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Surrogate markers predicting overall survival for lung cancer: elcwp recommendations.

The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers) in determining treatment efficacy instead of survival in patients with lung cancer.

Preliminarily, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer.

Some intermediate criteria can be early predictors, if not surrogates, for survival despite limitations in their potential application: these include time-to-progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced non-small cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers.

Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.

Combined Contrast-Enhanced Computed Tomography and 18-Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography in the Diagnosis and Staging of Non-small Cell Lung Cancer.

We present the current optimal uses and limitations of positron emission tomography/computed tomography (PET/CT) as it relates to the diagnosis and staging of non-small cell lung cancer (NSCLC).

PET/CT demonstrates increased accuracy in the workup of solitary pulmonary nodules for malignancy compared with CT alone, and we discuss its benefits and limitations. We review pitfalls in measured standardized uptake values of lung lesions caused by respiratory artifacts, the lower sensitivity for detection of small lung nodules on non-breath-hold CT, and the benefits of obtaining an additional diagnostic CT for the maximum sensitivity of lung nodule detection.

There are limitations of quantitatively comparing separate PET/CT examinations from different facilities with standardized uptake values. As for staging, we describe how PET/CT supplements clinical tumor-nodes-metastases (ie, TNM) staging, as well as mediastinoscopy, endobronchial ultrasound, and endoscopic ultrasound, which are the gold standard pathologic staging methods.

We touch on the 7th edition TNM staging system based on the work by the International Association for the Study of Lung Cancer, an anatomically based staging method.

Survival after resection of synchronous non-small cell lung cancer.

OBJECTIVES: Our objective was to determine the long-term survival of patients with resected synchronous multiple pulmonary malignant tumors.

METHODS: This is a multi-institutional retrospective study of patients who underwent surgical resection of synchronous (nonbronchioloalveolar) non-small cell lung cancer.
RESULTS: Between March 1996 and December 2009, 67 patients (30 men) underwent 121 operations. Forty-four patients had bilateral tumors. Positron emission tomographic scans were performed in 58 (87%) patients, computed tomographic scans and magnetic resonance imaging of the brain in 53 (79%), and mediastinoscopy in 56 (84%). N2 lymph nodes were benign in all patients before undergoing resection of bilateral tumors of the same histologic type. Types of resection were lobectomy in 62, sublobar in 73, and pneumonectomy in 1. Eleven patients (16%) had postoperative morbidities. Cancer-specific 3- and 5-year survivals were 73% and 69%, respectively, and overall 3- and 5-year survivals were 64% and 53%, respectively. Subgroup analysis demonstrated no difference in overall survival at 5 years between bilateral tumors of the same histologic type (M1a) (49%) versus different histologic types 42% (P = .88), or between bilateral tumors (50%) and ipsilateral tumors (54%) (P = .83).
CONCLUSIONS: The 5-year survival of surgically resected, synchronous, N2-negative, nonbronchioloalveolar, non-small cell lung cancer is excellent, even in patients who have bilateral lung lesions that harbor the same histologic features. Although the new TNM classification system labels this disease as clinical stage IV M1a, survival acts more like a separate T1 lesion after surgical resection. Thus, surgical resection should be considered in appropriately selected patients who have multiple pulmonary malignant tumors that are N2 negative.

Co-morbidities and 90-day Outcomes in Hospitalized COPD Exacerbations.

Co-morbidities and 90-day Outcomes in Hospitalized COPD Exacerbations.

COPD. 2011 Aug 24;

Authors: Roberts CM, Stone RA, Lowe D, Pursey NA, Buckingham RJ

Abstract
COPD exacerbations resulting in hospitalization are accompanied by high mortality and morbidity. The contribution of specific co-morbidities to acute outcomes is not known in detail: existing studies have used either administrative data or small clinical cohorts and have provided conflicting results. Identification of co-existent diseases that affect outcomes provides opportunities to address these conditions proactively and improve overall COPD care. Cases were identified prospectively on admission then underwent retrospective case note audit to collect data including co-morbidities on up to 60 unselected consecutive acute COPD admissions between March and May in each hospital participating in the 2008 UK National COPD audit. Outcomes recorded were death in hospital, length of stay, and death and readmission at 90 days after index admission. 232 hospitals collected data on 9716 patients, mean age 73, 50% male, mean FEV(1) 42% predicted. Prevalence of co-morbidities were associated with increased age but better FEV(1) and ex-smoker status and with worse outcomes for all four measures. Hospital mortality risk was increased with cor pulmonale, left ventricular failure, neurological conditions and non-respiratory malignancies whilst 90 day death was also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases were important factors in readmission. This study demonstrates that co-morbidities adversely affect a range of short-term patient outcomes related to acute admission to hospital with exacerbations of COPD. Recognition of relevant accompanying diseases at admission provides an opportunity for specific interventions that may improve short-term prognosis.

PMID: 21864116 [PubMed - as supplied by publisher]

Azithromycin for prevention of exacerbations of COPD.

Azithromycin for prevention of exacerbations of COPD.

N Engl J Med. 2011 Aug 25;365(8):689-98

Authors: Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR,

Abstract
BACKGROUND: Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.
METHODS: We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.
RESULTS: A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of -4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04).
CONCLUSIONS: Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.).

PMID: 21864166 [PubMed - in process]

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