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Background: Targeted therapies for advanced non-small cell lung cancer (NSCLC) with oncogenic drivers have caused a paradigm shift in care. Biomarker testing is needed to assess eligibility for these therapies. Pulmonologists often perform bronchoscopy, providing tissue for both pathologic diagnosis and biomarker analysis. We performed this survey to define the existing knowledge and practices regarding the pulmonologists' role in biomarker testing for advanced NSCLC., Research Question: What is the current knowledge and practice of pulmonologists regarding biomarker testing and targeted therapies in advanced NSCLC?, Study Design and Methods: This cross-sectional study was performed using an electronic survey of a random sample of 7,238 pulmonologists. Questions focused on diagnostic steps and biomarker analyses for NSCLC., Results: A total of 453 pulmonologists responded. Respondents vary by reported lung cancer patient volume, ranging from 51% evaluating one to four new cases per month to 19% evaluating > 10 cases per month. Interventional training, academic practice setting, and higher volume of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) were associated with increased knowledge of practice guidelines for the number of recommended passes during EBUS-TBNA (P < .05). Academic pulmonologists more commonly performed or referred for EBUS-TBNA than community pulmonologists (96% and 83%, respectively; P < .0005). Higher testing rates were associated with interventional training, academic setting, and the presence of an institutional policy, whereas lower testing rates were associated with general pulmonologists, practice in community settings, and lack of a guiding institutional policy (P < .05)., Interpretation: Substantial differences among pulmonologists' evaluation of advanced NSCLC, variation in knowledge of available biomarkers and the importance of targeted therapies, and differences in institutional coordination likely lead to underutilization of biomarker testing. Interventional training appears to drive improved knowledge and practice for biomarker testing more than practice setting. Improvements are needed in tissue acquisition and interdisciplinary coordination to ensure universal and comprehensive testing for eligible patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor., Methods: We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV., Results: Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively., Conclusions: A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Patients with non-small-cell lung cancer, including squamous-cell lung cancer (SqCLC), typically present at an advanced stage. The current treatment landscape, which includes chemotherapy, radiotherapy, surgery, immunotherapy, and targeted agents, is rapidly evolving, including for patients with SqCLC. Prompt molecular and immune biomarker testing can serve to guide optimal treatment choices, and immune biomarker testing is becoming more important for this patient population. In this review we provide an overview of current and emerging practices and technologies for molecular and immune biomarker testing in advanced non-small-cell lung cancer, with a focus on SqCLC., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The optimal extent of lung resection and lymph node (LN) assessment for surgical treatment of clinical stage T1aN0M0 typical carcinoid tumors is unclear. Using a cohort including only these patients, we aimed to determine the impact of extent of lung resection and LN assessment on overall survival., Methods: Patients undergoing lobectomy or sublobar resection for clinical stage T1aN0M0 intraparenchymal typical carcinoid tumor were identified in the National Cancer Data Base from 1998 to 2012. Kaplan-Meier analysis was used to determine overall survival. A multivariable Cox proportional hazards model was used to determine independent predictors of mortality., Results: Of 1,495 patients, 536 (35.9%) had sublobar resection (wedge resection, n = 429; segmentectomy, n = 91) and 959 (64.2%) had lobectomy. There were 366 patients (24.5%) with no LN assessment. As tumor size increased, sublobar resection decreased and LN assessment increased. Overall, 60 patients (4.0%) were upstaged. Fifty-two patients were upstaged because of LN metastases (40 pN1, 11 pN2, and 1 pN3). The 5-year overall survival rate was 87%. It was 88% for lobectomy versus 87% for sublobar resection (p = 0.3), 65% for LN upstaging versus 89% for patients without LN upstaging, and 86% for patients with no LN assessment (p = 0.002). Independent predictors of mortality included LN upstaging, age, male sex, and Charlson comorbidity index., Conclusions: For patients with clinical stage T1aN0M0 typical carcinoid, sublobar resection results in similar overall survival compared with lobectomy. However, regardless of resection type, LN assessment is important to identify LN upstaging, the strongest independent predictor of overall mortality., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas, including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for NSCLC, SCLC, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: This phase I/II trial was designed to determine the maximally tolerated dose of thoracic radiotherapy as part of a combined modality approach. This report includes the long-term outcomes of patients treated on this study. The phase II portion was never completed, as RTOG-0617 opened before it was concluded., Methods: In this study, the maximally tolerated dose was defined as 74 Gy of radiation in 37 fractions. Twenty-five patients with unresectable NSCLC were treated with 2-Gy daily fractions and concurrent weekly carboplatin and paclitaxel. Of these patients, 20 had stage III disease and five had stage I or II disease., Results: Patients were followed until death or for a minimum of 5 years in the case of survivors. The median and 5-year survivals were 42.5 months and 20% for all patients, 52.9 months and 40% in patients with stages I or II disease, and 39.8 months and 15% in patients with stage III disease., Conclusions: The median survival of the stage III patients was quite favorable. We believe that this may have been due to a robust central review program of radiotherapy plans before treatment, ensuring compliance with protocol guidelines along with very low exposure of the heart to radiotherapy. Further improvements in 5-year survival will likely require research on both systemic therapy and thoracic radiotherapy. Potential therapeutic modalities that may aid in these efforts include immunotherapy, targeted therapy, improved imaging, adaptive radiotherapy, simultaneous integrated boost techniques, novel dose fractionation regimens, and charged particle therapy., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Although preoperative chemotherapy (cisplatin-etoposide) and radiotherapy, followed by surgical resection, is considered a standard of care for superior sulcus cancers, treatment is rigorous and relapse limits long-term survival. The Southwest Oncology Group-Intergroup Trial S0220 was designed to incorporate an active systemic agent, docetaxel, as consolidation therapy., Methods: Patients with histologically proven and radiologically defined T3 to 4, N0 to 1, M0 superior sulcus non-small cell lung cancer underwent induction therapy with cisplatin-etoposide, concurrently with thoracic radiotherapy at 45 Gy. Nonprogressing patients underwent surgical resection within 7 weeks. Consolidation consisted of docetaxel every 3 weeks for 3 doses. The accrual goal was 45 eligible patients. The primary objective was feasibility., Results: Of 46 patients registered, 44 were eligible and assessable; 38 (86%) completed induction, 29 (66%) underwent surgical resection, and 20 (45% of eligible, 69% surgical, and 91% of those initiating consolidation therapy) completed consolidation docetaxel; 28 of 29 (97%) underwent a complete (R0) resection; 2 (7%) died of adult respiratory distress syndrome. In resected patients, 21 of 29 (72%) had a pathologic complete or nearly complete response. The known site of first recurrence was local in 2, local-systemic in 1, and systemic in 10, with 7 in the brain only. The 3-year progression-free survival was 56%, and 3-year overall survival was 61%., Conclusions: Although trimodality therapy provides excellent R0 and local control, only 66% of patients underwent surgical resection and only 45% completed the treatment regimen. Even in this subset, distant recurrence continues to be a major problem, particularly brain-only relapse. Future strategies to improve treatment outcomes in this patient population must increase the effectiveness of systemic therapy and reduce the incidence of brain-only metastases., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Small cell lung cancer (SCLC) is a lethal disease for which there have been only small advances in diagnosis and treatment in the past decade. Our goal was to revise the evidence-based guidelines on staging and best available treatment options., Methods: A comprehensive literature search covering 2004 to 2011 was conducted in MEDLINE, Embase, and five Cochrane databases using SCLC terms. This was cross-checked with the authors' own literature searches and knowledge of the literature. Results were limited to research in humans and articles written in English., Results: The staging classification should include both the old Veterans Administration staging classification of limited stage (LS) and extensive stage (ES), as well as the new seventh edition American Joint Committee on Cancer/International Union Against Cancer staging by TNM. The use of PET scanning is likely to improve the accuracy of staging. Surgery is indicated for carefully selected stage I SCLC. LS disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle 1 or 2 of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. ES disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in those individuals with both LS and ES disease who achieve a complete or partial response to initial therapy. To date, no molecularly targeted therapy agent has demonstrated proven efficacy against SCLC., Conclusion: Evidence-based guidelines are provided for the staging and treatment of SCLC. LS-SCLC is treated with curative intent with 20% to 25% 5-year survival. ES-SCLC is initially responsive to standard treatment, but almost always relapses, with virtually no patients surviving for 5 years. Targeted therapies have no proven efficacy against SCLC.

Background: In an effort to evaluate the single agent activity of temsirolimus in previously untreated non-small-cell lung cancer, the North Central Cancer Treatment Group undertook a frontline "window-of-opportunity" study., Methods: Patients received 25 mg of temsirolimus administered intravenously as a weekly 30 minute infusion, on a 4-week cycle. Based on a two-stage Fleming design, the treatment would be promising if at least four of the first 25 evaluable patients in stage I or at least six of the 50 evaluable patients at the end of stage II have a confirmed response. Fresh tumor biopsies were obtained to evaluate predictive markers of temsirolimus activity., Results: A total of 55 patients were enrolled with 52 patients being evaluable. The median age was 64 years. Adverse events (grade 3/4) occurring in 33 patients included dyspnea (12%), fatigue (10%), hyperglycemia (8%), hypoxia (8%), nausea (8%), and rash/desquamation (6%). The clinical benefit rate was 35% with four patients achieving a confirmed partial response and 14 patients with stable disease for 8 weeks or more. The 24-week progression-free survival rate was 25%. Median progression-free survival and overall survival were 2.3 and 6.6 months, respectively. Expression of p70s6 kinase, phospho-p70s6 kinase, Akt, phospho-Akt, and phosphatase and tensin homolog mutation did not correlate with clinical outcome., Conclusions: Temsirolimus given as a single agent in frontline therapy in patients with non-small-cell lung cancer was tolerable and demonstrated clinical benefit but did not meet the primary objective in this study. Patient selection will be needed to enhance the efficacy.

In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history, but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric CT scan analysis., Methods: Sixty-four cases of lung cancer were identified from a prospective cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial. Each case was matched to six control subjects for age, sex, and smoking history. Quantitative CT scan analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects., Results: Decreased FEV(1) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 (95% CI, 1.00-1.32; P = .046) and 1.29 (95% CI, 1.02-1.62; P = .031), respectively. The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 (95% CI, 0.816-1.329; P = .743). Additionally, there was no significant association between severe emphysema and lung cancer with OR of 1.57 (95% CI, 0.73-3.37)., Conclusions: We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic evidence of emphysema quantitation methodology, or absence of any relationship between emphysema and lung cancer risk.

Background: Although no study has prospectively documented the rate at which lung cancers grow, many have assumed exponential growth. The purpose of this study was to document the growth of lung cancers detected in high-risk participants receiving annual screening chest CT scans., Methods: Eighteen lung cancers were evaluated by at least four serial CT scans (4 men, 14 women; age range, 53 to 79 years; mean age, 66 years). CT scans were retrospectively reviewed for appearance, size, and volume (volume [v] = pi/6[ab(2)]). Growth curves (x = time [in days]; y = volume [cubic millimeters]) were plotted and subcategorized by histology, CT scan attenuation, stage, survival, and initial size., Results: Inclusion criteria favored smaller, less aggressive cancers. Growth curves varied, even when subcategorized by histology, CT scan attenuation, stage, survival, or initial size. Cancers associated with higher stages, mortality, or recurrence showed fairly steady growth or accelerated growth compared with earlier growth, although these growth patterns also were seen in lesser-stage lung cancers. Most lung cancers enlarged at fairly steady increments, but several demonstrated fairly flat growth curves, and others demonstrated periods of accelerated growth., Conclusions: This study is the first to plot individual lung cancer growth curves. Although parameters favored smaller, less aggressive cancers in women, it showed that lung cancers are not limited to exponential growth. Tumor size at one point or growth between two points did not appear to predict future growth. Studies and equations assuming exponential growth may potentially misrepresent an indeterminate nodule or the aggressiveness of a lung cancer.

Background: Malignant pleural mesothelioma (MPM) is a primary malignancy characterized by local invasion of the pleura and metastasis. Despite advances in computed tomography (CT) and magnetic resonance imaging (MRI), accurately staging patients remains challenging. Recent studies have examined the use of integrated CT-positron emission tomography (PET) for staging patients., Materials and Methods: Mayo Clinic databases were queried to identify cases with a histologic diagnosis of MPM from 2000 to 2006. Inclusion criteria were a diagnosis of MPM, an available CT scan, and an initial staging integrated CT-PET scan. A total of 35 patients were identified who met the inclusion criteria. Computed tomography and integrated CT-PET scans were reviewed by experienced radiologists. Laboratory parameters were reviewed. The Mayo Clinic tumor registry and Social Security database were queried for survival data in patients in which no follow-up was available., Results: Findings on integrated CT-PET excluded 14 of 35 patients from surgical intervention. Extrapleural pneumonectomies (EPPs) were performed in 8 patients, and partial pleurectomies were performed in 2 patients. Upstaging from integrated CT-PET occurred in 70% of the patients when surgical pathology was available, 2 cases to an inoperable stage. Although not statistically significant, median survival was 20 months for patients undergoing an EPP and 12 months for patients excluded from surgical intervention by integrated CT-PET., Conclusion: Malignant pleural mesothelioma is a difficult disease to accurately stage. The most common reason for upstaging in our series was an increase in T (tumor; tumor-node-metastasis staging system) disease. Our data suggest that integrated CT-PET is excellent for detecting nodal and distant metastases. However, the ability of this imaging modality to correctly stage locoregional disease is not superior to the combination of CT and MRI as reported in the literature.

Introduction: We evaluated the role of glutathione-related genotypes on overall survival, time to progression, adverse events, and quality of life (QOL) in stage IIIB/IV non-small cell lung cancer patients who were stable or responding from initial treatment with platinum-based chemotherapy and subsequently randomized to receive daily oral carboxyaminoimidazole or a placebo., Methods: Of the 186 total patients, 113 had initial treatment with platinum therapy and DNA samples of whom 46 also had QOL data. These samples were analyzed using six polymorphic DNA markers that encode five important enzymes in the glutathione metabolic pathway. Patient QOL was assessed using the Functional Assessment of Cancer Therapy-Lung and the UNISCALE QOL questionnaires. A clinically significant decline in QOL was defined as a 10% decrease from baseline to week-8. Multivariate analyses were used to evaluate the association of the genotypes on the four endpoints., Results: Patients carrying a GCLC 77 genotype had a worse overall survival (hazard ratio (HR) = 1.5, p = 0.05). Patients carrying the GPX1-CC genotype had a clinically significant decline in the UNISCALE (odds ratio (OR): 7.5; p = 0.04), total Functional Assessment of Cancer Therapy-Lung score (OR: 11.0; p = 0.04), physical (OR: 7.1; p = 0.03), functional (OR: 5.2; p = 0.04), and emotional well-being constructs (OR: 23.8; p = 0.01)., Conclusions: Genotypes of glutathione-related enzymes, especially GCLC, may be used as host factors in predicting patients' survival after platinum-based chemotherapy. GPX1 may be an inherited factor in predicting patients' QOL. Further investigation to define and measure the effects of these genes in chemotherapeutic regimens, drug toxicities, disease progression, and QOL are critical.

Objective: To develop evidence-based guidelines on best available treatment options for patients with stage IIIB non-small cell lung cancer (NSCLC)., Methods: A review was conducted of published English-language (abstract or full text) phase II or phase III trials and guidelines from other organizations that address management of the various categories of stage IIIB disease. The literature search was provided by the Duke University Center for Clinical Health Policy Research and supplemented by any additional studies known by the authors., Results: Surgery may be indicated for carefully selected patients with T4N0-1M0. Patients with N3 nodal involvement are not considered to be surgical candidates. For individuals with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemoradiotherapy results in better survival than radiotherapy (RT) alone. Concurrent chemoradiotherapy seems to be associated with improved survival compared with sequential chemoradiotherapy. Multiple daily fractions of RT when combined with chemotherapy have not been shown to result in improved survival compared with standard once-daily RT combined with chemotherapy. The optimal chemotherapy agents and the number of cycles of treatment to combine with RT are uncertain., Conclusion: Prospective trials are needed to answer important questions, such as the role of induction therapy in patients with potentially resectable stage IIIB disease. Future trials are needed to answer the questions of optimal chemotherapy agents and radiation fractionation schedule. The role of targeted novel agents in combination with chemoradiotherapy is just starting to be investigated.

Background: Lung cancer typically exhibits symptoms only after the disease has spread, making cure unlikely. Because early-stage disease can be successfully treated, a screening technique that can detect lung cancer before it has spread might be useful in decreasing lung cancer mortality., Objectives: In this article, we review the evidence for and against screening for lung cancer with low-dose CT and offer recommendations regarding its usefulness for asymptomatic patients with no history of cancer., Results: Studies of lung cancer screening with chest radiograph and sputum cytology have failed to demonstrate that screening lowers lung cancer mortality rates. Published studies of newer screening technologies such as low-dose CT and "biomarker" screening report primarily on lung cancer detection rates and do not present sufficient data to determine whether the newer technologies will benefit or harm. Although researchers are conducting randomized trials of low-dose CT, results will not be available for several years. In the meantime, cost-effectiveness analyses and studies of nodule growth are considering practical questions but producing inconsistent findings., Conclusions: For high-risk populations, no screening modality has been shown to alter mortality outcomes. We recommend that individuals undergo screening only when it is administered as a component of a well-designed clinical trial with appropriate human subjects' protections.

Background: The clinical significance of multiple carcinoid tumorlets in surgical lung specimens has not been systematically analyzed. We reviewed our experience to determine the range of clinical circumstances associated with this finding., Methods: We reviewed clinical records, available imaging, and pathology materials from patients evaluated at Mayo Clinic Rochester (from 1987 to 2000) with two or more carcinoid tumors or tumorlets in lung specimens., Results: Twenty-eight of 294 patients with a diagnosis of carcinoid tumor or tumorlet had two or more lesions. Twenty-six patients (93%) were women; mean age was 65 years. Patients were categorized into three groups: multiple nodules (n = 17), solitary lung nodules on preoperative imaging (n = 7), and airflow limitation (n = 4). Approximately half of patients with multiple nodules had respiratory complaints; two patients had Cushing syndrome. Ten patients (58.8%) were suspected of having pulmonary metastases, including 7 patients with previously diagnosed malignancies. Intrathoracic lymph node metastases were present in three patients, none of whom had recurrent disease. One patient had a carcinoid tumor resected 8 years later. Extrathoracic metastases developed in another patient 3 years after presentation, and the patient was alive with disease 2 years later. Only one patient with airflow limitation had a syndrome resembling diffuse idiopathic pulmonary neuroendocrine cell hyperplasia., Conclusions: Our series represents the largest compilation of multiple carcinoid tumors or tumorlets. Our analysis reveals that multiple carcinoid tumors or tumorlets occur most commonly in patients with multiple nodules resembling metastatic disease. Significant airflow limitation is rare. Long-term survival is excellent, although patients have persistent disease.

Background: Fluorodeoxyglucose positron emission tomography (FDG-PET) is sensitive for detection of neoplastic solitary pulmonary nodules but may have decreased sensitivity for detection of carcinoid tumors. Our purpose was to determine the sensitivity of FDG-PET to detect pulmonary carcinoid tumors., Methods: We performed a retrospective review of our institutional results regarding FDG-PET in the setting of thoracic carcinoid neoplasms. We identified 16 patients with a pathologic diagnosis of bronchial carcinoid who had an antecedent FDG-PET (from 2000 to 2004). All patients but one presented with pulmonary nodule(s)., Results: Sixteen patients had a diagnosis of carcinoid tumor, typical in 11 patients and atypical in 5 patients. The mean greatest pathologic dimension was 2.08 cm (range, 1.0 to 8.3 cm). Overall positron emission tomography (PET) sensitivity was 75% (12 true-positive and 4 false-negative results). The mean (+/- SD) size of carcinoids with false-negative PET results was not significantly different from carcinoids with true-positive results (1.6 +/- 0.81 cm and 2.35 +/- 1.87 cm, p = 0.54). Fifteen of 16 patients were staged pathologically, and positive nodes were found in 2 of these patients. PET lymph node staging agreed with pathologic staging in one stage 4 patient with positive lymph nodes and distant metastasis, but PET results were false negative in the other patient who had N2 with micrometastatic disease; stage IIIA., Conclusions: FDG-PET imaging is useful for evaluation of typical and atypical thoracic carcinoid tumors. Although overall PET sensitivity for detection of carcinoid tumors is somewhat reduced as compared to non-small cell lung cancer, it is much higher than prior reports suggest.

In the United States, lung cancer kills more men and woman than the next three most common cancers combined. Unfortunately, the long-term outcome of lung cancer is still dismal with a 5-year survival rate of 15%. However, significant improvements in median survival times and 1-year and 2-year survival rates have been achieved in the last decade. This progress has been accomplished not only because of better surgical techniques but also because of the use of platinum-based regimens with newer chemotherapy agents and, more recently, targeted therapy. The role of chemotherapy as an integral part of the treatment of lung cancer has expanded significantly, particularly in the last few years with the proven benefit of adjuvant chemotherapy. For advanced stage non-small cell lung cancer (NSCLC), chemotherapy prolongs survival and improves quality of life in patients with good performance status, and appears to provide symptomatic improvement in patients with decreased performance status. Platinum-based doublet chemotherapy regimens are now the standard of care in patients with advanced stage NSCLC, and non-platinum-based combination therapies are reasonable alternatives in certain populations. The combination of the vascular endothelial growth factor inhibitor bevacizumab and chemotherapy has proven to prolong survival. As agents such as monoclonal antibodies, small molecules inhibitors of tyrosine kinase, and direct inhibitors of proteins involved in lung cancer proliferation are being developed and tested, we are optimistic that these agents will result in improvement in the survival and quality of life of lung cancer patients.

Study Objectives: To determine the relative sensitivity and specificity of cytology and fluorescence in situ hybridization (FISH) for the detection of lung cancer in bronchoscopically obtained specimens., Design: Cytology and FISH were performed on brushing and washing specimens obtained from patients undergoing bronchoscopy for suspected lung cancer. FISH utilized the LAVysion probe set (Abbott Molecular; Des Plaines, IL), which contains locus-specific probes to 5p15, 7p12 (EGFR), 8q24 (C-MYC), and a centromeric probe to chromosome 6., Setting: Single-center, academic, tertiary medical center., Participants: One hundred thirty-seven patients referred for bronchoscopy for suspicion of lung cancer., Interventions: Cytology and FISH were performed on bronchoscopic brushings and washings., Measurements and Results: One hundred thirty-seven patients undergoing bronchoscopy had pathology, FISH, and cytology results. FISH and cytology were performed on 123 washing and 78 brushing specimens. Sensitivities of FISH and cytology were 71% and 51% (p = 0.007), respectively, for brushing specimens, and 49% and 44% (p = 0.541) for washing specimens. When FISH and cytology results were combined, sensitivities were 75% and 61%, respectively, for brushing and washing specimens, which was significantly better (p < 0.001) than cytology alone. Specificities of FISH and cytology for patients with negative findings at the time of initial bronchoscopy were 83% and 100% (p = 0.125), respectively, for brushing specimens, and 95% and 100% (p = 0.500) for washing specimens., Conclusions: These findings show that FISH is significantly more sensitive than conventional cytology for detecting lung cancer in bronchial brushing specimens; when combined with cytology, FISH can improve the diagnostic sensitivity of detecting malignancy in bronchial brushing and washing specimens.

Background: A blood test for non-small cell lung cancer (NSCLC) may be a valuable tool for use in a comprehensive lung cancer screening strategy. Here we report the potential of autoantibody profiling to detect early-stage and occult NSCLC., Methods: T7-phage NSCLC cDNA libraries were screened with patient plasma to identify phage-expressed proteins recognized by tumor-associated antibodies. Two hundred twelve immunogenic phage-expressed proteins, identified from 4000 clones, were statistically ranked for their individual reactivity with 23 stage I cancer patient and 23 risk-matched control samples. All 46 samples were used as a training set to define a combination of markers that were best able to distinguish patient from control samples; this set of classifiers was then examined using leave-one-out cross-validation. Markers were then used to predict probability of disease in 102 samples from the Mayo Clinic CT Screening Trial (six prevalence cancer samples, 40 drawn 1 to 5 years before diagnosis, and 56 risk-matched controls)., Results: Measurements of the five most predictive antibody markers in 46 cases and controls were combined in a logistic regression model that yielded area under the receiver operating characteristics curve of 0.99; leave-one-out validation achieved 91.3% sensitivity and 91.3% specificity. In testing this marker set with samples from the Mayo Clinic Lung Screening Trial, we correctly predicted six of six prevalence cancers, 32 of 40 cancers from samples drawn 1 to 5 years before radiographic detection on incidence screening, and 49 of 56 risk-matched controls., Conclusions: Antibody profiling may be a useful tool for early detection of NSCLC.

Introduction: This pooled analysis was performed to examine the impact of pretreatment factors on severe (grade 3 or higher) adverse events (AE) in patients with advanced stage non-small cell lung cancer (NSCLC)., Methods: A pooled data set of 1053 participants from nine North Central Cancer Treatment Group clinical trials was used. Age, gender, performance status, tumor stage, body mass index, serum creatinine levels, hemoglobin levels, white blood cell counts, and platelet counts were evaluated univariately and multivariately using logistic regression. The magnitude of the effects of the pretreatment factors after adjusting for type of chemotherapy agent (platinum versus no platinum) was explored in the final multivariate model., Results: Women and older participants had a significantly greater risk for experiencing severe hematologic and non-hematologic AE. Participants with performance status >0 had an increased risk for severe non-hematologic AE. For every one unit (10/L) increase in pretreatment white blood cell count, there was an 11% reduction in the odds of experiencing a severe hematologic AE. The magnitude of these effects on the end points remained similar after adjusting for type of chemotherapy agent., Conclusions: Pretreatment factors of gender, age, performance status, and hematologic parameters were significant predictors of severe AE among patients with advanced stage NSCLC. This suggests the need to control or adjust for factors that predispose patients to an increased risk of severe AE. These findings can aid in tailoring therapy to individual patients and in the proper design of future clinical trials.

Background: Lung cancer is the most common cause of cancer death in the world. Nonetheless, public policy organizations have consistently recommended against screening for lung cancer, with the result that screening is not widely practiced. The Como Conference was undertaken to consider the need for a change in the existing recommendations against screening., Purposes: The primary objective of the Como Conference was to consider whether there is sufficient scientific evidence to advise screening for lung cancer among asymptomatic individuals outside the context of a clinical trial. Methodological issues that are relevant to the proper interpretation of early detection trials were carefully considered. Advantages and problems associated with technological advances in CT scans and digital chest radiographs (CXRs) were fully explored. Economic issues relevant to screening were also considered., Recommendations: It is recommended that physicians assume responsibility for informing high-risk individuals regarding options for screening for lung cancer. Targeted high-risk individuals include middle-aged or elderly men and women who are current or former cigarette smokers of > 20 to 30 pack-years without serious medical comorbidities. It is recommended that such persons be informed that symptomatic lung cancer is usually advanced and incurable, while surgery for early lung cancer offers a far better chance of cure. They should also be informed about advances in imaging technology, as they relate to CT scans and CXRs., Conclusions: Whenever possible, high-risk individuals should be encouraged to enroll in ongoing trials. For subjects who, though eligible, do not have access to such trials, a process of shared decision-making between physicians and at-risk individuals is strongly recommended. After discussion of the existing state of knowledge, high-risk individuals should be made aware that it is reasonable for them to choose to undergo testing for lung cancer.

Background: Gender has been reported as a predictor for nonsmall cell lung cancer (NSCLC) survival. Most of the reports are limited to selected groups of patients. The magnitude of gender effect on NSCLC survival across disease stage, tumor histology, and therapies needs to be further characterized., Methods: A cohort of 4,618 patients diagnosed with NSCLC was prospectively enrolled and actively followed. Vital status of each patient was verified through multiple complementary sources. Cox proportional hazards models were developed to compare postdiagnosis survival between genders adjusting for age at diagnosis, tumor histology and grade, stage, pack-years smoked, and treatment received (resection, radiation, or chemotherapy)., Results: There were 2,724 men (59%) and 1,894 women (41%), with a median age at diagnosis of 68 years in men and 66 in women (p < 0.01). More men smoked and were heavier smokers than women. Adenocarcinoma was the most frequent histology in both genders. No difference was found in stage and treatment between genders. The estimated survival in men was 51% (95% CI: 49%, 53%) and 15% (95% CI: 12%, 17%) at one and five years, respectively, and in women was 60% (95% CI: 58%, 62%) and 19% (95% CI: 16%, 22%). Men were at a significantly increased risk of mortality compared to women following a diagnosis of NSCLC (adjusted relative risk: 1.20, 95% CI: 1.11, 1.30), particularly for patients with stage III/IV disease or adenocarcinoma., Conclusions: Male gender is confirmed to be an independent unfavorable prognostic indicator for NSCLC survival.

Stage IIIB includes patients with T4, any N, M0, and any T, N3, M0. Surgery may be indicated only for carefully selected T4N0M0 patients with or without neoadjuvant chemotherapy or chemoradiotherapy. Patients with N3 lymph node involvement are not considered as surgical candidates. For patients with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemotherapy and radiotherapy has resulted in better survival than treatment with radiotherapy alone. Multiple daily fractions of radiotherapy have not resulted in improved survival compared with standard fractionation once daily. Concurrent chemoradiotherapy appears to be associated with improved survival compared with sequential chemotherapy and radiotherapy. Treatment of stage IIIB due to malignant pleural effusion is addressed in the section that deals with stage IV disease.