[Rapid outpatient diagnostic pathways for lung cancer: Evaluation after one year]. / Parcours de diagnostic rapide du cancer du poumon : évaluation à un an.

INTRODUCTION: The introduction of coordinated care pathways for lung cancer diagnosis and treatment is a complex process. The purpose of the French Cancer Plan 2014-2019 was to improve referral to treatment waiting times in people with suspected malignancy. The aim of this study was to assess a rapid outpatient diagnostic program for lung cancer established in 2016. METHOD: This retrospective study was carried out in the Pulmonology Department at Tenon Hospital, Paris, France between May 2016 and May 2017. RESULTS: During this period, 118 patients (60%) of patients in the pathway were diagnosed with lung cancer. The median waiting time to first consultation (D1) was 4 (2-7) days. The median waiting time between diagnosis and treatment decision (D4) was 4 (0-8) days. The median waiting time to the first treatment (D5) was 10 (4-15) days for chemotherapy and 27 (16-34) days for surgery. The median waiting time between the first abnormal chest X-ray and the first treatment (D6) was 49 days (34-70). CONCLUSION: Referral to treatment waiting times was consistent with international recommendations. Coordinating nurses improved care pathways in lung cancer patients.

[How to reduce lung cancer mortality among people living with HIV?] / Comment réduire la mortalité par cancer du poumon chez les personnes vivant avec le VIH ? Du sevrage tabagique au dépistage radiologique.

Lung cancer is the leading cause of cancer related death among people living with HIV (PLHIV). Tobacco exposure is higher among PLHIV (38.5%) and mainly explains the increased risk of lung cancer. To reduce lung cancer mortality, two approaches need to be implemented: lung cancer screening with low-dose thoracic CT scan and smoking cessation. Low dose CT scan is feasible in PLHIV. The false positive rate is not higher than in the general population, except for cases with CD4 <200/mm3. The impact on survival remains to be assessed. Despite the high prevalence, smoking cessation research among PLHIV is scarce. Very low quality data from 11 studies showed that more intensive smoking cessation interventions were effective in achieving short-term abstinence. A single randomized phase 3 trial showed the superiority of varenicline compared to placebo in long-term smoking cessation. The maximum benefit of reducing lung cancer mortality should be obtained by combining smoking cessation and lung cancer screening.

Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group.

Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti-HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.

BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

2014 update on non-small cell lung cancer (excluding diagnosis).

Lung cancer (LC) is a major public health issue because of its frequency, but especially because of the severity of this disease. The epidemiology has changed with an increased incidence in non-smokers and women. The ATS/ERS/IASLC classification of adenocarcinomas was modified in 2011, and they are now the most frequent histological subtype. More than half the cases of LC are diagnosed at the metastatic stage. Biopsies must provide tissue samples that are quantitatively large enough and of a good enough quality for diagnosis and to search for biomarkers. When the cancer seems to be localized, precise staging must be obtained. Treatment is based on the TNM classification. In localized stages, lobectomy associated with lymph node dissection is the standard therapy. Intraoperative chemotherapy improves survival in case of lymph node infiltration. Stereotactic radiation therapy and radiofrequency can be considered as specific cases. In cases with local progression, treatment is more controversial. In the presence of metastases, the goal is not a cure, but improving survival and quality of life. Numerous advances have been made with personalized treatment, (in particular in relation to the histological type and oncogenic addiction in tumors, access to new drugs, and improved management). Clinical research in thoracic cancer is very active. The fight against tobacco should remain a priority.

[Lung cancer and HIV infection]. / Cancer du poumon et infection par le Virus de l'Immunodéficience Humaine.

AIDS was the cause of the majority of deaths from HIV infection before 1996 but since the introduction of antiretroviral therapies the causes of mortality have changed considerably. In 2010, 75 % of deaths were due to diseases other than AIDS, the majority being cancers. Lung cancer is the most common in terms of both incidence and mortality. It shows specific features when compared to the general population: there is an excess risk due to heavy smoking but also probably due to immunosuppression. The age of onset is younger and the prognosis worse than in the general population. Management is difficult, partly due to the aggressive nature of the tumor and partly to co-morbidities and potential interactions between anticancer and antiretroviral therapies. A phase II therapeutic trial (IFCT-CHIVA 1001) is under way nationally.

A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial).

HYPOTHESIS: There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC). METHODS: This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases. RESULTS: A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed. CONCLUSIONS: This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.

Clinical and molecular features in patients with advanced non-small-cell lung carcinoma refractory to first-line platinum-based chemotherapy.

Most of the cases of non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage and are treated with platinum-doublet chemotherapy. However, some patients are refractory to this treatment. The aim of this study was to identify the clinical and molecular characteristics of patients with refractory disease. All consecutive patients between 2003 and 2006, who received a platinum-doublet chemotherapy as first-line treatment for stage IIIb-IV NSCLC, were included. Refractory patients were defined as early progressive disease (PD) at the first evaluation of chemotherapy according to WHO criteria. The clinical, histo-pathological, and molecular characteristics (EGFR: exon 19, 20, 21 and KRAS: exon 2 by PCR sequencing; ALK by immunohistochemistry) and survival of refractory patients with initial PD (r-patients) and controlled disease (c-patients) were compared by univariate analyses. Factors that differed between the two groups (p-value <0.25 in univariate analyses) were entered into multivariate analysis. In this study, 178 patients were included. The first tumor assessment was carried out after a median of three cycles (range 1-4). Forty-six (25.8%) patients were refractory. Clinical presentation was similar between r- and c-patients. The sarcomatoid histological subtype was more common in r-patients than c-patients (10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%, p=0.224) and KRAS mutations (11.1% vs. 5.7%, p=0.357), and the expression of ALK (6.3% vs. 2.5%, p=0.327) did not differ significantly between the two groups. In multivariate analysis, sarcomatoid histological subtype was the only factor associated with early PD (OR=7.50; 95%CI: 1.02-55.45; p=0.048). r-Patients had significantly shorter survival than c-patients (median 5 months (IQR 3.2-9.9) vs. 15.4 months (IQR 9.9-22.5), respectively; p<0.0001). In conclusion, patients with early PD under platinum-doublet chemotherapy had shorter survival than c-patients. Sarcomatoid histological subtype was the only independent factor associated with early PD.

[Neurologic paraneoplastic syndrome with anti-CV2/CRMP5 antibodies revealing a small cell lung cancer. Effectiveness of the lung cancer treatment]. / Syndrome neurologique paranéoplasique à anticorps anti-CV2/CRMP5 révélateur d'un cancer bronchique à petites cellules. Efficacité du traitement du cancer bronchique.

INTRODUCTION: Paraneoplastic neurological syndrome associated with anti-CV2/CRMP5 antibodies are rare. Various clinical manifestations can occur, cerebellar ataxia, polyneuropathy, optic neuritis with NORB or uveitis. Small cell lung carcinoma is generally responsible. CASE REPORT: We report the case of a 64-year-old man who developed visual symptoms with papilledema, cerebellar signs, polyneuropathy confirmed with a neurophysiological studies. Anti-CV2/CRMP5 antibodies were present. A small cell lung carcinoma was responsible for this paraneoplastic syndrome revealing the cancer. The paraneoplastic syndrome improved with radio chemotherapy of the cancer alone. CONCLUSION: A paraneoplastic neurological syndrome must be evoked in case of an atypic neurological syndrome. This diagnostic can be confirmed by the presence of anti-neuronal antibodies. In this case, a small cells cancer of the lung must be research.

[A simple view on lung cancer biology: the MET pathway]. / Un regard simple sur la biologie du cancer bronchique : MET.

MET is a cell membrane tyrosine kinase receptor for its ligand the hepatocyte growth factor (HGF), also called scatter factor (SF). MET conveys mitogenic, motogenic and proangiogenic signals, important during embryonic development and during the development of cancer. Activation of the HGF-MET pathway seems to be associated with a poor prognosis in lung cancer. Activation in lung cancer may be related to several molecular anomalies: ligand overexpression, receptor overexpression, genomic amplification or MET mutation. In MET amplified or mutated lung cancer, MET may be an important oncogene, as the tumor appears "MET addicted". In other lung cancers, MET may be implicated in tumour progression by tissue invasion and formation of metastases. MET amplification is also a mechanism known to be implicated in 20% of secondary resistance to EGFR inhibitors in patients presenting EGFR mutated lung cancer. Different strategies of MET inhibition in lung cancer are being studied, particularly in EGFR mutated lung cancer. In this review we discuss the structure of the MET receptor, the activated pathways, the main genomic anomalies in lung cancer and the development of MET inhibitors.

Coexisting pulmonary nodules in operable lung cancer: prevalence and probability of malignancy.

INTRODUCTION: Coexistence of pulmonary nodules in operable non small cell lung cancer (NSCLC) may influence the therapeutic indication. The aim of this study was to evaluate prospectively the prevalence and the probability of malignancy of pulmonary nodules in operable lung cancer. METHODS: From a prospective database, all surgically treated patients diagnosed with NSCLC from 1998 to 2003 were retrospectively reviewed. Patients presenting pulmonary nodule(s) were identified. RESULTS: Two hundred thirty nine patients had a complete resection for a NSCLC and 56 patients (24%) presented altogether 88 nodules on thoracic CT. Twenty-four of these nodules (27%) were malignant, 28 (32%) benign and 36 (41%) of undetermined nature. Five factors associated with nodule's malignancy were identified: tumour histology (non-squamous (non-SCC) 44% vs. SCC 7%, p=0.001), localization of the nodules in an upper lobe (vs. other lobe, p=0.004), co localization in the same lobe as the NSCLC (vs. another lobe, p=0.03), nodule size (p=0.05) and shape (speculated vs. non spiculated, p=0.02). From these factors, a probability score was assessed with a malignancy rate in SCC of 0% in nodules presenting ≤ 1 feature, 33% with 2 features and 100% with ≥ 3 features and in non-SCC of 40% with 1 feature, 82% with 2 features and 100% with 3 ≥ features. CONCLUSION: Diagnosis of satellite nodules associated with early stage NSCLC is common. We developed a predictive score to estimate the probability of malignancy which may be a precious aid in the management of pulmonary nodules associated to a NSCLC.

[A phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non squamous, non-small cell lung cancer (NSCLC)]. / Protocole IFCT 0803--Étude de phase II évaluant l'association de cétuximab à une radiothérapie et chimiothérapie concomitante par cisplatine et pémétrexed dans le traitement des cancers bronchiques non à petites cellules non épidermoïdes de stade III, inopérables.

BACKGROUND: Cisplatin-based chemotherapy and concurrent radiotherapy are the standard treatments for locally advanced unresectable NSCLC. New therapeutic combinations using molecular targeted drugs are needed. METHODS: Eligible patients with previously untreated stage III non squamous, NSCLC will receive thoracic radiation (66 Gy) along with cisplatin (75 mg/m(2)) and pemetrexed (500 mg/m(2)) on day 1 administered intravenously every 21 days for four cycles; weekly cetuximab will be added from the first week of therapy. The primary objective of this phase II study (IFCT 0803) is to assess the disease control rate at the 16th week, one month after the completion of the treatment. Based on a two-stage Simon approach, a total of 106 patients are required with an interim analysis of the first 34 planned. EXPECTED RESULTS: This trial will provide information on the feasibility, efficacy and tolerability of this new therapeutic combination. Should the primary objective be achieved, a phase III randomised study testing the position of cetuximab could be considered.

[Association between thymic MALT lymphoma and Sjögren's syndrome]. / Association d'un lymphome thymique de type MALT et d'un syndrome de Gougerot-Sjögren.

INTRODUCTION: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare pathology, often associated with autoimmune diseases. The authors report the case of an Asian woman with Sjögren's syndrome. OBSERVATION: A 48-year-old Chinese woman, without past medical history and a non-smoker, presented an alteration in her overall condition, dyspnoea at exercise, inflammatory polyarthralgia, and a dry eye and mouth syndrome over the last few months. Thoracic tomodensitometry detected an anterior heterogenic cystic mediastinal mass. A mediastinotomy was performed. The diagnosis of the surgical biopsy was thymic MALT lymphoma. The authors also diagnosed Sjögren's syndrome with the presence of four diagnostic criteria. Chemotherapy by rituximab, cyclophosphamide, vincristine, prednisone induced major tumoral regression. The patient declined surgery and will be monitored. CONCLUSION: Thymic MALT lymphoma is a rare pathology. There is a high correlation with autoimmune diseases, like Sjögren's syndrome. Its appearance is that of an anterior mediastinal mass with a cystic component. The treatment is not well codified and is most often based on surgical resection, eventually followed by chemotherapy or radiotherapy. As far as the authors know, this is the second case of thymic MALT lymphoma treated by exclusive chemotherapy.

[Endobronchial lipoma: imaging findings. A case report]. / Lipome endobronchique: apport de l'imagerie. A propos d'un cas.

Endobronchial lipoma is a rare benign bronchial tumour. A search should be carried out on submillimetre MDCT scan slices in patients presenting segmental or lobar collapse or recurrent pulmonary infection in the same bronchial territories. The authors report MDCT and MR imaging in a patient with endobronchial lipoma discovered on an MDCT scan.

[Bevacizumab and invasive procedures: practical recommendations]. / Bevacizumab et actes invasifs: recommandations pratiques.

As first line chemotherapy Bevacizumab, associated with a platinum based regime, improves survival in patients with metastatic, non small cell, non epidermoid bronchial carcinoma. Marketing authorization for this indication was obtained in 2007. This treatment produces specific secondary effects related to its anti-angiogenic action. Physiologically, vascular endothelial growth factor (VEGF) is important in the process of scar formation. Bevacizumab inhibits scar formation and may encourage bleeding. The aim of this article is to analyse the specific risks associated with invasive procedures and to produce practical recommendations. Unfortunately there are few data in the literature. We depend, therefore, principally on studies of neo-adjuvant chemotherapy in metastatic colo-rectal cancer prior to excision of hepatic metastases and on our own experience of excision of pulmonary metastases from solid tumours treated with bevacizumab. We recommend a delay of 2 days between implantation of an intravenous device and the initiation of bevacizumab, a delay of at least 5 weeks between the last injection of bevacizumab and invasive surgery and a delay of 4 weeks between surgery and the initiation of bevacizumab treatment. Obviously, referral to a medico-surgical team experienced in the management of these patients is strongly recommended.