Potential lung cancer screening outcomes using different age and smoking thresholds in the ANRS-CO4 French Hospital Database on HIV cohort.

OBJECTIVES: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility. METHODS: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer. RESULTS: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer. CONCLUSIONS: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.

BACKGROUND: Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/ß. We explored the feasibility and efficacy of adjuvant pazopanib in this population. PATIENTS AND METHODS: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. RESULTS: A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23-55] with P800, increasing to 69% (95% CI 50-84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%-86%) with pazopanib and 83% (95% CI 74%-92%) with placebo [hazard ratio = 1.3 (95% CI 0.6-2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72-94) with pazopanib and 94% [95% CI 88-100] with placebo [hazard ratio = 1.8 (95% CI 0.6-5.5), P = 0.26]. CONCLUSIONS: In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the French intergroup (IFCT) and the groupe d'Oncologie de langue francaise (GOLF).

BACKGROUND: Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. METHODS: A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. RESULTS: The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55-74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. CONCLUSIONS: Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

[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.

[Brain and medullar neurosarcoidosis, complicated by stroke with local vasculitis]. / Neurosarcoïdose cérébrale et médullaire compliquée d'un accident vasculaire cérébral avec vasculite locale.

Central nervous system localizations of sarcoidosis remain rare. The brain, mainly the posterior fossa, or the spinal cord, mainly cervical, may be involved. We report the case of a white female presenting a stroke of the head of the caudate nuclei with spontaneous hemorrhage transformation related to and associated with rare encephalic and spinal cord sarcoidosis. The magnetic resonance angiography (MRA) of the intracranial vessels showed images of vasculitis. Treatment of the neurologic localizations was difficult.

[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.

[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.

[How to treat the relapse of NSCLC after surgery and chemotherapy? IFTC 0702 randomized phase III study]. / Comment traiter la rechute du CBNPC après une chirurgie et chimiothérapie?

BACKGROUND: As chemotherapy gains wider acceptance for the treatment of earlier stages of NSCLC, particularly in the adjuvant and neoadjuvant setting, physicians face a growing population of high performance status patients who have relapsed after their first-line chemotherapy. The type of second-line chemotherapy after initial adjuvant or neoadjuvant treatment with a platinum-based regimen remains largely undefined. The current study has been designed to compare the classical mono chemotherapy docetaxel with a docetaxel cisplatin doublet. METHODS: Patients will be randomized in 2 arms. Arm: docetaxel cisplatin (cycles repeated every 21 days), 4 cycles followed by 2 cycles of docetaxel alone in case of objective response or stabilisation. Arm B: docetaxel alone (cycles repeated every 21 days), 4 cycles followed by 2 cycles of docetaxel alone in case of objective response or stabilisation. EXPECTED RESULTS: 300 patients will be randomized with a statistical hypothesis of a progression free survival of 3 months in the control arm and of 4.5 months in the experimental arm.

[IoNESCO trial: Immune neoajuvant therapy in early stage non-small cell lung cancer]. / Inhibiteurs du check-point immunitaire en néo-adjuvant dans les cancers bronchiques non à petites cellules localisés : essai IoNESCO.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) is a checkpoint receptor that facilitates immune evasion by tumor cells, through interaction with programmed cell death-1 (PD-1), a receptor expressed by T-cells. Durvalumab is an anti-PD-L1 monoclonal antibody that blocks PD-L1 interaction with PD-1 on T-cells, countering the tumor's immune-evading tactics. Phase I/II studies demonstrated durable responses and manageable tolerability in heavily pre-treated patients with non-small cell lung cancer (NSCLC). METHODS: This phase II study is designed to administrate three durvalumab IV infusions (10mg/kg at day 1, 15, 29) before surgery, to patients with pathologically confirmed NSCLC, clinical stage IB (>4cm) or stage II, ≥18 years of age, WHO performans status 0-1, without selection on PD-L1 expression. Preoperative chemotherapy and radiation therapy are not permitted. The primary objective is feasibility of complete surgical resection. Major pathological response on surgical tissue, defined as 10% or less remaining tumor cells, will be a secondary objective. Additional secondary objectives include tolerance, adverse effects, delay between start of treatment and surgery, response rate (RECIST 1.1), metabolic response rate, postoperative adverse events, disease-free survival and overall survival. A rate of complete resection<85% (P0) is considered unacceptable. P1 hypothesis is of 95%, and with a study power of 90% and an alpha risk of 5% (two-steps Fleming's procedure), 81 patients are required. EXPECTED RESULTS: To establish whether neoadjuvant immunotherapy is feasible and could improve the survival of patients with early-stage NSCLC.

1,25(OH)2D2 production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemic patients with tuberculosis.

To compare extra-renal 1,25(OH)2D3 production in different types of granulomatous disease, and to identify the cell types responsible, we have evaluated the conversion of 25(OH)D3 in 1,25(OH)2D3 by uncultured cells recovered by bronchoalveolar lavage and blood mononuclear cells from normocalcemic patients with sarcoidosis and tuberculosis. 1,25(OH)2D3 was produced both by lavage cells (12/12 tuberculosis patients, 2/6 sarcoidosis patients) and blood mononuclear cells (3/5 tuberculosis patients, 0/3 sarcoidosis patients) from patients but not controls, but significantly greater amounts were produced by lavage cells from tuberculosis patients than those of sarcoidosis patients (P less than 0.001). 1,25(OH)2D3 production by lavage cells from tuberculosis patients correlated with the number of CD8+ T lymphocytes present but not other cell types. T lymphocytes appeared to be an important source of 1,25(OH)2D3 production, since purified T lymphocytes from all patients with tuberculosis produced 1,25(OH)2D3, and 1,25(OH)2D3 production by these cells correlated closely with that produced by unseparated lavage cells. Because 1,25(OH)2D3 can improve the capacity of macrophages to kill mycobacteria, our results support the conclusion that macrophage-lymphocyte interactions, mediated at least in part by 1,25(OH)2D3, may be an important component of a successful antituberculous immune response.

[Neoadjuvant chemoradiation in non-small cell lung cancer]. / La chimioradiothérapie préopératoire des cancers bronchiques non à petites cellules.

In 2006 preoperative chemoradiation is a major part of the treatment of stage III locally advanced non-small cell lung cancer. Previous studies have clearly demonstrated the feasibility both regarding toxicities and resectability rates of the sequential and concurrent combination of radiation to chemotherapy in a neoadjuvant setting. However, induction chemoradiation has never been randomly compared to exclusive preoperative chemotherapy. Besides, the doses of radiation and the optimal drug combination remain undetermined at the time. Regarding the global therapeutic strategy of stage III non-small cell lung cancer, recently reported phase III trials evaluating the role of surgical resection after induction chemotherapy or chemoradiation, all showed the prognostic importance of the tumoral and mediastinal downstaging to select patients really benefiting from surgery. These developments make of the treatment of locally advanced non-small cell lung cancer a model for multimodal therapeutic strategies combining chemotherapy, radiotherapy and surgery.

[Postoperative chemotherapy in non-small cell lung cancer]. / La chimiothérapie postopératoire des cancers bronchiques non à petites cellules.

Since 2000, seven prospective randomized studies were published or reported comparing surgery and surgery with post-operative chemotherapy for the treatment of non-small cell lung cancer (NSCLC). Four trials (IALT, UFT, JBR10 and ANITA) are positive and have proved the benefit obtained with post-operative chemotherapy for the stages II and IIIA. For the stage IB, this survival increase is also probable, especially for the tumors higher than 4 cm. Several biologic markers are under investigation as predictors of the benefit of the chemotherapy.

[Exogenous lipoid pneumonia associated with pulmonary and hepatic sarcoidosis]. / Pneumopathie lipidique exogène associée à une sarcoïdose systémique avec atteinte hépatique nodulaire.

INTRODUCTION: In a patient with basal alveolar shadowing the diagnosis of exogenous lipoid pneumonia (ELP) requires a past history of chronic ingestion of liquid paraffin and the presence of numerous macrophages containing oil droplets in the bronchial lavage (BL). Additional radiological abnormalities suggest an associated disease, notably infection or cancer, as has been described in the literature. CASE REPORT: We report the case of a 50 year old woman presenting with alveolar shadowing in the left lung associated with ipsilateral mediastinal nodes and a pleural effusion in addition to two hepatic nodules. As the diagnosis of ELP did not explain the radiological features a thoracotomy and liver biopsies were performed. Histological examination of the hepatic, pulmonary and lymph node biopsies excluded cancer and mycobacterial disease and showed a florid granulomatous foreign body reaction associated with pulmonary and hepatic sarcoidosis. After a 3 month course of oral corticosteroids the mediastinal lymphadenopathy, pleural effusion and hepatic nodules resolved. The patient has maintained her recovery without further treatment for 4 years. CONCLUSION: The final diagnosis was ELP and systemic sarcoidosis with nodular hepatic involvement.

[Predicting the response to chemotherapy in patients with non-small cell lung cancer]. / Prédiction de la réponse à la chimiothérapie dans les CBNPC : applications pratiques.

The prognosis of patients with non-small cell lung cancer continues to be poor. Multimodality treatment strategies including chemotherapy are indicated for almost all stages of the disease. To be able to customize chemotherapy based on individual patients' clinical or biological markers is a priority for translational research. Several possible markers need to be validated. In this review, we will discuss the potential of ERCC1 (excision repair cross complementary group 1) to predict sensitivity to cisplatinum, of tubuline-beta, class III for vinca-alkaloids and taxanes, RRM1 (ribonucleotide transferase subunit 1) for gemcitabine and lastly demographic parameters as well biological parameters for erlotinib. Data will be presented separately for patients with metastatic disease and for those where it is localized.

[IFCT-0302 trial: randomised study comparing two follow-up schedules in completely resected non-small cell lung cancer]. / Protocole IFCT-0302: essai randomisé de deux schémas de surveillance dans les cancers bronchiques non à petites cellules complètement réséqués.

BACKGROUND: The authorities advocate a minimalist attitude towards the follow-up of resected bronchial carcinoma (clinical examination and chest x-ray). A survey showed that 70% of French respiratory physicians have chosen to use the CT scanner and often endoscopy. The published data are equivocal and are often based on retrospective studies. Lung cancer is a good model for a study of post-operative surveillance. Recurrences often occur in easily observed areas, they may be detected while still asymptomatic and are sometimes potentially curable. Second primary tumours may develop at the same site. METHODS: The Intergroupe Francophone de Cancerologie Thoracique (IFCT) has initiated a trial comparing simple follow-up (clinical examination, chest x-ray) with a more intensive follow-up (CT scan, fibreoptic bronchoscopy). The surveillance will take place every 6 months for 2 years and then annually until 5 years. EXPECTED RESULTS: The main aim is to determine whether intensive follow-up improves patient survival. The opposite question is equally important. If an expensive and demanding follow-up does not affect the chances of cure these results will influence our practice.

[Therapeutic management of extensive bronchiolo-alveolar adenocarcinoma: chemotherapy or inhibitors of epidermal growth factor receptor tyrosine kinase?]. / Prise en charge thérapeutique des adénocarcinomes de type bronchiolo-alvéolaires étendus: chimiothérapie ou inhibiteurs de la tyrosine kinase du récepteur de l'epidermal growth factor?

Although the 1999 WHO classification, revised in 2004 excludes stage IIIB-IV tumors from the definition of bronchioloalveolar carcinoma (BAC) because they are unresectable, the first international workshop (November 2004, New York) devoted to this tumor emphasized the continuum between the BAC as defined by the WHO and adenocarcinomas with a BAC-like component which presents similar epidemiological, biological, clinical, radiological, prognostic and therapeutic features. These observations led to the suggestion to no include stage IIIB-IV ADC-BAC in studies designed for other non-small-cell lung cancers. The purpose of this review was to analyze the results of prospective studies currently available concerning the treatment of stage IIIB-IV ADC-BAC. No evidence is available with combination regimens using platine. Monotherapy with paclitaxel appears to have efficacy similar to inhibitors of epidermal growth factor receptor tyrosine kinase (gefitinib and erlotinib) (TKI-EGFR). The tolerance profile is in favor of using TKI-EGFR. It would appear that tumors responding to paclitaxel and to TKI-EGFR correspond to different diseases. These observations point out the importance of further studies examining the proper strategy and to search for new compounds for the treatment of extensive ADC-BAC.

[Tracheal replacement using the abdominal aorta. Comments on a case report]. / Remplacement de la trachée par l'aorte. Réflexions à propos d'un cas.

Tracheal replacement is an uncommon option because of the very limited number of indications and the large number of possibilities for resection anastomosis. There may nevertheless be situations were extensive resection leaves only one solution, tracheal replacement. To date, no prosthesis has provided long-term satisfaction. For tracheal replacement, the prosthesis must provide a large caliber airway which does not collapse during expiration and which enables the development of a ciliary lining, in addition to tolerance without rejection. Recent experimental work, then several clinical cases, would suggest that the abdominal aorta can be successfully transformed into a neotrachea. A temporary endoprosthesis is however necessary to prevent collapse until new tracheal rings develop. Experimental and early clinical work has provided promising results but with problems concerning the endoprosthesis. In our patient, we used the abdominal aorta as a tracheal substitute but replaced the endoprosthesis with an exoprosthesis leaving the aortic lumen free. The result was also encouraging, but the absence of integration of the aortic tissue did not confirm the observations reported by others. Other hypotheses concerning the regeneration of the neotrachea should be put forward.

[Diffuse interstitial pneumonitis with acute respiratory failure]. / Une pneumopathie infiltrante diffuse avec insuffisance respiratoire aiguë

Drug-induced pneumonia due to ibuprofen is exceptional. We report the case of hypoxic interstitial pneumonitis with eosinophilic alveolitis induced by ibuprofen. The resolution was spontaneously obtained by the stop of this drug.

[Lung screening]. / Le dépistage du cancer du poumon.

The NLST study found in more than 53,000 (former-) heavy smokers that annual screening with low-dose CT-scan (LDCT) reduced lung cancer mortality and overall mortality by 20% and 6.7% respectively. However, several potential harms of such screening strategy were underlined: over-diagnosis bias, irradiation risk, and the high rate of false-positive results that could lead to futile invasive (and potentially harmful) exams, to impact quality of life, to increase patient's anxiety and costs. All these concerns were largely debated in several recent publications. Most of them concluded in a risk/benefit ratio favoring screening strategy by LDCT. Conversely, most of American academic societies currently recommend LDCT-based lung cancer screening. In France, a taskforce edited a common statement recommending screening smokers or ex-smokers, from 55 to 75years old who have smoked at least 30packs/year. The taskforce also underlined the need for clinical trials aiming to translate screening strategy to the French setting. However, the French Health Authority recently claimed that lung cancer screening was not relevant in the current setting.

[Economic impact of lung cancer screening in France: A modeling study]. / Modélisation de l'impact économique d'un dépistage organisé du cancer du poumon en France.

INTRODUCTION: The National Lung Screening Trial found that, in a selected population with a high risk of lung cancer, an annual low-dose CT-scan decreased lung cancer mortality by 20% and overall mortality by 7% compared to annual chest X-Ray. In France, a work group stated that individual screening should be considered in this setting. However, the economic impact of an organized and generalized (to all eligible individuals) screening in France was never reported. METHODS: This is a modeling study using French population demographic data and published data from randomized screening trials. We used the same selection criteria as NLST: 55-74-year-old smokers for at least 30 pack-years, current smoker or quit less than 15 years. We computed a second model including also 50-54-year-old individuals. Then, we used different participation rates: 65%, 45%, and 32%. RESULTS: According to the considered model, there would be 1,650,588 to 2,283,993 subjects eligible to screening in France. According to the model and participation rate, lung cancer screening would diagnose 3600 to 10,118 stages 1/2 lung cancer each year. There would be 5991 to 16,839 false-positives, of whom 1416 to 3981 would undergo unnecessary surgery. Screening policy would cost 105 to 215 € million per year. However, increasing the price of a cigarette pack by 0.05 to 0.10 € would fully cover the screening costs. CONCLUSION: Participation rate is a key point for screening impact. Screening could be easily funded by a small increase in cigarette prices.