Implementation of Staging Guidelines in Early Esophageal Cancer: A Study of the Society of Thoracic Surgeons General Thoracic Surgery Database.

OBJECTIVE: To evaluate the adoption and clinical impact of endoscopic resection (ER) in early esophageal cancer. BACKGROUND: Staging for early esophageal cancer is largely inaccurate. Assessment of the impact of ER on staging accuracy is unknown, as is the implementation of ER. METHODS: We retrospectively reviewed 2608 patients captured in the Society of Thoracic Surgeons General Thoracic Surgery Database between 2015 and 2020. Patients with clinical T1 and T2 esophageal cancer without nodal involvement (N0) who were treated with upfront esophagectomy were included. Staging accuracy was assessed by clinical-pathologic concordance among patients staged with and without ER. We also sought to measure adherence to National Comprehensive Cancer Network staging guidelines for esophageal cancer staging, specifically the implementation of ER. RESULTS: For early esophageal cancer, computed tomography/positron emission tomography/endoscopic ultrasound (CT/PET/EUS) accurately predicts the pathologic tumor (T) stage 58.5% of the time. The addition of ER to staging was related to a decrease in upstaging from 17.6% to 10.8% ( P =0.01). Adherence to staging guidelines with CT/PET/EUS improved from 58.2% between 2012 and 2014 to 77.9% between 2015 and 2020. However, when ER was added as a staging criterion, adherence decreased to 23.3%. Increased volume of esophagectomies within an institution was associated with increased staging adherence with ER ( P =0.008). CONCLUSIONS: The use of CT/PET/EUS for the staging of early esophageal cancer is accurate in only 56.3% of patients. ER may increase staging accuracy as it is related to a decrease in upstaging. ER is poorly utilized in staging of early esophageal cancer. Barriers to the implementation of ER as a staging modality should be identified and corrected.

The Effect of Center Esophagectomy Volume on Outcomes in Clinical Stage I to III Esophageal Cancer.

OBJECTIVE: To determine the threshold annualized esophagectomy volume that is associated with improved survival, oncologic resection, and postoperative outcomes. BACKGROUND: Esophagectomy at high-volume centers is associated with improved outcomes; however, the definition of high-volume remains debated. METHODS: The 2004 to 2016 National Cancer Database was queried for patients with clinical stage I to III esophageal cancer undergoing esophagectomy. Center esophagectomy volume was modeled as a continuous variable using restricted cubic splines. Maximally selected ranks were used to identify an inflection point of center volume and survival. Survival was compared using multivariable Cox proportional hazards methods. Multivariable logistic regression was used to examine secondary outcomes. RESULTS: Overall, 13,493 patients met study criteria. Median center esophagectomy volume was 8.2 (interquartile range: 3.2-17.2) cases per year. On restricted cubic splines, inflection points were identified at 9 and 30 cases per year. A multivariable Cox model was constructed modeling annualized center surgical volume as a continuous variable using 3 linear splines and inflection points at 9 and 30 cases per year. On multivariable analysis, increasing center volume up to 9 cases per year was associated with a substantial survival benefit (hazard ratio: 0.97, 95% confidence interval, 0.95-0.98, P ≤0.001). On multivariable logistic regression, factors associated with undergoing surgery at a high-volume center (>9 cases per year) included private insurance, care at an academic center, completion of high school education, and greater travel distance. CONCLUSIONS: This National Cancer Database study utilizing multivariable analysis and restricted cubic splines suggests the threshold definition of a high-volume esophagectomy center as one that performs at least 10 operations a year.

Utilization Trends and Volume-outcomes Relationship of Endoscopic Resection for Early Stage Esophageal Cancer.

OBJECTIVES: We describe utilization trends and center volume-outcomes relationship of ER of early stage esophageal cancer using a large hospitalbased registry. SUMMARY OF BACKGROUND DATA: ER is increasingly accepted as the preferred treatment for early stage esophageal cancer, however its utilization and the center volume-outcomes relationship in the United States is unknown. METHODS: The National Cancer Database was used to identify patients with cT1N0M0 esophageal cancer treated with ER or esophagectomy between 2004 and 2015. Relative frequencies were plotted over time. Restricted cubic splines and maximally selected rank statistics were used to identify an inflection point of center volume and survival. RESULTS: A total of 1136 patients underwent ER and 2829 patients underwent esophagectomy during the study period. Overall utilization of ER, and relative use compared to esophagectomy, increased throughout the study period. Median annualized center ER volume was 1.9 cases per year (interquartile range 0.5-5.8). Multivariable Cox regression showed increasing annualized center volume by 1 case per year was associated with improved survival. Postoperative 30- or 90-day mortality, 30-day readmission, and pathologic T upstaging rates were similar irrespective of center volume. CONCLUSIONS: Utilization of ER compared to esophagectomy for stage I esophageal cancer has increased over the past decade, though many individual centers perform fewer than 1 case annually. increasing annualized center volume by one procedure per year was associated with improved survival. increased volume beyond this was not associated with survival benefit. Referral to higher volume centers for treatment of superficial esophageal cancer should be considered.

Multicenter Experience with Neoadjuvant Therapy in Melanoma Highlights Heterogeneity in Contemporary Practice.

OBJECTIVE: To determine the feasibility and impact of neoadjuvant therapy (NT) in patients who present with advanced melanoma amenable to surgical resection. SUMMARY BACKGROUND DATA: Given current effective systemic therapy for melanoma, the use of NT is being explored in patients with advanced melanoma with disease amenable to surgical resection. METHODS: Prospective data from 3 institutions was obtained in patients with clinically evident Stage III/IV melanoma who underwent NT. The primary objective was to compare recurrence-free survival between patients who had pathologic complete response (pCR) to those with persistent disease. RESULTS: NT was offered to 45 patients, with 43 patients initiating various NT regimens including PD-1 antagonist (PD-1) therapy (N = 16), PD-1 plus ipilimumab (N = 10), BRAF/MEK inhibitor therapy (N = 14), a combination of those three (N = 1), and talimogene laherparepvec (TVEC) (N = 2). Thirty-two (74.1%) patients underwent surgery whereas 11 patients did not undergo surgery for these reasons: clinical CR (N = 7), progressive disease not amenable to resection (N = 3), and ongoing therapy (N = 1). 12 of 32 patients (37.5%) had pCR with these therapies: PD-1 (N = 4), PD-1 plus ipilimumab (N = 2), BRAF/MEK (N = 4), combination (N = 1), and TVEC (N = 1). At median follow-up of 16.4 months there was only 1 recurrence in the pCR group and patients with a pCR had significantly improved recurrence-free survival compared to patients without pCR (p = 0.004). CONCLUSIONS: Despite variability in NT regimens across institutions, NT for melanoma is feasible and associated with improved prognosis in patients who achieve a pCR. Maximizing rates of pCR could improve prognosis for patients with advanced melanoma.

The Impact of Adjuvant Hemithoracic Radiation on Outcomes in Patients With Stage I-III Malignant Pleural Mesothelioma: A Dual Registry Analysis.

BACKGROUND: The outcomes associated with receipt of adjuvant radiation in patients after surgery for MPM are poorly understood. OBJECTIVE: The objective of this study was to use 2 registries to compare the outcomes of patients receiving adjuvant radiation or no radiation after definitive surgery for pathologic stage I-III MPM. METHODS: Patients with resected pathologic stage I-III MPM were identified from the Duke University registry (1996-2016) and National Cancer Database (NCDB) (2004-2015). The primary outcome was overall survival. Propensity score-matched and landmark subgroup analyses were performed. RESULTS: A total of 212 institutional and 1615 NCDB patients met criteria. In both cohorts, patients who underwent radiation were more likely to have margin-negative resection and more advanced pathologic stage. At a landmark time of 4.4 and 4.7 months from surgery, Duke [hazard ratio (HR) 1.14; 95% confidence interval (CI) 0.62-2.11] and NCDB patients (HR 0.97; 95% CI 0.81-1.17) who received adjuvant radiation did not experience improved survival compared to those who did not receive radiation in multivariable analysis. Duke patients who received radiation had similar incidence of recurrence and time to both overall recurrence and ipsilateral recurrence (HR 0.87; 95% CI 0.43-1.77) compared to those who did not. Duke patients experienced 100 grade 1/2, 21 grade 3/4, and one grade 5 toxicity events during radiation. CONCLUSIONS: In this dual registry analysis of patients with resected stage I-III MPM, the receipt of adjuvant hemithoracic radiation was not associated with improved survival compared to no radiation.

The Impact of Adjuvant Therapy on Survival After Esophagectomy for Node-negative Esophageal Adenocarcinoma.

OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2-4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: There is minimal literature to substantiate the NCCN guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2-4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004-2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: Four hundred three patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2-4aN0M0 esophageal adenocarcinoma.

Lung Transplantation After Ex Vivo Lung Perfusion Early Outcomes From a US National Registry.

OBJECTIVE: The objective of this study was to examine early lung transplant outcomes following EVLP using a large national transplant registry. SUMMARY OF BACKGROUND DATA: Lung transplantation in the United States continues to be constrained by a limited supply of donor organs. EVLP has the potential to significantly increase the available pool of donor lung allografts through the reconditioning of "marginal" organs. METHODS: The united network for organ sharing registry was queried for all adults (age ≥18) who underwent first-time lung transplantation between March 2018 (when united network for organ sharing began collecting confirmed donor EVLP status) and June 2019. Transplants were stratified by EVLP use. The primary outcome was short-term survival and secondary outcomes included acute rejection before discharge and need for extracorpo-real membrane oxygenation support post-transplant. RESULTS: A total of 3334 recipients met inclusion criteria including 155 (5%) and 3179 (95%) who did and did not receive allografts that had undergone EVLP, respectively. On unadjusted descriptive analysis, EVLP and non-EVLP cohorts had similar 180-day survival (92% vs 92%, P = 0.9). EVLP use was associated with a similar rate of acute rejection (13% vs 9%, P = 0.08) but increased rate of early extracorporeal membrane oxygenation use (12% vs 7%, P = 0.04). After adjustment, EVLP use was not associated with significantly increased mortality (adjusted hazard ratio 0.99, 95% confidence interval 0.62-1.58) or acute rejection (adjusted odds ratio 0.89, 95% confidence interval 0.40-1.97) compared to non-EVLP use. CONCLUSIONS: In the largest national series of EVLP lung transplant recipients, EVLP is associated with early recipient outcomes comparable to that of non-EVLP recipients with similar baseline characteristics. Longer term follow-up data is needed to further assess the impact of EVLP on post-lung transplant outcomes.

Tumor Size, Histology, and Survival After Stereotactic Ablative Radiotherapy and Sublobar Resection in Node-negative Non-small Cell Lung Cancer.

BACKGROUND: Although SABR is increasingly emerging as an alternative to surgery for node-negative non-small cell lung cancer, there is poor understanding of patients who may most benefit SABR compared to surgery. OBJECTIVE: This study examined the relationship between tumor size and the comparative outcomes of SABR and sublobar resection in patients with node-negative non-small cell lung cancer. RESULTS: A total of 59,949 patients met study criteria: 19,888 (33%) underwent SABR, 33,052 (55%) wedge resection, and 7009 (12%) segmental resection. In multivariable regression, a significant 3-way interaction was found between histology, tumor size, and type of treatment. After stratification by histology, a significant interaction between tumor size and treatment was preserved for patients with adenocarcinoma and squamous cell carcinoma. Sublobar resection was associated with greater survival compared to SABR for tumor sizes greater than 6 and 8 mm for patients with adenocarcinoma and squamous cell carcinoma, respectively. SABR was associated with similar survival compared to sublobar resection for patients with papillary and large cell histology. CONCLUSIONS: In this National Cancer Database analysis, sublobar resection was associated with greater survival compared to SABR for lesions >6or 8 mm in patients with adenocarcinoma or squamous cell carcinoma; however, SABR was associated with similar survival compared to sublobar resection in patients with aggressive tumors including papillary and large cell histology. Histologic diagnosis in patients with even small tumors may enable better treatment selection in those who cannot tolerate lobectomy.

The Relationship Between Lymph Node Ratio and Survival Benefit With Adjuvant Chemotherapy in Node-positive Esophageal Adenocarcinoma.

BACKGROUND: We hypothesized that the ratio of positive lymph nodes to total assessed lymph nodes (LNR) is an indicator of cancer burden in esophageal adenocarcinoma and may identify patients who may most benefit from AC. OBJECTIVE: The aim of this study was to discern whether there is a threshold LNR above which AC is associated with a survival benefit in this population. METHODS: The 2004-2015 National Cancer Database was queried for patients who underwent upfront, complete resection of pT1-4N1-3M0 esophageal adenocarcinoma. The primary outcome, overall survival, was examined using multivariable Cox proportional hazards models employing an interaction term between LNR and AC. RESULTS: A total of 1733 patients were included: 811 (47%) did not receive AC whereas 922 (53%) did. The median LNR was 20% (interquartile range 9-40). In a multivariable Cox model, the interaction term between LNR and receipt of AC was significant (P = 0.01). A plot of the interaction demonstrated that AC was associated with improved survival beyond a LNR of about 10%-12%. In a sensitivity analysis, the receipt of AC was not associated with improved survival in patients with LNR <12% (hazard ratio 1.02; 95% confidence interval 0.72-1.44) but was associated with improved survival in those with LNR ≥12% (hazard ratio 0.65; 95% confidence interval 0.50-0.79). CONCLUSIONS: In this study of patients with upfront, complete resection of node-positive esophageal adenocarcinoma, AC was associated with improved survival for LNR ≥12%. LNR may be used as an adjunct in multidisciplinary decision-making about adjuvant therapies in this patient population.

Patterns and Impact of Fragmented Care in Stage II and III Gastric Cancer.

BACKGROUND: Optimal management of stage II/III gastric cancer requires multidisciplinary care, often necessitating treatment at more than one facility. We aimed to determine patterns of "fragmented" care and its impact on outcomes, including concordance with National Comprehensive Cancer Network (NCCN) guidelines and overall survival. METHODS: The 2006-2016 National Cancer Database was queried for patients with clinical stage II/III gastric adenocarcinoma who received preoperative therapy in addition to surgery. Patients were stratified based on whether surgery and chemotherapy/chemoradiation were performed at one versus multiple facilities (termed "coordinated" and "fragmented" care, respectively). Multivariable logistic regression was performed to identify factors associated with fragmented care. Survival was compared using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Overall, 2033 patients met study criteria: 1043 (51.3%) received coordinated care and 990 (48.7%) fragmented care. There was no significant difference in time to surgery or pathologic upstaging by care structure. On adjusted analysis, factors associated with receipt of fragmented care included increasing age and distance traveled to the treating facility. Factors associated with coordinated care included metropolitan residence and treatment at academic and high-volume centers. Fragmented care was associated with a reduction in guideline-preferred perioperative chemotherapy (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63-0.97, p = 0.02) and increased mortality (HR 1.16, 95% CI 1.00-1.34, p = 0.05). CONCLUSIONS: For patients with stage II/III gastric cancer, fragmented care is associated with inferior outcomes, including a reduction in preferred perioperative treatment and survival. Further work is needed to ensure equitable outcomes among patients as complex cancer care becomes more regionalized.

A three-tier system for evaluation of organ procurement organizations' willingness to pursue and utilize nonideal donor lungs.

Lungs from "nonideal," but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not reflect the extent to which OPO-specific practices contribute to these trends. We developed a comprehensive system to evaluate nonideal lung donor avoidance, or risk aversion among OPOs. Adult donors in the UNOS registry who donated ≥1 organ for transplantation between 2007 and 2018 were included. Nonideal donors had any of age>50, smoking history ≥20 pack-years, PaO2 /FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPO-level risk aversion in donor pursuit, consent attainment, lung recovery, and transplantation was assessed. Among 83916 donors, 70372 (83.9%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 81 to 100%. In a three-tier system of overall risk aversion, tier 3 OPOs (least risk-averse) had the highest rates of nonideal donor pursuit, consent attainment, lung recovery, and transplantation. Tier 1 OPOs (most risk-averse) had the lowest rates of donor pursuit, consent attainment, and lung recovery, but higher rates of transplantation compared to tier 2 OPOs (moderately risk-averse). Risk aversion varies among OPOs and across the donation process. OPO evaluations should reflect early donation process stages to best differentiate over- and underperforming OPOs and encourage optimal OPO-specific performance.

A National Analysis of Short-term Outcomes and Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Clinical Stage II Non-Small-Cell Lung Cancer.

OBJECTIVE: To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC). BACKGROUND: There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival. METHODS: Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010-2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. RESULTS: Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90-1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups. CONCLUSION: In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC.

Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival.

OBJECTIVE: The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC. SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC. METHODS: Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of "early" versus "delayed" surgery (surgery received 0-30 vs 90-120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses. RESULTS: In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004). CONCLUSIONS: The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.

Association between levosimendan, postoperative AKI, and mortality in cardiac surgery: Insights from the LEVO-CTS trial.

OBJECTIVES: We aimed to evaluate the association between levosimendan treatment and acute kidney injury (AKI) as well as assess the clinical sequelae of AKI in cardiac surgery patients with depressed left ventricular function (ejection fraction <35%). METHODS: Patients in the LEVO-CTS trial undergoing on-pump coronary artery bypass grafting (CABG), valve, or CABG/valve surgery were stratified by occurrence and severity of postoperative AKI using the AKIN classification. The association between levosimendan infusion and AKI was modeled using multivariable regression. RESULTS: Among 854 LEVO-CTS patients, 231 (27.0%) experienced postoperative AKI, including 182 (21.3%) with stage 1, 35 (4.1%) with stage 2, and 14 (1.6%) with stage 3 AKI. The rate of AKI was similar between patients receiving levosimendan or placebo. The odds of 30-day mortality significantly increased by AKI stage compared to those without AKI (stage 1: adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI] 0.8-4.9; stage 2: aOR 9.1, 95% CI 3.2-25.7; stage 3: aOR 12.4, 95% CI 3.0-50.4). No association was observed between levosimendan, AKI stage, and odds of 30-day mortality (interaction P = .69). Factors independently associated with AKI included increasing age, body mass index, diabetes, and increasing baseline systolic blood pressure. Increasing baseline eGFR and aldosterone antagonist use were associated with a lower risk of AKI. CONCLUSIONS: Postoperative AKI is common among high-risk patients undergoing cardiac surgery and associated with significantly increased risk of 30-day death or dialysis. Levosimendan was not associated with the risk of AKI.

Magnetic Resonance Lymphangiography of the Central Lymphatic System: Technique and Clinical Applications.

Magnetic resonance lymphangiography (MRL) is a noninvasive imaging technique that can be used in the management of lymphatic disorders to delineate the central lymphatic system for treatment planning. This article reviews the MRL technique, its advantages, limitations, indications, and impact on patient management. Level of Evidence 5 Technical Efficacy Stage 3 J. MAGN. RESON. IMAGING 2021;53:374-380.

Dual Procurement of Lung and Heart Allografts Does Not Negatively Affect Lung Transplant Outcomes.

BACKGROUND: The data that exists regarding multiorgan procurement outcomes is conflicted. Given the increasing demand for pulmonary allografts, it is critical to assess the impact of dual procurement on lung transplant recipient outcomes. METHODS: The United Network for Organ Sharing transplant registry was queried for all first-time adult (age ≥18) lung transplant recipients between 2006 and 2018 and stratified by concurrent heart donor status. Multiorgan transplant recipients and recipients with missing survival time were excluded. Donors were excluded if they were donating after circulatory death, did not consent or were not approached for heart donation, the heart was recovered for nontransplant purposes, or the heart was recovered for transplant but not transplanted. Post-transplant survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression. RESULTS: A total of 18,641 recipients met inclusion criteria, including 6230 (33.4%) in the nonheart donor group (NHD) and 12,409 (66.6%) in the heart donor group (HD). HD recipients demonstrated longer survival at 10 years posttransplant, with a median survival of 6.5 years as compared with 5.9 years in NHD recipients. On adjusted analysis, HD and NHD recipients demonstrated comparable survival (AHR 0.95, 95% CI 0.90-1.01). CONCLUSIONS: Concomitant heart and lung procurement was not associated with worse survival. This finding encourages maximizing the number of organs procured from each donor, particularly in the setting of urgency-driven thoracic transplantation.

Aggressive pursuit and utilization of non-ideal donor lungs does not compromise post-lung transplant survival.

BACKGROUND: Organ procurement organizations (OPOs) vary in willingness to pursue and utilize non-ideal donor lungs; implications of these practices for lung transplant (LTx) recipients remain unclear. We examined associations between OPO-level behavior toward non-ideal donors and post-LTx outcomes. METHODS: Adult lung donors and corresponding adult first-time LTx recipients in the 2008-2019 UNOS registry were included. Non-ideal donors had any of age > 50, smoking history ≥20 pack-years, PaO2 /FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPOs were classified as least, moderately, or most aggressive based on non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. Post-transplant outcomes were compared among aggressiveness strata. RESULTS: Of 22,795 recipients, 6229 (27.3%), 8256 (36.2%), and 8310 (36.5%) received lungs from least, moderately, and most aggressive OPOs, respectively. Moderately aggressive OPOs had the highest recipient rates of pre-discharge acute rejection, grade 3 primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and longest lengths of stay. After adjustment, moderately and most aggressive OPOs had similar risks of recipient mortality as least aggressive OPOs. CONCLUSIONS: The most and least aggressive OPOs achieve similar patient survival and short-term post-LTx outcomes. Aggressive pursuit and utilization of non-ideal donor lungs by less aggressive OPOs would likely expand the donor pool, without compromising recipient outcomes.

Center volume and primary graft dysfunction in patients undergoing lung transplantation in the United States - a cohort study.

Lung transplantation primary graft dysfunction (PGD) is common and portends poor outcomes. We examined the association of lung transplant center volume with PGD and the risk of mortality. The United Network for Organ Sharing transplant registry was queried for adult lung transplants from March 2015 to March 2019. Recipients were stratified by the occurrence of grade 3 PGD 72 h post-transplant, defined using modified ISHLT criteria. The adjusted association between volume and PGD as well as post-PGD survival was analyzed. 7322 recipients were included, among whom approximately 21% (n = 1525) experienced grade 3 PGD. After adjustment, increasing annualized lung transplant volume was associated with a decrease in the odds of PGD in a near-linear fashion (OR 0.94 per 10 transplants, 95% CI 0.89-0.99). Furthermore, increasing annualized lung transplant center volume up to approximately 55 transplants per year was associated with improved survival among patients with grade 3 PGD (HR 0.87 per 10 transplants, 95% CI 0.79-0.94). Increasing annual lung transplant center volume is associated with a decreased incidence of grade 3 PGD. Further, increasing volume among low- and medium-volume centers is associated with improved survival of patients who experience PGD.

Stereotactic Body Radiotherapy Versus Delayed Surgery for Early-stage Non-small-cell Lung Cancer.

OBJECTIVE: To evaluate the overall survival of patients with operable stage IA non-small-cell lung cancer (NSCLC) who undergo "early" SBRT (within 0-30 days after diagnosis) versus "delayed" surgery (90-120 days after diagnosis). SUMMARY OF BACKGROUND DATA: During the COVID-19 pandemic, national guidelines have recommended patients with operable stage IA NSCLC to consider delaying surgery by at least 3 months or, alternatively, to undergo SBRT without delay. It is unknown which strategy is associated with better short- and long-term outcomes. METHODS: Multivariable Cox proportional hazards modeling and propensity score-matched analysis was used to compare the overall survival of patients with stage IA NSCLC in the National Cancer Data Base from 2004 to 2015 who underwent "early" SBRT (0-30 days after diagnosis) versus that of patients who underwent "delayed" wedge resection (90-120 days after diagnosis). RESULTS: During the study period, 570 (55%) patients underwent early SBRT and 475 (45%) underwent delayed wedge resection. In multivariable analysis, delayed resection was associated with improved survival [adjusted hazard ratio 0.61; (95% confidence interval (CI): 0.50-0.76)]. Propensity-score matching was used to create 2 groups of 279 patients each who received early SBRT or delayed resection that were well-matched with regard to baseline characteristics. The 5-year survival associated with delayed resection was 53% (95% CI: 45%-61%) which was better than the 5-year survival associated with early SBRT (31% [95% CI: 24%-37%]). CONCLUSION: In this national analysis, for patients with stage IA NSCLC, extended delay of surgery was associated with improved survival when compared to early treatment with SBRT.

Adjuvant Therapy is Effective for Melanoma Patients with a Positive Sentinel Lymph Node Biopsy Who Forego Completion Lymphadenectomy.

BACKGROUND: Multiple adjuvant therapies for melanoma have been approved since 2015 based on randomized trials demonstrating improvements in recurrence-free survival (RFS) with adjuvant therapy after surgical resection of high-risk disease. Inclusion criteria for these trials required performance of a completion lymph node dissection (CLND) for positive sentinel lymph node (pSLN) disease. OBJECTIVE: We aimed to describe current practice for adjuvant therapies in patients with pSLN without CLND (active surveillance [AS]), and to evaluate recurrence in these patients. METHODS: Melanoma patients with pSLN between 2016 and 2019 were identified at two institutions. Demographic information, disease and treatment characteristics, and recurrence details were reviewed retrospectively. Patients were stratified by recurrence and patient-, treatment- and tumor-related characteristics were compared using Fisher's exact test and t test for categorical and continuous variables, respectively. RESULTS: Overall, 245 SLN biopsies were performed, of which 36 (14.7%) were pSLN. Of 36 pSLN, 4 underwent CLND and 32 underwent AS, of whom 22 (68.8%) received adjuvant therapy with the anti-programmed death-1 (PD1) inhibitor nivolumab (16/22), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab (3/22), or BRAF/MEK inhibitors (3/22). At a median follow up of 13.3 months, 7/32 (21.9%) patients on AS recurred, including 4/22 (18.2%) who received adjuvant therapy and 3/10 (30.0%) who did not. Tumor ulceration was significantly associated with recurrence. While not significant, acral lentiginous subtype appeared more common among those with recurrence. CONCLUSION: The majority (68.8%) of patients with pSLN managed without CLND were treated with adjuvant therapy. The 1-year RFS for patients managed with adjuvant therapy without CLND was 82%, which is similar to modern adjuvant therapy trials requiring CLND.