Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology.

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. This study followed a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperformed existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heatmaps. The network was further tested using endobronchial biopsies from two data cohorts, containing normal to carcinoma in situ histology. It demonstrated a unique capability to differentiate carcinoma in situ lung squamous PMLs based on their progression status to invasive carcinoma. The network may have utility in stratifying PMLs for chemoprevention trials or more aggressive follow-up.

Aberrant epithelial polarity cues drive the development of precancerous airway lesions.

Molecular events that drive the development of precancerous lesions in the bronchial epithelium, which are precursors of lung squamous cell carcinoma (LUSC), are poorly understood. We demonstrate that disruption of epithelial cellular polarity, via the conditional deletion of the apical determinant Crumbs3 (Crb3), initiates and sustains precancerous airway pathology. The loss of Crb3 in adult luminal airway epithelium promotes the uncontrolled activation of the transcriptional regulators YAP and TAZ, which stimulate intrinsic signals that promote epithelial cell plasticity and paracrine signals that induce basal-like cell growth. We show that aberrant polarity and YAP/TAZ-regulated gene expression associates with human bronchial precancer pathology and disease progression. Analyses of YAP/TAZ-regulated genes further identified the ERBB receptor ligand Neuregulin-1 (NRG1) as a key transcriptional target and therapeutic targeting of ERBB receptors as a means of preventing and treating precancerous cell growth. Our observations offer important molecular insight into the etiology of LUSC and provides directions for potential interception strategies of lung cancer.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

The effects of high-dose calcitriol and individualized exercise on bone metabolism in breast cancer survivors on hormonal therapy: a phase II feasibility trial.

INTRODUCTION: Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. Both calcitriol and weight-bearing exercise improve bone metabolism for osteoporotic patients, but are unproven in a breast cancer population. We used a novel high-dose calcitriol regimen with an individualized exercise intervention to improve bone metabolism in breast cancer survivors. METHODS: We accrued 41 subjects to this open label, 2 × 2 factorial, randomized feasibility trial. Breast cancer survivors were randomized to receive the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise with progressive walking and resistance training, (3) both, or (4) a daily multivitamin (control condition) for 12 weeks. Primary outcomes included changes in biomarkers of bone formation, bone resorption, and the bone remodeling index, a composite measure of bone formation and resorption. Safety measures included clinical and biochemical adverse events. A main effect analysis was used for these endpoints. RESULTS: Hypercalcemia was limited to three grade I cases with no grade ≥ 2 cases. Among exercisers, 100% engaged in the prescribed aerobic training and 44.4% engaged in the prescribed resistance training. Calcitriol significantly improved bone formation (Cohen's d = 0.64; p < 0.01), resulting in a non-significant increase in the bone remodeling index (Cohen's d = 0.21; p = 31). Exercise failed to improve any of the bone biomarkers. CONCLUSIONS: Both calcitriol and exercise were shown to be feasible and well tolerated. Calcitriol significantly improved bone formation, resulting in a net increase of bone metabolism. Compliance with the exercise intervention was sub-optimal, which may have led to a lack of effect of exercise on bone metabolism.

Evaluation of a Dedicated Tobacco Cessation Support Service for Thoracic Cancer Center Patients.

CONTEXT: Cancer patients' continued tobacco use results in poorer therapeutic outcomes including decreased quality of life and survival. OBJECTIVE: To assess reach and impact of a free, opt-out, telephone-based tobacco cessation program for thoracic cancer center patients. DESIGN: Observational study. SETTING: Comprehensive Cancer Center in Western New York. PARTICIPANTS: Current or recent (within past 30 days) tobacco-using thoracic cancer center patients referred to a tobacco cessation support service between October 2010 and October 2012 at a Comprehensive Cancer Center (n = 942/1313 referrals were eligible for cessation support). INTERVENTION: A free, opt-out, telephone-based cessation service that was implemented as standard of care. Cessation specialists had patient-guided conversations that assessed readiness to quit; methods used in the past provided cessation strategies and worked to set up a quit date. There was an average of 35.9 days between referral and first contact. MAIN OUTCOME MEASURES: Program reach (referral and participation rates) and impact (as self-reported cessation outcomes measured twice after referral). RESULTS: Of 942 patients, 730 (77.5%) referred to and called by a tobacco cessation service participated in at least 1 cessation support call, of which 440 of 730 (60.3%) were called for follow-up and 89.5% (394/440) participated. In total, 20.2% (69/342) of current smokers at referral reported at least 7-day abstinence at follow-up. Among current smokers at referral and first contact, being married (odds ratio [OR] = 2.05; 95% confidence interval [CI], 1.01-4.18) and having a lower Eastern Cooperative Oncology Group (ECOG) performance score (OR = 4.05; 95% CI, 1.58-10.39) were associated with quitting at follow-up, after controlling for demographic, clinical, and health behavior characteristics. CONCLUSIONS: Our results demonstrate that 78% of thoracic cancer center patients, if contacted, participated at least once in this cessation support service; for current smokers at referral and first contact, being married and having a lower ECOG performance score were associated with self-reported quitting at follow-up. Other organizations may find our results useful while implementing a systematic way to identify tobacco-using patients as part of routine care and to improve available cessation support services.

Lung cancer screening, version 1.2015: featured updates to the NCCN guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide recommendations for selecting individuals for lung cancer screening, and for evaluation and follow-up of nodules found during screening, and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN Guidelines for Lung Cancer Screening, which include a revision to the recommendation from category 2B to 2A for one of the high-risk groups eligible for lung cancer screening. For low-dose CT of the lung, the recommended slice width was revised in the table on "Low-Dose Computed Tomography Acquisition, Storage, Interpretation, and Nodule Reporting."

Automated tobacco assessment and cessation support for cancer patients.

BACKGROUND: Tobacco assessment and cessation support are not routinely included in cancer care. An automated tobacco assessment and cessation program was developed to increase the delivery of tobacco cessation support for cancer patients. METHODS: A structured tobacco assessment was incorporated into the electronic health record at Roswell Park Cancer Institute to identify tobacco use in cancer patients at diagnosis and during follow-up. All patients who reported tobacco use within the past 30 days were automatically referred to a dedicated cessation program that provided cessation counseling. Data were analyzed for referral accuracy and interest in cessation support. RESULTS: Between October 2010 and December 2012, 11,868 patients were screened for tobacco use, and 2765 were identified as tobacco users and were referred to the cessation service. In referred patients, 1381 of those patients received only a mailed invitation to contact the cessation service, and 1384 received a mailing as well as telephone contact attempts from the cessation service. In the 1126 (81.4%) patients contacted by telephone, 51 (4.5%) reported no tobacco use within the past 30 days, 35 (3.1%) were medically unable to participate, and 30 (2.7%) declined participation. Of the 1381 patients who received only a mailed invitation, 16 (1.2%) contacted the cessation program for assistance. Three questions at initial consult and follow-up generated over 98% of referrals. Tobacco assessment frequency every 4 weeks delayed referral in < 1% of patients. CONCLUSIONS: An automated electronic health record-based tobacco assessment and cessation referral program can identify substantial numbers of smokers who are receptive to enrollment in a cessation support service.

Improving Guideline-Recommended Colorectal Cancer Screening in a Federally Qualified Health Center (FQHC): Implementing a Patient Navigation and Practice Facilitation Intervention to Promote Health Equity.

BACKGROUND: Colorectal cancer (CRC) screening is effective in the prevention and early detection of cancer. Implementing evidence-based screening guidelines remains a challenge, especially in Federally Qualified Health Centers (FQHCs), where current rates (43%) are lower than national goals (80%), and even lower in populations with limited English proficiency (LEP) who experience increased barriers to care related to systemic inequities. METHODS: This quality improvement (QI) initiative began in 2016, focused on utilizing patient navigation and practice facilitation to addressing systemic inequities and barriers to care to increase CRC screening rates at an urban FQHC, with two clinical locations (the intervention and control sites) serving a diverse population through culturally tailored education and navigation. RESULTS: Between August 2016 and December 2018, CRC screening rates increased significantly from 31% to 59% at the intervention site (p < 0.001), with the most notable change in patients with LEP. Since 2018 through December 2022, navigation and practice facilitation expanded to all clinics, and the overall CRC screening rates continued to increase from 43% to 50%, demonstrating the effectiveness of patient navigation to address systemic inequities. CONCLUSIONS: This multilevel intervention addressed structural inequities and barriers to care by implementing evidence-based guidelines into practice, and combining patient navigation and practice facilitation to successfully increase the CRC screening rates at this FQHC.

Smoking at diagnosis and survival in cancer patients.

The effect of smoking on survival in cancer patients is limited by the lack of structured prospective assessments of smoking at diagnosis. To assess the effect of smoking at diagnosis on survival, structured smoking assessments were obtained in a cohort of 5,185 cancer patients within 30 days of a cancer diagnosis between 1982 and 1998. Hazard ratios (HRs) or odds ratios were generated to analyze the effects of smoking at diagnosis on overall mortality (OM) and disease-specific mortality (DSM) in a patient cohort from 13 disease sites containing at least 100 patients in each disease site. With a minimum of 12 years of follow-up, current smoking increased OM risk versus recent quit (HR 1.17), former (HR 1.29) and never smokers (HR 1.38) in the overall cohort. Current smoking increased DSM risk versus former (HR 1.23) and never smokers (HR 1.18). In disease sites with proportionately large (>20%) recent quit cohorts (lung and head/neck), current smoking increased OM and DSM risks as compared with recent quit. Current smoking increased mortality risks in lung, head/neck, prostate and leukemia in men and breast, ovary, uterus and melanoma in women. Current smoking was not associated with any survival benefit in any disease site. Data using prospective structured smoking assessments demonstrate that current smoking increased long-term OM and DSM. Standardized smoking assessment at diagnosis is an important variable for evaluating outcomes in cancer patients.

Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort.

BACKGROUND: The objectives of this study were to evaluate survival among current smokers, former smokers, and never smokers who are diagnosed with non-small cell lung cancer (NSCLC). METHODS: The study included patients who participated in the National Comprehensive Cancer Network's NSCLC Database Project. Current, former, and never smokers were compared with respect to overall survival by fitting Cox regression models. RESULTS: Data from 4200 patients were examined, including 618 never smokers, 1483 current smokers, 380 former smokers who quit 1 to 12 months before diagnosis, and 1719 former smokers who quit >12 months before diagnosis. Among patients with stage I, II, and III disease, only never smokers had better survival than current smokers (hazard ratio, 0.47 [95% confidence interval, 0.26-0.85] vs 0.51 [95% confidence interval, 0.38-0.68], respectively). Among patients with stage IV disease, the impact of smoking depended on age: Among younger patients (aged ≤55 years), being a never smoker and a former smoker for ≥12 months increased survival. After age 85 years, smoking status did not have a significant impact on overall survival. CONCLUSIONS: Patients who were smoking at the time of diagnosis had worse survival compared with never smokers. Among younger patients with stage IV disease, current smokers also had worse survival compared with former smokers who quit >12 months before diagnosis. It is likely that tumor biology plays a major role in the differences observed; however, to improve survival, it is prudent to encourage all smokers to quit smoking if they are diagnosed with NSCLC.

Lung cancer screening update.

Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer.

Pretreatment weight status and weight loss among head and neck cancer patients receiving definitive concurrent chemoradiation therapy: implications for nutrition integrated treatment pathways.

PURPOSE: The purpose was to examine the effect of pretreatment weight status on loco-regional progression for patients with squamous cell carcinoma of the head and neck (SCCHN) after receiving definitive concurrent chemoradiation therapy (CCRT). METHODS: In an expanded cohort of 140 patients, we retrospectively reviewed weight status and loco-regional progression of SCCHN patients treated with CCRT between 2004 and 2010. RESULTS: Pretreatment ideal body weight percentage (IBW%) was statistically significantly different for patients with disease progression than for those without progression (p = 0.02) but was not an independent predictor of progression. Median pretreatment IBW% was 118 (72-193) for the progression-free group and was 101.5 (73-163) for the group with progression. Both groups suffered clinically severe weight loss of approximately 9 % from baseline to end treatment. CONCLUSIONS: Pretreatment weight status, a very crude indicator of nutrition status, may have prognostic value in patients with SCCHN undergoing definitive CCRT. Inadequate nutritional status in these patients has been associated with poor clinical outcomes and decreased quality of life. Based on this report and others, the best next steps include routine validated malnutrition screening and the testing of evidence-based nutrition care protocols with the goals of minimizing weight loss and improvement of quality of life.

Simultaneous Detection of Tumor Derived Exosomal Protein-MicroRNA Pairs with an Exo-PROS Biosensor for Cancer Diagnosis.

Tumor derived exosomes (TEXs) have emerged as promising biomarkers for cancer liquid biopsy. Conventional methods (such as ELISA and qRT-PCR) and emerging biosensing technologies mainly detect a single type of exosomal biomarker due to the distinct properties of different biomolecules. Sensitive detection of two different types of TEX biomarkers, i.e., protein and microRNA combined biomarkers, may greatly improve cancer diagnostic accuracy. We developed an exosome protein microRNA one-stop (Exo-PROS) biosensor that not only selectively captured TEXs but also enabled in situ, simultaneous detection of TEX protein-microRNA pairs via a surface plasmon resonance mechanism. Exo-PROS assay is a fast, reliable, low sample consumption, and user-friendly test. With a total of 175 cancer patients and normal controls, we demonstrated that TEX protein-microRNA pairs measured by Exo-PROS assay detected lung cancer and breast cancer with 99% and 96% accuracy, respectively. Exo-PROS assay also showed superior diagnostic performance to conventional ELISA and qRT-PCR methods. Our results demonstrated that Exo-PROS assay is a potent liquid biopsy assay for cancer diagnosis.

The effect of various vitamin D supplementation regimens in breast cancer patients.

Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects (bone loss, arthralgia, and falls). The first aim of this study was to assess vitamin D status, determined by 25-OH vitamin D levels, among women diagnosed with breast cancer according to demographic/clinical variables and bone mineral density (BMD). The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels. This retrospective study included 224 women diagnosed with stage 0-III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center. Total 25-OH vitamin D levels (D(2) + D(3)) were determined at baseline for all participants. Vitamin D deficiency was defined as a 25-OH vitamin D level < 20 ng/ml, insufficiency as 20-31 ng/ml, and sufficiency as ≥32 ng/ml. BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment. Based on the participants' baseline levels, they received either no supplementation, low-dose supplementation (1,000 IU/day), or high-dose supplementation (≥50,000 IU/week), and 25-OH vitamin D was reassessed in the following 8-16 weeks. Approximately 66.5% had deficient/insufficient vitamin D levels at baseline. Deficiency/insufficiency was more common among non-Caucasians, women with later-stage disease, and those who had previously received radiation therapy (P < 0.05). Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD (P = 0.03). Compared to the no-supplementation group, weekly high-dose supplementation significantly increased 25-OH vitamin D levels, while daily low-dose supplementation did not significantly increase levels. Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine. Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients.

Ultrafast Detection of Exosomal RNAs via Cationic Lipoplex Nanoparticles in a Micromixer Biochip for Cancer Diagnosis.

Exosomes are cell-derived, nanosized extracellular vesicles for intercellular communication. Exosomal RNAs have been shown as one type of promising cancer liquid biopsy biomarkers. Conventional methods to characterize exosomal RNAs such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) are limited by low sensitivity, large sample consumption, time-consuming process, and high cost. Many technologies have been developed to overcome these challenges; however, many hours are still required to complete the assays, especially when exosome lysis and RNA extraction are required. We have developed a microfluidic cationic lipoplex nanoparticles (mCLN) assay that utilizes a micromixer biochip to allow for the effective capture of exosomes by cationic lipoplex nanoparticles and thus enables ultrafast and sensitive exosomal RNA detection for cancer diagnosis. The sensing performance and diagnostic performance of the mCLN assay were investigated using non-small cell lung cancer (NSCLC) as the disease model and exosomal microRNA-21 and TTF-1 mRNA as the biomarkers. The limits of detection of the mCLN assay were 2.06 × 109 and 3.71 × 109 exosomes/mL for microRNA-21 and TTF-1 mRNA, respectively, indicating that the mCLN assay may require as low as 1 µL of serum for exosomal RNA detection. The mCLN assay successfully distinguished NSCLC from normal controls by detecting significantly higher microRNA-21 and TTF-1 mRNA levels in exosomes from both NSCLC patient serum samples and A549 NSCLC cells than those from normal controls and BEAS-2B normal bronchial epithelial cells. Compared with conventional qRT-PCR assay, the mCLN assay showed a higher diagnostic accuracy in lung cancer, required less sample volume (30 vs 100 µL), and consumed much less time (10 min vs 4 h).

Elevated T cell repertoire diversity is associated with progression of lung squamous cell premalignant lesions.

OBJECTIVE: The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features. METHODS: Endobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and PML outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (ie, found in one patient only) and public (ie, found in two or more patients) TCRs was quantified, and the CDR3 sequences were compared with those found in curated databases with known antigen specificities. RESULTS: We detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T cell mediated immune activation (p=4e-4) associated with PML outcome. Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3396 (8.6%) found in more than one sample and 1057 (2.7%) found in two or more patients (ie, public); however, when compared with a public database of CDR3 sequences, 4543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among public TCRs (p<0.001). CONCLUSIONS: Decreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.

The effect of secondhand smoke exposure on the association between active cigarette smoking and colorectal cancer.

BACKGROUND: Studies published prior to 1980 failed to find an association between smoking and colorectal cancer, while subsequent studies reported an association after accounting for a three to four decade initiation period. The aims of this study were to determine the effect of accounting for secondhand smoke (SHS) exposure on the association between smoking and colorectal cancer and to determine the association between SHS and colorectal cancer. METHODS: Approximately 1,200 colorectal cancer cases treated at Roswell Park Cancer Institute between 1982 and 1998 were matched to 2,400 malignancy-free controls. The effect of accounting for SHS exposure was determined by comparing the odds ratios (OR) for each smoking variable in the overall sample and then for those who reported no current SHS exposure. RESULTS: A small, significant increase in colorectal cancer odds was noted for heavy, long-term smoking males when not accounting for SHS exposure (>45 PY: OR = 1.34; 95% CI 1.04-1.72). OR increased when the analyses were restricted to individuals reporting no current SHS exposure (>45 PY: OR = 2.40; 95% CI 1.36-4.23). CONCLUSIONS: Accounting for SHS exposure resulted in a substantial increase in the odds of colorectal cancer for all smoking variables in this study. Future studies should account for SHS exposure when examining the association between smoking and colorectal cancer.

Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers: a case-control study.

BACKGROUND: Inverse associations between cruciferous vegetable intake and lung cancer risk have been consistently reported. However, associations within smoking status subgroups have not been consistently addressed. METHODS: We conducted a hospital-based case-control study with lung cancer cases and controls matched on smoking status, and further adjusted for smoking status, duration, and intensity in the multivariate models. A total of 948 cases and 1743 controls were included in the analysis. RESULTS: Inverse linear trends were observed between intake of fruits, total vegetables, and cruciferous vegetables and risk of lung cancer (ORs ranged from 0.53-0.70, with P for trend < 0.05). Interestingly, significant associations were observed for intake of fruits and total vegetables with lung cancer among never smokers. Conversely, significant inverse associations with cruciferous vegetable intake were observed primarily among smokers, in particular former smokers, although significant interactions were not detected between smoking and intake of any food group. Of four lung cancer histological subtypes, significant inverse associations were observed primarily among patients with squamous or small cell carcinoma - the two subtypes more strongly associated with heavy smoking. CONCLUSIONS: Our findings are consistent with the smoking-related carcinogen-modulating effect of isothiocyanates, a group of phytochemicals uniquely present in cruciferous vegetables. Our data support consumption of a diet rich in cruciferous vegetables may reduce the risk of lung cancer among smokers.

Analysis of second primary lung cancers in the SEER database.

BACKGROUND: We sought to examine the outcomes of second primary lung cancers in the large population-based Surveillance Epidemiology and End Results (SEER) database. We also sought to study the outcomes of synchronous second non-small-cell lung cancers (NSCLCs), classified as stage IVA (M1A) according to the seventh edition of the TNM staging for lung cancer. METHODS: Data of patients with at least two primary lung cancers were obtained. All available variables potentially associated with the incidence of a second primary lung cancer were examined. The overall survival of patients with synchronous NSCLC was compared with those with metachronous and stage IV NSCLC. RESULTS: A small proportion (1.5%) of patients with lung cancer developed a second primary. A second primary is associated with younger age, female gender, earlier stage, and white race. The median survival of patients with metachronous NSCLCs (n = 3352) was worse than those with synchronous NSCLCs (n = 1858) (median survival 22 mo versus 29 mo, respectively; P < 0.01). After adjusting for age, race, gender, stage, and histology of both primaries, this difference in survival between patients with synchronous and metachronous second primary lung cancers was not statistically significant, but was better than those with stage IV NSCLC (n = 127,654; median survival 4 mo). CONCLUSIONS: The incidence of second primary lung cancer is lower than that previously reported. Factors associated with good prognosis predict a second primary. Synchronous NSCLCs have an outcome better than a stage IV (M1a) designation. These patients should receive appropriate stage-specific multi-modality therapy suitable for the independent stage of each cancer without considering them unresectable.