Search

Objective: Lung cancer screening can decrease mortality. The majority of screen-detected cancers are early stage and undergo surgical resection. However, there are little data regarding the outcomes of surgical treatment outside of clinical trials. The purpose of this study was to compare the outcomes of curative resection for screen-detected lung cancers with nonscreened, incidentally detected cancers at an institution with a structured screening program., Methods: Patients undergoing lung cancer curative resection from January 2012 to June 2021 were identified from a prospective database. Baseline patient characteristics, tumor characteristics, and outcomes were compared between cancer detected from screening and cancer detected incidentally., Results: There were 199 patients in the incidental group and 82 patients in the screened group. Mean follow-up was 33.3 ± 25 months. The screened group had more African Americans (P = .04), a higher incidence of emphysema (P = .02), less prior cancers (P < .01), and more pack-years smoked (P < .01). The screened group had a smaller size (1.74 vs 2.31 cm, P < .01); however, pathologic stage was similar, with the majority being stage I. Postoperative morbidity, 30-day mortality, and overall and recurrence-free survival were similar between groups. Only 48.7% of the incidental group met current US Preventative Services Task Force screening criteria (age 50-80 years, ≥20 pack-year smoking history)., Conclusions: Screen-detected lung cancers have excellent postoperative and long-term outcomes with curative resection, similar to incidentally detected cancers. A large portion of incidentally detected lung cancers do not meet current screening guidelines, which is an opportunity for further refinement of eligibility., (Copyright © 2023 The American Association for Thoracic Surgery. All rights reserved.)

Background: Despite the rising incidence of lung cancer in patients who never smoked, environmental risk factors such as ambient air pollution in this group are poorly described. Our objective was to identify the relationship of environmental exposures with lung cancer in patients who never smoked., Methods: A prospectively collected database was reviewed for all patients with non-small cell lung carcinoma (NSCLC) who underwent resection from 2006 to 2021. Environmental exposures were estimated using the geocoded home address of patients. Logistic regression was used to determine the association of clinical and environmental variables with smoking status. Kaplan-Meier and Cox proportional hazards analyses were used to assess survival., Results: A total of 665 patients underwent resection for NSCLC, of which 67 (10.1%) were patients who never smoked and 598 (89.9%) were current/former smokers. Patients who never smoked were more likely of white race (p = 0.001) and had well-differentiated tumors with carcinoid or adenocarcinoma histology (p < 0.001). Environmental exposures were similar between groups, but patients who never smoked had less community material deprivation (p = 0.002) measured by household income, education, health insurance, and vacancies. They had improved overall survival (p = 0.012) but equivalent cancer recurrence (p = 0.818) as those who smoked. In univariable Cox analyses, fine particulate matter (HR: 1.447 [95% CI 1.197-1.750], p < 0.001), distance to nearest major roadway (HR: 1.067 [1.024-1.111], p = 0.002), and greenspace (HR: 0.253 [0.087-0.737], p = 0.012) were associated with overall survival in patients who never smoked., Conclusions: Lung cancer patients who never smoked have unique clinical and pathologic characteristics, including higher socioeconomic status. Interventions to reduce environmental exposures may improve lung cancer survival in this population., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Indeterminate pulmonary nodules (IPN) are a diagnostic challenge in regions where pulmonary fungal disease and smoking prevalence are high. We aimed to determine the impact of a combined fungal and imaging biomarker approach compared with a validated prediction model (Mayo) to rule out benign disease and diagnose lung cancer., Methods: Adults ages 40 to 90 years with 6-30 mm IPNs were included from four sites. Serum samples were tested for histoplasmosis IgG and IgM antibodies by enzyme immunoassay and a CT-based risk score was estimated from a validated radiomic model. Multivariable logistic regression models including Mayo score, radiomics score, and IgG and IgM histoplasmosis antibody levels were estimated. The areas under the ROC curves (AUC) of the models were compared among themselves and to Mayo. Bias-corrected clinical net reclassification index (cNRI) was estimated to assess clinical reclassification using a combined biomarker model., Results: We included 327 patients; 157 from histoplasmosis-endemic regions. The combined biomarker model including radiomics, histoplasmosis serology, and Mayo score demonstrated improved diagnostic accuracy when endemic histoplasmosis was accounted for [AUC, 0.84; 95% confidence interval (CI), 0.79-0.88; P < 0.0001 compared with 0.73; 95% CI, 0.67-0.78 for Mayo]. The combined model demonstrated improved reclassification with cNRI of 0.18 among malignant nodules., Conclusions: Fungal and imaging biomarkers may improve diagnostic accuracy and meaningfully reclassify IPNs. The endemic prevalence of histoplasmosis and cancer impact model performance when using disease related biomarkers., Impact: Integrating a combined biomarker approach into the diagnostic algorithm of IPNs could decrease time to diagnosis., (©2022 American Association for Cancer Research.)

Objective: Minority patients with lung cancer are less likely to undergo surgical resection and experience worse survival than non-Hispanic White patients. Currently, 40% of thoracic surgeons require smoking cessation before surgery, which may disproportionately affect minority patients. Our objective was to assess the risk of smoking status on postoperative morbidity and mortality among patients with lung cancer., Methods: A prospectively maintained institutional database was queried for all patients who underwent surgical resection of a primary lung malignancy between 2006 and 2020. Operative mortality, major morbidity, and a composite of morbidity and mortality were compared between current smokers and prior smokers., Results: A total of 601 patients underwent resection, and 236 (39.3%) were current smokers. Current smokers were more likely to be younger (P < .01), to have a greater pack-years history (P = .03), and to have worse pulmonary function test results (P < .01). Pretreatment stage, surgical approach, and extent of resection were similar between groups. There was no difference in operative mortality (0.9% vs 1.9%, P = .49), major morbidity (12.7% vs 9.3%, P = .19), or composite major morbidity and mortality between groups (13.1% vs 9.3%, P = .14). After adjusting for pulmonary function status, current smoking status was not associated with mortality or major morbidity on multivariable logistic regression (odds ratio, 1.51; 95% confidence interval, 0.76-3.03, P = .24)., Conclusions: Current smokers experienced similar rates of mortality and major morbidity as prior smokers. In the context of continued racial and ethnic disparities in lung cancer survival, in particular decreased resection rates among minorities, smoking cessation requirements should not delay or prevent operative intervention for lung cancer., (Published by Elsevier Inc.)

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, blocking either FASN or the Lands cycle in KMLC, promotes ferroptosis, a reactive oxygen species (ROS)- and iron-dependent cell death, characterized by the intracellular accumulation of oxidation-prone PC. Our work indicates that KM dictates a dependency on newly synthesized FA to escape ferroptosis, establishing a targetable vulnerability in KMLC., (© 2022. The Author(s).)

Background: Several studies suggest that patients with KRAS-mutant NSCLC fail to benefit from standard systemic therapies and do not respond to EGFR inhibitors. Most recently, KRAS 12c data suggest specific treatment for improving ORR and OS. There is a clear need for therapies specifically developed for these patients. Moreover, data that might be suggestive of a response to specific therapies, such as BRCA1, are needed, and two mutations that were studied in other malignancies show more response to PARP inhibitors. Molecular profiling has the potential to identify other potential targets that may provide better treatment and novel targeted therapy for KRAS-mutated NSCLC. Methods: We purified RNA from archived tissues of patients with stage I and II NSCLC with wild-type (wt) and mutant (mt) KRAS tumors; paired normal tissue adjacent to the tumor from 20 and 17 patients, respectively, and assessed, using real-time reverse transcriptase−polymerase chain reaction (RT-PCR), the expression of four genes involved in DNA synthesis and repair, including thymidylate synthase (TS), BRCA1, ECCR1, RAP80, and the proto-oncogene SRC. Additionally, we assessed the expression of PD-L1 in mt KRAS tumors with immunohistochemistry using an antibody against PD-L1. Results: Our results show that in mtKRAS tumors, the level of expression of ERCC1, TS, and SRC was significantly increased in comparison to paired normal lung tissue (p ≤ 0.04). The expression of BRCA1 and RAP80 was similar in both mt KRAS tumors and paired normal tissue. Furthermore, the expression of BRCA1, TS, and SRC was significantly increased in wt KRAS tumors relative to their expression in the normal lung tissue (p < 0.044). The expression of ERCC1 and RAP80 was similar in wt KRAS tumors and paired normal tissue. Interestingly, SRC expression in mtKRAS tumors was decreased in comparison to wt KRAS tumors. Notably, there was an expression of PD-L1 in the tumor and stromal cells in a few (5 out of 20) mtKRAS tumors. Our results suggest that a greater ERCC1 expression in mt KRAS tumors might increase platinum resistance in this group of patients, whereas the greater expression of BRCA1 in wt KRAS tumor might be suggestive of the sensitivity of taxanes. Our data also suggest that the combination of an SRC inhibitor with a TS inhibitor, such as pemetrexed, might improve the outcome of patients with NSCLC and in particular, patients with wt KRAS tumors. PD-L1 expression in tumors, and especially stromal cells, suggests a better outcome. Conclusion: mt KRAS NSCLC patients might benefit from a treatment strategy that targets KRAS in combination with therapeutic agents based on pharmacogenomic markers, such as SRC and BRCA1. mtKRAS tumors are likely to be platinum-, taxane-, and pemetrexed-resistant, as well as having a low level of PD-L1 expression; thus, they are less likely to receive single-agent immunotherapy, such as pembrolizumab, as the first-line therapy. wt KRAS tumors with BRCA1 positivity tend to be sensitive to taxane therapy and, potentially, platinum. Our results suggest the need to develop targeted therapies for KRAS-mutant NSCLC or combine the targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor.

Background: Lung cancer screening with low-dose computed tomography has demonstrated at least a 20% decrease in lung cancer-specific mortality, but it has the potential harm of unnecessary invasive procedures performed because of false-positive results. This study reports the outcomes of a structured multidisciplinary lung cancer screening program in an area of endemic histoplasmosis., Methods: A retrospective review of patients undergoing lung cancer screening from December 2012 to March 2019 was conducted. Findings suggestive of lung cancer were presented to a multidisciplinary thoracic tumor board. Patients were assigned to interval imaging follow-up, additional diagnostic imaging, or referral for an invasive procedure. Invasive procedures were then compared between benign and malignant diseases., Results: A total of 4087 scans were performed on 2129 patients; 372 (9.1%) were suspicious and were presented to a multidisciplinary thoracic tumor board. Ultimately, 108 procedures were performed: 55 bronchoscopies, 7 percutaneous biopsies, and 46 operations. A total of 25 patients (1.2%) underwent bronchoscopy resulting in benign pathologic findings, significantly associated with an indication of an endobronchial lesion (P = .01). All percutaneous biopsy specimens revealed malignancy. Five patients (0.2%) who underwent resection had benign disease. Lung cancer was diagnosed in 67 patients (3.1% of the entire cohort), 46 of whom had stage I or II disease., Conclusions: Lung cancer screening in a structured, multidisciplinary program successfully identifies patients with early-stage lung cancer with limited unnecessary surgical interventions. Patients with isolated endobronchial lesions should undergo short interval imaging follow-up to avoid bronchoscopy for benign disease. Future studies to minimize unnecessary procedures could incorporate biomarkers and advanced imaging analysis into risk assessment models., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Low-dose CT (LDCT) screening reduces lung cancer mortality by at least 20%. The COVID-19 pandemic required an unprecedented shutdown in our institutional LDCT program. The purpose of this study was to examine the impact of COVID-19 on lung cancer screening and subsequent cancer diagnosis., Study Design: We analyzed our prospective institutional LDCT screening database, which began in 2012. In all, 2,153 patients have participated. Monthly mean number of LDCTs were compared between baseline (January 2017 to February 2020) and COVID-19 periods (March 2020 to July 2020)., Results: LDCT was suspended on March 13, 2020 and 818 screening visits were cancelled. Phased reopening began on May 5, 2020 and full opening on June 1, 2020. Total monthly mean ± SD LDCTs (146 ± 31 vs 39 ± 40; p < 0.01) and new patient monthly LDCTs (56 ± 14 vs 15 ± 17; p < 0.01) were significantly decreased during the COVID-19 period. New patient monthly LDCTs have remained low despite resuming full operations. Three- and 6-month interval follow-up LDCTs were prioritized and were significantly increased compared with baseline (11 ± 4 vs 30 ± 4; p < 0.01). The "no-show" rate was significantly increased from baseline (15% vs 40%; p < 0.04). Most concerning, the percentage of patients with lung nodules suspicious for malignancy (Lung-RADS 4) were significantly increased after screenings resumed (8% vs 29%; p < 0.01)., Conclusions: COVID-19 caused significant disruption in lung cancer screening, leading to a decrease in new patients screened and an increased proportion of nodules suspicious for malignancy once screening resumed. Using lung cancer and the LDCT screening program as a model, this early analysis showed the unrecognized consequences related to the pandemic for screening programs and cancer care., (Published by Elsevier Inc.)

Background: The national opioid epidemic is a public health crisis. Thoracic surgery has also been associated with high incidence of new persistent opioid use. Our purpose was to describe the incidence and predictors of opioid use after lung cancer resection., Methods: Retrospective review of lung cancer resections from 2015 to 2018 was performed using the Ohio Automated Rx Reporting System. Opioid dosing was recorded as milligram morphine equivalents (MME). Patients were stratified by preoperative opioid use. Chronic preoperative opioid users (opioid dependent) filled > 120 days supply of opioid pain medication in the 12 months prior to surgery; intermittent opioid users filled < 120 days. Chronic postoperative opioid users continued monthly use after 180 days postoperatively., Results: 137 patients underwent resection. 16.1% (n = 22) were opioid dependent preoperatively, 29.2% (n = 40) were intermittent opioid users, and 54.7% (n = 75) were opioid naïve. Opioid dependent patients had higher daily inpatient opioid use compared to intermittent users and opioid naïve (43[30.0-118.1] MME vs 17.9[3.5-48.8] MME vs 8.8[2.1-25.0] MME, p < 0.001). Twenty-six percent (n = 35) of all patients were opioid users beyond 180 days postoperatively. Variables associated with opioid use > 180 days were: chronic preoperative opioid use (OR 23.8, p < 0.01), daily inpatient opioid requirement (1.02, p < 0.01), and neoadjuvant chemotherapy (28.2, p < 0.01)., Conclusions: A quarter of patients are opioid dependent after lung cancer resection. This is due to both preexisting and new persistent opioid use. Improved strategies are needed to prevent chronic pain and opioid dependence after lung cancer resection.

Background: Prior studies have suggested that low baseline quality-of-life (QOL) scores predict worse survival in patients undergoing lung cancer surgery. However, these studies involved average-risk patients undergoing lobectomy. We report QOL results from a multicenter trial, American College of Surgeons Oncology Group Z4032, which randomized high-risk operable patients to sublobar resection (SR), or SR with brachytherapy, and included longitudinal QOL assessments., Methods: Global QOL, using the 36-item Short-Form Health Survey (SF36), and the dyspnea score from the University of California, San Diego Shortness of Breath Questionnaire (SOBQ) scale, was measured at baseline, 3, 12, and 24 months. SF36 physical component summary (PCS) and mental component summary (MCS) scores were standardized and adjusted for age and gender normals, with scores <50 indicating below-average health status. SOBQ scores were transformed to a 0-100 (poor-excellent) scale. Aims were to: (1) determine the impact of baseline scores on recurrence-free survival, overall survival, and 30-day adverse events (AEs); and (2) identify subgroups (surgical approach, resection type. tumor location, tumor size, respiratory function) with a ≥ 10-point decline or improvement in QOL after SR., Results: Two hundred twelve eligible patients were included. There were no significant differences in baseline QOL scores between arms. Median baseline PCS, MCS, and SOBQ scores were 42.7, 51.1, and 70.8, respectively. There were no differences in grade-3+ AEs, overall survival, or recurrence-free survival in patients with baseline scores ≤ median versus > median values, except for a significantly worse overall survival for patients with baseline SOBQ scores ≤ median value. There were no significant differences between the study arms in percentage change of QOL scores from baseline to 3, 12, or 24 months. Further comparison combining the 2 arms demonstrated a higher percentage of patients with a ≥ 10-point decline in SOBQ scores with segmentectomy compared with wedge resection (40.5% vs 21.9%, P = .03) at 12 months, with thoracotomy versus video-assisted thoracic surgery (VATS) (38.8% vs 20.4%, P = .03) at 12 months, and T1b versus T1a tumors (46.9% vs 23.5%, P = .020) at 24 months. A ≥ 10-point improvement in PCS score was seen at 3 months with VATS versus thoracotomy (16.5% vs 3.6%, P = .02)., Conclusions: In high-risk operable patients, poor baseline QOL scores were not predictive for worse overall or recurrence-free survival, or for higher risk for AEs following SR. VATS was associated with improvement in physical function at 3 months, and improved dyspnea scores at 12 months, lending support for the preferential use of VATS when SR is undertaken., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: A major concern with sublobar resection (SR) for non-small-cell lung cancer (NSCLC) is high local recurrence (LR). Adjuvant brachytherapy may reduce LR This multicenter randomized trial compares SR to SR with brachytherapy (SRB)., Patients and Methods: High-risk operable patients with NSCLC ≤ 3 cm were randomly assigned to SR or SRB. The primary end point was time to LR, where LR included recurrence at the staple line (local progression), in the primary tumor lobe away from the staple line, and in ipsilateral hilar nodes. The trial was designed to have a 90% power to detect a hazard ratio (HR) of 0.315 in favor of SRB, using a one-sided type I error rate of 0.05 with a sample size of 100 eligible patients in each arm., Results: Two hundred twenty-four patients were randomly assigned; 222 patients were evaluable for intent-to-treat analysis. Median age was 71 years (range, 49 to 87 years). No differences were found in baseline characteristics. Median follow-up time was 4.38 years (range, 0.04 to 5.59 years). There was no difference in time to LR (HR, 1.01; 95% CI, 0.51 to 1.98; log-rank P = .98) or in the types of LR. Local progression occurred in only 17 (7.7%) of 222 patients. In patients with potentially compromised margins (margin < 1 cm, margin-to-tumor ratio < 1, positive staple line cytology, wedge resection, nodule size > 2.0 cm), SRB did not reduce LR, although trends favored the SRB arm. This was most marked in 14 patients with positive staple line cytology (HR, 0.22; P = .24). Three-year overall survival rates were similar for patients in the SR (71%) and SRB (71%) arms (P = .97)., Conclusion: Brachytherapy did not reduce LR after SR. This finding may have been related to closer attention to parenchymal margins by surgeons participating in this study., (© 2014 by American Society of Clinical Oncology.)

There are several methods to mitigate the pain that results from thoracic surgery. All of them may be associated with complications. We analyzed the morbidities associated with epidural and subpleural catheter analgesia in patients undergoing pulmonary resections for lung cancer. We conducted a retrospective review of our prospective lung cancer outcomes database for all patients undergoing lobectomy for lung cancer through a thoracotomy or thoracoscopy. All patients had either an epidural or subpleural catheter placed for pain control. One hundred twenty-nine patients met the inclusion criteria. Patients were stratified based on age and pain management technique and the 30-day outcomes were examined. Ninety-three patients had epidural catheters placed and 36 received subpleural catheters. Baseline demographics were similar except for two variables; the subpleural catheter group had a larger proportion of thoracoscopic surgery and more pack-years smoked. Patients in the epidural group were more likely to experience postoperative pruritus and had longer intensive care unit stays but were less likely to use a patient-controlled anesthesia pump. Patients in the subpleural group were more likely to develop intestinal complications. When a subset analysis was done by age (younger than 70 vs 70 years or older), there were no significant differences in postoperative outcomes in the older group. The younger cohort had more pruritus and longer intensive care unit stays in the epidural group. The differences between subpleural and epidural catheters are minimal across all ages and nonexistent for geriatric patients. Thus, the choice of pain management should be determined by individual patient characteristics and risk factors rather than based on age alone.

Objective: Conversion to an open thoracotomy during video-assisted thoracoscopic surgery lobectomy is reported to occur in up to 23% of cases and can be associated with increased morbidity. We developed a preoperative computed tomography calcification score based on anatomic location and extent of calcifications to evaluate the ability to predict video-assisted thoracoscopic surgery conversion., Methods: Patients undergoing planned video-assisted thoracoscopic surgery lobectomy between 2003 and 2009 were identified. Baseline demographics, comorbidities, operative data, and postoperative outcomes were reviewed. Preoperative chest computed tomography scans were examined by an attending thoracic surgeon. Calcifications were scored from 0 (none) to 6 (major hilar calcifications at the resection bronchus). Preoperative patient and tumor characteristics and the calcification score were analyzed for their ability to predict conversion. We then compared outcomes among patients undergoing video-assisted thoracoscopic surgery, converted video-assisted thoracoscopic surgery, and planned open thoracotomy., Results: Of the 193 patients undergoing planned video-assisted thoracoscopic surgery lobectomy, 148 (77%) had a completed video-assisted thoracoscopic surgery lobectomy, and 45 (23%) underwent conversion to thoracotomy. The calcification score was found to independently predict video-assisted thoracoscopic surgery conversion. Patients who were converted to a thoracotomy had significantly higher 30-day mortality, more atrial arrhythmias, increased blood loss, longer operative time, and increased length of stay compared with those who underwent completed video-assisted thoracoscopic surgery lobectomy and longer length of stay compared with those undergoing planned open lobectomy., Conclusions: Calcification score based on the location and degree of calcifications can predict the increased likelihood of video-assisted thoracoscopic surgery conversion. This scoring system could be one element used to choose the approach for a lobectomy, especially during a surgeon's learning curve., (Published by Mosby, Inc.)

Background: Five-year survival for early-stage lung cancer despite complete surgical resection is approximately 50%. Adjuvant chemotherapy has been shown to improve survival in some patients. Older cancer patients do not always receive standard therapy. The purpose of this study was to determine if there were age-related biases concerning the use of adjuvant chemotherapy after lobectomy for elderly patients with non-small cell lung cancer (NSCLC)., Methods: A prospective lung cancer outcomes database was queried for all patients undergoing lobectomy for NSCLC pathologic stage IB and higher between April 2006 and October 2010. Patients who received neoadjuvant treatment or who died within 30 days of operation were excluded. Ninety-nine patients met the inclusion criteria. Patients were divided into 2 groups based on age (<70 or ≥70 years). The use of adjuvant chemotherapy was compared between groups., Results: Sixty-nine patients (70%) were younger than 70 years and 30 (30%) were 70 years or older. There was a significant difference in the use of adjuvant chemotherapy between the 2 groups, with 46 (66.7%) of the younger patients and 7 (25%) of the elderly patients receiving adjuvant treatment (p<0.01). The difference persisted when analyzed by stage, with older patients less likely to receive chemotherapy among all patients with stage IB disease, stage II or more advanced disease, and stage IB lesions greater than or equal to 4 cm plus stage II or more advanced disease. In multivariate analysis of preoperative and postoperative factors, age remained the only independent predictor of chemotherapy use., Conclusions: Patients undergoing lobectomy who were 70 years of age or older received adjuvant chemotherapy less often than did younger patients., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with stage I lung cancer undergoing a complete resection have a 25% risk of recurrence. Factors predictive for recurrence are critically needed. In the present study, we prospectively examined clinical and molecular factors that may predict a poor outcome., Methods: Patients with stage I non-small cell lung cancer undergoing surgical resection were enrolled into an institutional registry. Clinical demographics and outcomes data were prospectively collected. Patients who received neoadjuvant therapy or patients who died within 30 days of surgery were excluded from this analysis. Molecular factors involved in cell proliferation, cell cycle control, apoptosis, and angiogenesis were analyzed. The primary endpoint was recurrence-free survival., Results: One hundred and two patients were enrolled between March 2006 and April 2009. There were 25 (25%) documented recurrences. In univariate analysis, male sex, increased tumor standard uptake value, tumor size, final pathology stage, arterial invasion, percent nuclear phosphorylated AKT, vascular endothelial growth factor score, negative cyclin D1 protein expression, and percent nuclear cyclin D1 expression were predictive of decreased recurrence-free survival. All factors with a p value of 0.1 or less were included in multivariate analysis. Male sex, final pathology stage, vascular endothelial growth factor score, and percent nuclear cyclin D1 expression were significant independent predictors for poor prognosis., Conclusions: Four clinical and molecular factors were associated with prognosis in a prospective study of stage I non-small cell lung cancer., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Sublobar resection (SR) is commonly used for patients considered high risk for lobectomy. Nonoperative therapies are increasingly being reported for patients with similar risk because of perceived lower morbidity. We report 30- and 90-day adverse events (AEs) from American College of Surgeons Oncology Group Z4032, a multicenter phase III study for high-risk patients with stage I non-small cell lung cancer., Methods: Data from 222 evaluable patients randomized to SR (n = 114) or SR with brachytherapy (n = 108) are reported. AEs were recorded using the Common Terminology Criteria for Adverse Events, Version 3.0, at 30 and 90 days after surgery. Risk factors (age, percent baseline carbon monoxide diffusion in the lung [DLCO%], percent forced expiratory volume in 1 second [FEV1%], upper lobe vs lower lobe resections, performance status, surgery approach, video-assisted thoracic surgery vs open and extent, and wedge vs segmentectomy) were analyzed using a multivariable logistic model for their impact on the incidence of grade 3 or higher (G3+) AEs. Respiratory AEs were also specifically analyzed., Results: Median age, FEV1%, and DLCO% were similar in the 2 treatment groups. There was no difference in the location of resection (upper vs lower lobe) or the use of segmental or wedge resections. There were no differences between the groups with respect to "respiratory" G3+ AEs (30 days: 14.9% vs 19.4%, P = .35; 0-90 days: 19.3% vs 25%, P = .31) and "any" G3+ AEs (30 days: 25.4% vs 30.6%, P = .37; 0-90 days: 29.8% vs 37%, P = .25). Further analysis combined the 2 groups. Mortality occurred in 3 patients (1.4%) by 30 days and in 6 patients (2.7%) by 90 days. Four of the 6 deaths were thought to be due to surgery. When considered as continuous variables, FEV1% was associated with "any" G3+ AE at days 0 to 30 (P = .03; odds ratio [OR] = 0.98) and days 0 to 90 (P = .05; OR = 0.98), and DLCO% was associated with "respiratory" G3+ AE at days 0 to 30 (P = .03; OR = 0.97) and days 0 to 90 (P = .05; OR = 0.98). Segmental resection was associated with a higher incidence of any G3+ AE compared with wedge resection at days 0 to 30 (40.3% vs 22.7%; OR = 2.56; P < .01) and days 0 to 90 (41.5% vs 29.7%; OR = 1.96; P = .04). The median FEV1% was 50%, and the median DLCO% was 46%. By using these median values as potential cutpoints, only a DLCO% of less than 46% was significantly associated with an increased risk of "respiratory" and "any" G3+ AE for days 0 to 30 and 0 to 90., Conclusions: In a multicenter setting, SR with brachytherapy was not associated with increased morbidity compared with SR alone. SR/SR with brachytherapy can be performed safely in high-risk patients with non-small cell lung cancer with low 30- and 90-day mortality and acceptable morbidity. Segmental resection was associated with increased "any" G3+ AE, and DLCO% less than 46% was associated with "any" G3+ AE and "respiratory" G3+ AE at both 30 and 90 days., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Z4032 was a randomized study conducted by the American College of Surgeons Oncology Group comparing sublobar resection alone versus sublobar resection with brachytherapy for high-risk operable patients with non-small cell lung cancer (NSCLC). This evaluates early impact of adjuvant brachytherapy on pulmonary function tests, dyspnea, and perioperative (30-day) respiratory complications in this impaired patient population., Methods: Eligible patients with stage I NSCLC tumors 3 cm or smaller were randomly allocated to undergo sublobar resection with (SRB group) or without (SR group) brachytherapy. Outcomes measured included the percentage predicted forced expiratory volume in 1 second (FEV1%), percentage predicted carbon monoxide diffusion capacity (DLCO%), and dyspnea score per the University of California San Diego Shortness of Breath Questionnaire. Pulmonary morbidity was assessed per the Common Terminology Criteria for Adverse Events version 3.0. Outcomes were measured at baseline and 3 months. A 10% change in pulmonary function test or 10-point change in dyspnea score was deemed clinically meaningful., Results: Z4032 permanently closed to patient accrual in January 2010 at 224 patients. At 3-month follow-up, pulmonary function data are currently available for 148 (74 SR and 74 SRB) patients described in this report. There were no differences in baseline characteristics between arms. In the SR arm, 9 patients (12%) reported grade 3 respiratory adverse events, compared with 12 (16%) in the SRB arm (P = .49). There was no significant change in percentage change in DLCO% or dyspnea score from baseline to 3 months within either arm. In the case of FEV1%, percentage change from baseline to 3 months was significant within the SR arm (P = .03), with patients reporting improvement in FEV1% at month 3. Multivariable regression analysis (adjusted for baseline values) showed no significant impact of treatment arm, tumor location (upper vs other lobe), or surgical approach (video-assisted thoracoscopic surgery vs thoracotomy) on 3-month FEV1%, DLCO%, and dyspnea score. There was no significant difference in incidence of clinically meaningful (10% pulmonary function or 10-point dyspnea score change) change between arms. Twenty-two percent of patients with lower-lobe tumors and 9% with upper-lobe tumors demonstrated 10% decline in FEV1% (odds ratio, 2.79; 95 confidence interval, 1.07-7.25; P = .04)., Conclusions: Adjuvant intraoperative brachytherapy in conjunction with sublobar resection did not significantly worsen pulmonary function or dyspnea at 3 months in a high-risk population with NSCLC, nor was it associated with increased perioperative pulmonary adverse events. Lower-lobe resection was the only factor significantly associated with clinically meaningful decline in FEV1%., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Low-dose chest computed tomography (CT) is being evaluated in several national trials as a screening modality for the early detection of lung cancer. The goal of the present study was to determine whether lung cancer screening could be done while minimizing the number of benign biopsy specimens taken in an area endemic for histoplasmosis., Methods: The subjects were recruited by letters mailed to area physicians and local advertisement. The inclusion criteria were age older than 50 years and at least a 20 pack-year smoking history. The exclusion criteria were symptoms suggestive of lung cancer or a history of malignancy in the previous 5 years. The participants completed a questionnaire and underwent a chest CT scan at baseline and annually for 5 years. The management of positive screening results was determined using a defined algorithm: annual follow-up CT scan for nodules less than 5 mm; 6-month follow-up CT scan for nodules 5 to 7 mm; review by our multidisciplinary tumor board for nodules 8 to 12 mm; and biopsy for nodules greater than 12 mm., Results: A total of 132 patients were recruited. Of the 132 patients, 61% had positive baseline CT findings and 22% had positive findings on the annual CT scans. Six cancers were detected. Of these 6 patients, 5 had stage I disease and underwent lobectomy, and 1 had stage IIIA disease and underwent induction chemotherapy and radiotherapy followed by lobectomy. All patients were alive and disease free at a mean follow-up of 41.7 ± 18.6 months. No biopsies were performed for benign lesions. Also, no cancers were missed when the protocol was followed., Conclusions: Screening with CT can be done effectively in an area endemic for histoplasmosis while minimizing benign biopsies., (Published by Mosby, Inc.)