Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use, accounting for over 300,000 deaths each year. Striking differences in the epidemiological, clinical and molecular characteristics of lung cancers arising in never smokers versus smokers have been identified, suggesting that they are separate entities. This Review summarizes our current knowledge of this unique and poorly understood disease.

Lung Cancer in Never Smokers - Different Disease

Background Determining the stage of non–small-cell lung cancer often requires multiple preoperative tests and invasive procedures. Whole-body positron-emission tomography (PET) may simplify and improve the evaluation of patients with this tumor. Methods We prospectively compared the ability of a standard approach to staging (computed tomography [CT], ultrasonography, bone scanning, and, when indicated, needle biopsies) and one involving PET to detect metastases in mediastinal lymph nodes and at distant sites in 102 patients with resectable non–small-cell lung cancer. The presence of mediastinal metastatic disease was confirmed histopathologically. Distant metastases that were detected by PET were further evaluated by standard imaging tests and biopsies. Patients were followed postoperatively for six months by standard methods to detect occult metastases. Logistic-regression analysis was used to evaluate the ability of PET and CT to identify malignant mediastinal lymph nodes. Results The sensitivity and sp...

Preoperative staging of non-small-cell lung cancer with positron-emission tomography.

Summary Background The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer (NSCLC). Methods Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy, stratified by ECOG performance status, previous bevacizumab treatment, histology, and presence of brain metastases, were allocated (by computer-generated sequence through an interactive third-party system, in 1:1 ratio), to receive docetaxel 75 mg/m 2 by intravenous infusion on day 1 plus either nintedanib 200 mg orally twice daily or matching placebo on days 2–21, every 3 weeks until unacceptable adverse events or disease progression. Investigators and patients were masked to assignment. The primary endpoint was progression-free survival (PFS) by independent central review, analysed by intention to treat after 714 events in all patients. The key secondary endpoint was overall survival, analysed by intention to treat after 1121 events had occurred, in a prespecified stepwise order: first in patients with adenocarcinoma who progressed within 9 months after start of first-line therapy, then in all patients with adenocarcinoma, then in all patients. This trial is registered with ClinicalTrials.gov, number NCT00805194. Findings Between Dec 23, 2008, and Feb 9, 2011, 655 patients were randomly assigned to receive docetaxel plus nintedanib and 659 to receive docetaxel plus placebo. The primary analysis was done after a median follow-up of 7·1 months (IQR 3·8–11·0). PFS was significantly improved in the docetaxel plus nintedanib group compared with the docetaxel plus placebo group (median 3·4 months [95% CI 2·9–3·9] vs 2·7 months [2·6–2·8]; hazard ratio [HR] 0·79 [95% CI 0·68–0·92], p=0·0019). After a median follow-up of 31·7 months (IQR 27·8–36·1), overall survival was significantly improved for patients with adenocarcinoma histology who progressed within 9 months after start of first-line treatment in the docetaxel plus nintedanib group (206 patients) compared with those in the docetaxel plus placebo group (199 patients; median 10·9 months [95% CI 8·5–12·6] vs 7·9 months [6·7–9·1]; HR 0·75 [95% CI 0·60–0·92], p=0·0073). Similar results were noted for all patients with adenocarcinoma histology (322 patients in the docetaxel plus nintedanib group and 336 in the docetaxel plus placebo group; median overall survival 12·6 months [95% CI 10·6–15·1] vs 10·3 months [95% CI 8·6–12·2]; HR 0·83 [95% CI 0·70–0·99], p=0·0359), but not in the total study population (median 10·1 months [95% CI 8·8–11·2] vs 9·1 months [8·4–10·4]; HR 0·94, 95% CI 0·83–1·05, p=0·2720). Grade 3 or worse adverse events that were more common in the docetaxel plus nintedanib group than in the docetaxel plus placebo group were diarrhoea (43 [6·6%] of 652 vs 17 [2·6%] of 655), reversible increases in alanine aminotransferase (51 [7·8%] vs six [0·9%]), and reversible increases in aspartate aminotransferase (22 [3·4%] vs three [0·5%]). 35 patients in the docetaxel plus nintedanib group and 25 in the docetaxel plus placebo group died of adverse events possibly unrelated to disease progression; the most common of these events were sepsis (five with docetaxel plus nintedanib vs one with docetaxel plus placebo), pneumonia (two vs seven), respiratory failure (four vs none), and pulmonary embolism (none vs three). Interpretation Nintedanib in combination with docetaxel is an effective second-line option for patients with advanced NSCLC previously treated with one line of platinum-based therapy, especially for patients with adenocarcinoma. Funding Boehringer Ingelheim.

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Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial

Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients.

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Oncologic photodynamic therapy: Basic principles, current clinical status and future directions

In 2010, approximately 222,520 new cases of lung or bronchial cancer will be diagnosed in the USA, and 157,300 patients are expected to die of this disease [1]. Lung cancer is the leading cause of cancer-related death in both men and women, and non-small cell lung cancer (NSCLC) accounts for about 80 % of these cases. Lung cancer is most often asymptomatic in its early stages; consequently, the disease is usually diagnosed at an advanced stage, when it is much more difficult to treat. One or more genes are believed to be responsible for an inherited increase in risk of developing lung cancer in the general population. Smoking remains one of the main environmental factors associated with the development of lung cancer [2]. Although the development of lung cancer seems to be the result of several sequential molecular abnormalities in individuals at high risk of developing the disease, the genetic mechanisms by which an individual develops lung cancer remain largely unknown. These steps involve abnormalities in the expression of angiogenic factors (e.g., vascular endothelial growth factor, or VEGF and epithelial growth factor receptors, or EGFRs) [3]. The heterogeneity of lung cancer and the diversity of its morphologic appearance and molecular properties make the application of molecular targeted therapies used in other cancers more complex, but such therapies are certainly a goal for the future.

Robert A. Figlin

Papers

Non–Small Cell Lung Cancer