Alex Balekian

Treatment of Stage I and II Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND The treatment of stage I and II non-small cell lung cancer (NSCLC) in patients with good or low surgical risk is primarily surgical resection. However, this area is undergoing many changes. With a greater prevalence of CT imaging, many lung cancers are being found that are small or constitute primarily ground-glass opacities. Treatment such as sublobar resection and nonsurgical approaches such as stereotactic body radiotherapy (SBRT) are being explored. With the advent of minimally invasive resections, the criteria to classify a patient as too ill to undergo an anatomic lung resection are being redefined. METHODS The writing panel selected topics for review based on clinical relevance to treatment of early-stage lung cancer and the amount and quality of data available for analysis and relative controversy on best approaches in stage I and II NSCLC: general surgical care vs specialist care; sublobar vs lobar surgical approaches to stage I lung cancer; video-assisted thoracic surgery vs open resection; mediastinal lymph node sampling vs lymphadenectomy at the time of surgical resection; the use of radiation therapy, with a focus on SBRT, for primary treatment of early-stage NSCLC in high-risk or medically inoperable patients as well as adjuvant radiation therapy in the sublobar and lobar resection settings; adjuvant chemotherapy for early-stage NSCLC; and the impact of ethnicity, geography, and socioeconomic status on lung cancer survival. Recommendations by the writing committee were based on an evidence-based review of the literature and in accordance with the approach described by the Guidelines Oversight Committee of the American College of Chest Physicians. RESULTS Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC. Lobectomy or greater resection remains the preferred approach to T1b and larger tumors. The use of sublobar resection for T1a tumors and the application of adjuvant radiation therapy in this group are being actively studied in large clinical trials. Every patient should have systematic mediastinal lymph node sampling at the time of curative intent surgical resection, and mediastinal lymphadenectomy can be performed without increased morbidity. Perioperative morbidity and mortality are reduced and long-term survival is improved when surgical resection is performed by a board-certified thoracic surgeon. The use of adjuvant chemotherapy for stage II NSCLC is recommended and has shown benefit. The use of adjuvant radiation or chemotherapy for stage I NSCLC is of unproven benefit. Primary radiation therapy remains the primary curative intent approach for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable. There is growing evidence that SBRT provides greater local control than standard radiation therapy for high-risk and medically inoperable patients with NSCLC. The role of ablative therapies in the treatment of high-risk patients with stage I NSCLC is evolving. Radiofrequency ablation, the most studied of the ablative modalities, has been used effectively in medically inoperable patients with small (< 3 cm) peripheral NSCLC that are clinical stage I.

Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

OBJECTIVES Stage III non-small cell lung cancer (NSCLC) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky nodal disease. This review updates the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients. METHODS Systematic searches were conducted through MEDLINE, Embase, and the Cochrane Database for Systematic Review up to December 2011, focusing primarily on randomized trials, selected meta-analyses, practice guidelines, and reviews. RESULTS For individuals with stage IIIA or IIIB disease, good performance scores, and minimal weight loss, treatment with combined chemoradiotherapy results in better survival than radiotherapy alone. Consolidation chemotherapy or targeted therapy following definitive chemoradiation for stage IIIA is not supported. Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation. Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a beneficial impact of this treatment strategy; however, weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate. The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery. Postoperative radiotherapy improves local control without improving survival. CONCLUSIONS Multimodality therapy is preferable in most subsets of patients with stage III lung cancer. Variability in the patients included in randomized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios. Future trials are needed to investigate the roles of individualized chemotherapy, surgery in particular cohorts or settings, prophylactic cranial radiation, and adaptive radiation.

Accuracy of clinicians and models for estimating the probability that a pulmonary nodule is malignant.

RATIONALE Management of pulmonary nodules depends critically on the probability of malignancy. Models to estimate probability have been developed and validated, but most clinicians rely on judgment. OBJECTIVES The aim of this study was to compare the accuracy of clinical judgment with that of two prediction models. METHODS Physician participants reviewed up to five clinical vignettes, selected at random from a larger pool of 35 vignettes, all based on actual patients with lung nodules of known final diagnosis. Vignettes included clinical information and a representative slice from computed tomography. Clinicians estimated the probability of malignancy for each vignette. To examine agreement with models, we calculated intraclass correlation coefficients (ICC) and kappa statistics. To examine accuracy, we compared areas under the receiver operator characteristic curve (AUC). MEASUREMENTS AND MAIN RESULTS Thirty-six participants completed 179 vignettes, 47% of which described patients with malignant nodules. Agreement between participants and models was fair for the Mayo Clinic model (ICC, 0.37; 95% confidence interval [CI], 0.23-0.50) and moderate for the Veterans Affairs model (ICC, 0.46; 95% CI, 0.34-0.57). There was no difference in accuracy between participants (AUC, 0.70; 95% CI, 0.62-0.77) and the Mayo Clinic model (AUC, 0.71; 95% CI, 0.62-0.80; P = 0.90) or the Veterans Affairs model (AUC, 0.72; 95% CI, 0.64-0.80; P = 0.54). CONCLUSIONS In this vignette-based study, clinical judgment and models appeared to have similar accuracy for lung nodule characterization, but agreement between judgment and the models was modest, suggesting that qualitative and quantitative approaches may provide complementary information.

Brain Imaging for Staging of Patients With Clinical Stage IA Non-small Cell Lung Cancer in the National Lung Screening Trial: Adherence With Recommendations From the Choosing Wisely Campaign

BACKGROUND The Choosing Wisely recommendations from the Society of Thoracic Surgeons include avoiding brain imaging in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). We aimed to describe use of brain imaging among National Lung Screening Trial participants with stage IA NSCLC and to identify factors associated with receipt of brain imaging. METHODS We identified patients with clinical stage IA NSCLC who received CT scans or magnetic resonance brain imaging within 60 days after diagnosis, but before definitive surgical staging. Using multivariate logistic regression, we identified variables associated with undergoing brain imaging. RESULTS Among 643 patients with clinical stage IA NSCLC, 77 patients (12%) received at least one brain imaging study. Of seven patients (1.1%) who were upstaged to stage IV, only two underwent brain imaging and neither had documentation of brain metastasis. Brain imaging frequency by enrollment center varied from 0% to 80%. All patients who underwent brain imaging subsequently underwent surgery with curative intent, suggesting strongly that imaging revealed no evidence of intracranial metastases. In multivariate analyses, primary tumor size >20 mm (OR, 2.50; 95% CI, 1.50-4.16; P < .001) and age 65 to 69 (OR, 2.78; 95% CI, 1.38-5.57; P < .01) were independently associated with greater use of brain imaging. CONCLUSIONS Among National Lung Screening Trial patients with stage IA NSCLC, one in eight underwent brain imaging, but none ultimately had intracranial metastases. Larger tumor size and older age were associated with greater use of brain imaging. Wide variation in use between centers suggests either lack of awareness or disagreement about this Choosing Wisely recommendation.

Factors Associated with a Positive Baseline Screening Exam Result in the National Lung Screening Trial

RATIONALE Lung cancer screening with low-dose computed tomography (LDCT) has been shown to decrease mortality in eligible high-risk patients. However, this mortality benefit comes with a high rate of false-positive findings, which require further evaluation. OBJECTIVES To identify patient- and center-specific factors associated with having a pulmonary nodule on baseline LDCT, and to develop a prediction rule to help in shared decision making. METHODS We identified individuals who underwent baseline LDCT screening as part of the National Lung Screening Trial. A positive screen was defined as a nodule 4 mm or greater in largest dimension. Using multiple logistic regression, we identified variables independently associated with having a positive screen. MEASUREMENTS AND MAIN RESULTS Among the 26,004 patients with complete data who underwent baseline LDCT, 7,123 patients (27%) had a positive screen. In a multivariate analysis, older age (odds ratio [OR] = 1.03 per 1-year increase, 95% confidence interval [CI] = 1.03-1.04), female sex (OR = 1.08, 95% CI = 1.01-1.14), white race (OR = 1.39, 95% CI = 1.25-1.55), heavier smoking history (OR = 1.02 per 5 pack-years smoked over 30, 95% CI = 1.00-1.04), history of chronic obstructive pulmonary disease (OR = 1.08, 95% CI = 1.01-1.17), being married (OR = 1.08, 95% CI = 1.02-1.15), hard rock mining (OR = 1.40, 95% CI = 1.04-1.89), and farm work (OR = 1.13, 95% CI = 1.03-1.23) were independently associated with having a positive screen, whereas having a college degree (OR = 0.94, 95% CI = 0.86-1.00) and abstinence from smoking (OR = 0.98 per year, 95% CI = 0.98-0.99) were associated with not having a positive screen. Patients enrolled at a site in an area highly endemic for histoplasma were 30% more likely to have a positive baseline LDCT screen (OR = 1.30, 95% CI = 1.21-1.40). The area under the receiver operator characteristic curve for the full model was 0.57 (0.56-0.58); including enrollment center as a random effect increased the area under the receiver operator characteristic curve to 0.65. CONCLUSIONS In the National Lung Screening Trial, both patient- and center-specific factors were associated with having a positive baseline screen. Although the model does not have sufficient accuracy to provide personalized risk estimates to guide shared decision making on an individual basis, it can nonetheless inform screening centers of the likelihood of further follow-up testing for their populations at large when allocating resources. Data collected from centers as broad-based screening is implemented can be used to improve model accuracy further.

Predicting in-hospital mortality among critically ill patients with end-stage liver disease ☆

PURPOSE Critically-ill patients with end-stage liver disease (ESLD) are at high risk for death during intensive care unit hospitalization, and currently available prognostic models have limited accuracy in this population. We aimed to identify variables associated with in-hospital mortality among critically ill ESLD patients and to develop and validate a simple, parsimonious model for bedside use. MATERIALS AND METHODS We performed a retrospective chart review of 653 intensive care unit admissions for ESLD patients; modeled in-hospital mortality using multivariable logistic regression; and compared the predictive ability of several different models using the area under receiver operating characteristic (AU-ROC) curves. RESULTS Multivariable predictors of in-hospital mortality included Model for End-stage Liver Disease (MELD) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mechanical ventilation, and gender; there was also an interaction between MELD score and gender (P < .02). MELD alone had better discrimination (AU-ROC 0.83) than APACHE II alone (AU-ROC 0.76), and adding mechanical ventilation to MELD achieved the single largest increase in model discrimination (AU-ROC 0.85; P < .01). In a parsimonious, 2-predictor model, higher MELD scores (OR 1.14 per 1-point increase; 95% CI 1.11-1.16), and mechanical ventilation (OR 6.20; 95% CI 3.05-12.58) were associated with increased odds of death. Model discrimination was also excellent in the validation cohort (AU-ROC 0.90). CONCLUSIONS In critically ill ESLD patients, a parsimonious model including only MELD and mechanical ventilation is more accurate than APACHE II alone for predicting in-hospital mortality. This simple bedside model can provide clinicians and patients with valuable prognostic information for medical decision-making.

Surgical Disparities Among Patients With Stage I Lung Cancer in the National Lung Screening Trial

BACKGROUND: Low‐dose CT scan reduces lung cancer mortality in high‐risk patients fit to undergo surgical resection. Racial disparities in resection of lung cancer in nonscreening populations are well described. We describe surgical resection patterns of patients with early stage non‐small cell lung cancer (NSCLC) in the National Lung Screening Trial (NLST) and examine whether racial disparities exist among blacks. METHODS: We identified all NLST participants with clinical stage I NSCLC. Covariates included demographics, smoking history, comorbidities, tumor characteristics, and timing of cancer detection. Using logistic regression, we assessed resection rates of blacks vs whites. RESULTS: Among 752 patients with clinical stage I disease, 692 patients (92%) underwent resection. Unadjusted surgical resection rates for white men, white women, black men, and black women were 92%, 91%, 61%, and 90%, respectively. In adjusted analyses, compared with white men, black men had a 28% lower risk (relative risk, 0.72; 95% CI, 0.50‐0.99) of undergoing surgery; however, white women and black women underwent surgery at comparable rates as white men. The odds of undergoing limited resection instead of full resection were 70% greater in white women than white men (OR, 1.69; 95% CI, 1.08‐2.65). CONCLUSIONS: Our study shows that disparities in the surgical treatment of lung cancer persist, even among NLST participants who were considered fit to undergo thoracic surgery. As lung cancer screening disseminates into clinical practice, efforts targeting black men should be prioritized.

Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline

Background: This Guideline, a collaborative effort from the American Thoracic Society, Society of Thoracic Surgeons, and Society of Thoracic Radiology, aims to provide evidence‐based recommendations to guide contemporary management of patients with a malignant pleural effusion (MPE). Methods: A multidisciplinary panel developed seven questions using the PICO (Population, Intervention, Comparator, and Outcomes) format. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the Evidence to Decision framework was applied to each question. Recommendations were formulated, discussed, and approved by the entire panel. Results: The panel made weak recommendations in favor of: 1) using ultrasound to guide pleural interventions; 2) not performing pleural interventions in asymptomatic patients with MPE; 3) using either an indwelling pleural catheter (IPC) or chemical pleurodesis in symptomatic patients with MPE and suspected expandable lung; 4) performing large‐volume thoracentesis to assess symptomatic response and lung expansion; 5) using either talc poudrage or talc slurry for chemical pleurodesis; 6) using IPC instead of chemical pleurodesis in patients with nonexpandable lung or failed pleurodesis; and 7) treating IPC‐associated infections with antibiotics and not removing the catheter. Conclusions: These recommendations, based on the best available evidence, can guide management of patients with MPE and improve patient outcomes.