Current Respiratory Medicine Reviews - Volume 7, Issue 5, 2011

Full text available.

Lung cancer is the major cause of cancer - related mortality in men and women worldwide. In the last three decades, the management of lung cancer has changed and the mortality of this disease has improved. This is partly due to rapid progress in the research, diagnosis, and treatment of lung cancer. The present Special Hot Topic Series entitled “Lung Cancer - What is New? ”reviews the progress of management of thoracic cancer. This work is the result of diligent efforts of many investigators, authors, reviewers and support personnel who we are indebted to for their perseverance. This special series on lung cancer is dedicated to my aunt Jade, and to all patients who have battled, or are battling this disease.

Smoking, air pollution and radon exposure are causally related to lung cancer. This review analyzes trends of smoking habits by age, sex and ethnicity and their correlation with incidence and mortality of lung cancer. Unfortunately the use of tobacco by adolescents is on the rise. Most developed countries are still showing the rising trend of mortality in female smokers. In Asia, cigarette smoking has become a major health risk with one in three of all cigarettes in the world today are smoked in China. Estimated one hundred million young (< 29 years old) Chinese smokers will eventually die from lung cancer. In Central and South America, occupational risk with exposure to respiratory carcinogens in Brazil correlated with increasing lung cancer incidence. In Chile an analysis revealed a trend in lung cancer odd ratios with increasing concentration of arsenic in drinking water. In Uruguay, in addition to tobacco consumption, diet with low consumption of plant foods, or high consumption of red meat, total fat and cholesterol contributed to a higher risk of lung cancer development. Although many Western governments and health authorities now try to persuade people not to smoke, and in some developed countries tobacco consumption has already begun to fall, promotion of cigarette sales in the third world has intensified. Adenocarcinoma has become the most common histological type recently. Research from various disciplines including radiation therapy, chemotherapy, and surgery are on-going to improve the relative dismal prognosis of lung cancer.

Lung cancer comprises of two major clinically relevant types, non-small cell lung cancer (NSCLC) representing about 85% of all cases and small cell lung cancer (SCLC) accounting for the remaining 15%. Despite recent advancements that include new understanding of the molecular mechanisms involved in cancer pathogenesis and introduction of new treatments, lung cancer continues to reign as the leading cause of cancer deaths worldwide. Innovations in genomics-based technologies are becoming rapidly integrated into lung cancer research and the results of these efforts have started to yield tangible advances in improved understanding and treatment of lung cancer.

Lung cancer is the most commonly diagnosed malignancy and the leading cause of cancer mortality worldwide. Radiation therapy (RT) plays an important role in the management of both small cell (SCLC) and non-small cell lung cancer (NSCLC), as 50 to 60% of patients diagnosed with lung cancer will require RT during the course of their disease. In NSCLC, in addition to the use of RT in advanced stage disease, inoperable patients with early-stage disease are now being treated with highly conformal hypofractionated RT as well as radiosurgery. In SCLC, the use of thoracic chemo-RT followed by prophylactic cranial irradiation (PCI) in limited-stage disease, and the use of PCI in extensive-stage disease have improved outcomes, and patient survival has steadily increased in the past decades. This article will review the role of RT in both SCLC and NSCLC, with emphasis at the most recent advances in the field as well as the topics of controversy.

New technological concepts have been evolving to manage the relative poor prognosis of lung cancer. Brachytherapy is becoming an option for both unresectable and early resectable lung cancer. Three-dimensional ultrasound (US) of lung tumours and image-guided minimally invasive robotics-assisted brachytherapy are feasible for dosimetry planning and management of lung tumours. The present article reviews the current knowledge of lung brachytherapy and discusses its potential in future management of lung cancer.

The paradigm of empiric treatment for advanced or metastatic non-small cell carcinoma of the lung (A-NSCLC) has been challenged in recent years, with an increasing emphasis on personalizing current therapies and utilizing new therapies that target the drivers of carcinogenesis. As more systemic therapies become available, decisions regarding the optimal type of therapy, timing and duration of treatment are becoming increasingly complex. Clinicians involved in the care of patients with lung cancer may wish to be kept up-to-date regarding the current approaches to treatment. Herein we provide an overview of the current systemic therapies for A-NSCLC, discussing evidence-based approaches to firstline, second-line and maintenance treatment. An outline of the pharmacology of the major classes of active drugs is given, and key evidence is outlined and organized by line of treatment. The characteristics of the target populations for treatment are discussed, along with the optimal combination and timing of therapy.

Mesothelioma is an uncommon tumor. It has a latency period of 20-40 years. The most important risk factor is asbestos exposure. Prognosis of mesothelioma is generally poor with high case-fatality rate, and research to improve the outcome of this disease is on-going worldwide. Due to its rarity, management by a multidisciplinary team with experience is recommended. Carefully selected patients may benefit from tri-modality (surgery, radiotherapy and chemotherapy) treatment. The management of pleural and peritoneal mesothelioma is summarized in this review. Recent advances in chemotherapy and biologic response modifiers are promising.

Thymic tumors are rare. The management remains controversial. The spectrum of behaviour ranges from benign indolent thymomas to highly aggressive and rapidly fatal undifferentiated thymic carcinomas. There remains inconsistency and controversy in histological classification. There appears to be some correlation between histological type and stage. Surgery is recognized as the mainstay of treatment. The goal of surgery is complete resection (RO) and this appears to be adequate for early stage disease. These tumors appear to be both radiation and chemotherapy responsive. There is controversy as to when adjuvant radiation is appropriate, but generally accepted as part of the treatment algorithm for invasive disease or incompletely resected disease. Induction therapy with chemotherapy alone or with radiation and or targeted therapies have been used to try and improve the RO resection rate. Systemic therapy with a cisplatin and anthracyclin containing regimen is often used for unresectable and metastatic disease, again with or without radiation and targeted agents. There is no good evidence to favour either concurrent or sequential therapies. The Thymoma Working Group of the NCIC has devised a treatment algorithm in an attempt to standardize treatment in Canada. In order to address the problems associated with this rare and varied tumor group the International Thymic Malignancies Interest Group (ITMIG) has been formed. It is only through worldwide collaboration through such a group that any real progress in the management of thymic tumors can be made.

Cigarette smoking which exposes the lung to high concentrations of reactive oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary disease (COPD). Recent studies indicate that the defense against oxidant stress is impaired in COPD and oxidant burden is increased in COPD even after smoking has ceased. ROS present in cigarette smoke interfere with protein folding in the endoplasmic reticulum thereby eliciting a compensatory response termed the “unfolded protein response.” The importance of the UPR lies in its ability to alter expression of a large number of gene programs involved in basic cellular processes including anti-oxidant defense. This article will review the several signaling pathways which mediate the unfolded protein response and, in particular, the role of the PERK (protein kinase R-like endoplasmic reticulum kinase) signaling pathway in protecting the lung against oxidant injury. Moreover, the impairment in oxidant defense present in the lung in COPD will be discussed.

Diving using compressed air involves the potential for changing lung function through several mechanisms, including bronchial responsiveness. Of particular interest is the effect self-contained underwater breathing apparatus (SCUBA) may have on airflow limitation following a dive such as a possible result of aerosolization of seawater within the regulator, breathing cold dry gas from the tank, or some other putative mechanisms. This cross-sectional observational study was conducted in the field and investigated the hypothesis that bronchoconstriction may occur during a SCUBA dive in some individuals. Measurements included forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and peak expiratory flow. Spirometry instrumentation provided immediate feedback regarding test quality. Data were collected from May 2007-May 2009, at which time we calculated the data had an 88% statistical power to detect the clinically significant mean change in FEV1 of 200mls. Post-dive lung function values showed no clinically important impairment (FVC fell by 80 mls on average, 95% confidential interval CI 20mls to 140 mls, t(131)=2.57, p=0.01) and the hypothesis was not supported. Of 209 eligible divers who participated in the study, 63% provided valid spirometry data to ERS/ATS standards for acceptability and reproducibility. This study was conducted in the field as opposed to the more commonly used laboratory setting. Although spirometry is a simple test, the ease of data collection was made more difficult by environmental conditions and variables outside the researchers' control.