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The frequency of hyponatraemia varies from less than 1% to more than 40% in series reported from general hospitals. We performed a prospective study to evaluate its incidence and to determine the types of hyponatraemia in a dedicated cancer hospital. All patients admitted to the Department of Medicine were prospectively studied over 11 months. Hyponatraemia was defined as a serum Na levelor =130 mEq/l. Urine and blood samples were collected at baseline, and all consecutive hyponatraemic episodes were studied. One hundred and six patients developed 123 episodes of hyponatraemia. The observed incidence of hyponatraemia was 3.7%. Sodium depletion and syndrome of inappropriate antidiuretic hormone secretion (SIADH) each accounted for almost one third of all aetiologies. Serum urea and uric acid, urinary Na and fractional excretions of Na and urea were most useful for the differential diagnosis. The percentage of deaths observed in the hyponatraemic group, 19.5%, was higher than in the whole cancer population (6.3%) although no death was apparently due directly to hyponatraemia. Hyponatraemia is regularly diagnosed in cancer patients, but it was related to SIADH in only about one third of the cases. A higher mortality was observed in hyponatraemic patients than in normonatraemic patients.

We reported the case of a patient with stage IV Hodgkin's disease (involving the nodes and Liver) presenting with paraneoplastic fever and who subsequently developed hypothermia during chemotherapy administration. We also reviewed the 12 other cases of hypothermia in Hodgkin's disease reported in the literature and discussed the most probable physiopathologic aetiologies.

SCOPUS: le.j, info:eu-repo/semantics/published

A 84 year-old woman presenting with evolving breast cancer was admitted in the intensive care unit for malaise. Profound hyponatremia in the context of symptomatic heart failure was documented. Intravenous infusion of NaCl 0.9% was unsuccessful. Treatment with oral urea was begun and sodium level returned to nearly normal values 5 days later. We report the case of a woman with acute cardiac failure and concurrent reduced sodium pool, who cannot tolerate saline supplementation and who was successfully treated with oral urea administration.

Background: Our objectives were to determine, for cancer patients dying in the ICU, the reasons for admission, the causes of death and the impact of life-support techniques limitations (LSTL). Methods: This is a retrospective study including only cancer patients dying in the ICU. Results: From 1st January 2008 to 31st December 2009, 658 patients were admitted in the ICU, 71 of whom had neoplastic disease and ultimately died after admission for a medical/surgical complications. Their principal characteristics were: men/women 38/33, median age 57 years, solid/haematological tumours 46/25. Solid tumours were mainly presenting at a metastatic stage (93.5%). Out of the 25 haematological patients, 6 were allograft recipients. The most frequent causes of admission were respiratory failure (36.6%) and infection (47.9%). Infection was the cause of death in 53.5%. Twenty-one patients had LSTL at or during the first 24 hours of ICU admission, especially because of cancer progression. Another 33 had LSTL later due to clinical deterioration. Seventeen patients did not receive any LSTL; all died with mechanical invasive ventilatory support. Early LSTL is mainly related to cancer progression while late LSTL are often decided in front of unfavourable evolution of the acute complications in patients with better cancer prognosis. Conclusions: This study, restricted to cancer patients dying in the ICU, showed that respiratory failure and infection were the leading cause of ICU admission. Infection was the first cause of death. The majority of the cancer patients dying in the ICU had LSTL. All patients with no LSTL died with mechanical invasive ventilatory support. Functional stages, the existence of an oncological treatment project and the evolution of complication leading to ICU admission have a major impact in the decision of LSTL.

The importance of clinical predictors in the treatment of non-small-cell lung cancer (NSCLC) has increased during the last decade. This retrospective study analyzed the combined patient-level data from two phase II trials that investigated the efficacy and safety of combination chemotherapy with vinorelbine and mitomycin in patients with locally advanced or metastatic NSCLC. The aim of this analysis was to determine if patients' baseline and disease characteristics, including histology, gender, smoking history, and expression of TTF-1, might be potential predictors of outcome.Response rates, unadjusted survival times, and Cox covariate-adjusted hazard ratios (HRs) were calculated. Results were reported separately for each subgroup in each individual trial and in the pooled data set.A total of 175 patients were included in this analysis. Adjusted HRs for both overall survival (OS) and progression free survival (PFS) favored the nonadenocarcinoma histology subgroup, achieving a statistical significance for OS in the pooled data (n = 175; HR 0.68; 95 % CI 0.49-0.94; p = 0.019). TTF-1-negative immunohistochemistry was associated with a significantly higher response rate (25 vs. 0 %; p = 0.04) and with a nonsignificant advantage in OS (n = 33; HR 1.23; 95 % CI 0.56-2.73; p = 0.608). Gender and smoking history were not strongly related to outcome.The results of this analysis indicate that patients with nonadenocarcinoma histology might get superior benefit from combination chemotherapy with vinorelbine and mitomycin. These results should be confirmed in a prospective study.

Thierry Berghmans,1 Myriam Remmelink,2 Ahmad Awada31Clinic of Thoracic Oncology and Department of Intensive Care, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; 2Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; 3Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, BelgiumAbstract: Targeted therapies are nowadays a treatment option in metastatic non-small cell lung cancer, for which oncogenic drivers have been identified. The epidermal growth factor-receptor tyrosine kinase inhibitors gefitinib and erlotinib, are the standard of care for patients in whom tumors are presenting with an activating epidermal growth factor-receptor mutation, with new active agents like afatinib reaching clinics in the near future. Other genetic abnormalities have been documented in squamous and non-squamous lung cancer. The EML4–ALK gene fusion is a rare event, occurring in around 5% of lung cancer, quite exclusively in adenocarcinoma with a predominance of young non/light smokers. Detection of ALK-positive tumors is challenging, as there is no gold-standard technique. Fluorescence in situ hybridization is the method used in prospective trials assessing the activity of crizotinib and is recommended by the American FDA. Crizotinib is the first orally active inhibitor of receptor tyrosine kinases, including ALK and ROS1, in clinical practice. Impressive results came from a phase I study and are now confirmed in a large phase II study with response rate of 60%, whatever the number of previous lines of chemotherapy. Other ALK inhibitors are currently in the preclinical phase, and some are showing promising results in early phase I/II studies. This review aims to present the current knowledge on the EML4–ALK gene fusion, the pitfalls for the pathologist and the clinician in searching this abnormality, and to review the existing literature on ALK inhibitors under development, focusing their role compared to chemotherapy in non-small cell lung cancer patients.Keywords: non-small cell lung cancer, EML4–ALK, crizotinib

While it may only be the third-leading neoplasm worldwide, lung cancer is the first cause of death by cancer in males and one of the first in females in industrialised countries. Overall, cure rate is only 10–15% and the majority of patients, most of whom are diagnosed at an advanced stage and will ultimately die from lung cancer progression or related complications. During the last few decades, palliative care has become a central element of the therapeutic approach to terminally ill cancer patients. Palliative care aims to improve quality of life and control symptoms but has no role in hastening death, although palliative care specialists can be involved in the end-of-life decision process when euthanasia or physician-assisted suicide are considered. The opinions of the cancer patient and their family, the treating physician, or both regarding their preferences in end-of-life decisions have been assessed in general studies not including a specific cancer type. Outside of religious or sociocultural particularities, suffering from pain or fatigue is a prominent factor associated with euthanasia requests and practice in cancer patients [1, 2]. Requests for euthanasia or assisted suicide are reported with higher frequency in poor-prognosis cancers, such as lung, pancreas, stomach, oesophagus, lip–mouth–throat or melanomas, in comparison with those having better life expectancy, such as as prostate or haematological tumours [3]. In this issue of the European Respiratory Journal , Pardon et al. [4] report the first study specifically dealing with euthanasia requests and practice in lung cancer patients. This prospective study was based on questionnaires sent to pulmonologists, oncologists and general practitioners immediately after the death of their patient. Among 115 deaths occurring during an 18-month period, 105 questionnaires were returned by the physicians, replies from specialists (91%) being more common than from general practitioners …

Background In the era of precision medicine, data obtained from sequencing the cancer genome of a patient can be integrated into clinical decision-making. Liquid biopsy using ctDNA is a non-invasive tool, which can circumvent unfeasible or unrepresentative tumor biopsies and allow continuous monitoring of the disease thereby contributing to rational drug delivery. Experimental procedures Precision-f is a feasibility molecular screening study that enrolled 34 patients with metastatic melanoma, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Results from targeted gene sequencing (TGS) of metastatic biopsies were presented at AACR 2015. The patients had a blood draw concomitantly with the metastatic biopsy for plasma isolation. Similar to biopsies, somatic mutations (substitutions, small insertions and deletions) were assessed using the Ion AmpliSeq™ Cancer Hotspot Panel v2, designed to amplify 207 amplicons covering 2800 COSMIC mutations from the 50 most commonly reported oncogenes and tumor suppressor genes with a sensitivity of 1%. All mutations identified in the biopsy and/or plasma samples using TGS are currently being validated using Droplet Digital PCR (ddPCR) technology. Results Evaluable ctDNA-derived sequencing data were available for 32 patients. The sequencing results between biopsies and plasma were fully concordant in 63% (20/32) of the patients. TGS of ctDNA failed to detect clinically relevant mutations (EGFR, PIK3CA, KRAS and BRAF) identified in the metastatic biopsies in 19% (6/32) of the patients. In contrast, biologically relevant mutations (STK11, KRAS, PIK3CA and SMO) not detected in tumor biopsies were found in the ctDNA in 9% (3/32) of the patients. Interestingly, in one CRC patient a KRAS G13D mutation still potentially associated with benefit to anti-EGFR therapy was detected only in the tumor biopsy whereas a KRAS A146T mutation mediating resistance to anti-EGFR therapy was detected solely in ctDNA. Tumor biopsies and plasma are currently being tested using ddPCR to validate the findings. The results of these analyses will be presented at the meeting. Conclusion Although technical challenges remain, ctDNA profiling appears to be a promising tool for precision oncology by allowing the identification of genomic alterations associated with drug resistance and tumor progression. Citation Format: Philippe G. Aftimos, Marion Maetens, Françoise Rothé, David Brown, Yacine Barèche, Alexandre Irrthum, Thierry Berghmans, Joseph Kerger, Alain Hendlisz, Michail Ignatiadis, Martine Piccart, Christos Sotiriou, Ahmad Awada. Circulating tumor DNA (ctDNA) as an alternative to tumor biopsies for precision oncology: The Jules Bordet Institute experience. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3962.

In a 56-year-old man with metastatic small-cell lung cancer, a persistent hiccup was refractory to classic treatments. Hyponatremia, neoplasic mediastinal involvement and liver metastases were though to be potential causative factors. Methylphenidate (MTP), a mild central nervous system (CNS) stimulant that is most commonly used for the treatment of attention deficit hyperactivity disorder, was started at a daily dose of 10 mg. It was rapidly efficient and well tolerated. This report suggests a potential advantage of MTP in the treatment of intractable hiccup in cancer patients.

Introduction Currently, there are limited data on the lung cancer patient at the emergency department. Our objective is to review the medical charts of those patients to determine the frequency and main causes of emergency consultations and the predicting factors for hospital admissions and deaths. Methods We conducted a retrospective study including all patients with lung cancer consulting at the emergency department of a cancer hospital. Results From January 1, 2008 to December 31, 2010, 269 patients with lung cancer presented at the emergency, corresponding to 548 consultations (8.3% of all 6575 visits). During the same period, 626 patients for lung cancer were treated in our institution meaning that 43% of them are consulting at least once the emergency department during the course of their disease. The main reasons for consultation were respiratory symptoms (22.3%) and fever (19.9%). Emergency visit leads to hospital admission in 63% of the cases. In multivariate analysis, the main independent predictor factor of hospitalisation is arrival by ambulance (odd ratio 12), which is also the principal predictor of death during hospitalisation (odd ratio 9.5). The presence of signs at physical examination is also an important factor. Conclusion Our study shows that emergency visit is a frequent event for lung cancer patients and has identified simple factors predicting hospitalisation and deaths.

Lung cancer is one of the most frequently occurring neoplasms and usually has a poor prognosis because most of the patients present with advanced or metastatic disease at the time of diagnosis. Numerous prognostic factors (PFs) have been studied, but the two most prominent, having both prognostic and operational values, are disease stage and performance status. Even if the literature on PFs in lung cancer is impressive, the number of publications specifically dealing with PFs in stage III non-small cell lung cancer (NSCLC) is limited. We reviewed the literature on this topic and separated the available information into three groups: conventional PFs, metabolic criteria (standardized uptake value [SUV] measured on18F-FDG-PET) and new biomarkers. Performance status and the distinction between stage IIIA and IIIB confirmed their prognostic value in stage III NSCLC. Other conventional PFs have been suggested such as age, weight loss, response to treatment and some characteristics describing the locoregional extension of the tumour. There is a place for the SUV as a PF for survival in early NSCLC, but its role in stage III NSCLC has to be further assessed. Some new biomarkers involved in cell cycle regulation or in apoptosis have been shown to have potential value. Their role needs to be confirmed in large prospective studies including conventional PFs to determine their independent value as a PF in stage III NSCLC. In conclusion, few PFs have been well evaluated in stage III NSCLC. New studies, taking into account the modifications derived from the 7th international staging system of the UICC, have to be performed.

The clinical impact of c-erbB-3 has seldom been assessed in patients with non small cell lung cancer (NSCLC).Forty-three NSCLC patients treated by erlotinib for c-erbB-3 and EGFR expression were investigated by immunohistochemistry analysis.Two partial responses, one minor response, two stable diseases and twenty progressive diseases were observed at the first evaluation. Seventeen patients died before evaluation. Median EGFR expression was 70% of the cancer cells. Forty-two percent of the tumours co-expressed c-erbB-3 and EGFR without any difference according to histology or disease stage. There was no correlation between c-erbB-3 and EGFR expression. Median survival time was 2.6 months and the six months survival rate was 21%. There was no detectable impact of EGFR (p=0.94) or c-erbB-3 (p=0.93) expression on survival.In this small particular cohort of NSCLC patients receiving salvage therapy with erlotinib, there was no correlation between c-erbB-3 expression and clinical parameters, nor between cerbB-3/EGFR expression and outcome.

Le patient cancereux peut presenter des complications tres diverses liees a son traitement. Ce chapitre, axe sur l’urgence, aura pour objet de mettre en evidence les plus importantes ou les plus specifiques d’entre elles (a l’exception de celles couvertes ailleurs dans ce livre), le lecteur etant invite a se referer au site web en acces libre www.oncorea.com pour des informations complementaires, notamment sur les attitudes pratiques.

Editorial, SCOPUS: ed.j, info:eu-repo/semantics/published

Though acute myocardial infarction is one of the most frequent causes of ST segment elevation, there are other, less frequent, reasons for such electrocardiographic changes. In the present case, a cardiac metastasis from a squamous cell lung carcinoma was responsible for these changes. The secondary lesion was located in the apex of the left ventricle and induced an ECG alteration mimicking myocardial ischaemia. The literature includes few reports that describe the relation between electrocardiographic changes and heart metastases, since heart metastases are not usually discovered except at autopsy.

Treatment with noninvasive ventilation (NIV) is feasible and effective in cancer patients. However, virtually no data are available on the role for NIV as a component of palliative care for patients with hematological malignancies. NIV can be used in patients with reversible causes of acute respiratory failure for whom potentially life-extending treatments are available. In patients with treatment-limitation decisions, NIV seems useful, producing hospital survival rates greater than 50%, although 90% of hospital survivors die within the next year. For patients who are very near the end of life and who are receiving comfort care only, NIV can be part of the palliative care and may improve distressing symptoms such as dyspnea, although there is no evidence that NIV is better than pharmacological treatments such as morphine. In all cases, the patient must be fully informed and asked to provide or deny consent.

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 similar to 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.

Background: The purpose of this study was to determine in limited small-cell lung cancer if locoregional irradiation concurrently with induction chemotherapy with cisplatin and etoposide prolongs survival when cisplatin is given daily as a radiosensitiser. Patients and methods: Two-hundred and four eligible patients were randomised between standard radiosensitised induction chemoradiotherapy (arm A) with cisplatin (90 mg/m 2 day 1) plus etoposide and daily radiosensitised induction chemoradiotherapy (arm B) with cisplatin (6 mg/m 2 /day) plus etoposide. Chemotherapy and chest irradiation (39.90 Gy in 15 fractions >3 weeks) both started on day 1. Results: There was no difference in survival between both arms with respective median, 2 and 5 years of 15.5 months, 35% and 18% in arm A and 17.0 months, 38% and 21% in arm B (P = 0.50). Performance status and T status were identified as independent prognostic factors for survival. In terms of local control rate, there was a statistical trend in favour of arm A with 2% only local relapse versus 10% in arm B. Daily cisplatin radiosensitisation was associated with more oesophagitis and thrombopenia but less nephrotoxicity. Conclusion: Induction chemoradiotherapy resulted in both arms in good long-term survival, comparable to the best reported results and without improvement by daily cisplatin administration.

The treatment of massive and/or symptomatic pericardial effusion in patients with cancer remains a subject of discussion. Medical and surgical management have been proposed. In the present study, we aimed to determine the prognostic factors influencing survival of cancer patients admitted in intensive care unit (ICU) with severe pericardial effusion to better select the treatment strategies. All patients with cancer and massive or symptomatic pericardial effusion were retrospectively analyzed. Patients were followed up until death or last time known to be alive. Univariate and multivariate analyses were performed to determine prognostic factors influencing survival. Between January 1999 and August 2004, 55 eligible patients were admitted in the ICU for pericardial effusion, including 30 with lung cancer, 9 with breast cancer, 5 with hematological malignancies, and 11 patients with other types of solid tumors. Forty-three patients underwent a surgical drainage. No operative death occurred. Four patients presented with an asymptomatic recurrence. Median survival of the entire group was 112 days. Survival rates for 1, 2, and 3 years were 27%, 17%, and 12%, respectively. In univariate analysis, the following variables were significantly associated with a reduced survival: histopathological diagnosis of malignant pericardial effusion, age (>60 years), the volume of pericardial effusion (

Hypothesis The 2-[ 18 F]-fluoro-2-deoxy-d-glucose positron emission tomography is an imaging tool for assessing clinical tumor, node, metastasis in non-small cell lung cancer (NSCLC). Primary tumor standardized uptake value (SUV) has been studied as a potential prognostic factor for survival. However, the sample sizes are limited leading to conduct a meta-analysis to improve the precision in estimating its effect. Methods We performed a systematic literature search. For each publication, we extracted an estimate of the hazard ratio (HR) for comparing patients with a low and a high SUV and we aggregated the individual HRs into a combined HR, using a random-effects model. Results We found 13 eligible studies dedicated to NSCLC. Most of them included patients with stages I to III/IV and used a SUV assessment corrected for body weight. Number of patients ranged from 38 to 315 (total: 1474); 11 studies identified a high SUV as a poor prognostic factor for survival although two studies found no significant correlation between SUV and survival. SUV measurement and SUV threshold for defining high SUV were study dependent, eight studies looked for a so-called best cutoff (maximizing the logrank test statistic) without adjusting the p value for multiplicity. Overall, the combined HR for the 13 reports was 2.27 (95% confidence interval [CI]: 1.70–3.02); excluding the studies proposing a "best" cutoff, it was 2.08 (95% CI: 1.431–3.04). Conclusion Our meta-analysis suggests that the primary tumor SUV measurement has a prognostic value in NSCLC; these results should be confirmed in a meta-analysis on individual patients' data.

The aim of the present study was to determine the potential benefit of conventional cisplatin-based chemotherapy on patients with advanced nonsmall cell lung cancer (NSCLC) and poor performance status (PS), defined as 60-70 on the Karnofsky scale. Retrospective analysis was carried out of a randomised trial performed in advanced NSCLC where 485 patients received three courses of gemcitabine+ifosfamide+cisplatin induction chemotherapy. Of the patients, 80% had good PS (Karnofsky 80-100) and 20% poor PS. Response rates were 38 and 28%, respectively. Clinical improvement, defined as achieving a good PS during chemotherapy, was observed overall in 25% of the poor PS patients, with rates of 38, 20 and 14%, respectively, in case of response, no change and progression. PS improved more quickly in the responders. Survival of patients with poor PS was significantly worse, but survival of responders was similar, irrespective of the initial poor or good PS. Although nonfatal toxicity was almost similar, there were more toxic deaths (including vascular and cardiac fatalities) in the poor PS patients (9.2 versus 2.1%). In conclusion, combination chemotherapy is associated with clinical improvement in a substantial number of patients with advanced nonsmall cell lung cancer of poor performance status.

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08-2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08-2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26-2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. Patients and methods: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m 2 on day 1, ifosfamide 3 g/m 2 on day 1 and gemcitabine 1 g/m 2 on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m 2 over 3 h every 3 weeks). Results: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and IP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. Conclusion: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment. © 2007 European Society for Medical Oncology.

8049 Background: Docetaxel (D) or Erlotinib (E) are registered second-line treatments for EGFR wild type NSCLC. Previous studies suggested a predictive value of the serum proteomic VeriStrat test (VS), assigning a good (VSG) or poor (VSP) classification in second-line therapy of patients (pts.) with NSCLC. EMPHASIS aimed at exploring a predictive interaction in SqNSCLC pts. The trial closed prematurely due to low accrual. Methods: EMPHASIS is a randomized phase III multicenter trial exploring the differential activity of second line E vs D on progression-free survival (PFS) in VSG vs VSP SqNSCLC. The expected hazard ratio (HR) of E vs D was 0.675 for the VSG patients (median PFS, E: 4.0 and D: 2.7 mo.), and 1.23 for the VSP patients (median PFS, E: 2.2 and D: 2.7 mo.). A sample size of 500 was needed to achieve 86% power for testing the expected interaction HR of 1.82 at a two-sided p-value of 0.05. Pts were randomized to receive treatment E150 mg p.o. daily or D 75 mg/m2 i.v. on day 1 of each 21 day cycl...

Un groupe de travail de l’ERS a mis en evidence de RPC en oncologie thoracique en Europe sans etude sur leur mise en pratique. Nous avons determine dans une population de patients atteints de cancer bronchique l’application pratique d’un PSO thoracique base sur des RPC Les dossiers de tous les patients non encore traites et pris en charge entre janvier 2009 et decembre 2012 ont ete revus apres accord du comite d’ethique. Tout nouveau traitement est propose en consultation multidisciplinaire (CMD) sur base d’un PSO base sur les RPC de l’European Lung Cancer Working Party. Sur les 354 patients, on compte 624 CMD (332, 174, 81 et 47 en 1re, 2e, 3e et suivantes lignes). Les principales caracteristiques des patients sont : hommes : 197 ; adenocarcinomes/epidermoides/petites cellules : 187, 79, 50 ; stades I & II, III, IV : 48, 75, 228. Le taux de CMD en 1re ligne a ete de 94 % avec 88 % en conformite avec le PSO et 77 % de traitements en accord avec les RPC. En 2e et 3e lignes, les taux ont ete respectivement de 93 et 91 % (CMD), 90 et 89 % (PSO), 55 et 63 % (RPC). En 1re ligne, les principales causes de non-application ont ete pour le PSO le refus du patient ou le choix du medecin et pour les RPC le manque de recommandations adequates pour des situations specifiques comme les comorbidites ou l’apparition de nouveaux traitements non encore abordes dans les RPC au moment de leur redaction. L’enorme majorite des patients fait l’objet d’une CMD avec un taux eleve d’application du PSO. Les RPC etre plus souvent mises a jour pour incorporer les nouveaux traitements des qu’ils deviennent disponibles.

Introduction Les doublets a base de cisplatine sont un standard therapeutique pour les CBNPC avances en 1 re ligne. Le but du travail est d’identifier des signatures biologiques predictives (reponse) et pronostiques (survie) afin de mieux selectionner les patients beneficiant d’une chimiotherapie. Methodes Les patients avec un CBNPC traites en 1 re ligne par cisplatine-vinorelbine et une lesion evaluable etaient eligibles. L’analyse de l’expression des ARNm (microarrays Agilent Technologies) et des miARN (TaqMan Low Density Arrays) a ete faite sur biopsies bronchiques pre-therapeutiques. Resultats Une biopsie pour les analyses transcriptomiques a ete obtenue chez 60 patients consecutifs. Aucune difference significative n’a ete observee entre les groupes de derivation et de validation pour les caracteristiques cliniques, le taux de reponse (43 % vs 41 %) ou la mediane de survie (25 vs 29 mois). Dans le groupe derivation ( n = 38), trois signatures predictives (deux basees sur ARNm et une sur miARN) ont ete obtenues. De meme, deux signatures basees sur l’expression des ARNm ou des miARN etaient associees a la survie. Aucune de ces signatures n’a pu etre confirmee dans un groupe de validation independant ( n = 22 patients). Conclusion Dans cette etude prospective, des signatures biologiques predisant la reponse et la survie dans un groupe de CBNPC traites par cisplatine-vinorelbine n’ont pu etre validees dans un groupe independant. Dans ce contexte, le role des ARNm et des miARN reste un sujet de recherche et l’utilisation des techniques a haut rendement est discutable.

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.

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., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Background. The MIP regimen (mitomycin, ifosfamide, cisplatin) demonstrated its effectiveness as firstline chemotherapy in phase II and III trials in NSCLC. We aimed to determine whether these results could be confirmed in a hospital population. Methods. Between 1987 and 2004, 204 patients with NSCLC received MIP in our institution. Patients treated in and off trials received the same combination of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6 mg/m2) every three weeks and were staged and followed in a similar way. Results. Response rates for patients treated in or outside trials were 36.8% and 40.7%, respectively. After multiple logistic regressions, the only statistically significant factor predicting objective response was stage. The median survival time was 54.6 and 43.7 weeks respectively for patients treated in and outside trials. In multivariate analysis, four factors were statistically significantly associated with better survival: good performance status (p = 0.003), normal LDH value (p < 0.001), early stage (p = 0.01) and active smoking (p = 0.03). Conclusion. Participation in a clinical trial was not associated with a significant difference in efficacy. This implementation study thus confirms the activity of the MIP regimen when used in the routine management of patients with NSCLC.

Summary 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.

New biological factors have not been extensively studied in stage III non-small cell lung cancer (NSCLC). We aimed to determine the role of p53 as a prognostic factor in such patients.p53 expression was assessed by immunohistochemistry and evaluated by three independent observers. The Cox model was used to assess the impact of clinical and biological factors on patient survival.Between 01/1987 and 07/2002, 93 stage III NSCLC patients were included. Twenty-eight had a p53-positive tumour. There was no survival difference among patients with p53-positive and -negative tumours (p = 0.46). In multivariate analysis, 3 factors were statistically significantly associated with survival: surgical resection (p = 0.009), good performance status (p = 0.02) and low creatinine level (p = 0.02).Good performance status, surgical resection and low creatinine level were independent favourable prognostic factors for survival in stage III NSCLC, while p53 was not, even in univariate analysis.

Summary Few chemotherapeutic agents have demonstrated their efficacy in malignant mesothelioma. The cisplatin plus doxorubicin combination has one of the highest response rates. Epirubicin is an anthracyclin, analogous to doxorubicin, with a different toxicologic pattern. As there are no data on the activity of the combination cisplatin plus epirubicin in malignant mesothelioma, the European Lung Cancer Working Party (ELCWP) designed a phase II study with response rate as primary objective. Sixty-nine eligible patients with malignant pleural mesothelioma were centrally registered. The majority of the patients were male ( n =59), had a Karnofsky performance status of 80 or more ( n =62) and presented with an epithelial histologic subtype ( n =43). Median age was 62 years. In nine patients, metastases were documented at the initial work-up, mainly in bone, lung and skin. Three hundred and twenty-four cycles of chemotherapy were administered. The main toxicities were nausea and vomiting, neutropenia and alopecia. Among 63 assessable patients, response rate was 19.0% (95% confidence interval [CI] 9–29%). Median survival was 13.3 months. In multivariate analysis, poor prognostic factors for survival were neutrophil count and CALGB groups 4–6. In conclusion, cisplatin plus epirubicin appears as an effective regimen in malignant mesothelioma, with a favourable toxicity profile. However, it does not demonstrate superior activity to other active regimens in this disease.

New biological factors have not been extensively studied in stage III nonsmall cell lung cancer (NSCLC). The aim of the present retrospective study was to determine the role of epidermal growth factor receptor (EGF-R) as a prognostic factor in stage III NSCLC, in addition to the stage and other known clinical factors. Clinical characteristics were retrieved from the patients' charts. Membrane immunostaining for EGF-R was evaluated by three independent observers. The Cox multivariate model, including all variables with a p-value of

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC., Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, SCOPUS: re.j, info:eu-repo/semantics/published

The recent publication of many randomised trials about (neo)adjuvant chemotherapy in resectable non-small cell lung cancer (NSCLC) has prompted our group to update a prior meta-analysis of the literature. Randomised studies published in French and English between 1965 and June 2004 were included in this analysis. A qualitative assessment of each trial was first performed using the European lung cancer working party (ELCWP) and the Chalmers' scales. In absence of statistically significant quality difference between positive and negative trials, a quantitative aggregation (meta-analysis) of the individual results was performed. Two trials for which data were available on ASCO virtual meeting website were also included in the meta-analysis. Twenty-five studies eligible for this analysis assessed chemotherapy as induction (n = 6) or adjuvant to surgery (n = 19). No quality difference was detected between positive and negative trials according to the two scores, whatever all trials were combined or only adjuvant chemotherapy studies were considered. The overall meta-analysis showed that the hazard ratio (HR) of the combined results was 0.66 (95% CI 0.48-0.93) in favour of the addition of induction chemotherapy to a standard surgical procedure and 0.84 (95% CI 0.78-0.89) in favour of adjuvant chemotherapy. The effect was significant for adjuvant chemotherapy in stages I and II with a HR of 0.88 (95% CI 0.83-0.94). It was not statistically significant in stage III although the trend was in favour of chemotherapy whatever adjuvant (HR = 0.85; 95% CI 0.69-1.04) or (neo)adjuvant (HR = 0.65; 95% CI 0.41-1.04) chemotherapy was tested. In conclusion, our meta-analysis shows the efficacy of adjuvant chemotherapy in stages I and II resected NSCLC. More data are needed to confirm such a role for induction chemotherapy. Further trials should separate stage III disease from earlier stages.

To evaluate the effectiveness of a specific oncologic scoring system-the ICU Cancer Mortality model (ICM)-in predicting hospital mortality in comparison to two general severity scores-the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Simplified Acute Physiology Score (SAPS II).All 247 patients admitted for a medical acute complication over an 18-month period in an oncological medical intensive care unit were prospectively registered. Their data, including type of complication, vital status at discharge and cancer characteristics as well as other variables necessary to calculate the three scoring systems were retrospectively assessed.Observed in-hospital mortality was 34%. The predicted in-hospital mortality rate for APACHE II was 32%; SAPS II, 24%; and ICM, 28%. The goodness of fit was inadequate except for the ICM score. Comparison of the area under the ROC curves revealed a better fit for ICM (area 0.79). The maximum correct classification rate was 72% for APACHE II, 74% for SAPS II and 77% for ICM. APACHE II and SAPS II were better at predicting outcome for survivors to hospital discharge, although ICM was better for non-survivors. Two variables were independently predicting the risk of death during hospitalisation: ICM (OR=2.31) and SAPS II (OR=1.05).Gravity scores were the single independent predictors for hospital mortality, and ICM was equivalent to APACHE II and SAPS II.

The present study was conducted to determine whether it is justifiable to adapt treatment to age in patients with non-small-cell lung cancer (NSCLC). All NSCLC patients treated at the Institut Jules Bordet who were 75 years old or over were prospectively entered in our database. Patients were divided into those who were "eligible" and those who were "ineligible" for clinical trials according to the standard criteria used by the ELCWP. The 604 consecutive patients treated for NSCLC between March 1995 and August 2001 included 60 (9.9%) aged 75 years or over. Their principal characteristics were as follows: median age 78 years (75-93); male-to-female ratio 45/15; stages I/II/III/IV in 16/1/23/18 cases (in 2 cases complete work-up was refused by the patient); squamous/glandular/other histology in 23/24/13 cases; the median performance status was 70 (30-100). Except for their age, 37 patients met the eligibility criteria for the ELCWP standard treatment study protocol in progress during the study period. Twenty-five (67.6%) of these patients received an adequate treatment according to the stage of the disease, and 5 (13.5%) refused conventional therapy and received less aggressive treatment or none at all. For 7 (18.9%) patients, an adapted treatment was chosen solely on the basis of their age. For patients with disease in stages I-III who underwent adequate treatment survival rates were equivalent to the results found in the literature, with median survival times of 770 days and 262 days for those with stage I-II and those with stage III disease, respectively. Survival rates for patients with stage IV disease ranged from 10 days to 17 months. NSCLC patients 75 years of age or more without significant co-morbidities can probably be treated in the same way as younger people with similar survival rates if their disease is in stages I-III. Because the number of patients was too small, our data do not allow us to provide meaningful conclusions for stage IV disease.

The prognostic value of epidermal growth factor receptor (EGF-R) for survival of patients with lung cancer remains controversial. The authors performed a systematic review of the literature in order to clarify its impact. Published studies were identified using an electronic search in order to aggregate the available survival results, after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to have dealt with EGF-R assessment in lung cancer patients on the primary site and to have analysed survival according to EGF-R expression. Among the 16 eligible studies, 14 assessed any nonsmall-cell lung cancer (NSCLC) subtype, one adenocarcinoma only and one squamous-cell carcinoma only. The overall median quality score was 56.3%, with no significant difference either between studies assessable or not assessable for meta-analysis or between studies with significant and nonsignificant results. One individual trial reported a survival benefit for patients with EGF-R expression, three a survival disadvantage and 12 no statistically significant difference. Eleven studies (2,185 patients) provided sufficient data to allow a meta-analysis of the survival results. EGF-R expression positivity was determined according to the cut-off as determined by the authors. The meta-analysis showed that EGF-R expression was not a statistically significant prognostic factor for survival in NSCLC. In the subgroup of studies using immunohistochemistry, statistical tests reached a significant level against EGF-R. Epidermal growth factor receptor might be a poor prognostic factor for survival in nonsmall-cell lung cancer. The amplitude of the impact is small, however, and may be subject to publication bias.

Vibrio cholerae was isolated from the blood cultures of a neutropenic patient treated with chemotherapy for non-small-cell lung cancer. Attempts to isolate Vibrio spp. from a rectal swab and stool were unsuccessful. Piperacillin/tazobactam treatment resulted in eradication of the microorganism from the patient's blood. Although Vibrio spp. have occasionally been the source of infection in immunocompromised patients, this report describes the first case of non-0:1 Vibrio cholerae bacteremia in a neutropenic patient with a solid tumour.

In order to clarify the role of haematological colony-stimulating factors (CSF) in the treatment of small-cell lung cancer, we performed a systematic review of the randomised trials published on this topic. Since 1991, 12 studies were eligible, including a total of 2107 randomised patients. They were divided into three groups: (1) maintenance of dose-intensity when chemotherapy was given at conventional doses and time intervals (seven trials); (2) accelerated chemotherapy with increased dose-intensity by reducing the delay between chemotherapy cycles (five trials); (3) concentration of chemotherapy on an overall shorter duration time with a lower number of cycles (one trial). Before quantitative aggregation, we performed a methodological assessment using two previously published quality scales (Chalmers and ELCWP). The median quality scores for the pooled 12 trials was 59.9% (range: 42.2-82.0%) for the ELCWP scale and 55.8% (range: 38.0-76.8%) for the Chalmers scale. No statistically significant difference was observed between positive (significant) and negative (non-significant) studies allowing us to perform a meta-analysis. A detrimental effect on response rate was associated with CSF administration in the maintenance group (RR 0.92; 95% confidence interval [CI] 0.87-0.97) without significant effect on survival (HR 1.004; 95% CI, 0.89-1.13). In the accelerated group, no significant impact on response rate (RR 1.02; 95% CI, 0.94-1.09) or survival (HR 0.82; 95% CI, 0.67-1.00) was found. Although no difference in response rate was observed, a reduced survival was associated with concentrated chemotherapy. In conclusion, the published data do not support the routine use of haematological colony-stimulating factors in the treatment of small-cell lung cancer (SCLC).

The role of p53, as a prognostic factor for survival in lung cancer, is controversial and the purpose of the present systematic review of the literature is to determine this effect.Published studies were identified with the objective to aggregate the available survival results after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to deal with p53 assessment in lung cancer (primary site) only, and to provide a survival comparison according to the p53 status.Among the 74 eligible papers, 30 identified p53 abnormalities as a univariate statistically significant poor prognostic factor and 56 provided sufficient data to allow survival results aggregation. There was no significant difference between the trials that either showed or did not show a prognostic effect of p53 according to the methodological score or to the laboratory technique used. The studies were categorized by histology, disease stage, treatment and laboratory technique. Combined hazard ratios suggested that an abnormal p53 status had an unfavourable impact on survival: in any stage nonsmall cell lung cancer (NSCLC) the mean (95% confidence interval) was 1.44 (1.20–1.72) (number of studies included in the subgroup was 11), 1.50 (1.32–1.70) in stages I–II NSCLC (n=19), 1.68 (1.23–2.29) in stages I–IIIB NSCLC (n=5), 1.68 (1.30–2.18) in stages III–IV NSCLC (n=9), 1.48 (1.29–1.70) in surgically resected NSCLC (n=20), 1.37 (1.02–1.85) in squamous cell carcinoma (n=9), 2.24 (1.70–2.95) in adenocarcinoma (n=9), 1.57 (1.28–1.91) for a positive immunohistochemistry with antibody 1801 (n=8), 1.25 (1.09–1.43) for a positive immunohistochemistry with antibody DO-;7 (n=16), and 1.65 (1.35–2.00) for an abnormal molecular biology test (n=13). Data were insufficient to determine the prognostic value of p53 in small cell lung cancer.In each subgroup of nonsmall cell lung cancer, p53 abnormal status was shown to be associated with a poorer survival prognosis.

Patients with locoregionally advanced and metastatic non-small cell lung cancer (NSCLC) have been shown to benefit from chemotherapy administration with improved survival in comparison to irradiation or best supportive care alone [1]. Meta-analyses have pointed out the central role of cisplatin [1]. Unfortunately, cisplatin use, particularly when high dosages are prescribed, is associated with chronic toxicity such as auditive, renal and neurological impairments, preventing long treatment. Carboplatin, a platinum analogue, has been developed with a different toxicological profile: chronic toxicity is minimal but haematological toxicity is much more severe. Now, the questions are —could carboplatin be used in combination with low-dose cisplatin in order to reduce chronic toxicity due to high-doses cisplatin and could cisplatin be substituted by carboplatin with an equivalent efficacy? In a phase II randomized trial, the European Lung Cancer Working Party (ELCWP) compared high-dose cisplatin (120 mg/m 2 ) with moderatedose cisplatin (60 mg/m 2 ) plus carboplatin (200 mg/m 2 ) in patients with advanced NSCLC [2]. The combined arm was significantly associated with less renal (19 vs. 36%), auditive (4 vs. 16%) and neurological (0 vs. 16%) toxicity without significantly different response rates (23 vs. 21%). The same group assessed the role of the co-administration of cisplatin and carboplatin in comparison with moderate dosage of cisplatin alone in a phase III trial [3]. Two hundred and ninety-seven patients were randomized between carboplatin (200 mg/m 2 ) and moderate-dose cisplatin (60 mg/ m 2 ) or cisplatin alone (50 mg/m 2 ) regimens, both including ifosfamide and mitomycin. The administration of the combined regimen was not associated with a survival advantage. The substitution of cisplatin by carboplatin in the management of NSCLC remains a controversial issue. Few randomized phase III studies have directly compared both drugs. The ELCWP randomized 228 eligible patients with advanced NSCLC to receive cisplatin (120 mg/m 2 ) or carboplatin (325 mg/m 2 ) in association with etoposide

Objective To assess the prevalence of synchronous roentgenographically occult lung carcinoma (ROLC) in patients with resectable roentgenographically visible lung cancer (RVLC). Methods Patients undergoing surgery for RVLC in the same University Hospital were prospectively evaluated before surgery by fluorescence bronchoscopy under local anesthesia to detect synchronous ROLC. All abnormal areas, with the exception of the RVLC, had biopsies made. Results From June 1996 to January 1999, 43 patients (male/female ratio: 1.7/1.0) were evaluated before lobectomy (n = 34) or pneumonectomy (n = 10) for 44 primary RVLC. There were 10 T1N0, 19 T2N0, 1 T1N1, 9 T2N1, 1 T3N0, 3 T1N2, and 1 T3N1 lesions. The histologic type was mainly squamous carcinoma (n = 21) and adenocarcinoma (n = 14). All but two patients were smokers or ex-smokers (mean ± SD, 48 ± 28 pack-years). A total of 177 endobronchial biopsies were performed (4.1 ± 2.5); 8 were too small to be informative, 43 showed non-preneoplastic alterations, and 50 were normal. There were 7 basal cell hyperplasias, 56 metaplasias, 9 dysplasias, and 4 carcinomas in situ (CIS). All the dysplasias and CIS lesions were observed in eight subjects. The synchronous CIS were treated by surgery (n = 1) or localized therapeutic modalities (n = 3). Conclusions The high prevalence of synchronous early lung cancers (9.3%) as well as metaplasia and dysplasia in this series of patients with resectable RVLC suggests that fluorescence bronchoscopy may be a useful adjunct in the preoperative evaluation of lung cancer.

Although cisplatin-based chemotherapy regimens were introduced in the late 1970s for the management of advanced non-small cell lung cancer, more than 15 years of randomized trials were required to produce convincing data showing survival improvement in comparison to best supportive care alone. The routine use of chemotherapy in this indication is still the object of considerable debate in Europe and North America as reflected by different recent editorials or reviews (Haskel 1991; Souhami 1996; Vokes 1995; White 1995; Souquet et al. 1995; Sorensen 1997).