Lobe-specific lymph node sampling is associated with lower risk of cancer recurrence.

Objective: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients. Methods: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data from operative and pathology reports for patients with clinical stage I NSCLC (2006-2016). For simplicity in comparison, we included patients who had right upper lobe (RUL) or left upper lobe (LUL) tumors. Based on modified European Society of Thoracic Surgeons guidelines, lobe-specific sampling was defined for RUL tumors (stations 2, 4, 7, and 10 or 11) and LUL tumors (stations 5 or 6, 7, and 10 or 11). Our primary outcome was the risk of cancer recurrence, as assessed by Fine and Gray competing risks modeling. Secondary outcomes included overall survival (OS) and pathologic upstaging. Analyses were adjusted for relevant patient, disease, and treatment variables. Results: Our study included 3534 patients with RUL tumors and 2667 patients with LUL tumors. Of these, 277 patients (7.8%) with RUL tumors and 621 patients (23.2%) with LUL tumors met lobe-specific assessment criteria. Comparatively, 34.7% of patients met the criteria for count-based assessment, and 25.8% met the criteria for station-based sampling (ie, any 3 N2 stations and 1 N1 station). Adherence to lobe-specific assessment was associated with lower cumulative incidence of recurrence (adjusted hazard ratio [aHR], 0.83; 95% confidence interval [CI], 0.70-0.98) and a higher likelihood of pathologic upstaging (aHR, 1.49; 95% CI, 1.20-1.86). Lobe-specific assessment was not associated with OS. Conclusions: Adherence to intraoperative LN sampling guidelines is low. Lobe-specific assessment is associated with superior outcomes in early-stage NSCLC. Quality metrics that assess adherence to intraoperative LN sampling, such as the CoC Operative Standards manual, also should consider lobe-specific criteria.

Exposure to Agent Orange is associated with increased recurrence after surgical treatment of stage I non-small cell lung cancer.

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.

Lung Transplant Procedure of Choice: Bilateral Transplantation Versus Single Transplantation Complications, Quality of Life, and Survival.

This article examines the existing literature regarding single (SLT) and bilateral lung transplantation (BLT) to help answer the question of which approach is preferable. Specifically, this review highlights the following subjects: disease-specific indications for SLT versus BLT; the impact of procedure type on posttransplantation functional status; the impact of procedure type on posttransplantation quality of life; chronic rejection after lung transplantation; ethical challenges facing the choice between single and bilateral transplants; and, novel strategies in this arena.

Comparison of perioperative outcomes among non-small cell lung cancer patients with neoadjuvant immune checkpoint inhibitor plus chemotherapy, EGFR-TKI, and chemotherapy alone: a real-world evidence study.

Background: The utilization of neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy has increased significantly for resectable non-small cell lung cancer (NSCLC). It is still unclear whether such a treatment paradigm affects perioperative outcomes compared with other neoadjuvant treatment. We aimed to evaluate the perioperative outcomes of pulmonary resection after neoadjuvant ICI plus chemotherapy and to compare them with neoadjuvant epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) and neoadjuvant chemotherapy alone for resectable NSCLC. Methods: A retrospective cohort including 194 stage IB-IIIB NSCLC underwent surgical resection after neoadjuvant treatment between 2018 and 2020 were reviewed. Perioperative complications were evaluated using the Common Terminology Criteria for Adverse Events, and were compared using one-way analysis of variance for continuous variables and Pearson chi-square test. Results: There were 42, 54, and 98 patients in the neoadjuvant ICI plus chemotherapy, EGFR-TKI, and chemotherapy alone groups, respectively. The tumor size before neoadjuvant treatment was well balanced among the three groups (P=0.122). A shorter median surgical time was observed in the EGFR-TKI group than ICI plus chemotherapy group and chemotherapy group alone (120 vs. 150 vs. 146 min, P=0.041). Video-assisted thoracoscopic surgery was performed in 37 (88.1%), 49 (90.7%), and 57 (58.7%) patients in the three groups, respectively (P<0.001). A higher incidence of pneumonia (P=0.014) was found in the chemotherapy group. Perioperative mortality was observed in 1 patient (2.4%) in the ICI plus chemotherapy group and in 3 patients (3.1%) in the chemotherapy alone group (P=0.440). Patients in the ICI plus chemotherapy group had higher proportions of pathological complete response (40.5% vs. 11.1% vs. 6.1%, P<0.001) and downstaging of clinical N2 status (68.6% vs. 42.9% vs. 31.7%, P=0.012) than patients in EGFR-TKI group and chemotherapy alone group. Conclusions: Surgical resection for NSCLC following neoadjuvant ICI plus chemotherapy was safe and feasible, the perioperative outcomes were similar with neoadjuvant EGFR-TKI and chemotherapy alone without unexpected perioperative complications. Additional prospective studies are necessary to validate our findings.

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.

Long-term patient-reported outcomes after non-small cell lung cancer resection.

OBJECTIVES: Patient-reported outcomes (PROs) are critical tools for evaluating patients before and after lung cancer resection. In this study, we assessed patient-reported pain, dyspnea, and functional status up to 1 year postoperatively. METHODS: This study included patients who underwent surgery for non-small cell lung cancer at a single institution (2017-2020). We collected PROs using the National Institutes of Health Patient Reported Outcome Measurement Information System (PROMIS). Data were prospectively collected and merged with our institutional Society of Thoracic Surgeons data. Using multivariable linear mixed effect models, we compared PROMIS scores for preoperative and several postoperative visits. RESULTS: From 2017 until 2020, 334 patients underwent lung cancer resection with completed PROMIS assessments. Pain interference, physical function, and dyspnea severity scores were worse 1 month after surgery (P < .001). Pain interference and physical function scores returned to baseline by 6 months after surgery. However, dyspnea severity scores remained persistently worse up to 1 year after surgery (1-month difference, 8.8 ± 1.9; 6-month difference, 3.6 ± 2.2; 1-year difference, 4.9 ± 2.8; P < .001). Patients who received a thoracotomy had worse physical function and pain interference scores 1 month after surgery compared with patients who received a minimally invasive operation; however, there were no differences in PROs by 6 months after surgery. CONCLUSIONS: PROs are important metrics for assessing patients before and after lung cancer resection. Patients may report persistent dyspnea up to 1 year after resection. Additionally, patients undergoing thoracotomy initially report worse pain and physical function but these impairments improve by 6 months after surgery.

Pilot Study of Patient-Reported Outcomes in Patients With Esophageal Cancer After Esophagectomy.

BACKGROUND: Patient-reported outcomes (PROs) are critical measures of patient well-being after esophagectomy. In this pilot study, we assessed PROs before and after esophagectomy using the Patient Reported Outcomes Measurement Information System (PROMIS) to assess patient recovery after surgery. METHODS: We prospectively collected PROMIS dyspnea severity, physical function, and pain interference measures from patients with esophageal cancer undergoing esophagectomy (2017-2020). We merged these data with our institutional Society of Thoracic Surgery esophagectomy database. We used linear mixed-effect multivariable models to assess changes in PROMIS scores (least square mean [LSM] differences) preoperatively and postoperatively at 1 and 6 months. RESULTS: The study included 112 patients undergoing esophagectomy. Pain interference, physical function, and dyspnea severity scores were significantly worse 1 month after surgery. While physical function and dyspnea severity scores returned to baseline 6 months after surgery, pain interference scores remained persistently worse (LSM difference, 2.7 ± 2.5; P = .036). PROMIS scores were further assessed among patients undergoing transhiatal esophagectomy compared with transthoracic esophagectomy. Physical function and dyspnea severity scores were similar between the groups at each assessment. However, pain interference scores were persistently better among patients undergoing THE at both 1 month (LSM difference, 6.5 ± 5.1; P = .013) and 6 months after surgery (LSM difference, 5.2 ± 3.9; P = .008). CONCLUSIONS: This pilot study assessing PROMIS scores after esophagectomy for cancer reveals that pain is a persistently reported symptom up to 6 months after surgery, particularly among patients receiving transthoracic esophagectomy.

Routine Collection of Patient-Reported Outcomes in Thoracic Surgery: A Quality Improvement Study.

BACKGROUND: Patient-reported outcomes are critical for delivering high-quality surgical care, yet they are seldom collected in routine clinical practice. The objective of this quality improvement study was to improve routine patient-reported outcomes collection in a thoracic surgery clinic. METHODS: Thoracic surgery patients at a single academic institution were prospectively monitored from April 2019 to March 2020. The National Institutes of Health-validated Patient-Reported Outcomes Measurement Information System (PROMIS) was used. Using a Model for Improvement design and through multidisciplinary participant observation, we performed multiple plan-do-study-act cycles, an iterative, 4-stage model for rapidly testing interventions, to improve routine collection reliability. RESULTS: During the study period, 2315 patient visits occurred. The baseline PROMIS assessment collection rate was 53%. After convening a multidisciplinary stakeholder team, the key drivers for PROMIS collection were having engaged staff, engaged patients, adequate technological capacity, and adequate time for survey completion, including when to complete the survey during the patient visits. Regular meetings between stakeholders were initiated to promote these key drivers. Several plan-do-study-act cycles were then used to test different interventions, resulting in several positive system shifts, as demonstrated on a statistical process control chart. Adherence to survey collection reached 91% of office visits by approximately 7 months, a 72% relative improvement, which was sustained. CONCLUSIONS: Routine collection of patient-reported outcomes, such as PROMIS, are critical for improving thoracic surgical care. Our study shows that reliably collecting these data is possible in a clinical setting with minimal additional hospital resources.

The Impact of Center Volume on Outcomes in Lung Transplantation.

BACKGROUND: Studies in lung transplantation have shown variable association between hospital volume and clinical outcomes. We aimed to identify the pattern of effect of hospital volume on individual patient survival after lung transplantation. METHODS: We performed a retrospective analysis using the United Network for Organ Sharing national thoracic organ transplantation database. Adult patients who underwent lung transplantation between January 2013 and December 2017 were included. The association between mean annual center volume and 1-year overall survival was examined using restricted cubic splines in a random effects multivariable Cox model. The volume threshold for optimal 1-year overall survival was subsequently approximated by the maximum likelihood approach using segmented linear splines in the same model. RESULTS: The study included 10,007 patients at 71 transplant centers. Median annual center volume was 22 cases (interquartile range, 10.6 to 38). A center volume threshold was identified at 33 cases per year (95% confidence interval, 28 to 37). Higher center volume, to 33 cases per year, was associated with better 1-year survival (hazard ratio 0.989, 95% confidence interval, 0.980 to 0.999 every additional case). Further increase in center volume above 33 cases per year showed no additional benefit (hazard ratio 1.000, 95% confidence interval, 0.996 to 1.003 every additional case). Twenty-three centers (32.4%) reached the volume threshold of 33 cases per year. CONCLUSIONS: One-year survival after lung transplantation improved with increasing center volume to as many as 33 cases per year. Low volume centers below the 33 cases per year threshold had large variations in their outcomes and had a higher risk of performing poorly, although many of them maintained good performance.

Paradoxical outcome of heart transplantation associated with institutional case volume.

BACKGROUND: Previous studies in heart transplantation have shown an association between institutional case volume and outcomes. We aim to determine the case volume associated with optimal 1-year survival after transplantation. METHODS AND RESULTS: The United Network for Organ Sharing (UNOS) national database was analyzed for adult patients who underwent orthotopic heart transplantation between January 2013 and December 2017. A total of 11,196 cases at 128 transplant centers were included. Risk-adjusted restricted cubic splines revealed a non-linear association between institutional case volume and 1-year post-transplant survival. In the risk-adjusted, random-effect Cox model with segmented linear splines, higher heart transplant volume up to 24 cases per year was associated with better 1-year survival (HR = .978 every additional case, 95% CI .963-.993), and optimal survival was maintained between 24 and 38 cases per year. However, further increase in volume above 38 transplants per year was associated with mildly decreased 1-year survival (HR = 1.007 every additional case, 95% CI 1.002-1.013). CONCLUSIONS: The relationship between institutional case volume and heart transplant 1-year survival is non-linear, with optimal survival observed at institutional case volume of 24-38 cases per year.

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.

Impact of Nighttime Lung Transplantation on Outcomes and Costs.

BACKGROUND: Previous studies in the field of organ transplantation have shown a possible association between nighttime surgery and adverse outcomes. We aim to determine the impact of nighttime lung transplantation on postoperative outcomes, long-term survival, and overall cost. METHODS: We performed a single-center retrospective cohort analysis of adult lung transplant recipients who underwent transplantation between January 2006 and December 2017. Data were extracted from our institutional Lung Transplant Registry and Mid-America Transplant services database. Patients were classified into 2 strata, daytime (5 AM to 6 PM) and nighttime (6 PM to 5 AM), based on time of incision. Major postoperative adverse events, 5-year overall survival, and 5-year bronchiolitis obliterans syndrome-free survival were examined after propensity score matching. Additionally we compared overall cost of transplantation between nighttime and daytime groups. RESULTS: Of the 740 patients included in this study, 549 (74.2%) underwent daytime transplantation and 191 (25.8%) underwent nighttime transplantation (NT). Propensity score matching yielded 187 matched pairs. NT was associated with a higher risk of having any major postoperative adverse event (adjusted odds ratio, 1.731; 95% confidence interval, 1.093-2.741; P = .019), decreased 5-year overall survival (adjusted hazard ratio, 1.798; 95% confidence interval, 1.079-2.995; P = .024), and decreased 5-year bronchiolitis obliterans syndrome-free survival (adjusted hazard ratio, 1.556; 95% confidence interval, 1.098-2.205; P = .013) in doubly robust multivariable analyses after propensity score matching. Overall cost for NT and daytime transplantation was similar. CONCLUSIONS: NT was associated with a higher risk of major postoperative adverse events, decreased 5-year overall survival, and decreased 5-year bronchiolitis obliterans syndrome-free survival. Our findings suggest potential benefits of delaying NT to daytime transplantation.

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.