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1.
Front Surg ; 10: 1150241, 2023.
Article in English | MEDLINE | ID: mdl-37304187

ABSTRACT

Bochdalek hernias are the most common congenital diaphragmatic hernias, followed by Morgagni hernias. The failure of closure of the pleuroperitoneal membrane results in a posterolateral foramen, which can remain silent until adulthood. They remain a rare pathology with nearly a hundred cases published. Its clinical presentation is variable, making its diagnosis challenging for clinicians. Additionally, its symptoms are not necessarily representative of the content of the hernia. Its management is balanced between the abdominal and the thoracic approaches. However, no guidelines or algorithms are available to help surgeons in the decision-making process. We report here four consecutive cases of symptomatic Bochdalek hernias. Each case has a singular presentation, and we share how they were approached at our institution. In particular, this series shows no reoccurrence in 10+ years of follow-up in two cases and 20+ in one case, underlying the importance of surgical management when Bochdalek hernias are symptomatic.

2.
Nat Genet ; 55(4): 607-618, 2023 04.
Article in English | MEDLINE | ID: mdl-36928603

ABSTRACT

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.


Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Pleural Neoplasms , Humans , Mesothelioma, Malignant/genetics , Mesothelioma, Malignant/complications , Mesothelioma/genetics , Mesothelioma/pathology , Multiomics , Pleural Neoplasms/genetics , Pleural Neoplasms/pathology , Lung Neoplasms/pathology , Biomarkers, Tumor/genetics
3.
Bull Cancer ; 107(9): 946-958, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32646604

ABSTRACT

It has been found that occurrence of immune-related adverse events (irAEs) is associated with outcome in the treatment of advanced non-small-cell lung cancer (NSCLC) with anti-programmed cell death (PD)-1 or anti-PDL1 agents. Independent correlation with survival was not consistently demonstrated and correlation with the number of toxicities was also not previously described. All patients treated with nivolumab for advanced NSCLC, in the second line setting, were retrospectively reviewed in a single-center from March 2015 to March 2017. Sixty-nine patients were identified. After a median follow-up of 13 months (95% CI: 10.8; 15.3), there were 46 tumor progressions and 37 deaths. The 6-month and one-year progression-free survival (PFS) and overall survival (OS) rates were 29%/61% and 24%/49%, respectively. Thirty-one patients (44.9%) presented irAEs. Patients presenting tumor response to previous chemotherapy had a higher rate of irAEs (P=0.01) and a better OS (HR=2, P=0.04). Occurrence of irAEs correlated with OS in multivariate analysis (HR=0.4, 95% CI [0.19; 0.8], P=0.02). The number of irAEs correlated with tumor response, PFS and OS in univariate analysis. Having≥2 irAEs correlated with better outcome compared with one irAE, which correlated with better tumor response and PFS in comparison with 0 irAE, in multivariate analysis. In this study, irAEs was associated with a better outcome in patients treated with nivolumab for advanced NSCLC in the second line setting. Interestingly, the number of irAEs correlated with tumor response and PFS.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Nivolumab/adverse effects , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Nivolumab/therapeutic use , Progression-Free Survival , Retrospective Studies , Survival Rate
4.
Eur Radiol ; 30(6): 3146-3151, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32065281

ABSTRACT

BACKGROUND: Percutaneous parasternal puncture is a common procedure that allows sampling of mediastinal lesions. The trans-pulmonary route is sometimes mandatory in the dorsal position and is associated with complications such as pneumothorax. METHODS: Our study explored the efficacy of the lateral decubitus position in avoiding the trans-pulmonary route. Sixteen patients were included between 2005 and 2019. In three patients, the procedure was intended to place fiducial markers. RESULTS: No pneumothorax or hematoma occurred. Access to the lesion was not possible in 1 patient. A histological diagnosis was made for all patients undergoing sampling. This technique seems to be safe and efficient. KEY POINTS: • Parasternal access to mediastinal and paramediastinal lesions whenever a trans-pulmonary crossing is mandatory in the dorsal position is safe, simple, and efficient in the lateral decubitus position.


Subject(s)
Image-Guided Biopsy/methods , Mediastinal Neoplasms/diagnostic imaging , Mediastinum/diagnostic imaging , Patient Positioning , Tomography, X-Ray Computed/methods , Adult , Aged , Female , Hematoma/etiology , Humans , Image-Guided Biopsy/adverse effects , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Pneumothorax/etiology
5.
J Minim Access Surg ; 16(1): 30-34, 2020.
Article in English | MEDLINE | ID: mdl-30178769

ABSTRACT

BACKGROUND: The aim of this study was to report our experience with video-assisted mediastinoscopy (VAM) in patients taking antiplatelet (AP) or anticoagulant therapies focusing on perioperative complications (especially haemorrhagic). PATIENTS AND METHODS: We have done a retrospective study from a prospectively maintained database with diagnostic VAM (01/2008-06/2012). We included 54 patients with AP (41 patients - Group A) and anticoagulant (13 patients - Group B) therapies. The control group was formed by 263 patients (Group C). Data regarding the clinical records of the patients, operative time, per- and post-operative complications, total numbers of biopsies and the results of the pathologic examination were collected. We compared the groups A+B versus C, and then A versus C. Statistical differences were calculated by Chi-square test. RESULTS: In Group A, we had two minor complications: cardiac arrhythmia and peroperative minor haemorrhage. The mean operative time was 29 min and the mean post-operative stay was 1.08 days. In Group B, we had one minor complication: Peroperative minor haemorrhage. The mean operative time was 35 min and the mean post-operative stay was 1.07 days. In Group C, the mean operative time was 28 min. One death occurred (mortality rate of 0.38%) because of cardiac arrest at the induction of anaesthesia. One major complication occurred (severe respiratory insufficiency needing re-intubation) and eight minor complications. Morbidity rate was 2.28%. Mean post-operative stay was 1.14 days. No statistical difference was noted between groups. CONCLUSION: VAM can be safely performed in patients receiving AP or anticoagulant treatments. There is no increase in peroperative bleeding or post-operative compressive cervico-mediastinal haematoma.

6.
EBioMedicine ; 48: 191-202, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31648983

ABSTRACT

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive disease related to asbestos exposure, with no effective therapeutic options. METHODS: We undertook unsupervised analyses of RNA-sequencing data of 284 MPMs, with no assumption of discreteness. Using immunohistochemistry, we performed an orthogonal validation on a subset of 103 samples and a biological replication in an independent series of 77 samples. FINDINGS: A continuum of molecular profiles explained the prognosis of the disease better than any discrete model. The immune and vascular pathways were the major sources of molecular variation, with strong differences in the expression of immune checkpoints and pro-angiogenic genes; the extrema of this continuum had specific molecular profiles: a "hot" bad-prognosis profile, with high lymphocyte infiltration and high expression of immune checkpoints and pro-angiogenic genes; a "cold" bad-prognosis profile, with low lymphocyte infiltration and high expression of pro-angiogenic genes; and a "VEGFR2+/VISTA+" better-prognosis profile, with high expression of immune checkpoint VISTA and pro-angiogenic gene VEGFR2. We validated the gene expression levels at the protein level for a subset of five selected genes belonging to the immune and vascular pathways (CD8A, PDL1, VEGFR3, VEGFR2, and VISTA), in the validation series, and replicated the molecular profiles as well as their prognostic value in the replication series. INTERPRETATION: The prognosis of MPM is best explained by a continuous model, which extremes show specific expression patterns of genes involved in angiogenesis and immune response.


Subject(s)
Disease Susceptibility , Lung Neoplasms/diagnosis , Lung Neoplasms/etiology , Mesothelioma/diagnosis , Mesothelioma/etiology , Neovascularization, Pathologic/immunology , Pleural Neoplasms/diagnosis , Pleural Neoplasms/etiology , Tumor Microenvironment/immunology , Biomarkers, Tumor , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Lung Neoplasms/pathology , Male , Mesothelioma/pathology , Mesothelioma, Malignant , Pleural Neoplasms/pathology , Transcriptome
7.
J Thorac Dis ; 11(9): 3732-3737, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31656645

ABSTRACT

BACKGROUND: The aim of this study was to assess the feasibility of major pulmonary resection for a limited non-small cell lung cancer (NSCLC) in octogenarians within a dedicated care protocol. METHODS: We retrospectively analyzed data of 55 octogenarians operated on in a single institution between January 2005 and December 2016. They were all included in a specific care protocol with systematic geriatric assessment and adaptation of the peri-operative care. We describe the results of post-operative morbidity, mortality, and survival after anatomical resection and radical lymphadenectomy. RESULTS: Mean age at the time of surgery was 82.1 years (80-86 years). Median Charlson's comorbidity score was 0 (0-3). All patients were classified Balducci 1 or 2. We performed 2 pneumonectomies (3%), 3 bilobectomies (5%), 47 lobectomies (85%) and 3 segmentectomies (5%). The median hospital stay was 11.5 days (7-31 days). The 30-day mortality rate was 3%. The total of relevant clinical complications (Clavien 3 to 5) was 16% (n=9). The Overall Survival at one, three and five years were, respectively: 83% (95% CI: 75-95%); 70% (95% CI: 56-87%); 58% (95% CI: 43-79%). CONCLUSIONS: Major pulmonary resection for primary lung cancer in octogenarians seems to be safe, with an acceptable morbidity, mortality and long-term survival rate, when processing to rigorous selection of the patients, within a dedicated care protocol.

8.
Thorac Cardiovasc Surg ; 67(7): 585-588, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30267389

ABSTRACT

BACKGROUND: Esophageal gastrointestinal stromal tumors (E-GISTs) represent less than 1% of all GISTs. The rarity of this lesion precludes the realization of randomized studies, and its treatment remains a matter of debate. We aimed to evaluate the feasibility of enucleation by video-assisted thoracic surgery (VATS) for low- to intermediate-risk E-GIST. METHODS: We performed a retrospective review of patients treated by enucleation through VATS between January 2004 and January 2014 and reviewed the literature. RESULTS: We included five patients (four men and one woman). Mean age was 53 years (range: 49-79). Three patients were diagnosed because of dysphagia and two others incidentally. The diagnosis was made by immunostaining demonstrating CD117 expression on tumor cells. The mitotic index of all E-GISTs was low (≤ 5 per 50 high-power field). Median postoperative follow-up was 5.5 years, and there was no recurrence. CONCLUSION: Thoracoscopic enucleation of E-GIST seems to represent a valuable option as the postoperative morbidity/mortality is low and the oncological outcome is good for low-to-intermediate grade of malignity tumors.This is a retrospective study focused on minimally invasive treatment of E-GIST. We evaluated the feasibility of VATS enucleation of low-to-medium grade of malignity E-GIST.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Gastrointestinal Stromal Tumors/surgery , Thoracic Surgery, Video-Assisted , Aged , Databases, Factual , Esophageal Neoplasms/pathology , Esophagectomy/adverse effects , Feasibility Studies , Female , Gastrointestinal Stromal Tumors/pathology , Humans , Male , Middle Aged , Neoplasm Grading , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , Treatment Outcome
9.
Cancers (Basel) ; 10(9)2018 Sep 13.
Article in English | MEDLINE | ID: mdl-30216999

ABSTRACT

With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays and automated digital quantification. The CD4⁺/CD8⁺ ratio was significantly higher in elderly patients. In patients <75 years, the density of CD4⁺, CD8⁺, and PD-L1 in TAICs showed a positive significant correlation with PD-L1 expression in tumor cells (TCs), while a lower correlation was observed in the elderly population. In the latter, a high CD4⁺/CD8⁺ ratio, and combined PD-L1 expression ≥1% TCs with a low CD8⁺ density, low CD33⁺ density, and a high CD4⁺ density correlated to worse overall survival. We identified differences according to age in the CD4⁺/CD8⁺ ratio and in correlation between PD-L1 expression and the density of TAICs in LADC patients. Distinct groups of tumor microenvironments had an impact on the OS of elderly patients with LADC.

10.
Eur J Cancer ; 100: 65-74, 2018 09.
Article in English | MEDLINE | ID: mdl-30014882

ABSTRACT

BACKGROUND: Predicting early death after a comprehensive geriatric assessment (CGA) is very difficult in clinical practice. The aim of this study was to develop a scoring system to estimate risk of death at 100 days in elderly cancer patients to assist the therapeutic decision. METHODS: This was a multicentric, prospective cohort study approved by an ethics committee. Elderly cancer patients aged older than 70 years were enrolled before the final therapeutic decision. A standardised CGA was made before the treatment decision at baseline. Within 100 days, event (death), oncologic and geriatric data were collected. Multivariate logistic regression was used to select the risk factors for the overall population. Score points were assigned to each risk factor using the ß coefficient. Internal validation was performed by a bootstrap method. Calibration was assessed with the Hosmer-Lemeshow goodness of fit test and accuracy with the mean c-statistic. FINDINGS: One thousand fifty patients (mean age: 82 years) joined the study from April 2012 to December 2014. The independent predictors were metastatic cancers (odds ratio [OR] 2.5; 95% confidence interval [CI], [1.7-3.5] p<0 .001); gait speed<0.8 m/s (OR 2.1; 95% CI [1.3-3.3] p=0.001); Mini Nutritional Assessment (MNA) < 17 (OR 8; 95% CI; [3.7-17.3] p<0.001), MNA ≤23.5 and ≥ 17 (OR 4.4; 95% CI, [2.1-9.1) p<0.001); performance status (PS) > 2 (OR 1.7; 95% CI, [1.1-2.6)] p=0.015) and cancers other than breast cancer (OR 4; 95% CI, [2.1-7.9] p<0.001). We attributed 4 points for MNA<17, 3 points for MNA between ≤23.5 and ≥ 17, 2 points for metastatic cancers, 1 point for gait speed <0.8 m/s, 1 point for PS > 2 and 3 points for cancers other than breast cancer. The risk of death at 100 days was 4% for 0 to 6 points, 24% for 7 to 8 points, 39% for 9 to 10 points and 67% for 11 points. INTERPRETATION: To our knowledge, this is the first score which estimates early death in elderly cancer patients. The system could assist in the treatment decision for elderly cancer patients.


Subject(s)
Decision Support Techniques , Geriatric Assessment/methods , Neoplasms/mortality , Age Factors , Aged , Aged, 80 and over , Clinical Decision-Making , Female , Frail Elderly , Frailty/diagnosis , Frailty/mortality , France/epidemiology , Gait , Humans , Male , Neoplasm Metastasis , Neoplasm Staging , Neoplasms/diagnosis , Neoplasms/therapy , Nutrition Assessment , Nutritional Status , Patient Selection , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors , Time Factors
11.
Cancers (Basel) ; 10(7)2018 Jun 29.
Article in English | MEDLINE | ID: mdl-29966305

ABSTRACT

Lung cancer is the major cause of death from cancer in the world and its incidence is increasing in women. Despite the progress made in developing immunotherapies and therapies targeting genomic alterations, improvement in the survival rate of advanced stages or metastatic patients remains low. Thus, urgent development of effective therapeutic molecules is needed. The discovery of novel therapeutic targets and their validation requires high quality biological material and associated clinical data. With this aim, we established a biobank dedicated to lung cancers. We describe here our strategy and the indicators used and, through an overall assessment, present the strengths, weaknesses, opportunities and associated risks of this biobank.

12.
Cancers (Basel) ; 10(6)2018 Jun 11.
Article in English | MEDLINE | ID: mdl-29891792

ABSTRACT

Collected specimens for research purposes may or may not be made available depending on their scarcity and/or on the project needs. Their protection against degradation or in the event of an incident is pivotal. Duplication and storage on a different site is the best way to assure their sustainability. The conservation of samples at room temperature (RT) by duplication can facilitate their protection. We describe a security system for the collection of non-small cell lung cancers (NSCLC) stored in the biobank of the Nice Hospital Center, France, by duplication and conservation of lyophilized (dried), encapsulated DNA kept at RT. Therefore, three frozen tissue collections from non-smoking, early stage and sarcomatoid carcinoma NSCLC patients were selected for this study. DNA was extracted, lyophilized and encapsulated at RT under anoxic conditions using the DNAshell technology. In total, 1974 samples from 987 patients were encapsulated. Six and two capsules from each sample were stored in the biobanks of the Nice and Grenoble (France) Hospitals, respectively. In conclusion, DNA maintained at RT allows for the conservation, duplication and durability of collections of interest stored in biobanks. This is a low-cost and safe technology that requires a limited amount of space and has a low environmental impact.

13.
Cancers (Basel) ; 10(4)2018 Mar 21.
Article in English | MEDLINE | ID: mdl-29561830

ABSTRACT

Background: With the integration of various targeted therapies into the clinical management of patients with advanced lung adenocarcinoma, next-generation sequencing (NGS) has become the technology of choice and has led to an increase in simultaneously interrogated genes. However, the broader adoption of NGS for routine clinical practice is still hampered by sophisticated workflows, complex bioinformatics analysis and medical interpretation. Therefore, the performance of the novel QIAGEN GeneReader NGS system was compared to an in-house ISO-15189 certified Ion PGM NGS platform. Methods: Clinical samples from 90 patients (60 Retrospectively and 30 Prospectively) with lung adenocarcinoma were sequenced with both systems. Mutations were analyzed and EGFR, KRAS, BRAF, NRAS, ALK, PIK3CA and ERBB2 genes were compared and sampling time and suitability for clinical testing were assessed. Results: Both sequencing systems showed perfect concordance for the overlapping genes. Correlation of allele frequency was r² = 0.93 for the retrospective patients and r² = 0.81 for the prospective patients. Hands-on time and total run time were shorter using the PGM system, while the GeneReader platform provided good traceability and up-to-date interpretation of the results. Conclusion: We demonstrated the suitability of the GeneReader NGS system in routine practice in a clinical pathology laboratory setting.

14.
Clin Chem Lab Med ; 56(6): 980-989, 2018 05 24.
Article in English | MEDLINE | ID: mdl-29397019

ABSTRACT

BACKGROUND: Circulating tumor cells (CTCs) hold potential for noninvasive diagnosis, prognosis and prediction testing in non-small cell lung cancer (NSCLC) patients. Minimizing degradation or loss of CTCs is pivotal for detection and profiling of the low abundance and fragile CTCs, particularly in clinical trials. We prospectively investigated (NCT02372448) whether a new blood collection device performed better compared to commonly used K3EDTA tubes, when subjected to long-term sample storage. METHODS: Blood samples were drawn into K3EDTA and blood collection tubes (BCT) (Streck), and filtered by the Isolation by SizE of Tumor/Trophoblastic Cells (ISET® system), for CTC detection in two study populations of NSCLC patients; the training set of 14 patients with stage II/IV NSCLC, and the validation set of 36 patients with stage IV NSCLC). MET expression was evaluated by immunocytochemistry (ICC) and anaplastic lymphoma kinase (ALK) gene rearrangement by break-apart fluorescence in situ hybridization (FISH) on ISET-enriched CTCs. RESULTS: Blood processed after 24 h and 48 h in BCT tubes showed stable CTCs counts and integrity, whereas CTCs in K3EDTA tubes showed an altered morphology in all patients. CTCs recovered in BCT or K3EDTA tubes at 24 and 48 h were evaluable by ICC for MET expression and by FISH for ALK rearrangement. CONCLUSIONS: The BCT tubes gave a high yield and preserved the integrity of CTCs after 24 and 48 h of storage at room temperature, which facilitate their molecular characterization in NSCLC patients entering clinical trials.


Subject(s)
Carcinoma, Non-Small-Cell Lung/blood , Clinical Trials as Topic , Lung Neoplasms/blood , Neoplastic Cells, Circulating , Adult , Carcinoma, Non-Small-Cell Lung/genetics , Cell-Free System , Edetic Acid/chemistry , Female , Humans , In Situ Hybridization, Fluorescence , Lung Neoplasms/genetics , Male , Middle Aged , Prospective Studies
16.
Thorac Cardiovasc Surg ; 66(2): 129-134, 2018 03.
Article in English | MEDLINE | ID: mdl-28992652

ABSTRACT

BACKGROUND: The aim of this study was to explore the feasibility of surgery after two induction cycles of cisplatin-docetaxel followed by concomitant 40 Gy chemoradiation in the treatment of initially unresectable stage III non-small cell lung cancer (NSCLC; TAXCIS protocol), and to evaluate overall survival (OS) and recurrence-free survival (RFS) and recurrence risk factors over a larger cohort of patients with a subgroup analysis of patients treated by pneumonectomy. METHODS: Between 2004 and 2014, a total of 37 patients were treated. Only patients responding to induction treatment were included. RESULTS: We operated on 32 stage IIIA and 5 stage IIIB patients. We performed 12 pneumonectomies, 1 bilobectomy, and 23 lobectomies. Status ypT0N0 was obtained for 35% of the patients. Surgery was considered R0 in 86% of the cases. Postoperative morbidity was 21.6% with a mortality of 10.8% (25% after pneumonectomy). OS was 50% at 5 years. The median RFS was 50 months. RFS was 47% at 5 years. Local or locoregional recurrence was diagnosed in 10.8% of the patients, and distant metastasis in 35.1%. Recurrence risk factors were pneumonectomy (p = 0.001) and a histologically incomplete response (p = 0.04). CONCLUSION: The TAXCIS protocol followed by surgery is feasible for initially unresectable NSCLC stage IIIA and B patients. Benefit was noted in responding lesions with better OS and PFS, except after pneumonectomy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Chemoradiotherapy, Adjuvant , Lung Neoplasms/therapy , Neoadjuvant Therapy , Pneumonectomy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/secondary , Chemoradiotherapy, Adjuvant/adverse effects , Chemoradiotherapy, Adjuvant/mortality , Cisplatin/administration & dosage , Disease Progression , Disease-Free Survival , Docetaxel , Feasibility Studies , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/mortality , Neoplasm Recurrence, Local , Neoplasm Staging , Pneumonectomy/adverse effects , Pneumonectomy/mortality , Proportional Hazards Models , Radiotherapy Dosage , Retrospective Studies , Risk Factors , Taxoids/administration & dosage , Time Factors , Treatment Outcome
17.
Oncotarget ; 8(61): 103055-103062, 2017 Nov 28.
Article in English | MEDLINE | ID: mdl-29262544

ABSTRACT

Treatment with EGFR inhibitors is limited to patients with advanced/metastatic non-small cell lung cancer who have known EGFR mutations. Currently, patient care has to respond to several imperatives to make these inhibitors broadly available to all patients; fast and accurate detection of EGFR mutations by a sensitive and specific standardized cost-effective method, easy-to-implement in settings with limited expertise in molecular diagnostics. We evaluated the Idylla™ EGFR Mutation Assay (Biocartis) for the detection of EGFR mutations in archived formalin-fixed paraffin-embedded (FFPE) tumor samples from a series of 55 patients with lung adenocarcinoma and compared these results with those obtained by a pyrosequencing ISO-15189 accredited laboratory method. The comparison was made on both whole surgical tumor sections and on three artificially constructed small biopsies (∼1 mm) from the same FFPE blocks. Cost-effectiveness and turnaround time comparison between the two methods was performed. On both whole tissue sections and on biopsy cores, the Idylla™ and pyrosequencing had an agreement of 95% (52/55). The Idylla™ EGFR Assay produced results faster and more cost-effective than pyrosequencing. The Idylla™ system showed a good sensitivity and was cost-saving in our setting. Because of the easy workflow, the Idylla™ system has the potential to expand EGFR testing to more pathology laboratories in a reliable and fast manner.

18.
BMJ Open ; 7(6): e012963, 2017 06 15.
Article in English | MEDLINE | ID: mdl-28619764

ABSTRACT

INTRODUCTION: In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. METHODS AND ANALYSIS: The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. ETHICS AND DISSEMINATION: The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02502318.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Pneumonectomy , Postoperative Complications/economics , Thoracic Surgery, Video-Assisted , Thoracotomy , Adult , Carcinoma, Non-Small-Cell Lung/economics , Carcinoma, Non-Small-Cell Lung/mortality , Cost-Benefit Analysis , Female , France , Humans , Length of Stay/economics , Length of Stay/statistics & numerical data , Male , Operative Time , Pneumonectomy/economics , Pneumonectomy/instrumentation , Reproducibility of Results , Retrospective Studies , Survival Analysis , Thoracic Surgery, Video-Assisted/economics , Thoracotomy/economics , Treatment Outcome
19.
Mod Pathol ; 29(12): 1552-1564, 2016 12.
Article in English | MEDLINE | ID: mdl-27562497

ABSTRACT

PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8+ and PD-1+ tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8+ and PD-1+ tumor-infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (κ range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (κ=0.883, and κ=0.721). Expression of PD-L1 correlated with a high content of CD8+ and PD-1+ tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8+ and PD-1+ tumor-infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8+ and PD-1+ tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay.


Subject(s)
B7-H1 Antigen/biosynthesis , Carcinoma, Squamous Cell/immunology , Lung Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Adult , Aged , B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies
20.
Ann Thorac Surg ; 99(3): 1025-31, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25620590

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the clinical characteristics and factors that influence the long-term outcomes of solitary fibrous tumors of the pleura. METHODS: We conducted a retrospective study in 2 centers and reviewed 80 patients who underwent surgery between May 1984 and April 2011. RESULTS: Of the 80 patients (29 male; median age, 60 years [33 to 85 years]), 47 were symptomatic (59%). The tumors originated from the visceral pleura in 62 cases (79%) and from the parietal pleura in 18 cases (22%). The tumors were pedunculated in 66 cases (83%) and sessile in 20 cases (17%). Surgical resection with histologically free margins was accomplished in 76 of 79 patients (93%). The tumors were classified as benign in 51 cases (65%) and as malignant in 28 (35%). The factors that were significantly associated with malignant tumors were the presence of symptoms (p = 0.03), a mean diameter 10 cm or greater (p = 0.0004), fibrous adherences (p = 0.003), pleural effusion (p = 0.003), and a Ki67 10% or greater (p = 0.003). The median follow-up was 69 months (range, 1 to 315). Local recurrence occurred in 3 cases. The overall 5- and 10-year survival rates were 90% and 86%, respectively, and the mean survival time was 255 ± 15 months. There were no differences between the benign and malignant tumors. CONCLUSIONS: The recurrence rates are low after surgeries for both benign and malignant solitary fibrous tumors of the pleura. However, the factors that are predictive of recurrence have yet to be specified and require additional immunohistochemical and genetic investigations.


Subject(s)
Solitary Fibrous Tumor, Pleural/diagnosis , Solitary Fibrous Tumor, Pleural/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment Outcome
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