Comparison of standard and penalized logistic regression in risk model development.

Objective: Regression models are ubiquitous in thoracic surgical research. We aimed to compare the value of standard logistic regression with the more complex but increasingly used penalized regression models using a recently published risk model as an example. Methods: Using a standardized data set of clinical T1-3N0 esophageal cancer patients, we created models to predict the likelihood of unexpected pathologic nodal disease after surgical resection. Models were fitted using standard logistic regression or penalized regression (ridge, lasso, elastic net, and adaptive lasso). We compared the model performance (Brier score, calibration slope, C statistic, and overfitting) of standard regression with penalized regression models. Results: Among 3206 patients with clinical T1-3N0 esophageal cancer, 668 (22%) had unexpected pathologic nodal disease. Of the 15 candidate variables considered in the models, the key predictors of nodal disease included clinical tumor stage, tumor size, grade, and presence of lymphovascular invasion. The standard regression model and all 4 penalized logistic regression models had virtually identical performance with Brier score ranging from 0.138 to 0.141, concordance index ranging from 0.775 to 0.788, and calibration slope from 0.965 to 1.05. Conclusions: For predictive modeling in surgical outcomes research, when the data set is large and the outcome of interest is relatively frequent, standard regression models and the more complicated penalized models are very likely to have similar predictive performance. The choice of statistical methods for risk model development should be on the basis of the nature of the data at hand and good statistical practice, rather than the novelty or complexity of statistical models.

Minimum Volume Standards for Surgical Care of Early-Stage Lung Cancer: A Cost-Effectiveness Analysis.

BACKGROUND: Multiple stakeholders have advocated for minimum volume standards for complex surgical procedures. The Leapfrog Group recommends that patients with non-small cell lung cancer (NSCLC) receive surgical resection at hospitals that perform at least 40 lung resections annually. However, the cost-effectiveness of this paradigm is unknown. METHODS: A cost-effectiveness analysis was performed on 90-day and 5-year horizons for patients with clinical stage I NSCLC undergoing surgical resection at hospitals stratified by Leapfrog standard. Model inputs were derived from either the literature or a propensity score-matched cohort using the National Cancer Database. For the 5-year horizon, we simulated using a Markov model with 1-year cycle. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. RESULTS: For the 90-day horizon, resection at a Leapfrog hospital was more costly ($25 567 vs $25 530) but had greater utility (0.185 vs 0.181 quality-adjusted life-years), resulting in an ICER of 10 506. Similarly, for the 5-year horizon, resection at a Leapfrog hospital was more costly ($26 600 vs $26 495) but more effective (3.216 vs 3.122 quality-adjusted life-years), resulting in an ICER of 1108. When the costs for long-distance travel, lodging, and loss of productivity for caregivers were factored in, the ICER was 20 499 during the 5-year horizon for resection at Leapfrog hospitals. Using a willingness-to-pay threshold of $50 000, resection at a Leapfrog hospital remained cost-effective. CONCLUSIONS: Receiving surgery for clinical stage I NSCLC at hospitals that meet Leapfrog volume standards is cost-effective. Payers and policymakers should consider supporting patient and caregiver travel to higher volume institutions for lung cancer surgery.

A Clinical Nomogram for Predicting Node-positive Disease in Esophageal Cancer.

OBJECTIVE: We developed and validated a nomogram predicting the likelihood of occult lymph node metastases in surgically resectable esophageal cancers. BACKGROUND: Patients with esophageal cancer with positive lymph nodes benefit from neoadjuvant therapy, but limitations in current clinical staging techniques mean nodal metastases often go undetected preoperatively. METHODS: The National Cancer Database was queried for patients with clinical T1-3N0M0 cancer undergoing upfront esophagectomy from 2004 to 2014. Multivariable logistic regression was used to develop the risk model using both statistical significance and clinical importance criteria for variable selection. Predictive accuracy was assessed and bootstrapping was used for validation. A nomogram was constructed for presentation of the final model. RESULTS: Of 3186 patients, 688 (22%) had pathologic lymph node involvement (pN+) and 2498 (78%) had pN0 status. Variables associated with pN+ status included histology [adenocarcinoma vs squamous: odds ratio (OR) 1.75], tumor stage (T1: reference, T2: OR 1.90, T3: OR 2.17), tumor size (<1 cm: reference, 1-2 cm: OR 2.25, 2-3 cm: OR 3.82, 3-4 cm: OR 5.40, 4-5 cm: OR 5.66, ≥5 cm: OR 6.02), grade (1: reference, 2: OR 2.62, 3: OR 4.39, 4: OR 4.15, X: OR 1.87), and presence of lymphovascular invasion (absent: reference, present: OR 4.70, missing: OR 1.87), all P < 0.001. A nomogram with these variables had good predictive accuracy (Brier score: 0.14, calibration slope: 0.97, c-index: 0.77). CONCLUSIONS: We created a nomogram predicting the likelihood of pathologic lymph node involvement in patients with esophageal cancer who are clinically node negative using a generalizable dataset. Risk stratification with this nomogram could improve delivery of appropriate perioperative care.

Assessment of Preoperative Opioid Use Prevalence and Clinical Outcomes in Pulmonary Resection.

BACKGROUND: Preoperative opioid use is associated with increased health care use after elective abdominal surgery. However, the scope of preoperative opioid use and its association with outcomes have not been described in elective pulmonary resection. This study aimed to characterize prevalent preoperative opioid use in patients undergoing elective pulmonary resection and compare clinical outcomes between patients with and without preoperative opioid exposure. METHODS: The study investigators assembled a retrospective cohort of adult patients undergoing elective pulmonary resection by using the IBM Watson Health MarketScan Database (2007 to 2015). The study compared opioid-naïve patients with patients with a history of preoperative opioid exposure (>0 morphine milligram equivalent prescription filled within 90 days before surgery). Multivariable logistic and linear regressions adjusting for patient sociodemographic, comorbidity, and operative characteristics were used to compare odds of postoperative complication, prolonged length-of-stay (>14 days), 30-day postdischarge emergency department visits, 90-day readmissions, and 90-day costs. RESULTS: The study identified 14,373 patients, 4502 (31.3%) of whom had opioid exposure before pulmonary resection. In multivariable regression, patients with preoperative opioid exposure had significantly higher odds of experiencing a prolonged length of stay (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.11 to 1.58), 30-day emergency department visits (OR, 1.24; 95% CI, 1.01 to 1.41), and 90-day readmissions (OR, 1.41; 95% CI, 1.28 to 1.55). Adjusted 90-day costs were approximately 5% higher for patients with preoperative opioid use (P < .001). CONCLUSIONS: One-third of patients who underwent pulmonary resection used opioids preoperatively and were at risk of experiencing adverse outcomes and having significantly higher health care use. They represent a unique high-risk population that will require novel, targeted interventions.

Utilization Trends, Outcomes, and Cost in Minimally Invasive Lobectomy.

BACKGROUND: Minimally invasive lobectomy is associated with decreased morbidity and length of stay. However, there have been few published analyses using recent, population-level data to compare clinical outcomes and cost by surgical approach, inclusive of robotic-assisted thoracoscopic surgery (RATS). The objective of this study was to compare outcomes and hospitalization costs among patients undergoing open, video-assisted thoracoscopic surgery (VATS) and RATS lobectomy. METHODS: We identified patients who underwent elective lobectomy in the Healthcare Cost and Utilization Project Florida State Inpatient Database (2008 to 2014). Hierarchical logistic and linear regression models were used to compare in-hospital mortality, postoperative complications, prolonged length of stay, 30-day readmissions, and index hospitalization costs among cohorts. RESULTS: We identified 15,038 patients, of whom 8501 (56.5%), 4608 (30.7%), and 1929 (12.8%) underwent open, VATS, and RATS lobectomy, respectively. Robotic-assisted lobectomies comprised less than 1% of total lobectomy volume in 2008, and grew to 25% of lobectomy volume by 2014. Both VATS and RATS lobectomies were associated with decreased in-hospital mortality compared to thoracotomy (VATS odds ratio 0.69, 95% confidence interval, 0.50 to 0.94; RATS odds ratio 0.58, 95% confidence interval, 0.35 to 0.96; P = .016). After adjusting for patient age, sex, income, comorbidities, and hospital teaching status, VATS lobectomy was 2% less expensive (P = .007) and robotic-assisted lobectomy was 13% more expensive (P < .001) than the open approach. CONCLUSIONS: Minimally invasive approaches were associated to improved clinical outcomes compared with open lobectomy. However, only robotic-assisted lobectomy has had rapid growth in utilization. Despite additional cost, RATS lobectomy appears to provide a viable minimally invasive alternative for general thoracic procedures.

Trends in Treatment of T1N0 Esophageal Cancer.

OBJECTIVE: The purpose of this study was to explore nationwide trends in treatment and outcomes of T1N0 esophageal cancer. BACKGROUND: Endoscopic treatment has become an accepted option for early-stage esophageal cancer, but nationwide utilization rates and outcomes are unknown. METHODS: T1N0 esophageal cancers were identified in the National Cancer Database from 2004 to 2014. We assessed trends in treatment; compared endoscopic therapy, esophagectomy, chemoradiation, and no treatment; and performed a subgroup analysis of T1a and T1b patients from 2010 to 2014 (AJCC 7). RESULTS: A total of 12,383 patients with clinical T1N0 esophageal cancer were analyzed. Over a decade, use of endoscopic therapy increased from 12.7% to 33.6%, whereas chemoradiation and esophagectomy decreased, P < 0.01. The rise in endoscopic treatment of T1a disease from 42.7% to 50.6% was accompanied by a decrease in esophagectomies from 21.7% to 12.8% (P < 0.01). For T1b disease, the rise in endoscopic treatment from 16.9% to 25.1% (P = 0.03) was accompanied by decreases in no treatment and chemoradiation, whereas the rate of esophagectomies remained approximately 50%. Unadjusted median survival was longer for patients undergoing resection: esophagectomy, 98.6 months; endoscopic therapy, 77.7 months; chemoradiation, 17.3 months; no treatment, 8.2 months; P < 0.01. Risk-adjusted Cox modeling showed esophagectomy was associated with improved survival [hazard ratio (HR): 0.85], and chemoradiation (HR: 1.79) and no treatment (HR: 3.57) with decreased survival, compared to endoscopic therapy (P < 0.01). CONCLUSIONS: Use of endoscopic therapy for T1 esophageal cancer has increased significantly: for T1a, as an alternative to esophagectomy; and for T1b, as an alternative to no treatment or chemoradiation. Despite upfront risks, long-term survival is highest for patients who can undergo esophagectomy.

Adjuvant Therapy for Node-Positive Esophageal Cancer After Induction and Surgery: A Multisite Study.

BACKGROUND: The benefit of adjuvant treatment for esophageal cancer patients with positive lymph nodes after induction therapy and esophagectomy is uncertain. This in-depth multicenter study assessed the benefit of adjuvant therapy in this population. METHODS: A retrospective cohort study from 9 institutions included patients who received neoadjuvant treatment, underwent esophagectomy from 2000 to 2014, and had positive lymph nodes on pathology. Factors associated with administration of adjuvant therapy were assessed using multilevel random-intercept modeling to account for institutional variation in practice. Kaplan-Meier analyses were performed based on adjuvant treatment status. Variables associated with survival were identified using Cox proportional hazards modeling. RESULTS: The study analyzed 1082 patients with node-positive cancer after induction therapy and esophagectomy: 209 (19.3%) received adjuvant therapy and 873 (80.7%) did not. Administration of adjuvant treatment varied significantly from 3.2% to 50.0% between sites (P < .001). Accounting for institution effect, factors associated with administration of adjuvant therapy included clinically positive and negative prognostic characteristics: younger age, higher pathologic stage, pathologic grade, no neoadjuvant radiotherapy nonsmoking status, and absence of postoperative infection. Kaplan-Meier analysis showed patients receiving adjuvant therapy had a longer median survival of 2.6 years vs 2.3 years (P = .02). Cox modeling identified adjuvant treatment as independently associated with improved survival, with a 24% reduction in mortality (hazard ratio, 0.76; P = .005). CONCLUSIONS: Adjuvant therapy was associated with improved overall survival. Therefore, consideration should be given to administration of adjuvant therapy to esophageal cancer patients who have persistent node-positive disease after induction therapy and esophagectomy and are able to tolerate additional treatment.

Imaging Surveillance for Surgically Resected Stage I Non-Small Cell Lung Cancer: Is More Always Better?

Objective: Routine surveillance imaging for patients with resected non-small cell lung cancer is standard for the detection of disease recurrence and new primary lung cancers. However, surveillance intensity varies widely in practice, and its impact on long-term outcomes is poorly understood. We hypothesized that surveillance intensity was not associated with 5-year overall survival in patients with resected stage I non-small cell lung cancer. Additionally, we examined patterns of recurrence and new primary lung cancer development. Methods: Cancer registrars at Commission on Cancer accredited institutions re-abstracted records to augment National Cancer Database patient data with information on comorbidities, imaging surveillance including intent and result of imaging, and recurrence (2007-2012). Pathologic stage I non-small cell lung cancer patients undergoing computed-tomography surveillance were placed into three imaging surveillance groups based on clinical practice guidelines: high intensity (3 month), moderate intensity (6 month), and low intensity (annual). Kaplan Meier analysis and Cox regression were used to compare overall survival among the three surveillance groups. Results: 2442 patients were identified, with 805 (33%), 1216 (50%), and 421 (17%) patients in the high, moderate, and low surveillance intensity groups, respectively. Five-year overall survival was similar between intensity groups (p=0.547). Surveillance on asymptomatic patients detected 210 (63%) cases of locoregional recurrences and 128 (72%) cases of new primary lung cancer. Conclusions: In a unique national dataset of long-term outcomes for stage I non-small cell lung cancer, surveillance intensity was not associated with 5-year overall survival.

The role of small or single-institution prospective studies in thoracic research.

Interventional studies are designed specifically to test the impact of a treatment or management strategy on an outcome of interest. In this article, we will highlight two viewpoints regarding the role of small or single-institution prospective interventional studies within the field of thoracic surgery: first, that these studies are beneficial and can positively impact the field, and second, that these studies can have such significant limitations that they may have no meaningful impact. We will also review elements that can make for successful design and execution of small prospective interventional studies.

Unintended consequences of changes to lung allocation policy.

Organ allocation for transplantation aims to balance the principles of justice and medical utility to optimally utilize a scarce resource. To address practical considerations, the United States is divided into 58 donor service areas (DSA), each constituting the first unit of allocation. In November 2017, in response to a lawsuit in New York, an emergency action change to lung allocation policy replaced the DSA level of allocation for donor lungs with a 250 nautical mile circle around the donor hospital. Similar policy changes are being implemented for other organs including heart and liver. Findings from a recent US Department of Health and Human Services report, supplemented with data from our institution, suggest that the emergency policy has not resulted in a change in the type of patients undergoing lung transplantation (LT) or early postoperative outcomes. However, there has been a significant decline in local LT, where donor and recipient are in the same DSA. With procurement teams having to travel greater distances, organ ischemic time has increased and median organ cost has more than doubled. We propose potential solutions for consideration at this critical juncture in the field of transplantation. Policymakers should choose equitable and sustainable access for this lifesaving discipline.

Induction Radiation Therapy for Esophageal Cancer: Does Dose Affect Outcomes?

BACKGROUND: Wide variation is seen in the dosage of preoperative induction radiation therapy for esophageal cancer. We investigated associations between outcomes after esophagectomy and dosage of induction radiation therapy. METHODS: Patients undergoing induction radiation therapy (30 to 70 Gy), followed by esophagectomy, were identified from the National Cancer Database and classified as low (<40 Gy), standard (40 to 50.4 Gy), and high dose (>50.4 Gy). Perioperative outcomes and overall survival were compared. Subgroup analysis compared two common dosages: 45 Gy and 50.4 Gy. RESULTS: From 2004 to 2014, 10,738 patients (84.7%) received standard-dose radiation, increasing from 69.7% in 2004 to 93.6% in 2014 (p < 0.001), 1,329 (10.5%) received low-dose radiation, and 608 (4.8%) received high-dose radiation. Higher rates of pathologic complete response (pCR; low: 11.7%, standard: 16.2%, high: 21.0%; p < 0.001) and downstaging (low: 52.0%, standard: 56.4%, high: 63.1%, p = 0.001) were observed as the dosage increased. On multivariable analysis, compared with standard-dose, high-dose radiation was associated with higher 30-day mortality (odds ratio [OR], 2.11; p < 0.001) without a higher likelihood of downstaging or pCR. Low-dose radiation was associated with lower likelihood of downstaging (OR, 0.85; p = 0.04) and pCR (OR, 0.67; p < 0.001) without lowering the risk of 30-day mortality. The dose of 50.4 Gy was associated with higher likelihood of pCR (OR, 1.12; p = 0.04), without affecting 30-day mortality, compared with 45 Gy. CONCLUSIONS: High-dose induction radiation (>50.4 Gy) is associated with increased perioperative death after esophagectomy, without a significant improvement in tumor response. Low-dose radiation (<30 Gy) is associated with worse tumor response without a lower risk of perioperative death. Within standard dosages, 50.4 Gy is associated with higher likelihood of pCR without adversely affecting perioperative mortality compared with 45 Gy.

Postoperative Pneumonia Prevention in Pulmonary Resections: A Feasibility Pilot Study.

BACKGROUND: Pneumonia after pulmonary resection occurs in 5% to 12% of patients and causes substantial morbidity. Oral hygiene regimens lower the incidence of ventilator-associated pneumonias; however, the impact in patients undergoing elective pulmonary resection is unknown. We conducted a prospective pilot study to assess the feasibility of an oral hygiene intervention in this patient cohort. METHODS: Patients undergoing elective pulmonary resection were prospectively enrolled in a single-arm interventional study with time-matched controls. Participants were asked to brush their teeth with 0.12% chlorhexidine three times daily for 5 days before their operations and 5 days or until the time of discharge after their operations. Patients were eligible if they had known or suspected lung cancer and were undergoing (1) any anatomic lung resection or (2) a wedge resection with forced expiratory volume in 1 second or diffusing capacity of lung for carbon monoxide less than 50% predicted. RESULTS: Sixty-two patients were enrolled in the pilot intervention group and compared with a contemporaneous cohort of 611 patients who met surgical inclusion criteria. Preoperative adherence to the chlorhexidine toothbrushing regimen was high: median 100% (interquartile range: 87% to 100%). Postoperatively, 80% of patients continued toothbrushing, whereas 20% declined further participation. Among those who participated postoperatively, median adherence was 86% (interquartile range: 53% to 100%). There was a trend toward reduction in postoperative pneumonia: 1.6% (1 of 62) in the intervention cohort versus 4.9% (30 of 611) in the time-matched cohort (p = 0.35). The number needed to treat to prevent one case of pneumonia was 30 patients. CONCLUSIONS: This pilot study demonstrated patients can comply with an inexpensive perioperative oral hygiene regimen that may be promising for reducing morbidity (Clinical Trials Registry: NCT01446874).

Enhanced Recovery After Surgery (ERAS) in Thoracic Surgery.

Enhanced Recovery After Surgery (ERAS) pathways are protocolled collections of perioperative decisions designed to improve outcomes that are becoming increasingly popular across surgical subspecialties. In this article, we review 5 recent manuscripts focused on ERAS for elective pulmonary resections, focusing on the components of the pathways and the resultant outcomes. Overall, we observed that ERAS protocols can be safely implemented without increasing hospital readmission or mortality. The benefit is largely seen in shortened length of stay, though there is some promise for decreasing rates of important perioperative complications, especially in patients receiving thoracotomies. More research is needed into the specific elements that impact care, as well as the effect on overall patient experience.

Surveillance versus esophagectomy in esophageal cancer patients with a clinical complete response after induction chemoradiation.

There currently exists an area of controversy in treatment of esophageal cancer for patients who have an apparent clinical complete response (cCR) after induction chemoradiation. A standard treatment is to offer these patients an esophagectomy, but increasingly there is interest from both the patient and provider for active surveillance with so-called "salvage" esophagectomies for local recurrence as an alternative treatment paradigm. In this article, we review the existing evidence that stakeholders should consider for clinical decision-making in this specific patient population, including: the accuracy of post-induction clinical restaging, the reliability of operative risk assessment, the feasibility and adherence to surveillance strategies, and the observed outcomes in these patients after salvage esophagectomy or continued active surveillance. We also briefly discuss quality of life and future directions for this field.