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.

[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.

[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.

[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.

[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.

[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.

[Other thoracic cancers. Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar carcinoma feature: a clinico-pathological spectrum]. / Carcinome bronchioloalvéolaire (CBA) et adénocarcinome pulmonaire avec composante bronchioloalvéolaire (ADC-CBA): un continuum anatomoclinique.

Bronchioloalveolar carcinoma (BAC) is a primary pulmonary adenocarcinoma (ADC) developed from the terminal respiratory unit. Its restrictive definition adopted by the 1999 WHO pathological classification needs a complete tumor resection to exclude any signs of histological invasion. Although IIIB-IV tumors were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 had focussed on the need to include in the same spectrum of disease pure BAC and ADC with BAC feature (ADC-WBF). BAC and ADC-WBF affect more frequently women, non-smokers and Asian people than other non small cell carcinoma. Their predominant lepidic and aerogenous tumor progression results in a frequent pneumonic, multifocal or diffuse presentation and explains why death is more frequently related to bilateral pulmonary involvement than extra-thoracic metastasis. Natural history is slower and prognosis better than for other ADC. Surgical resection remains the best therapeutic option for localized tumors. High frequency of epidermal growth factor receptor (EGFR) expression on tumor cells and its gene amplification and/or mutation as well as a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors offer new strategy of therapeutical management in patients with non resectable tumor. However, the place of chemotherapy has recently been revisited.

[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.

[Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features: a clinico-pathological spectrum]. / Carcinome bronchio-alvéolaire (CBA) et adénocarcinome pulmonaire avec composante bronchio-alvéolaire (ADC-CBA) : un continuum anatomoclinique.

Bronchioloalveolar carcinoma (BAC) is a pulmonary adenocarcinoma (ADC) developing in the terminal respiratory units. The restrictive definition adopted by the 1999 WHO pathological classification requires a complete resection of the tumour to exclude any evidence of histological invasion. Although IIIB-IV tumours were excluded from the strict WHO definition of BAC, the first international workshop on BAC in 2004 focussed on the need to include in the same disease spectrum both pure BAC and ADC with BAC features (ADC-BAC). BAC and ADC-BAC more frequently affect women, non-smokers and Asians than other non-small cell carcinomas. Their predominantly lepidic airway progression frequently results in a multifocal or diffuse pneumonic presentation and explains why death is more frequently due to bilateral pulmonary involvement than extrathoracic metastases. The natural history is slower and the prognosis better than other ADC. Surgical resection remains the best therapeutic option for localised tumours. The high incidence of epidermal growth factor receptor (EGFR) expression on tumour cells and its gene amplification and/or mutation together with a particular sensitivity of this entity to EGFR tyrosine kinase inhibitors, offer a new strategy of therapeutic management in patients with unresectable tumours. However, the place of chemotherapy has recently been re-evaluated.

[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.

[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.

[Lung cancer in HIV-positive patients]. / Le cancer broncho-pulmonaire chez les patients séropositifs pour le virus de l'immunodéficience humaine.

Since 1996, AIDS-related mortality has declined considerably with the introduction of tritherapy (HAART). This decline in mortality has been associated with an increase in the proportion of deaths caused by cancers unrelated to AIDS, particularly lung cancer. The risk of developing lung cancer is higher in the HIV-seropositive population than in the aged-matched general population, undoubtedly because of the high rate of smoking, particularly among drug abusers, but also because of other reasons which remain to be determined. Mean age at the discovery of lung cancer in HIV+ patients is 45 years, and most are symptomatic. The diagnosis is established at a locally advanced or metastatic stage in 75-90% of patients, as in the general population. Adenocarcinoma is the most common histological type. The prognosis is worse in HIV+ patients than in patients with an undetermined HIV status. Evidence on the efficacy and toxicity of chemotherapy is insufficient to draw any conclusions. Surgery remains the treatment of choice for locally advanced disease if allowed by the clinical status and respiratory function. Prospective clinical studies are needed to define a better management strategy for lung cancer in HIV-positive patients.

[Bronchopulmonary aspergillosis infections in the non-immunocompromised patient]. / Infections aspergillaires broncho-pulmonaires du sujet non immunodéprimé.

The definition of broncho-pulmonary aspergillosis infections in non-immunocompromised patients remains vague and a wide range of clinical, radiological and pathological entities have been described with a variety of names, i.e. simple aspergilloma, complex aspergilloma, semi-invasive aspergillosis, chronic necrotizing pulmonary aspergillosis, chronic cavitary and fibrosing pulmonary and pleural aspergillosis, pseudomembranous tracheobronchitis caused by Aspergillus, and invasive aspergillosis. However, these disease entities share common characteristics suggesting that they belong to the same group of pulmonary aspergillosis infectious disorders: 1- a specific diathesis responsible for the deterioration in local or systemic defenses against infection (alcohol, tobacco abuse, or diabetes); 2- an underlying bronchopulmonary disease responsible or not for the presence of a residual pleural or bronchopulmonary cavity (active tuberculosis or tuberculosis sequelae, bronchial dilatation, sarcoidosis, COPD); 3- generally, the prolonged use of low-dose oral or inhaled corticosteroids and 4- little or no vascular invasion, a granulomatous reaction and a low tendency for metastasis. There are no established treatment guidelines for broncho-pulmonary aspergillosis infection in non-immunocompromised patients, except for invasive aspergillosis. Bronchial artery embolization may stop hemoptysis in certain cases. Surgery is generally impossible because of impaired respiratory function or the severity of the comorbidity and when it is possible morbidity and mortality are very high. Numerous clinical cases and short retrospective series have reported the effect over time of the various antifungal agents available. Oral triazoles, i.e. itraconazole, and in particular voriconazole, appear to provide suitable treatment for broncho-pulmonary aspergillosis infections in non-immunocompromised patients.

[Clinical types of thoracic cancer. Bronchiolo-alveolar carcinoma and adenocarcinoma with bronchioloalveolar features: a clinico-pathological spectrum]. / Formes cliniques des cancers thoraciques. Carcinome bronchiolo-alvéolaire (CBA) et adénocarcinome pulmonaire avec composante bronchiolo-alvéolaire (ADC-CBA): un continuum anatomo-clinique.

Bronchioloalveolar carcinoma (BAC) is a primary pulmonary adenocarcinoma (ADC) arising in the cells of the terminal respiratory unit. Its restrictive definition adopted by the 1999 WHO pathological classification requires a complete surgical resection of the tumour to exclude any signs of invasion. Although stage IIIB and IV tumours were excluded from the strict WHO definition of BAC the first international workshop on this tumour in 2004 emphasised the clinico-pathological continuum that exists between BAC as defined by WHO and ADC with BAC features (ADC-BAC). BAC and ADC-BAC are distinguished from other non-small cell carcinomas by an increased incidence in women, non-smokers and Asians. The predominant spread through the airways explains the frequent presentation as diffuse or multifocal consolidation and death is more often due to bilateral pulmonary infiltration than extra-thoracic metastases. Progression is slower and the prognosis better than that of other ADC. Surgery offers the best treatment for localised disease. The high frequency of epidermal growth factor receptor (EGFR) expression and amplification and/or mutation of its gene, as well as the finding in some cases of a major response to EGFR tyrosine-kinase inhibitors, have lead to several therapeutic trials of these drugs. However, the place of chemotherapy has recently been reviewed.

[Improved prognosis in non small cell lung cancer--myth or reality?]. / Amélioration du pronostic des cancers bronchiques non à petites cellules: mythe ou réalité?

Some data suggest that survival in non small cell lung cancer (NSCLC) has improved in the last ten years. A comparison between large prospective therapeutic trials from 1979 to 2002 does show some progress but there are many biases, especially the Will Rogers effect, where stage migration due to new methods of diagnostic imaging and invasive staging procedures could improve actuarial survival in each stage. Prospective randomised trials comparing older and more recent treatments demonstrate some improvements, specifically perioperative chemotherapy in stages I-IIIA, chemo-radiation in unresectable stage III disease and new drugs in stage IV. However retrospective whole population studies fail to show a significant improvement in survival. These discrepancies could be explained by differences between whole populations and those selected for clinical trials. Moreover, the results of the therapeutic trials are not always applied in all unselected patients. In conclusion, NSCLC survival can be improved in a selected population. To reproduce this in the whole population all patients should be managed in accordance with the results of recent trials.

[Acute forms of diffuse interstitial hypoxemic pneumonia in immunocompetent patients]. / Les formes aiguës des pneumopathies infiltrantes diffuses hypoxémiantes de l'immunocompétent.

The large majority of patients with acute respiratory failure present diffuse pulmonary opacities resulting from pulmonary embolism, intra-alveolar hemorrhage, or a classical cause of ARDS. In a small number of patients however, these opacities correspond to diffuse interstitial pneumonia. This should be suspected in light of the context, the time of formation, and the unusual respiratory and/or extrarespiratory signs. If there is a clinical doubt, thoracic scan and bronchoalveolar lavage should be performed together with infectious and immunology tests. Treatment depends on the cause and/or the type of lesion.

[Non-small-cell bronchial cancers: improvement of survival probability by conformal radiotherapy]. / Cancers bronchiques non à petites cellules: amélioration des chances de survie par la radiothérapie conformationnelle?

The conformal radiotherapy approach, three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), is based on modern imaging modalities, efficient 3D treatment planning systems, sophisticated immobilization devices and demanding quality assurance and treatment verification. The main goal of conformal radiotherapy is to ensure a high dose distribution tailored to the limits of the target volume while reducing exposure of healthy tissues. These techniques would then allow a further dose escalation increasing local control and survival. Non-small cell lung cancer (NSCLC) is one of the most difficult malignant tumors to be treated. It combines geometrical difficulties due to respiratory motion, and number of low tolerance neighboring organs, and dosimetric difficulties because of the presence of huge inhomogeneities. This localization is an attractive and ambitious example for the evaluation of new techniques. However, the published clinical reports in the last years described very heterogeneous techniques and, in the absence of prospective randomized trials, it is somewhat difficult at present to evaluate the real benefits drawn from those conformal radiotherapy techniques. After reviewing the rationale for 3DCRT for NSCLC, this paper will describe the main studies of 3DCRT, in order to evaluate its impact on lung cancer treatment. Then, the current state-of-the-art of IMRT and the last technical and therapeutic innovations in NSCLC will be discussed.