Martin H. N. Tattersall

A meta-analysis of thoracic radiotherapy for small-cell lung cancer.

BACKGROUND In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. METHODS We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. RESULTS The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined-therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (+/- SD) was 5.4 +/- 1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients: the relative risk of death in the combined-therapy as compared with the chemotherapy group ranged from 0.72 for patients less than 55 years old (95 percent confidence interval, 0.56 to 0.93) to 1.07 (0.70 to 1.64) for patients over 70. CONCLUSIONS Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials.

Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies

Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer.

Sharing decisions in cancer care.

Previous studies have demonstrated that the majority of cancer patients fail to achieve their desired level of participation during treatment decision making. However, it is unclear whether this failure affects patient well-being and satisfaction. Furthermore, whilst shared decision making is currently espoused as the preferred model for doctor patient relations, little empirical evidence exists showing it has beneficial effects for patients. We aimed to evaluate the impact of shared decision making and the achievement of preferred role on patient anxiety, recall of information, and satisfaction. Patients with cancer indicated their preferred level of participation in decision making and preferences for information and emotional support prior to their initial consultation with an oncologist. Anxiety was assessed prior to and immediately after the consultation and recall seven days after the consultation. Anxiety was reassessed at two-weeks post-consultation at which time patients also reported their satisfaction with the consultation and perceived role of participation in treatment decision making. Satisfaction with the information and emotional support received was also evaluated. Of the 233 patients available for analysis, a match between preferred and perceived roles was found for over one-third of patients (34%), with 29% more active and 37% less involved in decision making than preferred. Multivariate analyses demonstrated that role mismatch significantly predicted changes in anxiety levels from pre to immediate postconsultation (p = 0.03). However, irrespective of preferred role in decision making, perceived role, but not role mismatch, significantly and independently predicted satisfaction with both the consultation (p = 0.0005) and the amount of information and emotional support received from the doctor (p = 0.004). Patients who reported a shared role in decision making were most satisfied with the consultation and with the information about treatment and emotional support received. Those who reported that either themselves or the doctor exclusively made the decision were least satisfied. These findings underscore the pre-eminence of the shared decision making model and suggest that encouraging participation may be the safest standard approach. Doctor - as well as patient - based interventions are required to promote patient participation.

Communicating With Realism and Hope: Incurable Cancer Patients' Views on the Disclosure of Prognosis

PURPOSE To identify preferences for the process of prognostic discussion among patients with incurable metastatic cancer and variables associated with those preferences. PATIENTS AND METHODS One hundred twenty-six (58%) of 218 patients invited onto the study participated. Eligible patients were the consecutive metastatic cancer patients of 30 oncologists, who were diagnosed within 6 weeks to 6 months before recruitment, over 18 years of age, and without known mental illness. Patients completed a postal survey measuring patient preferences for the manner of delivery of prognostic information, including how doctors might instill hope. RESULTS Ninety-eight percent of patients wanted their doctor to be realistic, provide an opportunity to ask questions, and acknowledge them as an individual when discussing prognosis. Doctor behaviors rated the most hope giving included offering the most up to date treatment (90%), appearing to know all there is to know about the patients cancer (87%), and saying that pain will be controlled (87%). The majority of patients indicated that the doctor appearing to be nervous or uncomfortable (91%), giving the prognosis to the family first (87%), or using euphemisms (82%) would not facilitate hope. Factor analysis revealed six general styles and three hope factors; the most strongly endorsed styles were realism and individualized care and the expert/positive/collaborative approach. A range of demographic, psychological, and disease factors were associated with preferred general and hope-giving styles, including anxiety, information-seeking behavior, expected survival, and age. CONCLUSION The majority of patients preferred a realistic and individualized approach from the cancer specialist and detailed information when discussing prognosis.

Cancer Patient Preferences for Communication of Prognosis in the Metastatic Setting

PURPOSE To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P =.047) and average survival (P =.049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P =.03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P =.02). CONCLUSION Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.

Promoting patient participation and shortening cancer consultations: a randomised trial.

Patient participation in medical consultations has been demonstrated to benefit their subsequent psychological well being. Question asking is one way in which patients can be active. We investigated 2 means of promoting cancer patient question asking. One was the provision of a question prompt sheet to patients prior to their initial consultation with their oncologist. The second was the active endorsement and systematic review of the question prompt sheet by their oncologist. 318 patients with heterogeneous cancers, seeing one of 5 medical and 4 radiation oncologists for the first time, were randomised to either receive or not receive a question prompt sheet. Doctors were randomised to either proactively address or passively respond to the question prompt sheet in the subsequent consultation. Anxiety was assessed prior to the consultation. Consultations were audiotaped and content analysed. Anxiety was assessed again immediately following the consultation. Within the next 10 days patients completed questionnaires assessing information needs, anxiety and satisfaction and were given a structured telephone interview assessing information recall. Patients provided with a question prompt sheet asked more questions about prognosis compared with controls and oncologists gave significantly more prognostic information to these patients. Provision of the question prompt sheet prolonged consultations and increased patient anxiety; however, when oncologists specifically addressed the prompt sheet, anxiety levels were significantly reduced, consultation duration was decreased and recall was significantly improved. A patient question prompt sheet, used proactively by the doctor, is a powerful addition to the oncology consultation.

Truth-telling in discussing prognosis in advanced life-limiting illnesses: a systematic review

Many health professionals (HPs) express discomfort at having to broach the topic of prognosis, including limited life expectancy, and may withhold information or not disclose prognosis. A systematic review was conducted of 46 studies relating to truth-telling in discussing prognosis with patients with progressive, advanced life-limiting illnesses and their caregivers. Relevant studies meeting the inclusion criteria were identified by searching computerized databases (MEDLINE, EMBASE, CINAHL, PsychINFO and Cochrane Register of Controlled Trials) up to November 2004, with handsearching of studies, as well as inclusion of studies satisfying selection criteria reported in 2005 by the authors. The reference lists of identified studies were hand-searched for further relevant studies. Inclusion criteria were studies of any design evaluating communication of prognostic information that included adult patients with an advanced, life-limiting illness; their caregivers; and qualified HPs. Results showed that although the majority of HPs believed that patients and caregivers should be told the truth about the prognosis, in practice, many either avoid discussing the topic or withhold information. Reasons include perceived lack of training, stress, no time to attend to the patients emotional needs, fear of a negative impact on the patient, uncertainty about prognostication, requests from family members to withhold information and a feeling of inadequacy or hopelessness regarding the unavailability of further curative treatment. Studies suggest that patients can discuss the topic without it having a negative impact on them. Differences and similarities in findings from different cultures are explored. Palliative Medicine 2007; 21: 507—517

Randomized Clinical Trials in Oncology: Understanding and Attitudes Predict Willingness to Participate

PURPOSE To explore the association at different time points in the trajectory of breast cancer care, between anxiety, knowledge, and attitudes, on womens willingness to participate in randomized clinical trials. MATERIALS AND METHODS A cross-sectional survey was undertaken among women attending a breast clinic for screening mammography or diagnostic assessment plus women with newly diagnosed breast cancer to assess attitudes toward and willingness to participate in randomized clinical trials of breast cancer treatment. RESULTS Five hundred forty-five women completed questionnaires assessing knowledge of and attitudes toward randomized clinical trials. The mean age of respondents was 48.9 years (SD, 11.3 years). Thirty-three percent of women would consider participating in a clinical trial if they had breast cancer. Women with breast cancer (31%) were significantly more likely to decline to participate than women attending for screening mammography (15%) or diagnostic assessment (15%, P =.0002). Women who might consider participating in a randomized clinical trial were more knowledgeable about randomized trials (mean difference, 0.7; 95% confidence interval [CI], 0.2 to 1.2; P =.003). In a multivariate analysis, women who would consider participating in a randomized trial were younger (odds ratio [OR], 0.96; 95% CI, 0.93 to 0.99), more likely to want an active role in decision-making (OR, 3.2; 95% CI, 1.3 to 7.6), and reported a greater impact from the positive aspects of clinical trials (OR, 2.2; 95% CI, 1.3 to 3.8) and less impact from the negative aspects of clinical trials (OR, 2.2; 95% CI, 1.3 to 3.2). CONCLUSION These findings suggest that women who have a better understanding of issues about clinical trials have more favorable attitudes toward randomized trials and are more willing to consider participation in a clinical trial.

New Approaches to Cancer Chemotherapy with Methotrexate

THE folic acid antagonists were shown to have antileukemic activity by Farber and his colleagues in 1948.1 Since then the prototypical folic acid antagonist, methotrexate, has been found effective ...

Initial Paclitaxel Improves Outcome Compared With CMFP Combination Chemotherapy as Front-Line Therapy in Untreated Metastatic Breast Cancer

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.