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CoronaVirus disease-2019 has changed the delivery of health care worldwide and the pandemic has challenged oncologists to reorganize cancer care. Recently, progress has been made in the field of precision medicine to provide to patients with cancer the best therapeutic choice for their individual needs. In this context, the Foundation Medicine (FMI)-Liquid@Home project has emerged as a key weapon to deal with the new pandemic situation. FoundationOne Liquid Assay (F1L) is a next-generation sequences-based liquid biopsy service, able to detect 324 molecular alterations and genomic signatures, from May 2020 available at patients' home (FMI-Liquid@Home). We analyzed time and costs saving for patients with cancer, their caregivers and National Healthcare System (NHS) with FMI-Liquid@Home versus F1L performed at our Department. Different variables have been evaluated. Between May 2020 and August 2021, 218 FMI-Liquid@Home were performed for patients with cancer in Italy. Among these, our Department performed 153 FMI-Liquid@Home with the success rate of 98% (vs. 95% for F1L in the hospital). Time saving for patients and their caregivers was 494.86 and 427.36 hours, respectively, and costs saving was 13 548.70. Moreover, for working people these savings were 1084.71 hours and 31 239.65, respectively. In addition, the total gain for the hospital was 163.5 hours and 6785, whereas for NHS was 1084.71 hours and 51 573.60, respectively. FMI-Liquid@Home service appears to be useful and convenient allowing time and costs saving for patients, caregivers, and NHS. Born during the COVID-19 pandemic, it could be integrated in oncological daily routine in the future. Therefore, additional studies are needed to better understand the overall gain and how to integrate this service in different countries.
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COVID-19 , Neoplasias , COVID-19/epidemiologia , Humanos , Biópsia Líquida , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Medicina de PrecisãoRESUMO
Pancreatic cancer represents one of the most lethal disease worldwide but still orphan of a molecularly driven therapeutic approach, although many genomic and transcriptomic classifications have been proposed over the years. Clinical heterogeneity is a hallmark of this disease, as different patients show different responses to the same therapeutic regimens. However, genomic analyses revealed quite a homogeneous disease picture, with very common mutations in four genes only (KRAS, TP53, CDKN2A, and SMAD4) and a long tail of other mutated genes, with doubtful pathogenic meaning. Even bulk transcriptomic classifications could not resolve this great heterogeneity, as many informations related to small cell populations within cancer tissue could be lost. At the same time, single cell analysis has emerged as a powerful tool to dissect intratumoral heterogeneity like never before, with possibility of generating a new disease taxonomy at unprecedented molecular resolution. In this review, we summarize the most relevant genomic, bulk and single-cell transcriptomic classifications of pancreatic cancer, and try to understand how novel technologies, like single cell analysis, could lead to novel therapeutic strategies for this highly lethal disease.
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Carcinoma Ductal Pancreático/genética , Genômica/métodos , Neoplasias Pancreáticas/genética , Análise de Célula Única/métodos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Humanos , Análise de Sequência de RNA , Microambiente TumoralRESUMO
OBJECTIVES: To evaluate secretin-enhanced MRCP (S-MRCP) findings of patients with pancreas divisum and Santorinicele, before and after minor papilla sphincterotomy. METHODS: S-MRCP examinations of 519 patients with suspected pancreatic disease were included. Size of the main pancreatic duct, presence and calibre of Santorinicele were evaluated. Duodenal filling was assessed on dynamic images. After sphincterotomy the same parameters and the clinical findings were re-evaluated. RESULTS: Pancreas divisum was depicted in 55/519 patients (11 %) by MRCP and an additional 26/519 by S-MRCP (total 81/519, 16 %). Santorinicele was detected in 7/81 patients (8.6 %) with pancreas divisum by MRCP and an additional 20/81 by S-MRCP (total 27/81, 33 %). Dorsal duct in patients with Santorinicele was significantly larger in the head compared with patients with only pancreas divisum (p < 0.01), in basal conditions (average 2.4 versus 1.9 mm) and after secretin administration (average 3.0 versus 2.4 mm). Duodenal filling was impaired in 11/27 patients (41 %) with Santorinicele. After sphincterotomy significant reduction in size of Santorinicele (-33 %) and dorsal duct (-17 %), increase of pancreatic juice and symptoms improvement were observed. CONCLUSION: Secretin administration increases the accuracy of MRCP in detecting Santorinicele and demonstrates the impaired duodenal filling. S-MRCP is useful to assess results of sphincterotomy. KEY POINTS: ⢠Secretin-enhanced MRCP gives anatomical and functional information on pancreatic outflow dynamics. ⢠Santorinicele is a cystic dilatation of the termination of the Santorini duct. ⢠S-MRCP images are the most useful to recognize the presence of Santorinicele. ⢠Minor papilla sphincterotomy during ERCP is indicated in patients with Santorinicele.
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Meios de Contraste , Pâncreas/anormalidades , Cisto Pancreático/patologia , Secretina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia por Ressonância Magnética/métodos , Dilatação Patológica/patologia , Dilatação Patológica/cirurgia , Duodeno/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/cirurgia , Ductos Pancreáticos/patologia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Esfincterotomia Transduodenal/métodos , Adulto JovemRESUMO
PURPOSE: To identify magnetic resonance (MR)/MR cholangiopancreatography (MRCP) imaging signs helpful in the differential diagnosis between serous cystadenomas (SCAs) and mucinous cystic neoplasms (MCNs), arising from the body/tail of the pancreas. MATERIAL AND METHODS: This retrospective study had institutional review board approval and informed consent was waived. Fifty-three patients with non-communicating cystic pancreatic neoplasm of the body/tail, undergoing MR/MRCP, were included. Qualitative image analysis assessed the macroscopic pattern, number of cysts, presence of central scar, contrast enhancement of peripheral wall, and mural nodules. Quantitative analysis assessed the maximum diameter of the neoplasm, thickness of the peripheral wall, and calibre of the upstream main pancreatic duct. RESULTS: Histopathology results revealed that 27/53 (51 %) were SCAs, 26/53 (49 %) were MCNs. Microcystic pattern was observed in 88.2 % of SCAs and 11.8 % of MCNs; macrocystic pattern was observed in 90.5 % of MCNs and 9.5 % of SCAs (p < 0.0001). Central scar was detected in 29.6 % of SCAs and no MCNs (p = 0.003). Contrast enhancement of the peripheral wall was evident in 99.5 % of MCNs and 11.5 % of SCAs (p < 0.0001); mural nodules were depicted in 94.1 % of MCNs and 5.9 % of SCAs (p < 0.0001). Median maximum diameter was 54 mm for MCNs, 32 mm for SCAs (p = 0.001); median wall thickness was 4 mm for MCNs, 2 mm for SCAs (p < 0.0001). CONCLUSIONS: Macrocystic pattern, enhancement of a peripheral wall and mural nodules are suggestive of MCNs; whereas microcystic pattern, lack of peripheral wall and central scar are suggestive of SCAs. KEY POINTS: ⢠MCNs have macrocystic patterns, contrast enhancement of the peripheral wall and mural nodules ⢠Microcystic pattern and central scar are suggestive of SCA ⢠Mural nodules detected in MCNs correlate with epithelial dysplasia ⢠Chronic obstructive pancreatitis is equally depicted in patients with MCNs and SCAs.
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Colangiopancreatografia por Ressonância Magnética , Cistadenoma Mucinoso/diagnóstico , Cistadenoma Seroso/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Idoso , Carcinoma in Situ , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: To evaluate the magnetic resonance (MR) imaging-MR cholangiopancreatographic (MRCP) findings of focal forms of autoimmune pancreatitis (AIP) to describe ductal involvement at diagnosis. METHODS: MR examinations of 123 patients affected by AIP were analysed. We included 26 patients who satisfied International Consensus Diagnostic Criteria and were suffering from focal AIP. Image analysis included: site of parenchymal enlargement, main pancreatic duct (MPD) diameter, MPD stenosis, stricture length, presence of upstream dilation within the stricture, signal intensity, and pancreatic enhancement. RESULTS: Signal intensity abnormalities were localized in the head in 10/26 (38.5%) and in the body-tail in 16/26 (61.5%) patients. MRCP showed a single MPD stenosis in 12/26 (46.1%) and multiple MPD stenosis in 14/26 (53.8%) patients, without a dilation of the upstream MPD (mean: 3.83 mm). Lesions showed hypointensity on T1-weighted images in all patients, and hyperintensity on T2-weighted images in 22/26 (84.6%) patients. The affected parenchyma was hypovascular during the arterial phase in 25/26 (96.2%) patients with contrast retention. CONCLUSIONS: MR-MRCP are effective techniques for the diagnosis of AIP showing the loss of the physiological lobulation and the typical contrastographic appearance. The presence of multiple, long stenoses without an upstream MPD dilation at MRCP suggests the diagnosis of AIP, and can be useful in differential diagnosis of pancreatic adenocarcinoma. KEY POINTS: ⢠MRI represents the gold standard in the diagnosis of AIP. ⢠MRCP is an increasingly useful technique in the diagnosis of focal AIP. ⢠MRCP could be a problem-solving tool in the differential diagnosis of AIP.
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Doenças Autoimunes/patologia , Pancreatite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia por Ressonância Magnética/métodos , Constrição Patológica/patologia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Adulto Jovem , Neoplasias PancreáticasRESUMO
PURPOSE: To evaluate the magnetic resonance imaging (MRI) findings of solid pseudopapillary neoplasm (SPN) of the pancreas. METHODS AND MATERIALS: From January 2006 to December 2013, 41 patients with SPN of the pancreas were retrospectively evaluated. Inclusion criteria were the execution of an MR examination and tumor resection with an histopathological evaluation at our Institute. Exclusion criteria were the execution of an MR examination at other centers (14/41) and the execution of CT or ultrasonography (10/41) at our Institute. The qualitative analysis evaluated: location (head/body-tail), shape (round/oval/lobulated), margins (regular/irregular), and signal intensity on T1- and T2-weighted images compared to the surrounding pancreas (hypo-, iso-, or hyperintense and homogeneous or heterogeneous), appearance of MPD and the secondary ducts, and the presence of metastases and/or vascular involvement. The quantitative analysis included: maximum size of the lesion, wall thickness, and maximum diameter of the main pancreatic duct (MPD). RESULTS: The population comprised 17 women (median age: 31 year) with a median tumor size of 50.6 mm, a median wall thickness of 2 mm and median diameter of the MPD of 1.8 mm. 9/17 were at the head; 8/17 on the body/tail: respectively, 8/17 round, 6/17 oval, and 3/17 lobulated. All showed regular margins. On T1-weighted images 8/17 appeared homogeneously hypointense, 7/17 heterogeneously hypointense, and 2/17 heterogeneously hyperintense. On T2-weighted images 1/17 appeared homogeneously hyperintense and 16/17 heterogeneously hyperintense. No secondary ducts dilatations were detected. During the follow-up, one patient presented disease recurrence 48 months after surgery. CONCLUSIONS: MR imaging features can be highly suggestive for the diagnosis of SPN.
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Carcinoma Papilar/diagnóstico , Imageamento por Ressonância Magnética/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Nanopartículas de Magnetita , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Siloxanas , Adulto JovemRESUMO
PURPOSE: We evaluated the evolution of ventriculomegaly (VM) by comparing foetal magnetic resonance imaging (MRI) with postnatal transcranial ultrasonography (US) and/or encephalic MRI. MATERIALS AND METHODS: Between January 2006 and April 2011, 70 foetuses with a mean gestational age of 28 weeks and 4 days (range, 18-36) weeks with VM on foetal MRI were assessed in this prospective study. Half-Fourier rapid acquisition with relaxation enhancement (RARE) T2-weighted, T1-weighted and diffusion-weighted (DWI) images along the three orthogonal planes according to the longitudinal axis of the mother, and subsequently of the foetal brain, were acquired. Quantitative image analysis included the transverse diameter of lateral ventricles in axial and coronal planes. Qualitative image analysis included searching for associated structural anomalies. RESULTS: Thirty-four of 70 patients with a diagnosis of VM on foetal MRI underwent postnatal imaging. Twenty-five of those 34 (73%) had mild, four (12%) had moderate and five (15%) had severe VM on MRI. Normalisation of the diameter of lateral ventricles was observed in 16 of the 34 (47%) newborns. Among these 16, 13 (81%) had mild and three (19%) had moderate VM (two isolated and one associated VM). VM stabilisation was observed in 16 of the 34 (47%) babies. Among them, 11 (69%) had mild (eight isolated and three associated), one (6%) had moderate associated and four (25%) had severe associated VM. Progression from mild to severe (associated) VM was observed in two of the 34 (6%) babies. CONCLUSIONS: The absence of associated anomalies and a mild VM are favourable prognostic factors in the evolution of VM.
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Ventrículos Cerebrais/anormalidades , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Recém-Nascido , Masculino , GravidezRESUMO
PURPOSE: The aim of our study was to follow the evolution over time of multifocal intraductal papillary mucinous neoplasms (IPMN) of the pancreatic duct side branches by means of magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 155 patients with multifocal IPMN of the side branches were examined with MRI and MR cholangiopancreatography (MRI/MRCP). Inclusion criteria were patients with ≥2 dilated side branches involving any site of the parenchyma; presence of communication with the main pancreatic duct and previous investigations by MRI/MRCP within at least six months. Median follow-up was 25.8 months (range, 12-217). Patients with a follow-up period shorter than 12 months (n=33) and those with a diagnosis of multifocal IPMN of the side branches without any follow-up (n=14) were excluded from the study. The final study population thus comprised 108 patients. A double, quantitative and qualitative, analysis was carried out. The quantitative image analysis included: number of dilated side branches in the head-uncinate process and body-tail; maximum diameter of lesions in the head-uncinate process; maximum diameter in the body-tail; maximum diameter of the main pancreatic duct in the head and body-tail. The qualitative image analysis included: presence of malformations or anatomical variants of the pancreatic ductal system; site of the lesions (head-uncinate process, body-tail, ubiquitous, bridge morphology); presence of gravity-dependent intraluminal filling defects; presence of enhancing mural nodules. RESULTS: At diagnosis, the mean number of cystic lesions of the side branches was 7.09. The mean diameter of the cystic lesions was 13.7 mm. The mean diameter of the main pancreatic duct was 3.6 mm. At follow-up, the mean number of cystic lesions was 7.76. The mean diameter of the cystic lesions was 13.9 mm. The mean diameter of the main pancreatic duct was 3.7 mm. Intraluminal filling defects in the side branches were seen in 18/108 patients (16.6%); enhancing mural nodules were seen in 3/108 patients (2.7%). CONCLUSIONS: Multifocal IPMN of the branch ducts shows a very slow growth and evolution over time. In our study, only 3/108 patients showed mural nodules which, however, did not require any surgical procedure, indicating that careful nonoperative management may be safe and effective in asymptomatic patients.
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Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/patologia , Carcinoma Ductal Pancreático/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia por Ressonância Magnética , Meios de Contraste , Progressão da Doença , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Compostos OrganometálicosRESUMO
Neoadjuvant chemotherapy (NACT) for breast cancer (BC) increases surgical and conservative surgery chances. However, a significant proportion of patients will not be eligible for conservative surgery following NACT because of large tumor size and/or low chemosensitivity, especially for hormone receptor (HR)-positive/ human epidermal growth factor receptor 2 (HER2)-negative tumors, for which pathological complete response rates are lower than for other BC subtypes. On the other hand, for luminal BC neoadjuvant endocrine therapy could represent a valid alternative. Several gene expression assays have been introduced into clinical practice in last decades, in order to define prognosis more accurately than clinico-pathological features alone and to predict the benefit of adjuvant treatments. A series of studies have demonstrated the feasibility of using core needle biopsy for gene expression risk testing, finding a high concordance rate in the risk result between biopsy sample and surgical samples. Based on these premises, recent efforts have focused on the utility of gene expression signatures to guide therapeutic decisions even in the neoadjuvant setting. Several prospective and retrospective studies have investigated the correlation between gene expression risk score from core needle biopsy before neoadjuvant therapy and the likelihood of 1) clinical and pathological response to neoadjuvant chemotherapy and endocrine therapy, 2) conservative surgery after neoadjuvant chemotherapy and endocrine therapy, and 3) survival following neoadjuvant chemotherapy and endocrine therapy. The purpose of this review is to provide an overview of the potential clinical utility of the main commercially available gene expression panels (Oncotype DX, MammaPrint, EndoPredict, Prosigna/PAM50 and Breast Cancer Index) in the neoadjuvant setting, in order to better inform decision making for luminal BC beyond the exclusive contribution of clinico-pathological features.
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Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Expressão Gênica , Hormônios/uso terapêutico , Humanos , Estudos Prospectivos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Approximately 45-50% of breast cancers (BCs) have a HER2 immunohistochemical score of 1+ or 2+ with negative in situ hybridization, defining the "HER2-low BC" subtype. No anti-HER2 agents are currently approved for this subgroup in Europe, where treatment is still determined by HR expression status. In this study, we investigated the prognostic significance of HER2-low status in HR+/HER2- metastatic BC (MBC) patients treated with endocrine therapy (ET) plus palbociclib as first line. METHODS: We conducted a retrospective study including 252 consecutive HR+/HER2- MBC patients who received first-line ET plus palbociclib at six Italian Oncology Units between March 2016 and June 2021. The chi-square test was used to assess differences in the distribution of clinical and pathological variables between the HER-0 and HER2-low subgroups. Survival outcomes, progression-free survival (PFS) and overall survival (OS), were calculated by the Kaplan-Meier method, and the log-rank test was performed to estimate the differences between the curves. RESULTS: A total of 165 patients were included in the analysis: 94 (57%) and 71 (43%) patients had HER2-0 and HER2-low disease, respectively. The median age at treatment start was 64 years. No correlation between patients and tumor characteristics and HER2 status was found. Median PFS (mPFS) for the entire study cohort was 20 months (95% CI,18-25 months), while median OS (mOS) was not reached at the time of analysis. No statistically significant differences, in terms of PFS (p = 0.20) and OS (p = 0.1), were observed between HER2-low and HER2-0 subgroups. CONCLUSIONS: In our analysis, HR+ MBC patients with low HER2 expression who received first-line treatment with ET plus Palbociclib reported no statistically different survival outcomes compared to HER2-0 patients. Further prospective studies are needed to confirm the clinical role of HER2 expression level.
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Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.
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Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) refer to heterogenous rare neoplasms constituted of at least a neuroendocrine population-either well-differentiated, or more frequently poorly differentiated-and a non-neuroendocrine population, both accounting for at least 30% of the whole tumor mass. Several studies recently focused on the key genetic and epigenetic changes underlying MiNENs to better understand how they develop, and explore biological similarities among the two components and their pure counterparts. However, their molecular landscape still remains poorly understood. NGS may represent a useful tool to study this orphan disease by detecting the main genetic alterations and possible therapeutic targets. NGS analysis on tissue and/or blood samples through the Foundation One (F1) platform was performed on consecutive samples collected from four patients diagnosed with MiNENs of the gastroenteric tract. Several genetic alterations were shared among samples from the same patients, thus suggesting a common origin between them, although morphology sometimes changed at histopathological evaluation. Common molecular alterations among samples from different patients that had not been previously described to our knowledge were also detected. Finally, it is of the utmost importance to clarify if the maintenance of the 30% cut-off is still essential in defining MiNENs and really manages to include all of the mixed neoplasms.
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Background: Recently, new evidence of the next-generation sequencing (NGS) liquid biopsy utility in clinical practice has been developed. This assay is emerging as a new promising tool to use as a noninvasive biomarker for cancer mutation profiling. Additional data supporting the clinical validity of cell free DNA (cfDNA) based testing is necessary to inform optimal use of these assays in the clinic. Materials and methods: A total of 398 cancer patients were analyzed by FoundationOne Liquid Analysis (F1LA), a genomic profiling assay and by standard NGS diagnostic ThermoFisher platform. The association between diagnostic technique was evaluated using a Poisson regression model. FoundationOne Liquid (F1L) and FoundationOne Liquid CDx (F1LCDx) detect 70 and 324 cancer-related genes alterations, respectively, including genomic signatures tumor fraction, blood tumor mutational burden (only for the 324 genes version), and microsatellite instability high status. Both assays used a single DNA extraction method to obtain cfDNA. The real-life clinical impact and feasibility of F1L and F1LCDx were evaluated across different solid tumors in our department. Results: Between 1 January 2019 and 28 February 2021, 398 samples of different tumor types from 398 patients were analyzed (overall success rate: 92%, in FoundationOne Liquid CDx Analysis success rate: 97%). Most frequent molecular alterations were TP53 (74), APC (40), DNMT3A (39), KRAS (23). The comprehensive clinical impact of F1LA compared with standard diagnostic was 64.7% versus 22.1% [risk ratio (RR)â=â2.94; pâ<â0.001] and the potential clinical impact was 58.6% versus 11.0% (RRâ=â5.32; pâ<â0.001), respectively. Furthermore, some clinical cases were selected, in which F1LA detected actionable alterations offering an unexpected therapeutic choice. Conclusions: Although additional studies are needed to better select patients and setting, NGS F1LA is a useful, noninvasive, and repeatable assay to guide therapeutic choice in oncology. It provides a snapshot of cancer heterogeneity profile that could be incorporated in routinely clinical practice.
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OBJECTIVES: To compare the conspicuity of lobular breast cancers at digital breast tomosynthesis (DBT) versus synthesized 2D mammography (synt2D). MATERIALS AND METHODS: Seventy-six women (mean age 61.2 years, range 50-74 years) submitted to biopsy in our institution, from 2019 to 2021, with proven invasive lobular breast cancer (ILC) were enrolled in this retrospective study. The participants underwent DBT and synt2D. Five breast radiologists, with different years of experience in breast imaging, independently assigned a conspicuity score (ordinal 6-point scale) to DBT and synt2D. Lesion conspicuity was compared, for each reader, between the synt2D overall conspicuity interpretation and DBT overall conspicuity interpretation using a Wilcoxon matched pairs test. RESULTS: A total of 50/78 (64%) cancers were detected on both synt2D and DBT by all the readers, while 28/78 (26%) cancers where not recognized by at least one reader on synt2D. For each reader, in comparison with synt2D, DBT increased significantly the conspicuity of ILC (p < 0.0001). The raw proportion of high versus low conspicuity by modality confirmed that cancers were more likely to have high conspicuity at DBT than synt2D. CONCLUSIONS: ILCs were more likely to have high conspicuity at DBT than at synt2D, increasing the chances of the detection of ILC breast cancer.
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PURPOSE: ATTRACTION-2 trial assessed the role of Nivolumab as a new standard treatment for Asian patients with pretreated metastatic gastric cancer (mGC). The aim of this analysis was to evaluate the safety and efficacy of Nivolumab in a real-life Western population, considering the lack of evidence to date. PATIENTS AND METHODS: Patients progressed after ≥2 chemotherapy regimens and able to receive Nivolumab (3 mg/kg q14) were eligible for the analysis. RESULTS: 16 patients received Nivolumab as third (81.3%) or fourth line (18.7%) from September 2017 to July 2019. The safety was in line with the literature and only one patient discontinued treatment due to persistent hematological toxicity. Overall response rate and disease control rate were 18.7% and 31.2%, respectively. Median duration of response was 5 months. With a median follow-up of 21 months, median OS was 6 months (7, 21 and 22 months in the responders) and median PFS 3 months. PD-L1 and microsatellite status were retrospectively collected in 12 patients. All the major responders were MSI, although no statistically significant difference in OS or PFS was observed according to molecular analysis. CONCLUSION: Nivolumab is feasible and effective in Western patients with mGC. Further investigation is urgently needed also in non-Asians.
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BACKGROUND: The emerging role of next-generation sequencing (NGS) targeted panels is revolutionising our approach to cancer patients, providing information on gene alterations helpful for diagnosis and clinical decision, in a short time and with acceptable costs. MATERIALS AND METHODS: In this work, we evaluated the clinical application of FoundationOne CDx test, a hybrid capture-based NGS. This test identifies alterations in 324 genes, tumour mutational burden and genomic signatures as microsatellite instability. The decision to obtain the NGS assay for a particular patient was done according to investigator's choice. RESULTS: Overall, 122 tumour specimens were analysed, of which 84 (68.85%) succeeded. The success rate was influenced by type of specimen formalin-fixed paraffin embedded (FFPE block vs FFPE slides), by origin of the sample (surgery vs biopsy) and by time of fixation (<5 years vs ≥5 years). The most frequent subgroups of effective reports derived from colorectal cancer (25 samples), non-small-cell lung cancer (16 samples), ovarian cancer (10 samples), biliary tract cancer (9 samples), breast cancer (7 samples), gastric cancer (7 samples). The most frequent alterations found in whole population referred to TP53 (45.9%), KRAS (19.6%) and APC (13.9%). Furthermore, we performed an analysis of patients in whom this comprehensive genomic profiling (CGP) had a relevance for the patient's disease. CONCLUSIONS: On our opinion, CGP could be proposed in clinical practice in order to select patients that could most benefit from the analysis proposed, like patients with good performance status without any available treatments or with unexpected resistance to a therapy.
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Genômica/métodos , Medicina de Precisão/métodos , Idoso , Estudos de Viabilidade , Humanos , Itália , Pessoa de Meia-Idade , Projetos PilotoRESUMO
PURPOSE: Tomosynthesis is proposed to improve breast cancer assessment and staging. We compared tomosynthesis and mammography in estimating the size of newly-diagnosed breast cancers. METHODS: All pathologically-confirmed cancers detected in the STORM-2 trial (90 cancers, 85 women) were retrospectively measured on tomosynthesis by two independent readers. One reader also measured cancers on mammography. Relative mean differences (MDs) and 95% limits of agreement (LOA) with pathology were estimated for tomosynthesis and mammography within a single reader (Analysis 1) and between two readers (Analysis 2). RESULTS: Where cancers were detected and hence measured by both tests, tomosynthesis overestimated pathologic size relative to mammography (Analysis 1: MD 5% versus 1%, Analysis 2: 7% versus 3%; P = 0.10 both analyses). There was similar, large measurement variability for both tests (LOA range: -60% to +166%). Overestimation by tomosynthesis was attributable to the subgroup with dense breasts (MDs = 12-13% versus 4% for mammography). There was low average bias for both tests in the low-density subgroup (MDs = 0-4%). LOA were larger in dense breasts for both tomosynthesis and mammography (P ≤ 0.02 all comparisons). Cancers detected only by tomosynthesis were more frequently in dense breasts (60-68%): for those tumours size was estimated with increased measurement variability (LOA ranging from -75% to +293%). CONCLUSIONS: On average, tomosynthesis overestimates pathologic tumour size in women with dense breasts; that difference is more likely to impact management in women with larger tumours. The main advantage of tomosynthesis appears to be detecting mammographically-occult cancers; however tomosynthesis less accurately measured those cancers in dense breasts (large measurement variability).
Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga TumoralRESUMO
Nab-paclitaxel plus gemcitabine (Nab-Gem) represents one of the standard regimen for first-line treatment of metastatic pancreatic adenocarcinoma (mPDAC). However, few data are available in mPDAC relapsed after gemcitabine as adjuvant treatment. Our study aims to evaluate the efficacy and feasibility of Nab-Gem as first-line treatment for mPDAC patients previously treated with adjuvant treatment. We retrospectively analyzed the safety and efficacy data of 36 patients, who received first-line Nab-Gem after gemcitabine as adjuvant treatment. All patients received gemcitabine after radical surgery. Median disease-free survival was 12 months (95% CI 9.7-14.3); at relapse, all patients received Nab-Gem. We observed an objective response rate and disease control rate of 11.1% and 63.9%, respectively. With a median follow-up of 47 months, median progression-free survival was 5 months (95% CI 1.0-9.0), whereas median overall survival (OS) was 13 months (95% CI 5.5-20.5). Median OS was higher in patients with a relapse ≥ 7 months after the end of adjuvant treatment than in patients relapsed < 7 months (14 vs. 8 months, respectively, p: 0.52). Our results show that first-line Nab-Gem is feasible and effective in patients previously treated with gemcitabine as adjuvant treatment.