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1.
Lung Cancer ; 167: 8-16, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367910

RESUMO

OBJECTIVE: In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs). MATERIALS AND METHODS: Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted. RESULTS: Completion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36-0.74]) and showed a trend in symptom delay versus chemotherapy. CONCLUSIONS: Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etiologia , Mesotelioma/tratamento farmacológico , Nivolumabe/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida
2.
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
3.
Clin Pharmacol ; 14: 1-9, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35082536

RESUMO

Rearrangement of anaplastic lymphoma kinase (ALK) gene is detected in approximately 5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors targeting ALK have significantly improved the prognosis of these patients. However, most patients experienced disease progression within a few years due to acquired resistance. Brigatinib is a second-generation ALK inhibitor effective in presence of several ALK mutations with demonstrated activity against central nervous system metastases. Currently, brigatinib is approved to treat ALK-positive metastatic NSCLC patients not previously treated with ALK inhibitors and patients who have progressed on or are intolerant to crizotinib. In this review, we provide a summary of results from clinical trials involving brigatinib, and we discuss its possible role in the management of ALK-positive NSCLC in the following years.

4.
Sci Rep ; 12(1): 1055, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35058539

RESUMO

Clinical observations have demonstrated that microsatellite instability-high (MSI-H) and/or deficient MMR (dMMR) status are associated with favorable prognosis and no benefit from 5-Fluorouracil (5-FU)-based adjuvant chemotherapy in patients with resected stage II colorectal cancer (CRC). This study represents a systematic review and meta-analysis exploring the predictive role of MSI-H status in stage III CRC undergoing or not adjuvant chemotherapy. Published articles that evaluated the role of adjuvant chemotherapy in resected stage III CRC from inception to September 2020 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. The random-effects model was conducted to estimate the pooled effect size of OS and DFS. The primary outcome of interest was OS. 21,590 patients with MSI-H/dMMR stage III CRC, from n = 17 retrospective studies, were analyzed. Overall, OS was improved with any adjuvant chemotherapy vs. any control arm (single-agent 5-FU or surgery alone): HR 0.42, 95% CI 0.26-0.66; P < 0.01. Conversely, DFS was not significantly improved (HR 0.7, 95% CI 0.45-1.09; P = 0.11). In patients with stage III MSI-H/dMMR CRC, adjuvant chemotherapy is associated with a significant OS improvement. Thus, MSI-H/dMMR status does represent a predictive factor for postoperative chemotherapy benefit in stage III CRC beyond its prognostic role.


Assuntos
Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Reparo de Erro de Pareamento de DNA , Instabilidade de Microssatélites , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Humanos , Análise de Sobrevida , Resultado do Tratamento
5.
Curr Med Chem ; 29(6): 960-969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34781861

RESUMO

Initially described as a factor involved in liver regeneration and neuronal differentiation, proprotein convertase subtilisin/kexin type 9 (PCSK9) has become one of the key regulators of low-density lipoprotein cholesterol. Beside that, a number of studies have suggested PCSK9 may play a role in cancer biology. This is particularly true for gastroenteric (gastric and liver cancers) and lung cancers, where higher PCSK9 levels were associated with the increased ability of the tumor to develop and give metastasis as well as with reduced overall survival. Accordingly, monoclonal antibodies blocking PCSK9 were recently shown to synergize with immunotherapy in different types of cancers to achieve tumor growth suppression through an increased intratumoral infiltration of cytotoxic T cells. Anti-PCSK9 vaccines have been tested in animal models with encouraging results only in colon carcinoma. As most of this evidence is based on pre-clinical studies, this has led to some controversies and inconsistencies, thus suggesting that additional research is needed to clarify the topic. Finally, modulation of intracellular PCSK9 levels by silencing RNA (siRNA) may help understand the physiological and pathological mechanisms of PCSK9.


Assuntos
Neoplasias Hepáticas , Pró-Proteína Convertase 9 , Animais , LDL-Colesterol , Humanos , Receptores de LDL
6.
Eur J Clin Invest ; 52(1): e13668, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34390488

RESUMO

BACKGROUND: High circulating levels of cellular adhesion molecules (CAMs) in non-small cell lung cancer (NSCLC) have been supposed to act as a negative prognostic factor. Here, we explored the predictive role of pre-treatment levels of CAMs in previously treated patients receiving nivolumab for NSCLC. MATERIALS AND METHODS: Seventy one patients with advanced NSCLC, treated with nivolumab at the dose of 3 mg/kg every 14 days, were enrolled. Maximum follow-up time was 3 years. Serum levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intracellular Adhesion Molecule-1 (ICAM-1) were measured at baseline and before each nivolumab administration. Endpoints of the study were a composite outcome of survival ≥2 years or absence of disease progression at the end of the follow-up, and the overall survival. RESULTS: Composite outcome and overall survival were positively associated with VCAM-1 baseline levels and with the reduction of VCAM-1 during the treatment. After adjustment for potential confounders, the change in VCAM-1 serum levels during the treatment was an independent predictor of overall survival. CONCLUSIONS: High baseline serum levels of VCAM-1 are associated with a longer survival in patients treated with nivolumab as second line treatment for NSCLC. Surviving patients experience also a significant reduction in CAMs expression during the treatment. Hence, CAMs might be promising prognostic factors in patients with NSCLC underoing immunotherapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Nivolumabe/uso terapêutico , Molécula 1 de Adesão de Célula Vascular/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida
7.
Cancer Immunol Immunother ; 71(4): 865-874, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34462870

RESUMO

BACKGROUND: The prognostic relevance of early immune-related adverse events (irAEs) in patients affected by non-small cell lung cancer (NSCLC) upon immunotherapy is not fully understood. METHODS: The Leading to Treatment Discontinuation cohort included 24 patients experiencing severe irAEs after one of two administrations of single anti-PD-1/PD-L1 in any line setting for metastatic NSCLC between November 2015 and June 2019. The control cohort was composed of 526 patients treated with single anti-PD-1/PD-L1 in any line setting with no severe irAE reported. The primary end points were median progression-free survival, overall survival, objective response rate, risk of progression of disease and risk of death. The correlation of clinic pathological features with early severe irAEs represented the secondary end point. RESULTS: Median PFS was 9.3 and 8.4 months, median OS was 12.0 months and 14.2 months at a median follow-up of 18.1 and 22.6 months in the LTD cohort and in the control cohort, respectively. The ORR was 40% (95% CI 17.2-78.8) in the LTD cohort and 32.7% (95% CI 27.8-38.2) in the control cohort. The risk of disease progression was higher in the LTD cohort (HR 2.52 [95% 1.10-5.78], P = .0288). CONCLUSIONS: We found no survival benefit in LTD cohort compared to the control cohort. However, early and severe irAEs might underly an immune anti-tumor activation. We identified a significant association with first-line immune checkpoints inhibitors treatment and good PS. Further studies on risk prediction and management of serious and early irAEs in NSCLC patients are needed.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/patologia , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos
8.
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
9.
Arch Ital Urol Androl ; 93(3): 268-273, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34839627

RESUMO

OBJECTIVE: To present a retrospective analysis on the oncological and functional outcomes of a single-center experience on a large series of extraperitoneal laparoscopic radical prostatectomies (eLRP) with an extended follow-up. MATERIALS AND METHODS: Herein we present a retrospective review of patients who underwent eLRP. Oncological and functional follow-up data were collected by means of outpatient visits and telephone interviews, assessing overall mortality and biochemical recurrence-free survival. Patients with clinical T4 stage prostate cancer (PCa), previous surgery for benign prostatic hyperplasia (BPH), previous androgen deprivation, radiotherapy, concomitant chemotherapy and/or experimental therapies, and with insufficient follow-up data were excluded. Preoperative data recorded were age, body mass index, ultrasound prostate volume, preoperative PSA and clinical stage of PCa. Operative data (operative time, nerve sparing technique and any perioperative complication) and pathological findings were obtained by consulting the surgical and pathological reports. Oncological and functional follow-up were collected during follow-up visits and telephone interview. RESULTS: Between January 2001 and December 2019, overall 938 eLRP were performed at our Institution. The median follow-up was 132 months. 69.7% of the patients had complete dataset. The estimated overall biochemical recurrence (BCR)-free survival was 71.4% at 5 years and 58.9% at 10 years. Cancer specific survival was 84,5%. Erectile function was preserved in the most of patients as postoperative IIEF-5 score within 12 months after surgery was > 12 in the 82.1%. About the urinary incontinence, 0.76% of the patients presented severe incontinence (continued and persistent loss of urine) and 7.0% were mildly incontinent (using up to one pad per day). Conclusions; eLRP has shown oncological and functional results comparable to other minimally invasive techniques and to open radical prostatectomy (ORP), with favorable perioperative outcomes than the open technique and a reduced complication rate.


Assuntos
Laparoscopia , Neoplasias da Próstata , Antagonistas de Androgênios , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
10.
Ann Transl Med ; 9(20): 1603, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790809

RESUMO

Superior pulmonary sulcus tumor is a cancer arising in the apex of the lung that with potential invasion of the brachial plexus, upper ribs, vertebrae, subclavian vessels, and stellate ganglion. Induction concurrent chemoradiotherapy followed by radical surgical resection with lobectomy combined with any structures in the thoracic inlet invaded by tumor and thorough mediastinal lymph node dissection is the preferred treatment. Both anterior and posterior approaches are applied for resection. Here, we report a 61-year-old man with an 8.6 cm × 5.1 cm mass arising from the right upper lobe invading the apex of the chest wall. Brachial plexus magnetic resonance imaging suggested tumor invasion of the inferior trunk of the brachial plexus, anterior portion of the first 2 ribs, and suspicious involvement of the subclavian artery. Biopsy of the mass showed stage cT4N2M0, IIIB, poorly differentiated adenocarcinoma. The patient was treated by induction concurrent chemoradiotherapy, which was followed by surgical resection of the right upper lobe and the affected chest wall via the transmanubrial approach. The patient suffered prolonged postoperative air leak and empyema. After continuous chest tube drainage and intrapleural fibrinolytic therapy, he recovered well and was discharged safely. Final pathology showed no viable residue tumor, pathologic complete response of the tumor to induction treatment, a tumor size of 4.1 cm, and no lymph nodes; therefore, the final stage was ypT0N0M0. The transmanubrial approach is feasible for resection of tumor invading the branches of the subclavian artery; however, postoperative empyema which might have resulted from prolonged air leak should be carefully treated by meticulous air leak management.

11.
Expert Rev Respir Med ; 15(11): 1427-1435, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34590937

RESUMO

INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive tumor with a severe prognosis. At the time of diagnosis, most patients present with extensive-stage (ES) disease. For decades, platinum-based chemotherapy has been the only pillar of SCLC treatment, but now, the clinical management of this disease is rapidly evolving thanks to the introduction of immune checkpoint inhibitors (ICIs). AREAS COVERED: In this review, we describe the most recent advances in the treatment of SCLC and discuss the emerging challenges associated with ICI treatments. Meaningful data were collected from the currently available literature on PubMed and in international oncology meetings. EXPERT OPINION: Recently, meaningful improvements in outcomes of SCLC patients have been achieved with anti-PD-L1 atezolizumab or durvalumab combined with chemotherapy in first line. Results of studies evaluating the role of ICIs in limited-stage (LS) SCLC patients are awaited. Further efforts are required to better understand the role of immunotherapy in the treatment of SCLC and to identify patients most likely to benefit from this treatment strategy.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Inibidores de Checkpoint Imunológico , Fatores Imunológicos/uso terapêutico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
12.
Lancet Oncol ; 22(10): 1438-1447, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34499874

RESUMO

BACKGROUND: There is a preclinical rationale for inhibiting angiogenesis in mesothelioma. We aimed to assess the efficacy and safety of the anti-VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated malignant pleural mesothelioma. METHODS: RAMES was a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial done at 26 hospitals in Italy. Eligible patients were aged 18 years or older, had Eastern Cooperative Oncology Group performance status 0-2, and histologically proven malignant pleural mesothelioma progressing during or after first-line treatment with pemetrexed plus platinum. Patients were randomly assigned (1:1) to receive intravenous gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks plus either intravenous placebo (gemcitabine plus placebo group) or ramucirumab 10 mg/kg (gemcitabine plus ramucirumab group) on day 1 every 3 weeks, until tumour progression or unacceptable toxicity. Central randomisation was done according to a minimisation algorithm method, associated with a random element using the following stratification factors: ECOG performance status, age, histology, and first-line time-to-progression. The primary endpoint was overall survival, measured from the date of randomisation to the date of death from any cause. Efficacy analyses were assessed in all patients who had been correctly randomised and received their allocated treatment, and safety analyses were assessed in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03560973, and with EudraCT, 2016-001132-36. FINDINGS: Between Dec 22, 2016, and July 30, 2018, of 165 patients enrolled 161 were correctly assigned and received either gemcitabine plus placebo (n=81) or gemcitabine plus ramucirumab (n=80). At database lock (March 8, 2020), with a median follow-up of 21·9 months (IQR 17·7-28·5), overall survival was longer in the ramucirumab group (HR 0·71, 70% CI 0·59-0·85; p=0·028). Median overall survival was 13·8 months (70% CI 12·7-14·4) in the gemcitabine plus ramucirumab group and 7·5 months (6·9-8·9) in the gemcitabine plus placebo group. Grade 3-4 treatment-related adverse events were reported in 35 (44%) of 80 patients in the gemcitabine plus ramucirumab group and 24 (30%) of 81 in the gemcitabine plus placebo group. The most common treatment-related grade 3-4 adverse events were neutropenia (16 [20%] for gemcitabine plus ramucirumab vs ten [12%] for gemcitabine plus placebo) and hypertension (five [6%] vs none). Treatment-related serious adverse events were reported in five (6%) in the gemcitabine plus ramucirumab group and in four (5%) patients in the gemcitabine plus placebo group; the most common was thromboembolism (three [4%] for gemcitabine plus ramucirumab vs two [2%] for gemcitabine plus placebo). There were no treatment-related deaths. INTERPRETATION: Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favourable safety profile. This combination could be a new option in this setting. FUNDING: Eli Lilly Italy. TRANSLATION: For the Italian translation of the abstract see Supplementary Materials section.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Mesotelioma Maligno/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Itália , Masculino , Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/mortalidade , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/mortalidade , Intervalo Livre de Progressão , Fatores de Tempo
13.
Ther Adv Med Oncol ; 13: 17588359211022905, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349841

RESUMO

OBJECTIVE: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC). PATIENTS AND METHODS: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60-80 mg/m2 OV days 1 and 8 in combination with 80 mg/m2 CDDP day 1 (arm A) or 1250 mg/m2 GEM days 1 and 8 in combination with 75 mg/m2 CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL). RESULTS: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4-100.0) in arm A and 75.0% (95%CI: 63.7-100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment. CONCLUSION: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients' QoL. TRIAL REGISTRATION: The study was registered under EudraCT number 2012-003531-40.

14.
Expert Rev Gastroenterol Hepatol ; 15(9): 999-1007, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34423721

RESUMO

Introduction: Cholangiocarcinoma (CCA) is a malignancy which arises from the biliary epithelium. Carcinogenesis of CCA is mainly linked to aberrant glucose metabolism and creation of an immunosuppressive environment around normal biliary epithelium. The incidence of CCA is higher in the East due to Opisthorchis viverrini, an endemic liver fluke. CCA has also be attributed to genetic, metabolic, and lifestyle risk factors.Areas covered: Differences in epidemiological risk factors are associated with varying phenotypes of CCA. Metabolic risk factors include diabetes, obesity, nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), dyslipidemia, and metabolic syndrome. Inherited metabolic risk factors include Wilson's disease and hemochromatosis. Metabolic disease is associated with a higher risk of CCA, with higher risk for the intrahepatic form. In this review, the authors provide an overview of available evidence regarding metabolic conditions associated with the development of CCA.Expert opinion: Metabolic disease is associated with a higher risk of intrahepatic CCA compared to its extrahepatic or hilar counterpart. As rates of obesity and metabolic syndrome increase, particularly in the West, it is conceivable that the incidence of CCA will also rise in the next years.


Assuntos
Neoplasias dos Ductos Biliares/epidemiologia , Colangiocarcinoma/epidemiologia , Doenças Metabólicas/epidemiologia , Ductos Biliares Intra-Hepáticos , Carcinogênese/metabolismo , Diabetes Mellitus/epidemiologia , Glucose/metabolismo , Hemocromatose/epidemiologia , Degeneração Hepatolenticular/epidemiologia , Humanos , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/epidemiologia , Fatores de Risco
15.
Melanoma Res ; 31(5): 490-493, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433198

RESUMO

COVID-19 vaccination has been rapidly implemented among patients with cancer. We present the case of a patient with high-risk resected cutaneous melanoma, who was a candidate for adjuvant treatment, with postsurgery 18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scan showing positive axillary lymph nodes after COVID-19 vaccination. This report presents a 50-year-old man with a history of stage IIA cutaneous melanoma. During follow-up, the patient experienced subcutaneous and lymph-node disease progression, documented with 18FDG PET/CT scan. The patient underwent laparoscopic left para-aortic lymphadenectomy and excision of subcutaneous lesion. Histologic examination showed presence of melanoma metastases in 2 lymph nodes out of total 17 excised and neoplastic emboli to the subcutaneous tissue. In view of starting adjuvant nivolumab, the patient underwent CT scan restaging, with evidence of suspect centimetric periaortic and paracaval lymph nodes, which were deemed worthy of 18FDG PET investigation. The 18FDG PET/CT was negative for abdominal hypercaptation, but showed left axillary pathologic lymph nodes. The medical history of the patient revealed that he had received intramuscular Moderna COVID-19 mRNA vaccine in the left deltoid, one week before 18FDG PET examination. Since the patient's clinical examination was negative and suspecting postvaccination false-positive adenopathy, bilateral axillary ultrasound was performed, excluding the presence of pathologic lymph nodes. The patient has started adjuvant treatment with nivolumab, which is currently ongoing. This case demonstrates unexpected findings in response to COVID-19 vaccination in a patient with melanoma. In this specific case, the detection of 18FDG PET hypercaptation could significantly change the patient's management. With growing evidence about the pattern and occurrence of adenopathies after mRNA COVID-19 vaccination, recommendations for scheduling and interpretation of 18FDG PET/CT scans among cancer patients will be implemented, in order to reduce equivocal findings and improve outcomes.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Linfonodos/patologia , Melanoma/patologia , Vacinas contra COVID-19/administração & dosagem , Progressão da Doença , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Masculino , Melanoma/diagnóstico por imagem , Pessoa de Meia-Idade
16.
Pharmaceutics ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371736

RESUMO

Over the last decades, cancer has become one of the most relevant health issues at a worldwide level [...].

17.
Cancers (Basel) ; 13(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206545

RESUMO

An emerging clinical need is represented by identifying reliable biomarkers able to discriminate between responders and non-responders among patients showing imaging progression during the administration of immune checkpoints inhibitors for advanced non-small cell lung cancer (NSCLC). In the present study, we analyzed the prognostic power of peripheral-blood systemic inflammation indexes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this clinical setting. In 45 patients showing radiological progression (defined as RECIST 1.1 progressive disease) during Nivolumab administration, the following lab and imaging parameters were collected: neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), systemic inflammation index (SII), maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTV and SII independently predicted OS. Their combination in the immune metabolic prognostic index (IMPI) allowed the identification of patients who might benefit from immunotherapy continuation, despite radiological progression. The combination of FDG PET/CT volumetric data with SII also approximates the immune-metabolic response with respect to baseline, providing additional independent prognostic insights. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden, and their combination might disclose the radiological progression in NSCLC patients receiving Nivolumab.

18.
Vaccines (Basel) ; 9(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200648

RESUMO

The novel coronavirus disease 2019 (COVID-19) has represented an overwhelming challenge for worldwide health systems. Patients with cancer are considered at higher risk for severe COVID-19 and increased mortality in case of infection. Although data on the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with cancer are limited, there is enough evidence supporting anti-infective vaccination in general in patients with active cancer, or with history of previous malignancy. Subjects with classic Kaposi's sarcoma (KS) represent a small subset of cancer patients, which should be considered at heightened risk for infections due to several factors including age, and impaired immune function status. Several cases of human herpesviruses reactivation among critically ill COVID-19 patients have been described. Moreover, in case of severe infection and treatment with immunomodulating agents, patients with CKS are exposed at significant risk of viral reactivation and disease progression. Considering the baseline clinical risk factors of patients with CKS, and the complex interplay of the two viral agents, SARS-CoV-2 vaccination should be strongly recommended among patients with KS. KS represents an interesting field to study the interactions among chronic viral infections, SARS-CoV-2 and the host's immune system. Prospective observational studies are needed to provide more insights on vaccine activity and safety among patients with cancer, optimal vaccine schedules, potential interactions with antineoplastic therapies, and other comorbidities including chronic viral infections.

19.
Biomedicines ; 9(6)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073463

RESUMO

Malignant melanoma represents the most fatal skin cancer due to its aggressive biological behavior and high metastatic potential. Treatment strategies for advanced disease have dramatically changed over the last years due to the introduction of BRAF/MEK inhibitors and immunotherapy. However, many patients either display primary (i.e., innate) or eventually develop secondary (i.e., acquired) resistance to systemic treatments. Treatment resistance depends on multiple mechanisms driven by a set of rewiring processes, which involve cancer metabolism, epigenetic, gene expression, and interactions within the tumor microenvironment. Prognostic and predictive biomarkers are needed to guide patients' selection and treatment decisions. Indeed, there are no recognized clinical or biological characteristics that identify which patients will benefit more from available treatments, but several biomarkers have been studied with promising preliminary results. In this review, we will summarize novel tumor metabolic pathways and tumor-host metabolic crosstalk mechanisms leading to melanoma progression and drug resistance, with an overview on their translational potential as novel therapeutic targets.

20.
Pharmaceutics ; 13(5)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064352

RESUMO

Activating mutations in RAS family proteins are found in ~25% of all human cancers. Different solid tumors are correlated with mutations in certain isoforms of RAS, with Kirsten RAS (KRAS) being the most frequently mutated isoform. Historically, KRAS has been acknowledged as "undruggable", largely because the RAS proteins do not appear to present suitable pockets to which small inhibitory molecules can bind. However, this scenario has changed over the last years with the advent of novel KRAS inhibitors. In this review, we describe the role of KRAS mutation across different solid tumors, providing data on novel KRAS inhibitors currently under development and an updated overview of ongoing research in this field. A literature search was performed to select papers, abstracts, and oral presentation on KRAS inhibitory strategies in KRAS mutated solid tumors. Overall, the most promising therapeutic results have been obtained with molecules targeting KRAS G12C, thus paving the way for a significant therapeutic improvement in non-small cell lung cancer. Unfortunately, KRAS G12C mutation is rather uncommon in other solid tumors, namely pancreatic ductal adenocarcinoma and colorectal cancer. Several combination strategies are currently under evaluation in clinical trials, in order to bypass the resistance mechanisms responsible for the intrinsic resistance of mutated KRAS to the main therapeutic strategies adopted to date. Results suggest that the therapeutic scenario of KRAS has started to change, and further research will bring therapeutic results in this field.

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