Genomic characteristics and clinical significance of CD56+ circulating tumor cells in small cell lung cancer.

Circulating tumor cells (CTC) have been studied in various solid tumors but clinical utility of CTC in small cell lung cancer (SCLC) remains unclear. The aim of the CTC-CPC study was to develop an EpCAM-independent CTC isolation method allowing isolation of a broader range of living CTC from SCLC and decipher their genomic and biological characteristics. CTC-CPC is a monocentric prospective non-interventional study including treatment-naïve newly diagnosed SCLC. CD56+ CTC were isolated from whole blood samples, at diagnosis and relapse after first-line treatment and submitted to whole-exome-sequencing (WES). Phenotypic study confirms tumor lineage and tumorigenic properties of isolated cells for the 4 patients analyzed with WES. WES of CD56+ CTC and matched tumor biopsy reveal genomic alteration frequently impaired in SCLC. At diagnosis CD56+ CTC were characterized by a high mutation load, a distinct mutational profile and a unique genomic signature, compared to match tumors biopsies. In addition to classical pathways altered in SCLC, we found new biological processes specifically affected in CD56+ CTC at diagnosis. High numeration of CD56+ CTC (> 7/ml) at diagnosis was associated with ES-SCLC. Comparing CD56+ CTC isolated at diagnosis and relapse, we identify differentially altered oncogenic pathways (e.g. DLL3 or MAPK pathway). We report a versatile method of CD56+ CTC detection in SCLC. Numeration of CD56+ CTC at diagnosis is correlated with disease extension. Isolated CD56+ CTC are tumorigenic and show a distinct mutational profile. We report a minimal gene set as a unique signature of CD56+ CTC and identify new affected biological pathways enriched in EpCAM-independent isolated CTC in SCLC.

[Pulmonary manifestations induced by osimertinib]. / Toxicité pulmonaire induite par l'osimertinib.

INTRODUCTION: The third-generation tyrosine kinase inhibitor (TKI) osimertinib is recommended as a first-line treatment in advanced non-small cell lung cancer harboring an activating mutation of Epidermal Growth Factor Receptor (EGFR). Adverse pulmonary events related to osimertinib exposure have been reported, primarily in Japanese patients. They rarely occur in the Caucasian population. OBSERVATION: Herein we report two clinical cases of osimertinib-induced lung toxicities in patients diagnosed with advanced lung adenocarcinoma harboring an EGFR mutation. In the first case, interstitial pneumonia was asymptomatic and evolved favorably after osimertinib discontinuation. The second patient presented a more extensive form of lung injuries and despite systemic corticosteroid therapy, the evolution was fatal. CONCLUSION: Osimertinib-related lung toxicities remain exceptional. While most forms are mild, consideration of TKI treatment discontinuation may be necessitated. Introduction of another TKI or rechallenge with osimertinib might be considered along with corticosteroid therapy if necessary. Diffuse alveolar damage is a pejorative prognostic factor.

[Randomised phase II study evaluating oral combination chemotherapy (CCNU, cyclophosphamide, etoposide) and intravenous chemotherapy as second-line treatment for relapsed small cell bronchial carcinoma (Trial GFPC0501)]. / Etude de phase 2, randomisée, évaluant une polychimiothérapie orale (CCNU, Cyclophosphamide, étoposide) et une polychimiothérapie intraveineuse dans les cancers bronchiques à petites cellules en seconde ligne en rechute (essai GFPC0501).

BACKGROUND: There is no standard second-line treatment for small cell lung cancer (SCLC). The prognosis of these patients is poor and special attention should be paid to both quality of life and economic factors. METHODS: The aim of this phase II randomised trial (GFPC0501) is to compare, in patients with progressive SCLC after first-line platinum based chemotherapy, oral multi drug chemotherapy (CCNU, cyclophosphamide, etoposide) and classical intravenous chemotherapy with cyclophosphamide, doxorubicin and vincristine (CAV) in terms of tolerability, efficacy (response rate, median one year survival and overall survival), quality of life and consumption of health care resources. Based on a two-stage Bryant and Day approach, this study will require a total of 138 patients with an interim analysis of the first 38. EXPECTED RESULTS: This trial will provide information on several aspects of second-line chemotherapy for patients with SCLC. Thirty six patients have been enrolled in 16 centres by December 2006 and the results of the interim analysis will be available in June 2007.

[Treatment of a compressive bronchogenic cyst by computed tomography-guided needle aspiration]. / Traitement d'un kyste bronchogénique compressif par ponction sous tomodensitométrie.

INTRODUCTION: Bronchogenic cysts are benign tumours of the posterior or middle mediastinum. Treatment usually consists of complete surgical resection. We report the case of an elderly woman presenting with an inoperable bronchogenic cyst causing tracheal compression which was treated successfully using computed-tomography (CT)-guided needle aspiration. CASE REPORT: A 92 years old woman was admitted for inspiratory dyspnoea associated with stridor. She reported the incidental discovery of a right paratracheal mass, 2 years previously. Thoracic CT scan and bronchoscopy revealed a large mediastinal bronchogenic cyst causing tracheal compression. Surgery was contraindicated because of the patient's age and cardiac disease. CT-guided needle aspiration of 250 ml of viscous fluid was performed, followed by rapid clinical improvement. The patient remained symptom free for several months. The procedure was repeated successfully one year later because of a recurrence of compression. CONCLUSION: This observation supports the potential use of CT guided transthoracic needle aspiration as an alternative to surgical treatment in cases of inoperable symptomatic bronchogenic cyst.

Radiation recall dermatitis with pemetrexed.

Pemetrexed has recently been approved for use in combination with cisplatin as first-line chemotherapy for malignant pleural mesothelioma (MPM). Radiation therapy is frequently administered to the thoracic orifices and no data are available about the interactions between radiotherapy and pemetrexed. We report the first case of radiation recall dermatitis occurring after pemetrexed chemotherapy in a patient with MPM previously treated with radiation therapy to the thoracoscopy and drainage orifices. The patient received chemotherapy with pemetrexed and cisplatin 19 days after completion of chest wall radiation therapy delivering 21 gray in 3 days. Conventional premedication by folic acid and intramuscular administration of Vitamin B12 and prednisolone was correctly performed. Twelve days later, confluent erythematous and pruritus rash of the irradiated skin was observed. The toxicity grade of this lesion was evaluated at 2 according to the Acute Radiation Morbidity Scoring Criteria proposed by the Radiation Therapy Oncology Group. Pemetrexed challenge was performed without worsening of skin lesions. Three weeks later, skin cicatrisation was observed after a desquamative phase. Persistent hyperpigmentation was seen in the irradiated skin. Pemetrexed could also act as a radiosensitizing agent that should be used with care for several weeks after radiotherapy.

[Chemoradiotherapy-chemotherapy for grade III inoperable non-small-cell lung cancer]. / Chimioradio-chimiothérapie des cancers broncho-pulmonaires non à petites cellules inopérables stade III.

PURPOSE: The purpose of this work was to assess results obtained with the MIP (mitomycin 6 mg/m(2) day 1, ifosfamide 1500 mg/m(2) days 1,2, 3, cisplatin 30 mg/m(2) days 1,2, 3) chemotherapy protocol combined with cisplatin-sensitized chest radiotherapy as developed in the French multicentric trial on perioperative chemotherapy. PATIENTS AND METHODS: Thirty-five patients with grade III non-small-cell lung cancer (NSCLC) were given two or three starter MIP cycles every 4 weeks then underwent radiation therapy for six weeks for a total dose of 60 Gy with injection of 8 mg/m(2) cisplatin every day for the first two weeks and the last two weeks of treatment. In case of objective response (OR) to MIP before radiotherapy, the MIP protocol was repeated for one to four supplementary cycles according to tolerance. RESULTS: The rate of OR after MIP was 51% and after chemoradiotherapy it was 69%. Toxic effects were limited to one death due to aplasia and 18 cases of grade 3-4 toxicity, mainly due to hematology disorders. Moderate esophagitis was observed in ten cases. Median survival was 13.5 months. Survival rates were 57% and 29% at one and two years. DISCUSSION: This novel scheme, which can be improved, has demonstrated its efficacy. Tolerance is satisfactory and the cost is low compared with associations using "new" drugs.

[Chemically-induced paraneoplastic hyperleukocytic lung]. / Poumon hyperleucocytaire paranéoplasique chimio-induit.

Dyspnea is the principal clinical feature of pulmonary leukostasis, a syndrome called "poumon hyperleucocytaire" in French. It is a common complication of chronic myeloid leukemia. In the course of pulmonary carcinoma, leukocytosis is frequently noted. One of the etiologies is a paraneoplastic syndrome with production of colony stimulating factor. We report a case of pulmonary hyperleukostasis following antineoplastic chemotherapy for pulmonary carcinoma.

[Treatment of coloboma pitS of the optic nerve complicated by serous detachment of the neuroepithelium]. / Traitement des fossettes colobomateuses de la papille compliquées de décollement séreux du neuroépithélium.

PURPOSE: The pathogenesis of the sensory retinal detachment of the macula associated with congenital pit of the optic nerve remains controversal. Based on our cases and the cases reported in literature, we propose a management plan for macular retinal detachment associated with optic nerve pit. METHODS: In this retrospective study ten eyes were treated for progressive visual loss. Treatment modalities were different depending on the time period: laser photocoagulation (to the juxtapapillary region) alone, laser combined with intraocular gas injection (C3 F8), laser combined with vitrectomy and intraocular gas tamponnade (S F6, C3 F8), laser combined with vitrectomy and temporary silicone oil tamponade. RESULTS: The follow-up period ranged between one and five years (mean follow-up thirty three months). We had eight successes and two definitive failures (an old macular detachment treated only by one laser session, and a young girl who had not kept the prone position after gas injection). In the group of six eyes treated by laser alone, only two retinal treatments were directly successfully treated; in three other eyes, the detachment recurred and was treated with success in a second step by a gas injection; the sixth eye is the first definitive failure (old detachment). In the five eyes treated by laser combined gas injection with or without pars plana vitrectomy (including three failures of laser alone), the retina remained attached in four eyes during the follow-up period; the sixth eye was the second definitive failure (the young girl). In the both eyes treated by vitrectomy and silicon oil injection, the retina has flattened. CONCLUSION: The results suggest that laser photocoagulation alone is not so efficient and that vitrectomy is not necessary with gas injection. Complete resorption of subretinal fluid occurred in eight eyes: two with laser photocoagulation alone, and six with a long term tamponnade combined with a peripapillary laser photocoagulation. In first treatment, this technique (laser with tamponade) is a valuable approach to manage serous macular detachment associated with optic nerve pit.

[N-aryl pyrrole derivatives with analgesic and anti-inflammatory activity 2. Pharmacologic modulation of the 1-arylpyrrole model]. / Dérivés N-aryl pyrroliques à activité analgésique et anti-inflammatoire. 2ème Partie--Pharmaco-modulation du modèle aryl-1 pyrrole.

In order to increase the pharmacological activities of the molecules described in the first part of the paper, an acetic or a 2-propionic group was introduced in to the fundamental structure, either on the aromatic ring, on the pyrrole nitrogen or on carbon 3 of the heterocycle. Moreover, a 4-chlorobenzoyl group was fixed on carbon 3 of the pyrrole via condensation of 4-chloroaniline with 4-chlorobenzoyl triketones. The structure of the adducts was demonstrated both by N.M.R. spectra and by using another unambiguous synthetic route. Finally, derivatives with the salicylic substructure on the nitrogen of the pyrrole are described. Their analgesic and anti-inflammatory properties are reported as well as some effects on the central nervous system.

[N-aryl pyrrol derivatives with analgesic and anti-inflammatory activity. 1. 1-Arylpyrroles substituted at positions 4 and 5]. / Dérivés N-aryl pyrroliques à activité analgésique et anti-inflammatoire. 1ère Partie. Aryl-1 pyrroles di substitués en 4 et 5.

The derivatives in question are prepared by reaction of substituted anilines with 1,4-ketones in an acidic medium. The diketones are themselves obtained either using Friedel and Crafts reaction with levulinic acid chloride, or by Stetter's method reacting Mannich bases with aryl aldehydes in the presence of sodium cyanide. The results of test of acute toxicity and of analgesic and anti-inflammatory activity are reported.