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1.
Eur J Cancer ; 171: 64-74, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35704976

RESUMO

BACKGROUND: Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined. METHODS: Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients. RESULTS: 2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p < 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320). CONCLUSIONS: This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.

2.
J Cancer Surviv ; 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689003

RESUMO

PURPOSE: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity. METHODS: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC. Women completed surveys at baseline and every 6 months for 3 years, then yearly for up to 10 years to assess, among other variables, employment status, sociodemographic, medical, and treatment data. Symptoms were assessed by the Breast Cancer Prevention Trial symptom scales and single items from the Cancer Rehabilitation Evaluation System. Univariable and multivariable multinomial logistic regression analyses identified factors associated with changes in employment status. RESULTS: Among the 245 women included in this analysis, 85% were employed at the last individual post-baseline assessment (1 to 10 years). At 5 years, women had a 29.4% probability (95% CI: 23.6-35.5) of experiencing any reduction and a 14.9% probability (95% CI: 10.6-19.9) of experiencing any increase in work activities. Being enrolled in Switzerland (vs. Italy) and reporting more trouble in performing daily activities were significantly associated with work reduction. CONCLUSION: Our results suggest that most young BC survivors remain employed in the long-term. IMPLICATIONS FOR CANCER SURVIVORS: Regular evaluation of symptoms which may interfere with daily life and identification of financial discomfort is critical in providing timely and individually tailored interventions and in limiting unwanted reductions in work activities.

3.
Oncol Lett ; 23(5): 159, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35399329

RESUMO

Recent breakthroughs in high-throughput technologies have enabled the development of a better understanding of the functionalities of rho-associated protein kinases (ROCKs) under various physiological and pathological conditions. Since their discovery in the late 1990s, ROCKs have attracted the attention of interdisciplinary researchers due to their ability to pleiotropically modulate a myriad of cellular mechanisms. A rapidly growing number of published studies have started to shed light on the mechanisms underlying the regulation of ROCK1 and ROCK2 via long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in different types of cancer. Detailed analyses have suggested that lncRNAs may be characteristically divided into oncogenic and tumor suppressor lncRNAs. Several exciting recent discoveries have also indicated how different lncRNAs and circRNAs modulate ROCK1/2 and mediate multistep cancer onset and progression. The present review chronicles the major advances that have been made in our understanding of the regulatory role of ROCK1/2 in different types of cancer, and how wide-ranging lncRNAs and circRNAs potentiate ROCK-driven signaling by blocking the targeting activities of tumor suppressor microRNAs.

4.
Eur J Cancer ; 166: 202-207, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35306318

RESUMO

BACKGROUND: International guidelines recommend severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for patients with cancer. A substantial risk of developing vaccine-related autoimmune toxicities could be hypothesised for patients with thymic epithelial tumours (TETs) due to their high risk of autoimmune disorders (ADs). Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various tissue proteins has been shown, and antibodies against nucleoproteins showed overlaps in the autoimmune cross-reaction with antibodies to spike protein. Due to the rarity of TETs, no data addressing this hypothesis are available. METHODS: Patients with TETs who received SARS-CoV-2 vaccine, treated in 4 referral centres of the Italian Collaborative Group for ThYmic MalignanciEs (TYME) network between February 2021 and September 2021, were interviewed through a standardised 15-items questionnaire in order to describe the safety of SARS-CoV-2 vaccine in patients affected by TETs. RESULTS: Data from 245 doses of vaccine administered to 126 patients (41 = thymic carcinoma, 85 = thymoma; 38 with AD, of which 26 with active AD) were collected. Nine patients had a previous COVID-19-positive swab. No cases of AD reactivation or worsening of a pre-existing AD were seen in the study population. A new diagnosis of myasthenia gravis likely unrelated to the vaccine was made in two patients after the vaccination. Sixty-four patients (51%) experienced a total of 103 adverse events, all G1/G2, most commonly fatigue, new or worsening muscle pain and chills. None AE required patients' hospitalisation. CONCLUSIONS: SARS-CoV-2 mRNA vaccines appear to be safe in patients with TET, even in case of active or pre-existing AD.


Assuntos
Doenças Autoimunes , COVID-19 , Neoplasias Epiteliais e Glandulares , Neoplasias do Timo , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
5.
Cancers (Basel) ; 14(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35205669

RESUMO

Uterine sarcoma (US) is a rare mesenchymal malignant cancer type, accounting for 3-7% of uterine malignancies. US prognosis is still poor due to high local and distant recurrence rates. As for molecular features, US may present variable oestrogen receptor (ER) and progesterone receptor (PR) expressions, mostly depending on histotype and grading. Surgery represents the mainstay of treatment for early-stage disease, while the role of adjuvant chemotherapy or local radiotherapy is still debated and defined on the basis of histotype, tumour grading and stage. In metastatic setting, uterine sarcomas' treatment includes palliative surgery, a metastases resection, chemotherapy, hormonal therapy and targeted therapy. As for the chemotherapy regimen used, drugs that are considered most effective are doxorubicin (combined with ifosfamide or alone), gemcitabine combined with docetaxel and, more recently, trabectedin or pazopanib. Hormonal therapies, including aromatase inhibitors (AIs), progestins and gonadotropin-releasing hormone analogues (GnRH-a) may also represent an effective option, in particular for low-grade endometrial stromal sarcoma (LGESS), due to their favourable toxicity profile and patients' compliance, while their role is still under investigation in uterine leiomyosarcoma (uLMS), high-grade endometrial stromal sarcoma (HGESS), undifferentiated uterine sarcoma (USS) and other rarer US. The present review aims to analyse the existing evidence and future perspectives on hormonal therapies in US, in order to clarify their potential role in daily clinical practice.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35184993

RESUMO

Few data from randomized clinical trials (RCTs) investigating the efficacy of post-induction strategies after the first-line treatment with anti-Epidermal Growth Factor Receptor (EGFR) in patients with metastatic colorectal cancer (mCRC) are available. A systematic review and metanalysis might therefore be useful to highlight and even strengthen these data. A literature search in Pubmed, Embase, American Society of Clinical Oncology (ASCO) Annual Meetings, ASCO Gastrointestinal Symposia, and European Society for Medical Oncology (ESMO) Congresses was performed. The search included RCTs of patients with mCRC treated with an initial period of cytotoxic chemotherapy (CT) in association with anti-EGFR (ie, panitumumab or cetuximab) as first-line regimen, and then switched to one of the following strategies: observation; maintenance with anti-EGFR, fluoropyrimidine (FP), or both; or continuing the induction regimen until disease progression or unacceptable toxicity. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the Mantel-Haenszel method fixed-effect model or the DerSimonian-Laird method random-effect model according to heterogeneity (I2). Analysis was performed on June 9, 2021. 7 studies (all phase II trials), including 1038 patients, were considered eligible for the meta-analysis. In all studies, CT (induction or maintenance with FP) + anti-EGFR until disease progression or unacceptable toxicity prolonged OS (HR = 0.72 [95%CI 0.61-0.86]; P < .01) and PFS (HR = 0.76, 95%CI 0.68-0.85; P < .01) compared to other agents (FP ± bevacizumab) or observation. Subgroup analyses for OS and PFS were performed according to type of maintenance therapy (containing or not containing single-agent anti-EGFR). Within patients evaluable for OS, CT + anti-EGFR combinations continued until disease progression were able to decrease the risk of death by 32% (HR 0.68; 95% CI 0.56-0.84; P < .01) and the risk of progression by 25% (HR 0.75; 95% CI 0.65-0.85; P < .01) over no maintenance or maintenance with anti-EGFR alone. Conversely, combination of CT + anti-EGFR were no better over anti-EGFR with FP in term of OS (HR = 0.81 [95%CI 0.60-1.09]; P = .17) and PFS (HR = 0.81 [95% 0.64, 1.01]; P = .06). Maintenance treatment with anti-EGFR + FP might be regarded as the better option following anti-EGFR based induction treatment in RAS wild-type mCRC, in terms of efficacy. This effect might be particularly amplified in left-sided BRAF wild-type mCRC patients. A higher level of evidence coming from phase III trials is auspicable.

7.
J Hematol Oncol ; 15(1): 9, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35062993

RESUMO

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/genética , Dano ao DNA , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/genética , Masculino , Resultado do Tratamento
8.
Psychooncology ; 31(1): 39-45, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34315188

RESUMO

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has been declared a global pandemic of unprecedented proportions. Italy is a country which has been heavily affected. Cancer patients are at a higher risk owing to their intrinsic fragility related to their underlying disease and oncologic treatment. Against this backdrop, we conducted a survey to investigate how patients perceived their condition, clinical management and availability of information during the pandemic. METHODS: Between 15 April and 1 May 2020 a survey was submitted to cancer patients at oncology departments in the Marche region. Questions regarding the perception of personal safety, continuity of cancer care, information quality and psychological distress. RESULTS: Seven hundred patients participated in the survey; 59% were female and 40% were aged between 46 and 65. The majority of the participants perceived compliance with appropriate safety standards by cancer care providers and 80% were reassured about their concerns during the medical interview. 40% were worried of being at a higher risk of infection and 71% felt they were at a greater risk because of chemotherapy. 55% felt that postponing cancer treatment could reduce its efficacy, however 76% declared they did not feel abandoned at the time of treatment postponement. Patients between 46 and 65 years declared a significant reduction in sleep (p < 0.01) and in concentration (p = 0.03). CONCLUSIONS: The emergency care offered to cancer patients has been deemed satisfactory in terms of both safety standards and care management. However, the majority of participants perceived the mutual negative influence between their oncologic disease and the risk of infection highlighting the need for special measures to ensure safe continuity of care.


Assuntos
COVID-19 , Neoplasias , Idoso , Feminino , Humanos , Oncologia , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
9.
Semin Cell Dev Biol ; 124: 63-71, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34090752

RESUMO

Advancements in single-cell RNA sequencing technologies have enabled us to deconvolve immune system heterogeneity by identification of functionally distinct immune cell subsets in disease and health. Discovery of non-coding RNAs has opened new horizons for re-interpretation of regulatory roles of myriad of cell signaling pathways in immunology and oncology. Role of miRNAs, circular RNAs and long non-coding RNAs (lncRNAs) in the context of immunomodulation has just begun to be uncovered and future studies may further expand the repertoire of non-coding RNAs implicated in the regulatory circuits. One of the most recent and exciting aspect in molecular immunology is the delivery of non-coding RNAs through exosomes to the recipient cells which results in the re-wiring of different pathways and protein networks in recipient cells. Broader understanding of all of the layers of regulation in this system can provide useful information that could be harnessed to rationally translate laboratory findings into clinically effective therapeutics.

10.
Thorac Cancer ; 13(3): 483-488, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34939342

RESUMO

BACKGROUND: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (mNSCLC) and ECOG performance status (PS) of 2 treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. METHODS: To explore the role of immune-inflammatory surrogates by the validated lung immuno-oncology prognostic score (LIPS) score, including the neutrophil-to-lymphocyte ratio (NLR) and the pretreatment use of steroids, alongside other prognostic variables. A retrospective analysis of 128 patients with PS2 and PD-L1 ≥50% mNSCLC treated between April 2018 and September 2019 with first-line pembrolizumab in a real-world setting was performed. RESULTS: With a median follow-up of 15.3 months, the 1-year overall survival (OS) and median progression-free survival (PFS) were 32.3% (95% CI: 30.9-33.9) and 3.3 months (95% CI: 1.8-4.7), respectively. The NLR, lactate dehydrogenase (LDH) and pretreatment steroids results were the only significant prognostic factors on the univariate analysis and independent prognostic factors by the multivariate analysis on both OS and PFS. The LIPS score, including the NLR and pretreatment steroids, identified 29 (23%) favourable-risk patients, with 0 factors, 1-year OS of 67.6% and median PFS of 8.2 months; 57 (45%) intermediate-risk patients, with 1 factor, 1-year OS 32.1% and median PFS 2.7 months; 42 (33%) poor-risk patients, with both factors, 1-year OS of 10.7% and median PFS of 1.2 months. CONCLUSIONS: The assessment of pre-existing imbalance of the host immune response by combined blood and clinical immune-inflammatory markers may represent a way to unravel the heterogeneous outcome and assessment of patients with mNSCLC and poor PS in the immune-oncology setting.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Prognóstico , Estudos Retrospectivos
11.
Cell Mol Biol (Noisy-le-grand) ; 67(3): 212-223, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34933706

RESUMO

Wealth of information has revolutionized our understanding related to the genetics and functional genomics of this heterogeneous disease. Keeping in view the heterogeneity of ovarian cancer, long-term survival might be achieved by translation of recently emerging mechanistic insights at the cellular and molecular levels to personalize individual strategies for treatment and to identify biomarkers for early detection. Importantly, the motility and invasive properties of ovarian cancer cells are driven by a repertoire of signaling cascades, many components of which have been experimentally verified as therapeutic targets in preclinical models as well as in clinical trials. Scientific evidence garnered over decades of research has deconvoluted the highly intricate intertwined network of intracellular signaling pathways which played fundamental role in carcinogenesis and metastasis. In this review we have provided a compendium of myriad of signaling cascades which have been documented to play critical role in the progression and metastasis of ovarian cancer. We have partitioned this multi-component review into different sections to individually discuss and summarize the roles of TGF/SMAD, JAK/STAT, Wnt/ß-Catenin, NOTCH, SHH/GLI, mTORC1/mTORC2, VEGFR and Hippo/YAP pathways in ovarian cancer metastasis.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Genômica/métodos , Neoplasias Ovarianas/genética , Transdução de Sinais/genética , Animais , Apoptose/genética , Carcinogênese/genética , Modelos Animais de Doenças , Feminino , Humanos , Modelos Genéticos , Metástase Neoplásica , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia
12.
Heliyon ; 7(11): e08252, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34765775

RESUMO

Given the benefits of physical activity for breast cancer survivals, this pilot study aims to assess the feasibility of the MOTIVE program at achieving and maintaining the recommended physical activity level in women diagnosed and treated breast cancer, over 16 weeks. We conduct a pilot-controlled study of 20 women diagnosed with breast cancer stage I, II or IIIa. In this study, women of Intervention Arm (n = 10) received the MOTIVE program. This group was compared to women of Control Arm (n = 10) who received only counselling. Health-related fitness measures, and quality of life were assessed at baseline (t0) and after 4 (t1), 8 (t2) and 16 (t3) weeks. Intervention Arm women reached the recommended physical activity guidelines at t1 and t2 (eff.size = 1.9 [1.0-3.1]), and 90% continued to be active, autonomously, at t3 (eff.size = 1.12 [0.21-2.12]). Intervention Arm participants' arm strength, fitness levels and quality of life also improved over time. No significant improvements in outcome measures were observed in Control Arm participants. These results are encouraging and suggest that the MOTIVE program may be a viable, well tolerated and effective option to help breast cancer women reaching a stable physical activity level over time, which meets prevention-related goals.

13.
Ther Adv Med Oncol ; 13: 17588359211053416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777582

RESUMO

BACKGROUND: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients. METHODS: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population. RESULTS: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like (n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common (n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications. CONCLUSION: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible.

14.
Cancers (Basel) ; 13(21)2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34771702

RESUMO

A healthy lifestyle plays a strategic role in the prevention of BC. The aim of our prospective study is to evaluate the effects of a lifestyle interventions program based on special exercise and nutrition education on weight, psycho-physical well-being, blood lipid and hormonal profile among BC patients who underwent primary surgery. From January 2014 to March 2017, a multidisciplinary group of oncologists, dieticians, physiatrists and an exercise specialist evaluated 98 adult BC female patients at baseline and at different time points. The patients had at least one of the following risk factors: BMI ≥ 25 kg/m2, high testosterone levels, high serum insulin levels or diagnosis of MS. Statistically significant differences are shown in terms of BMI variation with the lifestyle interventions program, as well as in waist circumference and blood glucose, insulin and testosterone levels. Moreover, a statistically significant difference was reported in variations of total Hospital Anxiety and Depression Scale (HADS) score, in the anxiety HADS score and improvement in joint pain. Our results suggested that promoting a healthy lifestyle in clinical practice reduces risk factors involved in BC recurrence and ensures psycho-physical well-being.

15.
J Thorac Dis ; 13(10): 5741-5751, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34795923

RESUMO

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM. METHODS: The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival. RESULTS: In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients. CONCLUSIONS: In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.

16.
Front Oncol ; 11: 736104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660299

RESUMO

BACKGROUND: KRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with first-line chemotherapy doublet + Bevacizumab among different KRAS variants. Secondary end-points were progression free survival (PFS) and overall survival (OS). METHODS: Patients with KRAS mutated mCRC treated with either FOLFIRI/FOLFOX/XELOX + Bevacizumab were eligible for enrollment. Patients whose tumor harbored NRAS mutations or that coexpressed also BRAF mutations were excluded from this retrospective analysis. Patients' individual data were collected from patients' records. Propensity score matching (nearest method, 1:2 ratio) was used to define the two different groups of patients for comparison (KRAS G12C mutated vs other KRAS variants). Eastern Cooperative Oncology Group Performance Status (ECOG PS), sex, metastatic site of involvement, synchronous vs metachronous metastatic disease, tumor sidedness, mucinous histology, primary tumor surgery, more than two lines of treatment for metastatic disease, and radical surgery of metastases were used as matching factors. Response rate (RR) was calculated by RECIST 1.1 criteria. Both progression free-survival and overall survival were calculated by Kaplan-Meier method. Categorical variables were compared by Fisher exact test for binomial variables and by chi-square test for all other instances. The level of statistical significance p was set at 0.05 for all tests. RESULTS: A total of 120 patients were assessed in the final analysis. Out of the 120 patients, 15 (12%) were KRAS G12C mutated. In the whole cohort of patients, 59/120 (49%) had partial response (PR), 42/120 (35%) had stable disease (SD), and 19/120 (16%) had progressive disease (PD) as the best response. In KRAS G12C patients, 4/15 (27%) had PR, 6/15 (40%) had SD, and the remaining 5/15 (33%) had PD as the best response. In patients with other KRAS mutations, 55/105 (52%) had PR, 37/105 (35%) had SD, and the remaining 13/105 (12%) had PD as the best response. The difference in RR between the two groups of patients was statistically significant (p=0.017). On the other hand, no difference in PFS (p=0.76) and OS (p=0.56) was observed. After matching procedures, the difference in response rates between KRAS G12C mutated patients vs the matched cohort of patients with other KRAS mutations remained statistically significant (p=0.016). KRAS G12C mutations were not associated with differences in sites of metastatic involvement, sex, and ECOG PS. On the other hand, synchronous vs metachronous metastatic disease (p=0.039), age > 75 years (p=0.043), and mucinous histology (p=0.008) were more frequent in G12C mutated tumors. CONCLUSIONS: In our cohort of patients, it was observed that KRAS G12C mutations are associated with worse response rates compared to other KRAS variants when treated with standard chemotherapy doublet + Bevacizumab. On the other hand, both PFS and OS were not significantly different. Based on these findings, we believe that new treatment options focused on KRAS G12C inhibition should be tested mainly in first-line setting and in addition to standard chemotherapy doublet + Bevacizumab for mCRC patients, as they might "fill the gap" in response rates that was seen in our study.

17.
Curr Oncol ; 28(5): 3525-3536, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34590611

RESUMO

Caveolin-1 (Cav-1) plays a key role in various neoplastic diseases and is upregulated in different cancers, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, Cav-1 is critical for the uptake of albumin as well as nab-paclitaxel in PDAC cells. Here, we investigated the prognostic impact of Cav-1 expression in a cohort of 39 metastatic PDAC patients treated with different first-line chemotherapy regimens. We also assessed the predictive value of Cav-1 in patients treated with gemcitabine and nab-paclitaxel. Cav-1 expression was evaluated by immunohistochemistry staining in neoplastic and stromal cells, using metastatic sites or primary tumor tissue specimens. Higher levels of Cav-1 expression were associated with significantly worse overall survival (OS) and progression-free survival (PFS). No differences in OS were found between patients treated with gemcitabine + nab-paclitaxel vs. other chemotherapy options. Multivariate analysis for OS and PFS confirmed the independent prognostic role of Cav-1 expression. Our study evidenced a negative prognostic role of Cav-1 in patients affected by metastatic/locally advanced unresectable PDAC. Moreover, Cav-1 expression seems not to predict different response rates to different types of first-line treatment. Future prospective trials will be necessary to confirm the prognostic role of Cav-1 and explore Cav-1 specific inhibitors as a therapeutic option for advanced PDAC patients.


Assuntos
Caveolina 1 , Neoplasias Pancreáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Caveolina 1/genética , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Prognóstico , Estudos Retrospectivos
18.
World J Clin Oncol ; 12(7): 565-580, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34367929

RESUMO

BRCA1/2 pathogenic variants are widely known as major risk factors mainly for breast and ovarian cancer, while their role in gastrointestinal (GI) malignancies such as colorectal cancer (CRC), gastric cancer and oesophageal cancer (OeC) is still not well established. The main objective of this review is to summarise the available evidence on this matter. The studies included in the review were selected from PubMed/GoogleScholar/ScienceDirect databases to identify published articles where BRCA1/2 pathogenic variants were assessed either as a risk factor or a prognostic/predictive factor in these malignancies. Our review suggests that BRCA1/2 might have a role as a risk factor for colorectal, gastric and OeC, albeit with differences among these diseases: In particular BRCA1 seems to be much more frequently mutated in CRC whereas BRCA2 appears to be much more closely associated with gastric and OeC. Early-onset cancer seems to be also associated with BRCA1/2 mutations and a few studies suggest a positive prognostic role of these mutations. The assessment of a potentially predictive role of these mutations is hampered by the fact that most patients with these diseases have been treated with platinum compounds, where it is expected that a higher probability of response should be seen. A few clinical trials focused on poly (ADP-ribose) polymerase inhibitors use in GI cancers are currently ongoing.

19.
Cancers (Basel) ; 13(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200267

RESUMO

In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.

20.
Sci Rep ; 11(1): 13770, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215766

RESUMO

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2-positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias da Mama/genética , Prognóstico , Receptor ErbB-2/genética , Ado-Trastuzumab Emtansina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Receptores de Progesterona/genética
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