Arnaud Scherpereel

Einleitung: Histologie ist inzwischen ein wichtiger klinischer prädiktiver Faktor bei der Behandlung des fortgeschrittenen NSCLC Ziel: Die Analyse von kombinierten Patienten-basierten Daten zweier Phase II Studien über die Wirksamkeit und Sicherheit von VM beim fortgeschrittenen und metastasierten NSCLC, mit dem Ziel den potenziellen prädiktiven Wert von Histologie und anderer klinischer Marker einschließlich Geschlecht, Raucheranamnese und TTF-1 Immunohistochemie (IHC) zu ermitteln. Methoden: Ansprechraten, nicht-adjustierte Überlebenszeiten sowie Cox Kovariaten-adjustierte Hazard Ratios (HR) wurden für jede Subgruppe in jeder einzelnen Studie sowie im gepoolten Datensatz berechnet. Ergbnisse: 175 Patienten wurden in diese retrospektive Analyse eingeschlossen. Adjustierte HRs für das Gesamtüberleben (OS) sowie das progressionsfreie Überleben (PFS) waren in den nicht-Adenocarcinom (non-AC) Subgruppen konsistent besser, wobei für das OS statistische Signifikanz sowohl im gepoolten Datensatz (n = 175; HR 0,677; 95% CI 0,488 – 0,938; p = 0,019) also auch innerhalb einer der beiden Studien (n = 65; HR 0,561; 95% CI 0,318 – 0,988; p = 0,045) erreicht wurde. Die TTF-1 negative IHC war in der Cox-Analyse nicht-signifikant mit einem besseren OS als die TTF-1 positive Subgruppe assoziiert (n = 33; HR 1,232; 95% CI 0,555 – 2,730; p = 0,608) und hatte eine signifikant höhere Ansprechrate (25% vs. 0%; p = 0,040). Für Geschlecht und Raucheranamnese wurde kein signifikanter Effekt beobachtet. Zusammenfassung: Diese Ergebnisse lassen vermuten, dass NSCLC-Patienten mit Non-AC Histologie mehr von einer Therapie mit VM profitieren als Patienten mit Adenokarzinom. Dies sollte in einer Phase III Studie überprüft werden.

7055 Background: (Neo)adjuvant cisplatin-based CT demonstrated its activity in improving survival in resectable NSCLC. We aimed to determine if a combination of cisplatin with second-generation drugs (GNP) and a standard neoadjuvant chemotherapy with first-generation drugs (MIP) can be performed in patients with initially resectable stage I-IIIA NSCLC, without reducing the resectability rate. Final results are presented. Methods: Patients with previously untreated pathologically proven stage I-IIIA resectable NSCLC, Karnofsky performance status ≥ 60, adequate haematological, hepatic, renal, lung and cardiac functions were eligible. After central randomisation, patients received three courses of MIP (ifosfamide 3g/m², mitomycine 6 mg/m², cisplatin 50 mg/m²) or GNP (gemcitabine 1g/m² D1-8, vinorelbine 25 mg/m² D1-8, cisplatin 50 mg/m²). The conclusion of feasibility of each regimen will be drawn if, at least, 50 patients per arm within a sample size of 67 can be completely resected (α 5%, β 20%). Results: From 2001 to 2007, 140 eligible patients were randomized, without any significant imbalance between both arms. The main characteristics were: stage I/II/III in 52, 37 and 51 pts, squamous histology in 82 pts, male 114 pts, median PS 90. All patients alive had at least a 5-years follow-up. No difference in postoperative complications was noted (p = 0.18). There were more thrombopenia with GNP (p = 0.03) and more nausea/vomiting with MIP (p = 0.03). Conclusions: The final results of this randomized study in resectable stage I-III NSCLC showed that both MIP and GNP are efficient neoadjuvant CT regimens but with different toxicity patterns.

恶性胸膜间皮瘤（malignant pleural mesothelioma, MPM）是一种罕见肿瘤，但发病率正逐渐上升，且预后较差。2008年，欧洲呼吸学会（European Respiratory Society, ERS）和欧洲胸外科医师学会（European Society of Thoracic Surgeons, ESTS）特别工作组召集各方专家计划制定MPM诊治经验及更新指南。

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM.To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in ∼10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed.Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

Malignant pleural mesothelioma (MPM) is an agressive and rare tumour, but with increasing incidence linked to previous exposure to asbestos fibers, its main etiological factor. The interest for this cancer has been stimulated by recent improvements in the diagnosis and in the treatment of mesothelioma, including new cytotoxic drugs and multimodal treatment, associating chemotherapy, radical surgery and radiotherapy in prospective, randomised and multicentric trials. The management of MPM is now better defined by the guidelines from the experts Conference of the Société de Pneumologie de Langue Française in 2005, actualised this year by the European Respiratory Society.

Malignant pleural mesothelioma (MPM) is a serious issue worldwide because of its increasing incidence and poor prognosis despite real recent improvements in the disease management. Most of the patients are diagnosed late in the course of the disease when radical treatment is no more an option. Therefore an earlier diagnosis of MPM is needed to significantly increase the survival of patients. Some soluble markers, including soluble mesothelin and osteopontin, have been previously proposed for MPM diagnosis but none has been validated yet. Soluble mesothelin, assessed in blood and in pleural effusion, seems to be the most promising candidate. However, even if it has a good diagnostic and prognostic value, it is quite specific for the epithelioid subtype, the most frequent one of mesothelioma, thus limiting its usefulness in practice. Despite sometimes a good sensitivity, other potential markers as osteopontin are of little interest for MPM diagnosis because of a low specificity. In conclusion, the present data do not justify the use of biology for MPM diagnosis in routine yet but rather suggest a need for a continuing evaluation of soluble mesothelin in clinical studies and the search for other potential tumor markers.

Background: Endocan was originally described as a dermatan sulfate proteoglycan found freely circulating in the blood. Endocan expression confers tumorigenic properties to epithelial cell lines or accelerate the growth of already tumorigenic cells. This molecule is the product of a single gene composed of 3 exons. Previous data showed that endocan mRNA is subject to alternative splicing with possible generation of two protein products. In the present study we identified, and functionally characterized, the alternative spliced product of the endocan gene: the exon 2-deleted endocan, called endocanΔ2.Methods: Stable, endocanΔ2-overexpressing cell lines were generated to investigate the biological activities of this new alternatively spliced product of endocan gene. Tumorigenesis was studied by inoculating endocan and endocanΔ2 expressing cell lines subcutaneously in SCID mice. Biochemical properties of endocan and endocanΔ2 were studied after production of recombinant proteins in various cell lines of human and murine origin.Results: Our results showed that the exon 2 deletion impairs synthesis of the glycan chain, known to be involved in the pro-tumoral effect of endocan. EndocanΔ2 did not promote tumor formation by 293 cells implanted in the skin of severe combined immunodeficient (SCID) mice.Conclusion: Our results emphasize the key role of the polypeptide sequence encoded by the exon 2 of endocan gene in tumorigenesis, and suggest that this sequence could be a target for future therapies against cancer.