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.

Minimally Invasive Lobectomy Is Associated With Lower Noncancer-specific Mortality in Elderly Patients: A Propensity Score Matched Competing Risks Analysis.

OBJECTIVE: To investigate cancer- and noncancer-specific mortality following lobectomy by minimally invasive surgery (MIS) versus open thoracotomy in elderly patients with nonsmall cell lung cancer (NSCLC). BACKGROUND: Two-thirds of patients with NSCLC are ≥65 years of age. As age increases, the risk of competing events, such as noncancer death, also increases. METHODS: Elderly patients (≥65 yrs of age) who have undergone curative-intent lobectomy for stage I-III NSCLC without induction therapy (2002-2013) were included (n=1,303). Of those, 607 patients had undergone MIS and 696 had undergone thoracotomy. Propensity-score matching was performed to identify pairs of thoracotomy and MIS patients with comparable clinical characteristics (eg, year of surgery, comorbidities, and pulmonary function). Association between surgical approach (MIS vs thoracotomy) and lung cancer-specific and noncancer-specific cumulative incidence of death (CID) was analyzed using competing risks approach. RESULTS: Following propensity score matching of patients who had undergone thoracotomy (n=338) versus MIS (n=338), MIS was associated with shorter length of stay (P <0.001), lower noncancer-specific 1-year mortality (P=0.027), and lower noncancer-specific CID (P=0.014) compared with thoracotomy; there was no difference in lung cancer-specific CID between surgical approaches. On multivariable analysis, thoracotomy was a significant risk factor for noncancer-specific death (subhazard ratio 2.45, 95% CI 1.18-5.06, P=0.016) independent of age, sex, and diffusion capacity of the lungs for carbon monoxide. CONCLUSION: In a propensity score-matched cohort, multivariable analysis has indicated that lobectomy performed by MIS is associated with lower incidence of noncancer-specific mortality compared with lobectomy performed by open thoracotomy in elderly patients with NSCLC.

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

BACKGROUND: The newest Commission on Cancer standards recommend sampling 3 mediastinal and 1 hilar lymph node stations, 3 (N2) 1 (N1), for lung cancer resections. However, the relationship between the Commission on Cancer standards and outcomes has not been thoroughly investigated. METHODS: A prospective institutional database was queried for clinical stage I-III lung resections before 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) was assessed with multivariable models and stratified by stage. RESULTS: Of 9289 pulmonary resections, 3048 (33%) were guideline concordant and 6241 (67%) were not. Compared with nonconcordant, those that were guideline concordant had higher rates of nodal upstaging (21% vs 13%; odds ratio [OR], 1.32 [95% CI, 1.14-1.51]; P < .001) and in-hospital complications (34% vs 27%; OR, 1.17 [95% CI, 1.05-1.30]; P = .004) but similar adjuvant systemic therapy administration (19% vs 13%; OR, 1.09 [95% CI, 0.95-1.24]; P = .2; 98% chemotherapy). Locoregional and distant recurrences 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 for guideline concordant clinical stage III patients (hazard ratio, 0.85 [95% CI, 0.74-0.97]; P = .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 for 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.

Feasibility of shape-sensing robotic-assisted bronchoscopy for biomarker identification in patients with thoracic malignancies.

OBJECTIVE: Molecular diagnostic assays require samples with high nucleic acid content to generate reliable data. Similarly, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) requires samples with adequate tumor content. We investigated whether shape-sensing robotic-assisted bronchoscopy (ssRAB) provides adequate samples for molecular and predictive testing. METHODS: We retrospectively identified diagnostic samples from a prospectively collected database. Pathologic reports were reviewed to assess adequacy of samples for molecular testing and feasibility of PD-L1 IHC. Tumor cellularity was quantified by an independent pathologist using paraffin-embedded sections. Univariable and multivariable linear regression models were constructed to assess associations between lesion- and procedure-related variables and tumor cellularity. RESULTS: In total, 128 samples were analyzed: 104 primary lung cancers and 24 metastatic lesions. On initial pathologic assessment, ssRAB samples were deemed to be adequate for molecular testing in 84% of cases; on independent review of cellular blocks, median tumor cellularity was 60% (interquartile range, 25%-80%). Hybrid capture-based next-generation sequencing was successful for 25 of 26 samples (96%), polymerase chain reaction-based molecular testing (Idylla; Biocartis) was successful for 49 of 52 samples (94%), and PD-L1 IHC was successful for 61 of 67 samples (91%). Carcinoid and small cell carcinoma histologic subtype and adequacy on rapid on-site evaluation were associated with higher tumor cellularity. CONCLUSIONS: The ssRAB platform provided adequate tissue for next-generation sequencing, polymerase chain reaction-based molecular testing, and PD-L1 IHC in >80% of cases. Tumor histology and adequacy on intraoperative cytologic assessment might be associated with sample quality and suitability for downstream assays.

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.

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.

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.

Long-term assessment of efficacy with a novel Thoracic Survivorship Program for patients with lung cancer.

OBJECTIVE: We developed a novel, nurse practitioner-run Thoracic Survivorship Program to aid in long-term follow-up. Patients with non-small cell lung cancer who were disease-free at least 1 year after resection could be referred to the Thoracic Survivorship Program by their surgeon. Our objectives were to summarize follow-up compliance and assess long-term outcomes between Thoracic Survivorship Program enrollment and non-Thoracic Survivorship Program. METHODS: Patients who underwent R0 resection for stages I to IIIA between 2006 and 2016 were stratified by enrollment in Thoracic Survivorship Program versus surgeon only follow-up (non-Thoracic Survivorship Program). Follow-up included 6-month chest computed tomography scans for 2 years and then annually. Lack of follow-up compliance was defined by 2 or more consecutive delayed annual computed tomography scans/visits ± 90 days. Relationships between Thoracic Survivorship Program and second primary non--small cell lung cancers, extrathoracic cancers, and survival were quantified using multivariable Cox proportional hazards regression with time-varying covariate reflecting timing of enrollment. RESULTS: A total of 1162 of 3940 patients (29.5%) were enrolled in the Thoracic Survivorship Program. The median time to enrollment was 2.3 years; 3279 of 3940 (83%) had complete computed tomography scan data, and 60 of 3279 (1.8%) had 2 or more delayed scans; 323 of 9082 (3.6%) non-Thoracic Survivorship Program visits were noncompliant versus 132 of 4823 (2.7%) of Thoracic Survivorship Program visits (P = .009); 136 of 1146 Thoracic Survivorship Program patients developed second primary non-small cell lung cancer, and 69 of 1123 developed extrathoracic cancer, whereas 322 of 2794 of non-Thoracic Survivorship Program patients developed second primary non-small cell lung cancer and 225 of 2817 patients developed extrathoracic cancer. In multivariable analyses, Thoracic Survivorship Program enrollment was associated with improved disease-free survival (hazard ratio, 0.57; 95% confidence interval, 0.48-0.67; P < .001). CONCLUSIONS: Our novel nurse practitioner-run Thoracic Survivorship Program is associated with high patient compliance and outcomes not different from those seen with physician-based follow-up. These results have important implications for health care resource allocation and costs.

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.

Intentional Segmentectomy for Clinical T1 N0 Non-small Cell Lung Cancer: Survival Differs by Segment.

BACKGROUND: Outcomes after segmentectomy compare favorably with those after lobectomy in patients with stage I non-small cell lung cancer (NSCLC). Whether long-term outcomes vary by segmentectomy location is unclear. We investigated whether disease-free survival (DFS) and overall survival (OS) differ by segmentectomy location after intentional segmentectomy for clinical T1 N0 M0 NSCLC. METHODS: Patients who received intentional segmentectomy for cT1 N0 M0 NSCLC from 2000 to 2018 were reviewed. Patients with prior lung cancer, forced expiratory volume in 1 second of less than 50%, or R1/R2 resection were excluded. Segmentectomy groups were left (L) basilar, L segment 6, L lingula, L trisegment; right (R): basilar (R_Bas), segment 6 (R_S6), and R upper. The 5- and 10-year DFS and OS were estimated using Kaplan-Meier and compared between groups using the log-rank test. Factors associated with DFS and OS were determined using Cox proportional hazards models. RESULTS: In total, 416 patients met the inclusion criteria. Segmentectomy groups differed with regard to surgical approach, mediastinal lymphadenectomy, lymphovascular invasion, tumor histology, margin distance, and adjuvant therapy. Long-term outcomes were worst after R_S6 resection (5-year DFS, 57.6% [95% confidence interval {CI}, 45.7%-72.7%]; OS, 66.3% [95% CI, 54.7%-80.3%]) and best after R_Bas resection (5-year DFS, 77.1% [95% CI, 59.2%-100%]; OS, 79.5% [95% CI, 60.9%-100%]). On multivariable analysis, R_S6 resection was independently associated with DFS vs R_Bas (hazard ratio, 2.89; 95% CI, 1.18-7.08; P = .02) and OS vs R_Bas (hazard ratio, 4.35; 95% CI, 1.61-11.76; P = .004). CONCLUSIONS: Resection of R_S6 is independently associated with worse DFS and OS in patients receiving intentional segmentectomy for cT1 N0 M0 NSCLC and may warrant more extensive resection, complete lymph node dissection, and closer postoperative surveillance.

Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma.

PURPOSE: The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes. METHODS: Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer-specific mortality as the primary outcome. RESULTS: In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer-specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14-2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer-specific mortality (HR=1.77; 95% CI, 1.18-2.66; P=0.006). Five-year lung cancer-specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer-specific survival (P<0.001 and 0.015, respectively), compared with low mPS. CONCLUSION: This study validates CCP score and mPS as independent prognostic markers for lung cancer-specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.

Airway spray cryotherapy: initial outcomes from a multiinstitutional registry.

BACKGROUND: Spray cryotherapy (SCT) uses a noncontact system to deliver liquid nitrogen (2 to 4 psi) through an endoscopic catheter. Rapid freezing and thawing of tissue causes cellular death and is also hemostatic. We report the preliminary results from 6 institutions in which SCT was used for the treatment of malignant airway tumors. METHODS: SCT was performed on patients with symptomatic airway tumors and reviewed retrospectively. Airway narrowing was graded as 25% or smaller, 26% to 50%, 51% to 75%, and exceeding 75%. All events were documented and assessed. RESULTS: Eighty patients (45 male [56%]) underwent 114 treatments. Median age was 66 years (range, 15 to 90 years). All patients were treated with minimal blood loss. Fifty-eight percent of the cases were outpatient procedures. Airway obstruction exceeded 75% in most of the lesions treated. There were 21 intraoperative events (19%), including hypotension, bradycardia and tachycardia, ST segment changes, desaturation, and an airway tear. Three pneumothoraces occurred, one requiring emergency chest tube placement. Two intraoperative deaths were associated with bradycardia. Three postoperative deaths occurred in patients who were transitioned to comfort care. All but 1 patient had airway patency after treatment. CONCLUSIONS: SCT can be used in patients with highly vascular tumors, with reduced bleeding complications and a low overall complication rate. Caution is needed before SCT is used on a widespread basis, given the intraoperative complications. Although the potential benefit of SCT is considerable, this needs to be confirmed in larger studies.