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1.
Expert Rev Gastroenterol Hepatol ; : 1-17, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34669536

RESUMO

INTRODUCTION: Biliary tract cancer represents a heterogeneous group of malignancies characterized by dismal prognosis and scarce therapeutic options. AREA COVERED: In the last years, a growing interest in BTC pathology has emerged, thus highlighting a significant heterogeneity of the pathways underlying the carcinogenesis process, from both a molecular and genomic point of view. A better understanding of these differences is mandatory to deepen the behavior of this complex disease, as well as to identify new targetable target mutations, with the aim to improve the survival outcomes. The authors decided to provide a comprehensive overview of the recent highlights on BTCs, with a special focus on the genetic, epigenetic and molecular alterations, which may have an interesting clinical application in the next future. EXPERT OPINION: In the last years, the efforts resulted from international collaborations have led to the identification of new promising targets for precision medicine approaches in the BTC setting. Further investigations and prospective trials are needed, but the hope is that these new knowledge in cooperation with the new technologies and procedures, including bio-molecular and genomic analysis as well radiomic studies, will enrich the therapeutic armamentarium thus improving the survival outcomes in a such lethal and complex disease.

2.
Hepatol Res ; 51(12): 1229-1241, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34591334

RESUMO

BACKGROUND: Advanced Hepatocarcinoma (HCC) is an important health problem worldwide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib. AIMS AND METHODS: With aim to evaluate the optimal choice between Sorafenib and Lenvatinib as primary treatment in clinical practice, we performed a multicentric analysis with the propensity score matching on 184 HCC patients. RESULTS: The median overall survival (OS) were 15.2 and 10.5 months for Lenvatinib and Sorafenib arm, respectively. The median progression-free survival (PFS) was 7.0 and 4.5 months for Lenvatinib and Sorafenib arm, respectively. Patients treated with Lenvatinib showed a 36% reduction of death risk (p = 0.0156), a 29% reduction of progression risk (p = 0.0446), a higher response rate (p < 0.00001) and a higher disease control rate (p = 0.002). Sorafenib showed to be correlated with more hand-foot skin reaction and Lenvatinib with more hypertension and fatigue. We highlighted the prognostic role of Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), bilirubin, alkaline phosphatase and eosinophils for Sorafenib. Conversely, albumin, aspartate aminotransferase (AST), alkaline phosphatase and Neutrophil-Lymphocyte Ratio (NLR) resulted prognostic in Lenvatinib arm. Finally, we highlighted the positive predictive role of albumin > Normal Value (NV), ECOG > 0, NLR < 3, absence of Hepatitis C Virus positivity, and presence of portal vein thrombosis in favor of Lenvatinib arm. Eosinophil < 50 and ECOG > 0 negatively predicted the response to Sorafenib. CONCLUSION: SLenvatinib showed to better perform in a real-word setting compared to Sorafenib. More researches are needed to validate the predictor factors of response to Lenvatinib rather than Sorafenib.

3.
Target Oncol ; 16(5): 653-661, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34491510

RESUMO

BACKGROUND: The results of the pivotal RESORCE trial led to the approval of the tyrosine kinase inhibitor regorafenib as second-line treatment in advanced hepatocellular carcinoma (HCC) after sorafenib failure. Data about prognostic factors in a second-line HCC setting are scarce. OBJECTIVE: The aim of the present study was to investigate prognostic factors in a cohort of patients with advanced HCC treated with regorafenib after progressing on sorafenib. METHODS: We retrieved the data of 259 patients affected by advanced HCC treated with regorafenib as second-line treatment from four different Italian institutions and one South Korean institution and performed a recursive partitioning analysis to build a score system. RESULTS: At the first-step univariate analysis for overall survival (OS), alkaline phosphatase (ALP) was the most significant parameter and was chosen as the first node in our tree model. In the subpopulation of patients presenting with ALP ≤122 U/L (n=155) at baseline, the most statistically significant split was by progression-free survival (PFS) on previous sorafenib treatment, between patients with a PFS ≥ 6 months (n = 59) and patients with a PFS < 6 months (n = 96). In the subpopulation of patients with ALP ≤ 122 U/L and PFS to sorafenib ≥ 6 months, the final split was determined between patients with hepatitis B virus (HBV)-related liver disease (n = 22) and patients with no HBV-related liver disease (n = 37). In the subpopulation of patients presenting ALP >122 U/L (n = 104) at baseline, the most statistically significant split was by aspartate aminotransferase (AST) value, between patients with AST ≤ 56 U/L (n = 48) and patients with AST > 56 U/L (n = 56). We built the Regorafenib Prognostic Index (REP index) stratifying the population into "low-risk," "medium-risk," and "high-risk" groups. The difference in median OS between the three risk groups was statistically significant, being 20.8 months (95% confidence interval [CI] 10.0-46.3) in the "low-risk" group, 8.4 months (95% CI 7.2-1435.8) in the "medium-risk" group, and 5.5 months (95% CI 3.5-13.2) in the "high risk" group. The median PFS was 7.7 months (95% CI 3.7-19.3), 2.5 months (95% CI 2.1-28.8), and 2.4 months (95% CI 1.6-9.1) for the "low-risk," "medium-risk," and "high-risk" groups, respectively. CONCLUSION: The REP index is an independent prognostic factor for OS and PFS in patients with advanced HCC treated with regorafenib.

4.
HPB (Oxford) ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34366240

RESUMO

BACKGROUND: Loco-regional treatments have improved the survival of patients with early hepatocellular carcinoma (HCC), but tumor relapse is a frequent event and survival rates remain low. Moreover, conflicting evidences address early HCC patients to surgery or radiofrequency ablation (RFA), with the clinical need to find predictive non-invasive biomarkers able to guide treatment choice and define patients survival. METHODS: Two independent case series of treatment-naïve HCC patients treated with local RFA, and a cohort of 30 HCC patients treated with liver surgery were enrolled. On the basis of literature evidence, we customized a panel of 21 miRNAs correlated with relapse and prognosis after local curative treatment of HCC. RESULTS: Expression levels of let-7c predict tumor relapse after RFA; we also investigated the same panel in a small cohort of HCC patients undergoing surgery, finding no statistically significance in predicting tumor relapse or survival. Moreover, interaction test indicated that let-7c expression levels are predictive for identifying a subset of patients that should be addressed to surgery. CONCLUSION: Results from this study could predict prognosis of early HCC patients, helping to address early HCC patients to surgery or RFA treatment.

5.
Liver Int ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34250737

RESUMO

BACKGROUND AND AIM: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. METHODS: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). RESULTS: The appearance of arterial hypertension G ≥ 2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93, P = .0188], whereas decreased appetite G ≥ 2 independently predicted decreased OS (HR 1.70, 95% CI 1.25-2.32, P = .0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56-0.93, P = .0149), whereas decreased appetite G ≥ 2 predicted decreased PFS (HR 1.36, 95% CI 1.04-1.77, P = .0277). CONCLUSIONS: Our main findings are that the occurrence of arterial hypertension G ≥ 2 is a predictor of longer survival, whereas decreased appetite G ≥ 2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients' quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.

6.
J Clin Med ; 10(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206930

RESUMO

BACKGROUND: The aim of the present study was to analyze the long-term outcomes of laparoscopic and open surgery for intrahepatic cholangiocarcinoma (iCCA) in a series, collected in a tertiary referral center with a high annual volume of laparoscopic activity. METHODS: Between January 2004 and June 2020, 446 liver resections (LR) were performed for iCCA: of these, 179 were performed by laparoscopic surgery (LS) and 267 with the open approach. The two groups were matched through a 1:1 propensity score using covariates representative of patient and disease characteristics. The study and control groups were compared, with specific attention given to oncological outcomes (rate of R0, depth of resection margins, overall and disease-free survival, rate, and site of recurrence). RESULTS: The number of retrieved nodes, rate, and depth of negative resection margins were comparable between the two groups. The interval time between surgery and subsequent adjuvant treatments was significantly shorter in LS patients. No differences were shown even in the comparison between the LS and the open group in terms of median disease-free and overall survival. Moreover, the disease recurrence rate was comparable between the LS and the open groups (45.2% versus 56.7%), and the recurrence pattern was similar. CONCLUSIONS: The minimally invasive approach for iCCA was once again confirmed to be associated with advantages in terms of intraoperative and short-term outcomes, but was also proven to be oncologically non-inferior to the open counterpart. In the present study, overall and disease-free survival were found to be similar between the two approaches.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34033000

RESUMO

BACKGROUND AND AIM: The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemotherapy is compelling. The aim of the study is to evaluate the ECSIPOT (psECogSIiPnigOT) index, influenced by PECS (PsECogSii) index, prognostic nutritional index (PNI), and GOT. METHODS: This international study was conducted on a training cohort of 126 patients and in three validation cohorts, both European and Korean. ECSIPOT index formula: (PECS:0 = 1 point; PECS:1 = 1.4 points; PECS:2 = 3.2 points) + (PNI > 36.7 = 1 point; PNI < 36.7 = 2 points) + (GOT < 100 = 1 point; GOT > 100 = 2 points). Event-time distributions were estimated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. RESULTS: In the training cohort, mOS was 12.9, 6.3, and 2.8 months for patients with ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 2.11; ECSIPOT-2: HR 4.93; p < 0.0001). In the first validation cohort, mOS was 11.5, 7.3, and 3.3 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 1.74; ECSIPOT-2: HR 3.41; p < 0.0001). In the second validation cohort, mOS was 25.2, 12.5, and 3.0 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 2.33; ECSIPOT-2: HR 8.46; p < 0.0001). In the third validation cohort, mOS was 11.8, 8.1, and 4.6 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 1.47; ECSIPOT-2: HR 3.17; p < 0.0001). Multivariate analysis in all cohorts confirmed the ECSIPOT index as an independent prognostic factor for OS. CONCLUSION: The easy assessment and good risk-stratification performance make the ECSIPOT index a promising tool to comprehensively estimate the prognosis of aBTC patients.

8.
Hepatol Res ; 51(7): 796-802, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34005839

RESUMO

AIM: A link has been established between malnutrition, immunological status, and hepatocellular carcinoma (HCC). The prognostic nutritional index (PNI) has been recognized as a prognostic indicator in early-stage HCC and in patients treated with first-line therapy. However, to date, the role of the PNI in HCC patients treated with regorafenib has not been reported. METHODS: We undertook a multicentric analysis on a cohort of 284 patients affected by advanced HCC treated with regorafenib. The PNI was calculated as follows: 10 × serum albumin concentration (g/dl) + 0.005 × peripheral lymphocyte count (number/mm3 ). Univariate and multivariate analyses were used to investigate the association between PNI and survival outcomes. RESULTS: A PNI cut-off value of 44.45 was calculated by a receiver operating characteristic analysis. The median overall survival was 12.8 and 7.8 months for patients with high (>44.45) and low (≤44.45) PNI, respectively (hazard ratio, 0.58; 95% confidence interval, 0.43-0.77; p = 0.0002). In the univariate and multivariate analyses, low PNI value and increased serum bilirubin level emerged as independent prognostic factors for overall survival. No differences were found between high and low PNI in terms of progression-free survival (p = 0.14). CONCLUSION: If validated, the PNI could represent an easy-to-use prognostic tool able to guide the clinical decision-making process in HCC patients treated with regorafenib.

9.
Cancers (Basel) ; 13(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803257

RESUMO

BACKGROUND: In recent years, the treatment of colorectal liver metastases (CRLM) has undergone significant evolution thanks to technical improvements as well as oncological advances, which have been the subject of targeted studies aimed at understanding the details of this heterogeneous disease. The purpose of this study is to put together pieces of this complex scenario by providing an overview of the evolution that has occurred in the context of a single center within a multidisciplinary management approach. METHODS: Between 2005 and 2020, 1212 resections for CRLM were performed at the Hepatobiliary Surgery Division of San Raffaele Hospital, Milan. The series was divided into three historical periods, which were compared in terms of disease characteristics and short- and long-term outcomes: Period 1, 2005-2009 (293 cases); Period 2, 2010-2014 (353 cases); Period 3, 2015-2020 (566 cases). The trends for surgical technical complexity, oncological burden of the disease, use of the laparoscopic approach and use of techniques for hepatic hypertrophy were analyzed year by year. Uni- and multivariate analyses were performed to identify factors associated with inclusion to a laparoscopic approach and with long-term prognosis. RESULTS: The number of resections performed over the years progressively increased, with an increase in the number of cases with a high Clinical Risk Score and a high profile of technical complexity. The proportion of cases performed laparoscopically increased, but less rapidly compared to other malignant tumors. The risk of postoperative morbidity and mortality was similar in the three analyzed periods. Long-term survival, stratified by Clinical Risk Score, improved in Period 3, while overall survival remained unchanged. CONCLUSION: The cultural background, the maturation of technical expertise and the consolidation of the multidisciplinary team have resulted in safe expansion of the possibility to offer a curative opportunity to patients, while continuously implementing into clinical practice evidence provided by the literature.

10.
J Cancer Res Clin Oncol ; 147(12): 3665-3671, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33745079

RESUMO

BACKGROUND: Recently, three published phase III trials highlighted the superiority of investigational drugs compared to placebo, thus leading to their approval in the second-line setting. We report here a MAIC of second-line MKI options for patients with HCC previously treated with sorafenib using individual real-world data of regorafenib and aggregate data of second-line cabozantinib from the CELESTIAL trial. METHODS: Data from 278 patients who received regorafenib as second-line therapy after sorafenib failure for unresectable HCC were used as IPD. Data inclusion were adapted to those reported in the CELESTIAL trial in the subset of patients who received sorafenib as the only prior therapy. Survival medians and rates were obtained from Kaplan-Meier curves, and differences between regorafenib and cabozantinib groups were explored through Cox regression adjusted for weights originating from MAIC. RESULTS: The median OS of the weighted regorafenib group was 11.1 months (IQR: 5.6-16.4) and 11.3 (IQR: 6.7-22.4) for cabozantinib; HR 0.83 (95%CI 0.62-1.09). The median PFS of the weighted regorafenib group was 3.0 months (IQR: 1.9-4.8) and 5.5 (IQR: 2.3-9.3) for cabozantinib; HR 0.50 (95%CI 0.41-0.62). In the subgroup who received prior sorafenib for < 3 months, the median OS of the regorafenib group was 6.5 months (IQR: 4.7-10.9) and 9.5 months (IQR: 5.9-18.2) for cabozantinib; HR 0.68 (95%CI 0.39-1.16). In the subgroup receiving prior sorafenib for 3 to < 6 months, the median OS of the regorafenib group was 8.0 months (IQR: 4.2-15.2) and 11.5 (IQR: 6.5-23.9) for cabozantinib; HR 0.66 (95%CI 0.42-1.02). In the subgroup receiving prior sorafenib for ≥ 6 months, the median OS of the regorafenib group was 13.4 (IQR: 8.1-46.5) and 12.3 (IQR: 6.6-22.9) for cabozantinib; HR 0.89 (95%CI 0.52-1.51). CONCLUSION: Our results confirmed no differences between regorafenib and cabozantinib in terms of OS. However, in earlier progressors on prior sorafenib a larger benefit might be expected from cabozantinib treatment.


Assuntos
Anilidas/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Terapia de Salvação/métodos , Adulto , Idoso , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Sorafenibe/uso terapêutico
11.
Target Oncol ; 16(3): 401-410, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33646487

RESUMO

BACKGROUND: Regorafenib has been shown to improve clinical outcomes compared to placebo, becoming a standard second-line therapy for sorafenib-progressed and -tolerated hepatocellular carcinoma (HCC) patients. OBJECTIVE: We performed a multicentre, retrospective study in Italy and Korea to evaluate the effectiveness of the treatment sequence sorafenib-regorafenib compared with sorafenib and physician's choice in a real-life setting. PATIENTS AND METHODS: A propensity score model was developed to control the results for baseline variable imbalances between the arm treated with sorafenib and regorafenib (S-R) and the arm treated with sorafenib and physician's choice (S-P). Survival analysis was conducted on the matched population. RESULTS: After the application of propensity score matching, we analysed 99 patients in the arm treated with S-R and 99 patients in the arm treated with S-P. For the S-R group, the median overall survival was 22.2 months (95% CI 17.1-27.4), compared to 17.9 months (95% CI 15.1-50.0) for the S-P group. The results of the univariate analysis showed a 31% reduction of death risk for patients treated with S-R (p = 0.0382) compared to patients treated with S-P. Interaction tests highlighted the predictive role of alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR), and extrahepatic spread. CONCLUSION: This study provides additional proof of the superiority of the S-R treatment over the S-P treatment approach in advanced HCC patients from a real-life setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Pontuação de Propensão , Piridinas/uso terapêutico , Sorafenibe/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia , Estudos Retrospectivos , Sorafenibe/farmacologia
13.
Pharmaceuticals (Basel) ; 14(2)2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33562158

RESUMO

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

14.
Med Oncol ; 38(2): 19, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543377

RESUMO

Biliary tract cancer is an uncommon cancer in developed countries. In localized stages, surgery is the cornerstone of treatment with curative purpose. Conversely in advanced stages, chemotherapy with platinum-gemcitabine combination is the standard of care. Biliary tract cancers are a biologically heterogeneous group of malignancies, which perhaps explains the failure of targeted therapies in unselected patient populations to demonstrate benefit in advanced disease, although there are promises in selected populations (e.g. PD1/PD-L1 positive, BRAFV600E-mutated or IDH1-mutant). In view of the limited benefit of second line therapies in metastatic biliary tract cancer, various targeted agents have been tested in progressive disease. Furthermore, several ongoing trials are using next-generation sequencing of multiple genes to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially be used in pretreated disease (e.g. FGFR or IDH genes). Immunotherapy with immune checkpoint inhibitors may be interesting for patients whose tumors have programmed cell death 1 ligand 1 (PD-L1) overexpression. Ongoing and future trials will further advance our knowledge toward the optimal treatment strategy for the management of biliary tract cancer in its different stages, starting from metastatic and then reaching early stages of disease. We here provided an overview of these novel treatment strategies for advanced biliary tract cancers not amenable of curative treatment modalities.


Assuntos
Neoplasias do Sistema Biliar/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/mortalidade , Ensaios Clínicos como Assunto , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores
15.
Cancers (Basel) ; 13(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430142

RESUMO

Treatment of hepatocellular carcinoma (HCC) is rapidly evolving, with many new therapeutic options; in particular, immunotherapy (IT) is acquiring a major role, even in combination regimens. Despite these promising results, an important limitation is the lack of prognostic and predictive factors that prevent provision of a tool for patient stratification in order to select the most appropriate strategy. Furthermore, response assessment can be challenging with IT due to peculiar patterns such as mixed responses or pseudoprogression. We analyzed biological and clinical features from the first 10 HCC patients treated with nivolumab in our institution. Analysis of patterns of response in CT assessment revealed complete response in pulmonary lesions, along with heterogeneous behavior in the liver and other organ lesions. Peripheral blood mononuclear cells (PBMC) analysis in the first four patients showed unique alterations in a patient with poor prognosis, both at baseline (lower percentage of effector T cells, higher percentage of natural killer T [NK/T] cells) and during treatment with nivolumab (decrease in nonclassical monocytes, increase in monocytic myeloid-derived suppressor cells [MO-MDSC]), suggesting a possible prognostic role for these features. Although obtained in a small cohort of patients, our results open a new perspective for understanding mechanisms underlying IT outcomes in HCC patients.

16.
Cancer Manag Res ; 13: 9379-9389, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992463

RESUMO

Background: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib. Aims and Methods: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival. Results: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34-0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue. Conclusion: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.

17.
Sci Rep ; 10(1): 14613, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32884036

RESUMO

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39-89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6-136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1-G2: 50% vs. 12%; G3-G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3-G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.


Assuntos
Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela
18.
Radiother Oncol ; 149: 174-180, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417346

RESUMO

BACKGROUND AND PURPOSE: A previously introduced index based on early tumor (GTV) regression (ERITCP) during neo-adjuvant radio-chemotherapy of rectal cancer was used to investigate the impact of changes of oxaliplatin (OXA) delivery on the prediction of pathological complete response (pCR) and residual vital cell (RVC) fraction. MATERIALS AND METHODS: Ninety-five patients were treated following an adaptive protocol (41.4 Gy/18fr; 2.3 Gy/fr) delivering a simultaneous integrated boost to the residual GTV in the last 6 fractions (3 Gy/fr). OXA was delivered on days -14, 0 (start of RT) and +14. Based on the oncologist's preference, the last OXA cycle was not administered for 36 patients. MRIs taken at planning and at mid-RT were used to calculate ERITCP, before the timing of the third OXA cycle. The impact of OXA cycles and the discriminative power of ERITCP in predicting the pathological response (pCR, RVC >10%) were quantified. Multivariate logistic regression was performed to assess predictive models. RESULTS: Two patients with complete clinical remission refused surgery (cCR_ww). Complete post-surgical data of 54/59 and 35/36 patients were available for the two groups (3 vs 2 OXA cycles). pCR/pCR + cCR_ww/RVC >10% rates were 31.5/33.9/27.8% and 14.3/14.3/54.3% respectively (p = 0.01-0.07). ERITCP showed high negative predictive value (85-91%) for all end-points. The logistic predictive model for pCR included ERITCP (OR: 0.93) and OXA cycles (OR: 3.5), with AUC = 0.78. Internal validation through bootstrap confirmed the robustness of the results. CONCLUSIONS: Late omission of OXA dramatically reduced the pathological response. OXA delivery after the assessment of ERITCP significantly influenced the relationship between ERITCP and pCR.


Assuntos
Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Humanos , Terapia Neoadjuvante , Oxaliplatina , Neoplasias Retais/tratamento farmacológico , Indução de Remissão , Resultado do Tratamento
19.
Cells ; 8(8)2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344983

RESUMO

: It has now been established that in biological fluids such as blood, it is possible to detect cancer causing genomic alterations by analysing circulating tumour DNA (ctDNA). Information derived from ctDNA offers a unique opportunity to enrich our understanding of cancer biology, tumour evolution and therapeutic efficacy and resistance. Here, we propose a workflow to identify targeted mutations by a customized microarray-based assay for the simultaneous detection of single point mutations in different oncogenes (KRAS, NRAS and BRAF) followed by droplet digital PCR (ddPCR) to determine the fractional abundance of the mutated allele. Genetic variants were determined in the plasma of 20 metastatic colorectal cancer (mCRC) patients previously genotyped on tissue biopsy at the diagnosis for medication planning (T0) and following the tumour genetic evolution during treatment phase (T1 and T2) with the objective of allowing therapy response prediction and monitoring. Our preliminary results show that this combined approach is suitable for routine clinical practice. The microarray platform enables for a rapid, specific and sensitive detection of the most common mutations suitable for high-throughput analysis without costly instrumentation while, the ddPCR, consents an absolute quantification of the mutated allele in a longitudinal observational study on patients undergoing targeted therapy.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Biópsia , Humanos , Biópsia Líquida/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase/métodos
20.
Clin Chim Acta ; 489: 136-143, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30550935

RESUMO

A major effort has been focused on the detection of oncogenes' mutations in diverse types of clinical specimens including formalin-fixed and paraffin embedded tissues, presently the gold-standard samples, up to plasma, that constitute a noninvasive alternative source of tumor DNA. The reliable detection of mutations in circulating tumor DNA requires a high analytical sensitivity. Here, we applied three different highly sensitive methodologies (COLD-PCR, a microarray-based approach and the droplet digital PCR, ddPCR) to identify mutations in the plasma of 30 metastatic colorectal cancer patients previously genotyped on tissue biopsy. The methods showed a modest concordance rate with respect to the results obtained on tissue biopsies: 63.3% by ddPCR, 63% by microarray and 55.6% by COLD-PCR. This could be ascribed either to the different timing between tissue and liquid biopsy collection, which could reflect a different stage of disease progression or to the diverse sensitivity of the methodologies applied. Indeed, if we compare the results obtained on plasma samples, the concordance rates were higher especially by comparing ddPCR versus COLD-PCR (92.6%). Thus, we consider both methodologies as useful procedures easily transferable in a clinical setting. Notably, the ddPCR allows a quantitative assessment of the fractional abundance of the mutation.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise Mutacional de DNA/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , Humanos , Biópsia Líquida , Metástase Neoplásica , Proteínas Proto-Oncogênicas p21(ras)/genética
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