Impact of adjuvant radiotherapy and chemotherapy on thymoma.

PURPOSE: Thymoma is a rare tumour. The most common treatment for thymoma is surgical resection, while the use of radiotherapy and chemotherapy remains controversial. PATIENTS AND METHODS: We conducted a monocentric observational study of 31 patients diagnosed with thymoma from June 2004 to July 2020 at cancer centre in Strasbourg, France. We analysed the outcomes of the patients. RESULTS: The 2- and 5- year locoregional relapse-free survival rates were 96.3% (95% confidence interval [CI]: 76.5-99.5%) and 68.0% (95% CI: 43.8-83.5%), respectively. Radiotherapy and chemotherapy significantly improved local tumour control (P=0.0008 and 0.04, respectively), while a larger initial tumour size significantly worsened local control rates (P=0.04). The 5- and 10-year overall survival rates were 87.1% (95% CI: 69.2-95%) and 81.7% (95% CI: 60.3-92.2%), respectively. The median overall survival was not reached, and no favourable factor was retrieved. For relapsed patients, the median overall survival after relapse was 115 months. CONCLUSION: Despite the inherent limitations of retrospective studies with a limited patient sample size, we demonstrated that chemotherapy and radiotherapy in addition to surgery were effective in achieving local control and contributed to improving patient outcomes in thymoma. Notably, an aggressive treatment strategy at the time of relapse resulted in favourable outcomes for retreated patients.

Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

[Therapeutic strategies in advanced ALK positive non-small cell lung cancer]. / Stratégies thérapeutiques dans le cancer bronchique non à petites cellules ALK positif de stade IV.

Anaplastic lymphoma kinase (ALK) rearrangement is a therapeutically targetable oncogenic driver found in 5% of patients with non-small-cell lung cancer (NSCLC). The objective of this paper is to synthesise current knowledge on ALK rearrangement and its impact on the management of advanced NSCLC. Several inhibitors of the tyrosine kinase of ALK (crizotinib, ceritinib, alectinib) have been approved as first line therapies in patients with advanced ALK positive NSCLC, which are associated with a better median progression-free survival than conventional chemotherapy. Unfortunately, the emergence of drug resistance leads to tumor progression. In patients with oligoprogressive disease if local ablative therapy can be effected, continuing with the same ALK tyrosine kinase inhibitor is one option. In patients with progression, clinicians may consider switching to another therapy. Rebiopsy of the tumor or liquid biopsy could be attempted to identify the mechanisms of resistance and to customize ALK-target therapy. The emergence of crizotinib drug resistance has prompted the development of next generation drugs including ceritinb, alectinib, brigatinib and lorlatinib. The ability to quickly develop targeted therapies against specific oncogenic drivers will require close co-operation between pathologists, pulmonologists and oncologists in the future to keep pace with drug discoveries and to define optimal therapeutic strategies.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

[Autoimmune-related bleeding occurring during combined immunotherapy for lung cancer - Case report]. / Complication hémorragique inattendue pour un cancer bronchique sous double immunothérapie.

INTRODUCTION: Specific immune-related adverse events in lung cancer treatment are rare and it is important that they are identified as they may have important adverse consequences. We report such a case here. CASE REPORT: A Caucasian female diagnosed with KRAS mutant advanced adenocarcinoma of the lung was enrolled in a phase Ib trial assessing the combination of an anti cytotoxic T-lymphocyte- associated protein 4 antibody and a programmed death-Ligand 1 inhibitor. For several years, she had also been taking warfarin for recurrent pulmonary embolism. At day 15 of treatment, she presented with grade 1 haematomas and signs of grade 2 hyperthyroidism. Blood tests revealed a normal number of platelets but an INR increased to 6.5. Thyroid function tests and auto antibodies confirmed the presence of an autoimmune thyroitidis. The study treatment was then stopped and the patient received 1mg/kg of prednisone and 40mg of propranolol. At day 28, the thyroid function and symptoms were normalized. No direct interactions exist between immunotherapy and vitamin K antagonists (VKA) but hyperthyroidism, through pharmacokinetic and metabolic mechanisms, can boost VKA plasma levels and increase INR, leading to hemorrhagic complications. CONCLUSIONS: This case emphasizes that special consideration should be given to patients with VKA treatment planned to receive immunotherapy.

Identification of microRNA-based signatures for response and survival for non-small cell lung cancer treated with cisplatin-vinorelbine A ELCWP prospective study.

UNLABELLED: Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate individual prediction. MicroRNA (miRNA) are non-coding RNAs regulating gene expression. In a prospective study, we assessed the predictive value for response and survival of tumour miRNA in NSCLC patients treated by 1st line cisplatin and vinorelbine. miRNA expression was analysed on a biopsy obtained during the diagnostic bronchoscopy, using TaqMan Low Density Arrays. The signature for response was derived using logistic regression with stepwise variable selection. The associations between overall survival and miRNA expression levels were estimated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models to estimate the hazard ratios. In total, 38 patients with adequate tumour biopsies, treated with cisplatin-vinorelbine were included: male (n = 27), 80-100 Karnofsky PS (n = 27), adenocarcinoma (n = 20), stage IV (n = 30). One patient was considered not assessable for response but remained included in the survival analyses. Out of the 37 patients assessable for response, 16 partial responses (43%) were observed. A two miRNA signature (miR-149 and miR-375) was found predictive for response and was also associated to progression-free survival (p = 0.05). Using a linear combination of the miR CT values with Cox's regression coefficients as weights, we constructed a prognostic score for overall survival including four miRNA (miR-200c, miR-424, miR-29c and miR-124). The signature distinguished patients with good (n = 18) and poor (n = 20) prognosis with respective median survival times of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p < 0.001; hazard ratio 21.1, 95% CI 4.7-94.9). CONCLUSIONS: miRNA signature allows predicting response and is of prognostic value for survival in patients with NSCLC treated with first line cisplatin and vinorelbine.

Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer.

BACKGROUND: Treatments of non-small-cell lung cancer (NSCLC)-particularly of the squamous subtype-are limited. In this article, we describe the immunomodulatory environment in NSCLC and the potential for therapeutic targeting of the immune system through cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) immune-checkpoint pathway blockade. MATERIALS AND METHODS: We searched PubMed and presented abstracts for publications describing the clinical benefit of checkpoint blockade in NSCLC. RESULTS: Antibody-mediated checkpoint molecule blockade is being investigated in NSCLC, and of these approaches, the anti-CTLA-4 antibody ipilimumab has undergone the most extensive clinical study. By targeting the immune system rather than specific antigens, checkpoint blockade agents differ from vaccine therapy. In a phase II study in advanced NSCLC, phased ipilimumab with chemotherapy demonstrated the greatest efficacy in squamous NSCLC. A phase I study of nivolumab, an anti-PD-1 antibody, has suggested that this agent is also active against squamous and non-squamous NSCLC. Ongoing phase III studies are evaluating the therapeutic potential of these agents. CONCLUSIONS: Although treatment options for NSCLC are limited, a better understanding of the immune profile of this disease has facilitated the development of immunotherapeutics that target checkpoint blockade molecules, and clinical evaluation to date supports combining checkpoint blockade with chemotherapy for squamous NSCLC.

Screening and early detection of lung cancer.

The greatest news of the past year in this field was the first large-scale early detection trial that could prove a 20% reduction in lung cancer-related mortality by screening high-risk individuals with low-dose computed tomography (LDCT). Several expert groups and medical societies have assessed the data and concluded that LDCT screening for lung cancer is, however, not ready for large-scale population-based implementation. Too many open questions remain, such as definition of the at-risk population, timing and intervals of screening, optimal method of acquisition and interpretation of the images, how to handle (false) positive findings, and especially cost-effectiveness in relation to other lung cancer prevention strategies, mainly smoking cessation. Further analyses and several ongoing European trials are eagerly awaited. Much hope also resides in the use of biomarkers, as their use in, e.g., blood or exhaled air may provide more easy-to-use tests to better stratify high-risk populations for screening studies. While exciting research is ongoing in this domain--e.g. with microRNAs--none of the tests has yet reached sufficient validation for clinical use. Early central lung cancers are more difficult to visualise by CT. For these patients, standard bronchoscopy, complemented by autofluoresence endoscopy, has been studied in different screening and follow-up settings.

Evolution of microRNA expression during human bronchial squamous carcinogenesis.

MicroRNAs, negative post-transcriptional regulators of gene expression, are involved in cancer. Their role in early bronchial carcinogenesis was analysed in 60 biopsies obtained by fluorescence bronchoscopy (six per stage: normal tissue of nonsmokers, normal normofluorescent and hypofluorescent bronchial tissue of smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive squamous cell carcinoma (SQCC)). In total, 69 microRNAs were found to be differentially expressed in the course of bronchial carcinogenesis. Among them, some microRNAs showed a linear evolution of their expression level, such as miR-32 and miR-34c, whose expression progressively decreased from normal bronchial tissues of nonsmokers to SQCC. Others behaved differently at successive stages, such as miR-142-3p or miR-9, or are only altered from a specific stage, such as miR-199a or miR-139. MicroRNAs globally followed a two-step evolution, first decreasing (a reverse of their increase during embryogenesis) during the earliest morphological modifications of bronchial epithelium, and thereafter increasing at later stages of lung carcinogenesis. Moreover, microRNA expression was very efficient for the prediction of the histological classification between low- and high-grade lesions and between in situ and invasive carcinoma. The present data show, for the first time, that microRNAs are involved in bronchial carcinogenesis from the very early steps of this process and, thus, could provide tools for early detection of lung cancer.

[Study of the genesis of bronchial epidermoid carcinoma: evolution or the expression of proteins, messenger RNAs and microRNAs at all stages of the process of carcinogenesis]. / Etude de la genèse du carcinome epidermoìde bronchique: evolution de l'expression des protéines, des ARNs messagers et des microARNs a tous les stades du processus de cancérisation.

We characterized the successive and cumulative molecular modifications associated with transition in the histological stages of lung squamous carcinogenesis (normal epithelium from smokers, hyperplasia, metaplasia, mild, moderate and severe dysplasia, in situ carcinoma and invasive carcinoma) to improve our understanding of the mechanisms involved and identify new biomarkers for the early detection of lung squamous cell carcinoma. We employed immunohistochemistry, immunofluorescence, gene expression microarrays and quantitative RT-PCR to successively assess the expression of various proteins involved in cellular proliferation and apoptosis as well as messenger RNAs and microRNAs expression. Based on our data, we have improved the classification of bronchial preneoplastic lesions and furthered our understanding of the pathways involved in early lung carcinogenesis. The large number of biomarkers highlighted in these studies has opened two major and interesting perspectives: 1) the development of non invasive tests based on biomarkers for lung cancer detection at pre-invasive and early invasive stages and 2) new avenues of fundamental research whose goal is to understand the mechanisms underlying lung carcinogenesis.

[Etiology, epidemiology, biology. Lung carcinogenesis]. / Cancérogenèse bronchique.

Lung cancer is a complex disease involving various oncogenic pathways. Its early detection, at pre-invasive stages, could offer the opportunity of improving the bad prognosis of this cancer. Pre-invasive stages exist for different forms of lung cancer and some of them are recognized as being preneoplastic: dysplasias and in situ carcinoma, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia are supposed to be precursors of squamous cell carcinomas, adenocarcinomas and carcinoid tumors, respectively. The sequence of histological modifications of bronchial mucosa preceding the development of a squamous cell carcinoma are well documented while those preceding other histological types are less known. This paper summarizes available data about histological modifications defining those preneoplastic and/or pre-invasive lesions, their principal clinical characteristics and the possibilities for their diagnosis. It also discusses arguments for their preneoplastic nature, their evolution and risk of progression risk, molecular abnormalities involved in lung carcinogenesis and clinical relevance of these lesions.

The role of NPM, p14arf and MDM2 in precursors of bronchial squamous cell carcinoma.

Murine double minute clone 2 (MDM2), p14 alternate reading frame (p14arf), and nucleophosmin (NPM) regulate p53 activity. A total of 200 biopsies, including normal bronchial, pre-invasive and invasive tissues, were examined for changes in NPM, p14arf, MDM2 and p53 expression patterns by immunohistochemistry and immunofluorescence with confocal microscopy. NPM and p14arf displayed a diffuse nuclear staining in most normal bronchial tissue. The fraction of biopsies displaying an increased MDM2 staining or a nucleolar relocalisation of NPM increased at mild and moderate dysplasia, respectively. Two different modifications occurred in p14arf expression, i.e. its loss or its nucleolar relocalisation, both increasing at severe dysplasia and both being associated with high MDM2 expression. In addition, the nucleolar relocalisation of p14arf was associated with that of NPM. Immunofluorescence staining indicated that NPM and p14arf either co-localised in the nucleoplasm or in the nucleoli, before and as a result of severe dysplasia, respectively. MDM2 was not detected in the nucleoli. Thus, changes occur in murine double minute clone 2, p14 alternate reading frame and nucleophosmin level of expression and/or cellular distribution during early steps of lung carcinogenesis. Their relative localisation as determined by immunofluorescence, supports the hypothesis that p14 alternate reading frame nucleolar relocalisation impairs p14 alternate reading frame-murine double minute clone 2 complex formation and that nucleophosmin might sequester p14 alternate reading frame. The demonstration of this hypothesis requires further functional studies.

EGFR, TTF-1 and Mdm2 expression in stage III non-small cell lung cancer: a positive association.

New biological factors have not been extensively studied in stage III NSCLC as yet. The aim of this retrospective study was to assess the association between the expression and the prognostic role on survival of four biological markers in stage III NSCLC. Clinical characteristics were retrieved from the patients charts. EGF-R, Mdm2, p53 and TTF-1 expressions were evaluated by immunohistochemistry by three independent observers. Cox multivariate model was used to assess the impact of clinical and biological factors on patients' survival. A total of 84 stage III NSCLC patients, treated between 03/1987 and 08/2003, were included in the study. There was a statistically significant association between the expression of TTF-1 and EGFR (p=0.01) or TTF-1 and Mdm2 (p=0.04). Positive expressions for EGFR or TTF-1 were almost mutually exclusive. The status EGFR+/TTF-1--was mainly found in squamous cell carcinoma (18 among 19tumours). In multivariate analysis, only treatment with curative intent was independently associated with better survival (p=0.0004). In stage III NSCLC, there was a significant association between TTF-1 and EGFR or TTF-1 and Mdm2. The status EGFR+/TTF-1--was associated with squamous cell carcinoma.

Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses.

BACKGROUND: The aim of this study was to estimate the efficiency of a recent five-category urinary cytological classification. METHODS: A total of 592 bladder washings were fixed immediately with Saccomanno's fixative. All samples were centrifuged in a Hettich cyto-centrifuge. For each sample, the reference standard was the histology when a lesion was present at the time of cystoscopy. A five-category cytological classification was used: negative, suspicious of low (S-Lg) or high (S-Hg) grade neoplasia and consistent with low (Lg) or high (Hg) grade neoplasia. RESULTS: For cytological diagnoses of S-Lg and Lg, sensitivity was 37% and specificity was 95% for the histological diagnosis of low-grade non-invasive urothelial papillary tumour (Lg-UPT), which included papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma. For cytological diagnosis of S-Hg and Hg, sensitivity was 44% for high-grade non-invasive urothelial papillary carcinoma (Hg-UPC), 70% for carcinoma in situ (CIS) and 81% for invasive carcinoma (T1 and higher). Specificity was 99% in each case. Cytological diagnosis of S-Hg or Hg was not found for Lg-UPT (0/59) and no cytological diagnosis of S-Lg or Lg was found for invasive carcinoma, but was seen for Hg-UPC in 10% (3/28) and for CIS in 6% (3/50) of cases. CONCLUSION: Despite the absence of international consensus, the recent five-category cytological classification for urine is accurate for current urological practice.

Thyroid transcription factor 1--a new prognostic factor in lung cancer: a meta-analysis.

BACKGROUND: The aim of this study was to determine the prognostic role for survival of thyroid transcription factor 1 (TTF-1) in lung cancer. METHODS: Studies evaluating survival and TTF-1 in lung cancer patients, published until August 2005, were assessed with a methodological scoring system. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and a combined HR was calculated. RESULTS: We identified 10 eligible papers, all dealing with non-small-cell lung cancer (NSCLC). Eight were meta-analysed (evaluable studies). Seven studies included patients with local and/or locoregional diseases and three dealt only with adenocarcinoma. Median methodological quality score was 65.9% (range = 31.8%-70.5%). TTF-1 positivity was associated with statistically significant reduced or improved survival in one and four studies, respectively. Combined HR for the eight evaluable studies was 0.64 [95% confidence interval (CI) = 0.41-1.00]. In the subgroup of adenocarcinoma, the combined HR was 0.53 (95% CI = 0.29-0.95). CONCLUSION: TTF-1 is a good prognostic factor for survival in NSCLC. Its effect appears also significant when the analysis is restricted to patients with adenocarcinoma. This study supports the fact that TTF-1 could be included in further prospective trials studying prognostic factors in NSCLC.

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results.

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.

Prognostic role of thyroid transcription factor-1 in stage III non-small cell lung cancer.

UNLABELLED: Stage III NSCLC represents a heterogeneous group and the ISS remains unsatisfactory in term of prognosis prediction. The aim of the present study was to determine the role of TTF-1 as prognostic factor in stage III NSCLC in addition to other known clinical factors. All stage III NSCLC patients treated in our hospital were retrieved and searched for biopsy specimens. TTF-1 was assessed by immunohistochemistry (Novocastra SPT24). Between 01/1987 and 07/2003, 108 assessable stage III NSCLC patients were included in the study. Their principal characteristics were: median age 64 years (range 37-83), male/female 81/27, squamous/non squamous 52/56, IIIA/IIIB 44/64, median Karnofsky PS 80 (range 20-100). Forty-four patients were positive for TTF-1 (squamous 25.0% versus non-squamous 55.4%). In multivariate analysis, only three factors were statistically significantly associated with better survival: good PS, surgery and creatinine level. CONCLUSION: In stage III NSCLC patients, good PS, resectability and low creatinine level but not TTF-1 are prognostic factors for survival.

EGFR, c-erbB-2 and ki-67 in NSCLC and preneoplastic bronchial lesions.

BACKGROUND: The relationships between EGF-R and c-erbB-2 with other factors involved in tumour regulation are not well understood. The aim of this study was to correlate the expression of these markers with tumour proliferation. MATERIALS AND METHODS: The presence of EGF-R, c-erbB-2 and Ki-67 was evaluated by immunohistochemistry in non-small cell lung cancer (NSCLC) and preneoplastic lesions. RESULTS: Forty-two percent of the tumours were positive for EGF-R, 22% for c-erbB-2 and 97% for Ki-67. No statistically significant correlation was found between EGF-R and Ki-67, EGF-R and c-erbB-2 or between c-erbB-2 and Ki-67. With regards to Ki-67, a significant difference in survival was noted in favour of patients who did not express the marker. In preneoplastic lesions, most of the low-grade lesions showed neither EGF-R nor Ki-67 staining. In contrast, most of the high-grade lesions stained positively for these proteins. CONCLUSION: EGF-R and c-erbB-2 do not seem to be correlated with Ki-67 in NSCLC.

COX-2 expression during early lung squamous cell carcinoma oncogenesis.

Cyclooxygenase (COX)-2 is implicated in the oncogenesis of many cancers, and COX-2 inhibitors are effective in preventing the development of tumours, such as in colon cancer. Its expression is increased in nonsmall cell lung cancer and is associated with poor prognosis. The present study assessed COX-2 expression in normal bronchial epithelium, as well as in all the putative precursors of squamous cell carcinomas. COX-2 expression was studied by immunohistochemistry in 106 biopsies collected during autofluorescence bronchoscopy in consecutive patients at high-risk for lung cancer. All biopsies corresponding to normal epithelium or low-grade lesions (lesions up to moderate dysplasia) did not show increased COX-2 expression. Lesions were positive for COX-2 in eight out of 14 severe dysplasia patients, eight out of 14 in situ carcinomas and five out of eight invasive carcinomas. A strong statistically significant difference in COX-2 expression was found between normal epithelium or low-grade lesions and high-grade lesions (severe dysplasia or worse). The positive and negative predictive values of COX-2 expression for high-grade lesion were 100% and 82.35%, respectively. In conclusion, bronchial precursors of squamous cell carcinoma showed increased cyclooxygenase-2 expression and were segregated into low- versus high-grade with a high positive predictive value. Thus, cyclooxygenase-2 appears as a potential early marker of squamous cell carcinoma.

[Docetaxel as salvage treatment for non-small cell lung cancer: implementation study]. / Le docétaxel comme traitement de rattrapage pour les cancers bronchiques non à petites cellules: étude d'implementation.

Salvage treatment with docetaxel after failure of cisplatin-based chemotherapy in non-small cell lung cancer (NSCLC) has already been tested in the context of clinical prospective trials but only dealing with selected patients. The aim of the present study is to assess the generalizability of these results in an unselected population. We retrospectively analysed the data of all patients not included in clinical studies and treated at the Jules Bordet Institute between September 1996 and July 2003 by docetaxel after a previous chemotherapy containing platinum. Patients were separated in two groups: eligible or not studies according to the selection criteria of the published phase II and III prospective trials. There were 27 patients treated by docetaxel after relapse or failure of prior first-line platinum-based chemotherapy. Among them, 15 were ineligible according to the criteria of published phase II and III trials. The global response rate was 7.41%. All responders had a partial response to first line chemotherapy. Toxicity consisted mainly in grade III/IV neutropenia and was similar between the two group of patients. The median survival time was 25 weeks. In conclusion, our implementation study confirms the activity of docetaxel as salvage therapy after failure of first line cisplatin-based chemotherapy in an unselected population of patients with NSCLC, with a response rate similar to that obtained in propective trials.