Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the metaanalysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less fromchemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enablepatients and their clinicians to make more informed treatment choices

Impact of a Prior Cancer Diagnosis on Quality of Care and Survival Following Acute Myocardial Infarction: Retrospective Population-Based Cohort Study in England

BACKGROUND: An increasing proportion of patients with cancer experience acute myocardial infarction (AMI). We investigated differences in quality of AMI care and survival between patients with and without previous cancer diagnoses. METHODS: A retrospective cohort study using Virtual Cardio-Oncology Research Initiative data. Patients aged 40+ years hospitalized in England with AMI between January 2010 and March 2018 were assessed, ascertaining previous cancers diagnosed within 15 years. Multivariable regression was used to assess effects of cancer diagnosis, time, stage, and site on international quality indicators and mortality. RESULTS: Of 512388 patients with AMI (mean age, 69.3 years; 33.5% women), 42187 (8.2%) had previous cancers. Patients with cancer had significantly lower use of ACE (angiotensin-converting enzyme) inhibitors/angiotensin receptor blockers (mean percentage point decrease [mppd], 2.6% [95% CI, 1.8–3.4]) and lower overall composite care (mppd, 1.2% [95% CI, 0.9–1.6]). Poorer quality indicator attainment was observed in patients with cancer diagnosed in the last year (mppd, 1.4% [95% CI, 1.8–1.0]), with later stage disease (mppd, 2.5% [95% CI, 3.3–1.4]), and with lung cancer (mppd, 2.2% [95% CI, 3.0–1.3]). Twelve-month all-cause survival was 90.5% in noncancer controls and 86.3% in adjusted counterfactual controls. Differences in post-AMI survival were driven by cancer-related deaths. Modeling improving quality indicator attainment to noncancer patient levels showed modest 12-month survival benefits (lung cancer, 0.6%; other cancers, 0.3%). CONCLUSIONS: Measures of quality of AMI care are poorer in patients with cancer, with lower use of secondary prevention medications. Findings are primarily driven by differences in age and comorbidities between cancer and noncancer populations and attenuated after adjustment. The largest impact was observed in recent cancer diagnoses (<1 year) and lung cancer. Further investigation will determine whether differences reflect appropriate management according to cancer prognosis or whether opportunities to improve AMI outcomes in patients with cancer exist

Prophylactic irradiation of tracts in patients with malignant pleural mesothelioma : an open-label, multicenter, phase III randomized trial

PURPOSE Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM. METHODS After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy. Open thoracotomies, needle biopsies, and indwelling pleural catheters were excluded. Prophylactic radiotherapy was delivered at a dose of 21 Gy in three fractions over three consecutive working days, using a single electron field adapted to maximize coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CWM within 6 months from random assignment, assessed in the intention-to-treat population. Stratification factors included epithelioid histology and intention to give chemotherapy. RESULTS Between July 30, 2012, and December 12, 2015, 375 patients were recruited from 54 centers and randomly assigned to receive prophylactic radiotherapy (n = 186) or no prophylactic radiotherapy (n = 189). Participants were well matched at baseline. No significant difference was seen in the incidence of CWM at 6 months between the prophylactic radiotherapy and no radiotherapy groups (no. [%]: 6 [3.2] v 10 [5.3], respectively; odds ratio, 0.60; 95% CI, 0.17 to 1.86; P = .44). Skin toxicity was the most common radiotherapy-related adverse event in the prophylactic radiotherapy group, with 96 patients (51.6%) receiving grade 1; 19 (10.2%), grade 2; and 1 (0.5%) grade 3 radiation dermatitis (Common Terminology Criteria for Adverse Events, version 4.0). CONCLUSION There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with MPM

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Responses of consecutive patients to reassurance after gastroscopy: results of self administered questionnaire survey

Objective: To study the time course and prediction of responses to reassurance after gastroscopy showing no serious illness. Design: Selection of consecutive patients were assessed before gastroscopy, immediately after reassurance, and at follow up at 24 hours, 1 week, 1 month, and 1 year. Responses of subgroups of patients identified as high, medium, and low health anxiety by the health anxiety questionnaire were analysed. Setting: Endoscopy clinic in a general hospital. Intervention: Oral reassurance that there was "nothing seriously wrong." Subjects: One consultant physician and 60 patients aged 18-74 referred for gastroscopy. Main outcome measures: Physician's and patients' ratings of the extent of the reassurance and patients' ratings of their anxiety about their health and of their illness belief. Results: There was good agreement between the patients and the physician about whether reassurance had been given. Health anxiety and illness belief decreased markedly after reassurance. Patients with high health anxiety showed a significant resurgence in their worry and illness belief at 24 hours and 1 week, and these levels were maintained at 1 month and 1 year later. Patients with medium levels of health anxiety showed a reduction in worry and illness belief after reassurance, and this was generally maintained during follow up. Patients with low health anxiety maintained low levels of health worry and illness belief throughout the study. Partial correlation analyses showed that the levels of worry and illness belief after reassurance were predicted by the health anxiety questionnaire. This measure also had predictive value beyond that of a measure of general anxiety. Conclusions: Medical reassurance results in a reduction of worry about health and of illness belief, but this may be very short term. Measurable individual differences in health anxiety can be used to predict the response to reassurance

Biased perception and recall of reassurance in medical patients

Objectives. We tested the hypothesis that compared with patients with low health anxiety those with high health anxiety would perceive and recall reassurance given by a physician as less reassuring than the physician reported giving. Design. A quasi-experimental repeated measures design; three time periods (immediate, one month and one year pose-consultation) in three groups of patients (total N = 50) defined by a ternary split on a questionnaire. Methods. Patients' health anxiety was measured prior to gastroscopic investigation and consultation with a physician for unexplained symptoms. All the investigations were negative for serious pathology. Immediately after consultation the physician and patients rated the given and perceived reassurance message on a five-point scale describing the probability of there being something seriously wrong. Patients repeated their ratings at one month and one year. Results. Patients in the high-health anxiety group were more likely to recall the reassurance given as less certain that there was nothing seriously wrong with them than were either the low or medium groups immediately pose-consultation. This difference persisted after one month but not one year later. Conclusions. These data provide preliminary support for the hypothesis that high health anxiety may bias the perception and recall of reassurance-related information

Knowledge of lung cancer symptoms and risk factors in the UK: development of a measure and results from a population-based survey

Objectives To develop and validate a Lung Cancer Awareness Measure (Lung CAM) and explore the demographical and social predictors of lung cancer awareness in the general population. Methods study 1 Symptoms and risk factors for lung cancer were identified from the medical literature and health professional expertise in an iterative process. Test–retest reliability, internal reliability, item analyses, construct validity and sensitivity to changes in awareness of the Lung CAM were assessed in three samples (total N=191). Results study 1 The Lung CAM demonstrated good internal (Cronbach's α=0.88) and test–retest reliability (r=0.81, p<0.001). Validity was supported by lung cancer experts scoring higher than equally educated controls (t(106)=8.7, p<0.001), and volunteers randomised to read lung cancer information scoring higher than those reading a control leaflet (t(81)=3.66, p<0.001). Methods study 2 A population-based sample of 1484 adults completed the Lung CAM in a face-to-face, computer-assisted interview. Results study 2 Symptom awareness was low (average recall of one symptom) and there was little awareness of risk factors other than smoking. Familiarity with cancer, and being from a higher socioeconomic group, were associated with greater awareness. Conclusions Using a valid and reliable tool for assessing awareness showed the UK population to have low awareness of lung cancer symptoms and risk factors. Interventions to increase lung cancer awareness are needed to improve early detection behaviour

Domicilary chemotherapy with gemcitabine is safe and acceptable to advanced non-small cell lung cancer patients – results of a feasibility study

A study was conducted to investigate the feasibility and acceptability of administering single-agent gemcitabine to patients with advanced non-small-cell lung cancer (NSCLC) in their own homes. Gemcitabine is an active agent in NSCLC with a good toxicity profile and lends itself to this type of investigation. A total of 24 patients were studied; as only one patient required gemcitabine to be changed from home administration to hospital administration, domiciliary gemcitabine is feasible. A total of 249 injections of gemcitabine were given, the mean number of courses being 3.5, range 1-6. The gemcitabine was given at 1000 mg m-2 on days 1, 8 and 15, the courses being repeated every 28 days. All patients received their first course in hospital and in total 147 were given at home and only 14 in hospital on courses 2-6. Furthermore, both the patients and carers reported positively on the use of domiciliary gemcitabine and preferred it over hospital administration. There was no evidence of increasing burden to community services during the domiciliary chemotherapy. Further studies investigating this approach are warranted

A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer

A randomized trial was conducted to determine whether administration of Amifostine with chemotherapy for small cell lung cancer could decrease the toxicity. 84 patients with small cell lung cancer of favourable prognosis (limited disease, performance status 0-1; limited disease with performance status 2 but normal sodium and alkaline phosphatase, or extensive diseas with performance status 0-1, normal sodium and alkaline phosphatase) received treatment with Ifosfamide 3 g/m2intravenously, Carboplatin (Glomerular filtration rate + 25) ´6 mg intravenously, Etoposide 50 mg orally, twice daily, for 7 days, every 3 weeks. Patients were randomized to receive amifostine 740 mg/m2immediately prior to the intravenous drugs (n = 42) or to receive chemotherapy alone (n = 42). The two groups were similar with respect to baseline prognostic factors. There was no significant difference in the occurrence of grade III or IV neutropenia or thrombocytopenia between the two groups, nor in the response rate or overall survival, for which the median was 11 months in the chemotherapy only group and 14 months in the group treated with amifostine. This study has not shown a protective effect from the use of amifostine with this regimen and there does not appear to be any effect upon the efficacy of treatment