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The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.
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Fibromatose Agressiva , Adulto , Humanos , Masculino , Fibromatose Agressiva/complicações , Fibromatose Agressiva/epidemiologia , Dor/epidemiologia , Dor/etiologia , Prevalência , Prognóstico , Qualidade de VidaRESUMO
This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2−3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging.
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Neoplasias Ósseas , Condrossarcoma , Osteossarcoma , Adulto , Humanos , Condrossarcoma/diagnóstico , Condrossarcoma/genética , Condrossarcoma/terapia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Radiografia , Osteossarcoma/patologia , BiologiaRESUMO
Biallelic pathogenic variants in the NTHL1 (Nth like DNA glycosylase 1) gene cause a recently identified autosomal recessive hereditary cancer syndrome predisposing to adenomatous polyposis and colorectal cancer. Half of biallelic carriers also display multiple colonic or extra-colonic primary tumors, mainly breast, endometrium, urothelium, and brain tumors. Published data designate NTHL1 as an important contributor to hereditary cancers but also underline the scarcity of available informations. Thanks to the French oncogenetic consortium (Groupe Génétique et Cancer), we collected NTHL1 variants from 7765 patients attending for hereditary colorectal cancer or polyposis (n = 3936) or other hereditary cancers (n = 3829). Here, we describe 10 patients with pathogenic biallelic NTHL1 germline variants, that is, the second largest NTHL1 series. All carriers were from the "colorectal cancer or polyposis" series. All nine biallelic carriers who underwent colonoscopy presented adenomatous polyps. For digestive cancers, average age at diagnosis was 56.2 and we reported colorectal, duodenal, caecal, and pancreatic cancers. Extra-digestive malignancies included sarcoma, basal cell carcinoma, breast cancer, urothelial carcinoma, and melanoma. Although tumor risks remain to be precisely defined, these novel data support NTHL1 inclusion in diagnostic panel testing. Colonic surveillance should be conducted based on MUTYH recommendations while extra-colonic surveillance has to be defined.
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Desoxirribonuclease (Dímero de Pirimidina)/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/genética , Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Feminino , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Rhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy. OBJECTIVE: We report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS. METHODS: Considering the poor prognosis and the few systemic therapeutic options, we decided to carry out a whole exome sequencing (WES) of the tumour and germline DNA. RESULTS: WES identified a germline variation (c.1863_1864insT) in the MLH1 gene corresponding to a pathogenic mutation: (p. Leu622Serfs*10), whereas the family history did not fit with classical criteria for Lynch syndrome. Loss-of-heterozygosity at MLH1 locus was found in the tumour. Immunohistochemistry showed loss of MLH1 and PMS2 nuclear expression in the tumour cells. In view of the mismatch repair defects and a high programmed cell death ligand 1 (PD-L1) expression (60% of tumour cells expressed PD-L1), we administrated an anti-PD-1 antibody to the patient. He achieved a rapid complete response of the lung metastases, which appears sustained after a 1-year follow-up. CONCLUSION: This observation of an RMS revealing an unexpected Lynch syndrome underlines the overlap between tumorous and germline molecular genetics and emphasises the major impact of cancer genomic medicine in clinical practice for guiding treatment decision.
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Antígeno B7-H1/imunologia , Neoplasias Pulmonares/terapia , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Rabdomiossarcoma/terapia , Adulto , Anticorpos Anti-Idiotípicos , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/genética , Criança , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Humanos , Perda de Heterozigosidade/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Rabdomiossarcoma/genética , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/patologia , Sequenciamento do Exoma , Adulto JovemRESUMO
BACKGROUND: Palliative care (PC) referral is recommended early in the course of advanced cancer. This study aims to describe, in an integrated onco-palliative care program (IOPC), patient's profile when first referred to this program, timing of this referral and its impact on the trajectory of care at end-of-life. METHODS: The IOPC combined the weekly onco-palliative meeting (OPM) dedicated to patients with incurable cancer, and/or the clinical evaluation by the PC team. Oncologists can refer to the multidisciplinary board of the OPM the patients for whom goals and organization of care need to be discussed. We analyzed all patients first referred at OPM in 2011-2013. We defined the index of precocity (IP), as the ratio of the time from first referral to death by the time from diagnosis of incurability to death, ranging from 0 (late referral) to 1 (early referral). RESULTS: Of the 416 patients included, 57% presented with lung, urothelial cancers, or sarcoma. At first referral to IOPC, 76% were receiving antitumoral treatment, 63% were outpatients, 56% had a performance status ≤2 and 46% had a serum albumin level > 35 g/l. The median [1st-3rd quartile] IP was 0.39 [0.16-0.72], ranging between 0.53 [0.20-0.79] (earliest referral, i.e. close to diagnosis of incurability, for lung cancer) to 0.16 [0.07-0.56] (latest referral, i.e. close to death relatively to length of metastatic disease, for prostate cancer). Among 367 decedents, 42 (13%) received antitumoral treatment within 14 days before death, and 157 (43%) died in PC units. CONCLUSIONS: The IOPC is an effective organization to enable early integration of PC and decrease aggressiveness of care near the end-of life. The IP is a useful tool to model the timing of referral to IOPC, while taking into account each cancer types and therapeutic advances.
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Tomada de Decisão Compartilhada , Serviço Hospitalar de Oncologia/normas , Encaminhamento e Consulta/normas , Fatores de Tempo , Idoso , Prestação Integrada de Cuidados de Saúde/métodos , Prestação Integrada de Cuidados de Saúde/normas , Prestação Integrada de Cuidados de Saúde/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Neoplasias/terapia , Serviço Hospitalar de Oncologia/organização & administração , Serviço Hospitalar de Oncologia/tendências , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Cuidados Paliativos/tendências , Encaminhamento e Consulta/tendências , Estudos Retrospectivos , Assistência Terminal/organização & administração , Assistência Terminal/normas , Assistência Terminal/tendênciasRESUMO
Prognosis and oncologic treatment feasibility in solid organ transplant patients with de novo cancer remain poorly described. We investigated the impact of immunosuppressive therapy modifications after de novo cancer diagnosis on oncologic treatment feasibility, toxicities, and prognosis. Patients with de novo cancer (excluding nonmelanoma skin cancers) were selected from a monocentric cohort of 4,637 kidney and liver allograft recipients. We assessed oncologic treatment optimality according to guidelines and analyzed immunosuppressive drug modifications and oncologic treatment impacts on treatment feasibility, toxicities, and graft/patient survivals. A total of 180 patients with 205 cancers were included: mean age 60 years, median delay from transplantation to first de novo cancer 5 years. In 46% of cases, immunosuppressive therapy was modified after cancer diagnosis: 24% dose reduction and 22% mTOR inhibitor introduction. Optimal oncologic treatment was performed in 80% and 38% of patients with localized and advanced cancer respectively. Transplantation and immunosuppression hindered optimal oncologic treatment in 11% instances. Immunosuppressive therapy modifications did not affect oncologic treatment tolerance nor graft survival. In multivariate analysis, optimal oncologic treatment and mTOR inhibitor introduction improved survival of patients with de novo carcinoma. Optimal oncologic treatment is feasible in kidney and liver allograft recipients without safety concerns. Optimal oncologic treatment and mTOR inhibitor introduction seem to markedly improve survival of patients with de novo carcinoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Rim/métodos , Transplante de Fígado/métodos , Neoplasias/terapia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Aloenxertos , Terapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Análise de Sobrevida , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: The 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care. METHODS: The CERTIM cohort is a prospective cohort which includes patients receiving immune checkpoint inhibitors in Cochin University hospital. RNA extracted from 58 archival formalin fixed paraffin embedded tumor blocks (including 38 lung cancers, 5 melanomas, 10 renal carcinomas, 4 urothelial carcinomas and 1 colon carcinoma) was hybridized to a beta version of the NanoString® PanCancer IO360™ CodeSet using nCounter® technology. Gene expression signatures were correlated with tumor responses (by RECIST criteria) and overall survival. PD-L1 immunostaining on tumor cells was assessed in 37 non-small cell lung cancer (NSCLC) samples and tumor mutational burden (TMB) measured by whole exome sequencing in 19 of these. RESULTS: TIS scores were significantly associated with complete or partial response to anti-PD-1 treatment in the whole cohort (odds ratio = 2.64, 95% CI [1.4; 6.0], p = 0.008), as well as in the NSCLC population (odds ratio = 3.27, 95% CI [1.2; 11.6], p = 0.03). Patients whose tumor had a high TIS score (upper tertile) showed prolonged overall survival compared to patients whose tumor had lower TIS scores, both in the whole cohort (hazard ratio = 0.37, 95% CI [0.18, 0.76], p = 0.005) and in the NSCLC population (hazard ratio = 0.36, 95% CI [0.14, 0.90], p = 0.02). In the latter, the TIS score was independent from either PD-L1 staining on tumor cells (spearman coefficient 0.2) and TMB (spearman coefficient - 0.2). CONCLUSIONS: These results indicate that validated gene expression assay measuring the level of tumor microenvironment inflammation such as TIS, are accurate and independent predictive biomarkers and can be easily implemented in the clinical practice.
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Inflamação/genética , Inflamação/terapia , Neoplasias/genética , Neoplasias/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Estudos de Coortes , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Transcriptoma , Pesquisa Translacional Biomédica , Resultado do TratamentoRESUMO
BACKGROUND: Cancer and aging are both frequently associated with malnutrition, a factor of poor prognosis. In adult cancer patients, this may be related in part to impaired energy metabolism, with higher than predicted resting energy expenditure (REE) in about 50% of patients. We hypothesized that frequently impaired energy metabolism in elderly patients could potentiate cancer-associated hypermetabolism, further promoting risk of malnutrition. OBJECTIVE: To study the hypermetabolic response to cancer in a predominantly aged population and the potential underlying determinants. METHODS: This was a cross-sectional exploratory study in patients with non-small-cell lung cancer. REE was measured by indirect calorimetry. Body composition was determined from a single CT scan imaging at L3 level. Endocrine, inflammatory, nutritional and metabolic status were evaluated. RESULTS: Twenty-seven patients, of median age 68 years (range 32-81) completed the study. In this population, mean measured REE was 7.5% higher than calculated REE. Sex and weight accounted for about 51% of REE variations, whereas age accounted only for 4%. However, these parameters did not explain the REE-to-lean body mass (LBM) ratio variations, suggesting that they influenced REE only through their effect on LBM. Among the other parameters evaluated, only the thyroid-stimulating hormone and interleukin-6 plasma levels appeared to have an influence on REE. The study of the consequences of this increase in REE-to-LBM ratio showed a growing inability of patients to meet their energy needs but showed no effect on nutritional markers such as transthyretin. CONCLUSIONS: The results of this pilot study suggest that in our population, age was not an important factor of REE. The elevated energy metabolism was associated with patients' failure to increase their energy intakes sufficiently, which can contribute to the development of cachexia. CLINICAL TRIAL: This trial is registered at clinicaltrials.gov under NCT0314.
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Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Metabolismo Energético , Neoplasias Pulmonares/fisiopatologia , Descanso , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Caquexia/sangue , Caquexia/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Estudos Transversais , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Projetos Piloto , Estudos Prospectivos , Tireotropina/sangueRESUMO
Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC consecutive pts. treated with erlotinib. The plasma concentration of erlotinib (Ce) was measured at steady state on day 15. We studied the relationship between age > 75 years, and Ce, using the Mann-Whitney U test and with the occurrence of acute toxicity, using a Fisher's test. Results A total of 53 pts. were analyzed. Median age was 68 years (31-83), 56 % were female. All pts. > 75 years experienced toxicity: all grade acute adverse events were 1.6 fold more frequent (100 % vs 61 %; OR 95 % CI [1.9-INF]; p = 0.003). At day 15, Ce increased with age. Over 75 years old, the mean Ce was 1.5 fold higher: 2091 ng/mL (95 % CI [1476; 2706]) vs 1359 (95 % CI [1029; 1689]; p = 0.024). In pts. over 80 years old, the mean Ce was doubled: 2729 (95 % CI [1961; 3497]) vs 1358 ng/mL (95 % CI [1070; 1646]; p = 0.0019). Reduced lean body mass over 75 years (median 36.6 kg versus 49.1 kg) might account for these differences. Finally, the risk of early erlotinib discontinuation was increased by 11 in older pts. (33 % vs 3 % OR 17.2; 95 % CI [1.7; 892.5] p = .005). Conclusion The risk of overexposure to erlotinib increases with age. Reduced lean body mass may explain erlotinib pharmacokinetics and excessive acute toxicity in the elderly.
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Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Cloridrato de Erlotinib/efeitos adversos , Cloridrato de Erlotinib/farmacocinética , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Estatura , Índice de Massa Corporal , Peso Corporal , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cloridrato de Erlotinib/sangue , Cloridrato de Erlotinib/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
BACKGROUND: Heterozygous NSD1 mutations were identified in 60%-90% of patients with Sotos syndrome. Recently, mutations of the SETD2 and DNMT3A genes were identified in patients exhibiting only some Sotos syndrome features. Both NSD1 and SETD2 genes encode epigenetic 'writer' proteins that catalyse methylation of histone 3 lysine 36 (H3K36me). The DNMT3A gene encodes an epigenetic 'reader' protein of the H3K36me chromatin mark. METHODS: We aimed at confirming the implication of DNMT3A and SETD2 mutations in an overgrowth phenotype, through a comprehensive targeted-next generation sequencing (NGS) screening in 210 well-phenotyped index cases with a Sotos-like phenotype and no NSD1 mutation, from a French cohort. RESULTS: Six unreported heterozygous likely pathogenic variants in DNMT3A were identified in seven patients: two nonsense variants and four de novo missense variants. One de novo unreported heterozygous frameshift variant was identified in SETD2 in one patient. All the four DNMT3A missense variants affected DNMT3A functional domains, suggesting a potential deleterious impact. DNMT3A-mutated index cases shared similar clinical features including overgrowth phenotype characterised by postnatal tall stature (≥+2SD), macrocephaly (≥+2SD), overweight or obesity at older age, intellectual deficiency and minor facial features. The phenotype associated with SETD2 mutations remains to be described more precisely. The p.Arg882Cys missense de novo constitutional DNMT3A variant found in two patients is the most frequent DNMT3A somatic mutation in acute leukaemia. CONCLUSIONS: Our results illustrate the power of targeted NGS to identify rare disease-causing variants. These observations provided evidence for a unifying mechanism (disruption of apposition and reading of the epigenetic chromatin mark H3K36me) that causes an overgrowth syndrome phenotype. Further studies are needed in order to assess the role of SETD2 and DNMT3A in intellectual deficiency without overgrowth.
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INTRODUCTION: CDH1 predisposes primarily to diffuse gastric cancer (DGC). Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC. METHODS AND RESULTS: We report all index cases from Ile-de-France in which a germline CDH1 mutation has been identified. Out of 18 cases, 7 do not fulfil the HDGC-defining criteria. Three of them are women who presented initially with bilateral LBC below age 50, without personal or family history of DGC, and who subsequently developed symptomatic DGC. DISCUSSION: Our series of CDH1 mutation carriers is the largest to date and demonstrates that LBC might be the first manifestation of HDGC. A personal or family history of multiple LBCs at a young age, even without DGC, should prompt CDH1 mutation screening. It is paramount to identify mutation carriers early, so that they can benefit from prophylactic gastrectomy before they develop symptomatic, highly lethal DGC. We recommend a revision of the HDGC-defining criteria and propose for consideration the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' instead of HDGC.
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Neoplasias da Mama/genética , Caderinas/genética , Mutação em Linhagem Germinativa , Neoplasias Gástricas/genética , Adulto , Antígenos CD , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , SíndromeRESUMO
Little is known about immune checkpoint inhibitors (ICI) response of NF1-mutated lung adenocarcinomas. 341/4,181 (8.2%) TCGA lung adenocarcinomas samples have a somatic NF1 mutation. NF1-mutated tumors have higher TMB (p < 0.0001), higher expression of immune genes ("hot phenotype") and higher CD8 + T cell (p = 0.03) and macrophage (p = 0.02) infiltrations compared to NF1 wild-type tumors. NF1 mutation status appears as a candidate predictive biomarker for ICI response in lung adenocarcinoma patients.
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OBJECTIVES: To evaluate the performance of artificial intelligence (AI) in the preoperative detection of lung metastases on CT. MATERIALS AND METHODS: Patients who underwent lung metastasectomy in our institution between 2016 and 2020 were enrolled, their preoperative CT reports having been performed before an AI solution (Veye Lung Nodules, version 3.9.2, Aidence) became available as a second reader in our department. All CT scans were retrospectively processed by AI. The sensitivities of unassisted radiologists (original CT radiology reports), AI reports alone and both combined were compared. Ground truth was established by a consensus reading of two radiologists, who analyzed whether the nodules mentioned in the pathology report were retrospectively visible on CT. Multivariate analysis was performed to identify nodule characteristics associated with detectability. RESULTS: A total of 167 patients (men: 62.9 %; median age, 59 years [47-68]) with 475 resected nodules were included. AI detected an average of 4 nodules (0-17) per CT, of which 97 % were true nodules. The combination of radiologist plus AI (92.4 %) had significantly higher sensitivity than unassisted radiologists (80.4 %) (p < 0.001). In 27/57 (47.4 %) patients who had multiple preoperative CT scans, AI detected lung nodules earlier than the radiologist. Vascular contact was associated with non-detection by radiologists (OR:0.32[0.19, 0.54], p < 0.001), whilst the presence of cavitation (OR:0.26[0.13, 0.54], p < 0.001) or pleural contact (OR:0.10[0.04, 0.22], p < 0.001) was associated with non-detection by AI. CONCLUSION: AI significantly increases the sensitivity of preoperative detection of lung metastases and enables earlier detection, with a significant potential benefit for patient management.
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The National College of Cancerology Teachers (CNEC) was created in September 1986. Its missions are to develop the teaching of oncology, to promote educational actions in the discipline, to participate in the development of teaching content and the definition of curricula and the control of knowledge for the training of medical students and specialists, to develop and validate educational documents relating to the above teaching, to ensure the representation of oncology teaching to of the National University Council (CNU) and administrative authorities, to ensure and coordinate relations with other university disciplines, scientific societies, national, European, and international professional groups, and to contribute to the development of research in the discipline. The current office was elected in September 2022 for three years.
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Pessoal de Educação , Estudantes de Medicina , Humanos , Universidades , CurrículoRESUMO
Sarcomas are a diverse group of rare malignancies composed of multiple different clinical and molecular subtypes. Due to their rarity and heterogeneity, basic, translational, and clinical research in sarcoma has trailed behind that of other cancers. Outcomes for patients remain generally poor due to an incomplete understanding of disease biology and a lack of novel therapies. To address some of the limitations impeding preclinical sarcoma research, we have developed Sarcoma_CellMinerCDB, a publicly available interactive tool that merges publicly available sarcoma cell line data and newly generated omics data to create a comprehensive database of genomic, transcriptomic, methylomic, proteomic, metabolic, and pharmacologic data on 133 annotated sarcoma cell lines. The reproducibility, functionality, biological relevance, and therapeutic applications of Sarcoma_CellMinerCDB described herein are powerful tools to address and generate biological questions and test hypotheses for translational research. Sarcoma_CellMinerCDB (https://discover.nci.nih.gov/SarcomaCellMinerCDB) aims to contribute to advancing the preclinical study of sarcoma.
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De novo germline pathogenic variants (gPV) of the BReast CAncer 1 (BRCA1) gene are very rare. Only a few have been described up to date, usually in patients with a history of ovarian or breast cancer. Here, we report the first case of an incidental de novo BRCA1 germline pathogenic variant which was identified within the framework of the Plan France Médecine Génomique (PFMG) 2025 French national tumor sequencing program. The proband was a 29-year-old man diagnosed with metastatic osteosarcoma. Tumor whole exome sequencing identified a BRCA1 c.3756_3759del p.(Ser1253Argfs*10) pathogenic variant without loss-of-heterozygosity. A low genomic instability score and the absence of single base substitution signatures of homologous recombination deficiency suggested that the BRCA1 variant was not driver in the osteosarcoma tumorigenesis. Germline whole genome sequencing asserted the germline nature of this variant, with a 36% allele frequency, suggesting a mosaicism caused by a post-zygotic mutational event. The proband's family (parents and siblings) were not carriers of this variant confirming the de novo occurrence. Tumor sequencing programs like the French PFMG 2025 have been implemented worldwide and may help identify new gPV, including de novo variants.
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A case series evaluating efficacy and safety of immune checkpoint blockade in Li-Fraumeni syndrome.
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Inibidores de Checkpoint Imunológico , Síndrome de Li-Fraumeni , Humanos , Síndrome de Li-Fraumeni/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: NF1 is a tumor suppressor gene encoding neurofibromin, an inhibitor of the RAS/MAPK and PI3K-AKT-mTOR signaling pathways. NF1 germline pathogenic variants cause the tumor predisposition syndrome neurofibromatosis type 1. Targeted therapies (MEK inhibitors) have been approved for benign nerve sheath tumors in neurofibromatosis type 1 patients. NF1 somatic alterations are present in ~5% of all human sporadic cancers. In melanomas, acute myeloid leukemias and lung adenocarcinomas, the NF1 somatic alteration frequency is higher (~15%). However, to date, the therapeutic impact of NF1 somatic alterations is poorly investigated. AREAS COVERED: This review presents a comprehensive overview of targeted therapies and immunotherapies currently developed and evaluated in vitro and in vivo for NF1-altered cancer treatment. A PubMed database literature review was performed to select relevant original articles. Active clinical trials were researched in ClinicalTrials.gov database in August 2022. TCGA and HGMD® databases were consulted. EXPERT OPINION: This review highlights the need to better understand the molecular mechanisms of NF1-altered tumors and the development of innovative strategies to effectively target NF1-loss in human cancers. One of the current major challenges in cancer management is the targeting of tumor suppressor genes such as NF1 gene. Currently, most studies are focusing on inhibitors of the RAS/MAPK and PI3K-AKT-mTOR pathways and immunotherapies.
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Neurofibromatose 1 , Humanos , Neurofibromatose 1/genética , Neurofibromatose 1/metabolismo , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Genes da Neurofibromatose 1 , Proteínas Proto-Oncogênicas c-akt , Medicina de Precisão , Fosfatidilinositol 3-Quinases/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Sarcopenia is observed in about 50% of cancer patients. Cancer-related sarcopenia negatively affects survival and is a predictive factor of anticancer drug toxicity. Sarcopenia diagnosis is challenging in routine care. We investigated whether plasma creatinine and cystatin C predict sarcopenia diagnosis in the specific population of cancer patients. METHODS: Two common diagnostic criteria of cancer-related sarcopenia based on skeletal muscle mass ± handgrip strength were separately applied as the "gold standard" sarcopenia definition. Four sarcopenia indexes based on creatinine and cystatin C values were evaluated: Creatinine/Cystatin C, Glomerular Filter rate (GFR) Cockroft-Gault/GFR CKD-EPI, GFR Cockroft-Gault/GFR Grubb and GFR Cockroft-Gault/GFR simple. The receiver operating characteristic (ROC) curves and the area under the ROC curves were applied to evaluate the sarcopenia diagnostic accuracy of the four different sarcopenia indexes. RESULTS: A total of 99 patients were included. Among them, 47.5% were overweight or obese. The ratio creatinine/cystatin C (ratio value at 0.8) more accurately predicts the diagnosis of sarcopenia in the entire population based on low skeletal muscle mass and low handgrip strength (sensitivity, specificity, accuracy and Youden index at 0.77, 0.57, 0.90, 0.34 respectively). The other evaluated ratios predict sarcopenia with a lower specificity in all conditions. In the overweight/obese group, the results are similar. The ratio creatinine/cystatin C (ratio value at 1) accurately predicts sarcopenia with a sensitivity, a specificity, an accuracy and a Youden index at 0.50, 0.86, 0.95, 0.36 respectively in overweight/obese population. CONCLUSIONS: The creatinine/cystatin C ratio is a useful and simple biomarker to predict sarcopenia in cancer patients. Moreover, this sarcopenia index also seems to be a strong sarcopenia diagnosis biomarker in overweight and obese cancer patients. Our results must be confirmed in a larger cohort.
Assuntos
Antineoplásicos , Nefropatias , Neoplasias , Sarcopenia , Biomarcadores , Creatinina , Cistatina C , Taxa de Filtração Glomerular/fisiologia , Força da Mão , Humanos , Nefropatias/diagnóstico , Músculos , Neoplasias/complicações , Obesidade , Sobrepeso , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Background: Nuclear protein in testis (NUT) carcinomas (NC) are a rare, highly aggressive, subset of squamous cell carcinomas, characterized by a translocation involving the NUTM1 gene. Thyroid location of NUT carcinomas has rarely been described. Methods: We report here two cases of thyroid NC with NSD3::NUTM1 translocation. Results: The first case presented as a very aggressive undifferentiated thyroid carcinoma in a 38-year-old man who died 21 months after the diagnosis. The second case was diagnosed after multiple lymphadenopathy recurrences mainly in the neck in a 37-year-old woman 7 years after total thyroidectomy for papillary thyroid carcinoma with a classic and a solid/trabecular component. Conclusions: Our case reports highlight the challenges in diagnosing these exceptional carcinomas. The therapeutic impact of the administration of pharmacological compounds with epigenetic action, in line with the physiopathology of these carcinomas, is also discussed.