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1.
BMC Cancer ; 22(1): 168, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35164713

RESUMO

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) accounts for only about 5-10% of all urothelial cancers and is characterized by an aggressive and frequently rapidly fatal behavior. However, detailed knowledge of its molecular profile is still lacking. MATERIALS AND METHODS: We identified, by chart analysis, patients who underwent radical nephroureterectomy or diagnostic biopsy for UTUC between January 2015 and August 2020 at the Santa Maria Hospital of Terni, in Italy. Eligible patients were required to have also adequate clinical informations and follow-up details. The primary objective of the study was to evaluate DNA mismatch repair (MMR) proteins and Nectin-4 immunohistochemical expression in UTUC, looking also for an eventual correlation between these molecular features. The secondary objective was to investigate genomic instability in the case of a MMR protein loss. Expression of proteins was assessed by using immunohistochemistry and microsatellite instability (MSI) performed by next generation sequencing. Nectin-4 expression was reported using an intensity scoring system (score, 0-3+), instead the expression of DNA MMR proteins was indicated as present (no loss) or not present (loss). RESULTS: Thirty four cases have been evaluated and 27 considered eligible for the study with their tumor samples analyzed. Nectin-4 was found to be expressed in 44% of cases and 18.5% of patients showed defective-MMR phenotype. We found a significant correlation between Nectin-4 expression and MSH2/MSH6 protein loss. Out of 7 patients with DNA MMR proteins loss or equivocal phenotype, 3 showed MSI. CONCLUSIONS: Our pilot study suggest a possible relationship between Nectin-4 and DNA MMR protein expression in UTUC and a clinically significant correlation between defective MMR phenotype and genomic instability. Because of the possible implications of these data for innovative treatment approaches, the need for further studies in this area is warranted.


Assuntos
Carcinoma/genética , Moléculas de Adesão Celular/metabolismo , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Urológicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Itália , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Nefroureterectomia , Fenótipo , Projetos Piloto , Estudos Retrospectivos , Neoplasias Urológicas/cirurgia , Urotélio/metabolismo
2.
Br J Clin Pharmacol ; 85(6): 1283-1289, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30740760

RESUMO

AIMS: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients. METHODS: We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation. RESULTS: The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0). CONCLUSIONS: This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.


Assuntos
Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Idoso , Biomarcadores/sangue , Carcinoma de Células Renais/secundário , Cardiotoxicidade , Feminino , Humanos , Incidência , Itália/epidemiologia , Neoplasias Renais/patologia , Masculino , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Troponina I/sangue , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular/efeitos dos fármacos
3.
Future Oncol ; 14(26): 2691-2699, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30207488

RESUMO

AIM: To collect efficacy and safety data of enzalutamide after docetaxel, we retrospectively evaluated the Italian Named Patient Program results. PATIENTS & METHODS: Two hundred and nine metastatic castration-resistant prostate cancer patients were enrolled. Median age was 73 years. Total 42.1% patients had pain, 14.4% had a performance status of two and 59.8% had a Gleason score ≥8. Total 31.1% had previously received ≥2 chemotherapies, 15.3 and 12% had been previously treated with abiraterone and cabazitaxel, respectively and 14.8% had received both. RESULTS:  Median progression-free survival and overall survival were 4.8 and 13.1 months, respectively. A prostate-specific antigen reduction ≥50% was observed in 49.1%. Total 32.7% abiraterone-pretreated patients achieved a biochemical response compared with 56% of abiraterone-naive patients. CONCLUSION:  Enzalutamide was safe and well tolerated. Its antitumor activity in abiraterone-pretreated patients was limited.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenos/farmacologia , Androstenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzamidas , Progressão da Doença , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Itália/epidemiologia , Calicreínas/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
5.
Cancer Treat Rev ; 128: 102766, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763054

RESUMO

DNA-damage repair (DDR) pathways alterations, a growing area of interest in oncology, are detected in about 20% of patient with prostate cancer and are associated with improved sensitivity to poly(ADP ribose) polymerases (PARP) inhibitors. In May 2020, the Food and Drug Administration (FDA) approved two PARP inhibitors (olaparib and rucaparib) for prostate cancer treatment. Moreover, germline aberrations in DDR pathways genes have also been related to familial or hereditary prostate cancer, requiring tailored health-care programs. These emerging scenarios are rapidly changing diagnostic, prognostic and therapeutic approaches in prostate cancer management. The aim of this review is to highlight the five W-points of DDR pathways in prostate cancer: why targeting DDR pathways in prostate cancer; what we should test for genomic profiling in prostate cancer; "where" testing genetic assessment in prostate cancer (germline or somatic, solid or liquid biopsy); when genetic testing is appropriate in prostate cancer; who could get benefit from PARP inhibitors; how improve patients outcome with combinations strategies.


Assuntos
Dano ao DNA , Reparo do DNA , Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Reparo do DNA/efeitos dos fármacos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Dano ao DNA/efeitos dos fármacos , Terapia de Alvo Molecular/métodos
6.
Cancer Treat Rev ; 124: 102698, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359590

RESUMO

In the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment.


Assuntos
Medicina de Precisão , Neoplasias da Próstata , Masculino , Humanos , Nanomedicina Teranóstica , Neoplasias da Próstata/terapia
7.
Clin Genitourin Cancer ; 22(6): 102225, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39405768

RESUMO

BACKGROUND: Pembrolizumab/Axitinib combination is approved as first-line therapy in mRCC. The aim of this study is to evaluate outcomes of PAXI combo in the real-world in Italy. METHODS: This is a prospective study including patients diagnosed with mRCC who received combination as first-line therapy in recruiting Italian Centers. Data about patient characteristics, safety and outcome were collected. RESULTS: 170 pts have been treated from December 2020 to September 2023. The majority had clear-cell histology (83%). Sarcomatoid feature was present in 33%of available cases. About one half of patients (55%) had synchronous metastasis. In 58% of cases nephrectomy was performed, of which 27% were cytoreductive and 4% were deferred nephrectomies. Lung metastases were identified in 106 patients (62%), bone and liver involvement in 66 and 29 patients (38.8% and 17.1%) respectively. Stratifying by IMDC criteria, 32 patients (18.8%) were at favorable-risk, 106 (62.4%) at intermediate-risk, and 32 (18.8%) at poor-risk. At time of analysis, treatment was ongoing in 49% of patients. Progression occurred in 45% of patients. Median PFS was 19.2 months (95% CI: 15-NR). With a median follow-up of 19.3 months (range 1.3-34.5), at 24-months and 36-months landmark analysis 62% (95% CI, 53-70) and 58% (95% CI, 47-69) of treated patients are still alive respectively. Disease control rate was achieved in 84.6% of patients: 4.3% reached a complete response, 52% had a partial response and 28.8% a stable disease. Primary progression was observed in 15.3% of patients. In the multivariate analysis, the prognostic significance of age ≥ 65 years, non-clear cell histology, IMDC score, and adverse events and gender interaction as predictors of worse OS were confirmed. CONCLUSION: This is the first available prospective study on first-line Pembrolizumab/Axitinib combination in real world scenario. Our findings support the effectiveness and safety of first-line this combination in mRCC and reveal that gender emerged as a prognostic factor in relation to the occurrence of adverse events.

8.
EClinicalMedicine ; 61: 102044, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37434748

RESUMO

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.

9.
Cancers (Basel) ; 14(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077726

RESUMO

Prostate cancer is the second most common diagnosed cancer and the fifth leading cause of cancer-related deaths in men worldwide. Despite significant advances in the management of castration-sensitive prostate cancer, the majority of patients develop a castration-resistant disease after a median duration of treatment of 18-48 months. The transition to a castrate resistance state could rely on alternative survival pathways, some related to androgen-independent mechanisms. Although several agents have been approved in this setting, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Recent studies revealed some of the complex pathways underlying inherited and acquired mechanisms of resistance to available treatments. A better understanding of these pathways may lead to significant improvements in survival by providing innovative therapeutic targets. The present comprehensive review attempts to provide an overview of recent progress in novel targeted therapies and near-future directions.

10.
Anticancer Res ; 42(1): 165-172, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969722

RESUMO

BACKGROUND: Outcomes of castration-sensitive prostate cancer (CSPC) have improved owing to new therapies and early treatment, previously reserved for castration-resistant disease (CRPC). Prostatic-specific antigen (PSA) remains the most used marker to follow-up patients under treatment, but only limited data are available about the prognostic role of its changes over time and the impact of response to subsequent therapies. This analysis aims to assess the prognostic role of the magnitude and velocity of PSA response in CSPC and describe how this may affect the outcome to subsequent treatment outcomes in CRPC. PATIENTS AND METHODS: A retrospective analysis was performed on patients with de novo CSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. PSA response (PSA50), defined as a decrease > 50% compared to baseline, PSA velocity (PSAv), defined as any decrease in PSA levels over time and the deep and fast PSA response (4mPSA50), defined as the PSA response reached within the threshold of 4 months from the beginning of androgen deprivation therapy (ADT) have been evaluated for their impact on survival. Survivals were estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional-hazard models, stratified according to baseline characteristics, were used to estimate hazard ratios for overall survival (OS). RESULTS: A totals of 94.4% of patients had PSA50, which was correlated to longer OS compared to patients without PSA50 (56.0 vs. 14.8 months; p<0.001). The median PSAv was 6.9 (ng/dl)/month, which was predictive for longer OS: Each decrease of 1 (ng/dl)/month was able to improve OS by 0.2% (HR=0.998, 95%CI=0.997-1.000; p=0.008). A total of 47.9% of patients reached 4mPSA50, with a median OS and progression-free survival (PFS) to ADT-based therapy of 101.0 and 23.4 months compared to 41.9 and 11.0 months for those who did not (p<0.001), respectively. The independent prognostic role of 4mPSA50 was retained even when evaluated in multivariable analysis adjusted for other baseline characteristics and early docetaxel for CSPC. In CRPC, 4mPSA50 evaluated during CSPC retains its prognostic role even if it does not predict a different outcome between patients treated with abiraterone/enzalutamide or taxanes. CONCLUSION: Achieving a deep and fast PSA response correlates with a better outcome in patients with de novo mCSPC, also positively influencing the prognosis of the subsequent first-line therapy for CRPC disease.


Assuntos
Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Humanos , Masculino , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
11.
Cancers (Basel) ; 14(6)2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35326693

RESUMO

The recurrent genetic anomalies used to classify prostate cancer (PC) into distinct molecular subtypes have limited relevance for clinical practice. In consideration of WHO 2016 histological classification, which includes the introduction of Gleason Score 4 for patients with cribriform component and the definition of intraductal carcinoma as a new entity, a retrospective pilot study was conducted to investigate, by histological review, if there were any variations of Gleason Score and the incidence of intraductal carcinoma and cribriform pattern, intended as "phenotypic" markers of potentially lethal PC, among metastatic castration-sensitive PC (mCSPC) and metastatic castration-resistant PC (mCRPC) samples. Potentially predictive factors were also assessed. Among 125 cases, a variation in the Gleason Score was reported in 26% of cases. A cribriform (36%) or intraductal (2%) pattern was reported in a higher percentage. Of them, a primary Gleason pattern 4 was reported in 80% of cases. All patients with intraductal carcinoma present a BRCA2 mutation, also found in 80% of cases with a cribriform pattern. This pilot study documented some hypothesis-generating data, as the evaluation of de novo mCSPC and mCRPC as phenotypic/biologic model to be translated in clinical practice. A cribriform pattern/intraductal carcinoma might be a marker of potentially lethal PC. The high incidence of TP53 and BRCA2 mutations in de novo mCSPC may also have a therapeutic implication.

12.
Emerg Med Int ; 2021: 9913076, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34123430

RESUMO

Microwave ablation is a safe and effective interventional approach, widely used in the treatment of unresectable primary or metastatic hepatic lesions. Thoracobiliary fistula is a rare postablation complication that can be treated with a conservative or surgical approach. We reviewed aetiology, pathogenesis, clinical picture, diagnostic possibilities, and therapeutic options for biliothoracic fistula developed after microwave ablation of liver metastasis. Furthermore, we reported our experience of successful conservative management of a nonhealing thoracobiliary fistula occurred after percutaneous thermal ablation of colorectal cancer liver metastasis. Our case supports a conservative approach based on percutaneous biliary system decompression and synthetic glue embolization for the treatment of combined biliopleural and biliobronchial fistula.

13.
World J Gastrointest Surg ; 13(11): 1463-1483, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34950434

RESUMO

BACKGROUND: Gastric cancer is an aggressive disease with frequent lymph node (LN) involvement. The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs. This threshold has been the subject of great debate, not only for the extent of surgery but also for more appropriate staging. The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number. Furthermore, studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastric cancer. AIM: To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation. METHODS: Eligible patients were identified from the Surveillance, Epidemiology, and End Results database. Those with stage II-III gastric cancer were considered for inclusion. Three groups were compared based on the number of analyzed LNs. They were inadequate LN assessment (ILA, < 16 LNs), adequate LN assessment (ALA, 16-29 LNs), and optimal LN assessment (OLA, ≥ 30 LNs). The main outcomes were overall survival (OS) and cancer-specific survival. Data were analyzed by the Kaplan-Meier product-limit method, log-rank test, hazard risk, and Cox proportional univariate and multivariate models. Propensity score matching (PSM) was used to compare the ALA and OLA groups. RESULTS: The analysis included 11607 patients. Most had advanced T stages (T3 = 48%; T4 = 42%). The pathological AJCC stage distribution was IIA = 22%, IIB = 18%, IIIA = 26%, IIIB = 22%, and IIIC = 12%. The overall sample divided by the study objective included ILA (50%), ALA (35%), and OLA (15%). Median OS was 24 mo for the ILA group, 29 mo for the ALA group, and 34 mo for the OLA group (P < 0.001). Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group [ALA hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.79-0.88, P < 0.001 and OLA HR = 0.73, 95%CI: 0.68-0.79, P < 0.001]. The OS outcome was confirmed by multivariate analysis (ALA HR = 0.68, 95%CI: 0.64-0.71, P < 0.001 and OLA: HR = 0.48, 95%CI: 0.44-0.52, P < 0.001). A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group (OS: OLA median = 34 mo vs ALA median = 26 mo, P < 0.001, which was confirmed by univariate analysis (HR = 0.81, 95%CI: 0.75-0.89, P < 0.001) and multivariate analysis: (HR = 0.71, 95%CI: 0.65-0.78, P < 0.001). CONCLUSION: Proper nodal staging is a critical issue in gastric cancer. Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.

14.
Cancers (Basel) ; 13(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34572753

RESUMO

BACKGROUND: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. RESULTS: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). CONCLUSION: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

15.
J Immunother ; 43(3): 95-103, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32080018

RESUMO

Limited prospective data about the activity of immune checkpoint inhibitors (ICIs) are available for elderly patients. The aim of our analysis was to determine the relative efficacy of ICIs versus available standard therapies [standard of care (SOC)] in subgroups defined by patients' age. Searching the MEDLINE/PubMed, Cochrane Library, and American Society of Clinical Oncology (ASCO) Meeting abstracts randomized clinical trials were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The measured outcome was overall survival (OS). Twenty-nine randomized clinical trials (18,839 patients) were selected. As for the distribution of patients by age, all but 3 of the selected studies considered young the patients younger than 65 years (n=10,832) and elderly those with 65 years and older (n=7723); 7 studies identified a third subgroup of very elderly patients aged 75 years and above (n=421). In elderly and very elderly patients ICIs significantly reduced the risk of death by 23% compared with SOC [hazard ratio (HR), 0.77; P<0.00001)]. On the contrary, a lack of a survival advantage of immunotherapy was observed in the subgroup of very elderly patients (HR, 0.85; P=0.39). When comparing the efficacy of ICIs between the 2 subpopulations (elderly vs. young), no significant difference in OS was observed (HR, 0.76; P=0.66). ICIs prolonged OS compared with SOC in both elderly and young patients affected by lung cancer, melanoma, and renal carcinoma, regardless of the age. In conclusion, ICIs (as monotherapy or combinations) significantly improved OS compared with SOC in both young and elderly patients with advanced cancers, regardless of the tumor type. The magnitude of this benefit is debated in patients aged 75 years and above.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Fatores Etários , Biomarcadores Tumorais , Suscetibilidade a Doenças , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Proteínas de Checkpoint Imunológico , Terapia de Alvo Molecular/métodos , Neoplasias/diagnóstico , Neoplasias/etiologia , Neoplasias/mortalidade , Prognóstico , Viés de Publicação , Resultado do Tratamento
16.
Prostate Cancer Prostatic Dis ; 23(4): 654-660, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32651468

RESUMO

BACKGROUND: Cancer-related pain, usually associated with bone metastases, is a frequent and debilitating morbidity in patients with prostate cancer. To date there are only limited data regarding the prognostic role of pain in men with metastatic castration-sensitive prostate cancer (mCSPC). The objective of our analysis was to assess if the presence of pain can be considered an independent prognostic factor in mCSPC patients. METHODS: A retrospective analysis was performed on patients with mCSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. Patients were considered to have pain if this was reported within the patient's file or in case of a chronic analgesic therapy was found among the concomitant medications. Survivals were estimated by the Kaplan-Meier method, and compared across groups using the log-rank test. Cox proportional hazard models, stratified according to the baseline characteristics, were used to estimate hazard ratios for overall survival (OS). All the variables were significant if p < 0.05. RESULTS: Data about pain were available for 365 cases and pain was present in 34.8% of patients. Pain was mainly associated with high value of prostate-specific antigen, metastatic bone extension regardless of the site, and lymph node involvement. mCSPC patients with pain had in most of the cases high-volume or Hr disease, and significant shorter OS (27.0 vs. 58.2 months, p < 0.001) and PFS (10.1 vs. 17.4 months, p < 0.001) compared to those without pain. The negative impact of pain on OS remained significant even if adjusted for CHAARTED or LATITUDE classification, and other significant baseline prognostic factors. CONCLUSIONS: This analysis supports the poor prognostic role of cancer-related pain in the setting of mCSPC patients. A prospective validation is required.


Assuntos
Dor do Câncer/epidemiologia , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/sangue , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Dor do Câncer/diagnóstico , Dor do Câncer/mortalidade , Dor do Câncer/patologia , Ensaios Clínicos como Assunto , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxa de Sobrevida
17.
Eur J Cancer ; 128: 17-26, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32109847

RESUMO

BACKGROUND: Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. PATIENTS AND METHODS: We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. RESULTS: One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. CONCLUSIONS: Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Índice de Massa Corporal , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico , Obesidade/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Obesidade/diagnóstico , Obesidade/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
18.
Oncoimmunology ; 9(1): 1710389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002308

RESUMO

Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48-0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39-0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.


Assuntos
Antineoplásicos Imunológicos , Neoplasias , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/genética , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias/diagnóstico , Receptor de Morte Celular Programada 1/uso terapêutico , Estudos Retrospectivos
19.
Semin Oncol ; 46(1): 65-72, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30665685

RESUMO

There is no second-line standard of care universally accepted for platinum-refractory metastatic urothelial carcinoma. Immunotherapy and anti-VEGF(R) targeted therapies are 2 emerging strategies with promising though inconclusive results. We perform a systematic meta-analysis to assess the available options. We searched MEDLINE/PubMed, the Cochrane Library, and American society of clinical oncology (ASCO) Meeting abstracts to identify prospective studies. Data extraction was conduced according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The measured outcomes were overall survival (OS) and progression free survival (PFS). Seven randomized controlled trials were selected for final analysis, with a total of 2,451 evaluable patients. Chemotherapy with vinflunine did not reduce the risk of progression (HR = 1.11; 95%CI 0.78-1.57; P = .56) or death (HR = 0.97; 95%CI 0.70-1.34; P = .87) compared to taxanes. Immunotherapy with anti-PD-1/PD-L1 mAb improved OS over chemotherapy (HR = 0.81; 95% CI 0.71-0.92; P<.0009). The OS benefit of immunotherapy was retained when compared to taxanes, but not compared to vinflunine, although without a significant difference between the 2 subgroups (P = .30). A lack of PFS (HR = 0.73; P = .08) and OS (HR = 1.0; P = .99) benefit was observed with an anti-VEGF(R) plus chemotherapy compared to chemotherapy alone. No PFS (P = .14) or OS (P = .13) differences were detected when comparing anti-VEGF(R) ± chemotherapy and immunotherapy. Immunotherapy significantly improved OS compared to chemotherapy in metastatic urothelial carcinoma unselected for PD-L1 status. The addition of anti-VEGF(R) to chemotherapy did not provide any statistically significant benefit in terms of PFS or OS. Single agent taxanes or vinflunine can be considered given their similar efficacy but different toxicity profiles.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma/tratamento farmacológico , Urotélio/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma/imunologia , Carcinoma/patologia , Intervalo Livre de Doença , Tratamento Farmacológico/tendências , Humanos , Imunoterapia/tendências , Estadiamento de Neoplasias , Resultado do Tratamento , Urotélio/patologia
20.
J Immunother ; 42(7): 269-273, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31261165

RESUMO

De novo metastatic castration-sensitive prostate cancer (mCSPC) is small subgroup of prostate cancer associated with poor prognosis. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) in tumor cells of de novo mCSPC patients. Patients referred to our institution from January 2007 to October 2017 with de novo mCSPC and available diagnostic tissue were included. We tested the PD-L1 pharmaDx qualitative immunohistochemical assay, a monoclonal rabbit anti-PD-L1, clone 28-8 intended for use in the detection of PD-L1 protein in formalin-fixed paraffin-embedded. Kaplan-Meier method was used to estimate survivals according to the expression of PD-L1. The study population included 32 de novo mCSPC patients, analyzed for PD-L1 expression using 2 cut-off values (1% and 5%) to define the positivity. Total of 46.9% of cases had tumor PD-L1 expression ≥1%, and 31.3% had expression ≥5%. No differences were found between the PD-L1 expression ≥1% and the involvement of liver, lung, and number of bone metastases, and the disease volume based on CHAARTED classification. PD-L1 tumors had higher incidence of Gleason score ≥8 compared with PD-L1 tumors (P=0.037), while the incidence of lymph node metastases was higher in PD-L1 tumors (P=0.044). No difference in the median overall survival (mOS) was observed between the PD-L1 population and the PD-L1 patients (43.8 vs. 29.6 mo; P=0.88). The tumor PD-L1 expression cannot be considered a prognostic factor for de novo mCSPC, even if its prognostic and predictive significance have to be thoroughly investigated to better define the selected group of prostate cancer patients that might benefit from checkpoint blockade immunotherapy.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
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