Recent advances: oncology.
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Biomedical subjects
Publications and source records attributed to M H Tattersall.
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AIM: We aimed to document the prevalence of misunderstanding in cancer patients and investigate whether patient denial is related to misunderstanding. PATIENTS AND METHODS: Two hundred forty-four adult cancer outpatients receiving treatment completed a survey assessing levels of understanding and denial. Doctors provided the facts against which patient responses were compared. Multiple logistic regression analyses determined the predictors of misunderstanding. RESULTS: Most patients understood the extent of their disease (71%, 95% CI: 65%-77%) and goal of treatment (60%, 95% CI: 54%-67%). Few correctly estimated the likelihood of treatment achieving cure (18%, 95% CI: 13%-23%), prolongation of life (13%, 95% CI: 8%-17%) and palliation (18%, 95% CI: 10%-27%). Patient denial predicted misunderstanding of the probability that treatment would cure disease when controlling for other patient and disease variables (OR = 2.20, 95% CI: 0.99-4.88, P = 0.05). Patient ratings of the clarity of information received were also predictive of patient understanding. CONCLUSIONS: Patient denial appears to produce misunderstanding, however, doctors' ability to communicate effectively is also implicated. The challenge that oncologists face is how to communicate information in a manner which is both responsive to patients' emotional status and sufficiently informative to allow informed decision-making to take place.
A range of measures have been proposed to enhance the provision of information to cancer patients and randomized controlled trials have demonstrated their impact on patient satisfaction and recall. The current study explored the practice and views of oncologists, surgeons and general practitioners (GPs) with regards to providing patients with consultation audiotapes and summary letters. In stage 1, 28 semi-structured interviews with doctors were conducted to provide qualitative data on which to base a questionnaire. In stage 2, 113 medical oncologists, 43 radiation oncologists, 55 surgeons and 108 GPs completed questionnaires. Only one-third of doctors had ever provided patients with a copy of the letter written to the oncologist or referring doctor, and one-quarter had provided a summary letter or tape. The majority of doctors were opposed to such measures; however, a substantial minority were in favour of providing a letter or tape under certain conditions. More surgeons and GPs (> two-thirds) were opposed to specialists providing a consultation audiotape than oncologists (one-third). Gender, years of experience and attitude to patient involvement in decision-making were predictive of doctors' attitudes. The majority of doctors remain opposed to offering patients personalized information aids. However, practice and perspectives appear to be changing.
Active participation in the medical consultation has been demonstrated to benefit aspects of patients' subsequent psychological well-being. We investigated two interventions promoting patient question-asking behaviour. The first was a question prompt sheet provided before the consultation, which was endorsed and worked through by the clinician. The second was a face to face coaching session exploring the benefits of, and barriers to, question-asking, followed by coaching in question-asking behaviour employing rehearsal techniques. Sixty patients with heterogeneous cancers, seeing two medical oncologists for the first time, were randomly assigned to one of three groups: two intervention groups and one control group. Sociodemographic variables and anxiety were assessed prior to the intervention which preceded the consultation. The consultations were audiotaped and subsequently analysed for question-asking behaviour. Anxiety was assessed again immediately following the consultation. Questionnaires to assess patient satisfaction, anxiety and psychological adjustment were sent by mail 2 weeks following the consultation. Presentation and discussion of the prompt sheet significantly increased the total number of questions asked and the number of questions asked regarding tests and treatment. Coaching did not add significantly to the effects of the prompt sheet. Psychological outcomes were not different among the groups. We conclude that a question prompt sheet addressed by the doctor is a simple, inexpensive and effective means of promoting patient question asking in the cancer consultation.
Referral and reply letters are common means by which doctors exchange information pertinent to patient care. Twenty-eight semi-structured interviews were conducted exploring the views of oncologists, referring surgeons and general practitioners. Twenty-seven categories of information in referral letters and 32 in reply letters after a consultation were defined. The letters to and from six medical oncologists relating to 20 consecutive new patients were copied, and their content analysed. Oncologists, surgeons and general practitioners Australia wide were surveyed using questionnaires developed on data obtained above. Only four of 27 categories of referral information appear regularly (in > 50%) in referral letters. Oncologists want most to receive information regarding the patient's medical status, the involvement of other doctors, and any special considerations. Referring surgeons and family doctors identified delay in receiving the consultant's reply letter as of greatest concern, and insufficient detail as relatively common problems. Reply letters include more information regarding patient history/background than the recipients would like. Referring surgeons and family doctors want information regarding the proposed treatment, expected outcomes, and any psychosocial concerns, yet these items are often omitted. Consultants and referring doctors need to review, and modify their letter writing practices.
BACKGROUND: Doctors' discomfort with the randomized trial process may significantly impact on accrual rates to clinical trials. However, there is little information regarding factors that influence accrual to clinical trials in Australia. The present study examines Australian cancer specialists' attitudes towards and participation in current breast cancer clinical trials. METHODS: All medical and radiation oncologists across Australia and surgeons listed as participants in the Australian and New Zealand Breast Cancer Trials Group were sent questionnaires assessing attitudes towards and participation in current clinical trials for early stage breast cancer. RESULTS: The response rate was 71% (269/381). The mean age of respondents was 45 years and 85% were male. Respondents estimated that a mean of 5.2 (SD = 8.2) of their patients had been enrolled in a breast cancer clinical trial in the previous 12 months. Participation (in any trial) by medical oncologists (60.6%, 95% CI 54.5-66.7%) and surgeons (63.1%, 95% CI 57.1-69.1%) was significantly higher than for radiation oncologists (43.2%, 95% CI 37-49.4%, P = 0.03). The major barriers to participation in current breast cancer trials were lack of resources (44%) or issues related to specific trials (44%; e.g. relevance of the research questions or choice of standard therapies). CONCLUSIONS: The results of this study suggest that efforts to improve doctors' participation in clinical trials need to address a number of issues. More empirical research is needed to evaluate new strategies to raise participation in clinical trials.
A cross-sectional survey of all medical and radiation oncologists in Australia was undertaken, plus surgeons listed as participants of the ANZ Breast Cancer Trials Group, to examine whether doctors' participation in randomized trials of adjuvant systemic therapy for breast cancer, is associated with their recommendations for adjuvant therapy in two clinical scenarios. Two-hundred and sixty-nine questionnaires were returned (response rate 71%). Fifty-six per cent of respondents, were participating in current adjuvant systemic therapy trials. Radiation oncologists were significantly more likely than surgeons or medical oncologists to recommend radiotherapy, while medical oncologists and surgeons were significantly more likely than radiation oncologists to recommend chemotherapy, in both clinical scenarios. In a multivariate analysis adjusting for the differences between specialist groups, respondents recommending chemotherapy were more likely to be high accruers to clinical trials (OR 3.6, 95% CI 0.93 to 13.9, P=0.08) in scenario 1, or participants of a breast cancer trials organization (OR 3.1, 95% CI 1.6 to 5.9, P=0.001) in scenario 2. Some of the variation in adjuvant systemic therapy recommendations is associated with participation in adjuvant systemic therapy trials. However, this study is unable to determine if trial participation influences opinions about adjuvant therapy, or opinions influence trial participation.
PURPOSE: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. RESULTS: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). CONCLUSION: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.
The majority of doctors in North America, Australia and much of Europe now inform patients about a cancer diagnosis. However, many doctors report that they have difficulty disclosing a cancer diagnosis. Poor doctor-patient communication skills may lead to psychological distress including increased anxiety and depression and poorer psychological adjustment to cancer. Presenting 'bad' news in an unhurried, honest, balanced and empathic fashion has been shown to produce greater satisfaction with communication of the news. Consensus guidelines have been developed to assist doctors to disclose a cancer diagnosis. Important aspects include exploring the patient's expectations, warning him/her that the news is bad, giving the news at the patient's own pace, allowing time for the patient to react and eliciting the patient's concerns. Doctor-patient communication can be improved by including training courses in communication skills for medical students and clinicians and providing audiotapes of bad news consultations to enhance patient recall of information and increase patient satisfaction with communication. Additional research is needed to investigate effects of strategies to implement guidelines for delivering a cancer diagnosis.
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This study describes sequence variation in both the enhancer and promoter segments of the upstream regulatory region (URR) of 28 human papillomavirus (HPV) type 18 isolates from cervical cancers, 25 from women treated at an Australian center and three from overseas included for comparison. No large-scale changes were found in either region. Fourteen substitutions were identified in the enhancer region with the number in individual isolates ranging from one to eight. Four substitutions impacted cellular transcription factor binding sites but there were no obvious associations with clinicopathological variables. The promoter segment was found to be more highly conserved than the enhancer, but four of the five point mutations identified involved cellular transcription factor binding motifs including a substitution of C for T at nt 104 which affected 21 samples. This change was found to impact upon a previously unrecognized Yin Yang (YY1) binding site. Electrophoretic mobility shift assays (EMSA) showed that this substitution significantly reduced protein-DNA binding and evidence was sought for its possible clinical implications. Of the 24 women with less than Stage III disease and known clinical outcome, tumor recurrence was observed in all of the 6 women whose isolates had the "prototype" T at nt 104, whereas only 8 of the 18 cancers with the mutation at this YY1 site recurred. This is the first report on URR variation in HPV 18 isolates from the South Pacific region. The study also provides initial data on diversity in the promoter region and preliminary evidence suggesting that a specific point mutation in this region may be clinically significant.
Advances in information technology, and changing patient expectation in regard to provision of information and participation in clinical decisions are already influencing the cancer consultation. In future, the oncologist's role will evolve further, and the cancer consultation beyond the year 2000 will be an opportunity for information relating to the particular patient's circumstances to be presented according to the patient's wishes. Patients' desired input into clinical decisions will be respected, and consultation audiotapes will be a widely used aid for patients after the consultation.
OBJECTIVES: To review the outcome of men with Stage I nonseminomatous germ cell tumors managed with a policy of active surveillance following orchiectomy. METHODS: The clinical records of all men with Stage I nonseminomatous germ cell tumors seen at Royal Prince Alfred Hospital, Australia between 1982 and 1995 were reviewed. Data were obtained concerning the histologic type of tumor, levels of serum tumor markers, relapse and subsequent treatment, and survival. RESULTS: Seventy-seven patients were entered into the active surveillance protocol between 1982 and 1995. With a minimum follow-up of 2 years, 27 (35%) have relapsed, with a median time to relapse of 5 months. Two late relapses occurred at 37 and 57 months after diagnosis. Relapses occurred most commonly in the retroperitoneal lymph nodes, with the lungs the second most common site. Following treatment with chemotherapy and surgery, all patients achieved complete remission, with 1 patient subsequently relapsing and ultimately dying of progressive tumor. One other patient died of acute myeloid leukemia, thought to be secondary to chemotherapy. Overall, 75 patients (97%) remain alive and free of disease. CONCLUSIONS: Active surveillance is a safe and effective approach to the management of Stage I nonseminomatous germ cell tumors. Although most relapses occur within the first 2 years, late relapses may occur.
BACKGROUND: While the importance of providing individualised communication to cancer patients is now well recognised, little is known about the stability and validity of patients' expressed preferences for information and involvement in decision-making. This study explored the stability and possible predictors of such preferences over time. PATIENTS AND METHODS: Cancer patients seeing two Medical Oncologists in an out-patient clinic at an Australian teaching hospital completed a questionnaire battery before and directly after one consultation, and before their next consultation. Eighty consecutive patients with heterogeneous cancers participated in the study. Preferences for general and specific information, involvement and support were elicited at each assessment. Locus of control and patient familiarity with the clinic were measured before the first consultation. Patient satisfaction with the consultation was assessed directly after the consultation. Demographic and disease data were recorded for each patient. RESULTS: General preferences for information and involvement were relatively stable, at least in the short term; however there was considerable variability in preferences for specific topics of information. Patients whose condition had recently worsened were more likely to want progressively less involvement in decision-making. Gender, the doctor seen and religion were also predictive of patient preferences. CONCLUSIONS: Situational factors, such as change in disease status, may alter a patient's preferences for information and involvement. If we wish to match the provision of information and support to the expressed needs of patients, we must ask patients at each consultation what those needs are.
BACKGROUND: The outcome of management in patients with osteosarcoma and pulmonary metastases at a Sydney teaching hospital was reviewed. METHODS: A retrospective review was undertaken of all patients diagnosed with osteosarcoma and treated by the Bone and Soft Tissue Unit and the Medical Oncology Department, Royal Prince Alfred Hospital between 1979 and January 1995. Information was collected on demographics, tumour site, tumour histology, primary management including surgery and adjuvant therapy, and the subsequent development and management of pulmonary metastases. RESULTS: A total of 56 patients with localized osteosarcoma was seen. Overall survival and survival following pulmonary metastases was assessed. There were 33 (59%) males and 23 (41%) females, with a median age of 27 years. Survival at 5 years, for patients with non-axial osteosarcoma was 60% (95% CI, 44-77%). Pulmonary metastases without other metastatic disease being apparent, developed in 22 patients, of whom 12 underwent surgical resection. The median disease-free interval of these latter patients was 20 months (95% CI, 8-32 months). Median survival among patients not undergoing surgical resection was 5 months from detection of metastases. Patients undergoing resection of pulmonary metastases had a median survival of 17 months following detection of pulmonary metastases (95% CI, 7-27 months). Actuarial 5-year survival was 16% (95% CI, 0-42%). CONCLUSIONS: A small proportion of patients with resectable pulmonary metastases from osteosarcoma achieve long-term disease-free survival following surgical resection. It is not possible to accurately identify these patients prospectively.
PURPOSE: To determine whether a strategy of adding medroxyprogesterone acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for TAM among women with advanced breast cancer and disease progressing on TAM. To assess the patterns or response and subsequent progression in sites and tissues according to prior involvement and treatment. PATIENTS AND METHODS: Two-hundred-fifteen postmenopausal women with advanced breast cancer progressing on TAM after receiving TAM for at least six months were randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop TAM and to substitute MPA. RESULTS: There were no significant differences between the groups with respect to complete plus partial response rates: TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA 4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4 months. In a multivariate model, prognostic factors significant for a shorter time to disease progression were worse for performance status, involvement of more than one tissue, prior radiotherapy, and shorter time from recurrence after primary therapy to randomization. Adjusting for these factors, treatment with TAM + MPA was associated with a higher relative risk for disease progression, with a hazards ratio of 1.31, but this was not significant (95% confidence interval, 0.98 to 1.74; P = .067). However, in an exploratory analysis, the time to disease progression, among patients with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95% confidence interval, 1.12 to 3.32; P = .02). There was a significant interaction, P = .04, between PR status and treatment, indicating an advantage to treatment substitution for those who have PR+ tumors. Tumor response occurred in 14% of assessed metastatic sites. Subsequent progression occurred in a new tissue alone in 13% of patients, in both new and previously involved (old) tissues in 76%, and in old tissues only in 11%. In 23% of patients, progression occurred only at a new site, in 50% at both old and new sites, and in 27% only at old sites. No significant differences in the patterns of response or progression were seen in the different treatment groups. CONCLUSION: Among women with breast cancer whose disease is progressing after at least six months of treatment with TAM, there is no advantage to maintaining TAM when MPA is to be given. An overall effect of treatment on the pattern of failure at old sites or at new sites or tissues cannot be discerned.
When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line therapy for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14, intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for six cycles (6 months). Patients whose disease progressed or relapsed were recommended to receive second-line epirubicin. Accrual has been completed with 208 patients randomized, but a preplanned interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by a linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months for paclitaxel-treated patients and 6.4 months for those given CMFP, with median survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4 neutropenia occurred in 64% of patients treated with paclitaxel and in 63% treated with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses. Nine percent of the patients had major infections with CMFP, but none were seen with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel-treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results on paclitaxel treatment as compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides comparable control of metastatic cancer to CMFP combination therapy when used as front-line treatment.