Search

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., Competing Interests: Disclosures James M. Isbell has served as an advisory board member for AstraZeneca and Merck; has served as an uncompensated steering board member for Genentech; has received travel support from Intuitive Surgical; and has equity or ownership interest in LumaCyte. Daniela Molena has served on a steering committee for AstraZeneca; has served as a consultant for Johnson & Johnson, Bristol Myers Squibb, AstraZeneca, and Boston Scientific; and has been an invited speaker for Merck and Genentech. Bernard J. Park has received honoraria from Intuitive Surgical, AstraZeneca, and Medtronic; and has served as a consultant for Ceevra. Gaetano Rocco has a financial relationship with Scanlan, Merck, and Medtronic. Valerie W. Rusch has received other support from DaVinci Surgery; has received nonfinancial support from Bristol Myers Squibb; and has received personal fees from the NIH Coordinating Center for Clinical Trials. Smita Sihag has served as a member of the AstraZeneca advisory board. David R. Jones has served as a member of the advisory council for AstraZeneca and the Advisory Committee for More Health; and has been a speaker for DAVA Oncology. Matthew J. Bott has served as a consultant for AstraZeneca Pharmaceuticals, Iovance Biotherapeutics, and Intuitive Surgical., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The study objectives were to assess the outcomes of lung resection in patients with non-small cell lung cancer previously treated with nonoperative treatment and to identify prognostic factors associated with survival., Methods: Patients who underwent surgery (2010-2022) after initial nonoperative treatment at a single institution were identified from a prospectively maintained database. Exclusion criteria included metachronous cancer, planned neoadjuvant therapy, and surgery for diagnostic or palliative indications. Cox models were constructed for overall survival and event-free survival. Survival of patients with stage IV disease was compared with survival of a nonstudy cohort who did not undergo surgery., Results: In total, 120 patients met the inclusion criteria. Initial clinical stage was early stage in 16%, locoregionally advanced in 25%, and metastatic in 59% of patients. The indication for surgery was recurrence in 18%, local persistent disease in 23%, oligoprogression in 22%, and local control of oligometastatic disease in 38% of patients. Grade 3 or greater complications occurred in 5% of patients; 90-day mortality was 3%. Three-year event-free survival and overall survival were 39% and 73%, respectively. Male sex and lymphovascular invasion were associated with shorter event-free survival and overall survival; younger age and prior radiation therapy were associated with shorter overall survival. Patients with stage IV disease who received salvage lung resection had better overall survival than similar patients who received subsequent systemic therapy and no surgery., Conclusions: In this selected, heterogeneous population, lung resection after initial nonoperative treatment for non-small cell lung cancer was safe. Surgery as local consolidative therapy was associated with encouraging outcomes and should be considered for these patients., Competing Interests: Conflict of Interest Statement Dr Adusumilli declares research funding from ATARA Biotherapeutics; is a scientific advisory board member and consultant for ATARA Biotherapeutics, Bayer, Bio4T2, Carisma Therapeutics, Imugene, ImmPactBio, Johnson & Johnson, Orion, and Outpace Bio; has patents, royalties, and intellectual property on mesothelin-targeted chimeric antigen receptor and other T-cell therapies, which have been licensed to ATARA Biotherapeutics; and has an issued patent method for detection of cancer cells using virus and pending patent applications on PD-1 dominant negative receptor, a wireless pulse-oximetry device, and an ex vivo malignant pleural effusion culture system. MSK Cancer Center has licensed intellectual property related to mesothelin-targeted chimeric antigen receptors and T-cell therapies to ATARA Biotherapeutics and has associated financial interests. Dr Rocco has financial relationships with Scanlan International, Medtronic, and Merck. Dr Molena serves on a steering committee for AstraZeneca and as a consultant for Johnson & Johnson, Bristol Myers Squibb, Merck, and Genentech. Dr Park is a consultant for Intuitive Surgical, Medtronic, AstraZeneca, and CEEVRA. Dr Bott is a consultant for AstraZeneca. Dr Rusch reports grant support (institutional) from Genelux and Genentech, travel support from Intuitive Surgical, and travel support and payments from National Institutes of Health/Coordinating Center for Clinical Trials. Dr Sihag is a member of the AstraZeneca Advisory Board. Dr Isbell has stock ownership in LumaCyte and is a consultant/advisory board member for Roche Genentech. Dr Chaft serves as a consultant for AstraZeneca, Bristol Myers Squibb, Flame Biosciences, Regeneron-Sanofi, Guardant Health, and Arcus Biosciences and receives institutional research funding from AztraZeneca, Bristol Myers Squibb, Merck, and Novartis. Dr Li has served as an uncompensated advisor and consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, and Lilly; has received research grants to his institution from Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, and Lilly; has received academic travel support from Amgen, Jiangsu Hengrui Medicine, and MORE Health; and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. Dr Gomez reports research funding from Merck, AstraZeneca, Varian, and Bristol Myers Squibb and serves on the advisory boards of MedLearning Group, Medtronic, GRAIL, Johnson & Johnson, AstraZeneca, and Varian. Dr Rimner is a consultant for AstraZeneca, Merck, and MoreHealth, serves as an advisory board member for Merck, and reports institutional grant support from Varian Medical Systems, AstraZeneca, Merck, Pfizer, and Boehringer Ingelheim. Dr Jones serves as a consultant for Merck, AstraZeneca, Genentech, and DAVA Oncology. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Targeted therapy improves outcomes in patients with advanced-stage non-small cell lung cancer (NSCLC) and in the adjuvant setting, but data on its use before surgery are limited. We sought to investigate the safety and feasibility of preoperative targeted therapy in patients with operable NSCLC., Methods: We retrospectively reviewed 51 patients with clinical stage I to III NSCLC who received targeted therapy, alone or in combination with chemotherapy, before surgical resection with curative intent, treated from 2004 to 2021. The primary outcome was the safety and feasibility of preoperative targeted therapy; secondary outcomes included objective response rate, major pathologic response (defined as ≤10% viable tumor) rate, recurrence-free survival (RFS), and overall survival., Results: Of the 51 patients included, 46 had an activating epidermal growth factor receptor gene alteration and 5 had an anaplastic lymphoma kinase fusion. Overall, 37 of 46 evaluable patients experienced at least 1 adverse event before surgery; however, only 3 patients experienced a grade 3 or 4 event. The objective response rate was 38% (17/45) for all evaluable patients and 44% (14/32) for patients with clinical stage II or III disease. The major pathologic response rate was 20% (9/44); 2 patients had a complete pathologic response. Median RFS was 3.8 years (95% CI, 2.8 to not reached). Targeted therapy alone was associated with better RFS than combination therapy (P = .009) in patients with clinical stage II or III disease., Conclusions: Preoperative targeted therapy was well tolerated and associated with good outcomes, with or without induction chemotherapy. In addition, radiographic response and pathologic response were strongly correlated., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The optimal treatment strategy for pathologic single-station N2 (pN2a1) non-small cell lung cancer (NSCLC)-surgery first followed by adjuvant treatment (SF) or neoadjuvant therapy followed by surgery (NS)-remains unclear. We compared disease-free survival (DFS) and overall survival (OS) after NS versus SF for pN2a1 NSCLC. We retrospectively identified patients with pN2a1 NSCLC resected between 2000 and 2018. Patients in the SF group had cN0 disease and were treated with surgery before adjuvant chemotherapy; patients in the NS group had known preoperative nodal disease, cN2 disease, and were treated with neoadjuvant therapy before surgery. The matching-weights procedure was applied to generate a cohort with similar characteristics between groups. DFS and OS were calculated using the Kaplan-Meier approach and compared between groups using weighted log-rank test and Cox proportional hazards models. We identified 227 patients with pN2a1 disease: 121 treated with SF and 106 with NS. After the matching-weights procedure, 5- and 10-year DFS were 45% and 27% for SF versus 26% and 21% for NS (log-rank P = 0.056; hazard ratio [HR], 1.61; 95% confidence interval [CI], 0.98-2.65); 5- and 10-year OS were 49% and 30% for SF versus 43% and 20% for NS (log-rank P = 0.428; HR, 1.24; 95% CI, 0.67-2.28). SF and NS for pN2a1 NSCLC resulted in similar survival. A study comparing SF for known preresectional pN2a1 with occult pN2a1 disease could be a next step. Further investigation of SF for known N2a1 versus occult pN2a1 disease could power a clinical trial focused on N2a NSCLC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Locally advanced non-small-cell lung cancer (NSCLC) with chest wall invasion carries a high risk of recurrence and portends poor survival (30-40% and 20-50%, respectively). No studies have identified prognostic factors in patients who underwent R0 resection for non-superior sulcus NSCLC., Methods: A retrospective review was conducted for all chest wall resections for NSCLC from 2004 to 2018. Patients with superior sulcus tumours, partial (<1 rib) or incomplete (R1/R2) resection or distant metastasis were excluded. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards modelling was used to determine factors associated with DFS and OS., Results: A total of 100 patients met inclusion criteria. Seventy-three (73%) patients underwent induction therapy, and all but 12 (16%) patients experienced a partial radiological response. A median of 3 ribs was resected (range 1-7), and 67 (67%) patients underwent chest wall reconstruction. The 5-year DFS and OS were 36% and 45%, respectively. Pathological N2 status [hazard ratio (HR) 3.12, confidence interval (CI) 1.56-6.25; P = 0.001], intraoperative blood transfusion (HR 2.24, CI 1.28-3.92; P = 0.005) and preoperative forced vital capacity (per % forced vital capacity, HR 0.97, CI 0.96-0.99; P = 0.013) were associated with DFS. Increasing pathological stage, lack of radiological response to induction therapy (HR 7.35, CI 2.35-22.99; P = 0.001) and cardiovascular comorbidity (HR 2.43, CI 1.36-4.36; P = 0.003) were associated with OS., Conclusions: We demonstrate that blood transfusion and forced vital capacity are associated with DFS after R0 resection for non-superior sulcus NSCLC, while radiological response to induction therapy greatly influences OS. We confirm that pathological nodal status and pathological stage are reproducible determinants of DFS and OS, respectively., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: There has been growing interest in limited resection and nonsurgical treatment for small lung cancers. We examined the pattern and rate of occult N1 nodal metastasis in patients with peripheral, small (≤2 cm), clinically node-negative non-small cell lung cancer (NSCLC)., Methods: Patients with peripheral small (≤2 cm) NSCLC with no evidence of locally advanced or metastatic disease (clinical T1a-b N0 M0, American Joint Committee on Cancer 8th Edition Cancer Staging Manual), who were deemed eligible for lobectomy or sublobar resection, were identified from preregistration eligibility screening logs for the Alliance/Cancer and Leukemia Group B 140503 trial at our institution. Pathologic outcomes were examined in all patients undergoing anatomic resection with mediastinal and hilar lymphadenectomy., Results: Included were 58 patients treated between November 2014 and January 2017 who met the inclusion criteria: 51 underwent lobectomy, and 7 underwent segmentectomy. Mean tumor diameter on computed tomography was 1.5 cm, and mean positron emission tomography maximal standardized uptake value was 3.9. The mean consolidation-to-tumor ratio was 0.77. Occult nodal metastases in N1 stations were found in 8 of 58 patients (14%), and most of these nodes were found in interlobar or peribronchial stations (11 or 12). An additional 2 patients (3%) had occult positive N2 nodes. Overall, the false-negative rate for clinical staging was 16%., Conclusions: Occult nodal disease was frequently identified in peripheral N1 stations (11-13) in patients with small (≤2 cm) clinical N0 NSCLC. Hilar lymphadenectomy is essential for accurate staging in the management of patients with small clinical N0 NSCLC., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Perioperative blood transfusions have been implicated in decreased overall survival (OS) and disease-free survival (DFS) after resection for non-small cell lung cancer (NSCLC). We investigated the effects of single- and multiple-unit blood transfusions on OS, DFS, and recurrence after anatomic pulmonary resection., Methods: From January 1, 2000, to June 30, 2016, 5709 consecutive patients underwent pulmonary resection for NSCLC at our institution. Exclusion criteria were stage IIIB-IV disease, incomplete resections, ill-defined histologic subtypes, and nonanatomic wedge resections. For the 0 versus single-unit analysis, propensity scores were calculated from a logistic regression model that predicted the probability of patients receiving a single-unit transfusion. The resulting matching weights were incorporated into Cox models for OS, DFS, and cumulative incidence of recurrence, to compare no versus single-unit blood transfusion. We determined whether increasing numbers of blood transfusions influenced survival or recurrence using multivariable Cox models., Results: Approximately 10% of patients received perioperative blood transfusion (median follow-up, 7.46 years [25th-75th percentile, 3.98-11.8]). There was no difference in OS, DFS, or cumulative incidence of recurrence between patients receiving no transfusion and those receiving single-unit transfusion (P > .05). However, a dose-response relationship was observed, demonstrating worse OS (overall P < .001), DFS (overall P < .001), and recurrence (overall P = .010) with increasing units of blood transfused., Conclusions: Although a single-unit blood transfusion did not affect survival in patients undergoing resection for NSCLC, greater unit perioperative blood transfusions were associated with significantly decreased long-term outcomes in a dose-dependent manner, suggesting avoidance or minimization of transfusions could improve long-term survival after lung resection., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the long-term outcomes among robotic, video-assisted thoracic surgery (VATS), and open lobectomy in stage I nonsmall cell lung cancer (NSCLC)., Background: Survival comparisons between robotic, VATS, and open lobectomy in NSCLC have not yet been reported. Some studies have suggested that survival after VATS is superior, for unclear reasons., Methods: Three cohorts (robotic, VATS, and open) of clinical stage I NSCLC patients were matched by propensity score and compared to assess overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analyses were performed to identify factors associated with the outcomes., Results: From January 2002 to December 2012, 470 unique patients (172 robotic, 141 VATS, and 157 open) were included in the analysis. The robotic approach harvested a higher number of median stations of lymph nodes (5 for robotic vs 3 for VATS vs 4 for open; P < 0.001). Patients undergoing minimally invasive approaches had shorter median length of hospital stay (4 d for robotic vs 4 d for VATS vs 5 d for open; P < 0.001). The 5-year OS for the robotic, VATS, and open matched groups were 77.6%, 73.5%, and 77.9%, respectively, without a statistically significant difference; corresponding 5-year DFS were 72.7%, 65.5%, and 69.0%, respectively, with a statistically significant difference between the robotic and VATS groups (P = 0.047). However, multivariate analysis found that surgical approach was not independently associated with shorter OS and DFS., Conclusions: Minimally invasive approaches to lobectomy for clinical stage I NSCLC result in similar long-term survival as thoracotomy. Use of VATS and robotics is associated with shorter length of stay, and the robotic approach resulted in greater lymph node assessment., Competing Interests: All authors declare no conflicts of interest.

Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non-small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer-specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer-specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer-specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

Introduction: Bevacizumab improves survival in patients with advanced non-small-cell lung cancer (NSCLC). This phase II clinical trial assessed the effects of the addition of bevacizumab to neoadjuvant chemotherapy in resectable nonsquamous NSCLC., Methods: Patients with resectable stage IB-IIIA nonsquamous NSCLC were treated with bevacizumab followed by imaging 2 weeks later to assess single-agent effect. After this they received two cycles of bevacizumab with four cycles of cisplatin and docetaxel followed by surgical resection. Resected patients were eligible for adjuvant bevacizumab. The primary endpoint was the rate of pathological downstaging (decrease from pretreatment clinical stage to post-treatment pathological stage). Secondary endpoints included overall survival, safety, and radiologic response., Results: Fifty patients were enrolled. Thirty-four (68%) were clinical stage IIIA. All three doses of neoadjuvant bevacizumab were delivered to 40 of 50 patients. Six patients (12%) discontinued because of bevacizumab-related adverse events. The rate of downstaging (38%), response to chemotherapy (45%), and perioperative complications (12%) were comparable with historical data. No partial responses were observed to single-agent bevacizumab, but 18% of the patients developed new intratumoral cavitation, with a trend toward improved pathologic response (57% versus 21%; p = 0.07). A major pathologic response (≥90% treatment effect) was associated with survival at 3 years (100% versus 49%; p = 0.01). No patients with KRAS-mutant NSCLC (0 of 10) had a pathologic response as compared with 11 of 31 with wild-type KRAS., Conclusion: Although preoperative bevacizumab plus chemotherapy was feasible, it did not improve downstaging in unselected patients. New cavitation after single-agent bevacizumab is a potential biomarker. Alternative strategies are needed for KRAS-mutant tumors.

Objective: We previously reported a high mortality after induction therapy and pneumonectomy for non-small cell lung cancer. Recent reports suggest that operative mortality in these patients is declining. We analyzed our contemporary results to define operative mortality and factors determining surgical risk., Methods: Eligible patients were identified from our prospective surgical database. Complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0. Uni- and multivariate logistic regression models assessed the association of preoperative tests and clinical characteristics with outcome. Receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) statistics were calculated in a leave-one-out crossvalidation scheme to evaluate the predictive value of various models., Results: From January 2000 to December 2006, 549 patients underwent surgery after induction therapy. Median patient age was 64 years (range: 30-86), and 54% were women (298/549). All received chemotherapy, and 17% also had radiation. Lobectomy (388/549, 71%) and pneumonectomy (70/549, 13%) were the most common procedures. Complications occurred in 250 patients (46%), with grade 3 or higher in 23% (126/549). Inhospital mortality was 1.8% (10/549), with only one death after right pneumonectomy (1/30, 3%). Multivariate analysis showed that predicted postoperative (PPO) pulmonary function was associated with postoperative morbidity. By receiver operating characteristic curves, PPO product (AUC = 0.75, p < 0.001), PPO diffusion capacity (AUC = 0.70, p < 0.001), and preoperative % predicted PPO diffusion capacity (AUC = 0.66, p < 0.001) predicted mortality., Conclusion: Our current experience shows that resection of non-small cell lung cancer after induction therapy, including pneumonectomy, is associated with low mortality. PPO pulmonary function is the strongest predictor of operative risk and should be used to select patients for surgery.

Objective: The objective of our study was to illustrate the potential for phrenic nerve injury during percutaneous lung ablation, to discuss the importance of this complication, and to review the expected location of the phrenic nerve on chest CT., Conclusion: Knowledge of the expected location of the phrenic nerve-a structure that is usually not visible on imaging but is important-is essential for avoiding injury to the nerve during pulmonary ablation.

Purpose: A retrospective review of surgically treated lung cancer patients imaged preoperatively by F-18 fluorodeoxyglucose-positron emission tomography ([(18)F]FDG-PET) to determine if the primary tumor standardized uptake value (SUV) predicts survival., Patients and Methods: Non-small-cell lung cancer or carcinoid pT1-4, N0-2, M0 patients treated by R0 surgical resection alone were imaged with computed tomography scan and PET within 90 days before surgery. Prognostic variables were assessed by log-rank test; survival was assessed by the method of Kaplan and Meier., Results: One hundred consecutive patients (48 men, 52 women) were retrospectively reviewed. Median follow-up for surviving patients was 28 months (range, 16 to 81 months). Median maximal SUV (SUV(MAX)) was 9. The 2-year survival for patients with SUV(MAX) more than 9 was 68% and for those with SUV(MAX) less than 9, it was 96% (P <.01, log-rank test). In a multivariate analysis including pathologic tumor size, involved nodes, histology, and SUV(MAX), only tumor size (T) more than 3 cm and SUV(MAX) more than 9 and their interaction were significant predictors of survival (P =.01, 0.02, and < 0.01, respectively). The 3-year survivals for patients with both T less than 3 cm and SUV(MAX) less than 9 was 97%; for those with T less than 3 cm and SUV(MAX) more than 9, it was 94%; for those with T more than 3 cm and SUV(MAX) less than 9, it was 93%; and for those with T more than 3 cm and SUV(MAX) more than 9, it was 47% (P <.01)., Conclusion: In surgically managed lung cancer patients, SUV is a predictor of overall survival after resection. The addition of SUV(MAX) to pathologic tumor size identifies a subgroup of patients at highest risk for death as a result of recurrent disease after resection.

Purpose: Retrospective reports suggest that selected patients with non-small cell lung cancer (NSCLC) and a solitary synchronous site of M(1) disease may be effectively treated by resection of all disease sites. The feasibility and potential benefit of combining surgery and chemotherapy in this setting are unclear. Therefore, we performed a prospective trial to test this therapeutic approach., Methods: Patients with solitary synchronous M(1) NSCLC with or without N(2) disease were to receive three cycles of mitomycin, vinblastine, cisplatin (MVP) chemotherapy, followed by resection of all disease sites, and then two cycles of VP chemotherapy. Solitary brain metastases were to be resected before chemotherapy., Results: From 10/92-2/99, 23 patients (12 men, 11 women, median age = 55 years) were enrolled. Mediastinoscopy, performed in 22 patients, showed involved N(2) nodes in 12. The M(1) sites included brain (14 patients) adrenal (3), bone (3), spleen (1), lung (1), and colon (1). Of 12 patients who completed all three induction therapy cycles, 8 underwent R(0) resections. Another 5 patients had R(0) resections without completing induction therapy. Eight of the 13 patients undergoing R(0) resections completed postoperative chemotherapy. The median survival was 11 months; 2 patients survived to 5 years without disease., Conclusions: (1) The number of patients with solitary M(1) disease who qualified for this combined modality therapy was small; (2) MVP was poorly tolerated as induction chemotherapy in this patient population; (3) Compared to historical experience with surgery alone, overall survival does not appear to be superior with this treatment strategy., (Copyright 2002 Elsevier Science Ireland Ltd.)

Object: Non-small cell lung carcinomas with spinal and brachial plexus involvement have traditionally been considered to be Stage IIIb lesions and therefore unresectable. Advances in spinal surgery, the application of magnetic resonance (MR) imaging, and improvements in neoadjuvant therapy require a reassessment of the potential for complete resection., Methods: The authors conducted a retrospective review of all procedures involving the resection of superior sulcus tumors with spinal or brachial plexus involvement performed between 1985 and 1999. Assessment or resectability and operative planning were based on an MR imaging classification scheme in which the extent of spinal involvement was considered. Class A tumors involved the periosteum of the vertebral body (VB) (16 patients); Class B, distal neural foramen without epidural compression (eight patients); Class C, proximal neural foramen with epidural compression (four patients); and Class D, bone involvement (VB or posterior elements) with or without epidural involvement (14 patients). Brachial plexus involvement was present in 21 patients, including 17 with T-1 nerve root only and four with C-8 or lower-trunk infiltration. Complete tumor resection was achieved in 27 patients and incomplete resection in 15. Complications occurred in 14 patients, two of which were related to instrumentation failures. The overall median survival was 1.44 years. The median survival for the complete and incomplete resection groups were 2.84 and 0.79 years, respectively (p = 0.0001). There was no statistical difference in survival among classification groups., Conclusions: Complete tumor resection of superior sulcus tumors is possible in selected patients in whom involvement of the spinal column and/or brachial plexus is present. Preoperative MR imaging is essential for evaluation of the spine and surgical planning. Survival and cure are dependent on complete resection, regardless of the extent of spinal involvement.

Purpose: Assessment of long-term results of combined-modality therapy for resectable non-small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience., Patients and Methods: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression., Results: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P <.001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival., Conclusion: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.

Background: The risks of complications in patients undergoing thoracotomy after neoadjuvant therapy for nonsmall cell lung cancer remain controversial. We reviewed our experience to define it further., Methods: All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events., Results: Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate., Conclusions: Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.

Background: The treatment of superior sulcus lung cancers is evolving and preoperative chemotherapy is increasingly used. To establish a historical benchmark against which new therapies can be assessed, we reviewed our 24-year experience with patients undergoing thoracotomy for lung cancers of the superior sulcus., Methods: Data were acquired through retrospective chart review. Overall survival was calculated by the method of Kaplan and Meier, and prognostic factors were examined by log rank and Cox proportional hazards modeling., Results: From 1974 to 1998, 225 patients underwent thoracotomy. The patients included 144 men (64%) and 81 women with a median age of 55 years. The majority of patients (55%) received preoperative radiation, but 35% did not have any preoperative treatment. Tumor stages were IIB (T3 N0) in 52%, IIIA in 15%, and IIIB in 27% of patients. Complete resection was achieved in 64% of T3 N0 tumors, 54% of T3 N2 tumors, and 39% of T4 N0 tumors. Operative mortality was 4%. Median survival was 33 months for stage IIB and 12 months for both stages IIIA and IIIB. Actuarial 5-year survivals were 46% for stage IIB, 0% for stage IIIA, and 13% for stage IIIB. By univariate and multivariable analyses, T and N status and complete resection had a significant impact on survival. Locoregional disease was the most common form of relapse., Conclusions: Our results provide a benchmark against which new treatment regimens can be evaluated. Control of locoregional disease remains the major challenge in treating lung cancers of the superior sulcus. The potential benefit of preoperative chemotherapy or chemoradiotherapy must be assessed by whether it leads to higher rates of complete resection and a lower risk of local relapse.

Background: The long-term survival after operation of patients with lung cancer involving the chest wall is known to be related to regional nodal involvement and completeness of resection, but it is not known whether the depth of chest wall involvement or the type of resection (extrapleural or en bloc) affects either the rate of local recurrence or survival., Methods: We retrospectively reviewed the Memorial Sloan-Kettering Cancer Center experience between 1974 and 1993 of 334 patients undergoing surgical exploration for lung cancer involving the chest wall or parietal pleura., Results: Of 334 patients who underwent exploration, 175 had apparently complete (R0) resections, 94 had incomplete (R1 or R2) resections, and 65 underwent exploration without resection. The overall 5-year survival of R0 patients was 32%, of R1 or R2 patients 4%, and of patients undergoing exploration without resection 0%. In the patients undergoing R0 resections, the extent of chest wall involvement was limited to the parietal pleura in 80 patients, and extended into the ribs or soft tissues in 95. The 5-year survival of R0 patients with T3 N0 M0 disease was 49%, T3 N1 M0 disease 27%, and T3 N2 M0 disease 15% (p < 0.0003). Independent of lymph node involvement, a survival advantage was observed in R0 patients if the chest wall involvement was limited to parietal pleura only, rather than invading into the chest wall musculature or ribs., Conclusions: Survival of patients with lung cancer invading the chest wall after resection with curative intent is highly dependent on the extent of nodal involvement and the completeness of resection, and much less so on the depth of chest wall invasion.

Background: Patients often undergo limited resection instead of lobectomy for non-small cell lung cancer because of a low preoperative forced expiratory volume in 1 second (FEV1). Our goal is to define criteria that will preoperatively identify a group of patients who will not lose further function after lobectomy., Methods: Patients who underwent lobectomy with a preoperative FEV1 of less than 80% of predicted were retrospectively identified. Data collected included preoperative and postoperative pulmonary function tests, age, sex, the lobe resected, and preoperative ventilation-perfusion scan result., Results: Thirty-two patients were included in this study. The median preoperative FEV1 was 60% of predicted (1.65 L) and the mean change in FEV1 was a loss of 7.8% after lobectomy. The patients were divided into two groups. Group 1 (n = 13) had a preoperative FEV1 of less than or equal to 60% of predicted (median, 49%; 1.35 L) combined with an FEV1 to forced vital capacity ratio of less than or equal to 0.6. Group 2 (n = 19) includes all other patients (median preoperative FEV1, 69% of predicted; 1.87 L). The mean changes in FEV1 after lobectomy were +3.7% and -15.7% for groups 1 and 2, respectively (p < 0.005). A chronic obstructive pulmonary disease index was defined and then calculated for each patient. The relationship between this index and the change in FEV1 after lobectomy for all 32 patients appears linear (r = -0.43; p = 0.015)., Conclusions: Patients with a very low preoperative FEV1 and FEV1 to forced vital capacity ratio are less likely to lose ventilatory function after lobectomy and may actually improve it.

From 1973 to 1985, 598 patients underwent resection for stage I non-small-cell lung cancer. There were 291 T1 lesions and 307 T2 lesions. The male/female ratio was 1.9:1. The histologic type was squamous carcinoma in 233 and nonsquamous carcinoma in 365. Lobectomy was performed in 511 patients (85%), pneumonectomy in 25 (4%), and wedge resection or segmentectomy in 62 (11%). A mediastinal lymph node dissection was carried out in 560 patients (94%) and no lymph node dissection in 38 (6%). Fourteen postoperative deaths occurred (2.3%). Ninety-nine percent of the patients were observed for a minimum of 5 years or until death with an overall median follow-up of 91 months. The overall 5- and 10-year survivals (Kaplan-Meier) were 75% and 67%, respectively. Survival in patients with T1 N0 tumors was 82% at 5 years and 74% at 10 years compared with 68% at 5 years and 60% at 10 years for patients with T2 tumors (p < 0.0004). The overall incidence of recurrence was 27% (local or regional 7%, systemic 20%) and was not influenced by histologic type. Second primary cancers developed in 206 patients (34%). Of these, 70 (34%) were second primary lung cancers. Despite complete resection, 31 of 62 patients (50%) who had wedge resection or segmentectomy had recurrence. Five- and 10-year survivals after wedge resection or segmentectomy were 59% and 35%, respectively, significantly less than survivals of those undergoing lobectomy (5 years, 77%; 10 years, 70%). The 5- and 10-year survivals in the 38 patients who had no lymph node dissection were reduced to 59% and 32%, respectively. Apart from the favorable prognosis observed in this group of patients, three facts emerge as significant: (1) Systematic lymph node dissection is necessary to ensure that the disease is accurately staged; (2) lesser resections (wedge/segment) result in high recurrence rates and reduced survival regardless of histologic type; and (3) second primary lung cancers are prevalent in long-term survivors.

The results of surgical treatment were analyzed for 102 patients with non-small cell lung cancer invading the mediastinum by direct extension (T3 and T4), but those who had N2 disease were excluded to eliminate the adverse prognostic effect of this nodal subset. The histologic type was squamous cell carcinoma in 55 patients, adenocarcinoma in 40, and large cell carcinoma in 7. There were 58 T3 tumors invading the mediastinal pleura or fat, phrenic nerve, vagus nerve, pericardium, or pulmonary vessels and 44 T4 lesions invading the aorta, vena cava, esophagus, trachea, spine, or atrium. Resection included lobectomy (33 patients), pneumonectomy (32 patients), and limited resection (6 patients). Complete resection was possible in 46 patients and incomplete or no resection was possible in 56. The interstitial implantation of radioactive sources to control residual tumor also was undertaken in 43 patients. The operative mortality was 6%. The overall survival (Kaplan-Meier) was 19% at 5 years (median survival time, 18 months). Factors found to be significantly affect survival were complete resectability and the histologic type. With complete resection, the 5-year survival was 30% (p = 0.005). The 5-year survival in patients with adenocarcinoma or large-cell carcinoma was 30%, compared with 14% in patients with squamous cell carcinoma (p = 0.002). The extent of mediastinal involvement (T3 versus T4) influenced resectability and survival, and this approached statistical significance (p = 0.055). We conclude that most patients with non-small cell carcinoma and mediastinal invasion do poorly with primary surgical treatment.

This prospective randomized trial was performed to determine whether postoperative chemotherapy with vindesine and cisplatin could lengthen time to progression and overall survival in stage III (T1-3N2M0) non-small cell lung cancer (NSCLC) patients. Seventy-two patients were entered; 36 were randomized to receive chemotherapy. Patients were stratified by extent of resection (complete vs. incomplete) and histology (squamous vs. nonsquamous). All had surgery and mediastinal irradiation 6-7 weeks post-thoracotomy. Incompletely resected patients had intraoperative 125I and/or 192Ir implantation. Vindesine (3 mg/m2) weekly x 5, then every 2 weeks x 8, and cisplatin (120 mg/m2) days 1, 29, 71, 113 were planned for those randomized to chemotherapy. No difference in time to progression (median 9.2 months for radiation + chemotherapy vs. 9.0 months for radiation, P = 0.35) or overall survival (16.3 months for radiation + chemotherapy vs. 19.1 months for radiation, P = 0.42) was found. Postoperative vindesine and cisplatin did not prolong time to progression or survival in this population of stage III NSCLC.

Unlabelled: We designed a prospective study to evaluate the accuracy of magnetic resonance imaging in distinguishing a benign from a malignant adrenal mass in patients with otherwise operable non-small-cell lung cancer., Methods: Potentially operable non-small-cell lung cancer was prospectively staged. If a unilateral adrenal mass was found by computed tomographic scanning, respiratory compensated and cardiac gated thin section magnetic resonance imaging of the adrenal glands was done. One radiologist interpreted the magnetic resonance imaging scan blinded and, on the basis of the relative signal strengths of the T1- and T2-weighted images, judged whether the adrenal mass was benign or malignant. The patients then underwent a percutaneous needle biopsy of the adrenal mass, if technically feasible. If the result of the needle biopsy was nondiagnostic or if the biopsy was not feasible, an adrenalectomy through a posterior approach was performed., Results: Twenty-seven patients with a unilateral adrenal mass entered the study-11 men and 16 women whose ages ranged from 42 to 75 years (median 58 years). Four patients had epidermoid and 23 adenocarcinoma of the lung. The clinical locoregional stage was I in 9, II in 1, IIIA in 16, and IIIB in 1. Twenty-five completed the magnetic resonance imaging procedure. Five adrenal masses (19%) were metastatic non-small-cell lung cancer (adenocarcinoma = 4, epidermoid = 1); 22 masses (81%) were benign (adenoma = 20, hyperplasia = 2). There were no significant differences in age, sex, histologic type, or locoregional stage between those with a benign versus a malignant mass. However, the malignant masses were significantly larger (3.8 +/- 1.9 cm; range 2.5 to 7.1; median 3.1) than the benign masses (2.0 +/- 0.4 cm, range 1.2 to 2.8; median 2.0) (p < 0.001). Among those having magnetic resonance imaging (n = 25), the technique correctly predicted a malignant mass in the four patients with a histologically confirmed metastasis from non-small-cell lung cancer. However, among the 21 histologically benign masses, the magnetic resonance imaging was interpreted as benign in 5, malignant in 14, and indeterminate in 2. Therefore, although the false-negative rate was 0%, the false-positive rate was 67%., Conclusion: Most adrenal masses in patients with otherwise operable non-small-cell lung cancer are benign. Currently available magnetic resonance imaging methods cannot replace biopsy.

From 1984 to 1991, 136 patients with histologically confirmed non-small cell lung cancer and stage IIIa (N2) disease received two to three cycles of MVP (mitomycin + vindesine or vinblastine + high-dose cisplatin) chemotherapy. All patients had clinical N2 disease, defined as bulky mediastinal lymph node metastases or multiple levels of lymph node involvement in the ipsilateral mediastinum or subcarinal space on chest roentgenograms, computed tomographic scans, or mediastinoscopy. The overall major response rate to chemotherapy was 77% (105/136). Thirteen patients had a complete response and 92 patients had a partial but major response (> 50%). The overall complete resection rate was 65% (89/136) with a complete resection rate of 78% (82/105) in patients with a major response to chemotherapy. There was no histologic evidence of tumor in the resected specimens of 19 patients. The overall survival was 28% at 3 years and 17% at 5 years (median, 19 months). For patients who had complete resection, the median survival was 27 months and the 3-year and 5-year survivals were 41% and 26%, respectively. There were seven treatment-related deaths, five of which were postoperative deaths. To date, 33 patients, all of whom had complete resection, have had no recurrence after treatment. These results demonstrate that (1) preoperative chemotherapy with MVP produces high response rates in stage IIIa (N2) disease, (2) high complete resection rates occur after response to chemotherapy, and (3) survival is longest in patients who have a complete resection after major response to chemotherapy.

From 1973 to 1989, 214 patients with stage II non-small cell lung cancer were treated by resection and complete mediastinal lymph node dissection. There were 116 adenocarcinomas and 98 squamous cancers. There were 35 T1 N1 and 179 T2 N1 tumors. Whereas T1 tumors were mainly adenocarcinomas (83%), this difference was not apparent in T2 lesions. Regardless of histology, half of the patients had a single involved N1 lymph node. Lobectomy was performed in 68% of the patients, pneumonectomy in 31%, and wedge resection or segmentectomy in 1%. Lobectomy was sufficient to encompass all disease in 34 of 35 T1 N1 tumors. Only 48 patients (22%) received postoperative external irradiation and 11 patients (5%) received chemotherapy. The overall 5-year disease-free survival was 39%. The best survival rates were in patients who had a single node involved and tumors 3 cm or less in diameter (48%). The pattern of recurrence differed by histology. Local or regional recurrence was more frequent in patients with squamous carcinoma whereas distant metastases were more commonly seen in adenocarcinomas (87%) with brain as the most frequent site (adenocarcinoma, 52%; squamous, 34%). It is concluded that in stage II carcinomas, resection remains the treatment of choice, that mediastinal lymph node dissection provides the most accurate staging, and that the best adjuvant treatment to improve survival is yet to be determined.

From 1974 to 1984, 225 patients underwent thoracotomy at Memorial Sloan-Kettering Cancer Center for primary non-small cell lung cancer invading only the mediastinum (T3). The perioperative mortality was 2.7 per cent, and the nonfatal complication rate 13 per cent. Forty-nine patients underwent complete resection of all intrathoracic disease, with a median survival of 17 months, 3-year survival of 21 per cent, and 5-year survival of 9 per cent. Thirty-three patients underwent pulmonary resection with simultaneous iodine-125 interstitial implantation or iridium-192 delayed afterloading to areas of unresectable primary or nodal disease, with a median survival of 12 months, 3-year survival of 22 per cent, and 5-year survival of 22 per cent. One hundred and one patients underwent interstitial implantation without resection, with a median survival of 11 months, 3-year survival of 9 per cent, and no 5-year survivors. Forty-two patients had incomplete resection without intraoperative radiation therapy and fared no better than a cohort group of 44 unoperated patients with clinical evidence of mediastinal invasion--both groups had a median survival of 8 months and no 3-year survivors. An aggressive surgical approach with pulmonary resection and/or brachytherapy appears to offer some survival advantage to this group of patients. In particular, 5-year survival rates ranging from 7 to 15 per cent were observed in subsets of intraoperatively treated patients with invasion of pulmonary vein, phrenic nerve, esophagus, or pericardium and in those with clinically occult T3 disease.

We have defined "clinical N2" disease in non-small cell lung cancer to mean the presence of enlarged metastatic mediastinal nodes evident on plain chest roentgenograms or widening of the carina at bronchoscopy. Forty-one patients with non-small cell carcinoma of the lung and clinical N2 M0 disease presumed operable received 2 to 3 cycles of high-dose cisplatin with vindesine (or vinblastine sulfate) with or without mitomycin-C. Following chemotherapy, 30 patients (73%) had a major radiographic response. Of these patients, 28 had thoracotomy, and 21 (75%) of them had complete resection of the disease, 8 of whom had total sterilization of the tumor proven histologically. An additional 4 patients had limited microscopic foci of residual tumor either in lung or lymph nodes. Survival at 3 years from diagnosis was 34% for all patients, 40% for those who completed the combined treatment (chemotherapy and surgery), and 54% for those who had complete resection with a median follow-up of 44 months and a median survival not yet attained.