Clinical characteristic and survival outcomes of patients with advanced NSCLC according to KRAS mutational status in the French real-life ESME cohort.

PURPOSE: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. PATIENTS AND METHODS: We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. RESULTS: Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P = 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. CONCLUSION: We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.

RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. PATIENTS AND METHODS: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. RESULTS: The first patient will be enrolled in January 2021, with results expected in 2028.

[Prophylactic radiotherapy in a single fraction of 10Gy at intervention pleural site in patient with malignant pleural mesothelioma: A retrospective monocentric cohort study]. / Irradiation préventive en une séance de 10Gy des sites d'intervention pleurale des patients atteints de mésothéliome pleural malin : étude de cohorte rétrospective monocentrique.

PURPOSE: Prophylactic radiotherapy to prevent procedure-tracts metastases from malignant pleural mesothelioma remains controversial and clinical practice varies. The purpose was to assess the efficacy of local radiotherapy in a single fraction of 10Gy in preventing malignant seeding at intervention pleural site in patients with malignant pleural mesothelioma. MATERIAL AND METHODS: This is a retrospective cohort study, including patients with histological confirmed malignant pleural mesothelioma treated by prophylactic irradiation to prevent interventional site metastases with a unique fraction of 10Gy with 6 to 18MeV, from January 1990 to December 2013 in the institut de cancérologie de Lorraine (Nancy, France). RESULTS: Ninety-one patients were treated by irradiation in intervention site, involving 120 intervention pleural sites, 91 thoracoscopies, 17 thoracotomies with chest drain and 12 CT or ultrasound guided needle biopsies. The median follow-up was 7 months (interquartile between 3 and 15 months). The overall survival was 43.5% at 12 months. The local progression free survival was 43.7% at 12 month. The incidence of local recurrence was 8% at 12 months. The median interval from radiotherapy to local recurrence was 4 months (2; 32). No grade II or higher toxicity was observed. CONCLUSION: Irradiation of pleural intervention sites with a single fraction of 10Gy is effective, well tolerated, simple, fast and cost effective.

[Hypofractionated stereotactic radiotherapy for brain metastasis: Benefit of additional whole brain radiotherapy?] / Radiothérapie stéréotaxique hypofractionnée des métastases cérébrales : bénéfice de l'irradiation encéphalique totale ?

PURPOSE: To study overall survival, risk of neurological death, local recurrence and development of new brain metastasis in patients treated for brain oligometastases with hypofractionated stereotactic radiotherapy with CyberKnife®, according to the association or not with an additional whole brain irradiation. PATIENTS AND METHODS: Institutional retrospective study of 102 patients treated for one to three brain metastasis: 76 with exclusive hypofractionated stereotactic radiotherapy and 26 with hypofractionated stereotactic radiotherapy and whole brain irradiation. Objectives were assessed and compared between these two groups according to the Kaplan-Meier method and Cox model. RESULTS: Median follow-up was 18.8 months. There were no difference between exclusive hypofractionated stereotactic radiotherapy and hypofractionated stereotactic radiotherapy with whole brain irradiation for overall survival (respective median 21.5 and 20.1 months), risk of neurological death (respectively 9.2% and 15.4% at one year). At one year: the risk of cerebral progressive disease was greater in the group receiving exclusive hypofractionated stereotactic radiotherapy (respectively 43.4% vs. 26.2%, P=0.043), the risk of local recurrence was 25% versus 17.6% (P=0.28) and the development of new brain metastasis was 23.7% versus 11.5% (P=0.27). After salvage treatments, crude local control was similar in the two groups, respectively 78.6% and 73.5%. Whole brain irradiation has been avoided for 72.4% of patients in the group receving exclusive hypofractionated stereotactic radiotherapy. CONCLUSION: Whole brain irradiation improves local control of brain metastatic disease in addition to hypofractionated stereotactic radiotherapy. Sparing whole brain irradiation for salvage treatments only does not affect overall survival or risk of neurological death in selected patients with favourable prognosis.

[Complementary and alternative medicine use by lung cancer patients]. / Le recours aux médecines « complémentaires et alternatives ¼ par les patients atteints d'un cancer bronchique.

INTRODUCTION: Complementary and alternative medicine (CMA) use is frequent among cancer patients. Only few results are available about lung cancer patients. The aim of this study was to evaluate how often the CMA were used by lung cancer patients and to define the type of CMA used. METHODS: Every lung cancer patients with an ongoing chemotherapy in the respiratory department of the University Hospital of Nancy were approached between November 2014 to July 2015. A detailed and anonymous survey was conducted and the socioeconomic characteristics were collected from medical records. RESULTS: Ninety-one patients were questioned. On 82 patients having answered, 19.5 % had used at least a CMA. The main CMA used was the physical exercise in 50 % of the patients. CMA users were significantly younger with a mean age of 56.4 years versus 65.4 years (P=0.0007). More than half patients did not indicate to their specialist that they used a CMA. The main information source was the circle of acquaintances. CONCLUSIONS: CMA use is frequent among lung cancer patients. The physical exercise is quoted most of the time among the various CMA. There is a real lack of communication on the subject between the physician and the patient. It is thus imperative that the pulmonologists give much interest to these practices in order to give better advices and to reinforce the patient-physician relationship.

[Malignant rhabdoid tumor of the lung]. / Tumeur pulmonaire maligne de type rhabdoïde.

INTRODUCTION: Rhabdoid tumours usually develop in brain and spinal cord or kidney; they are highly malignant neoplasms that typically arise in infancy and early childhood. However, rare cases of pulmonary localization have been described, particularly among young adults. CASE REPORT: A 26-year-old man, smoker, had a right apical lung mass associated with a Pancoast syndrome leading to haemoptysis. There was also a tumour of the left thigh and scalp. Histological samples taken at these three locations were in favour of an undifferentiated carcinoma. The lack of nuclear integrase interactor 1 expression, and immunohistochemical appearance supported the diagnosis of rhabdoid tumour. Despite treatment, unfavourable progression confirmed this hypothesis, doubling time was less than six weeks with development of multiple metastases resulted in death within only three months after diagnosis. CONCLUSION: The lack of expression of integrase interactor 1 should suggest the diagnosis of rhabdoid tumour, especially when there is quick progression. The prognosis of these tumours remains poor and therapeutic options are limited.

Capillary solitons on a levitated medium.

A water cylinder deposited on a heated channel levitates on its own generated vapor film owing to the Leidenfrost effect. This experimental setup permits the study of the one-dimensional propagation of surface waves in a free-to-move liquid system. We report the observation of gravity-capillary waves under a dramatic reduction of gravity (up to a factor 30), leading to capillary waves at the centimeter scale. The generated nonlinear structures propagate without deformation and undergo mutual collisions and reflections at the boundaries of the domain. They are identified as Korteweg-de Vries solitons with negative amplitude and subsonic velocity. The typical width and amplitude-dependent velocities are in excellent agreement with theoretical predictions based on a generalized Korteweg-de Vries equation adapted to any substrate geometry. When multiple solitons are present, they interact and form a soliton turbulencelike spectrum.

[Management of chemotherapy-induced anemia in lung cancer]. / Prise en charge de l'anémie chimio-induite dans le cancer bronchique.

INTRODUCTION: The prevalence of chemotherapy-induced anemia in lung cancer is estimated at about 80%. STATE OF ART: There are currently no specific recommendations for the management of chemotherapy-induced anemia in lung cancer. In this paper, we propose a synthesis of currently existing data in the literature on the management of chemotherapy-induced anemia in general, supplemented with specific data about the efficacy and safety of erythropoietic therapy in lung cancer. PERSPECTIVES: Better management of chemotherapy-induced anemia improves patient's quality of life and reduces red blood cell transfusion requirement. In the meantime, in respect to currently missing data, thoracic oncologists should develop specific recommendations for the management of chemotherapy-induced anemia in lung cancer, with specific studies in this domain. CONCLUSIONS: Since the prevalence of chemotherapy-induced anemia in patients with lung cancer is high and has a significant impact on these patients quality of life, a specific prospective management should be implemented as early as possible.

[Evaluation of requests for a second medical opinion by patients with lung cancer]. / Évaluation de la demande de deuxième avis par les patients atteints de cancer bronchique.

INTRODUCTION: Getting a second opinion seems common in oncology, even though the management of these serious diseases results from a multidisciplinary approach. Our aim was to determine the incidence of requests for a second opinion in thoracic oncology at the university hospital of Nancy, since the establishment of the Cancer Plan in 2003. This plan formalized multidisciplinary staff meetings, which should help to reassure patients and therefore reduce the recourse to additional consultations. METHODS: A detailed and anonymous questionnaire was conducted on 77 patients suffering from lung cancer, followed-up over 2years in the respiratory department of the University Hospital of Nancy. The socio-economic characteristics were collected from the medical records. RESULTS: Recourse to a second practitioner was reported by 14 % of the patients suffering from lung cancer. It concerned more women than men and more patients with a higher educational level and socio-professional category. CONCLUSION: Requests for a second opinion by patients with lung cancer are not as frequent as expected. However, when they are made, it is more frequently by women and patients with a higher socio-economic status.

[Primary lateral sclerosis and lung adenocarcinoma]. / Sclérose latérale primitive et adénocarcinome bronchique. Syndrome paranéoplasique ou association fortuite ?

INTRODUCTION: Lung cancer is frequently associated with paraneoplastic syndromes, sometimes uncommon, among which motor neurone disease is sometimes described, including primary lateral sclerosis, a disorder characterized by slowly progressive cortico-spinal dysfunction due to the degeneration of the upper motor neurone. CASE REPORT: We report a case of primary lateral sclerosis developing in a young woman 9 months after the diagnosis of metastatic adenocarcinoma of the lung. Our patient showed a spastic quadriparesis, dysarthria and bulbar symptoms without amyotrophy nor fasciculation. The electromyogram showed isolated upper motor neurone involvement. Cerebral and medullary imaging and CSF analysis showed no abnormality and onconeuronal antibodies were negative. The neurological symptoms and the cancer deteriorated simultaneously and our patient died 6 months after the onset of neurological symptoms. CONCLUSION: Motor neurone involvement is rare but some case reports describe an association with neoplasia without formal confirmation of a paraneoplastic syndrome. Our case is the first report of primary lateral sclerosis in a young woman diagnosed during the treatment of lung adenocarcinoma.

Occupational risk factors have to be considered in the definition of high-risk lung cancer populations.

BACKGROUND: The aim of this study was to compute attributable fractions (AF) to occupational factors in an area in North-Eastern France with high lung cancer rates and a past of mining and steel industry. METHODS: A population-based case-control study among males aged 40-79 was conducted, including confirmed primary lung cancer cases from all hospitals of the study region. Controls were stratified by broad age-classes, district and socioeconomic classes. Detailed occupational and personal risk factors were obtained in face-to-face interviews. Cumulative occupational exposure indices were obtained from the questionnaires. Attributable fractions were computed from multiple unconditional logistic regression models. RESULTS: A total of 246 cases and 531 controls were included. The odds ratios (ORs) adjusted on cumulative smoking and family history of lung cancer increased significantly with the cumulative exposure indices to asbestos, polycyclic aromatic hydrocarbons and crystalline silica, and with exposure to diesel motor exhaust. The AF for occupational factors exceeded 50%, the most important contributor being crystalline silica and asbestos. CONCLUSION: These AFs are higher than most published figures. This can be because of the highly industrialised area or methods for exposure assessments. Occupational factors are important risk factors and should not be forgotten when defining high-risk lung cancer populations.

[Anti-angiogenic agents in the treatment of lung cancer: indications and toxicities]. / Thérapeutiques antiangiogéniques dans le cancer bronchique: indications et toxicités.

Lung cancer is the leading cause of cancer-related death. Targeting the vascular endothelial growth factor (VEGF) pathways in combination with standard chemotherapy can improve response rate and survival in non-small cell lung cancer. Since October 2006, a new class of drugs targeting angiogenesis has been introduced for the treatment of advanced lung cancer. Bevacizumab, an antibody directly targeting VEGF was the first agent to be approved. Other small molecule tyrosine kinase inhibitors targeting the VEGF receptor are also active in the treatment of advanced lung cancer and are currently under development. Most of these new drugs are well tolerated though potentially significant toxicities such as haemoptysis and hypertension have been observed. This article will review these new-targeted anti-angiogenic agents with a focus on their use in lung cancer and on their important side effects.

[Do all cryptogenic organizing pneumonias require lung biopsy and steroid treatment?]. / Pneumopathie organisée cryptogénique : biopsie et corticoïdes sont-ils constamment utiles ?

INTRODUCTION: Diagnostic guidelines recommend a lung biopsy to make the diagnosis of cryptogenic organizing pneumonia (COP). However, in some cases, in the presence of a typical clinical picture, the diagnosis can be made without histological proof: the combination of a "reversed halo sign" and migratory areas of patchy alveolar consolidation on the CT-scan is strongly suggestive. Steroids are the recommended treatment, but relapses and complications of steroids occur frequently whereas the morbidity of COP is usually low and the evolution is often the same with or without treatment. CASE REPORT: We report the case of a 51 year old woman with mild COP. The diagnosis was made according to the clinico-radiological criteria that we propose, without any formal histological proof. Treatment consisted of a short course of steroids, which led to spectacular clinical and radiological improvement but was withdrawn due to poor tolerance. The patient refused further treatment but clinical progress was favourable. After a follow-up period of 2.5 years a CT-scan showed evidence of a radiological relapse but the patient remained asymptomatic. CONCLUSION: In this article, we do not attempt to prove that lung biopsy and steroid treatment are unnecessary in the management of COP, but we would like to propose that, in some situations with the coexistence of a "reversed halo sign" and migratory areas of patchy consolidation on the CT-scan, in the context of a typical clinical presentation and mild symptoms, the usefulness of lung biopsy and steroid treatment is debatable.

[Protocols for lung cancer screening: Limitations, and consequences]. / Les protocoles de dépistage du cancer bronchique: limites et conséquences.

Lung cancer is the leading cause of cancer mortality in the world. Its incidence is still rising, especially in women, and its prognosis is poor with a 5-year survival of 15%. Since 1970, several studies on lung cancer screening have been conducted using different investigations. Screening by chest X-ray and sputum cytology does not lead to improved survival in lung cancer. Screening by CT scan has the same outcome but the detection of lung cancer, especially in its early stages, is better than with chest X-ray and sputum cytology. Fluorescence endoscopy is a valuable examination for the detection of pre-invasive bronchial lesions. Genetic studies and identification of circulating tumour cells are being developed. All these examinations are very stressful for the patients. Only few trials have studied the consequences of lung cancer screening on the quality of life. In this review, we analyze the various screening strategies, their impact on quality of life and health and their adverse effects.

[Cannabis-induced cerebral and myocardial infarction in a young woman]. / Infarctus cérébral et myocardique après consommation de cannabis chez une femme jeune.

INTRODUCTION: Cannabis is the most consumed drug in the world particularly in young adults. Few reports have suggested a causal role of cannabis in the development of cerebral or cardiovascular events. We describe the first association of myocardial infarction and stroke after heavy cannabis consumption in a 45-year-old woman. OBSERVATION: Stroke occurred in relation with a right carotid and middle cerebral artery thrombosis after cannabis abuse. The patient was successfully treated with intravenous rt-PA. Two days after her admission, she presented a myocardial infarction due to a coronary thrombosis. Cerebral and coronary arteries were angiographically normal. Etiological tests were negative and a toxic cause in relation with cannabis consumption was concluded. CONCLUSION: Cannabis can be associated with vascular events by different mechanisms. Thrombosis may occur in cerebral and/or coronary arteries. We suggest that it might be useful to search for cannabis consumption systematically in young subjects victims of stroke and myocardial infarction.

Relationships between lung adenocarcinoma and gender, age, smoking and occupational risk factors: A case-case study.

BACKGROUND: The hypothesis that some risk factors for lung cancer may have more specific associations with particular histologic types remains controversial. The aim of this study was to investigate possible associations between adenocarcinoma and gender, age, smoking characteristics and selected occupational carcinogens in relation to other histologic types. METHODS: This study included all histologically confirmed lung cancer cases diagnosed consecutively in two French University hospitals from 1997 to 2006. All medical data were obtained by face-to-face patient interviews. Occupational carcinogen exposures of each patient were assessed by an industrial hygienist. Relationships between risk factors and adenocarcinoma were analyzed by case-case comparisons using unconditional logistic regressions (ULRs). RESULTS: A total of 1493 subjects were enrolled in this study, comprising 1303 men (87.3%), 67 nonsmokers (4.5%) and 489 adenocarcinomas (32.7%). Using ULR, no associations were observed between adenocarcinoma and age, gender or smoking characteristics except for a negative relationship with smoking duration (p<0.0001). Significant associations were observed between ADC and exposure to welding fumes and silica in the whole population and with polycyclic aromatic hydrocarbons in ever smokers. CONCLUSION: This study demonstrated that some risk factors, such as duration of smoking and certain occupational exposures but not gender or age, have a more important influence on the incidence of lung ADC than on other histologic types. As the distribution of histologic types may reflect underlying biological mechanisms, these findings also suggest that lung carcinogenesis pathways should be studied in relation to smoking duration and other lung cancer risk factors.

[Crohn's disease during the course of multiple sclerosis: role of interferon-beta therapy]. / Maladie de Crohn au cours d'une sclérose en plaques: rôle de l'interféron bêta.

Interferon-beta (IFN-beta) therapy can trigger immune adverse effects. We report a patient, who was treated for multiple sclerosis (MS) by IFN-beta during 3 years before developing a severe colitis due to Crohn's disease (CD). Neurological manifestations may occur in CD but rarely mimic MS. This report's points highlight the possible association of MS and CD, where IFN-beta therapy probably unmasked CD. Indeed, similar cases of CD flares have been reported after IFN-alpha therapy for chronic C hepatitis.

[Stroke in young adults with celiac disease]. / Accident vasculaire cérébral ischémique de l'adulte jeune au cours de la maladie coeliaque. A propos de deux observations.

INTRODUCTION: Celiac disease is a common condition with a prevalence of about 1%. Clinical extradigestive presentations are various and stroke can be one of the neurological manifestations. EXEGESIS: Two cases of stroke occurring in young adults are described, leading to the diagnosis of celiac disease. Hyperhomocysteinemia or cerebral arterial vasculopathy in one case and antiphospholipid syndrome in the other case are thought to be involved in the pathogenesis of stroke during celiac disease. CONCLUSION: The possible presence of celiac disease should be discussed in unexplained young adult stroke.

Tissue-specific cadmium accumulation and metallothionein-like protein levels during acclimation process in the Chinese crab Eriocheir sinensis.

Aquatic organisms chronically exposed to cadmium can increase their resistance to a subsequent elevated exposure. In order to investigate mechanisms involved in acclimation process in the Chinese crab Eriocheir sinensis, we compared Cd level as well as metallothionein-like protein (MTLP) content in different tissues after direct acute exposure (i.e. 500 microg Cd L(-1) for 3 days), and after acute following chronic (i.e. 10 or 50 microg Cd L(-1) for 30 days) exposure. Cadmium accumulation occurred in the following order: anterior gill>hepatopancreas>posterior gill>carapace>hemolymph>muscle. As high concentrations as 188 microg Cd g(-1) w.w. were reported in anterior gills and seem to reach a saturation level. In these gills, the highest MTLP induction was observed after a direct acute exposure, for which a correlation with Cd content occurred. However, the Cd-binding potential by MTLPs was exceeded for any exposure condition. In hepatopancreas, the highest Cd level was reported for crabs acclimated during 30 days to 50 microg Cd L(-1) before challenging with an acute exposure. Moreover, we showed that MTLPs were induced during the acclimation process. In this organ, MTLPs are theoretically sufficient to bind all Cd. These results suggest that during a chronic exposure to 50 microg Cd L(-1), Chinese crabs acquire the capacity to hold more cadmium in hepatopancreas where it can be sequestrated by MTLPs. On the contrary, MTLP induction seems to be a rapid response to acute exposure in anterior gill, but is not sufficient to sequester all Cd. Other sequestration and/or detoxification mechanisms must take place in anterior gill to cope with high Cd levels.

Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse.

The microrchidia, or morc, autosomal recessive mutation results in the arrest of spermatogenesis early in prophase I of meiosis. The morc mutation arose spontaneously during the development of a mouse strain transgenic for a tyrosinase cDNA construct. Morc -/- males are infertile and have grossly reduced testicular mass, whereas -/- females are normal, indicating that the Morc gene acts specifically during male gametogenesis. Immunofluorescence to synaptonemal complex antigens demonstrated that -/- male germ cells enter meiosis but fail to progress beyond zygotene or leptotene stage. An apoptosis assay revealed massive numbers of cells undergoing apoptosis in testes of -/- mice. No other abnormal phenotype was observed in mutant animals, with the exception of eye pigmentation caused by transgene expression in the retina. Spermatogenesis is normal in +/- males, despite significant transgene expression in germ cells. Genomic analysis of -/- animals indicates the presence of a deletion adjacent to the transgene. Identification of the gene inactivated by the transgene insertion may define a novel biochemical pathway involved in mammalian germ cell development and meiosis.