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1.
Lung Cancer ; 192: 107800, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38728972

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) without oncogenic driver mutations is considered to have a poor prognosis, although recent therapeutic progress. This study aims to assess the real-life integration of palliative care (PC) and the intensity of end-of-life (EOL) care for this population. METHODS: This was an observational cohort study of decedent patients from metastatic NSCLC without oncogenic driver mutations over the period 01/2018 to 12/2022, treated in first line with immunotherapy +/- chemotherapy. We analysed PC integration and aggressiveness criteria of EOL care in the last month before death: systemic anti-cancer treatment administration, emergency room visits, intensive care unit admission, hospitalization, hospitalization duration > 14 days, and hospital death. RESULTS: Among 149 patients, 75 (50 %) met the PC team at least once, and the median time from the first encounter to death was 2.3 months. In the last month before death, at least one criterion of aggressive EOL care was present for 97 patients (70 %). For patients with PC use < 30 days and for patients with PC use < 90 days before death, there were significant changes: increase in the frequency of systemic anti-cancer treatment (respectively 51.1 % vs 20 %; p < 0.001 and 58.7 % vs 6.2 %; p < 0.001); decrease in hospitalization lasting > 14 days (respectively 30 % vs 7 %; p = 0.001 and 36 % vs 6.2 %; p = 0.018) and in death hospitalisation (respectively 66 % and 18 %; p < 0.001 and 58.7 % and 10.3 %; p < 0.001). After adjusting for the factors tested, patients with no PC or late PC use in the last month before death or in the last three month before death, the odds ratio (OR) remained significantly greater than 1 (respectively OR = 3.97 [1.70; 9.98]; p = 0.001 and OR = 23.1 [5.21-177.0], p < 0.0001). CONCLUSION: PC is still insufficiently integrated for patients with NSCL cancer. Cancer centres should monitor key indicators such as PC use and aggressiveness criteria of EOL care.

2.
Ann Oncol ; 35(1): 77-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37879444

RESUMO

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.


Assuntos
Acrilamidas , Compostos de Anilina , Anticorpos Biespecíficos , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Morfolinas , Pirazóis , Pirimidinas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Progressão da Doença , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico
3.
J Plast Reconstr Aesthet Surg ; 85: 202-209, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37524032

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are associated with improved management, reduced hospital stays, and lower complication rates. OBJECTIVE: To evaluate the impact of ERAS on mean length of stay (LOS) and postoperative morbidity in breast reconstruction with latissimus dorsi flap (LDF) compared with conventional recovery program. PATIENTS AND METHOD: All patients operated by LDF between December 2014 and October 2020: those managed before April 2018, when the ERAS protocol was introduced, were included in the "no ERAS" group, and beyond in the "ERAS" group. RESULTS: Out of 193 patients, 129 were included in the "ERAS" group and 64 in the "no ERAS" group. There was a significant difference between the two groups in LOS (4.2 ± 1.5 days in the "ERAS" group vs. 5.4 ± 1.9 days in the "no ERAS" group; p < 0.001), high-grade complications at 30 days (9.3% in the "ERAS" group vs. 25% in the "no ERAS" group; p = 0.01), reintervention rate (13.9% vs. 26.6%, respectively; p = 0.02), and 30-day rehospitalization rate (6.2% in the "ERAS" group vs. 15.6% in the "no ERAS" group; p = 0.03). CONCLUSION: The ERAS protocol has a positive impact on breast reconstruction with LDF without generating additional adverse effects. These results support the democratization of these programs for breast reconstruction surgery.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Mamoplastia , Músculos Superficiais do Dorso , Humanos , Músculos Superficiais do Dorso/transplante , Complicações Pós-Operatórias/etiologia , Mamoplastia/métodos , Retalhos Cirúrgicos , Tempo de Internação , Estudos Retrospectivos
4.
ESMO Open ; 8(3): 101576, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37285717

RESUMO

BACKGROUND: Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. MATERIALS AND METHODS: NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. RESULTS: From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. CONCLUSIONS: Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab.


Assuntos
Timoma , Neoplasias do Timo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Timoma/tratamento farmacológico , Timoma/induzido quimicamente , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/induzido quimicamente , Intervalo Livre de Progressão
6.
J Small Anim Pract ; 64(4): 296-305, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36573276

RESUMO

OBJECTIVES: The aim of this case series was to collect preliminary data on safety and efficacy of treating cats suffering from refractory feline chronic gingivostomatitis with a single intravenous therapy of cryopreserved placenta-derived mesenchymal stromal cells. MATERIALS AND METHODS: We planned the prospective inclusion of cats suffering from refractory chronic gingivostomatitis in three veterinary clinics. All cats received a single infusion of 10×106 cryopreserved cells. Follow-up evaluations were done at day 15 and at 2-, 3- and 6-months following infusion. Clinical disease severity was evaluated by dental specialists using a published stomatitis disease activity index scoring system coupled with an owners' assessment questionnaire. RESULTS: All eight cats attended all follow up visits. Cryopreserved ready-to-use placenta-derived cells administered systemically were safe and resulted in notable clinical improvement in all cats as reported by stomatitis disease activity index scoring and owner's survey. CLINICAL SIGNIFICANCE: Infusion of cryopreserved freshly thawed placenta-derived mesenchymal stromal cells appears to promote clinical and consequently behavioural benefits in cats with refractory chronic gingivostomatitis after having undergone full-mouth or premolar-molar tooth extraction. Future randomised studies are required to confirm safety and efficacy of this treatment.


Assuntos
Doenças do Gato , Células-Tronco Mesenquimais , Estomatite , Gatos , Animais , Estudos Prospectivos , Estomatite/tratamento farmacológico , Estomatite/veterinária , Doenças do Gato/terapia
7.
AJNR Am J Neuroradiol ; 43(9): 1363-1368, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36007951

RESUMO

BACKGROUND AND PURPOSE: Brain AVMs represent the main etiology of pediatric intracranial hemorrhage. Noninvasive imaging techniques to monitor the treatment effect of brain AVMs remain an unmet need. In a large cohort of pediatric ruptured brain AVMs, we aimed to investigate the role of arterial spin-labeling for the longitudinal follow-up during treatment and after complete obliteration by analyzing CBF variations across treatment sessions. MATERIALS AND METHODS: Consecutive patients with ruptured brain AVMs referred to a pediatric quaternary care center were prospectively included in a registry that was retrospectively queried for children treated between 2011 and 2019 with unimodal or multimodal treatment (surgery, radiosurgery, embolization). We included children who underwent an arterial spin-labeling sequence before and after treatment and a follow-up DSA. CBF variations were analyzed in univariable analyses. RESULTS: Fifty-nine children with 105 distinct treatment sessions were included. The median CBF variation after treatment was -43 mL/100 mg/min (interquartile range, -102-5.5), significantly lower after complete nidal surgical resection. Following radiosurgery, patients who were healed on the last DSA follow-up demonstrated a greater CBF decrease on intercurrent MR imaging, compared with patients with a persisting shunt at last follow-up (mean, -62 [SD, 61] mL/100 mg/min versus -17 [SD, 40.1] mL/100 mg/min; P = .02). In children with obliterated AVMs, recurrences occurred in 12% and resulted in a constant increase in CBF (mean, +89 [SD, 77] mL/100 mg/min). CONCLUSIONS: Our results contribute data on the role of noninvasive arterial spin-labeling monitoring of the response to treatment or follow-up after obliteration of pediatric AVMs. Future research may help to better delineate how arterial spin-labeling can assist in decisions regarding the optimal timing for DSA.


Assuntos
Malformações Arteriovenosas Intracranianas , Radiocirurgia , Humanos , Criança , Seguimentos , Estudos Retrospectivos , Marcadores de Spin , Resultado do Tratamento , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/terapia , Encéfalo , Radiocirurgia/métodos
8.
Rev Neurol (Paris) ; 178(7): 666-674, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35568516

RESUMO

Rasmussen's encephalitis (RE) is a rare chronic inflammatory brain disorder resulting in progressive neurodegeneration in one cerebral hemisphere. The inflammatory process is accompanied by progressive loss of function of the affected hemisphere, associated with drug-resistant partial epilepsy. The diagnosis is based on a range of clinical, electroencephalographic, radiological and biochemical arguments, without any specific formal marker, which makes the diagnosis of the disease complex, especially in its initial phase. Seizures are refractory to anti-seizures medication (ASM) and to classical immunomodulatory treatments. These treatments are also ineffective to stop the degenerative process. Only surgical treatment with hemispherotomy (surgical disconnection of a cerebral hemisphere) allows definitive cessation of seizures but this leads to definitive motor and cognitive deficits. The etiology of RE is not known, but there is strong evidence for an immunopathogenic mechanism involving T-cell mediated immunity. The emergence of biotherapies targeting against various cytokines offers potential therapeutic perspectives. This disease is currently a real challenge in terms of: (i) early diagnosis, before the constitution of marked hemispheric atrophy and the appearance of neurological and cognitive consequences; (ii) recognition of incomplete form; (iii) therapeutic management due to advances in the field of targeted treatment of inflammation; (iv) surgery and recovery possibilities.


Assuntos
Encefalite , Atrofia , Encéfalo/patologia , Criança , Doença Crônica , Diagnóstico Precoce , Eletroencefalografia , Encefalite/complicações , Encefalite/diagnóstico , Encefalite/terapia , Humanos , Imageamento por Ressonância Magnética
9.
ESMO Open ; 7(2): 100418, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35227966

RESUMO

INTRODUCTION: ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program. METHODS: Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival. RESULTS: Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data. CONCLUSIONS: Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Aminopiridinas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Lactamas , Lactamas Macrocíclicas/farmacologia , Lactamas Macrocíclicas/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/uso terapêutico , Pirazóis
10.
J Fr Ophtalmol ; 45(2): 173-184, 2022 Feb.
Artigo em Francês | MEDLINE | ID: mdl-34972579

RESUMO

INTRODUCTION: Optic pathway glioma (OPG) is a classic complication of neurofibromatosis type 1 (NF1) and can impair visual function in children with this condition. The objective of this study is to describe clinical, paraclinical and prognostic characteristics of OPG associated with NF1. MATERIALS AND METHODS: In this retrospective observational study of children followed for OPG associated with NF1 in a University Hospital, we analyzed the ophthalmological examination, brain and orbital imaging, management and the presence of associated endocrinopathy. RESULTS: We examined 114 children with NF1, of which 26 (22.81%) presented with OPG. Mean ages at diagnosis of NF1 and OPG were 3.83 years and 6.23 years, respectively. Mean visual acuity was 20/24.4 for the worse eye and 20/23.1 for the better eye. The RNFL (retinal nerve fiber layer) was thinner in subjects than in age-matched controls (p <0.0001). Retrochiasmal location of the OPG (DodgeC) was associated with lower binocular visual acuity than other locations and <20/32 (p=0.028); 28.03% of OPG (5 girls and 1 boy) were treated with chemotherapy, and the others were monitored; 19.23% had an associated endocrinopathy. CONCLUSIONS: OPG complicates 22.81% of NF1 cases in our series. Our study shows that retrochiasmal location of the glioma and female sex are poor prognostic factors. It also highlights the important role of OCT, since a decrease in RNFL is statistically associated with the presence of an OPG.


Assuntos
Neurofibromatose 1 , Glioma do Nervo Óptico , Criança , Feminino , Humanos , Masculino , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/epidemiologia , Glioma do Nervo Óptico/complicações , Glioma do Nervo Óptico/diagnóstico , Glioma do Nervo Óptico/epidemiologia , Prognóstico , Estudos Retrospectivos , Acuidade Visual
12.
ESMO Open ; 7(1): 100353, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34953398

RESUMO

BACKGROUND: Immunotherapy using inhibitors targeting immune checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is currently the standard of care in patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We carried out a nationwide cohort retrospective study of consecutive patients with advanced, refractory NSCLC who received nivolumab as second to later lines of treatment as part of the expanded access program. Key objectives were to assess the efficacy and safety of nivolumab and the efficacy of first post-nivolumab treatment. RESULTS: Nine hundred and two patients were enrolled: 317 (35%) with squamous cell carcinoma and 585 (65%) with non-squamous cell carcinoma. Median age was 64 years; there were 630 (70%) men, 795 (88%) smokers, 723 (81%) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0/1, 197 (22%) patients with brain metastases, and 212 (27%) with liver metastases. Best response was partial response for 16.2% and stable disease (SD) for 30.5%. Progression-free survival and overall survival (OS) rates at 2, 3, and 5 years were 8% and 25%, 6% and 16%, and 4% and 10%, respectively. At multivariate analysis, ECOG PS ≥2 [hazard ratio (HR) = 2.13, 95% confidence interval (95% CI) 1.78-2.55, P < 0.001], squamous histology (HR = 1.17, 95% CI 1.01-1.36, P = 0.04), and presence of central nervous system metastases (HR = 1.29, 95% CI 1.08-1.54, P = 0.005) were significantly associated with lower OS. Four hundred and ninety-two patients received at least one treatment after discontinuation of nivolumab, consisting of systemic therapies in 450 (91%). Radiation therapy was delivered to 118 (24%) patients. CONCLUSION: The CLINIVO cohort represents the largest real-world evidence cohort with the use of immune checkpoint inhibitor in advanced, metastatic NSCLC after failure of first-line chemotherapy, with long-term follow-up and analysis of subsequent therapies. Our data confirm the efficacy of nivolumab in a cohort larger than that reported in landmark clinical trials and identify prognostic factors, which reinforces the need for accurate selection of patients for treatment with immune checkpoint inhibitors. Our data indicate that oligoprogression is frequent after nivolumab exposure and provide a unique insight into the long-term survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/farmacologia , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos
13.
J Bone Oncol ; 29: 100364, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34150488

RESUMO

More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients. Serum periostin was assessed at diagnosis in a prospective cohort of 133 patients with lung adenocarcinoma of all stages. Patients were divided into localized and bone metastatic groups. Both groups were matched to healthy controls. Survival analysis and Cox proportional hazards models were conducted in the total population and in bone metastatic group. The median serum periostin level was higher in bone metastatic (n = 67; median: 1752 pmol/L) than in the localized group (n = 66; 861 pmol/L; p < 0.0001). Patients with high periostin (>median) had a poorer overall survival in the whole population (33.3 weeks vs. NR; p < 0.0001) and the bone metastatic group (24.4 vs. 66.1 weeks; p < 0.001). In multivariate analysis, patients with high periostin had increased risk of death (HR = 2.09, 95%CI [1.06-4.13]; p = 0.03). This was also found in the bone metastatic group (HR = 3.62, 95%CI [1.74-7.52]; p = 0.0005). Immunohistochemistry on bone metastasis biopsies showed periostin expression in the bone matrix and nuclear and cytoplasmic staining in cancer cells. Serum periostin was an independent survival biomarker in all-stage and in bone metastatic lung adenocarcinoma patients. IHC data suggest that periostin might be induced in cancer cells in bone metastatic niche in addition to bone microenvironment expression.

14.
Rev Mal Respir ; 38(5): 477-488, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34020835

RESUMO

The development of new targeted therapies in non-small cell lung carcinoma (NSCLC) depends on a better understanding of the molecular basis of carcinogenesis, a knowledge of the role of molecular aberrations in disease progression and the development of molecular biology platforms with the capacity to identify new biomarkers. In the current article, we review the techniques routinely used in cancer molecular biology platforms as well as new techniques under development. These new NSCLC biomarkers have been made available to clinicians and biologists in parallel with the development of targeted drugs. New molecular abnormalities of EGFR exon 20, HER2, MET, RET, BRAF, ROS1 and NTRK have been identified and there have been clinical trials of the most innovative targeted drugs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinogênese , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Terapia de Alvo Molecular , Mutação , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas/genética
15.
ESMO Open ; 6(3): 100106, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33865192

RESUMO

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Imunoterapia , Papillomaviridae , Estudos Prospectivos
17.
Neuroradiology ; 63(8): 1353-1366, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33506349

RESUMO

PURPOSE: Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) perfusion MRI are applied in pediatric brain tumor grading, but their value for clinical daily practice remains unclear. We explored the ability of ASL and DSC to distinguish low- and high-grade lesions, in an unselected cohort of pediatric cerebral tumors. METHODS: We retrospectively compared standard perfusion outcomes including blood volume, blood flow, and time parameters from DSC and ASL at 1.5T or 3T MRI scanners of 46 treatment-naive patients by drawing ROI via consensus by two neuroradiologists on the solid portions of every tumor. The discriminant abilities of perfusion parameters were evaluated by receiver operating characteristic (ROC) over the entire cohort and depending on the tumor location and the magnetic field. RESULTS: ASL and DSC parameters showed overall low to moderate performances to distinguish low- and high-grade tumors (area under the curve: between 0.548 and 0.697). Discriminant abilities were better for tumors located supratentorially (AUC between 0.777 and 0.810) than infratentorially, where none of the metrics reached significance. We observed a better differentiation between low- and high-grade cancers at 3T than at 1.5-T. For infratentorial tumors, time parameters from DSC performed better than the commonly used metrics (AUC ≥ 0.8). CONCLUSION: DSC and ASL show moderate abilities to distinguish low- and high-grade brain tumors in an unselected cohort. Absolute value of K2, TMAX, tMIP, and normalized value of TMAX of the DSC appear as an alternative to conventional parameters for infratentorial tumors. Three Tesla evaluation should be favored over 1.5-Tesla.


Assuntos
Neoplasias Encefálicas , Meios de Contraste , Neoplasias Encefálicas/diagnóstico por imagem , Circulação Cerebrovascular , Criança , Humanos , Imageamento por Ressonância Magnética , Gradação de Tumores , Perfusão , Estudos Retrospectivos , Marcadores de Spin
19.
Arch Pediatr ; 28(1): 87-92, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33342683

RESUMO

We describe the clinical, electroencephalography (EEG), and developmental features of a patient with developmental and epileptic encephalopathy due to a homozygous pathogenic variation of mitochondrial glutamate/H+ symporter SLC25A22. Epilepsy began during the first week of life with focal onset seizures. Interictal EEG revealed a suppression-burst pattern with extensive periods of non-activity. The prospective follow-up confirmed developmental encephalopathy as well as ongoing active epilepsy and almost no sign of development at 8 years of age. We confirm in the following paper that SLC25A22 recessive variations may cause a severe developmental and epileptic encephalopathy characterized by a suppression-burst pattern. On the basis of an in-depth literature review, we also provide an overview of this rare genetic cause of neonatal onset epilepsy.


Assuntos
Encefalopatias/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Epilepsia/diagnóstico , Proteínas de Transporte da Membrana Mitocondrial/genética , Fenótipo , Encefalopatias/genética , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Eletroencefalografia , Epilepsia/genética , Feminino , Genes Recessivos , Homozigoto , Humanos , Lactente , Recém-Nascido , Mutação
20.
Ann Oncol ; 31(10): 1320-1335, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745693

RESUMO

We established an international consortium to review and discuss relevant clinical evidence in order to develop expert consensus statements related to cancer management during the severe acute respiratory syndrome coronavirus 2-related disease (COVID-19) pandemic. The steering committee prepared 10 working packages addressing significant clinical questions from diagnosis to surgery. During a virtual consensus meeting of 62 global experts and one patient advocate, led by the European Society for Medical Oncology, statements were discussed, amended and voted upon. When consensus could not be reached, the panel revised statements until a consensus was reached. Overall, the expert panel agreed on 28 consensus statements that can be used to overcome many of the clinical and technical areas of uncertainty ranging from diagnosis to therapeutic planning and treatment during the COVID-19 pandemic.


Assuntos
Betacoronavirus , Consenso , Infecções por Coronavirus , Oncologia , Neoplasias , Pneumonia Viral , Sociedades Médicas , Humanos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , COVID-19 , Gerenciamento Clínico , Europa (Continente)/epidemiologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Oncologia/métodos , Oncologia/normas , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias/terapia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , SARS-CoV-2 , Sociedades Médicas/normas , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Telemedicina/métodos , Telemedicina/normas
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