Background. Mesothelioma is a rare cancer with a historically dire prognosis. We sought to calculate life expectancies for patients with pleural or peritoneal mesothelioma, both at time of diagnosis and several years later, and to examine whether survival has improved in recent years. Methods. Data on 10,258 pleural and 1,229 peritoneal patients from the SEER US national cancer database, 1973–2011, were analyzed using the Cox proportional hazards regression model. Results. The major factors related to survival were age, sex, stage, grade, histology, and treatment. Survival improved only modestly over the study period: 0.5% per year for pleural and 2% for peritoneal. Conclusions. Life expectancies were markedly reduced from normal, even amongst 5-year survivors with the most favorable characteristics and treatment options.
Objectives. There have been advances in the identification and understanding of molecular subsets of lung cancer, defined by specific oncogenic aberrations. A number of actionable genetic alterations have been identified, such as the epidermal growth factor receptor (EGFR) mutation. We aimed to establish the reasons why patients were not undergoing EGFR mutation testing at the time of histological diagnosis. Methods. The records of 70 patients with advanced adenocarcinoma of the lung managed through a single multidisciplinary team at a single institution were reviewed. Data were collected on method of tumour sample collection, whether this was sent for EGFR testing, and the result. Results. Seventy patients were identified. In 21/25 (84%) cases, cytological sampling was sufficient for EGFR mutation analysis, compared with 40/45 (89%) cases with histological sampling. EGFR mutation testing was not carried out in 22/70 (31.4%) patients. There was insufficient tumour sample for EGFR testing in 9/22 (40.9%) patients. Other reasons for not testing included poor patient fitness and problems in the diagnostic pathway. Conclusions. In this series, cytological tumour sampling was not the predominant reason why cancers failed to have EGFR mutation status established.
OBJECTIVES:The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma.MATERIALS AND METHODS:NCBI's built-in statistical tool, GEO2R, was used to calculate Student's t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak's multiple comparison correction.RESULTS:Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT2 angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p < 0.01). AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT1 angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed. AGT, which encodes angiotensinogen, the angiotensin peptide precursor, was overexpressed in adenocarcinoma tissue.CONCLUSION:The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.
As the life expectancy of people with intellectual disability (ID) has progressed, they have become similarly at risk of cancer as individuals of the general population. Epidemiological studies indicate a reduced incidence and mortality from lung cancer in the total population of persons with ID. However, the pattern is heterogeneous and the risk is strongly correlated with the impairment level; persons with mild intellectual impairment have higher cancer risk, and this subgroup also has the highest tobacco consumption (the major risk factor for lung cancer) compared to individuals with more severe impairment. Clinical presentation of lung cancer in persons with ID is often atypical, with symptoms frequently hidden by the mental state and communication impairments. Treatment can be impeded by incomplete understanding and lack of cooperation on the part of the patient; nevertheless, general principles for treating lung cancer must be applied to persons with ID. Early diagnosis and implementation of an adapted treatment plan may result in lung cancer outcomes similar to those of individuals in the general population. Physicians facing the difficult task of treating lung cancer in persons with ID are called to carry out their mission of care in a responsible, free, and creative way.
Purpose. To report our experience with high dose rate endobronchial brachytherapy (HDR-EBBT) and to assess its efficacy and tolerability with possibility of its use in selected cases with curative intent.Method. Retrospective review of patients with endobronchial tumors treated at our institution in 2007–2013 with HDR-EBBT. Subjective response and treatment related toxicity were extracted from patients’ records. Clinical response was evaluated by chest CT +/− bronchoscopy 2-3 months after treatment. Local control (LC) and overall survival (OS) were analyzed.Results. Overall 23 patients were identified. Ten patients were treated with curative intent, in 8 of them HDR-EBBT was combined with external beam radiotherapy. Short term palliation was as follows: dyspnea (13/15), cough (12/14), and hemoptysis (3/3). Seventeen patients were evaluated, of whom 9 (53%) showed complete response. Four patients developed local failure (only 1 of them treated with curative intent) and were salvaged with HDR-EBBT (n=1), chemotherapy (n=2), and laser (n=1). Among patients treated with curative intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4 deaths were cancer-related. Late toxicity included bronchial stenosis (n=1). Only 1 patient had fatal hemoptysis and postmortem examination indicated local recurrence.Conclusion. HDR-EBBT is promising treatment with tolerable complication if used in properly selected patients.
Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.
An increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue; so we performed a retrospective study of our patients to demonstrate how elderly patients with NSCLC are treated in real-life, clinical practice. All patients aged ≥70 years with NSCLC at our department were reviewed retrospectively. In total, 1059 patients (50.8% of all NSCLC patients). Of these patients, 243 (22.9%) received chemotherapy, 164 (70.4%) of whom were treated with a platinum doublet using carboplatin. Second- and third-line chemotherapy were given to 31.4% and 13.9% of patients, respectively. Median overall survival was 289 and 320 days for male and female patients, respectively. Patients with performance status (PS) 0 experienced significantly better survival than patients with PS1 or PS 2: 410, 314, and 204 days, respectively. Age was of less importance, with patients aged 70–79 years versus those aged ≥80 years. Treatment of elderly NSCLC patients with chemotherapy is feasible if they have a good PS and appears to prolong survival. In this study, we found no significant differences in survival either between age groups or genders.
The aim of this study is to determine if COPD patients undergoing lung resection with perioperative β-blocker use are more likely to suffer postoperative COPD exacerbations than those that did not receive perioperative β-blockers. Methods. A historical cohort study of COPD patients, undergoing lung resection surgery at Memorial Sloan-Kettering Cancer Center between 2002 and 2006. Primary outcomes were the rate of postoperative COPD exacerbations, defined as any initiation or increase of glucocorticoids for documented bronchospasm. Results. 520 patients with COPD were identified who underwent lung resection. Of these, 205 (39%) received perioperative β-blockers and 315 (61%) did not. COPD was mild among 361 patients (69% of all patients), moderate in 117 patients (23%), and severe in 42 patients (8%). COPD exacerbations occurred among 11 (5.4%) patients who received perioperative β-blockers and among 20 (6.3%) patients who did not. Secondary outcomes, which included respiratory failure, 30-day mortality, and the presence or absence of any cardiovascular complication, ICU transfer, cardiovascular complication, or readmission within 30 days, did not differ in prevalence between the two groups. Conclusions. This study implies that perioperative β-blockers use among COPD patients undergoing lung resection surgery does not impact the rate of exacerbations.
Background. Evaluation of Ki-67 index in lung carcinoid tumors (LCTs) has been of interest in order to identify high risk subsets. Our objectives are (1) to evaluate the usefulness of Ki-67 index, mitoses, and tumor size in predicting metastasis and (2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CIAM) for Ki-67 calculation. Methods. We studied 48 patients with LCTs from two academic centres in Canada. For Ki-67 calculation, digital images of 5000 cells were counted using an image processing software and 2000 cells by MCM. Mitoses/10 HPF was counted. Results. We had 37 typical carcinoids (TCs) and 11 atypical carcinoids (ACs). 7/48 patients developed metastasis. There was a positive relationship between metastasis and carcinoid type (P = 0.039) and metastasis and mitoses (≥2) (P = 0.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs (0.95% versus 0.72%, CIAM, P = 0.299). Similarly, although not statistically significant, the mean Ki-67 index for metastatic group (MG) was higher than for nonmetastatic group (NMG) (1.01% versus 0.71% by CIAM, P = 0.281). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P = 0.106, CIAM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P = 0.033) compared to other patients. Similarly patients with tumor size ≥3 cm and Ki-67 ≥0.50% had a greater percentage of metastases than others (P = 0.039). Although there was a strong correlation between two (MCM versus CIAM) counting methods (r = 0.929, P = 0.001), overall the calculated Ki-67 index was slightly higher by MCM (range 0 to 6.4, mean 1.5) compared to CIAM (range 0 to 2.9, mean 0.75). Conclusion. This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Although this is a small sample size, there is suggestion that analysis of Ki-67 index along with mitoses and tumor size may be a useful adjunct for predicting metastasis in LCTs.
Aim . We describe our experience of a simple, safe, and reproducible technique for lung nodule marking prethoracoscopic metastasectomy. Thoracoscopic lung nodule resection reduces patient discomfort, complications, higher level of care, hospital stay, and cost; however, small deeply placed lung nodules are difficult to locate and resect thoracoscopically. Materials and Methods . We describe and review the success of our novel technique, where nodules are identified on a low dose CT and marked with methylene blue using CT fluoroscopy guidance immediately prior to surgery. Results . 30 nodules were marked with a mean size of 8 mm (4–18 mm) located at a mean depth of 17 mm, distributed through both lungs. Dye was detected at the pleural surface in 97% of the patients and at the nodule in 93%. There were no major complications. Thoracoscopic resection was possible in 90%. Conclusion . This is a simple and safe method of lung nodule marking to facilitate thoracoscopic resection in cases where this may not be technically possible due to nodule location.
Objectives . Environmental factors expose an individual to heavy metals that may stimulate cancer growth preclinically including non-small cell lung cancer (NSCLC) cells. Here, we examine the prevalence of four heavy metals present in postsurgical tissues from individuals with and without NSCLC. Materials and Methods . Thoracic tissue samples from two separate sample sets were analyzed for cadmium (Cd), arsenic (As), mercury (Hg), and lead (Pb) content. Results . In the first sample set, there was no significant measurable amount of Pb and Hg found in either NSCLC tissue or nonmalignant lung tissue samples. Cd was the most prevalent heavy metal and As was present in moderate amounts. In the second sample set, Cd was measurable across all tissue types taken from 28 NSCLC patients and significantly higher Cd was measurable in noncancer benign lung (n=9). In the NSCLC samples, As was measurable in moderate amounts, while Hg and Pb amounts were negligible. Conclusion . Cd and As are present in lung tissues for patients with NSCLC. With existing preclinical evidence of their tumorigenecity, it is plausible that Cd and/or As may have an impact on NSCLC development. Additional studies examining the prevalence and association between smokers and nonsmokers are suggested.
The role of alveolar macrophages in lung cancer is multifaceted and conflicting. Alveolar macrophage secretion of proinflammatory cytokines has been found to enhance antitumour functions, cytostasis (inhibition of tumour growth), and cytotoxicity (macrophage-mediated killing). In contrast, protumour functions of alveolar macrophages in lung cancer have also been indicated. Inhibition of antitumour function via secretion of the anti-inflammatory cytokine IL-10 as well as reduced secretion of proinflammatory cytokines and reduction of mannose receptor expression on alveolar macrophages may contribute to lung cancer progression and metastasis. Alveolar macrophages have also been found to contribute to angiogenesis and tumour growth via the secretion of IL-8 and VEGF. This paper reviews the evidence for a dual role of alveolar macrophages in lung cancer progression.
We studied argyrophilic proteins associated with nucleolar organizer regions (AgNOR) in non-small-cell cancer. We determined the area index (AI) and coefficient of variation (CV) of AgNOR. AI is associated with the key clinicomorphological parameters within the TNM system: T and N values, greatest tumor dimension up to 3 cm and more, disease stage, histogenesis, and tumor differentiation. CV is associated with T value, greatest tumor dimension up to 3 cm and more, histogenesis, and tumor differentiation. Survival of patients is longer in low AI or CV values versus high AI or CV values, longer in low AI and CV values (−AI/−CV type), shorter in high AI and CV values (+AI/+CV type), and intermediate in opposite AI and CV values (−AI/+CV and +AI/−CV types). Independent predictors in non-small-cell lung cancer include N value, greatest tumor dimension, histogenesis, and CV. Assessment of quantitative values and heterogeneity of AgNOR is important for differential diagnosis and prognosis of non-small-cell lung cancer.
Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR). Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P = 0.016). Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P = 0.062). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance.
Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer.
The National Mesothelioma Virtual Bank (NMVB), developed six years ago, gathers clinically annotated human mesothelioma specimens for basic and clinical science research. During this period, this resource has greatly increased its collection of specimens by expanding the number of contributing academic health centers including New York University, University of Pennsylvania, University of Pittsburgh Medical Center, and Mount Sinai School of Medicine. Marketing efforts at both national and international annual conferences increase awareness and availability of the mesothelioma specimens at no cost to approved investigators, who query the web-based NMVB database for cumulative and appropriate patient clinicopathological information on the specimens. The data disclosure and specimen distribution protocols are tightly regulated to maintain compliance with participating institutions' IRB and regulatory committee reviews. The NMVB currently has over 1120 annotated cases available for researchers, including paraffin embedded tissues, fresh frozen tissue, tissue microarrays (TMA), blood samples, and genomic DNA. In addition, the resource offers expertise and assistance for collaborative research. Furthermore, in the last six years, the resource has provided hundreds of specimens to the research community. The investigators can request specimens and/or data by submitting a Letter of Intent (LOI) that is evaluated by NMVB research evaluation panel (REP).
Objectives. To determine whether persons at high risk of lung cancer would participate in lung cancer screening test if available in Australia and to elicit general attitudes towards cancer screening and factors that might affect participation in a screening program. Methods. We developed a 20-item written questionnaire, based on two published telephone interview scripts, addressing attitudes towards cancer screening, perceived risk of lung cancer, and willingness to be screened for lung cancer and to undertake surgery if lung cancer were detected. The questionnaire was given to 102 current and former smokers attending the respiratory clinic and pulmonary rehabilitation programmes. Results. We gained 90 eligible responses (M:F, 69:21). Mean [SD] age was 63 [11] and smoking history was 32 [21] pack years. 95% of subjects would participate in a lung cancer screening test, and 91% of these would consider surgery if lung cancer was detected. 44% of subjects considered that they were at risk of lung cancer. This was lower in ex-smokers than in current smokers. Conclusions. There is high willingness for lung cancer screening and surgical treatment. There is underrecognition of risk among ex-smokers. This misperception could be a barrier to a successful screening or case-finding programme in Australia.
Objective . Talc pleurodesis is a common procedure performed to treat complications related to lung cancer. The purpose of our study was to characterize any thoracic nodal findings on FDG PET/CT associated with prior talc pleurodesis. Materials and Methods . The electronic medical record identified 44 patients who underwent PET/CT between January 2006 and December 2010 and had a history of talc pleurodesis. For each exam, we evaluated the distribution pattern, size, and attenuation of intrathoracic lymph nodes and the associated standardized uptake value. Results . High-attenuation intrathoracic lymph nodes were noted in 11 patients (25%), and all had corresponding increased FDG uptake (range 2–9 mm). Involved nodal groups were anterior peridiaphragmatic (100%), paracardiac (45%), internal mammary (25%), and peri-IVC (18%) nodal stations. Seven of the 11 patients (63%) had involvement of multiple lymph nodal groups. Mean longitudinal PET/CT and standalone CT followups of 15 ± 11 months showed persistence of both high-attenuation and increased uptake at these sites, without increase in nodal size suggesting metastatic disease involvement. Conclusions . FDG avid, high-attenuation lymph nodes along the lymphatic drainage pathway for parietal pleura are a relatively common finding following talc pleurodesis and should not be mistaken for nodal metastases during the evaluation of patients with history of lung cancer.
Background. Recent evidence showed that Helicobacter pylori seropositivity is a risk factor for gastric and several other cancers. However, evidence on H. pylori infection and risk of lung cancer has been controversial, with a limited number of underpowered studies. We therefore examined the association between H. pylori infection and risk of lung cancer. Methods. A comprehensive literature search was performed using PubMed, EMBASE (until October 2012) for studies investigating an association between Helicobacter pylori (H. pylori) infection and risk of lung cancer. Pooled odds ratio (OR) was calculated using random-effects model. Subgroup and sensitivity analysis were also done. Results. A total of seven studies (6 case-control and 1 cohort study) were included for the analysis. There was a significant heterogeneity among the studies, but no publication bias was observed. We found that H. pylori infection was associated with significantly increased risk of lung cancer (pooled OR, 2.29 (95% CI, 1.34–3.91) P=0.01). Conclusions. Our meta-analysis suggests a significant increased risk of lung cancer in patients with H. pylori infection. Further research is needed to confirm these findings and to identify the underlying biological mechanisms.
In recent years, major strides in cancer research have made it possible to select personalized chemotherapy recommendations based on an individual patient's tumor biology. The prognostic and/or predictive ability of biomarkers seeks to tailor the use of targeted chemotherapy and can result in improved clinical outcomes with reduced toxicity. A proliferation of new technology and pharmacotherapeutics in the setting of current FDA Clinical Laboratory Improvement Amendment (CLIA) standards has resulted in a recent surge in direct-to-physician biomarker tests. However, in the absence of clinical validation, there is the concern that the biomarkers may be utilized prematurely, resulting in improper chemotherapy selection and patient harm. Thymidylate synthase (TS) has been marketed as a predictive biomarker for the use of pemetrexed in NSCLC. We will examine the evidence behind the use of TS as a predictive biomarker to predict response to pemetrexed in NSCLC. At this time, the evidence does not currently support using TS assays to guide chemotherapy selection outside of a clinical research protocol.
