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Postoperative radiotherapy for elderly patients with stage III lung cancer.

The potential role of postoperative radiation therapy (PORT) for patients who have completely resected, stage III nonsmall cell lung cancer (NSCLC) with N2 disease remains controversial. By using population-based data, the authors of this report compared the survival of a concurrent cohort of elderly patients who had N2 disease treated with and without PORT.

METHODS: By using the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records, 1307 patients were identified who had stage III NSCLC with N2 lymph node involvement diagnosed between 1992 and 2005. Propensity scoring methods and instrumental variable analysis were used to compare the survival of patients who did and did not receive PORT after controlling for selection bias.

RESULTS: Overall, 710 patients (54%) received PORT. Propensity score analysis indicated that PORT was not associated with improved survival in patients with N2 disease (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.97-1.27). Analyses that were limited to patients who did or did not receive chemotherapy, who received intermediate-complexity or high-complexity radiotherapy planning, or adjusted for time trends produced similar results. The instrumental variable estimator for the absolute improvement in 1-year and 3-year survival with PORT was -0.04 (95% CI, -0.15 to 0.08) and -0.08 (95% CI, -0.24 to 0.15), respectively.

CONCLUSIONS: The current data suggested that PORT is not associated with improved survival for elderly patients with N2 disease. These findings have important clinical implications, because SEER data indicate that a large percentage of elderly patients currently receive PORT despite the lack of definitive evidence about its effectiveness. The potential effectiveness of PORT should be evaluated further in randomized controlled trials.

Retreatment of gefitinib in patients with non-small-cell lung cancer who previously controlled to gefitinib: A single-arm, open-label, phase II study.

Most patients with non-small-cell lung cancer (NSCLC) who initially respond to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) eventually experience progression of disease. Based on previous trials which showed second response after switching to another EGFR-TKI, we hypothesized that the reintroduction of gefitinib would lead to disease control rate (DCR) in more than 30% of patients.

This was a single-arm, open-label, prospective, phase II trial of gefitinib for the treatment of advanced or metastatic NSCLC. Eligible patients had previously responded to, or had experienced disease stabilization with, initial gefitinib treatment for at least 3 months. Prior to retreatment, progressive disease (PD) should be observed, with at least one cytotoxic treatment following initial gefitinib failure.

Twenty-three patients were recruited and defined as the intention to treat (ITT) group. Most of the enrolled patients were female (86.9%), never-smokers (91.3%), and adenocarcinoma patients (95.7%). Responses to initial gefitinib were partial response (PR) in 10 cases (43.5%) and stable disease (SD) in 13 cases (56.5%). PR and DCR were observed in 21.7% (5 patients) and 65.2% (15 patients) in the ITT group. Among 14 DNA samples, 13 cases had either exon 19 deletion or L858R point mutation, whereas one patient evidenced the wild-type EGFR gene.

Re-initiation of EGFR-TKI can be considered as an option after failure of chemotherapy for those patients who previously controlled to EGFR-TKI treatment.

Does radiographic emphysema correlate with low bone mineral density?

Purpose of review: Several large epidemiologic studies have shown an association between chronic obstructive pulmonary disease (COPD) and osteoporosis. Recent studies have further implied an emphysema-specific association with low bone mineral density independent of obstruction severity.

Recent findings: This review will outline the studies demonstrating an independent association between radiographic emphysema and decreased bone mineral density and will discuss potential disease mechanisms, including systemic inflammation and immune-mediated factors, linking these disease processes.

Summary: Radiographic emphysema should be considered an independent risk factor in studies examining the mechanisms underlying COPD-related bone loss. Future research focused on the relationship between emphysema and low bone mineral density could provide mechanistic insight and result in the development of targeted therapies designed to halt progression of both disease processes.

Should androgenic anabolic steroids be considered in the treatment regime of selected chronic obstructive pulmonary disease patients?

Purpose of review: Chronic obstructive pulmonary disease (COPD) is a widespread disease with high morbidity rates. Advanced stages can be complicated by unintentional weight loss and muscle wasting, which may contribute to increased morbidity and mortality. Reversal of weight loss increases muscle strength and exercise capacity and improves survival. This can partly be achieved by nutritional support, preferably combined with increase in exercise. Androgenic anabolic steroids (AASs), of which testosterone is the parent hormone, increase muscle size and strength. Due to these anabolic effects, AASs may emerge as a treatment option in COPD patients suffering from muscle wasting.

Recent findings: Seven trials investigated the effects of AAS in patients with COPD. Some studies also included nutritional therapy and/or a pulmonary rehabilitation program. Compared with placebo, AASs increase lean body mass (LBM) and muscle size. However, no consistent effects on muscle strength, exercise capacity, or pulmonary function are seen.

Summary: AASs increase LBM in patients with advanced stages of COPD. No consistent beneficial effect on other endpoints was demonstrated in the reviewed trials. However, probably higher doses of AASs are needed to exert a clinically meaningful effect on muscle strength or exercise capacity. Currently, no evidence is available to recommend AASs to all patients with COPD. In individual cases, treatment with AASs can be considered, particularly in men with advanced COPD, moderate-to-severe functional impairment, muscle wasting and on chronic corticosteroid therapy. Treatment with AASs should preferably be combined with a rehabilitation program and nutritional support. AASs should not be used in women or in men with symptomatic heart disease. When treatment with AASs is considered, intramuscular nandrolone-decanoate is preferred in a dose of 50–200 mg per week for a period of 12 weeks. However, the efficacy of AAS treatment in COPD patients needs further clarification in well designed, adequately powered clinical studies.

Incidence, treatment options, and outcomes of lung cancer in patients with chronic obstructive pulmonary disease

Purpose of review: An associative and mechanistic link between chronic obstructive pulmonary disease (COPD) and lung cancer has long been suspected. This review describes the current understanding of the incidence, mechanism of association, treatment options, and outcome for lung cancer with COPD.

Recent findings: COPD patients have an increased risk of lung cancer that is independent of smoking. New evidence suggests that there is an inverse relationship between the severity of airflow obstruction and the risk of lung cancer. Chronic inflammation associated with COPD may play a role in the development of lung cancer, and targeting airway inflammation with inhaled corticosteroids has been suggested as a possible preventive strategy. Although surgical lobectomy remains the standard of care for early stage lung cancer, less invasive approaches such as sublobar resection, stereotactic body radiation therapy, and radiofrequency ablation are promising techniques for patients with limited pulmonary reserve.

Summary: Progress is being made in identifying mechanistic links between COPD and lung cancer, which may lead to novel therapeutic strategies for both disorders. Patients with COPD are likely to benefit from less-invasive surgical and nonsurgical treatment strategies for lung cancer, but further study is needed to determine the safety and efficacy of these procedures.

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