific module. European Organization for Research and Treatment of Cancer.

INTRODUCTION: The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) was developed to be a pragmatic outcome measure for clinical trials in symptomatic men with advanced hormone-resistant prostate cancer. DESIGN AND SETTING: A comparative assessment of responsiveness was made with longitudinal data from a positive multicenter randomized trial of palliative chemotherapy in 161 symptomatic men with advanced hormone-resistant prostate cancer. INSTRUMENTS: The PROSQOLI, the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30), and a specific quality of life module for advanced prostate cancer [QLM-P14] were administered every 3 weeks while patients received their allocated treatment. FINDINGS: Sixteen of the 19 health-related quality of life (HRQL) scales demonstrated improvements in palliative responders. All three pain scales detected a beneficial effect of palliative chemotherapy. The relative efficiency statistics favored the PROSQOLI for physical symptoms and physical function but the QLQ-C30 for emotional function, social function, and global perceptions. The PROSQOLI linear analog scale was the most responsive measure of pain. Bootstrap confidence intervals for the relative efficiency statistics were wide. CONCLUSIONS: Both the PROSQOLI and the analogous scales from the QLQ-C30 were responsive to improvements in HRQL. Differences between the instruments were generally subtle. The PROSQOLI is a short, simple, responsive measure of HRQL in men receiving systemic treatment for advanced hormone-resistant prostate cancer.

Aged↗

Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.

PURPOSE: To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. PATIENTS AND METHODS: We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. RESULTS: Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. CONCLUSION: Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Adenocarcinoma↗