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BACKGROUND: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment. PATIENTS AND METHODS: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study. RESULTS: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence. CONCLUSION: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib.
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Antineoplásicos , Tumores do Estroma Gastrointestinal , Humanos , Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-kit/genética , Recidiva Local de Neoplasia , Receptores Proteína Tirosina Quinases/genética , Mutação , Frequência do GeneRESUMO
BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Renais/mortalidade , Neoplasias Renais/imunologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Adulto , Idoso , Adulto Jovem , Adolescente , Fatores Sexuais , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de Sobrevida , Idoso de 80 Anos ou maisRESUMO
The transformative role of artificial intelligence (AI) and multiomics could enhance the diagnostic and prognostic capabilities of liquid biopsy (LB) for lung cancer (LC). Despite advances, the transition from tissue biopsies to more sophisticated, non-invasive methods like LB has been impeded by challenges such as the heterogeneity of biomarkers and the low concentration of tumour-related analytes. The advent of multiomics - enabled by deep learning algorithms - offers a solution by allowing the simultaneous analysis of various analytes across multiple biological fluids, presenting a paradigm shift in cancer diagnostics. Through multi-marker, multi-analyte and multi-source approaches, this review showcases how AI and multiomics are identifying clinically valuable biomarker combinations that correlate with patients' health statuses. However, the path towards clinical implementation is fraught with challenges, including study reproducibility and lack of methodological standardization, thus necessitating urgent solutions to solve these common issues.
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BACKGROUND: Sexual function is an important concern for adolescent and young adult (AYA) with cancer. The aim of this study was to explore the attitude of Italian health care professionals who deal with AYA patients with cancer toward sexual health communication. MATERIALS AND METHODS: A 11-question survey was developed by the AIOM (Associazione Italiana di Oncologia Medica) and AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) AYA workgroup and sent to AIOM and AIEOP members. RESULTS: The sample comprised 360 respondents, 54.2% AIEOP and 45.8% AIOM members. Eighty percent were physicians, 14.5% nurses, 4.7% psychologists, and 0.8% other professionals. Medical oncologists are more used to investigate about AYA sexual health than pediatric oncologists (58.2% vs. 46.2%), even if pediatrics more frequently refer patients to specific and shared protocol (40% vs. 26.1%). Both AIOM and AIEOP participants mostly talk about sexual health only on request or occasionally (78.8% and 79%, respectively). Clinician-reported barriers to communication identified in this study are lack of preparation and embarrassment for both the categories, plus the presence/interference of parents for pediatrics and lack of time for medical oncologists. Overall, less than 5% of clinicians in our survey received specific training on potential sexual health issues in AYA patients with cancer and only 2% felt adequately prepared to speak about it. CONCLUSION: Sexual health is a key component of comprehensive care for AYA with cancer during treatments. This study highlighted the need of Italian providers for specific training and guidelines on sex-related health issues encountered by AYA patients.
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Neoplasias , Saúde Sexual , Criança , Humanos , Adolescente , Adulto Jovem , Neoplasias/complicações , Neoplasias/terapia , Atenção à Saúde , Pessoal de Saúde , Itália , ComunicaçãoRESUMO
The increasing number of examinations and interventional radiological procedures that require the administration of contrast medium (CM) in patients at risk for advanced age and/or comorbidities highlights the problem of CM-induced renal toxicity. A multidisciplinary group consisting of specialists of different disciplines-radiologists, nephrologists and oncologists, members of the respective Italian Scientific Societies-agreed to draw up this position paper, to assist clinicians increasingly facing the challenges posed by CM-related renal dysfunction in their daily clinical practice.The major risk factor for acute renal failure following CM administration (post-CM AKI) is the preexistence of renal failure, particularly when associated with diabetes, heart failure or cancer.In accordance with the recent guidelines ESUR, the present document reaffirms the importance of renal risk assessment through the evaluation of the renal function (eGFR) measured on serum creatinine and defines the renal risk cutoff when the eGFR is < 30 ml/min/1.73 m2 for procedures with intravenous (i.v.) or intra-arterial (i.a.) administration of CM with renal contact at the second passage (i.e., after CM dilution with the passage into the pulmonary circulation).The cutoff of renal risk is considered an eGFR < 45 ml/min/1.73 m2 in patients undergoing i.a. administration with first-pass renal contact (CM injected directly into the renal arteries or in the arterial district upstream of the renal circulation) or in particularly unstable patients such as those admitted to the ICU.Intravenous hydration using either saline or Na bicarbonate solution before and after CM administration represents the most effective preventive measure in patients at risk of post-CM AKI. In the case of urgency, the infusion of 1.4% sodium bicarbonate pre- and post-CM may be more appropriate than the administration of saline.In cancer patients undergoing computed tomography, pre- and post-CM hydration should be performed when the eGFR is < 30 ml/min/1.73 m2 and it is also advisable to maintain a 5 to 7 days interval with respect to the administration of cisplatin and to wait 14 days before administering zoledronic acid.In patients with more severe renal risk (i.e., with eGFR < 20 ml/min/1.73 m2), particularly if undergoing cardiological interventional procedures, the prevention of post-CM AKI should be implemented through an internal protocol shared between the specialists who treat the patient.In magnetic resonance imaging (MRI) using gadolinium CM, there is a lower risk of AKI than with iodinated CM, particularly if doses < 0.1 mmol/kg body weight are used and in patients with eGFR > 30 ml/min/1.73 m2. Dialysis after MRI is indicated only in patients already undergoing chronic dialysis treatment to reduce the potential risk of systemic nephrogenic fibrosis.
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Injúria Renal Aguda , Nefrologia , Radiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Meios de Contraste , Feminino , Humanos , Rim/fisiologia , Masculino , Oncologia , Fatores de RiscoRESUMO
OBJECTIVES: To investigate the correlation between CT imaging features and risk stratification of gastrointestinal stromal tumors (GISTs), prediction of mutation status, and prognosis. METHODS: This retrospective dual-institution study included patients with pathologically proven GISTs meeting the following criteria: (i) preoperative contrast-enhanced CT performed between 2008 and 2019; (ii) no treatments before imaging; (iii) available pathological analysis. Tumor risk stratification was determined according to the National Institutes of Health (NIH) 2008 criteria. Two readers evaluated the CT features, including enhancement patterns and tumor characteristics in a blinded fashion. The differences in distribution of CT features were assessed using univariate and multivariate analyses. Survival analyses were performed by using the Cox proportional hazard model, Kaplan-Meier method, and log-rank test. RESULTS: The final population included 88 patients (59 men and 29 women, mean age 60.5 ± 11.1 years) with 45 high-risk and 43 low-to-intermediate-risk GISTs (median size 6.3 cm). At multivariate analysis, lesion size ≥ 5 cm (OR: 10.52, p = 0.009) and enlarged feeding vessels (OR: 12.08, p = 0.040) were independently associated with the high-risk GISTs. Hyperenhancement was significantly more frequent in PDGFRα-mutated/wild-type GISTs compared to GISTs with KIT mutations (59.3% vs 23.0%, p = 0.004). Ill-defined margins were associated with shorter progression-free survival (HR 9.66) at multivariate analysis, while ill-defined margins and hemorrhage remained independently associated with shorter overall survival (HR 44.41 and HR 30.22). Inter-reader agreement ranged from fair to almost perfect (k: 0.32-0.93). CONCLUSIONS: Morphologic contrast-enhanced CT features are significantly different depending on the risk status or mutations and may help to predict prognosis. KEY POINTS: ⢠Lesions size ≥ 5 cm (OR: 10.52, p = 0.009) and enlarged feeding vessels (OR: 12.08, p = 0.040) are independent predictors of high-risk GISTs. ⢠PDGFRα-mutated/wild-type GISTs demonstrate more frequently hyperenhancement compared to GISTs with KIT mutations (59.3% vs 23.0%, p = 0.004). ⢠Ill-defined margins (hazard ratio 9.66) were associated with shorter progression-free survival at multivariate analysis, while ill-defined margins (hazard ratio 44.41) and intralesional hemorrhage (hazard ratio 30.22) were independently associated with shorter overall survival.
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Tumores do Estroma Gastrointestinal , Idoso , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Medição de Risco , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Fatigue is a common distressing symptom for patients living with chronic or acute diseases, including liver disorders and cancer (Cancer-Related Fatigue, CRF). Its etiology is multifactorial, and some hypotheses regarding the pathogenesis are summarized, with possible shared mechanisms both in cancer and in chronic liver diseases. A deal of work has investigated the role of a multifunctional molecule in improving symptoms and outcomes in different liver dysfunctions and associated symptoms, including chronic fatigue: S-adenosylmethionine (SAM; AdoMet). The aim of this work is actually to consider its role also in oncologic settings. PATIENTS AND METHODS: Between January 2006 and December 2009, at the University Campus Bio-Medico of Rome, 145 patients affected by colorectal cancer in adjuvant (n = 91) or metastatic (n = 54; n = 40 with liver metastases) setting and treated with oxaliplatin-based regimen (FOLFOX for adjuvant and bevacizumab + XELOX for metastatic ones), 76 of which with the supplementation of S-adenosylmethionine (AdoMet; 400 mg b.i.d.) (57% of adjuvant patients and 44% of metastatic ones) and 69 without AdoMet supplementation, were evaluated for fatigue prevalence using the Functional Assessment of Chronic Illnesses Therapy-Fatigue (FACIT-F) questionnaire, at 3 and 6 months after the beginning of oncologic treatment. Notably, the number of patients with liver metastases was well balanced between the group of patients treated with AdoMet and those who were not. RESULTS: Among patients receiving oxaliplatin-based chemotherapy, both in adjuvant and in metastatic settings, after just 3 months from the beginning of chemotherapy, mean scores from questionnaire domains like FACIT-F subscale (7.9 vs. 3.1, p = 0.006), FACIT physical (6.25 vs. 3.32, p = 0.020), FACIT emotional (4.65 vs. 2.19, p = 0.045), and FACIT-F total score (16.5 vs. 8.27, p = 0.021) were higher in those receiving supplementation of AdoMet, resulting in reduced fatigue; a significant difference was maintained even after 6 months of treatment. DISCUSSION AND CONCLUSIONS: Mechanisms and strategies for managing CRF are not fully understood. This work aimed at investigating the possible role of S-adenosylmethionine supplementation in improving fatigue scores in a specific setting of cancer patients, using a FACIT-F questionnaire, a well-validated quality of life instrument widely used for the assessment of CRF in clinical trials.
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Neoplasias do Colo , S-Adenosilmetionina , Suplementos Nutricionais , Humanos , Oxaliplatina , Qualidade de Vida , S-Adenosilmetionina/uso terapêutico , Inquéritos e QuestionáriosRESUMO
In recent years, multiple strategies for eliciting anti-tumor immunity have been developed in different clinical studies. Currently, immunotherapy was clinically validated as effective treatment option for many tumors such as melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Some surface receptors of immune cells, called immune checkpoint receptors, may inhibit activity of proinflammatory lymphocytes, following binding with specific ligands. Cancer cells exploit these mechanisms to inactivate tumor-infiltrating lymphocytes (TILs) to escape from immunosurveillance. Among the different tumor-infiltrating immune cell populations, including leucocytes, macrophages, dendritic cells and mast cells, TILs are considered a selected population of T-cells with a higher specific immunological reactivity against tumor cells than the non-infiltrating lymphocytes. In this review we will discuss the promising role of TILs as biomarkers reflecting the immune response to the tumor, describing their potential ability to predict the prognosis and clinical outcome of immunotherapy in some solid tumors.
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Imunoterapia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Animais , Biomarcadores Tumorais , Humanos , Neoplasias/terapia , PrognósticoRESUMO
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK1 receptor antagonist (NK1-RA), a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK1-RA, netupitant, and second-generation 5HT3-RA, palonosetron. So far, no data has been published in literature about the efficacy of a single dose of NEPA in MD-CT. METHODS: We performed a prospective, non-comparative study to assess the efficacy of one shot of NEPA plus dexamethasone in sarcoma patients receiving MD-CT. The primary efficacy endpoint was a complete response (CR: no emesis, no rescue medication) during the overall phase (0-120 h) in cycle 1. The main secondary endpoints were CR during the overall phase of cycles 2 and 3. RESULTS: The primary endpoint was reached in 88.9% of patients. Cycles 2 and 3 overall CR rates were 88.9% and 82.4%, respectively. The antiemetic regimen was well tolerated. CONCLUSIONS: This pilot study showed the benefit of one shot of NEPA to prevent CINV in sarcoma patients receiving MD-chemotherapy.
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Antieméticos/uso terapêutico , Dexametasona/uso terapêutico , Náusea/prevenção & controle , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Humanos , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Palonossetrom/uso terapêutico , Projetos Piloto , Estudos Prospectivos , Piridinas/uso terapêutico , Quinuclidinas/uso terapêutico , Receptores da Neurocinina-1/efeitos dos fármacos , Sarcoma/tratamento farmacológico , Vômito/induzido quimicamenteRESUMO
The title of the original paper is incorrect and is now corrected in this aticle.
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Soft tissue sarcomas (STSs) represent a rare and heterogeneous group of solid tumours derived from mesenchymal progenitors and account for 1% of all adult malignancies. Although in the last decade anthracycline-based chemotherapy single agent or in combinations has been able to improve clinical benefits, prognosis is still poor and STSs represent an important unmet medical need. Continuous advances in cancer genetics and genomics have contributed to change management paradigms of STSs as it occurred for other solid tumours. Several treatments have been recently developed with the specific aim of targeting different cell pathways and immune-checkpoints that have been recognized to drive tumour progression. The following attempts to provide a review of literature focusing on the available data concerning novel treatments and future prospective for the management of metastatic STSs.
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Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Terapia de Alvo Molecular/métodos , Medicina de Precisão , Sarcoma/tratamento farmacológico , Previsões , Humanos , Sarcoma/patologiaRESUMO
Immune-checkpoint inhibitors represent the new standard of care in patients with advanced NSCLC who progressed after first-line treatment. This work aim to assess any difference in both efficacy and safety profiles among Nivolumab, Pembrolizumab and Atezolizumab in pre-treated NSCLC patients. Randomized clinical trials comparing immune-checkpoint inhibitor versus docetaxel in pre-treated patients with advanced NSCLC were included and direct comparison meta-analysis of selected trials have been performed. Subsequently the summary estimates of Nivolumab, Pembrolizumab and Atezolizumab emerging from the direct meta-analysis were selected to provide the pooled estimates of hazard ratio (HR) and relative risk (RR) for the indirect comparisons among these agents. A total of 5 studies met the selection criteria and were included in the meta-analysis. Indirect comparisons for efficacy outcomes showed the RR for ORR nivolumab versus atezolizumab 1.66 (95% CI 1.07-2.58), pembrolizumab versus atezolizumab 1.94 (95% CI 1.30-2.90). No significant differences in both PFS and OS have been observed. Indirect comparisons for safety showed the RR for G3-5 AEs nivolumab versus pembrolizumab 0.41 (95% CI 0.29-0.60), nivolumab versus atezolizumab 0.50 (95% CI 0.35-0.72). No significant differences in both pneumonitis and discontinuation rate have been observed. The results of this work revealed that nivolumab and pembrolizumab are associated with a significant increase of ORR as compared to atezolizumab and nivolumab is associated with a significant lower incidence of G3-5 AEs as compared to the other drugs. These evidences could support the oncologists to select the best drug for each patient.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores Coestimuladores e Inibidores de Linfócitos T/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Docetaxel , Humanos , Incidência , Neoplasias Pulmonares/mortalidade , Nivolumabe , Pneumonia/induzido quimicamente , Pneumonia/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: Low body mass index (BMI) and/or low lean body mass have been shown to be risk factors for chemotherapy-related toxicities in a number of different cancers. However, no data are available regarding the role of BMI as a risk factor for developing toxicities related to the novel anticancer agent, trabectedin, in patients with soft-tissue sarcoma (STS). We evaluated the role of BMI as a risk factor for trabectedin-related toxicity in patients with STS. METHODS: Data from 51 patients with metastatic/advanced STS treated with trabectedin after progression on ≥1 anthracycline ± ifosfamide regimen were retrospectively reviewed. RESULTS: Eighteen patients (35.3%) were underweight, and the remainder were of normal bodyweight (45.1%) or overweight (19.6%). Neutropenia of any grade (77.8 vs. 33.3%) and grade 3-4 neutropenia (50.0 vs. 18.2%) occurred more frequently in the underweight versus normal/overweight patients (p = 0.025). Febrile neutropenia also occurred more frequently in underweight patients. Differences remained statistically significant after adjusting for other predictors of toxicity. There were no significant differences in other hematological and nonhematological toxicities between the groups. CONCLUSIONS: The data suggest for the first time that BMI should be considered a risk factor for neutropenia in patients with STS treated with trabectedin.
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Antineoplásicos Alquilantes/efeitos adversos , Índice de Massa Corporal , Dioxóis/efeitos adversos , Dioxóis/uso terapêutico , Neutropenia/induzido quimicamente , Sarcoma/tratamento farmacológico , Tetra-Hidroisoquinolinas/efeitos adversos , Tetra-Hidroisoquinolinas/uso terapêutico , Magreza/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/fisiopatologia , TrabectedinaRESUMO
This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively. Therefore, these proteins may have a clinical role as circulating biomarkers in the diagnosis and therapeutic monitoring of breast cancer patients.
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Ativinas/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Catepsina L/sangue , Cistatina C/sangue , Folistatina/sangue , Idoso , Biomarcadores Tumorais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/secundário , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Osteoporose/sangue , Curva ROCRESUMO
Post-contrast acute kidney injury is defined as a nephropathy with an increase in serum creatinine of >0.3 mg/dL (or >26.5 µmol/L) or >1.5-times the baseline within 48-72 h of intravascular administration of a contrast medium. Patients with cancer have an increased risk of post-contrast acute kidney injury not only related to the frequent use of contrast medium for computed tomography scans but also to other factors, including the type of tumour, age, oncological therapies, use of other nephrotoxic agents and dehydration. Preventive strategies were developed and may be applied to different risk profiles. Patients at risk may be detected by recently published risk scores.
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Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell-cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer.
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Introduction: Combinations of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors (AIs) have been investigated for the treatment of several tumor types. Both ICIs and AIs may lead to cardiovascular adverse events, and their combination may potentially increase the risk for cardiovascular toxicity. In the present meta-analysis, we aim to assess the cardiovascular toxicity of ICIs plus AIs vs. AIs alone. Secondary objectives are non-cardiovascular adverse events and efficacy. Methods: Systematic review was performed according to PRISMA statement. Phase II and III randomized clinical trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception to June 2022. The pooled risks for overall response rate (ORR), 1-year progression-free survival (PFS), adverse events (AEs), immune-related AEs, (irAEs), hypertension, and vascular events defined as stroke, myocardial infarction and pulmonary embolisms, were calculated. Results: In terms of cardiovascular toxicity, we found higher risk for severe hypertension among patients treated with ICIs plus AIs as compared with those receiving AIs (OR 1.24, 95% CI: 1.01-1.53), but no significant difference was found for any-grade hypertension, and for vascular events. There was also no difference in terms of overall AEs, whereas the incidence of irAEs was increased in the ICIs plus AIs arm, as expected. In terms of efficacy, ICIs plus AIs achieved better ORR (OR 2.25, 95% CI: 1.70-2.97) and PFS (HR 0.49, 95% CI: 0.39-0.63) as compared to AIs alone. Conclusion: The addition of ICIs to AIs significantly increased the risk of high-grade hypertension, but not that of acute vascular events.
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The most remarkable finding in synthetic lethality (SL) is the hypersensitivity to PARP inhibitors (PARPis) of the tumors harboring defects in genes involved in homologous repair (HR) such as BRCA1/2. Despite initial responsiveness to PARPi, the penetrance of the synthetic lethal interactions between BRCA1/2 genes and PARPi is incomplete. Thus, a significant proportion of HR-defective tumors experience intrinsic or acquired resistance, representing a key challenge of clinical research. An expanded concept of SL is opening new ways and includes novel forms of genetic interactions, investigating not only traditional SL of pairs genes but also SL between biological pathways that regulate the same essential survival cell function. In this context, recent research showed that HR and theta-mediated end-joining (TMEJ) pathways exhibit SL. DNA polymerase theta (Polθ) is encoded by the POLQ gene and is a key component of the TMEJ, an essential backup pathway, intrinsically mutagenic, to repair resected double-strand breaks (DSBs) when the non-homologous end joining (NHEJ) and HR are impaired. Polθ is broadly expressed in normal tissues, overexpressed in several cancers, and typically associated with poor outcomes and shorter relapse-free survival. Notably, HR-deficient tumor cells present the characteristic mutational signatures of the error-prone TMEJ pathway. According to this observation, the loss of HR proteins, such as BRCA1 or BRCA2, contributes to increasing the TMEJ-specific genomic profile, suggesting synthetic lethal interactions between loss of the POLQ and HR genes, and resulting in the emerging interest for Polθ as a potential therapeutic target in BRCA1/2-associated tumors.This review summarizes the converging roles of the POLQ and HR genes in DNA DSB repair, the early-stage clinical trials using Polθ inhibitor to treat HR-defective tumors and to overcome BRCA-reversion mutations responsible for therapeutic resistance, and the novel pleiotropic effects of Polθ, paving the way for the development of unexplored synthetic lethality strategies.
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The ongoing global health challenge of cancer is driving the pursuit of innovative avenues for prevention, treatment, and enhanced outcomes. The convergence of nutrition and immune modulation, known as immunonutrition, is ready to act as a catalyst for transformative change in cancer research and therapy. Our study employs a bibliometric analysis to uncover the evolving trends within immunonutrition and cancer research across the past 25 years. Bibliometric data, including authors, journals, affiliations, and countries, were analyzed using the Bibliometrix R package. Clustering algorithms were applied to keywords to identify thematic areas and their evolution. A total of 489 documents were analyzed, showing an annual growth rate of 8.7%, with a collaboration index of 5.41, highlighting comprehensive multidisciplinary involvement within this landscape. Core authors demonstrated sustained productivity, while occasional authors indicated widespread interest. The Medical University of Warsaw led in institutional contributions. Country-wise, Italy, France, and the USA emerged as forerunners in fostering research productivity. Key journals like 'Clinical Nutrition' served as beacons, emphasizing the multidimensional nature of this topic. The analysis highlighted growing research output and several collaborations, indicating the importance of immunoenriched nutrition in cancer treatment. The interplay of core authors and diversified engagement harmoniously accentuates the cross-disciplinary nature of this burgeoning field. International collaboration facilitated knowledge exchange. Prominent documents shaped the field, emphasizing the significance of nutritional interventions. Thematic clusters revealed varied focuses, including pharmaconutrients, surgical approaches, inflammation, and specific cancers. The expanding research output suggests further development, particularly in exploring immunoenriched nutrition's impact on cancer types and patient populations. The multidisciplinary nature and international collaborations enhance the field's progress. Gaps in research underscore the need for original studies and personalized approaches. This study guides future research, informing evidence-based nutritional interventions and advancing cancer care practices.
Assuntos
Dieta de Imunonutrição , Neoplasias , Humanos , Algoritmos , Bibliometria , Análise por Conglomerados , França , Neoplasias/terapiaRESUMO
AIM: COVID-19 pandemic had a big impact on our life, it has revolutionized the practice of cardiology and the organization of hospital and outpatient activities. Thus the aim of our study was to assess the impact of the COVID-19 pandemic on the development of cancer therapy-related cardiac dysfunction (CTRCD). METHODS AND RESULTS: A single center retrospective study was carried out evaluating 96 cancer patients treated with anthracyclines and admitted to our Cardio-Oncology unit from June to August 2019 and 60 patients from June to August 2021. The incidence of CTRCD was assessed performing an echocardiogram at the time of the enrollment. We found a significantly higher incidence of CTRCD in the second period compared to first period (13% vs. 2%, p value 0.0058). In addition we found that fewer yearly visits were performed in our Cardio-oncology unit in 2021 compared to 2019 (300 patients/year in 2019 vs. 144 patients/year in the COVID era). CONCLUSION: COVID-19 pandemic seems to influence the onset of CTRCD in cancer patients by indirectly reducing hospital access of cancer patients and cardiological checks. In addition our data reflect the impact of the COVID-19 pandemic in the late diagnosis of cancer, in the reduction of hospital admissions and regular medical checks, in the increase of comorbidities and cardiovascular complications.