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Many patients with advanced non-small-cell lung cancer (NSCLC) receive only active supportive care because of poor performance status or presence of several comorbidities. We investigated whether erlotinib improves clinical outcome in these patients. TOPICAL was a double-blind, randomised, placebo-controlled, phase 3 trial, done at 78 centres in the UK. Eligibility criteria were newly diagnosed, pathologically confirmed NSCLC; stage IIIb or IV; chemotherapy naive; no symptomatic brain metastases; deemed unsuitable for chemotherapy because of poor (≥2) Eastern Cooperative Oncology Group performance status or presence of several comorbidities, or both; and estimated life expectancy of at least 8 weeks. Patients were randomly assigned (by phone call, in a 1:1 ratio, stratified by disease stage, performance status, smoking history, and centre, block size 10) to receive oral placebo or erlotinib (150 mg per day) until disease progression or unacceptable toxicity. Investigators, clinicians, and patients were masked to assignment. The primary endpoint was overall survival. Analyses were by intention to treat, and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment. This study is registered, number ISRCTN 77383050. Between April 14, 2005, and April 1, 2009, we randomly assigned 350 patients to receive erlotinib and 320 to receive placebo. We followed up patients until March 31, 2011. 657 patients died; median overall survival did not differ between groups (erlotinib, 3·7 months, 95% CI 3·2–4·2, vs placebo, 3·6 months, 3·2–3·9; unadjusted hazard ratio [HR] 0·94, 95% CI 0·81–1·10, p=0·46). 59% (178 of 302) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash, which was the only independent factor associated with overall survival. Patients with first-cycle rash had better overall survival (HR 0·76, 95% CI 0·63–0·92, p=0·0058), compared with placebo. Compared with placebo, overall survival seemed to be worse in the group that did not develop first-cycle rash (1·30, 1·05–1·61, p=0·017). Grade 3 or 4 diarrhoea was more common with erlotinib than placebo (8% [28 of 334] vs 1% [four of 313], p=0·0001), as was high-grade rash (23% [79 of 334] vs 2% [five of 313], p<0·0001); other adverse events were much the same between groups. Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib. Patients who develop a first-cycle rash should continue to receive erlotinib, whereas those who do not have a rash after 28 days should discontinue erlotinib, because of the possibility of decreased survival. Cancer Research UK, Roche.

The preoperative physiologic assessment of a patient being considered for surgical resection of lung cancer must consider the immediate perioperative risks from comorbid cardiopulmonary disease, the long-term risks of pulmonary disability, and the threat to survival due to inadequately treated lung cancer. As with any planned major operation, especially in a population predisposed to atherosclerotic cardiovascular disease by cigarette smoking, a cardiovascular evaluation is an important component in assessing perioperative risks. Measuring the FEV1 and the diffusing capacity of the lung for carbon monoxide (Dlco) measurements should be viewed as complementary physiologic tests for assessing risk related to pulmonary function. If there is evidence of interstitial lung disease on radiographic studies or undue dyspnea on exertion, even though the FEV1 may be adequate, a Dlco should be obtained. In patients with abnormalities in FEV1 or Dlco identified preoperatively, it is essential to estimate the likely postresection pulmonary reserve. The amount of lung function lost in lung cancer resection can be estimated by using either a perfusion scan or the number of segments removed. A predicted postoperative FEV1 or Dlco < 40% indicates an increased risk for perioperative complications, including death, from lung cancer resection. Exercise testing should be performed in these patients to further define the perioperative risks prior to surgery. Formal cardiopulmonary exercise testing is a sophisticated physiologic testing technique that includes recording the exercise ECG, heart rate response to exercise, minute ventilation, and oxygen uptake per minute, and allows calculation of maximal oxygen consumption ( V˙o2max). Risk for perioperative complications can generally be stratified by V˙o2max. Patients with preoperative V˙o2max > 20 mL/kg/min are not at increased risk of complications or death; V˙o2max < 15 mL/kg/min indicates an increased risk of perioperative complications; and patients with V˙o2max < 10 mL/kg/min have a very high risk for postoperative complications. Alternative types of exercise testing include stair climbing, the shuttle walk, and the 6-min walk. Although often not performed in a standardized manner, stair climbing can predict V˙o2max. In general terms, patients who can climb five flights of stairs have V˙o2max > 20 mL/kg/min. Conversely, patients who cannot climb one flight of stairs have V˙o2max < 10 mL/kg/min. Data on the shuttle walk and 6-min walk are limited, but patients who cannot complete 25 shuttles on two occasions will have V˙o2max < 10 mL/kg/min. Desaturation during an exercise test has been associated with an increased risk for perioperative complications. Lung volume reduction surgery (LVRS) for patients with severe emphysema is a controversial procedure. Some reports document substantial improvements in lung function, exercise capability, and quality of life in highly selected patients with emphysema following LVRS. Case series of patients referred for LVRS indicate that perhaps 3 to 6% of these patients may have coexisting lung cancer. Anecdotal experience from these case series suggest that patients with extremely poor lung function can tolerate combined LVRS and resection of the lung cancer with an acceptable mortality rate and good postoperative outcomes. Combining LVRS and lung cancer resection should probably be limited to those patients with heterogeneous emphysema, particularly emphysema limited to the lobe containing the tumor.

Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life. 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]); to ASC plus MVP (four cycles of mitomycin 6 mg/m 2, vinblastine 6 mg/m 2, and cisplatin 50 mg/m 2 every 3 weeks [n=137]); or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m 2 every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112. At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0·89 [95% CI 0·72–1·10]; p=0·29). Median survival was 7·6 months in the ASC alone group and 8·5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0·80 [0·63–1·02]; p=0·08), with a median survival of 9·5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0·99 [0·78–1·27]; p=0·95). We observed no between-group differences in four predefined quality-of-life subscales (physical functioning, pain, dyspnoea, and global health status) at any of the assessments in the first 6 months. The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life. However, exploratory analyses suggested that vinorelbine merits further investigation. Cancer Research UK and the Medical Research Council (UK).

Background and objective: The initial results of a survey of 588 patients with a clinical presentation of cryptogenic fibrosing alveolitis (CFA) also known as idiopathic pulmonary fibrosis, have been published. This article reports further results pertaining to response to treatment and survival. Methods: Data on the treatment given and lung function response were collected over 4–6 years. Survival data were collected over 10 years. Results: Treatment was given to 445 (76%) patients, 55% were given prednisolone alone and the remainder another immunosuppressive agent, usually with prednisolone. Treated patients had worse lung function initially. At 3 months after study entry, treated patients were more likely to have improved forced vital capacity (FVC) than the untreated patients. Patients whose FVC improved were younger (p = 0.001 analysis of variance (ANOVA)) and had lower initial FVC (p<0.001, ANOVA). Patients who responded to treatment at 3 months or at 1 year survived longer than those who remained stable, who in turn survived longer than those who deteriorated (p = 0.002). These differences were largely accounted for by patients with better lung function surviving longer. Younger age at entry, female sex and higher percentage predicted FVC and reduced carbon monoxide transfer factor at study entry were associated with greater chances of survival at 4 years. Overall median survival from entry was 2.43 years (95% confidence interval (CI) 2.17 to 3.18). Conclusions: About a third of patients with CFA showed improved lung function after initiation of corticosteroid or immunosuppressive treatment, and those who improved survived longer. Poorer lung function, male sex and age are adverse prognostic features. Overall survival was poor.

This chapter describes the components of the initial evaluation for a patient either suspected or known to have lung cancer. The components of the initial evaluation are based on the recognized manifestations of localized lung cancer, ie, symptoms referable to the primary tumor, intrathoracic spread of lung cancer, and patterns of metastatic dissemination. Features of the history and physical signs may be useful indicators of the extent of disease. A standardized evaluation, relying on symptoms, signs, and routinely available laboratory tests, can serve as a useful screen for metastatic disease. Also described are the common features of the various paraneoplastic syndromes associated with lung cancer.

Because of a lack of effective treatments, survival from diffuse pleural mesothelioma remains poor. Many people do not think that treatments for this disease are effective. The understanding of the biology of mesothelioma relevant to the apoptosis-resistant phenotype has been slow to advance. However, this is now changing, and strategies for rational therapeutic drug development are emerging that have the potential to change the natural history and improve survival in the increasing number of patients that will be diagnosed in the next two decades. This review discusses recent developments in apoptosis biology that are specific to mesothelioma and the therapeutic implications for this aggressive cancer.

Approximately 30-40% of non-small cell lung cancer patients will present with metastatic disease, and its associated poor prognosis. Chemotherapy has an established palliative role within late-stage disease, but is also being used increasingly in the neoadjuvant and adjuvant settings. Platinum-based chemotherapy has been shown to produce definite improvements in efficacy and quality of life in non-small cell lung cancer patients, and is now the standard of care. Carboplatin has similar biochemical properties to those of cisplatin. However, carboplatin has much less renal, otologic, neurologic and upper gastrointestinal toxicities than cisplatin, and treatment can be conveniently delivered in an out-patient setting. Furthermore, platinum combinations with third-generation cytotoxics have shown additional gains in survival rates. Gemcitabine and carboplatin is a well-tolerated regime. Recent meta- and cost analyses have discovered that gemcitabine-based regimes may have an advantage over other third-generation agent platinum combinations. This article reviews the evidence demonstrating that gemcitabine-carboplatin is effective, convenient and cost effective.

This chapter describes the components of the initial evaluation for a patient either suspected or known to have lung cancer. The components of the initial evaluation are based on the recognized manifestations of localized lung cancer, ie, symptoms referable to the primary tumor, intrathoracic spread of lung cancer, and patterns of metastatic dissemination. Features of the history and physical signs may be useful indicators of the extent of disease. A standardized evaluation, relying on symptoms, signs, and routinely available laboratory tests, can serve as a useful screen for metastatic disease. Also described are the common features of the various paraneoplastic syndromes associated with lung cancer.

The technology principle in the Principles and Standards for School Mathematics (NCTM, 2000) states that technology plays an important role in how teachers teach mathematics and in how students learn mathematics. The purpose of this sequential explanatory mixed methods study was to examine the impact of interactive applets on students’ understanding of parameter changes to parent functions. Students in the treatment classes were found to have statistically significantly higher posttest scores than students in the control classes. Although the data analysis showed a statistically significant difference between classes on procedural understanding, no statistically significant difference was found with regard to conceptual understanding. Student and teacher interviews provided insight on how and why the use of applets helped or hindered students’ understanding of parameter changes to parent functions. KEYWORDS: Technology, Mathematics Education, Procedural Understanding, Conceptual Understanding, Algebra.