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Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.

STK11 is commonly mutated in lung cancer. In light of recent experimental data showing that specific STK11 mutants could acquire oncogenic activities due to the synthesis of a short STK11 isoform, we investigated whether this new classification of STK11 mutants could help refine its role as a prognostic marker. We conducted a retrospective high-throughput genotyping study in 567 resected non-squamous non-small-cell lung cancer (NSCLC) patients. STK11 exons 1 or 2 mutations (STK11ex1-2) with potential oncogenic activity were analyzed separately from exons 3 to 9 (STK11ex3-9). STK11ex1-2 and STK11ex3-9 mutations occurred in 5% and 14% of NSCLC. STK11 mutated patients were younger (P = .01) and smokers (P< .0001). STK11 mutations were significantly associated with KRAS and inversely with EGFR mutations. After a median follow-up of 7.2 years (95%CI 6.8-.4), patients with STK11ex1-2 mutation had a median OS of 24 months (95%CI 15-57) as compared to 69 months (95%CI 56-93) for wild-type (log-rank, P = .005) and to 91 months (95%CI 57-unreached) for STK11ex3-9 mutations (P = .003). In multivariate analysis, STK11ex1-2 mutations remained associated with a poor prognosis (P = .002). Results were validated in two public datasets. Western blots showed that STK11ex1-2 mutatedtumors expressed short STK11 isoforms. Finally using mRNAseq data from the TCGA cohort, we showed that a stroma-derived poor prognosis signature was enriched in STK11ex1-2 mutated tumors. All together our results show that STK11ex1-2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.

Introduction: Management of non-small cell lung cancer (NSCLC) is getting better and results on long-term survival have improved. We reviewed the modifications observed in surgery over a 32-year time period., Patients and Method: Data of 6105 patients who underwent surgery from 1979 to 2010 were analyzed over three equal time-periods: gender, age, type of surgery, histology, pTNM, tobacco addiction, comorbidity and time periods., Results: Age, number of females and high-risk patients with comorbidity (including the history of a previous cancer) increased with time periods. Number of exploratory thoracotomy (7.7 % to 1.6 %) and pneumonectomy (48 % to 18 %) decreased. Number of wedge resection (0.5 % to 6 %) and lobectomy (42 % to 64 %) increased. Rates of the other types of resection were unchanged. Neoadjuvant treatments accounted for more than 20 % of patients in the last time period. Postoperative mortality (4 %) did not vary but non-lethal complication rates increased (16.9 % to 27.7 %). Global 5-year survival rates dramatically increased with time going from 37.4 % to 49.8 % (P<10(-6)). Survival improvement was observed in the different components of the pTNM and whatever the type of treatment. However, survival was affected by increasing age and multiplication of comorbidities but without impairing the general better outcome trend., Conclusion: NSCLC itself, its diagnostic and therapeutic management, and patient's characteristics evolved with time. Survival improved in most studied prognosis factors. Time period factor was of paramount importance and might be included in research dealing with NSCLC., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Lung cancer prognosis is mainly based on the TNM, histology and molecular biology. Our aim was to analyze the prognostic value of certain clinical and paraclinical variables., Patients and Methods: We studied among 6105 patients operated on, divided during 3 time-periods (1979 to 2010), the following prognostic factors: type of surgery, pTNM, histology, age, sex, smoking history, clinical presentation, and paraclinical variables., Results: Postoperative mortality was 4% (243/6105), rate of complications was 23.3% (1424/6105). The 5-year overall survival was 43.2% and 10-year was 27%. Best survival was observed after complete resection (R0) (P<10(-6)), lobectomy (P<10(-6)), lymph node dissection (P=0.0006), early pTNM stages (P<10(-6)), absence of a solid component in adenocarcinoma. Other pejorative factors were: male gender (P=10(-5)), age (P=0.0000002), comorbidity (P=0.016), history of cancer (P<10(-5)), postoperative complications (P=0.0018), FEV lower than 80% (P=0.0000025), time-periods (P<10(-6)). All these factors were confirmed by multivariate analysis, except gender. Smoking was not poor prognostic factor in univariate analysis (P=0.09) but became significant in the multivariate one (P=0.013)., Conclusion: Medical and human factors, and the general physiological state, play an important role in prognosis after surgery. We do not know their exact meaning and, like studies on chemotherapy, they justify special research., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: Results of surgery for non-small-cell lung cancer (NSCLC) are poorer after limited resection, wedge and segmentectomy, than after lobectomy. Guidelines recommend avoiding wedge-resection, which new techniques (radiofrequency ablation and cyberknife) tend to replace. This work aimed to study the wedge-resection carcinological value., Patients and Methods: NSCLC without previous other cancer history and neoadjuvant therapy measuring less than 31 millimetres and operated from 1980 to 2009 were reviewed. Analyzed variables were: location, gender, age, FEVS, type of resection, histology, pT and pN., Results: There were 66 wedge-resections (10.9%), 32 segmentectomies (5.3%), 507 lobectomies (83.8%), nine postoperative deaths (1.5%), 136 complications (22.5%), 557 complete resections (R0=92%); 72.2% of NSCLC upper lobe location (437/605). Age was more advanced in wedge-resection and segmentectomy, FEVS lower and NSCLC most often a squamous cell pN0 and pStage I carcinoma than in lobectomy. Lymphadenectomy was not performed in half the wedge-resections. Five-year survival rates were poorer after wedge-resection: 50% versus segmentectomy 59.8% (P=0.09), and lobectomy 66% (P=0.0035), but the number of recurrences was similar. Multivariate analysis demonstrated that age, FEVS, type of surgery and lymphadenectomy, pN in pTNM were the only prognosis factors., Conclusion: Wedge-resection is less carcinological than segmentectomy when the patient-status and NSCLC location allow performing the latter, but more than the new techniques, because of its pathological yield, when the patient-status and nodule peripheral location allow wedging., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: Non-small cell lung carcinoma (NSCLC) with N1 involvement is associated with 5-year survival rates ranging from 7% to 55%. Numerous factors have been independently reported to explain this heterogeneous prognosis, but their relative weight on long-term survival is unknown., Methods: Patients who underwent surgical resection for NSCLC in two French centers from 1993 to 2010 were prospectively recorded and retrospectively reviewed. The overall survival (OS) of patients undergoing first-line surgery for pN1 disease was analyzed according to the type of extension, number of metastatic LN, number and anatomic location of metastatic stations., Results: The study group included 450 patients (male 80.2%, mean age 63.3 ± 9.9 years, 5-year overall survival 46%). The number of metastatic station was 1 in 340 (75.6%, single-station disease) and ≥2 in 110 patients (24.4%, multi-station disease). The number of metastatic stations was correlated with the number of metastatic LN (p < .001), and associated with adverse OS (p = .0014). The presence of intralobar metastatic LN (station 12-13-14) was associated with a mechanism of direct extension (p < .001), but did not impact OS (p = .71). The location of metastatic stations was of prognostic significance only in case of multi-station disease, with hilar (station 10) involvement being associated with adverse OS (p = .005). The 110 patients with multi-station pN1 disease and the 134 patients operated on for single-station pN0N2 (skip-N2) disease during the study period yield comparable outcome (p = .52)., Conclusions: In patients with resected pN1 NSCLC, the number of metastatic stations and their location in case of multi-station disease have a prognostic value., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The diagnosis of a second lung cancer in a patient with a previous medical history of lung cancer is no longer a rarity. Also, it is possible to observe a new location in a patient who underwent pneumonectomy in the past. Surgery remains the best treatment. Our objective was to overview this subject., Patients and Methods: Among 5611 patients operated in our institution, 186 (3.3%) had metachronous cancer and 17 had previous pneumonectomy (0.7% of pneumonectomies and 0.2% of NSCLC treated in our department). The procedure was diagnostic and therapeutic in 88% of cases (n=15)., Results: There were 16 males and 1 female, mean age was 62.5-years. All were smokers (11 were former smokers) and 6 had other medical history. Mean FEV was 52% (range 35-95%). Types of resection were 2 lobectomies, 4 segmentectomies, and 11 wedge resections. There were no postoperative deaths, but two complications. Histological subtype of the first and second cancer was the same in 11 patients. All patients were pN0 after second surgery. The long-term survival (median 33 months) was 35.3% at 5-years and 14.1% at 10-years. Two patients treated with pneumonectomy for their first cancer were pN2. Patients who underwent upper right lobectomy for treatment of their second cancer survived longer than 5-years., Conclusion: Surgical resection for lung cancer on single-lung is associated with acceptable morbidity and mortality. Prolonged survival can be achieved in selected patients., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Lung cancer is the leading cause of death by cancer and cirrhosis is the fourteenth, all causes included. Surgery increases postoperative risks in cirrhotic patients. Our purpose was to analyze this point in lung cancer surgery., Methods: We collected, among 7162 patients, the data concerning those operated for lung cancer (n=6105) and compared patients with hepatic disease (n=448) to those presenting other medical disorder (n=2587). We analyzed cirrhotic patients' characteristics (n=49)., Results: Five-year survival of patients with hepatic disease was lower (n=5657/6105): 35.3% versus 43.8% for patients with no hepatic disease, P=0.0021. Survival of cirrhotic patients was not statistically different from the one of patients with other hepatic disorder, but none survived beyond 10 years (0% versus 26.4%). Surgery in cirrhotic patients consisted in one explorative thoracotomy, three wedges resections, two segmentectomies, 33 lobectomies and 10 pneumonectomies. Postoperative mortality (8.2%; 4/49) was not different for patients without hepatic disease (4.2%; 239/5657) (P=0.32), as well as the rate of complications (40.8%; 20/49 and 24.8%; 1404/5657, P=0.11). Only one postoperative death was associated to a hepatic failure. Multivariate analysis pointed age, histological subtype of the tumour and stage of disease as independent prognosis factors., Conclusion: When cirrhosis is well compensated, surgical resection of lung cancer can be performed with acceptable postoperative morbidity and satisfactory rates of survival. Progressive potential of this disease is worse after five years., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Obesity and lung cancer are major public health problems. The purpose of this work is to review the data concerning this association., Method: We report clinical and epidemiological data on obesity and discuss the impact on the incidence of lung cancer, as well as the safety and efficiency of anti-tumor treatments., Results: Obesity does not contribute to the occurrence of lung cancer, unlike other malignancies. Patients may be more likely to undergo treatment at lower risk. Regarding surgery, obesity makes anaesthesia more difficult, increases the operative duration but does not increase postoperative morbidity and mortality. Chemotherapy and radiotherapy seem to be administered according to the same criteria as patients with normal weight. Paradoxically, survival rates of lung cancer are better in obese patients as well after surgery than after non-surgical treatment., Conclusion: Obesity is related to many neoplasms but not to lung cancer. Regarding long-term survival all treatments combined, it has a favorable effect: this is the "obesity paradox"., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: The pleural involvement (PLI) in non-small cell lung cancer (NSCLC) has a poor prognosis, even though it might be very heterogeneous., Patients and Methods: A multicentric retrospective descriptive study was performed over 2329 patients who were operated for NSCLC between 1979 and 2010. The patients with PLI were classified in P(Parietal)PLI and V(visceral)PLI and then each subdivided : VPLI to peripheric (VPLI-P) and fissural (VPLI-F) and PPLI to mediastinal (PPLI-M) and costal (PPLI-C). Characteristics and survival were compared between the subgroups as well as with patients without PLI (WPLI, n=1439)., Results: The sex-ratio was 2.8 (males: n=1713). The PLI patients were significantly younger, with a less sex-ratio, less R0 resections (96% versus 98.7%, P=0.000076), and less N0 (60% vs 70%, P<10(-6)) as their 5-year survival (45.7% vs 55.5%, P<10(-6)). The PLI was related to the size of NSCLC (P<10(-6)) and N2 involvement (P=0.0020). It was less frequent after neoadjuvant treatment (36.2% vs 39.1% P=0.03). In the VPLI-F or PPLI-M, pneumonectomies were more frequent (P<10(-6)). In VPLI-P (n=196/561), there were more pN1 and pN2 (P=0.0065) with a 5-year survival of 42.9% vs 54.4%, P=0.013. In multivariate analysis, the PLI was not an independent prognostic factor contrary to age, sex, type of resection, pT and pN., Conclusion: The pleura play a major role in NSCLC dissemination. Its involvement affects pN, the type of surgical resection and justifies the use of neoadjuvant treatment., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Bilobectomy may be performed for different reasons and lung tumors. There are still controversies regarding the results of this procedure. We reviewed our experience of bilobectomy to evaluate the particularities of this resection., Methods: The clinical files of patients operated on for lung tumors in two French centers between 1980 and 2009 were prospectively recorded and retrospectively analyzed. The characteristics, management, pathology, and survival after right-sided resections for non-small cell lung cancer (NSCLC) were then compared., Results: During the study period, 3280 right-sided resections were performed, including 235 bilobectomy (7%), for NSCLC in 192 cases (82%). Lower-middle lobectomy (LML) represented 60% of bilobectomy, with carcinoid tumors and squamous cell carcinoma being more frequent in this group. Upper-middle lobectomy (UML) represented 40% of bilobectomy, with less postoperative complications and mortality in this group. In N0-NSCLC, the rate of postoperative mortality and 5-year survival rates after bilobectomy (4.7% and 46.1%, respectively) were intermediate between lobectomy (2.7% and 52.6%) and pneumonectomy (9.6% and 31.7%, P<10(-6) for both comparisons). There was no significant difference in 5-year survival rates according to the type of bilobectomy and the performance of any induction therapy., Conclusion: Bilobectomy is associated with acceptable in-hospital mortality and encouraging 5-year survival rates despite an increased incidence of postoperative complications. Approximation in survival of UML and pneumonectomy and of LML and lobectomy may be due to differences in histologic features with different fissure extension and interlobar node involvement., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction/background: An individual patient data metaanalysis was performed to determine clinical outcomes, and to propose a risk stratification system, related to the comprehensive treatment of patients with oligometastatic NSCLC., Materials and Methods: After a systematic review of the literature, data were obtained on 757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical external-beam radiotherapy, and curative treatment of the primary lung cancer, from hospitals worldwide. Factors predictive of overall survival (OS) and progression-free survival were evaluated using Cox regression. Risk groups were defined using recursive partitioning analysis (RPA). Analyses were conducted on training and validating sets (two-thirds and one-third of patients, respectively)., Results: Median OS was 26 months, 1-year OS 70.2%, and 5-year OS 29.4%. Surgery was the most commonly used treatment for the primary tumor (635 patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS were: synchronous versus metachronous metastases (P < .001), N-stage (P = .002), and adenocarcinoma histology (P = .036); the model remained predictive in the validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low-risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous metastases and N1/N2 disease (5-year OS, 13.8%)., Conclusion: Significant OS differences were observed in oligometastatic patients stratified according to type of metastatic presentation, and N status. Long-term survival is common in selected patients with metachronous oligometastases. We propose this risk classification scheme be used in guiding selection of patients for clinical trials of ablative treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: pT4 is a group of miscellaneous tumors: our goal was to revisit their surgical reality., Methods: The different characteristics and prognostic factors of lung pT4 (n=403) were analysed according to three subgroups: G1 - by direct extension; G2 - by nodule in other ipsilateral lobe; G3 - because of both., Results: There were 332 males and 71 females mean aged 61.5 years. Surgery [exploratory: 89 (22.1 %), lobectomy: 149 (37 %), pneumonectomy: 169 (41.9 %)] was followed by 26 postoperative deaths (6.5 %), 82 complications (20.3 %) and concerned few pN0 (47.6 %). G1 (n=196) and G3 (n=53) were not different. By comparison with them, G2 (n=53) were mainly females (24\13 %), with less explorative thoracotomy (2.6\34 %), more complete R0 resections (77\29 %), less pneumonectomy (31\47 %), more small sized tumors (mean: 37\57 mm), more adenocarcinoma (67\32 %), more N0 tumors (48\31.7 %) and stages IIIA disease (46.7\56 %). G2 5-year survival rates were higher (G2: 22 %; G1: 13 %; G3: 15 %); G1 rates depended of the invaded structure (20.9 % for the vertebra down to 0 % for the esophagus and carina). pN2 rates were not very high but not different between groups (G1: 13.6 %; G2: 15.6 %; G3: 14.3 %; P=0.52). Multivariate analysis demonstrated completeness and type of resection, stage and age as independent factors of prognosis., Conclusion: Surgery for pT4 is justified provided rigorous selection of extension forms. However, assimilating extension and ipsilateral lobe nodule in a same group does not obey to surgical reality., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: It has been proposed that examining a greater number of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) treated by surgical resection may increase the likelihood of proper staging and affect outcome. Our purpose was to evaluate the interindividual variability and prognostic relevance of the number of LNs harvested during complete pulmonary and mediastinal lymphadenectomy performed for NSCLC., Methods: We prospectively collected and retrospectively reviewed the data from 1,095 patients who underwent lung cancer resection in association with systematic lymphadenectomy and pulmonary and mediastinal LN counts from 2004 to 2009. We analyzed the interindividual variability and prognostic impact of the number of LNs on overall survival (OS)., Results: The mean number of harvested pulmonary and mediastinal LNs was 17.4±7.3 (range, 1-65) and was higher in male patients, right lung surgical procedures, lobectomy and pneumonectomy, N2 disease, and pIII stage. The mean number of harvested mediastinal LNs was 10.7±5.6 and was normally distributed (range, 0-49; median, 10). The 5-year survival rate was 53.8%. Overall survival was influenced by the number of involved stations (single-station versus multi-station disease, 5-year survival rates 31.5% versus 16.9%, respectively; p=0.041) but not by the number of harvested LNs, the number of harvested mediastinal LNs, or the number of positive mediastinal LNs., Conclusions: After lung cancer resection and complete lymphadenectomy, the number of LNs is subject to normally distributed interindividual variability, with no significant impact on OS. Recommending an optimal number of nodes is therefore arbitrary. Instead, our recommendation is to perform a complete systematic pulmonary and mediastinal lymphadenectomy following established anatomical boundaries., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: During the last decades, pneumonectomy has been increasingly seen as a risky procedure, first reserved for tumours not amenable to lobectomy, and now discouraged even in advanced stages of non-small-cell lung cancer (NSCLC). Our purpose was to assess the long-term survival following pneumonectomy for NSCLC and its prognostic factors., Methods: We set a retrospective study including every patient who underwent a pneumonectomy for NSCLC in 2 French centres from 1981 to 2002. We then described the demographic and pathological characteristics of patients who survived >10 years, and studied the prognostic factors of long-term survival., Results: During the study period, 1466 pneumonectomies were performed for NSCLC, including 1121 standard and 345 extended, and accounted for the overall population. Postoperative complications occurred in 396 patients (27%), including 93 deaths (6.3%). Five- and 10-year survival rates were 32 and 19%, respectively. Two-hundred and fifty patients survived >10 years after surgery, and accounted for the study group. The study group included a majority of males (n = 230, 92%), a mean age of 57 ± 9.2 years and a majority of clinical stage IIIA (n = 117, 46.8%). Induction, right-sided pneumonectomy, extended resection and adjuvant therapy were performed in 41 (16.4%), 109 (43.6%), 40 (16%) and 97 patients (38.8%), respectively. Histology revealed a majority of squamous cell carcinoma (n = 181, 72.4%), T2 tumours (n = 117, 36.8%) and N1 disease (n = 105, 42%). In multivariate analysis, factors associated with adverse outcomes included older age, advanced stage, extended resection, non-lethal postoperative complication, adenocarcinoma, lymphatic vessel microinvasion, N1 and N2 disease and R1 and R2 resection., Conclusions: During the last 30 years, pneumonectomy was effectively performed for advanced NSCLC, allowing a 10-year survival rate of 19%. Such results have not been reported with other non-surgical treatments and confirm that pneumonectomy is still an essential weapon in the armamentarium against lung cancer.

Background: N2 involvement has dramatic consequences on the prognosis and management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may present with or without N1 involvement, constituting non-skip (pN1N2) and skip (pN0N2) diseases, respectively. As the prognostic impact of this subclassification is still a matter of debate, we analyzed the prognosis of pN2 patients according to the pN1-involvement and the number of N2-stations concerned., Methods: The medical records of consecutive patients who underwent surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were prospectively collected and retrospectively reviewed. Patients undergoing induction therapy, exploratory thoracotomy, incomplete mediastinal lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2 and pN0N2 patients were first compared, and then deciphered according to the number of N2 stations involved (single-station: 1S, multi-station: 2S)., Results: All together, 871 patients underwent first-line complete surgical resection for pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2 (70.4%) patients. Mean follow-up was 72.8±48 months. Median, 5- and 10-year survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months, 21%, and 14% for pN1N2 patients (p<0.001). Multivariate analysis revealed 3 different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease (p<0.001)., Conclusions: Among pN2 patients, the combination of N1 involvement (pN0N2 vs pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic factors. These results might be taken into consideration to sub-classify the heterogeneous pN2-NSCLC group of patients., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Lymph node metastasis is a major adverse prognostic factor of malignant tumors, including non-small cell lung carcinoma (NSCLC). However the characterization of tumor associated lymphatic vessels and lymphangiogenic mediators in NSCLC are recent and their prognostic role is debated. Lymphatic vascular invasion (LVI) appears like a robust adverse prognostic factor when reported in NSCLC. This parameter should be better standardized and could be of use in adjuvant therapy indications. Moreover, anti-lymphangiogenesis therapies are currently under investigation and may become part of the anti-cancer strategy., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Historically, right middle lobe (RML) non-small cell lung cancer (NSCLC) has been reported to be associated with a higher rate of pneumonectomy than other right-sided locations. Because this would discourage minimally invasive approaches in RML-NSCLC, we sought to update this assertion through the study of a large surgical series., Methods: Clinical records of patients who underwent operations for right-sided NSCLC in 2 French surgical centers were prospectively entered and retrospectively reviewed. Demographic and pathologic characteristics of RML NSCLC were compared with other right-sided NSCLC., Results: This study included 3,234 right-sided and 211 RML (6.5%) NSCLC patients. After exclusion of 14 patients who underwent exploratory thoracotomy, patients were a mean age of 61.5 years, most RML resections occurred in men (134 [72.8%]), and most were lobectomies (wedge, n=4; lobectomy, n=102; bilobectomy, n=22; pneumonectomy, n=56). Pathologic analysis revealed adenocarcinoma in 88 patients (47.8%) and squamous cell carcinoma in 80 (43.5%). pStaging was stage I in 86 patients (46.7%), II in 42 (22.8%), III in 47 (25.5%), and IV in 9 (4.9%). Superior and inferior mediastinal N2 were found in 45.4% and 54.6% of patients, respectively, when 1 station was involved. When compared with other right-sided NSCLC, RML was characterized by higher T status and higher rates of bilobectomy (10.9% vs 5.6%, p=0.0017) and pneumonectomy (30.3% vs 22.3%, p=0.0071) but similar 5-year survival (47.4%)., Conclusions: Compared with other right-sided NSCLC, RML location is associated with a higher albeit limited rate of pneumonectomy., (Copyright © 2014. Published by Elsevier Inc.)

Unlabelled: The management of localized non-small cell lung cancer (NSCLC) has been modified over the last decades, with induction therapies being increasingly recommended as a prerequisite to surgical resection. However, the relative impact of chemo- and chemoradiotherapy on tumours' pathology and patients' survival is still discussed., Methods: We set a retrospective study including every patient who underwent surgical resection for NSCLC in 2 French centres from 1980 to 2009. We then compared the tumours' pathology and patients' survival according to the use of induction chemotherapy (group 1) or induction chemoradiotherapy (group 2)., Results: There were 733 patients in group 1 and 126 patients in group 2. In group 1, 669 patients (91%) had platinum-based chemotherapy, for 2 to 3 cycles in 564 cases (77%). In group 2, chemoradiotheray was concomitant in 68 patients (54%), and sequential in 58 patients (46%). As compared with group 1, group 2 was characterized by younger age (mean 59.8±9.5 vs 56.4±9.6, respectively, P<.001), a higher rate of tumours deemed unresectable before induction treatment (25% vs 44%, P<.001), and a higher proportion of T4 (25% vs 44%, P<.001) or N2 diseases (56% vs 69%, P=.005). The type of resection, postoperative complications, and postoperative mortality were not significantly different between groups. On final pathologic report, as compared with group 1, there were more N0 and N1 disease in group 2 (N0: 43% vs 58%, P=.002; N1: 22% vs 10%, P=.002) while the rate of N2 disease was comparable (34% vs 32%, P=ns). The median, 5-, and 10-year survivals were 28 months, 35%, and 21% for group 1, and 29 months, 36%, and 23% for group 2, respectively (P=ns)., Conclusion: As compared with induction chemotherapy, induction chemoradiotherapy was performed in more advanced NSCLC, and resulted in better downstaging, similar postoperative course, and comparable long-term outcome after surgical resection., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: The extension of non-small-cell lung cancer (NSCLC) to supraclavicular (SC) and contralateral (CL) mediastinal lymph nodes is termed N3 and usually forbids surgical resection. However, scarce surgical series have reported encouraging results, and we sought to analyse our experience with this particular subgroup of patients., Methods: We retrospectively reviewed the charts of 5857 patients undergoing surgery for NSCLC during the last 30 years in two French centres. Eleven patients presenting with pathological-N3 were found, and more closely analysed concerning lymphatic spread, surgical indication and prognosis., Results: N3 consisted of tumoural extension to the SC (n = 5), CL mediastinal (n = 5) or both (SC + CL, n = 1) stations. Patients underwent induction treatment with chemotherapy alone (n = 4), chemoradiotherapy (n = 3) or first-line surgery (n = 4). All patients underwent a complete surgical resection of the tumour associated with ipsilateral systematic mediastinal lymph node dissection. Additional resection of N3 lymph nodes was performed in 8 cases. Adjuvant treatment included chemoradiotherapy (n = 6), chemotherapy alone (n = 1) or radiation therapy alone (n = 1). All 5 patients with SC-N3 presented with ipsilateral disease; 3 of them survived 5 years. Four patients with CL-N3 presented with left-sided tumour and nodal extension to the 4R station, and none of them survived., Conclusions: Some N3-patients with specific anatomical location may benefit from multimodality treatment including surgery. These results support further prospective studies for selected N3-patients.

Objectives: Non-small-cell lung cancer (NSCLC) following pulmonary or pharyngolaryngeal malignancies has been widely studied, but only a few articles have focussed on lung cancers following other solid malignancies. Our purpose was to compare the characteristics and prognosis of patients with NSCLC according to the medical history of the extra-pulmonary and extra-pharyngolaryngeal solid malignancy., Methods: Patients who underwent surgery for NSCLC from January 1980 to December 2009 in two French thoracic centres were reviewed. We compared patients with no history of cancer (Group 1) and patients with a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy (Group 2)., Results: There were 4992 patients: 4603 (92%) in Group 1 and 389 (8%) in Group 2. In comparison with Group 1, Group 2 showed an increasing incidence over the last 3 decades (2-8%), an older population (65.9 vs 61 years, P < 0.001), a higher proportion of women (34 vs 18%, P < 0.001), non-smokers (20 vs 10%, P < 0.001), adenocarcinomas (53 vs 40%, P < 0.001), T1 (16 vs 14%, P = 0.047) and second nodule in the same lobe (4 vs 2%, P < 0.001). The overall survival was not significantly different between the two groups (P = 0.09). In multivariate analysis, older age, male gender, pneumonectomy, higher T, higher N, incomplete resection and history of extra pulmonary-extra pharyngolaryngeal solid malignancy were significantly associated with a worse prognosis., Conclusions: Despite an earlier diagnosis, a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy is associated with a worse prognosis in patients with NSCLC undergoing surgical resection. Overall survival is particularly low after a history of bladder and upper gastrointestinal malignancies.

M1A disease is a recent concept appearing in the 7th TNM classification of lung cancer. M1A encompasses two different entities, malignant pleural or pericardial effusions and separate tumor nodules in the contralateral lung, who constitute very different diseases, with very different management and prognoses. On one hand, patients with pleural dissemination have extremely poor survival, with median and 5-year survivals of 4 months and 3.1%, respectively. Only selected patients whose limited pleural extension has been diagnosed at the time of thoracotomy and completely resected, may experience prolonged survival. On the other hand, recent progress in molecular biology still failed to establish whether a contralateral lesion is a second primary or a metastasis. These contralateral lesions are now gathered as multiple lung cancers in the surgical literature, and misleadingly classified as M1A disease in the TNM classification. Patients with contralateral nodules may experience prolonged survival after the surgical treatment of both localizations. Changing the staging by establishing the diagnosis of metastasis is probably an important issue warranting further biologic research, but according to current results this diagnosis must not in any case preclude surgery., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Only patients with a complete resection of non-small-cell lung cancer (NSCLC) may expect long-term survival. Despite the recent progress in imaging and induction therapy, a thoracotomy may remain exploratory or with incomplete resection (R2). Our purpose was to revisit these situations., Methods: A total of 5305 patients who underwent surgery for NSCLC between 1980 and 2009 were reviewed. We compared the epidemiology, pathology, causes and prognosis characteristics of exploratory thoracotomy (ET) and R2 resections., Results: ET and R2 resections were observed in 223 (4%) and 197 (4%) patients, respectively. The frequency of ET decreased with time, while the frequency of R2 resection remained almost stable. The indications for ET and R2 resections were not significantly different. In comparison with ET, R2 resections were characterized by a significantly higher frequency of induction therapy (22 vs 17%, P < 10(-3)), adenocarcinomas (49 vs 15%, P < 10(-6)), T1-T2 (53 vs 29%, P < 10(-6)) and N0-N1 extension (67 vs 42%, P = 10(-6)). R2 resections were also characterized by a higher rate of postoperative complications (19.1 vs 9.9%, P = 0.014), with no significant difference in postoperative mortality (6.9 vs 4.9%, P = non significant). R2 resections resulted in a higher 5-year survival compared with ET (11.1 vs 1.2%, P = 10(-3)). There was no long-term survivor after ET, except during the last decade., Conclusions: ET and R2 remain unavoidable. In comparison with ET, R2 resection is associated with a higher rate of postoperative complications, but a higher long-term survival.

Background: Some reports suggest that patients with synchronous multiple foci of nonsmall-cell lung cancers (NSCLC) distributed in multiple lobes have a poor prognosis, even when there is no extrathoracic metastasis. The vast majority of such patients do not receive surgical treatment. For those who undergo surgery, prognostic factors are unclear., Patients and Methods: We systematically reviewed the literature on surgery for synchronous NSCLC in multiple lobes published between 1990 and 2011. Individual patient data were used to obtain adjusted hazard ratios (HRs) in each dataset and pooled analyses were carried out., Results: Six studies contributed 467 eligible patients for analysis. The median overall survival was 52.0 months [95% confidence interval 45.6-63.7]. Male gender and advanced age were associated with a decreased survival: HRs 1.64 (1.22, 2.22) and 1.40 (1.20, 1.80) per 20-year increment, respectively. Patients with cancers distributed in one lung had a higher mortality risk than those with bilateral disease: HRs 1.45 (1.06, 2.00). N1 or N2 had a decreased survival compared with N0: HRs 1.68 (1.12, 2.51) and 1.94 (1.33, 2.82), respectively. There was a trend toward increased mortality among patients with different histology: HRs 1.29 (0.96, 1.75)., Conclusion: Advanced age, male gender, nodal involvement, and unilateral tumor location were poor prognostic factors.

Background: Patients with a history of previous malignancy are often encountered in a discussion of surgical resection of non-small-cell lung cancer (NSCLC). The outcome of patients with 2 or more previous cancers remains unknown., Methods: We performed a retrospective study including all patients undergoing resection for NSCLC from January 1980 to December 2009 at 2 French centers. We then compared the survival of patients without a history of another cancer (group 1), those with a history of a single malignancy (group 2), and those with a history of 2 or more previous malignancies (group 3)., Results: There were 5,846 patients: 4,603 (78%) in group 1, 1,147 (20%) in group 2, and 96 (2%) in group 3. The proportion of patients included in group 3 increased from 0.3% to 3% over 3 decades. Compared with groups 1 and 2, group 3 was associated with older age, a larger proportion of women, earlier tumor stage, less induction therapy, and fewer pneumonectomies. Despite this, postoperative complications and mortality were similar in groups 2 and 3, and higher than in group 1. Five-year survival rates were 44.6%, 35.1%, and 23.6% in groups 1, 2, and 3, respectively (p < 0.000001 for comparison between 3 groups; p = 0.18 for comparison between groups 2 and 3). In multivariate analysis, male sex, higher T stage, higher N stage, incomplete resection, and study group were significant predictors of adverse prognosis., Conclusions: Despite earlier diagnosis and acceptable long-term survival, patients operated on for NSCLC after 2 or 3 previous malignancies carried a worse prognosis than did those undergoing operation after 1 malignancy or if there was no previous diagnosis of cancer., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The prognostic value of vascular microinvasion (VMI) in non-small cell lung cancer (NSCLC) has been a matter of discussion in recent decades. The last T N M classification does not take VMI into account, but many points remain questionable., Methods: A retrospective study was performed of patients undergoing operations for NSCLC during a 20-year period. Lymphatic VMI (LVMI) was classified as group (G) 1, blood VMI (BVMI) as G2, LVMI and BVMI as G3, and no VMI as G4. The demographic, pathologic, T N M characteristics, and long-term survival of each group were analyzed., Results: A total of 3,868 patients (G1, 334; G2, 642; G3, 172; G4, 2,720), mean age 61.9 ± 10.1 years, underwent different types of resection, with complete lymphadenectomy in 88.5%. Adenocarcinomas were more frequent in G1 and G3, and squamous cell carcinomas in G2. In G2, more N1 tumors needed more extensive resections. G1 was equally distributed regardless of tumor size, but G2 prevalence increased with augmenting size. Nodules in the same lobe were significantly more frequent in LVMI than in BVMI. After exclusion of patients with R1 and R2 resections, multivariate analysis confirmed that LVMI and BVMI were independent prognostic factors as well as age, sex, type of resection, T extension, and N involvement., Conclusions: VMI is generally associated with a poorer prognosis. LVMI is less frequent than BVMI but has lower survival rates. The benefit of adjuvant therapy in VMI patients needs to be evaluated., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Lung cancer management has changed due to emergence of new imaging techniques and of multimodal therapies. Our purpose was to analyse how lung cancer evolved in surgical practice., Methods: The records of patients who underwent surgical resection for lung cancer from 1983 to 2006 in two centres were reviewed. Data were split into four time periods of 6 years. We analysed and compared the epidemiological, pathological and prognostic characteristics of each period., Results: There were 832, 1148, 1493 and 1195 patients during the periods 1983-88, 1989-94, 1995-2000 and 2001-06, respectively. The main changed characteristics were increasing numbers of older patients, females, past history of another cancer and/or cardio-vascular disease, adenocarcinomas and undifferentiated large-cell carcinomas, smaller tumour size, T1-T2, N0 (47.2-61.2%) and neoadjuvant therapy (NAT) (3.8-24.9%). There were also a decreasing number of exploratory thoracotomies, pneumonectomies and adjuvant therapy (AT) (48.5-30%). The 5-year survival rates improved (34.5-46.3%, P < 10(-6)), mainly after lobectomy, and in the case of adenocarcinoma, N0 and N2 patients. Multivariate analysis confirmed that time trend was an independent factor of prognosis (P < 10(-6)), just as important as N involvement, complete resection (R0), tumour size, age, another cancer history and more significant than the type of resection, histology, NAT and AT., Conclusions: During the last 25 years, the clinico-pathological features of operated patients have progressively changed and the results following surgery improved. Earlier stage diagnosis might explain overall survival improvement, and play a more major role than associated peri-operative treatments. Therefore, it is advisable to consider the time-related factor in future studies on lung cancer surgery.

Objectives: Lung cancer invading beyond the interlobar pleura, classified as T2a in the new TNM, is a rare entity with a poor outcome. Our purpose was a better understanding of the mechanisms of this particular behaviour and its prognostic value., Methods: Patients who underwent surgery between 1984 and 2007 were reviewed. We focused on T1 and T2 tumours. Tumours not traversing the pleural elastic layer were defined as PL0, extending through the layer as PL1 and extending to the surface of the visceral pleura as PL2. We considered three groups: group 1, tumours invading the lobar fissure, group 2, PL0-tumours and group 3, PL1 + PL2 tumours and studied their pathology and prognostic characteristics., Results: The distribution was as follows: group 1 n = 154, group 2 n = 2310 and group 3 n = 651. Pneumonectomy was necessary in 55.2% and bilobectomy in 19.5% of group 1, and N-involvement was present in 55.8% (significantly more than other groups). The mean tumour size (42.7 ± 12 mm) was bigger in group 1. Post-operative mortality was as follows: -5.2, -3.5 and 3.2% in groups 1, 2 and 3, respectively (P = 0.49). Five-year survival rates were: group 1: 38.9%, group 2: 52.5% and group 3: 43.4%; P = 0.00002. Survival was not different between groups concerning pN1 and pN2, but poorer in groups 1 and 3 than in group 2 in pN0 patients, P = 0.0057. Survival was 48.1, 37.9 and 38.4% for tumours between 31 and 70 mm in groups 2, 1 and 3, respectively, P = 0.0024 (but P = 0.65 between groups 1 and 3). Pneumonectomy was a poor prognostic factor in all groups, but survival between pneumonectomy and bilobectomy was not different in group 1. Multivariate analysis confirmed intralobar invasion to be an independent factor of poor prognosis, as well as visceral pleura invasion., Conclusions: Tumours invading through the fissure have a significant effect on long-term survival in the first stages of lung cancer but also in all stages because of their size and important locoregional spread. Their prognostic value is due to pleural invasion, whose role in lung cancer dissemination is worth further research.

Unlabelled: OBJECTIVES; Patients with extrathoracic synchronous solitary metastasis and non-small cell lung cancer (NSCLC) are rare. The effectiveness of both tumour sites resection is difficult to evaluate because of the high variability among clinical studies. We reviewed our experience regarding the management and prognosis of these patients., Methods: The charts of 4668 patients who underwent lung cancer surgery from 1983 to 2006 were retrospectively reviewed. We analysed the epidemiology, treatment, pathology and prognostic characteristics of those with extrathoracic synchronous solitary metastasis amenable to lung cancer surgery on a curative intend., Results: There were 94 patients (sex ratio M/F 3.2/1, mean age 56 years). Surgery included pneumonectomy (n = 27), lobectomy (n = 65) and exploratory thoracotomy (n = 2). Pathology revealed adenocarcinomas (n = 57), squamous cell carcinoma (n = 20), large cell carcinoma (n = 14) and other NSCLC histology (n = 3). Lymphatic extension was N0 (n = 46), N1 (n = 17) and N2 (n = 31). Metastasis involved the brain (n = 57), adrenal gland (n = 12), bone (n = 14), liver (n = 5) and skin (n = 6). Sixty-nine metastases were resected. Five-year survival rate was 16% (median 13 months). Induction therapy, adenocarcinoma, N0 staging and lobectomy were criteria of better prognosis, but metastasis resection was not., Conclusions: These results suggest that extrathoracic synchronous solitary metastasis of pN0 adenocarcinoma may achieve long-term survival in the case of lung resection with or without metastasis resection. This pattern may reflect a specific tumour biology whose solitary metastasis benefits both from surgical or non-surgical treatment.

Background: Metastatic lung cancer may be M1a (contralateral lung nodule, malignant pleural or pericardial effusion or pleural nodules) or M1b (distant metastases). Surgery is not usually considered in their treatment., Method: After exclusion of contralateral lung nodules, we reviewed the demographics, management, survival and prognostic factors in M1 patients, among a total of 4668 patients who underwent surgery for lung cancer between January 1983 and December 2006., Results: There were 164 patients (70 M1a, 94 M1b). Surgical procedures included exploratory thoracotomy (n=40), lobectomy (n=88), and pneumonectomy (n=38). Histology revealed adenocarcinoma (n=97), squamous cell carcinoma (n=36) or other (n=27). Nodal extension was N0 (n=60), N1 (n=23), N2 (n=64), or not available (n=17). Overall median survival was 14 months and 5-year survival was 12.7%. In M1a median survival was 15 months and 5-year survival 9%. In M1b, median survival was 11 months and 5-year survival 15%, regardless of whether the metastasis was resected or not. The 5-year survival rates were 0% after exploratory thoracotomy, 3.9% after pneumonectomy, 14.8% after lobectomy; 15.2% in adenocarcinoma, 30.4% after induction chemotherapy, and 31.5% in N0 patients. In cases of M1a disease, complete surgical resection resulted in a 5-year survival rate of 16.2%. In case of M1b disease undergoing pulmonary resection, surgical metastasis management did not change the prognosis, with 5-year survival rates of 16.7% in case of metastasis resection (n=66) versus 15.6% without resection (n=19, P=0.67)., Conclusion: In patients with M1a disease, complete surgical resection allowed some long-term survivals, suggesting that surgery may be underestimated. Conversely, in patients with M1b disease undergoing pulmonary resection, surgical resection of the metastasis is not associated with better survival than non-surgical management, suggesting that surgery may be overestimated., (Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Malignant cells in the pleural fluid or pleural metastases are now classified stage IV in lung cancer and alter the treatment. Our purpose was to question the role of surgery in such patients., Methods: The clinical records of 4668 patients, who underwent lung cancer surgery, were reviewed. In some, an undiagnosed pleural malignant disease (M1a) was discovered during thoracotomy. When feasible, selected patients underwent complete surgical resection of the primary tumor and pleural nodules. We analyzed the epidemiology, pathology, and prognosis characteristics of that group (study group), as compared with the population undergoing pulmonary resection in a curative attempt (overall population) or exploratory thoracotomy in case of unexpected disseminated carcinomatous pleuritis (control group)., Results: The study group included 32 patients (25 males), mean age 59 ± 8.8 years, who underwent pneumonectomy (n = 9) or lobectomy (n = 23), associated with mediastinal lymph nodes dissection and surgical resection of associated pleural nodules. There were 21 adenocarcinomas, seven squamous cell carcinomas, two undifferentiated large cell carcinomas, and two miscellaneous tumors. Pathological node (pN) was: N0 in 10 patients (31.3%), N1 in four (12.5%), and N2 in 18 (56.3%). Five-year survival rate was 16% after resection, and 21% if the resection was a lobectomy., Conclusion: Complete surgical resection of non-small-cell lung cancer (NSCLC) associated with limited metastatic pleural involvement is associated with long-term survival in 16% of the cases. A review of the published data, together with the results of this series, may justify the inclusion of surgery in multimodality treatment of NSCLC patients with metastatic pleural extension., (Copyright © 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Non-Small cell lung cancer invading the chest wall represents an advanced stage of the disease. Chest wall resection may be achieved in up to 100% of the patients, and the ensuing defect requires to be reconstructed in 40% to 64% of cases. Once a surgical challenge, chest wall resection is no longer a technical problem and en bloc chest wall and lung resections regularly provide good results. However, survival rates are jeopardized by incompleteness of the resection and mediastinal lymph node involvement. Nowadays, the challenge is represented by the use of the other nonsurgical modalities (chemotherapy and radiation therapy) to increase the chance of performing a complete resection, the need to achieve a better control of probable lymphatic or hematogenous spread, and the reduction of the recurrence rate.

Objectives: Pleural lavage cytology is the microscopic study of cells obtained from saline instilled into and retrieved from the chest during surgery for non-small-cell lung cancer. The aims of this study were to collate multi-institutional individual patient data for meta-analysis to determine independence as a prognostic marker and to characterize the impact of positive results on stage-adjusted survival., Methods: We identified 31 publications from 22 centers/research groups that performed pleural lavage cytology during surgery for non-small-cell lung cancer and invited submission of individual patient data. Actuarial survival was calculated using Kaplan-Meier methods, and comparisons were performed using the log-rank test. Cox proportional hazards regression was used to ascertain the covariates associated with survival., Results: By January 1, 2008, submissions were received internationally from 11 centers with individual data from 8763 patients. In total, 511 (5.8%) patients had a positive pleural lavage cytology result, and this was shown to be an independent predictor of adverse survival associated with a hazard ratio of 1.465 (1.290-1.665; P < .001) compared with a reference hazard ratio of 1 for a negative result. On statistical modeling, the best adjustment for patients with a positive pleural lavage cytology result was a single increase in the T category assigned to the case, up to a maximum of T4. Correction for differences in survival were obtained in stages IB (P = .315) and IIB (P = .453), with a degree of correction in stage IIIA (P = .07)., Conclusions: Pleural lavage cytology should be considered in all patients with non-small-cell lung cancer suitable for resection. A positive result is an independent predictor of adverse survival, and the impact on survival suggests that it may be appropriate to upstage patients by 1 T category., (Copyright 2010 The American Association for Thoracic Surgery. All rights reserved.)

Background: Many studies focus on bronchial microscopic residual disease (R1) after resection for lung cancer, although R1 also concerns vascular and soft tissues. Our purpose was to study the R1 prognosis at different resection margins and to compare it with the prognosis for those having complete resection (R0)., Methods: We reviewed the clinical records of 4,026 patients from two centers who underwent surgery in view of cure. Despite perioperative frozen section, 216 patients (5.4%) proved R1 and were classified into seven types according to R1 anatomic site: bronchus, peribronchus, great vessels and atrium, mediastinum and pericardium, chest wall, lung tissue, and lymph nodes. Patients who were classified as R0 and R1 were compared, and R1 patients were further studied according to R1 margins., Results: Frequency of R1 increased with the T and N values and type of resection (lobectomies, 3.3% [70 of 2,041 patients]; pneumonectomies, 8.8% [126 of 1,308 patients]; p < 10(-6)). Five-year survival rates for R1 patients were lower than those for R0 patients (20% versus 46%; p < 10(-6)), and were not modified by the degree of T and N involvement or adjuvant therapy, but were better in bronchial and peribronchial (48.4% of R1 patients) than in extrabronchial R1 (26.3% versus 15.6%; p = 0.023). Multivariate analysis confirmed R1 to be an independent factor of poor prognosis (p = 0.0008), after N, T, and age., Conclusions: Long-term survival is possible in case of an R1 margin, but 5-year survival rates are jeopardized. Poor efficacy of adjuvant therapy and global outcome indicate advanced disease or reflect tumor cell aggressiveness, rather than surgical insufficiency, when prevention of R1 margins is guided by frozen-section examination and scrupulously respected., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Non-small cell lung cancer (NSCLC) of early stage (stage I and II) form a wide variety of numerous heterogeneous tumors in respect to the T, the N and the histology. However, they share the common characteristic of being resectable, so providing the best chances of cure in patients amenable to surgery. A wide range of resections is available and the tendency at the present time is to favour resections permitting to avoid performing pneumonectomy, an operation whose postoperative mortality may be considerable, particularly on the right side. The place of surgery is of paramount importance in view of cure on condition that the resection is complete, that is without any tumor left behind, and includes a radical mediastinal lymphadenectomy. The place of surgery is also often diagnostic as well as therapeutic, and surgery provides the best histologic classification, the most accurate staging, and thus the best adapted adjuvant therapy and global management.

Background: Among multiple lung cancers (MLC), some may have similar histologic classification. Demonstrating that the second tumor is a metastasis would change the stage and consequently the management. Our purpose was to reconsider this consequence., Methods: We reviewed 234 patients (194 male and 40 female, from 37 to 83 years of age) with synchronous and metachronous non-small cell MLC. Surgery consisted of a potentially curative complete resection with lymphadenectomy. Patients with similar histologic MLC (considered as metastasis) were compared with those with different histologic classification in terms of MLC chronology, type of resection, pT and pN, stage, and overall survival., Results: There were 116 metachronous (ipsilateral, n = 48; contralateral, n = 68) and 118 synchronous MLCs (bilateral, n = 10; same lobe, n = 57; other lobe, n = 51). Pneumonectomy was performed in 77 patients, lobectomy in 103, and lesser resection in 54. Histologic classification was similar in 57.9% of patients and different in 42.1%. The 5-year survival rates tended to be lower in patients with synchronous MLCs (23.4% versus 31.6%; p = 0.07). They were higher when synchronous MLCs were located in the same lobe than if they were located in another lobe (29.9% versus 15.6%; p = 0.022). Whatever the type of MLC, the 5-year survival rates were not correlated with similar or different histologic classification., Conclusions: Our analysis supports that surgery is safe and warranted in MLC patients even if synchronous MLCs present ominously. Changing the staging by establishing the diagnosis of metastasis is probably an important issue warranting further biologic research, but according to our results this diagnosis must not in any case preclude surgery.

Background: Non-small cell lung cancer (NSCLC) mediastinal (N2) metastases are indicators of poor prognosis. Survival rates decrease with increasing number of N2 stations and involved lymph nodes as well as lymph node size and capsular invasion. Our purpose was to elucidate the impact lymph node-related variables on the outcome after surgical resection., Methods: We reviewed data of 2344 NSCLC patients who underwent curative resections with mediastinal lymphadenectomy, and 586 (25%) had N2 metastases. We studied the overall survival of N2 patients according to some important covariates., Results: Metastases involved single N2 stations in 386 patients (66%) and two or more in 200 (34%). Survival was not related with histology or pathologic tumor (pT), but was better when only one N2 station was involved (5-year overall survival 28.5% [median, 24 months] versus 17.2% [median, 14 months] respectively; p = 0.0002. For single N2 stations, capsular rupture, number, and size of lymph nodes were not significant prognostic factors. When the size of lymph node was analyzed (micrometastases, 53; nonbulky, 207; or bulky metastases, 126), overall survival differences between nonbulky and bulky N2 were significant: 5-year overall survival was 34% (median, 28 months) versus 23% (median, 23 months), respectively (p = 0.026). Presence of micrometastases was associated with a poor prognosis: 5-year overall survival of 21.4% (median, 23 months)., Conclusions: Prognosis was better for patients with single N2 stations when metastatic lymph nodes were not enlarged. However, the presence of lymph nodes micrometastases does not seems associated with a better outcome.

Lung cancer rarely affects patients at the extreme ages of life. However, changes in epidemiology and therapy led us to review characteristics of both these younger and older populations. We retrospectively reviewed epidemiologic, clinical and pathological characteristics of patients aged 40 years or less (group 1, n=113) and 80 years or more (group 2, n=78) who underwent surgery between 1983 and 2003. Carcinoid tumors were more frequent in the group 1 (n=59 vs 5). Non small cell lung cancer (NSCLC) occurrence rates decreased with time in group 1, whereas increasing rates were observed in group 2 (p=0.0017). Concomitant diseases were significantly more frequent in group 2. The pneumonectomy rates of non small cell lung cancer were the same in each group (group 1, 35.5%; group 2, 34.8%). Five-year survival rates were better in group 1 (58.9% vs 30%, p=0.0048). No 5-year survival was observed for N2 disease in group 2 and mortality unrelated to cancer was more frequent in this group. Otherwise, both groups were similar except for higher rates of adenocarcinomas in group 1. Lung cancer is more and more frequent in the octogenarians. Surgery remains the best treatment in this population except in case of stage III due to N2 involvement.

Induction treatments in non-small cell lung cancer are usually discussed. Long-term survival after surgery and resecability are enhanced in locally advanced cancers. Morbidity and mortality observed after surgery limit the use of these treatments, despite they depend on many other factors: comorbidities in patient, smoking status, cancer staging, and type of surgery. Right pneumectomy enhances this risk more than left pneumectomy or other limited resections allowed by neoadjuvant treatments, especially in case of downstaging.