Christopher G. Slatore

Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation

BACKGROUND Lung cancer is the leading cause of cancer-related death in the United States. Because early-stage lung cancer is associated with lower mortality than late-stage disease, early detection and treatment may be beneficial. PURPOSE To update the 2004 review of screening for lung cancer for the U.S. Preventive Services Task Force, focusing on screening with low-dose computed tomography (LDCT). DATA SOURCES MEDLINE (2000 to 31 May 2013), the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2012), Scopus, and reference lists. STUDY SELECTION English-language randomized, controlled trials or cohort studies that evaluated LDCT screening for lung cancer. DATA EXTRACTION One reviewer extracted study data about participants, design, analysis, follow-up, and results, and a second reviewer checked extractions. Two reviewers rated study quality using established criteria. DATA SYNTHESIS Four trials reported results of LDCT screening among patients with smoking exposure. One large good-quality trial reported that screening was associated with significant reductions in lung cancer (20%) and all-cause (6.7%) mortality. Three small European trials showed no benefit of screening. Harms included radiation exposure, overdiagnosis, and a high rate of false-positive findings that typically were resolved with further imaging. Smoking cessation was not affected. Incidental findings were common. LIMITATIONS Three trials were underpowered and of insufficient duration to evaluate screening effectiveness. Overdiagnosis, an important harm of screening, is of uncertain magnitude. No studies reported results in women or minority populations. CONCLUSION Strong evidence shows that LDCT screening can reduce lung cancer and all-cause mortality. The harms associated with screening must be balanced with the benefits. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Obesity and COPD: associated symptoms, health-related quality of life, and medication use.

Background: There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD. Methods: We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. Georges Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and co-morbidities. Results: The majority of our population was male (n = 355, 98%) and either overweight (n = 115, 32%) or obese (n = 138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV1 55.4% ±19.9% predicted, overweight: mean FEV1 50.0% ±20.4% predicted) than normal weight subjects (mean FEV1 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2 = 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients. Conclusions: Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended.

Lung Cancer and Hormone Replacement Therapy: Association in the Vitamins and Lifestyle Study

PURPOSE Lung cancer is the leading cause of cancer-related mortality among women. The role of hormone replacement therapy (HRT) in lung cancer development is unclear. PATIENTS AND METHODS We evaluated a prospective cohort of 36,588 peri- and postmenopausal women aged 50 to 76 years from Washington State recruited in 2000 to 2002 (Vitamins and Lifestyle [VITAL] Study). Lung cancer cases (n = 344) were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry during 6 years of follow-up. Hazard ratios (HRs) associated with use and duration of specific HRT formulations were calculated for total incident lung cancer, specific morphologies, and cancer by stage at diagnosis. RESULTS After adjusting for smoking, age, and other potential confounders, there was an increased risk of incident lung cancer associated with increasing duration of estrogen plus progestin (E+P) use (HR = 1.27 for E+P use 1 to 9 years, 95% CI, 0.91 to 1.78; and HR = 1.48 for E+P use > or = 10 years, 95% CI, 1.03 to 2.12; P for trend = .03). There was no association with duration of unopposed estrogen use. Duration of E+P use was associated with an advanced stage at diagnosis (P for trend = .03). CONCLUSION Use of E+P increased the risk of incident lung cancer in a duration-dependent manner, with an approximate 50% increased risk for use of 10 years or longer. These findings may be helpful for informing women of their risk of developing lung cancer and delineating important pathways involved in hormone metabolism and lung cancer.

Follow-up and Surveillance of the Patient With Lung Cancer After Curative-Intent Therapy: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND These guidelines are an update of the evidence-based recommendations for follow-up and surveillance of patients after curative-intent therapy for lung cancer. Particular updates pertain to whether imaging studies, health-related quality-of-life (HRQOL) measures, tumor markers, and bronchoscopy improve outcomes after curative-intent therapy. METHODS Meta-analysis of Observational Studies in Epidemiology guidelines were followed for this systematic review, including published studies on posttreatment outcomes in patients who received curative-intent therapy since the previous American College of Chest Physicians subject review. Four population, intervention, comparison, and outcome questions were formulated to guide the review. The MEDLINE and CINAHL databases were searched from June 1, 2005, to July 8, 2011, to ensure overlap with the search strategies used previously. RESULTS A total of 3,412 citations from MEDLINE and 431 from CINAHL were identified. Only 303 were relevant. Seventy-six of the 303 articles were deemed eligible on the basis of predefined inclusion criteria after full-text review, but only 34 provided data pertaining directly to the subject of the questions formulated to guide this review. In patients undergoing curative-intent surgical resection of non-small cell lung cancer, chest CT imaging performed at designated time intervals after resection is suggested for detecting recurrence. It is recommended that treating physicians who are able to incorporate the patients clinical findings into decision-making processes be included in follow-up and surveillance strategies. The use of validated HRQOL instruments at baseline and during follow-up is recommended. Biomarker testing during surveillance outside clinical trials is not suggested. Surveillance bronchoscopy is suggested for patients with early central airway squamous cell carcinoma treated by curative-intent photodynamic therapy and for patients with intraluminal bronchial carcinoid tumor who have undergone curative-intent bronchoscopic treatment with Nd:YAG laser or electrocautery. CONCLUSIONS There is a paucity of well-designed prospective studies specifically targeting follow-up and surveillance modalities aimed at improving survival or QOL after curative-intent therapy. Additional research is warranted to clarify which curative-intent treatment modalities affect HRQOL the most and to identify patients who are at the most risk for recurrence or impaired QOL after treatment. Further evidence is needed to determine how the frequency and duration of surveillance programs that include imaging studies, QOL measurements, tumor markers, or bronchoscopy affect patient morbidity, survival, HRQOL, and health-care costs.

An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice.

RATIONALE Annual low-radiation-dose computed tomography (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple organizations. However, LDCT screening is complex, and implementation requires careful planning to ensure benefits outweigh harms. Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs. OBJECTIVES To promote successful implementation of comprehensive LDCT screening programs that are safe, effective, and sustainable. METHODS The American Thoracic Society (ATS) and American College of Chest Physicians (ACCP) convened a committee with expertise in lung cancer screening, pulmonary nodule evaluation, and implementation science. The committee reviewed the evidence from systematic reviews, clinical practice guidelines, surveys, and the experience of early-adopting LDCT screening programs and summarized potential strategies to implement LDCT screening programs successfully. MEASUREMENTS AND MAIN RESULTS We address steps that sites should consider during the main three phases of developing an LDCT screening program: planning, implementation, and maintenance. We present multiple strategies to implement the nine core elements of comprehensive lung cancer screening programs enumerated in a recent ACCP/ATS statement, which will allow sites to select the strategy that best fits with their local context and workflow patterns. Although we do not comment on cost-effectiveness of LDCT screening, we outline the necessary costs associated with starting and sustaining a high-quality LDCT screening program. CONCLUSIONS Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective.

Implementation of Lung Cancer Screening in the Veterans Health Administration

Importance The US Preventive Services Task Force recommends annual lung cancer screening (LCS) with low-dose computed tomography for current and former heavy smokers aged 55 to 80 years. There is little published experience regarding implementing this recommendation in clinical practice. Objectives To describe organizational- and patient-level experiences with implementing an LCS program in selected Veterans Health Administration (VHA) hospitals and to estimate the number of VHA patients who may be candidates for LCS. Design, Setting, and Participants This clinical demonstration project was conducted at 8 academic VHA hospitals among 93 033 primary care patients who were assessed on screening criteria; 2106 patients underwent LCS between July 1, 2013, and June 30, 2015. Interventions Implementation Guide and support, full-time LCS coordinators, electronic tools, tracking database, patient education materials, and radiologic and nodule follow-up guidelines. Main Outcomes and Measures Description of implementation processes; percentages of patients who agreed to undergo LCS, had positive findings on results of low-dose computed tomographic scans (nodules to be tracked or suspicious findings), were found to have lung cancer, or had incidental findings; and estimated number of VHA patients who met the criteria for LCS. Results Of the 4246 patients who met the criteria for LCS, 2452 (57.7%) agreed to undergo screening and 2106 (2028 men and 78 women; mean [SD] age, 64.9 [5.1] years) underwent LCS. Wide variation in processes and patient experiences occurred among the 8 sites. Of the 2106 patients screened, 1257 (59.7%) had nodules; 1184 of these patients (56.2%) required tracking, 42 (2.0%) required further evaluation but the findings were not cancer, and 31 (1.5%) had lung cancer. A variety of incidental findings, such as emphysema, other pulmonary abnormalities, and coronary artery calcification, were noted on the scans of 857 patients (40.7%). Conclusions and Relevance It is estimated that nearly 900 000 of a population of 6.7 million VHA patients met the criteria for LCS. Implementation of LCS in the VHA will likely lead to large numbers of patients eligible for LCS and will require substantial clinical effort for both patients and staff.

Intensive Care Unit Outcomes Among Patients With Lung Cancer in the Surveillance, Epidemiology, and End Results–Medicare Registry

PURPOSE Lung cancer is the leading cause of cancer-related mortality. Intensive care unit (ICU) use among patients with cancer is increasing, but data regarding ICU outcomes for patients with lung cancer are limited. PATIENTS AND METHODS We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare registry (1992 to 2007) to conduct a retrospective cohort study of patients with lung cancer who were admitted to an ICU for reasons other than surgical resection of their tumor. We used logistic and Cox regression to evaluate associations of patient characteristics and hospital mortality and 6-month mortality, respectively. We calculated adjusted associations for mechanical ventilation receipt with hospital and 6-month mortality. RESULTS Of the 49,373 patients with lung cancer admitted to an ICU for reasons other than surgical resection, 76% of patients survived the hospitalization, and 35% of patients were alive 6 months after discharge. Receipt of mechanical ventilation was associated with increased hospital mortality (adjusted odds ratio, 6.95; 95% CI, 6.89 to 7.01; P < .001), and only 15% of these patients were alive 6 months after discharge. Of all ICU patients with lung cancer, the percentage of patients who survived 6 months from discharge was 36% for patients diagnosed in 1992 and 32% for patients diagnosed in 2005, whereas it was 16% and 11% for patients who received mechanical ventilation, respectively. CONCLUSION Most patients with lung cancer enrolled in Medicare who are admitted to an ICU die within 6 months of admission. To improve patient-centered care, these results should guide shared decision making between patients with lung cancer and their clinicians before an ICU admission.

Patient-Centered Outcomes among Lung Cancer Screening Recipients with Computed Tomography: A Systematic Review

Introduction: Lung cancer screening using low-dose computed tomography (LDCT) is now widely recommended for adults who are current or former heavy smokers. It is important to evaluate the impact of screening on patient-centered outcomes. Among current and former smokers eligible for lung cancer screening, we sought to determine the consequences of screening with LDCT, and subsequent results, on patient-centered outcomes such as quality of life, distress, and anxiety. Methods: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth Quarter 2012), MEDLINE (2000 to May 31, 2013), reference lists of articles, and Scopus for relevant English-language studies and systematic reviews. To evaluate the effect of LDCT screening on patient-centered outcomes, we included only randomized controlled trials (RCTs) involving asymptomatic adults. To evaluate the association of particular results and/or recommendations from a screening LDCT with patient-centered outcomes, we included results from RCTs as well as from cohort studies. Results: A total of 8215 abstracts were reviewed. Five publications from two European RCTs and one publication from a cohort study conducted in the United States met inclusion criteria. The process of LDCT lung cancer screening was associated with short-term psychologic discomfort in many people but did not affect distress, worry, or health-related quality of life. False-positive results were associated with short-term increases in distress that returned to levels that were similar to those among people with negative results. Negative results were associated with short-term decreases in distress. Conclusions: As lung cancer screening is implemented in the general population, it will be important to evaluate its association with patient-centered outcomes. People considering lung cancer screening should be aware of the possibility of distress caused by false-positive results. Clinicians may want to consider tailoring communication strategies that can decrease the distress associated with these results.

Adherence to Long-Acting Inhaled Therapies among Patients with Chronic Obstructive Pulmonary Disease (COPD)

Abstract Background: Long-acting inhaled medications are an important component of the treatment of patients with chronic obstructive pulmonary disease (COPD), yet few studies have examined the determinants of medication adherence among this patient population. Objective: We sought to identify factors associated with adherence to long-acting beta-agonists (LABA) and inhaled corticosteroids (ICS) among patients with COPD. Methods: We performed secondary analysis of baseline data collected in a randomized trial of 376 Veterans with spirometrically confirmed COPD. We used electronic pharmacy records to assess adherence, defined as a medication possession ratio of ≥0.80. We investigated the following exposures: patient characteristics, disease severity, medication regimen complexity, health behaviors, confidence in self-management, and perceptions of provider skill. We performed multivariable logistic regression, clustered by provider, to estimate associations. Results: Of the 167 patients prescribed LABA, 54% (n = 90) were adherent to therapy while only 40% (n = 74) of 184 the patients prescribed ICS were adherent. Higher adherence to LABA and ICS was associated with patient perception of their provider as being an “expert” in diagnosing and managing lung disease [For LABA: OR = 21.70 (95% CI 6.79, 69.37); For ICS OR = 7.93 (95% CI 1.71, 36.67)]. Factors associated with adherence to LABA, but not ICS, included: age, education, race, COPD severity, smoking status, and confidence in self-management. Conclusions: Adherence to long-acting inhaled medications among patients with COPD is poor, and determinants of adherence likely differ by medication class. Patient perception of clinician expertise in lung disease was the factor most highly associated with adherence to long-acting therapies.

Patient-clinician communication: associations with important health outcomes among veterans with COPD.

BACKGROUND High quality patient-clinician communication is widely advocated, but little is known about which health outcomes are associated with communication for patients with COPD. METHODS Using a cross-sectional study of 342 veterans enrolled in a randomized controlled trial, we evaluated the association of communication, measured with the quality of communication (QOC) instrument, with subject-reported quality of clinician care, breathing problem confidence, and general self-rated health. We measured these associations using general estimating equations and adjusted odds ratios (OR) of patient-reported outcomes associated with one-point changes in QOC scores. RESULTS Nearly one-half of the subjects reported receiving the best imaginable care (47%), whereas fewer reported being confident with their breathing problems all the time (29%) or in very good or excellent health (15%). General communication was associated with best-imagined quality of care (OR, 4.29; 95% CI, 2.84-6.48; P < .001) and confidence in dealing with breathing problems all the time (OR, 1.74; 95% CI, 1.34-2.25; P < .001) but not general self-rated health (OR, 1.19; 95% CI, 0.92-1.55; P = .19). Specific clinician behaviors with larger associations with higher quality care included listening, caring, and attentiveness. The associations between general communication and quality care increased over time (P for interaction .03). CONCLUSIONS Communication between patients and clinicians is associated with quality of care and confidence in dealing with breathing problems, and this association may change over time. Attention to specific communication strategies may lead to improvements in the care of patients with COPD.