Commission on Cancer Standards for Lymph Node Sampling and Oncologic Outcomes after Lung Resection.

BACKGROUND: The newest Commission on Cancer (CoC) standards recommend sampling 3 mediastinal and 1 hilar lymph node station, 3(N2)1(N1), for lung cancer resections. However, the relationship between the CoC standards and outcomes has not been thoroughly investigated. METHODS: A prospective institutional database was queried for clinical stage I-III lung resections prior to the implementation of the new standards. The relationship between the 3(N2)1(N1) standard ("guideline concordant") and outcomes (upstaging, complications, receipt of adjuvant therapy, locoregional/distant recurrence, and survival) were assessed using multivariable models and stratified by stage. RESULTS: Of 9,289 pulmonary resections 3048 (33%) were guideline concordant and 6241 (67%) were not. Compared to non-concordant, those who were guideline-concordant had higher rates of nodal upstaging (21% vs 13%; OR 1.32 [95% CI 1.14-1.51] p<0.001) and in-hospital complications (34% vs 27%), (OR 1.17 [95% CI 1.05-1.30], p=0.004), but similar adjuvant systemic therapy administration (19% vs 13%; OR 1.09 [95% CI 0.95-1.24], p=0.2), (98% chemotherapy). Locoregional and distant recurrence were not significantly improved with guideline concordance across clinical stage I, II and III subsets. Overall survival was similar in clinical stages I and II but improved survival was observed among guideline concordant clinical stage III patients (HR 0.85 [95% CI 0.74-0.97], p=0.02). CONCLUSIONS: Sampling 3(N2)1(N1) was associated with increased upstaging and complications but not with decreased recurrence or mortality in clinical stage I or II patients. Survival was improved among concordant, clinical stage III patients. Further study is indicated to determine the ideal lymph node sampling strategy across heterogeneous lung cancer patients.

Determinants of successful minimally invasive surgery for resectable non-small cell lung cancer after neoadjuvant therapy.

OBJECTIVE: Minimally invasive surgery (MIS) (video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery) for pulmonary resection is standard in early-stage non-small cell lung cancer because it is associated with better perioperative outcomes than thoracotomy. MIS for resection of more advanced non-small cell lung cancer (Stages IB-IIIB) treated with neoadjuvant therapy has been utilized. However, the determinants of success are not well defined. METHODS: A single institution retrospective review of a prospectively maintained database was conducted, querying for patients with clinical Stage IB through IIIB non-small cell lung cancer who had resection after neoadjuvant systemic therapy without radiation from 2013 to 2022. Patients were grouped by surgical approach; that is, open versus MIS. Successful MIS was defined by no conversion, R0 resection, and no major (grade 3 or greater) morbidity. Analyses by intent-to-treat assessed outcomes by Wilcoxon rank-sum test and Fisher exact test. (Multivariable regression analysis identified variables that contributed to successful MIS resection.) RESULTS: Of 627 eligible patients, 360 (57%) had open and 267 (43%) had MIS procedures. Most patients (79.1%) received neoadjuvant platinum-based chemotherapy, and 21.9% were treated with immunotherapy or targeted therapy alone or combined with chemotherapy. Among MIS resections, 179 (67%) were performed by video-assisted thoracoscopic surgery and 88 (33%) by robot-assisted thoracoscopic surgery. The conversion rate was 16% (n = 43). Successful MIS resection was achieved in 77% of patients. Multivariable regression analysis showed that pretreatment clinical N stage was a significant determinant of success, but not pretreatment clinical T stage or type of neoadjuvant therapy. CONCLUSIONS: Following neoadjuvant systemic therapy for clinical stage IB or IIIB non-small cell lung cancer, MIS resection can be successfully accomplished and should be considered in appropriate patients. Presence of pretreatment nodal disease is associated with higher odds of conversion, major morbidity, and incomplete resection.

A Novel Frailty Index Can Predict the Short-Term Outcomes of Esophagectomy in Older Patients with Esophageal Cancer.

Background: Frailty, rather than age, is associated with postoperative morbidity and mortality. We sought to determine whether preoperative frailty as defined by a novel scoring system could predict the outcomes among older patients undergoing esophagectomy. Methods: We identified patients 65 years or older who underwent esophagectomy between 2011 and 2021 at our institution. Frailty was assessed using the MSK-FI, which consists of 1 component related to functional status and 10 medical comorbidities. We used a multivariable logistic regression model to test for the associations between frailty and short-term outcomes, with continuous frailty score as the predictor and additionally adjusted for age and Eastern Cooperative Oncology Group performance status. Results: In total, 447 patients were included in the analysis (median age of 71 years [interquartile range, 68-75]). Most of the patients underwent neoadjuvant treatment (81%), an Ivor Lewis esophagectomy (86%), and minimally invasive surgery (55%). A total of 22 patients (4.9%) died within 90 days of surgery, 144 (32%) had a major complication, 81 (19%) were readmitted, and 31 (7.2%) were discharged to a facility. Of the patients who died within 90 days, 19 had a major complication, yielding a failure-to-rescue rate of 13%. The risk of 30-day major complications (OR, 1.24 [95% CI, 1.09-1.41]; p = 0.001), readmissions (OR, 1.31 [95% CI, 1.13-1.52]; p < 0.001), and discharge to a facility (OR, 1.86 [95% CI, 1.49-2.37]; p < 0.001) increased with increasing frailty. Frailty and 90-day mortality were not associated. Conclusions: Frailty assessment during surgery decision-making can identify patients with a high risk of morbidity.

Outcomes of Patients Undergoing Segmentectomy for Occult Node-Positive Clinical Stage IA Lung Cancer.

BACKGROUND: Results of recent clinical trials suggest that segmentectomy may be an acceptable alternative to lobectomy for selected patients with early-stage non-small cell lung cancer (NSCLC). Increased use of segmentectomy may result in a concomitant increase in occult node-positive (N+) disease on surgical pathology examination. The optimal management for such patients remains unknown. METHODS: Clinicopathologic data were abstracted from a prospective institutional database to identify patients with pathologic N+ disease after segmentectomy for cT1 N0 M0 NSCLC. Propensity score matching identified a comparable lobectomy cohort for assessment of cumulative incidence of recurrence and overall survival (OS). RESULTS: Of 759 included patients, 27 (4%) had nodal upstaging on the final pathology report. Of these 27 patients, 4 (15%) had skip metastasis to N2 stations, and 20 (74%) received adjuvant therapy; no completion lobectomies were performed. Ten patients (37%) had disease recurrence: 3 isolated locoregional (11%) and 7 distant (26%). The median time to recurrence among patients with recurrence was 1.8 years; OS after recurrence was 3.4 years. After 5:1 matching with 109 patients who underwent lobectomy, all variables were balanced between the groups, except pathologic N2 stage and open surgical approach. The 5-year cumulative incidence of recurrence was not significantly different between segmentectomy and lobectomy (42% vs 52%, respectively; Gray's P = .1). The 5-year OS (63% and 50%) and rate of locoregional recurrence (12% vs 13%) were not statistically different between the groups. CONCLUSIONS: Patients with occult N+ disease after segmentectomy for cT1 N0 M0 NSCLC had limited isolated locoregional recurrences and outcomes similar to those in patients who underwent lobectomy. Lobectomy may not provide an advantage in these patients.

A Real-World Assessment of Stage I Lung Cancer Through Electronic Nose Technology.

INTRODUCTION: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer. METHODS: This phase IIc trial (NCT04734145) included patients diagnosed with a single greater than or equal to 50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into three risk groups (low-risk, [<0.2]; moderate-risk, [≥0.2-0.7]; high-risk, [≥0.7]). The primary outcome was the diagnostic performance of E-nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models. RESULTS: Based on the predefined cutoff (<0.20), E-nose agreed with histopathologic results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, two false negatives, and 12 false positives (n = 100). E-nose would refer fewer patients with malignant nodules to observation (low-risk: 2 versus 9 and 11, respectively; p = 0.028 and p = 0.011) than would the Swensen and Brock models and more patients with malignant nodules to treatment without biopsy (high-risk: 27 versus 19 and 6, respectively; p = 0.057 and p < 0.001). CONCLUSIONS: In the setting of clinical stage I lung cancer, E-nose agrees well with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a "multiomics" platform.

A New Functional Threshold for Minimally Invasive Lobectomy.

OBJECTIVE: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy. SUMMARY BACKGROUND DATA: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment. METHODS: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al. RESULTS: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values. CONCLUSIONS: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

Preoperative frailty predicts postoperative falls in older patients with cancer.

INTRODUCTION: Patient falls in the hospital lead to adverse outcomes and impaired quality of life. Older adults with cancer who are frail may be at heightened risk of falls in the postoperative period. We sought to evaluate the association between degree of preoperative frailty and risk of inpatient postoperative falls and other outcomes among older adults with cancer. MATERIALS AND METHODS: We identified 7,661 patients aged 65 years or older who underwent elective cancer surgery from 2014 to 2020, had a hospital stay of ≥1 day, and had Memorial Sloan Kettering-Frailty Index (MSK-FI) data to allow assessment of frailty. Univariable logistic regression analysis was performed to evaluate the association between frailty and falls. Multivariable logistic regression analysis was performed to evaluate the composite outcome of 30-day readmission or 90-day death, with frailty, falls, and the interaction between frailty and falls as predictors; the analysis was adjusted for age, sex, race, and preoperative albumin level. RESULTS: In total, 7,661 patients were included in the analysis. Seventy-one (0.9%) had a fall, of whom eight (11%) were readmitted to the hospital within 30 days and seven (10%) died within 90 days. Higher MSK-FI score was associated with higher risk of falls (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.21-1.59]). The risk of falls for a patient with an MSK-FI score of 1 was 0.6%, compared with 1.7% for a patient with an MSK-FI score of 4. Poor outcome was associated with frailty (OR, 1.07 [95% CI, 1.02-1.13]) but not with falls (OR, 1.17 [95% CI, 0.57-2.22]). DISCUSSION: Preoperative frailty is associated with risk of inpatient postoperative falls and with other adverse outcomes after surgery among older adults with cancer. Screening for frailty in the preoperative setting would enable healthcare institutions to implement interventions aimed at reducing the incidence of inpatient postoperative falls to reduce fall-related adverse events.

Biologic versus synthetic prosthesis for chest wall reconstruction: a matched analysis.

OBJECTIVES: The aim of this study was to compare postoperative outcomes between biologic and synthetic reconstructions after chest wall resection in a matched cohort. METHODS: All patients who underwent reconstruction after full-thickness chest wall resection from 2000 to 2022 were reviewed and stratified by prosthesis type (biologic or synthetic). Biologic prostheses were of biologic origin or were fully absorbable and incorporable. Integer matching was performed to reduce confounding. The study end point was surgical site complications requiring reoperation. Multivariable analysis was performed to identify associated risk factors. RESULTS: In total, 438 patients underwent prosthetic chest wall reconstruction (unmatched: biologic, n = 49; synthetic, n = 389; matched: biologic, n = 46; synthetic, n = 46). After matching, the median (interquartile range) defect size was 83 cm2 (50-142) for the biologic group and 90 cm2 (48-146) for the synthetic group (P = 0.97). Myocutaneous flaps were used in 33% of biologic reconstructions (n = 15) and 33% of synthetic reconstructions (n = 15) in the matched cohort (P = 0.99). The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic reconstructions in the unmatched (3 [6%] vs 29 [7%]; P = 0.99) and matched (2 [4%] vs 4 [9%]; P = 0.68) cohorts. On the multivariable analysis, operative time [adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI), 1.00-1.01; P = 0.006] and operative blood loss (aOR = 1.00, 95% CI, 1.00-1.00]; P = 0.012) were associated with higher rates of surgical site complications requiring reoperation; microvascular free flaps (aOR = 0.03, 95% CI, 0.00-0.42; P = 0.024) were associated with lower rates. CONCLUSIONS: The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic prostheses in chest wall reconstructions.

Superior sulcus non-small cell lung cancers (Pancoast tumors): Current outcomes after multidisciplinary management.

OBJECTIVE: Despite neoadjuvant chemoradiotherapy, Pancoast tumors still present surgical and oncologic challenges. To optimize outcomes, we used a multidisciplinary care paradigm with medical and radiation oncology, and involvement of spine neurosurgery for most T3 and all T4 tumors. Spine neurosurgery permitted resection of transverse process for T3 and vertebral body resection for T4 tumors. METHODS: Retrospective analysis of single institution, prospective database of patients undergoing resection for cT3 4M0 Pancoast tumors. Patients were grouped as cT3 with combined resection with spine neurosurgery (T3 Neuro), cT3 without spine neurosurgery (T3 NoNeuro), and cT4. Overall survival, progression-free survival were analyzed by Kaplan-Meier and compared between groups using log-rank test. Cumulative incidence of local-regional and distant recurrence were compared using Gray test. P value <.05 was considered significant. RESULTS: From 2000 to 2021, 155 patients underwent surgery: median age was 58 years, and 81 were (52%) men. Most patients received neoadjuvant platinum-based neoadjuvant chemoradiotherapy (n = 127 [82%]). Operations were 48 cT3 Neuro, 41 cT3 NoNeuro, 66 cT4. R0 resection was achieved in 49 (94%) cT3 NoNeuro, 35 (85%) cT3 Neuro, and 57 (86%) cT4 patients (P = .4). Complete or major pathologic response occurred in 71 (55%) patients. Lower local-regional cumulative incidence was seen in cT3 Neuro versus cT3 NoNeuro (P = .05) and after major pathologic response. Overall survival and progression-free survival were associated with complete response, pathologic stage, and nodal status but not cT category. CONCLUSIONS: This treatment paradigm was associated with a high frequency of R0 resection, complete response, and major pathologic response. cT3 and cT4 tumors had similar outcomes. Novel therapies are needed to improve complete response.

The contribution of microvascular free flaps and pedicled flaps to successful chest wall surgery.

OBJECTIVE: Pedicled flaps (PFs) have historically served as the preferred option for reconstruction of large chest wall defects. More recently, the indications for microvascular-free flaps (MVFFs) have increased, particularly for defects in which PFs are inadequate or unavailable. We sought to compare oncologic and surgical outcomes between MVFFs and PFs in reconstructions of full-thickness chest wall defects. METHODS: We retrospectively identified all patients who underwent chest wall resection at our institution from 2000 to 2022. Patients were stratified by flap reconstruction. End points were defect size, rate of complete resection, rate of local recurrence, and postoperative outcomes. Multivariable analysis was performed to identify factors associated with complications at 30 days. RESULTS: In total, 536 patients underwent chest wall resection, of whom 133 had flap reconstruction (MVFF, n = 28; PF, n = 105). The median (interquartile range) covered defect size was 172 cm2 (100-216 cm2) for patients receiving MVFF versus 109 cm2 (75-148 cm2) for patients receiving PF (P = .004). The rate of R0 resection was high in both groups (MVFF, 93% [n = 26]; PF, 86% [n = 90]; P = .5). The rate of local recurrence was 4% in MVFF patients (n = 1) versus 12% in PF patients (n = 13, P = .3). Postoperative complications were not statistically different between groups (odds ratio for PF, 1.37; 95% confidence interval, 0.39-5.14]; P = .6). Operative time >400 minutes was associated with 30-day complications (odds ratio, 3.22; 95% confidence interval, 1.10-9.93; P = .033). CONCLUSIONS: Patients with MVFFs had larger defects, a high rate of complete resection, and a low rate of local recurrence. MVFFs are a valid option for chest wall reconstructions.

Waiting to Operate: The Risk of Salvage Esophagectomy.

OBJECTIVE: To assess postoperative morbidity, disease-free survival (DFS), and overall survival (OS) in patients treated with salvage esophagectomy (SE). BACKGROUND DATA: A shift toward a "surgery as needed" approach for esophageal cancer has emerged, potentially resulting in delayed esophagectomy. METHODS: We identified patients with clinical stage I-III esophageal adenocarcinoma or squamous cell carcinoma who underwent chemoradiation followed by esophagectomy from 2001 to 2019. SE was defined as esophagectomy performed >90 days after chemoradiation ("for time") and esophagectomy performed for recurrence after curative-intent chemoradiation ("for recurrence"). The odds of postoperative serious complications were assessed by multivariable logistic regression. The relationship between SE and OS and DFS were quantified using Cox regression models. RESULTS: Of 1137 patients identified, 173 (15%) underwent SE. Of those, 61 (35%) underwent SE for recurrence, and 112 (65%) underwent SE for time. The odds of experiencing any serious complication [odds ratio, 2.10 (95% CI, 1.37-3.20); P =0.001] or serious pulmonary complication [odds ratio, 2.11 (95% CI, 1.31-3.42); P =0.002] were 2-fold higher for SE patients; SE patients had a 1.5-fold higher hazard of death [hazard ratio, 1.56 (95% CI, 1.25-1.94); P <0.0001] and postoperative recurrence [hazard ratio, 1.43 (95% CI, 1.16-1.77); P =0.001]. Five-year OS for nonsalvage esophagectomy was 45% [(95% CI, 41.6%-48.6%) versus 26.5% (95% CI, 20.2%-34.8%) for SE (log-rank P <0.001)]. Five-year OS for SE for time was 27.1% [(95% CI, 19.5%-37.5%) versus 25.2% (95% CI, 15.3%-41.5%) for SE for recurrence ( P =0.611)]. CONCLUSIONS: SE is associated with a higher risk of serious postoperative complications and shorter DFS and OS.

The association between perioperative frailty and ability to complete a web-based geriatric assessment among older adults with cancer.

INTRODUCTION: The aim of this study was to assess the degree to which patient frailty is associated with both need for assistance and time required to complete the eRFA, a web-based GA tool. MATERIALS AND METHODS: We retrospectively identified patients who underwent surgery for cancer from 2015 to 2020, had a hospital length of stay ≥1 day, and completed the eRFA before surgery. Frailty was assessed using two methods: the MSK-FI (score 0-11) and the AGD (score 0-13). Time to complete the eRFA was automatically recorded by a web-based tool; assistance with eRFA completion was self-reported by the patient. RESULTS: In total, 3456 patients were included (median age, 78 years). Overall, 58% of surveys were completed without assistance, 30% were completed with assistance, and 12% were completed by someone other than the patient. Younger age (median age: without assistance, 77 years; with assistance, 80 years; completed by someone else, 80 years) and lower frailty score (median AGD: 4, 6, and 8, respectively; median MSK-FI: 2, 3, and 3, respectively) were associated with independency (all p < 0.001). Higher frailty score was associated with longer time to complete the eRFA (all nonlinear association p < 0.001). CONCLUSION: Frail patients are more likely to benefit from completion of GA to determine appropriate treatment. Given that not all cancer patients have a caregiver who can assist completing a digital questionnaire, innovative solutions are needed to help frail patients complete the eRFA without assistance.

Operative Time is Associated With Postoperative Complications After Pulmonary Lobectomy.

OBJECTIVE: To investigate the association between operative time and postoperative outcomes. BACKGROUND: The association between operative time and morbidity after pulmonary lobectomy has not been characterized fully. METHODS: Patients who underwent pulmonary lobectomy for primary lung cancer at our institution from 2010 to 2018 were reviewed. Exclusion criteria included clinical stage ≥IIb disease, conversion to thoracotomy, and previous ipsilateral lung treatment. Operative time was measured from incision to closure. Relationships between operative time and outcomes were quantified using multivariable mixed-effects models with surgeon-level random effects. RESULTS: In total, 1651 patients were included. The median age was 68 years (interquartile range, 61-74), and 63% of patients were women. Median operative time was 3.2 hours (interquartile range, 2.7-3.8) for all cases, 3.0 hours for open procedures, 3.3 hours for video-assisted thoracoscopies, and 3.3 hours for robotic procedures ( P =0.0002). Overall, 488 patients (30%) experienced a complication; 77 patients (5%) had a major complication (grade ≥3), and 5 patients (0.3%) died within 30 days of discharge. On multivariable analysis, operative time was associated with higher odds of any complication [odds ratio per hour, 1.37; 95% confidence interval (CI), 1.20-1.57; P <0.0001] and major complication (odds ratio per hour, 1.41; 95% CI, 1.21-1.64; P <0.0001). Operative time was also associated with longer hospital length of stay (ß, 1.09; 95% CI, 1.04-1.14; P =0.001). CONCLUSIONS: Longer operative time was associated with worse outcomes in patients who underwent lobectomy. Operative time is a potential risk factor to consider in the perioperative phase.

Spatial intra-tumor heterogeneity is associated with survival of lung adenocarcinoma patients.

Intra-tumor heterogeneity (ITH) of human tumors is important for tumor progression, treatment response, and drug resistance. However, the spatial distribution of ITH remains incompletely understood. Here, we present spatial analysis of ITH in lung adenocarcinomas from 147 patients using multi-region mass spectrometry of >5,000 regions, single-cell copy number sequencing of ~2,000 single cells, and cyclic immunofluorescence of >10 million cells. We identified two distinct spatial patterns among tumors, termed clustered and random geographic diversification (GD). These patterns were observed in the same samples using both proteomic and genomic data. The random proteomic GD pattern, which is characterized by decreased cell adhesion and lower levels of tumor-interacting endothelial cells, was significantly associated with increased risk of recurrence or death in two independent patient cohorts. Our study presents comprehensive spatial mapping of ITH in lung adenocarcinoma and provides insights into the mechanisms and clinical consequences of GD.

Brief Report: Contralateral Lobectomy for Second Primary NSCLC: Perioperative and Long-Term Outcomes.

Introduction: Anatomical resection-often by lobectomy-is the standard of care for patients with early stage NSCLC. With increased diagnosis, survival, and prevalence of persons with early stage NSCLC, the incidence of second primary NSCLC, and consequently, the need for contralateral lobectomy for a metachronous cancer, is increasing. Perioperative outcomes after contralateral lobectomy are unknown. Methods: Among patients who underwent contralateral lobectomy for second primary NSCLC during 1995 to 2020, we evaluated 90-day mortality and major morbidity (Clavien-Dindo grades 3-5) rates and their association with clinicopathologic variables, including the year of contralateral lobectomy and duration between lobectomies. Results: A total of 98 patients underwent contralateral lobectomy for second primary NSCLC; 51 during an early time period (1995-2009) and 47 from a late time period (2010-2020). There were five mortalities and 23 patients with major morbidities after contralateral lobectomy; both rates decreased in 2010 to 2020 compared with 1995 to 2009 (mortality 10%-0%, major morbidity 35%-11%). Major morbidity was associated with an interval of less than 1 year between lobectomies, a diffusing capacity of the lung for carbon monoxide <80%, and right lower lobe resections. Mortality was associated with squamous cell carcinoma. Patients who underwent contralateral lobectomy for stage I NSCLC had 74% (95% confidence interval: 64%-85%) 3-year overall survival and 15% (95% confidence interval: 6.5%-24%) 3-year lung cancer cumulative incidence of death. Conclusions: Contralateral lobectomy for second primary early stage NSCLC was associated with poor outcomes before 2010. Since 2010, perioperative and long-term outcomes of contralateral lobectomy have been comparable with reported outcomes after unilateral lobectomy.

Propensity-matched Analysis Demonstrates Long-term Risk of Respiratory and Cardiac Mortality After Pneumonectomy Compared With Lobectomy for Lung Cancer.

OBJECTIVE: We sought to quantify and characterize long-term consequences of pneumonectomy, with particular attention to nononcologic mortality. SUMMARY OF BACKGROUND DATA: Pneumonectomy is associated with profound changes in cardiopulmonary physiology. Studies of long-term outcomes after pneumonectomy typically report generalized measures, such as disease-free and overall survival. METHODS: Patients undergoing lobectomy or pneumonectomy for lung cancer at our institution from 2000 to 2018 were reviewed. Propensity-score matching was performed for 12 clinicopathologic factors. Ninety-day complications and deaths were compared. Five-year cumulative incidence of oncologic and nononcologic mortality were compared using competing risks approaches. RESULTS: From 3339 lobectomy and 355 pneumonectomy patients identified, we derived 318 matched pairs. At 90 days, rates of overall complications were similar (46% for pneumonectomy vs 43% for lobectomy; P = 0.40), but rates of major complications (21% vs 13%; P = 0.005) and deaths (6.9% vs 1.9%; P = 0.002) were higher the pneumonectomy cohort. The cumulative incidence of oncologic mortality was not significantly different between cohorts (P = 0.9584). However, the cumulative incidence of nononcologic mortality was substantially higher in the pneumonectomy cohort for both date of surgery and 1-year landmark analyses (P < 0.0001 and P = 0.0002, respectively). Forty-five pneumonectomy patients (18%) died of nononcologic causes 1-5 years after surgery; pneumonia (n = 21) and myocardial infarction (n = 10) were the most common causes. In pneumonectomy patients, preexisting cardiac comorbidity and low diffusion capacity of the lungs for carbon monoxide were predictive of nononcologic mortality. CONCLUSIONS: Compared to lobectomy, excess mortality after pneumonectomy extends beyond 1 year and is driven primarily by nononcologic causes. Pneumonectomy patients require lifelong monitoring and may benefit from expeditious assessment and intervention at the initial signs of illness.

Effects of Postactivation Potentiation on Maximal Vertical Jump Performance After a Conditioning Contraction in Upper-Body and Lower-Body Muscle Groups.

ABSTRACT: Downey, RJ, Deprez, DA, and Chilibeck, PD. Effects of postactivation potentiation on maximal vertical jump performance after a conditioning contraction in upper-body and lower-body muscle groups. J Strength Cond Res 36(1): 259-261, 2022-Postactivation potentiation (PAP) involves preperformance contractions that can condition a muscle to enhance subsequent force generation and power output. Our purpose was to examine the effects of conditioning contractions that are specific or nonspecific to the target performance on PAP. Resistance-trained subjects (14 males and 10 females) performed a 7-second isometric contraction involving back squat, bench press (as conditioning contractions), or a control condition (rest) on different days in random order, before maximal vertical jump performance. The back squat as a conditioning contraction increased maximal vertical jump by 1.1 ± 3.0 cm (p < 0.05); however, the bench press as a conditioning contraction unexpectedly reduced maximal vertical jump performance by 1.4 ± 2.7 cm (p < 0.05). Conditioning contractions used to elicit a PAP response should use muscles that are specific to the performance movement. Contractions that are not biomechanically similar to the performance movement may hinder subsequent performance.

Prediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies.

BACKGROUND & AIMS: Tools for stratification of relapse risk of Crohn's disease (CD) after anti-tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. METHODS: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. RESULTS: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2-4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11-1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18-172), smoking (HR, 1.4; 95% CI, 1.15-1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01-1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96-1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99-1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1-1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00-1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98-1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). CONCLUSIONS: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation.

Intraoperative haemodynamics and postoperative intensive care unit admission in older patients with cancer.

PURPOSE: Research on the impact of various intraoperative haemodynamic variables on the incidence of postoperative ICU admission among older patients with cancer is limited. In this study, the relationship between intraoperative haemodynamic status and postoperative intensive care unit admission among older patients with cancer is explored. METHODS: Patients aged ≥75 who underwent elective oncologic surgery lasting ≥120min were analysed. Chi-squared and t-tests were used to assess the associations between intraoperative variables with postoperative intensive care unit admission. Multivariable regressions were used to analyse potential predict risk factors for postoperative intensive care unit admission. RESULTS: Out of 994 patients, 48 (4.8%) were admitted to the intensive care unit within 30 days following surgery. Intensive care unit admission was associated with the presence of ≥4 comorbid conditions, intraoperative blood loss ≥100mL, and intraoperative tachycardia and hypertensive urgency. On multivariable analysis, operation time ≥240min (Odds Ratio [OR] = 2.29, p = 0.01), and each minute spent with intraoperative hypertensive urgency (OR = 1.06, p = 0.01) or tachycardia (OR = 1.01, p = 0.002) were associated with postoperative intensive care unit admission. CONCLUSION: Intraoperative hypertensive urgency and tachycardia were associated with postoperative intensive care unit admission in older patients undergoing cancer surgery.