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1.
Cancer Genet ; 256-257: 158-161, 2021 08.
Article in English | MEDLINE | ID: mdl-34157597

ABSTRACT

The C797S mutation encoded by EGFR exon 20 is classically observed as a tertiary event in EGFR-mutant non-small-cell lung carcinoma (NSCLC) primarily treated by first generation tyrosine kinase inhibitors (TKI) and secondarily treated by third-generation TKI, such as osimertinib, if the EGFR-T790M resistance mutation is detected. Recently, significant prolonged progression free survival has been observed following first-line osimertinib, in EGFR-mutant NSLC. While mechanisms of molecular resistance to first-generation TKI have been well studied, little is known about resistance induced by primary third-generation TKI treatments. We report the case of a 65 year-old female treated by first-line osimertinib for a multimetastatic exon 19-EGFR-mutant NSCLC. EGFR-C797S resistance mutation and PIK3CA mutation were detected together with the remaining EGFR-exon 19 deletion. This observation provides insights of acquired resistance to first line-osimertinib. It also highlights the importance of making molecular platforms which perform routine EGFR testing in lung cancer aware of the kind of therapeutic protocols given to the patient. Indeed, for rapid results or low-costs procedures, some targeted methods specifically targeting T790M may be used at relapse and may overlook alterations such as C797S or PIK3CA mutations. Targeted next generation sequencing is therefore a recommended option.


Subject(s)
Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation/genetics , Base Sequence , Bone Neoplasms/secondary , Drug Resistance, Neoplasm/genetics , ErbB Receptors/genetics , Fatal Outcome , Female , Follow-Up Studies , High-Throughput Nucleotide Sequencing , Humans , Lung Neoplasms/diagnostic imaging , Middle Aged , Tomography, X-Ray Computed
2.
Rev Mal Respir ; 36(4): 553-556, 2019 Apr.
Article in French | MEDLINE | ID: mdl-30853279

ABSTRACT

Tuberculosis is a disease that is still a too frequent. Its treatment depends on prolonged, multi-antibiotic, chemotherapy. Progress following treatment is generally good but there is the possibility of parenchymatous or pleural sequelae such as bronchial stenosis due to post tuberculous bronchial fibrosis or bronchiolithiasis. On the other hand, bronchial obstruction after treatment by an inflammatory granuloma is rare. It causes wheezing dyspnoea. In this case, relapse of the tuberculosis was feared, possibly with the development of multi-drug resistance. Treatment with corticosteroids allowed a rapid improvement.


Subject(s)
Antitubercular Agents/therapeutic use , Bronchial Diseases/diagnosis , Granuloma/diagnosis , Tuberculosis, Pulmonary/drug therapy , Adult , Bronchial Diseases/pathology , Constriction, Pathologic/diagnosis , Constriction, Pathologic/pathology , Disease Progression , Granuloma/pathology , Humans , Male , Radiography, Thoracic , Recurrence , Treatment Failure , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/pathology
4.
Ann Dermatol Venereol ; 144(4): 279-283, 2017 Apr.
Article in French | MEDLINE | ID: mdl-27839728

ABSTRACT

BACKGROUND: Dermatomyositis associated with anti-MDA-5 autoantibodies is a recently-described clinical entity. Herein we report two lethal cases involving pneumocystis pneumonia. PATIENTS AND METHODS: Case no 1. A 56-year-old male patient developed cutaneous symptoms consistent with dermatomyositis without muscular involvement. Antinuclear antibodies were present and anti-MDA5 auto-antibodies were identified. The scan showed interstitial lung disease without infection. Significant improvement was obtained with corticosteroids. One month later, the patient presented acute respiratory illness (hypoxemia: PaO2 60mmHg, exacerbation of lung disease evidenced by a scan, and diagnosis of pneumocystis pneumonia on bronchoalveolar lavage). He died despite appropriate antibiotic therapy and immunosuppressant therapy. Case no 2. The second case concerned a 52-year-old Vietnamese man who developed more atypical cutaneous symptoms of dermatomyositis without muscular involvement. ANAb responses were positive (1/400) and MDA5 was present. The patient was treated with corticosteroids (40mg/d), hydroxychloroquine, and intravenous immunoglobulin. After significant improvement, the patient developed an acute respiratory illness due to superinfection with pneumocystis and he died despite specific treatment and cyclophosphamide bolus. CONCLUSION: In dermatomyositis, anti-MDA5 antibody screening is essential for the prognosis since the disease carries a risk of complication with severe lung disease. Bronchial fibroscopy with bronchoalveolar lavage should be considered at the time of diagnosis. Our two cases suggest the need for early screening for pneumocystis pneumonia in the event of respiratory distress and possibly for prophylactic treatment at the start of immunosuppressant therapy.


Subject(s)
Autoantibodies/immunology , Dermatomyositis/complications , Interferon-Induced Helicase, IFIH1/immunology , Pneumonia, Pneumocystis/etiology , Antibodies, Antinuclear/immunology , Autoantibodies/blood , Coinfection , Dermatomyositis/immunology , Disease Susceptibility , Fatal Outcome , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Interferon-Induced Helicase, IFIH1/blood , Male , Middle Aged , Pneumonia, Bacterial/diagnostic imaging , Pneumonia, Bacterial/etiology , Pneumonia, Pneumocystis/diagnostic imaging , Prognosis , Pseudomonas Infections/diagnostic imaging , Pseudomonas Infections/etiology , Respiratory Distress Syndrome/etiology , Tomography, X-Ray Computed
5.
Rev Mal Respir ; 32(9): 953-5, 2015 Nov.
Article in French | MEDLINE | ID: mdl-26037683

ABSTRACT

INTRODUCTION: In the context of bronchial cancers, the most frequent sites for metastases to occur are the lung, bone, brain, liver and adrenal glands. However, metastasis to other sites does additionally occur and this might be influenced by the biological characteristics of the tumour. OBSERVATION: We report the case of a 54-year-old woman with a primary bronchial adenocarcinoma with an EML4-ALK translocation. During her treatment with crizotinib, the patient developed a lesion in her right breast. The initial pathological diagnosis was of an invasive ductal adenocarcinoma of the breast. However, an additional immuno-histochemical analysis revealed it to be a metastasis from her bronchial tumour. CONCLUSION: This case is an illustration that, in the context of a lung cancer with ALK rearrangement, synchronous or secondary lesions must be interpreted with caution. Specific biological analysis - ALK immunohistochemistry or FISH - must be performed to confirm a primary or metastatic origin for these lesions.


Subject(s)
Adenocarcinoma/pathology , Breast Neoplasms/secondary , Carcinoma, Ductal, Breast/secondary , Lung Neoplasms/pathology , Adenocarcinoma/genetics , Adenocarcinoma of Lung , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/genetics , Cytogenetic Analysis , Diagnosis, Differential , Female , Humans , Lung Neoplasms/genetics , Middle Aged , Oncogene Proteins, Fusion/genetics , Translocation, Genetic
6.
Rev Mal Respir ; 32(9): 949-52, 2015 Nov.
Article in French | MEDLINE | ID: mdl-25725978

ABSTRACT

INTRODUCTION: Ipilimumab (anti CTLA-4 antibody) aims to activate antitumor immunity. This treatment is being evaluated in non-small cell lung cancer. CASE REPORT: We report a case of a stage IV adenocarcinoma patient randomized in 2008 in the phase II trial CA 184-104 evaluating the combination of ipilimumab to chemotherapy with carboplatin and paclitaxel. After an initial partial response to chemotherapy, the patient achieved a complete response with ipilimumab as maintenance therapy. However, it was complicated by grade 3 gastro-intestinal toxicity leading to stop the ipilimumab. However, this complete response persists after 6 years. CONCLUSIONS: Our case illustrates the contribution of immunotherapy at least in some patients. The mechanisms of action, relationship between efficacy and toxicity and predictors of efficacy remain to be defined.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antibodies, Monoclonal/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Clinical Trials, Phase II as Topic , Gastrointestinal Diseases/chemically induced , Humans , Ipilimumab , Male , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Remission Induction , Treatment Outcome
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