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Background: Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC., Methods: In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling., Findings: Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported., Interpretation: The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures., Funding: French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests VW reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol Myers Squibb (BMS), Merck Sharpe and Dohme, Pfizer, and Roche outside the submitted work; support for attending meetings or travel from AstraZeneca, BMS, and Sanofi outside the submitted work; and participation on a data safety monitoring board or advisory board from MSD and Takeda outside the submitted work. JT reports support for attending meetings or travel from Roche and BMS, outside the submitted work. EQ reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Chugai and BMS, outside the submitted work; and support for attending meetings or travel from BMS, Roche, and Takeda, outside the submitted work. GZ reports grants or contracts from Fondation Roche, Takeda, and BMS outside the submitted work; consulting fees from BMS and AstraZeneca, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from BMS, AstraZeneca, Pfizer, and MDS, outside the submitted work; support for attending meetings or travel from BMS, AstraZeneca, and AbbVie, outside the submitted work. FB reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F Hoffmann–La Roche, Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: The prognosis of patients with non-small-cell lung cancer (NSCLC), traditionally determined by anatomic histology and TNM staging, neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying patients with NSCLC at increased risk of recurrence after curative-intent surgery remains an important unmet need so that known effective adjuvant treatments can be offered to those at highest risk of recurrence., Methods: Relative gene expression level in the primary tumor and normal bronchial tissues was used to retrospectively assess their association with disease-free survival (DFS) in a cohort of 120 patients with NSCLC who underwent curative-intent surgery., Results: Low versus high Digital Display Precision Predictor (DDPP) score (a measure of relative gene expression) was significantly associated with shorter DFS (highest recurrence risk; P = .006) in all patients and in patients with TNM stages 1-2 ( P = .00051; n = 83). For patients with stages 1-2 and low DDPP score (n = 29), adjuvant chemotherapy was associated with improved DFS ( P = .0041). High co-overexpression of CTLA-4 , PD-L1 , and ICOS in normal lung (28 of 120 patients) was also significantly associated with decreased DFS ( P = .0013), suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS ( P = 2.12E-11)., Conclusion: TNM stage, DDPP score, and immune competence status of normal lung are independent prognostic factors in multivariate analysis. Our findings open new avenues for prospective prognostic assessment and treatment assignment on the basis of transcriptomic profiling of tumor and normal lung tissue in patients with NSCLC., Competing Interests: Vladimir LazarPatents, Royalties, Other Intellectual Property: I am inventor on patentes filed by WIN Consortium I do not receive money Nicolas GirardEmployment: AstraZeneca (I)Consulting or Advisory Role: Roche, Lilly, AstraZeneca, Novartis, Pfizer, Bristol Myers Squibb, MSD, Takeda, Janssen, Sanofi, AmgenResearch Funding: Roche (Inst), AstraZeneca (Inst), BMS (Inst)Travel, Accommodations, Expenses: Roche Eric RaymondEmployment: Genoscience Pharma, SCOR, StromaCare, Onward TherapeuticsLeadership: AFR-OncologyStock and Other Ownership Interests: Neuronax, Oncoethix, Genoscience Pharma, SCORConsulting or Advisory Role: Lilly, Pfizer, Merck Serono, PharmaEngine, Novartis/lpsen, Celgene Jean-François MartiniEmployment: PfizerStock and Other Ownership Interests: Pfizer Susan GalbraithEmployment: AstraZenecaLeadership: BB Biotech VenturesStock and Other Ownership Interests: AstraZeneca Benjamin SolomonConsulting or Advisory Role: BayerResearch Funding: AstraZeneca/Merck (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/358846 Hovav NechushtanResearch Funding: AstraZeneca (Inst), Spectrum Pharmaceuticals (Inst), Lilly (Inst), Merck KGaA (Inst)Uncompensated Relationships: MSD Amir OnnHonoraria: Boehringer Ingelheim, Roche, MSD, AmgenConsulting or Advisory Role: Boehringer Ingelheim, MSDSpeakers' Bureau: AstraZeneca Raanan BergerStock and Other Ownership Interests: BelongHonoraria: Bristol Myers Squibb, Roche Israel, AstraZeneca, Pfizer, MSDConsulting or Advisory Role: Belong, MSD Oncology, BMSSpeakers' Bureau: Mitra Biotech, BMS, MSD OncologyTravel, Accommodations, Expenses: Mitra Biotech, Bristol Myers Squibb, MSD, AstraZeneca Sadakatsu IkedaHonoraria: Chugai Pharma, Novartis, AstraZeneca, Taiho Pharmaceutical, Guardant Health, Bristol Myers Squibb-Ono Pharmaceutical, MSD, ACT Genomics, Roche, Canon Medical System, ACT MedConsulting or Advisory Role: Genodive Pharma (Inst)Research Funding: ACT Genomics (Inst), Hitachi (Inst), Canon Medical System (Inst) Ulrik LassenHonoraria: Bayer, Pfizer, NovartisConsulting or Advisory Role: Bayer, PfizerResearch Funding: BMS (Inst), Roche (Inst), Pfizer (Inst), GlaxoSmithKline (Inst), Incyte (Inst), Lilly (Inst) Enriqueta FelipConsulting or Advisory Role: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Lilly, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Pfizer, Sanofi, Takeda, Peptomyc, Daiichi Sankyo Europe GmbH, F. Hoffmann La Roche, Merck Sharp & DohmeSpeakers’ Bureau: AstraZeneca, Bristol Myers Squibb, Lilly, Medscape, Merck Sharp & Dohme, PeerVoice, Pfizer, Takeda, Amgen, F. Hoffmann La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, TouchONCOLOGYResearch Funding: Merck (Inst), Merck KGaA (Inst)Other Relationship: GRiFOLS Josep TaberneroStock and Other Ownership Interests: Oniria TherapeuticsConsulting or Advisory Role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, Seattle Genetics, Array BioPharma, AstraZeneca, Genentech, Menarini, Servier, HalioDx, F. Hoffmann La Roche, Mirati Therapeutics, Pierre Fabre, Tessa Therapeutics, TheraMyc, Daiichi Sankyo, Samsung Bioepis, IQvia, Ikena Oncology, Merus, Neophore, Orion Biotechnology, Hutchison MediPharma, Scandion Oncology, Ona Therapeutics, Sotio, Inspirna, Scorpion TherapeuticsOther Relationship: Imedex, Medscape, MJH Life Sciences, Peerview, Physicans' Education Resource Alan SpatzConsulting or Advisory Role: Janssen, Bristol Myers Squibb, Pfizer/EMD Serono, Merck, Roche, AstraZeneca, Novartis, Bayer, AbbVieResearch Funding: Merck (Inst), Bristol Myers Squibb (Inst) C.S. PrameshStock and Other Ownership Interests: Aurobindo Philippe GirardHonoraria: Bayer, LEO Pharma, BMS/PfizerConsulting or Advisory Role: LEO Pharma, Bayer, BMS/PfizerTravel, Accommodations, Expenses: Bayer, LEO Pharma, BMS/Pfizer Jean-Yves BlayLeadership: Innate PharmaHonoraria: Roche, AstraZeneca, PharmaMar, MSD, BMS, Bayer, Ignyta, DecipheraConsulting or Advisory Role: Roche, Pharmamar, Deciphera, Blueprint Medicines, Bayer, Karyopharm TherapeuticsResearch Funding: GlaxoSmithKline (Inst), Pharmamar (Inst), Novartis (Inst), Bayer (Inst), Roche (Inst), BMS (Inst), MSD (Inst), Deciphera (Inst), AstraZeneca (Inst), OSE Pharma (Inst)Travel, Accommodations, Expenses: Roche Angel PorgadorStock and Other Ownership Interests: PooldiConsulting or Advisory Role: PiNKPatents, Royalties, Other Intellectual Property: Ben-Gurion University, Israel, several patents Eitan RubinStock and Other Ownership Interests: Pfizer Razelle KurzrockLeadership: CureMatch, CureMetrixStock and Other Ownership Interests: CureMatch, IDbyDNA, CureMetrixHonoraria: Roche, EUSA Pharma, NeoGenomics Laboratories, Biocom, NeoMed, Advanced Therapeutics, LEK, AACR, Chugai Pharma USA, Wiley, Merck, Pfizer, Meyer Consulting, Foundation Medicine, Turning Point Therapeutics, Bicara TherapeuticsConsulting or Advisory Role: Actuate Therapeutics, Loxo, XBiotech, NeoMed, Roche, Gaido, Soluventis, Pfizer, Merck, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics, AstraZeneca, Biological Dynamics, Daiichi Sankyo, Eisai, EOM Pharmaceuticals, lylon, ProsperdtxSpeakers' Bureau: RocheResearch Funding: Guardant Health (Inst), Sequenom (Inst), Merck Serono (Inst), Genentech (Inst), Pfizer (Inst), Foundation Medicine (Inst), Incyte (Inst), Konica Minolta (Inst), Grifols (Inst), OmniSeq (Inst), Debiopharm Group (Inst), Boehringer Ingelheim (Inst), Top Alliance BioScience (Inst), Takeda (Isnt), Medlmmune (Inst), Biological Dynamics (Inst)Travel, Accommodations, Expenses: Roche, EUSA Pharma, NeoGenomics Laboratories, Biocom, NeoMed, Advanced Therapeutics, LEK, AACR, Chugai Pharma USA, Wiley Richard L. SchilskyLeadership: Clarified Precision MedicineStock and Other Ownership Interests: EQRxConsulting or Advisory Role: Cellworks, Scandion Oncology, Bryologyx, IIIumina, EQRx, Syapse, ZephyrAIResearch Funding: AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Lilly (Inst), Merck (Inst), Pfizer (Inst), Boehringer Ingelheim (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/I138818/summaryNo other potential conflicts of interest were reported.

Background: Stage IIIA/B-N2 is a very heterogeneous group of patients and accounts for one third of NSCLC at diagnosis. The best treatment strategy is established at a Multidisciplinary Tumor Board (MTB): surgical resection with neoadjuvant or adjuvant therapy versus definitive chemoradiation with immune checkpoint inhibitors consolidation. Despite the crucial role of MTBs in this complex setting, limited data is available regarding its performances and the reproducibility of the decision-making., Methods: Using a large cohort of IIIA/B-N2 NSCLC patients, we described patient's characteristics and treatment strategies established at the initial MTB: with a "surgical strategy" group, for potentially resectable disease, and a "medical strategy" group for non-resectable patients. A third group consisted of patients who were not eligible for surgery after neoadjuvant treatment and switched from the surgical to the medical strategy. We randomly selected 30 cases (10 in each of the 3 groups) for a blinded re-discussion at a fictive MTB and analyzed the reproducibility and factors associated with treatment decision., Results: Ninety-seven IIIA/B-N2 NSCLC patients were enrolled between June 2017 and December 2019. The initial MTB opted for a medical or a surgical strategy in 44% and 56% of patients respectively. We identified histology, tumor size and localization, extent of lymph node involvement and the presence of bulky mediastinal nodes as key decision-making factors. Thirteen patients were not eligible for surgical resection after neoadjuvant therapy and switched for a medical strategy. Overall concordance between the initial decision and the re-discussion was 70%. The kappa correlation coefficient was 0.43. Concordance was higher for patients with limited mediastinal node invasion. Survival did not appear to be impacted by conflicting decisions., Conclusions: Reproducibility of treatment decision-making for stage IIIA/B-N2 NSCLC patients at a MTB is moderate but does not impact survival., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Evaluating morbidity and survival of patients operated on for a second primary non-small-cell lung cancer (NSCLC)., Methods: Retrospective collection of data from patients operated on for a second NSCLC between 2009 and 2018., Results: Fifty-two patients met the inclusion criteria. At the time of second pulmonary resection, the median time between the 2 surgeries was 25 months (5-44.5 months). Patients' median age was 65 years (61-68 years). Median tumour size was 16 mm (10-22 mm). Thoracoscopy was used in 75% of cases. The resection was a pneumonectomy (n = 1), bilobectomy (n = 1), lobectomy (n = 15), segmentectomy (n = 32) or wedge resection (n = 3). The length of stay was 7 days (5-9 days). Mortality was null and morbidity was 36.5%, mainly from grade I-II complications according to the Clavien-Dindo classification. The median follow-up was 28 months (13-50 months). The median overall survival was 67 months (95% confidence interval 60.8-73.1 months). Survival at 5 years and specific survival were 71.1% and 67.7%, respectively., Conclusions: A second surgical resection of either synchronous or metachronous NSCLC has a morbidity that is not superior to the morbidity of the first operation. The new tumour is usually diagnosed at an early stage. An anatomical sublobar resection is most likely the best compromise. It might also be considered for the first operation when there is a suspicious synchronous lesion that may require surgery at a later stage., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The full thoracoscopic approach to major pulmonary resections is considered challenging and controversial as it might compromise oncological outcomes. The aim of this work was to analyse the results of a full thoracoscopic technique in terms of nodal upstaging and survival in patients with non-small-cell lung carcinoma (NSCLC)., Methods: All patients who underwent a full thoracoscopic major pulmonary resection for NSCLC between 2007 and August 2016 were analysed from an 'intent-to-treat' prospective database. Overall survival and disease-free survival were estimated using the Kaplan-Meier curves and comparisons in survival using the log-rank test., Results: A total of 648 patients met the inclusion criteria, of whom 621 patients had clinical Stage I and 27 had higher stages (16 oligometastatic patients were excluded from the analysis, 11 cT3 or cT4). The mean follow-up was 34.5 months. There were 40 conversions to thoracotomy (6.3%). Thirty-day or in-hospital mortality was 0.95%. Complications occurred in 29.3% of patients. On pathological examination, 22.5% of clinical Stage I patients were upstaged. Nodal upstaging to N1 or N2 was observed in 15.8% of clinical Stage I patients. Five-year overall survival of the whole cohort was 75% and was significantly different between clinical Stages IA (76%) and IB (70.9%). For tumours <2 cm, no significant difference in overall survival was found for the segmentectomy group compared to the lobectomy group: 74% versus 78.9% (P = 0.634)., Conclusions: Long-term survival is not compromised by a full thoracoscopic approach. Our results compared favourably with those of video-assisted techniques.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg -1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents., Competing Interests: Conflict of interest: G. Meyer reports grants and non-financial support from Leo Pharma, outside the submitted work. Conflict of interest: B. Besse has nothing to disclose. Conflict of interest: H. Doubre has nothing to disclose. Conflict of interest: A. Charles-Nelson has nothing to disclose. Conflict of interest: S. Aquilanti reports non-financial support from Leo Pharma, outside the submitted work. Conflict of interest: A. Izadifar has nothing to disclose. Conflict of interest: R. Azarian has nothing to disclose. Conflict of interest: I. Monnet has nothing to disclose. Conflict of interest: C. Lamour has nothing to disclose. Conflict of interest: R. Descourt has nothing to disclose. Conflict of interest: G. Oliviero has nothing to disclose. Conflict of interest: L. Taillade has nothing to disclose. Conflict of interest: C. Chouaid has nothing to disclose. Conflict of interest: F. Giraud has nothing to disclose. Conflict of interest: P-E. Falcoz has nothing to disclose. Conflict of interest: M-P. Revel has nothing to disclose. Conflict of interest: V. Westeel has nothing to disclose. Conflict of interest: A. Dixmier has nothing to disclose. Conflict of interest: J. Tredaniel has nothing to disclose. Conflict of interest: S. Dehette has nothing to disclose. Conflict of interest: C. Decroisette has nothing to disclose. Conflict of interest: A. Prevost has nothing to disclose. Conflict of interest: E. Pichon has nothing to disclose. Conflict of interest: E. Fabre has nothing to disclose. Conflict of interest: J-C. Soria has nothing to disclose. Conflict of interest: S. Friard has nothing to disclose. Conflict of interest: J-B. Stern has nothing to disclose. Conflict of interest: L. Jabot has nothing to disclose. Conflict of interest: G. Dennewald has nothing to disclose. Conflict of interest: G. Pavy has nothing to disclose. Conflict of interest: P. Petitpretz has nothing to disclose. Conflict of interest: J-M. Tourani has nothing to disclose. Conflict of interest: M. Alifano has nothing to disclose. Conflict of interest: Dr. Chatellier has nothing to disclose. Conflict of interest: P. Girard reports personal fees and non-financial support from Leo Pharma, outside the submitted work., (Copyright ©ERS 2018.)

Background: Routine collection of cytology specimens from bronchial aspirate or washing is thought to increase the sensitivity of bronchoscopy for diagnosing malignant lung lesions. However, the added value of this practice has not been reappraised in a context of changing epidemiology., Patients and Methods: In a retrospective monocenter study, all cytology specimens from bronchial aspirate or washing collected between May 2011 and December 2014 and the corresponding patients' files were reviewed. The final diagnosis of malignancy was based on all available pathologic information., Results: Bronchoscopy was performed in 2750 patients, and bronchial cytology specimens were collected during 667 procedures, including 474 aspirate or washing cytology specimens collected during conventional (n = 366) or ultrasound-guided (EBUS) (n = 108) bronchoscopy in 455 patients with malignant lung lesion(s). The predominant histologic types were lung adenocarcinoma (43.9%) and squamous cell carcinoma (25.2%), and 271 tumors (59.6%) were endoscopically visible. At least 1 endoscopic sample (bronchial cytology and/or biopsies and/or endobronchial ultrasound-guided samples) was positive for malignancy during 329 (69.4%) of the 474 endoscopies, including 79 samples obtained in nonvisible lesions. Only 67 bronchial cytology specimens proved positive (sensitivity, 14.7%; 95% confidence interval, 11.8%-18.3%), and only 1 specimen (0.2%) produced a diagnosis not made by other samples during the same procedure., Conclusion: In contrast with older studies, the added value of collecting cytology specimens from bronchial aspirate or washing during bronchoscopy in this series proved negligible, reflecting mainly the increasing prevalence of adenocarcinomas. Abandoning this technique could be considered in centers with similar expertise and patient populations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Resectable non-small cell lung cancer (NSCLC) treatment options most often consist of surgical resection along with adjuvant chemotherapy (ACT). The benefit of ACT however is modest and is accompanied by important side effects., Objective: One central quest in the field is therefore the identification of a predictive marker of the response to ACT., Methods: We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort., Results: We identified MMS19, a component of the cytoplasmic Iron-Sulfur Assembly (CIA) machinery important for the Nucleotide Excision Repair (NER) pathway as a pivotal gene for cisplatin toxicity. We then confirmed the association between MMS19 expression and the response to Cisplatin treatment in a panel of NSCLC cell lines. Finally we validated these pre-clinical data in a subgroup of JBR.10 trial patients through a hypothesis-driven analysis, and showed that MMS19 levels associated with ACT benefit., Conclusions: We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.

Background: The hypothesis of an infectious etiology of the formerly named bronchiolo-alveolar carcinoma (BAC) has raised controversy. We investigated tumor lung tissues from five patients with former BAC histology using high-throughput sequencing technologies to discover potential viruses present in this type of lung cancer. Around 180 million single reads of 100 bases were generated for each BAC sample., Results: None of the reads showed a significant similarity for Jaagsiekte sheep retrovirus (JSRV) and no other viruses were found except for endogenous retroviruses., Conclusions: In conclusion, we have demonstrated the absence of JSRV and other known human viruses in five samples of well-characterized lepidic adenocarcinoma.

Background: In lung adenocarcinoma, inactivation of the tumor suppressor p53 may abrogate a safeguard mechanism preventing the development of tumors with activating mutations in EGFR or KRAS. To assess this hypothesis, we analyzed TP53 mutations and downregulation of p14(arf), a negative regulator of p53 activated by oncogenic signals, in a retrospective series of 96 patients with primary adenocarcinoma of the lung., Patients and Methods: Mutations in TP53 (exons 4-9), KRAS (exon 1), and EGFR (exons 18-21) were identified by direct sequencing of DNA from formalin-fixed, paraffin-embedded resected tumors. Expression of p14(arf) was semiquantitatively evaluated by immunohistochemical analysis., Results: TP53, KRAS, and EGFR mutations were detected in 42 of 93 (45.2%), 15 of 95 (15.8%), and 31 of 90 (34.4%) cases, respectively. Low p14(arf) expression was observed in 19 of 91 cases (20.9%). Disruption of the p53/p14(arf) pathway (defined as TP53 mutation or decreased p14(arf) expression, or both) was observed in 18 of 31 EGFR-mutated (58.1%) tumors and in 9 of 13 KRAS-mutated (69.2%) tumors., Conclusion: Inactivation of the p53/p14(arf) pathway is common but not systematic in EGFR- or KRAS-mutated lung adenocarcinomas. Our work highlights the need to better investigate the association between EGFR and KRAS mutations and alterations in tumor suppressor pathways., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC., Methods: Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC., Results: At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1 and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944., Conclusions: Integrated molecular characterization of AC and SCC helped identify clinically relevant markers and potential drivers, which are recurrent and stable changes at DNA level that have functional implications at RNA level and have strong association with histological subtypes.

In this study, we have analyzed human primary lung adenocarcinoma tumors using global mass spectrometry to elucidate the biological mechanisms behind relapse post surgery. In total, we identified over 3000 proteins with high confidence. Supervised multivariate analysis was used to select 132 proteins separating the prognostic groups. Based on in-depth bioinformatics analysis, we hypothesized that the tumors with poor prognosis had a higher glycolytic activity and HIF activation. By measuring the bioenergetic cellular index of the tumors, we could detect a higher dependency of glycolysis among the tumors with poor prognosis. Further, we could also detect an up-regulation of HIF1α mRNA expression in tumors with early relapse. Finally, we selected three proteins that were upregulated in the poor prognosis group (cathepsin D, ENO1, and VDAC1) to confirm that the proteins indeed originated from the tumor and not from a stromal or inflammatory component. Overall, these findings show how in-depth analysis of clinical material can lead to an increased understanding of the molecular mechanisms behind tumor progression.

Non-small cell lung carcinoma patients are frequently treated with cisplatin (CDDP), most often yielding temporary clinical responses. Here, we show that PARP1 is highly expressed and constitutively hyperactivated in a majority of human CDDP-resistant cancer cells of distinct histologic origin. Cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PAR(high)) responded to pharmacologic PARP inhibitors as well as to PARP1-targeting siRNAs by initiating a DNA damage response that translated into cell death following the activation of the intrinsic pathway of apoptosis. Moreover, PARP1-overexpressing tumor cells and xenografts displayed elevated levels of PAR, which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP1 expression itself. Thus, a majority of CDDP-resistant cancer cells appear to develop a dependency to PARP1, becoming susceptible to PARP inhibitor-induced apoptosis., (©2013 AACR.)

Purpose: To identify genetic changes that could drive cancer pathogenesis in never and ever smokers with lung adenocarcinoma., Experimental Design: We analyzed the copy number and gene expression profiles of lung adenocarcinomas in 165 patients and related the alterations to smoking status. Having found differences in the tumor profiles, we integrated copy number and gene expression data from 80 paired samples., Results: Amplifications at 8q24.12 overlapping MYC and ATAD2 were more frequent in ever smokers. Unsupervised analysis of gene expression revealed two groups: in the group with mainly never smokers, the tumors expressed genes common to normal lung; in the group with more ever smokers, the tumors expressed "proliferative" and "invasive" gene clusters. Integration of copy number and gene expression data identified one module enriched in mitotic genes and MYC targets. Its main associated modulator was ATAD2, a cofactor of MYC. A strong dose-response relationship between ATAD2 and proliferation-related gene expression was noted in both never and ever smokers, which was verified in two independent cohorts. Both ATAD2 and MYC expression correlated with 8q24.12 amplification and were higher in ever smokers. However, only ATAD2, and not MYC, overexpression explained the behavior of proliferation-related genes and predicted a worse prognosis independently of disease stage in a large validation cohort., Conclusions: The likely driving force behind MYC contribution to uncontrolled cell proliferation in lung adenocarcinoma is ATAD2. Deregulation of ATAD2 is mainly related to gene amplification and is more frequent in ever smokers., (©2012 AACR)

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC., (Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Although major pulmonary resections for early-stage non-small cell lung cancer (NSCLC) are more and more frequently performed through thoracoscopy, the adequacy of lymphadenectomy achieved via this approach is still questioned. The aim of this study was to evaluate the results of lymph node dissection (LND) during totally thoracoscopic (TT) major pulmonary resections., Methods: Clinical and pathological data of consecutive patients who underwent lobectomy or segmentectomy for clinical-N0 NSCLC between 1 January 2007 and 31 December 2009 were reviewed. The main evaluation criterion was the number of mediastinal lymph nodes (LNs) and mediastinal stations dissected through a TT approach when compared with the classical posterolateral thoracotomy (PLT) approach., Results: A total of 296 major pulmonary resections (278 lobectomies and 18 anatomic segmentectomies) for clinical stages I-II NSCLC were performed, 96 via a TT approach and 200 through PLT. Patients' clinical characteristics were similar in both groups. The overall-i.e mediastinal and lobar-number of dissected mediastinal LNs and of dissected mediastinal stations were similar in both groups (TT: mean ± SD = 17.7 ± 8.2; PLT: 18.2 ± 9.3(P < 0.937) and 3.2 ± 0.9 vs 3.4 ± 0.9, respectively). The overall numbers of stations (TT: mean ± SD 5.1 ± 1.1; PLT: 4.5 ± 1.2) and LNs (TT: 22.6 ± 9.4, PLT: 25.4 ± 10.8) were slightly but significantly different between the two groups (P < 0.001 and P = 0.033, respectively); there was no difference in terms of post-operative complications, although patients from the TT group had significantly fewer days with the chest tube (mean ± SD = 4.0 ± 1.8 vs 5.7 ± 3.9, P < 0.001) and shorter length of stay (7.0 ± 2.5 days vs 10.3 ± 7.4, P < 0.001)., Conclusions: For patients undergoing thoracoscopic lobectomy or segmentectomy for clinical early-stage NSCLC, the quality of mediastinal LND is equivalent to that performed by thoracotomy.

Purpose: Excision repair cross-complementation group 1 (ERCC1) is a protein involved in repair of DNA platinum adducts and stalled DNA replication forks. We and others have previously shown the influence of ERCC1 expression upon survival rates and benefit of cisplatin-based chemotherapy in patients with resected non-small-cell lung cancer (NSCLC). However, little is known about the molecular characteristics of ERCC1-positive and ERCC1-negative tumors., Experimental Design: We took advantage of a cohort of 91 patients with resected NSCLC, for which we had matched frozen and paraffin-embedded samples to explore the comparative molecular portraits of ERCC1-positive and ERCC1-negative tumors of NSCLC. We carried out a global molecular analysis including assessment of ERCC1 expression levels by using both immunohistochemistry (IHC) and quantitative reverse transcriptase PCR (qRT-PCR), genomic instability, global gene and miRNA expression, and sequencing of selected key genes involved in lung carcinogenesis., Results: ERCC1 protein and mRNA expression were significantly correlated. However, we observed several cases with clear discrepancies. We noted that ERCC1-negative tumors had a higher rate of genomic abnormalities versus ERCC1-positive tumors. ERCC1-positive tumors seemed to share a common DNA damage response (DDR) phenotype with the overexpression of seven genes linked to DDR. The miRNA expression analysis identified miR-375 as significantly underexpressed in ERCC1-positive tumors., Conclusions: Our data show inconsistencies in ERCC1 expression between IHC and qRT-PCR readouts. Furthermore, ERCC1 status is not linked to specific mutational patterns or frequencies. Finally, ERCC1-negative tumors have a high rate of genomic aberrations that could consequently influence prognosis in patients with resected NSCLC., (©2011 AACR.)

Reported experience with video-assisted anatomic pulmonary segmentectomy is still limited. Over a 28-month period, totally thoracoscopic (TT) anatomic segmentectomies, i.e. using only endoscopic instrumentation and video-display without utility incision, were attempted on 50 patients (25 males and 25 females), aged 18-81 years (mean: 57 years). The indication was a clinical N0 non-small cell lung carcinoma in 25 cases, a solitary metastasis in nine cases and a benign lesion in 16 cases. The following segmentectomies were performed: right apicosuperior (9) right superior (6), right basilar (7), lingula sparing left upper lobectomy (7), left apicosuperior (4), lingula (4), left superior (6) and left basilar (7). It was associated with a radical lymphadenectomy in 20 cases. There was one conversion to thoracotomy. The mean operative time was 188±54 min, the mean intraoperative blood loss was 91±82 ml (range: 0-450 ml). There were four minor postoperative complications (11.7%). The median postoperative stay was 5.6±2.4 days. Out of the 25 patients operated on for a cN0 lung carcinoma, two were finally upstaged to N2. TT anatomic pulmonary segmentectomies are feasible and safe.

Background: Lung cancer in never smokers would rank as the seventh most common cause of cancer death worldwide., Methods and Findings: We performed high-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in sixty never smokers and identified fourteen new minimal common regions (MCR) of gain or loss, of which five contained a single gene (MOCS2, NSUN3, KHDRBS2, SNTG1 and ST18). One larger MCR of gain contained NSD1. One focal amplification and nine gains contained FUS. NSD1 and FUS are oncogenes hitherto not known to be associated with lung cancer. FISH showed that the amplicon containing FUS was joined to the next telomeric amplicon at 16p11.2. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. Other cancer genes present in aberrations included ARNT, BCL9, CDK4, CDKN2B, EGFR, ERBB2, MDM2, MDM4, MET, MYC and KRAS. Unsupervised hierarchical clustering with adjustment for false-discovery rate revealed clusters differing by the level and pattern of aberrations and displaying particular tumor characteristics. One cluster was strongly associated with gain of MYC. Another cluster was characterized by extensive losses containing tumor suppressor genes of which RB1 and WRN. Tumors in that cluster frequently harbored a central scar-like fibrosis. A third cluster was associated with gains on 7p and 7q, containing ETV1 and BRAF, and displayed the highest rate of EGFR mutations. SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity., Conclusions: The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers.

We report a 54-year-old man who presented with abdominal pain and severe hyponatremia a few days after a left lower lobectomy for lung cancer. An abdominal computed tomography scan without contrast showed a bilateral adrenal hemorrhagic infarction, mainly on the right side. Serum sodium level was 113 mmol/L, and cortisol level was 0 microg/L. Anticardiolipin-type antibodies (immunoglobulin G isotype) level was 75 GPL/mL (normal value < 10). With hydrocortisone supplementation and curative doses of low-molecular-weight heparin, the patient recovered progressively and was discharged on postoperative day 17. Final diagnosis was bilateral adrenal gland hemorrhagic necrosis leading to adrenal insufficiency, associated with antiphospholipid syndrome. We discuss the mechanism and the role of the operation in the occurrence of this particularly rare and potentially life-threatening complication. Recommendations to prevent thrombosis in surgical patients who have antiphospholipid antibodies are lacking., (Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: For many years, surgery has been the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). Recent randomized trials demonstrated that cisplatin-based adjuvant chemotherapy increases overall survival. The aim of this study was to analyze the precise use of adjuvant chemotherapy in patients with resected NSCLC in routine practice., Patients and Methods: Between January 2004 and May 2005, we retrospectively analyzed 219 patients with early-stage NSCLC who had undergone surgery at one major surgical center in Paris, Institut Mutualiste Montsouris. Patient characteristics, the type of surgery, and indications for adjuvant chemotherapy were analyzed., Results: Eighty-seven of the 219 patients (40%) in this study had been treated with adjuvant chemotherapy. Different factors were associated with doctors not prescribing this treatment: age, comorbidity, tumor, node, metastasis stage, and postoperative complications. More than eight different cisplatin-based regimens were used, highlighting considerable heterogeneity in the use of adjuvant chemotherapy in daily practice. There is an increase of adjuvant chemotherapy during the study period., Conclusion: Cisplatin-based chemotherapy is the standard treatment for patients with resected stage II and IIIA NSCLC. However, such therapy is used quite heterogeneously in daily practice and specific regimens, and the percentage of patients receiving adjuvant chemotherapy vary from standard recommendations. A prospective follow-up of daily practice regarding the use of adjuvant chemotherapy is warranted.

Background: Although video-assisted metastasectomy has been proposed for some solitary metastases, its value has not been investigated in patients with pulmonary metastases from sarcoma for which open resection remains the usual approach., Methods: In all, 113 consecutive patients underwent curatively intended lung resection for metastases from sarcomas. Of these 113 patients, 31 were selected for a thoracoscopic wedge resection (group TS). These patients were compared with 29 patients operated on by thoracotomy but whose features could have made them possible candidates for a thoracoscopic resection (group TT). Follow-up was complete for all patients (mean follow-up, 34 months)., Results: No mortality occurred. No morbidity was observed in group TT, and 1 complication occurred in group TS. The mean postoperative hospital stay was 3.7 days for group TS and 6.2 days for group TT (p < 0.0001). Overall survival rates at 1, 3, and 5 years were, respectively, 87.4%, 70.9%, and 52.5% in group TS, and 82.3%, 63.6%, and 34% in group TT (p = 0.20). Disease-free survival rates at 1 and 3 years were, respectively, 50.5% and 26.4% in group TS and 60% and 24.8% in group TT (p = 0.74). Local recurrence occurred in 1 patient in each group. Survival without a homolateral recurrence (i.e., in the operated lung) at 1 and 3 years was 66.7% and 44.4% in group TS and 83.5% and 45% in group TT, respectively (p = 0.54)., Conclusions: In selected patients with a maximum of two pulmonary nodules, thoracoscopic resections yield survival rates similar to open resections while being less invasive and preserving the patient's ability to undergo possible repeat operations.

Purpose: There are major differences affecting genes in adenocarcinomas in ever and never smokers. However, data on whether mitogen-activated protein kinase (MAPK) activation state differs according to smoking status are limited., Experimental Design: Expression of activated extracellular signal-regulated kinases, c-Jun NH(2)-terminal kinases, and P38 enzymes (pP38) were evaluated by means of immunohistochemistry in 188 chemonaïve patients with surgically resected lung adenocarcinoma. Cell viability of the lung adenocarcinoma cell line HCC827 was studied after treatment with cisplatin or the P38 MAPK inhibitor SB 203580., Results: Thirty-seven of 44 never smokers [84%; 95% confidence intervals (95% CI), 70-92%] expressed high pP38 levels compared with 45 of 104 ever smokers (43%; 95% CI, 34-53%; P < 0.0001). The proportion of never smokers expressing high c-Jun NH(2)-terminal kinase levels (72%; 95% CI, 57-83%) was greater than that of ever smokers (53%; 95% CI, 44-62%; P = 0.03). The proportion of ever smokers expressing high extracellular signal-regulated kinase levels (51%; 95% CI, 42-59%) was similar to that of never smokers (57%; 95% CI, 42-71%; P = 0.47). Never smokers were 10.5 times (95% CI, 3.5-31.5) more likely to express high pP38 levels after adjustment for variables linked to smoking status, including age, sex, and histologic subtype. None of the activated MAPKs predicted for overall survival. Cell viability of HCC827 was significantly reduced after exposure to SB203580 alone or when combined with cisplatin., Conclusions: Life-long nonsmoking is associated with high activated P38 levels in patients with lung adenocarcinoma. Activated P38 can contribute to the viability of adenocarcinoma cells in never smokers, but is not predictive for overall survival.

Purpose: This study was designed to evaluate the prognostic effect of erythropoietin (EPO) and EPO receptor (EPO-R) expression in stage I non-small cell lung cancer (NSCLC) patients., Experimental Design: EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue array technology., Results: EPO-R and EPO were highly expressed in 20.9% and 35.4% of tumors, respectively. High EPO-R expression compared with negative or low-level expression was associated with a poor 5-year disease-specific survival (60.6% versus 80.8%; P = 0.01, log-rank test). High EPO expression compared with negative and low-level expression was associated with a trend toward a poor 5-year disease-specific survival (69.6% versus 80.4%; P = 0.13, log-rank test). A high level of EPO-R and EPO coexpression was associated with a poor 5-year disease-specific survival compared with other groups of patients (50.0% versus 80.0% survival at the end of follow-up; P = 0.005, log-rank test). In multivariate analysis for disease-specific survival, high-level EPO-R and EPO coexpression was an independent prognostic factor for disease-specific survival (hazard ratio, 2.214; 95% confidence interval, 1.012-4.848; P = 0.046)., Conclusion: These results establish the pejorative prognostic value of EPO and EPO-R expression in early-stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness.

Lung adenocarcinomas with bronchioalveolar features (ABAF), formerly called bronchioloalveolar cancers (BAC), constitute a distinct clinical, radiological and pathological entity among lung malignancies. Epidermal growth factor receptor (EGFR) and to a less extent, HER-2/neu, are known to be overexpressed in non-small lung cancers, but their exact status in ABAF is not well-documented. Stimulation of these two receptors results in the initiation of two major cascades, namely phosphatidylinositol 3-kinase (PI-3K) and Ras-dependent pathways. We have therefore studied the expressions of EGFR, HER-2/neu as well as phosphorylated AKT (pAKT) and phosphorylated extracellular-signal regulated kinase (ERK), which are key molecules in these two pathways, in 15 ABAF patients. EGFR was found to be overexpressed in 9 of 15 patients (60%). HER-2/neu overexpression was detected in 6 of the 14 tumors tested (43%). pAKT and pERK were both found to be positive in 13 of 15 patients (87%). Six of the seven tumors with mucinous pattern were negative for EGFR, while all of the other eight cases were positive (P=0.001). Mucinous tumors were also less likely than non-mucinous tumors to overexpress HER-2/neu (17% versus 63%, respectively). These findings suggest that ABAF, particularly those with non-mucinous histology, commonly harbors EGFR and HER-2/neu overexpression. PI-3K and Ras-dependant pathways that lie downstream are generally activated, even in the absence of EGFR and/or HER-2/neu overexpression. ABAF may be a particularly promising candidate for EGFR-targeted strategies and this possibility merits extensive evaluation in clinical trials.

Background: Isolated lung metastases have been reported to occur in 10-20% of all women with breast carcinoma. The authors described a series of patients who underwent surgery for lung metastases from breast carcinoma., Methods: They reviewed the files of 125 consecutive patients who underwent surgery with a curative intent for lung metastases from breast carcinoma between 1972 an 1998 at a single institution. Survival curves were plotted by the Kaplan-Meier method. Prognostic factors were identified using the log-rank test and a Cox proportional hazards model for univariate and multivariate analyses, respectively., Results: The median age at surgery was 53 years. There was a median of 1 resected metastasis (range, 1-16 resected metastases). The median size of the largest metastasis was 19 mm (range, 5-70 mm). The median disease-free interval (DFI) was 3 years. The median follow-up time after surgery was 8.5 years (range, 25 days to 22 years). The 3-year, 5-year, and 10-year probabilities of survival were 58% (95% confidence interval [95% CI], 49-67%), 45% (95% CI, 36-55%), and 30% (95% CI, 21-41%), respectively. The median survival time after surgery was 4.2 years. Complete resection was achieved in 96 patients. The quality of the resection (complete vs. incomplete) was not a statistically significant prognostic factor by univariate analysis and there was no significant difference between these two groups in terms of adjuvant postoperative therapy. The characteristics of the primary tumor and the number of metastases (one vs. two or more) had no detectable influence on survival. The size of the largest metastasis (> 20 mm or < or = 20 mm) and the DFI (< or = 3 years vs. > 3 years) were highly significant prognostic factors (P = 0.006 and P = 0.003, respectively). This was confirmed by multivariate analysis. Patients with a DFI < or = 3 years and/or the largest metastasis > 20 mm reportedly had a poor outcome (median survival, 2.6 years vs. 8.5 years for patients with none of these poor prognostic factors)., Conclusions: Resection of lung metastases from breast carcinoma was associated with a significant 5-year survival rate of 45%. Whether these encouraging findings resulted from the surgical procedure itself or the preoperative selection of patients remained uncertain. When surgery is considered in this setting, the size of the largest metastasis and the DFI should be taken into account.

Objective: We reviewed our 8-year experience with en bloc partial and total vertebrectomy for lung cancer invading the spine and report outcome and survival., Methods: Nineteen patients with lung cancers involving the spine underwent en bloc resection. Eleven received induction treatment (chemotherapy, n = 5; chemoradiotherapy, n = 4; and radiation, n = 2). Pneumonectomy was performed in 3 patients, lobectomy in 13 patients, and wedge resection in 3 patients. Hemivertebrectomy was performed in 15 patients, and total vertebrectomy was performed in 4 patients. The median number of resected vertebral bodies was 3 (range, 1-4). Tumor stage was IIIB in 14 patients, IIIA in 1 patient, and IIB in 4 patients (hemivertebrectomy is performed in the case of T3 disease to obtain free margins). Surgical nodal status was N0 in 13 patients, N1 in 3 patients, N2 in 1 patient, and N3 (supraclavicular) in 2 patients. Complete macroscopic and microscopic resection was achieved in 15 (79%) patients., Results: There was no immediate postoperative mortality. Morbidity was observed in 10 patients, including 4 (21%) complications related to the spinal surgery. The median hospital stay was 30 days. Seven patients were alive after a mean follow-up of 26 months (range, 7-74 months). The 1- and 5-year predicted survivals (updated) are 59% and 14%, respectively. Nine local recurrences were observed., Conclusions: En bloc resection of chest tumors with vertebrectomy is technically demanding, and postoperative morbidity should be critically addressed with this aggressive surgical intervention. However, an encouraging long-term survival observed in this series suggests that en bloc resection could be a valid option in selected patients with vertebral involvement of chest tumors.