Background: Complete thymectomy is recommended for thymic malignancies to reduce local recurrence... more Background: Complete thymectomy is recommended for thymic malignancies to reduce local recurrence and the likelihood of the long-term development of myasthenia gravis (MG). Thymus-conserving surgery (thymomectomy) seems to yield similar results, but evidence is still limited. The objective of this study was to assess if the oncological outcome, in terms of overall survival (OS) and disease-free survival (DFS), are comparable between radical thymectomy vs. conservative thymomectomy patients, and to assess if the outcome of the video-assisted thoracoscopic surgery (VATS) approach was similar to open surgery approach. Methods: We retrospectively analyzed 157 consecutive patients with either resectable thymoma or thymic carcinoma from two Italian centers (Humanitas Research Hospital, Milan, and Humanitas Gavazzeni, Bergamo) between 1997 and 2013 who underwent thymomectomy or extended thymectomy with the VATS or open approach; the patients with Miastenia Gravis underwent radical thymectomy. The patients were followed through physical examinations and phone interviews. Results: Thymomectomy and thymectomy were performed on 86 (54.8%) and 71 (45.2%) patients, respectively. Prognostic factors and comorbidities were comparable in the two groups. The median followup was 77 months. Cox proportional hazards model revealed that Masaoka advanced stage and thymic carcinoma of WHO classification were independent predictive factors for overall survival, but that the extent of surgery and the approach used (minimally invasive versus open) were not. Notably, five-and ten-year survival rates were similar in the two groups. Conclusions: In our experience, radical thymectomy and conservative thymomectomy did not differ in terms of disease-free and overall survival rates. In nonmyasthenic patients with early-stage resectable thymic malignancy, minimally invasive thymomectomy provided equivalent results to open thymectomy. Our results should be interpreted with caution due to the retrospective nature of the study. Well-designed, adequatelypowered studies should be very welcome to increase the quantity and the quality of clinical evidence before incorporating this procedure in future guidelines.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ten cases of benign primary pulmonary meningioma have been reported in the English literature. We... more Ten cases of benign primary pulmonary meningioma have been reported in the English literature. We describe herein an additional case of a benign meningioma arising in the lung showing comparable histologic features of sheets and whorls of epithelioid and meningothelial cells with numerous psammoma bodies. Immunohistochemistry showed that the tumor expressed vimentin and epithelial membrane antigen and was negative for keratin, CD34, glial fibrillary acidic protein, CAM 5.2 and S-100, in keeping with previously reported findings. Our review of the literature reveals similar clinical presentations and follow-up behavior and, where reported, similar electron microscopic and immunostaining features.
Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire... more Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.
In the overall cohort, withregards to prediction of sensitivity to PD-1 axis IO, CBM predicted th... more In the overall cohort, withregards to prediction of sensitivity to PD-1 axis IO, CBM predicted the majority of patients with KRAS/KEAP1and KRAS/STK11/KEAP1 to not benefit from IO, whereas CBM predicted the majority of patients with KRAS/ TP53, KRAS/PI3KCA, and KRAS without co-mut to benefit. No definitive predictions could be made for KRAS/STK11and KRAS/CDKN2A. In the clinical cohort of 36 patients treated with PD-1 axis IO during their treatment course, CBM was able to assess 27 of these patients, identifying patients with OS > 12 months, with 82.8% positive predictive value, 42.9% negative predictive value, and 75% concordance. Conclusions: CBM predicted certain subsets of KRASmutated NSCLC based on comut are more likely to be sensitive to PD-1 axis IO. In a small clinical cohort of KRASmutated NSCLC treated with PD-1 axis IO, in light of existing biomarkers, CBM identified patients with improved prognosis with good positive predictive value. Legal entity responsible for the study: Cellworks Group.
While aggressive tobacco control and help to stop smoking are essential weapons in the fight agai... more While aggressive tobacco control and help to stop smoking are essential weapons in the fight against lung cancer, screening with low-dose computed tomography (LDCT) in high-risk populations and chemoprevention may also contribute to reducing lung cancer deaths. Persons undergoing LDCT screening are an ideal population to be tested for agents potentially able to prevent the development of lung cancer by the regression of precancerous lesions, which are routinely monitored as part of the screening process. Peripheral subsolid nodules appear as particularly suitable targets, since many are adenocarcinoma precursors. A study on inhaled budesonide (a potential chemopreventive drug) for 1 year found that the mean size of non-solid lung nodules was significantly reduced over 5 years of follow-up, compared to inhaled placebo, in a population of high-risk individuals with indeterminate lung nodules not requiring immediate specific investigation for lung cancer and detected as part of a lung cancer screening program with LDCT. A new randomised placebo-controlled phase-II trial to test the ability of aspirin to induce the regression of non-solid and partially solid nodules detected by LDCT screening has been started. The effect of aspirin on a miRNA signature able to predict the presence of both cancer and precancerous lesions in high-risk asymptomatic individuals is also being monitored in the trial. This signature was previously shown to predict the presence of both lung cancer and non-solid lung nodules in asymptomatic individuals.
Background. Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few pat... more Background. Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score. Methods. From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using c 2 , Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model. Results. Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free
We would like to thank J. Domagala-Kulawik and colleagues for their interesting and useful commen... more We would like to thank J. Domagala-Kulawik and colleagues for their interesting and useful comments on our previously published article on T-regulatory (Treg) cells in chronic obstructive pulmonary disease (COPD) [1].
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the Nati... more Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and pr...
NSCLC rates among the most frequent and lethal neoplasm world-wide and a significant decrease in ... more NSCLC rates among the most frequent and lethal neoplasm world-wide and a significant decrease in morbidity and mortality relies only upon effective early diagnostic strategies. We investigated K-ras mutations and p16(INK4A) hypermethylation in tumor tissue and sputum of 50 patients with NSCLC and correlated them with sputum cytology and with tumor staging, grading and location, to ascertain, in sputum, their potential diagnostic impact. The same genetic/epigenetic abnormalities and cytological features were also evaluated in sputum from 100 chronic heavy smokers. Genetic analysis identified molecular abnormalities in 64% tumors (14/50 K-ras mutations and 24/50 p16(INK4A) hypermethylation) and in 48% sputum (11/50 K-ras mutations and 16/50 p16(INK4A) hypermethylation). In tumors K-ras mutations and p16(INK4A) hypermethylation were mostly mutually exclusive, being found in the same patients in 3 cases only. Genetic abnormalities in sputum were detected only in molecular abnormal tumors. Molecular changes in sputum had rates of detection similar to cytology (42%) but the cyto-molecular combination increased the diagnostic yield up to 60%. Interestingly, the rate of detection of genetic changes in sputum of tumors at early stage (T1) was not significantly different from that of tumors at more advanced stage (T2-T4). In fact K-ras point mutations were frequently recognised in tumors at early stage while p16(INK4A) inactivation prevailed in tumors at advanced stage ( P=0.0063). As expected, diagnostic cytological findings were more frequently found in tumors at advanced stage (P=0.004). No correlation was found between tumor grading and location (central versus peripheral) and molecular changes. p16(INK4A) hypermethylation, but not K-ras mutations, was documented in sporadic cases of asymptomatic heavy smokers (4%) where it was uncoupled from cytological abnormalities. In conclusion the cyto-molecular diagnostic strategy adopted in this study was able to detect the majority of tumors but in order to be proposed as effective and early diagnostic tool, this molecular panel needs to be tested in prospective studies with adequate follow-up.
]. The final publication of the NELSON trial data [1] has corroborated the findings of the Nation... more ]. The final publication of the NELSON trial data [1] has corroborated the findings of the National Lung Screening Trial (NLST) confirming the ability of lung cancer screening with low-dose computed tomography (LDCT) to detect lung cancer at an early stage and significantly reduce lung cancer mortality in high-risk groups [2].
Background Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-... more Background Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. Materials and methods Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. Results All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. Conclusions These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).
This paper reports our results with sublobar resections for stage I non small cell lung cancer. S... more This paper reports our results with sublobar resections for stage I non small cell lung cancer. Sixty-one cases of wedge or segmental resection were compared with 517 standard resections (411 lobectomies and 106 pneumonectomies), performed during the years 1971–88. Operative mortality was 0% in the limited resection group and 4 % (19/517) in the standard resection group; cancer recurrence was detected in 36 % of both groups; actuarial survival at 5 years was 55% versus 48% overall. In 28 patients with pre-existing cardiac or pulmonary co-morbidity, limited resection yielded a similar 5-year survival than standard resection (53 % vs 49 %) with no perioperative deaths (0 vs 6 %). Our data support the experience of other authors on conservative management of stage I lung cancer. Particularly in patients with concomitant cardiopulmonary disease, previous cancer or small peripheral tumors, limited resection combined with adequate nodal staging may be as effective as standard lobar resect...
Background: Complete thymectomy is recommended for thymic malignancies to reduce local recurrence... more Background: Complete thymectomy is recommended for thymic malignancies to reduce local recurrence and the likelihood of the long-term development of myasthenia gravis (MG). Thymus-conserving surgery (thymomectomy) seems to yield similar results, but evidence is still limited. The objective of this study was to assess if the oncological outcome, in terms of overall survival (OS) and disease-free survival (DFS), are comparable between radical thymectomy vs. conservative thymomectomy patients, and to assess if the outcome of the video-assisted thoracoscopic surgery (VATS) approach was similar to open surgery approach. Methods: We retrospectively analyzed 157 consecutive patients with either resectable thymoma or thymic carcinoma from two Italian centers (Humanitas Research Hospital, Milan, and Humanitas Gavazzeni, Bergamo) between 1997 and 2013 who underwent thymomectomy or extended thymectomy with the VATS or open approach; the patients with Miastenia Gravis underwent radical thymectomy. The patients were followed through physical examinations and phone interviews. Results: Thymomectomy and thymectomy were performed on 86 (54.8%) and 71 (45.2%) patients, respectively. Prognostic factors and comorbidities were comparable in the two groups. The median followup was 77 months. Cox proportional hazards model revealed that Masaoka advanced stage and thymic carcinoma of WHO classification were independent predictive factors for overall survival, but that the extent of surgery and the approach used (minimally invasive versus open) were not. Notably, five-and ten-year survival rates were similar in the two groups. Conclusions: In our experience, radical thymectomy and conservative thymomectomy did not differ in terms of disease-free and overall survival rates. In nonmyasthenic patients with early-stage resectable thymic malignancy, minimally invasive thymomectomy provided equivalent results to open thymectomy. Our results should be interpreted with caution due to the retrospective nature of the study. Well-designed, adequatelypowered studies should be very welcome to increase the quantity and the quality of clinical evidence before incorporating this procedure in future guidelines.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ten cases of benign primary pulmonary meningioma have been reported in the English literature. We... more Ten cases of benign primary pulmonary meningioma have been reported in the English literature. We describe herein an additional case of a benign meningioma arising in the lung showing comparable histologic features of sheets and whorls of epithelioid and meningothelial cells with numerous psammoma bodies. Immunohistochemistry showed that the tumor expressed vimentin and epithelial membrane antigen and was negative for keratin, CD34, glial fibrillary acidic protein, CAM 5.2 and S-100, in keeping with previously reported findings. Our review of the literature reveals similar clinical presentations and follow-up behavior and, where reported, similar electron microscopic and immunostaining features.
Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire... more Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.
In the overall cohort, withregards to prediction of sensitivity to PD-1 axis IO, CBM predicted th... more In the overall cohort, withregards to prediction of sensitivity to PD-1 axis IO, CBM predicted the majority of patients with KRAS/KEAP1and KRAS/STK11/KEAP1 to not benefit from IO, whereas CBM predicted the majority of patients with KRAS/ TP53, KRAS/PI3KCA, and KRAS without co-mut to benefit. No definitive predictions could be made for KRAS/STK11and KRAS/CDKN2A. In the clinical cohort of 36 patients treated with PD-1 axis IO during their treatment course, CBM was able to assess 27 of these patients, identifying patients with OS > 12 months, with 82.8% positive predictive value, 42.9% negative predictive value, and 75% concordance. Conclusions: CBM predicted certain subsets of KRASmutated NSCLC based on comut are more likely to be sensitive to PD-1 axis IO. In a small clinical cohort of KRASmutated NSCLC treated with PD-1 axis IO, in light of existing biomarkers, CBM identified patients with improved prognosis with good positive predictive value. Legal entity responsible for the study: Cellworks Group.
While aggressive tobacco control and help to stop smoking are essential weapons in the fight agai... more While aggressive tobacco control and help to stop smoking are essential weapons in the fight against lung cancer, screening with low-dose computed tomography (LDCT) in high-risk populations and chemoprevention may also contribute to reducing lung cancer deaths. Persons undergoing LDCT screening are an ideal population to be tested for agents potentially able to prevent the development of lung cancer by the regression of precancerous lesions, which are routinely monitored as part of the screening process. Peripheral subsolid nodules appear as particularly suitable targets, since many are adenocarcinoma precursors. A study on inhaled budesonide (a potential chemopreventive drug) for 1 year found that the mean size of non-solid lung nodules was significantly reduced over 5 years of follow-up, compared to inhaled placebo, in a population of high-risk individuals with indeterminate lung nodules not requiring immediate specific investigation for lung cancer and detected as part of a lung cancer screening program with LDCT. A new randomised placebo-controlled phase-II trial to test the ability of aspirin to induce the regression of non-solid and partially solid nodules detected by LDCT screening has been started. The effect of aspirin on a miRNA signature able to predict the presence of both cancer and precancerous lesions in high-risk asymptomatic individuals is also being monitored in the trial. This signature was previously shown to predict the presence of both lung cancer and non-solid lung nodules in asymptomatic individuals.
Background. Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few pat... more Background. Despite ongoing efforts to improve therapy in malignant pleural mesothelioma, few patients undergoing extrapleural pneumonectomy experience long-term survival (LTS). This study aims to explore predictors of LTS after extrapleural pneumonectomy and to define a prognostic score. Methods. From January 2000 to December 2010, we retrospectively reviewed clinicopathologic and oncological factors in a multicenter cohort of 468 malignant pleural mesothelioma patients undergoing extrapleural pneumonectomy. LTS was defined as survival longer than 3 years. Associations were evaluated using c 2 , Student's t, and Mann-Whitney U tests. Logistic regression, Cox regression hazard model, and bootstrap analysis were applied to identify outcome predictors. Survival curves were calculated by the Kaplan-Meier method. Receiver operating characteristic analyses were used to estimate optimal cutoff and area under the curve for accuracy of the model. Results. Overall, 107 patients (22.9%) survived at least 3 years. Median overall, cancer-specific, and disease-free
We would like to thank J. Domagala-Kulawik and colleagues for their interesting and useful commen... more We would like to thank J. Domagala-Kulawik and colleagues for their interesting and useful comments on our previously published article on T-regulatory (Treg) cells in chronic obstructive pulmonary disease (COPD) [1].
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the Nati... more Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and pr...
NSCLC rates among the most frequent and lethal neoplasm world-wide and a significant decrease in ... more NSCLC rates among the most frequent and lethal neoplasm world-wide and a significant decrease in morbidity and mortality relies only upon effective early diagnostic strategies. We investigated K-ras mutations and p16(INK4A) hypermethylation in tumor tissue and sputum of 50 patients with NSCLC and correlated them with sputum cytology and with tumor staging, grading and location, to ascertain, in sputum, their potential diagnostic impact. The same genetic/epigenetic abnormalities and cytological features were also evaluated in sputum from 100 chronic heavy smokers. Genetic analysis identified molecular abnormalities in 64% tumors (14/50 K-ras mutations and 24/50 p16(INK4A) hypermethylation) and in 48% sputum (11/50 K-ras mutations and 16/50 p16(INK4A) hypermethylation). In tumors K-ras mutations and p16(INK4A) hypermethylation were mostly mutually exclusive, being found in the same patients in 3 cases only. Genetic abnormalities in sputum were detected only in molecular abnormal tumors. Molecular changes in sputum had rates of detection similar to cytology (42%) but the cyto-molecular combination increased the diagnostic yield up to 60%. Interestingly, the rate of detection of genetic changes in sputum of tumors at early stage (T1) was not significantly different from that of tumors at more advanced stage (T2-T4). In fact K-ras point mutations were frequently recognised in tumors at early stage while p16(INK4A) inactivation prevailed in tumors at advanced stage ( P=0.0063). As expected, diagnostic cytological findings were more frequently found in tumors at advanced stage (P=0.004). No correlation was found between tumor grading and location (central versus peripheral) and molecular changes. p16(INK4A) hypermethylation, but not K-ras mutations, was documented in sporadic cases of asymptomatic heavy smokers (4%) where it was uncoupled from cytological abnormalities. In conclusion the cyto-molecular diagnostic strategy adopted in this study was able to detect the majority of tumors but in order to be proposed as effective and early diagnostic tool, this molecular panel needs to be tested in prospective studies with adequate follow-up.
]. The final publication of the NELSON trial data [1] has corroborated the findings of the Nation... more ]. The final publication of the NELSON trial data [1] has corroborated the findings of the National Lung Screening Trial (NLST) confirming the ability of lung cancer screening with low-dose computed tomography (LDCT) to detect lung cancer at an early stage and significantly reduce lung cancer mortality in high-risk groups [2].
Background Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-... more Background Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. Materials and methods Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. Results All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. Conclusions These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).
This paper reports our results with sublobar resections for stage I non small cell lung cancer. S... more This paper reports our results with sublobar resections for stage I non small cell lung cancer. Sixty-one cases of wedge or segmental resection were compared with 517 standard resections (411 lobectomies and 106 pneumonectomies), performed during the years 1971–88. Operative mortality was 0% in the limited resection group and 4 % (19/517) in the standard resection group; cancer recurrence was detected in 36 % of both groups; actuarial survival at 5 years was 55% versus 48% overall. In 28 patients with pre-existing cardiac or pulmonary co-morbidity, limited resection yielded a similar 5-year survival than standard resection (53 % vs 49 %) with no perioperative deaths (0 vs 6 %). Our data support the experience of other authors on conservative management of stage I lung cancer. Particularly in patients with concomitant cardiopulmonary disease, previous cancer or small peripheral tumors, limited resection combined with adequate nodal staging may be as effective as standard lobar resect...
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