Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program.

BACKGROUND: EGFR mutations cause inconsistent response to EGFR tyrosine-kinase inhibitors (TKI). To better understand these features, we reviewed all cases of EGFR-mutated non-small-cell lung cancer collected in the Biomarkers France database. PATIENTS AND METHODS: Of 17 664 patients, 1837 (11%) with EGFR-mutated non-small-cell lung cancer were retrospectively analyzed for clinical and molecular characteristics. Results were correlated with survival and treatment response for the 848 stage IV patients. RESULTS: EGFR exon 18, 19, 20 and 21 mutations were found in 102 (5.5%), 931 (51%), 102 (5.5%) and 702 (38%) patients, respectively. Over 50% of exon 18 and 20 mutated patients were smokers. The median follow-up was 51.7 months. EGFR mutation type was prognostic of overall survival (OS) versus wild-type {exon 19: hazard ratio (HR)=0.51 [95% confidence interval (CI): 0.41-0.64], P < 0.0001; exon 21: HR = 0.76 (95% CI: 0.61-0.95), P = 0.002; exon 20: HR = 1.56 (95% CI: 1.02-2.38), P = 0.004}. EGFR mutation type was prognostic of progression-free survival versus wild-type [exon 19: HR = 0.62 (95% CI: 0.49-0.78), P < 0.0001; exon 20: HR = 1.46 (95% CI: 0.96-2.21), P = 0.07]. First-line treatment choice did not influence OS in multivariate analysis. First-line TKI predicted improved progression-free survival versus chemotherapy [HR = 0.67 (95% CI: 0.53-0.85), P = 0.001]. OS was longer for del19 versus L858R, which was associated with better OS compared with other exon 21 mutations, including L861Q. TKI improved survival in patients with exon 18 mutations, while chemotherapy was more beneficial for exon 20-mutated patients. CONCLUSION: EGFR mutation type can inform the most appropriate treatment. Therapeutic schedule had no impact on OS in our study, although TKI should be prescribed in first-line considering the risk of missing the opportunity to use this treatment.

Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma.

BACKGROUND: Immunohistochemistry has been proposed as a specific and sensitive method to identify EGFR mutations or ALK rearrangements in lung tumours. PATIENTS AND METHODS: We assessed EGFR and KRAS by direct sequencing in 154 patients with lung adenocarcinoma. ALK rearrangements were assayed by FISH and RT-PCR. Immunohistochemistry was carried out and evaluated closely following published methods using recommended monoclonal rabbit or mouse antibodies. RESULTS: Thirteen of 36 exon 19 EGFR-mutated tumours (36%)-including 12 of 22 with p.Glu746_Ala750del (55%)-were positive with the 6B6 antibody that was raised against p.Glu746_Ala750del. One hundred eleven of 114 EGFR exon 19 wild-type tumours (97%) were negative with 6B6. Four of 21 exon 21 EGFR-mutated tumours (19%)-including 4 of 17 with p.Leu858Arg (24%)-were positive with the 43B2 antibody that was raised against p.Leu858Arg. One hundred twenty-two of 124 (98%) EGFR exon 21 wild-type tumours were negative with 43B2. Two of four ALK rearrangements-including two of three with ELM4-ALK fusion transcripts-were identified with the 5A4 antibody. Eleven of 13 tumours without ALK rearrangement (85%) were negative with 5A4. CONCLUSIONS: Immunohistochemistry is a specific means for identification of EGFR mutations and ALK rearrangements. It suffers, however, from poor sensitivity.

[A rare pulmonary tumour, primary malignant melanoma]. / Une tumeur rare du poumon, le mélanome primitif.

INTRODUCTION: Malignant melanoma most commonly presents as a primary neoplasm of the skin, but has been described in other mucosal sites. Rarely, malignant melanomas have been reported as primary visceral neoplasms, including the lung. Most such lesions have been dismissed as metastases from undocumented or regressed primary cutaneous or ocular melanomas. CASE REPORT: We report an original observation of an 82-year-old man with a pulmonary nodule presenting with chest pain. The diagnosis of melanoma was established on biopsies carried out under computerized tomography scanning and confirmed after right upper lobectomy two months later. DISCUSSION: Melanomas of the respiratory tract are usually metastatic in origin and a primary melanoma in very rare. Strict criteria must be applied before a diagnosis of primary malignant melanoma of lower respiratory tract can be accepted. Melanoma may be confused with more conventional types of lung cancer and other pigmented tumours.

[Erlotinib and nonsmall cell lung cancer with brain metastases: a case study with a complete and prolonged response over 17 months]. / Erlotinib et métastases cérébrales d'un cancer bronchique non à petites cellules : une réponse complète et prolongée de 17 mois.

The prognosis of stage IV nonsmall cell lung cancer, in particular with brain metastases, is extremely poor. The impact of targeted therapy, in particular erlotinib, on patient survival has still not been determined. The authors report the case of a patient diagnosed with nonsmall cell lung cancer with bone and brain metastases. The patient presented a complete cerebral response for 17 months with erlotinib prescribed as a third line therapy.

[Pleuro-pulmonary manifestations disclosing hepatic amoebiasis]. / Manifestations pleuropulmonaires révélatrices de l'amibiase hépatique.

During a mission in ex-Yugoslavia between 2001 and 2004, three French soldiers were sent home because of right pneumopathy, right pleurisy after appendicectomy, haemoptysis and liver haematoma, respectively. They previously were stationed in Africa and/or South America. The initial diagnosis was quickly modified: pleuropulmonary manifestations of amoebic hepatic abscess in two cases, and pleuropulmonary amoebiasis in the last case. The outcome was favourable with standard anti-amoebic treatment. The reports illustrate the possibility of hepatic amoebiasis with local pleuropulmonary manifestations and an exceptional case of pleuropulmonary amoebiasis with hepatobronchial fistula. The authors report this experience because it demonstrates that amoebiasis in European countries remains an often forgotten diagnosis. Although known for a long time in developing countries, amoebiasis in the military or in tourists should be systematically considered.

[Positron emission tomography using 18F-fluorodeoxyglucose in the management of nonsmall cell lung cancers in 2006]. / La tomographie par émission de positons au 18fluorodésoxyglucose (18FDG-TEP) dans la prise en charge du cancer bronchique non à petites cellules en 2006.

Technological progress and numerous published studies allow to estimate the best place of the 18F-fluorodeoxyglucose positron emission tomography, a real functional metabolic imagery, in the clinical and therapeutic strategy of non small cell lung cancers.

[A case of atypical pericarditis]. / Une péricardite atypique.

INTRODUCTION: An acute viral pericarditis may reveal a congenital pericardial abnormality. CASE HISTORY: We report the case of a young man of 29 years in whom the development of rapidly progressive dyspnoea and fever led to the echocardiographic diagnosis of a pericardial tumour. The thoracic CT scan showed a mass arising in the superior mediastinum with no evidence of spread. Surgical exploration allowed the excision of a soft mutilobular mass adherent only to the aorta. Histological examination revealed an intrapericardial bronchogenic cyst. CONCLUSION: After a review of bronchogenic cysts we point out the properties of this rare intra-pericardial localisation, one of which is the frequently observed secretion of CA 19-9.

[Positron emission tomography in the diagnosis and follow up of non-small cell lung cancer]. / 18F-FDG-TEP : sa place dans le diagnostic et la surveillance du cancer bronchique non à petites cellules.

In the space of a few years 18F-FDG PET scanning has acquired a place in the management of all stages of the clinical care of patients with lung cancer. Its contributions are being more and more precisely understood during the assessment of mediastinal and metastatic extension and it carries the hope of better therapeutic management and surveillance.

[Lung cancer in the elderly subject]. / Cancer bronchique du sujet âgé.

INTRODUCTION: In France, the average age for the diagnosis of bronchial carcinoma is 64. It is 76 in the population of over 70. In fact, its incidence increases with age linked intrinsic risk of developing a cancer and with general ageing of the population. Diagnosis tools are the same for elderlies than for younger patients, and positive diagnosis mainly depends on fibreoptic bronchoscopy, complications of which being comparable to those observed in younger patients. STATE OF THE ART: The assessment of dissemination has been modified in recent years by the availability of PET scanning which is increasingly becoming the examination of choice for preventing unnecessary surgical intervention, a fortiori in elderly subjects. Cerebral imaging by tomodensitometry and nuclear magnetic resonance should systematically be obtained before proposing chirurgical treatment. An assessment of the general state of health of the elderly subject is an essential step before the therapeutic decision is made. This depends on the concept of geriatric evaluation: Geriatric Multidimensional Assessment, and the Comprehensive Geriatric Assessment which concerns overall competence of the elderly. PERSPECTIVES: This is a global approach that allows precise definition and ranking of the patient's problems and their impact on daily life and social environment. Certain geriatric variables (IADL, BADL, MMSE, IMC etc) may be predictive of survival rates after chemotherapy or the incidence of complications following thoracic surgery. The main therapeutic principles for the management of bronchial carcinoma are applicable to the elderly subject; long term survival without relapse after surgical resection is independent of age. Whether the oncological strategy is curative or palliative, the elderly patient with bronchial carcinoma should receive supportive treatments. They should be integrated into a palliative programme if such is the case. In fact, age alone is not a factor that should detract from optimal oncological management. CONCLUSIONS: The development of an individual management programme for an elderly patient suffering from bronchial carcinoma should be based on the combination of oncological investigation and comprehensive geriatric assessment.

[Lung cancer in Senegal]. / Le cancer bronchique au Sénégal.

In Africa the incidence of lung cancer is rising rapidly. The purpose of this prospective study was to analyze clinical, therapeutic, and prognostic features of lung cancer patients treated at the Principal Hospital in Dakar between 2002 and 2007. A total of 72 cases were compiled over the 5-year study period. In 88% of cases the patient was a male smoker with a mean age of 59.2 years. Histological samples were obtained in 79.1% of cases by bronchial fibroscopy (n=33), CT-guided transthoracic needle biopsy (n=17), or from a metastatic site (n=7). The histological diagnosis was squamous cell carcinoma in 23 cases, adenocarcinoma in 14, large-cell carcinoma in 17, small-cell lung cancer in 2, and bronchiolo-alveolar cancer in 1. Tumor staging demonstrated grades I-II in 6 cases, grade II in 17, and grade IV in 49. Symptomatic management was performed in 68% of patients. In the remaining cases management consisted of chemotherapy in 22 cases, radiotherapy for pain relief in 5, and surgery in 1. Ten patients were lost from follow-up. Median survival was 7 or 3 months depending on whether or not chemotherapy was performed. The much higher rate of histological diagnosis than in the sub-region is due mainly to the availability of trained personnel with access to bronchial endoscopy and CT-scan needle biopsy since September 2003. Administration of cytotoxins is feasible but the cost is excessive due to the lack of universal health care coverage: two-thirds of cases were abandoned whereas chemotherapy significantly improved median survival by 4 months (p < 0.0001). Prognosis of the disease is poor because management is undertaken at an advanced stage. Lung cancer is a health issue in Dakar, Senegal. It is urgent to develop therapeutic standards adapted to the African socio-economic setting as well as an anti-tobacco prevention policy.

[Spontaneous regression of hepatic and splenic involvements during sarcoidosis]. / Nodules hépato-spléniques d'évolution spontanément favorable au cours d'une sarcoïdose.

Splenic and hepatic involvements are frequent and usually clinically silent during systemic sarcoidosis. Imaging findings are extremely rare. We report hepatic and splenic nodules diagnosed on abdominal computed tomography with spontaneous regression.

[Three-year survival after treatment of a primary pulmonary angiosarcoma]. / Trois ans de survie après traitement d'un angiosarcome pulmonaire primitif.

We report an observation of angiosarcoma of the pulmonary artery in a 65-year-old man hospitalized for acute dyspnea revealing a left mass hilaire which arose from the pulmonary artery before the development of obstructive endobronchial extension. The therapeutic sequence associated removal of the lobar bronchus obstruction by interventional endoscopy, chemotherapy using ifosfamide-doxorubicin, complete left pneumonectomy and auxiliary chemotherapy with 2 additional cycles. The patient was free of tumor relapse at nearly 3 years follow-up.

[Filling the thymic space after treatment of Hodgkin's disease: rebound or relapse]. / Comblement de la loge thymique après traitement d'une maladie de Hodgkin: rebond ou rechute?

We report the case of a 36-year-old women with Hodgkin's disease treated with polychemotherapy and bone marrow autograft. Progressive growth of a thymic mass suggested possible relapse four months after treatment withdrawal. This mass did not exhibit gallium-67 uptake but showed strong affinity for 18-FDG (SUV=6.8). Surgical biopsy ruled out recurrence of Hodgkin's disease of the thymus and led to the diagnosis of thymic rebound. The aspect of the thymic compartment returned to normal spontaneously at one year.

[Mycobacterial pulmonary infection due to Mycobacterium simiae]. / Mycobactériose pulmonaire à Mycobacterium simiae.

INTRODUCTION: Mycobacterium simiae pulmonary infections remain exceptional in France. CASE REPORT: We report a case of M. simiae lung infection and a 10-year follow-up in a non-immunocompromised host. CONCLUSION: This case emphasizes the difficulties of choosing the appropriate drugs and their side effects in the absence of any existing gold standard.

[Respiratory dysfunction in burned patients]. / Lésions respiratoires et brûlures.

INTRODUCTION: Smoke inhalation and respiratory complications are still the major causes of mortality in severely burned patients. STATE OF THE ART: The diagnosis is suspected clinically on the basis of history and physical examination and can be confirmed bronchoscopically. Respiratory failure in burned patients occurs through a number of associated mechanisms. Pneumonitis and adult respiratory distress syndrome (ARDS) are common early complications. New pulmonary treatments and advances in ventilation have reduced the incidence of both barotrauma and infectious complications. Tracheal stenosis can occur as a late complication of prolonged mechanical ventilation. PERSPECTIVES: Clinical and experimental studies have shown that damage to the mucosal barrier and the release of inflammatory mediators are the most important pathophysiological events following smoke inhalation. Manipulation of the inflammatory response following inhalation may be a treatment option in the distant future. CONCLUSION: Inhalation injury occurring in burned patients can produce severe respiratory and systemic complications.

[PET scanning in the initial assessment of lung cancer]. / La tomographie par émission de positons au 18Fluoro-deoxy-glucose (18FDG-TEP) et le bilan initial du cancer bronchique.

18FDG-PET scanning enables the imaging of metabolic activity giving an assessment of the local extent of thoracic malignancies as well as an indication of the presence of nodal or metastatic spread. This enables more accurate staging and has revolutionised the management of lung cancer. National and international guidelines describe the role of this technique.

[The therapeutic impact of PET-FDG scanning in broncho-pulmonary cancer]. / Impact thérapeutique de l'imagerie TEP-FDG en carcinologie bronchopulmonaire.

BACKGROUND: Because of the expected high performances of scintigraphic scans with [18F]-fluorodeoxyglucose (FDG) not only in diagnostics and but also in therapeutic impact, especially in thoracic oncology, there are a lot of French nuclear medicine departments which will soon be equipped with a positron emission tomograph (PET). MATERIAL AND METHODS: The Nuclear Medicine Department of the Hôpital d'Instructions des Armées du Val-de-Grâce, Paris, led a retrospective study among physicians interested in 338 FDG-PET exams performed between may 2000 and march 2002 in order to compare its own results with international literature concerning four indications for lung cancer: pulmonary nodule or mass malignancy diagnostic, lung carcinoma extension evaluation, therapeutic efficiency, recurrence suspicion. RESULTS: There seems to be no divergence, regarding limitation induced by the not exhaustive analysis of the retrospective study: more than every two FDG-PET exam highly influenced the effective therapy. CONCLUSION: That is why clinical FDG-PET has to be widely developed to investigate lung cancer.

[18-FDG positon emission tomography and distal metastasis from lung cancer]. / Tomographie à émission de positons au [18F]-FDG et métastases distales dans les cancers broncho-pulmonaires.

"Whole body" FDG-PET usually covers the body from the base of the skull to the upper third of the thighs, arms in abduction. Thus, the upper part of the head and the lower limbs are not included in the acquisition field. We report the cases of three patients with non-small-cell lung cancer who developed secondary distal localizations beyond the acquisition field of "whole body" FDG-PET. Lung cancer is known to favor hematogenic dissemination, raising the possibility of early distal metastasis. A pretherapeutic PET scan which includes the extremities can be useful to search for distal extension. These true whole body scans are time consuming and can thus limit machine availability. Furthermore, the diagnostic yield of this type of examination may be low since it can be estimated that about 1% of patients will develop isolated distal metastases (3 out of 293 patients in our series initially treated for non-metastatic non-small-cell lung cancer). In the current context of technical availability, systematic inclusion of the lower limbs in the PET scan acquisition field would not appear warranted for the initial work-up of patients with non-small-cell lung cancer. However, clinicians must be aware that distal metastases (brain, lower limbs) may not be detected.

[Pseudotumoral presentation of American pulmonary histioplasmosis]. / Présentation pseudo-tumorale de l'histoplasmose pulmonaire américaine.

In France, American pulmonary histoplasmosis is an imported deep mycosis, caused by inhalation of Histoplasma capsulatum. Clinical and radiological features of this exotic disease are multiple, simulating tuberculosis or cancer. We report two cases of American histoplasmosis with pseudo-tumoral form, in immunocompetent subjects working in Venezuela, with a multinodular pulmonary presentation.