Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.687
Filtrar
1.
Radiat Oncol ; 17(1): 89, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525985

RESUMO

BACKGROUND: Recently, stereotacitc radiosurgery (SRS) has been in the spotlight as an alternative therapeutic option for jugular foramen schwannomas (JFS). While most reported studies focus on the long-term efficacy and safety issues of SRS, none describe the early-onset adverse events (eAEs). We aimed to investigate the incidence, clinical characteristics, and mid-term outcomes of eAEs occurring within six months after SRS for JFS. METHODS: In this retrospective review, patients who underwent at least six months of follow-up were included among all patients with JFS who have performed SRS at our institution between July 2008 and November 2019. And eAEs were defined as a newly developed neurological deficit or aggravation of pre-existing symptoms during the first six months after SRS. RESULTS: Forty-six patients were included in the analysis. The median follow-up period was 50 months (range 9-136). The overall tumor control rate was 91.3%, and the actuarial 3-, 5-, and 10-year progression-free survival rates were 97.8%, 93.8%, and 76.9%, respectively. Of the 46 patients, 16 had eAEs, and the median time to onset of eAEs was one month (range 1-6 months), and the predominant symptoms were lower cranial nerve dysfunctions. Thirteen of 16 patients showed improved eAE symptoms during the follow-up period, and the median resolution time was six months (range 1-52). In 11 (68.8%) of 16 patients with eAEs, transient expansions were observed with a mean of 3.6 months after the onset of eAEs, and the mean difference between the initial tumor volume and the transient expansion volume was more prominent in the patients with eAEs (3.2 cm3 vs. 1.0 cm3; p = 0.057). In univariate analysis, dumbbell-shaped tumors (OR 10.56; p = 0.004) and initial tumor volume (OR 1.32; p = 0.033) were significantly associated with the occurrence of eAEs. CONCLUSIONS: Although acute adverse events after SRS for JFS are not rare, these acute effects were not permanent and mostly improved with the steroid treatment. Dumbell-shaped and large-volume tumors are significant predictive factors for the occurrence of eAEs. And the transient expansion also seems to be closely related to eAEs. Therefore, clinicians need to be more cautious when treating these patients and closely monitor the occurrence of eAEs.


Assuntos
Neoplasias de Cabeça e Pescoço , Forâmen Jugular , Neurilemoma , Radiocirurgia , Seguimentos , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Neurilemoma/etiologia , Neurilemoma/cirurgia , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
4.
Cancer Discov ; 12(5): 1180, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491620

RESUMO

Combining the live bacterial product CBM588 with checkpoint inhibitors improved progression-free survival.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Ciclopropanos , Feminino , Humanos , Indóis , Masculino , Intervalo Livre de Progressão
5.
J Immunol Res ; 2022: 4510462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35497877

RESUMO

Emerging studies have demonstrated that Prostate transmembrane protein androgen induced 1 (PMEPA1) plays crucial roles in the carcinogenesis of many developing human tumors. However, the clinical significance of PMEPA1 expression in cervical cancer (CC) and its contribution to cancer immunity have not been investigated. In this study, we identified PMEPA1 as a survival-related gene in CC based on TCGA datasets. Univariate and multivariate analysis showed that PMEPA1 expression was an independent predictor for overall survival in CC patients. We could observe a strong negative correlation between PMEPA1 expression and PMEPA1 methylation. Two CpG sites of PMEPA1 were associated with overall survival, and one CpG site of PMEPA1 was associated with progression-free survival. The low level of PMEPA1 methylation was associated with advanced clinical stage of CC patients. KEGG assays revealed the genes associated with PMEPA1 expression were mainly enriched in several tumor-related pathways. Increased PMEPA1 expressions were observed to be positively related to high immune infiltration levels in several immune cells. Finally, the pan-cancer assays revealed that PMEPA1 expression was associated with the overall survival of UVM, PAAD, LUSC, BLCA, CESC, and LUAD. Taken together, PMEPA1 is a prognosis-related biomarker for multiple cancer types, especially CC. PMEPA1 is involved in tumor immunity, suggesting PMEPA1 may be a potential immunotherapeutic target in CC.


Assuntos
Neoplasias do Colo do Útero , Biomarcadores , Carcinogênese , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Prognóstico , Intervalo Livre de Progressão , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética
6.
Zentralbl Chir ; 147(2): 137-144, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-35378551

RESUMO

According to current revised Fukuoka guidelines, there is an indication for resection of BD-IPMN of the pancreas with "worrisome features", as there is a risk of malignant degeneration of up to 30%. This can be performed as a non-anatomical local excision in the absence of clinical, radiological and laboratory signs of malignancy.Robotic enucleation for benign tumours of the pancreas is a very good alternative to resecting procedures, especially those using open techniques. This surgical treatment option is recommended by the "International consensus statement on robotic pancreatic surgery" in a case of a minimum distance to the main pancreatic duct of at least 2 mm.In addition to the known advantages of minimally invasive surgery, this parenchyma-sparing approach results in preservation of endo- and exocrine function (ca. 90%) and 10-year progression-free survival of ca. 75% with slightly increased morbidity (ca. 60%) compared with resecting procedures.The following video article presents the surgical video of a robotic cyst enucleation (for suspected BD-IPMN with "worrisome features") in the pancreatic head and uncinate process in a 62-year-old female patient with special emphasis on the most important vascular landmarks, special features of the approach and advantages of the robotic technique.


Assuntos
Cistos , Procedimentos Cirúrgicos Robóticos , Consenso , Feminino , Humanos , Pessoa de Meia-Idade , Pâncreas/cirurgia , Intervalo Livre de Progressão
7.
JCO Clin Cancer Inform ; 6: e2100173, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35467964

RESUMO

PURPOSE: Overall survival (OS) is the gold standard end point for establishing clinical benefits in phase III oncology trials. However, these trials are associated with low success rates, largely driven by failure to meet the primary end point. Surrogate end points such as progression-free survival (PFS) are increasingly being used as indicators of biologic drug activity and to inform early go/no-go decisions in oncology drug development. We developed OSPred, a digital health aid that combines actual clinical data and machine intelligence approaches to visualize correlation trends between early (PFS-based) and late (OS) end points and provide support for shared decision making in the drug development pipeline. METHODS: OSPred is based on a trial-level data set of 81 reports (35 anticancer drugs with various mechanisms of action; 156 observations) in non-small-cell lung cancer (NSCLC). OSPred was developed using R Shiny, with packages ggplot2, metafor, boot, dplyr, and mvtnorm, to analyze and visualize correlation results and predict OS hazard ratio (HR OS) on the basis of user-inputted PFS-based data, namely, HR PFS, or the odds ratio of PFS at 4 (OR PFS4) or 6 (OR PFS6) months. RESULTS: The three main features of the tool are as follows: prediction of HR OS on the basis of user-inputted early end point values; visualization of comparisons of the user's investigational drug with other drugs in the NSCLC setting, including by specific MoA; and creation of a probability density chart, providing point prediction and CIs for HR OS. A working version of the tool for download is linked. CONCLUSION: The OSPred tool offers interactive visualization of clinical trial end point correlations with reference to a large pool of historical NSCLC studies. Its focused capability has the potential to digitally transform and accelerate data-driven decision making as part of the drug development process.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Determinação de Ponto Final , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais
8.
BMC Res Notes ; 15(1): 140, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35422007

RESUMO

OBJECTIVE: This study was to explore the most appropriate radiomics modeling method to predict the progression-free survival of EGFR-TKI treatment in advanced non-small cell lung cancer with EGFR mutations. Different machine learning methods may vary considerably and the selection of a proper model is essential for accurate treatment outcome prediction. Our study were established 176 discrimination models constructed with 22 feature selection methods and 8 classifiers. The predictive performance of each model were evaluated using the AUC, ACC, sensitivity and specificity, where the optimal model was identified. RESULTS: There were totally 107 radiomics features and 7 clinical features obtained from each patient. After feature selection, the top-ten most relevant features were fed to train 176 models. Significant performance variations were observed in the established models, with the best performance achieved by the logistic regression model using gini-index feature selection (AUC = 0.797, ACC = 0.722, sensitivity = 0.758, specificity = 0.693). The median R-score was 0.518 (IQR, 0.023-0.987), and the patients were divided into high-risk and low-risk groups based on this cut-off value. The KM survival curves of the two groups demonstrated evident stratification results (p = 0.000).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Intervalo Livre de Progressão
9.
J Transl Med ; 20(1): 179, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449104

RESUMO

As part of the 2021 Immunotherapy Bridge virtual congress (December 1-2, Naples, Italy), the Great Debate sessions featured experts who were assigned counter opposing views on four important questions in immunotherapy today. The first topic was whether oncolytic viruses or other specific immunomodulators were the more promising approach for intralesional therapy. The second was whether early surrogate endpoints, such as response rate or progression-free survival, correlate with long-term overall survival was considered. Thirdly, whether vaccines can transform cold into hot tumors was discussed and, finally, broad versus deep analytic profiling approaches to gain insights into immune-oncology development were compared. As with previous Bridge congresses, presenters were invited by the meeting Chairs and positions taken during the debates may not have reflected their respective personal view. In addition, the views summarised in this article are based on available evidence but may reflect personal interpretation of these data, clinical experience and subjective opinion of the speaker.


Assuntos
Melanoma , Humanos , Fatores Imunológicos , Imunoterapia , Oncologia , Melanoma/patologia , Intervalo Livre de Progressão
10.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443542

RESUMO

Gallbladder carcinoma (GBC) is likely to be diagnosed at progressive stages and shows a very poor prognosis. Combination of gemcitabine and cisplatin (GEMCIS) has been widely used as first line palliative chemotherapy. Prognostic significance of inflammatory markers Neutrophil to lymphocyte ratio (NLR) and Platelet to lymphocyte ratio (PLR) in advanced gallbladder carcinoma (GBC) is not well established. MATERIAL: 30 patients who were diagnosed as advanced/ metastatic gallbladder carcinoma with age more than 18 years were included. All patients who were fit to receive chemotherapy was started on gemcitabine 1000mg/m2 and cisplatin 25mg/m2 (GEMCIS) administered intravenously on days 1 and 8 every 3 weeks. The treatment was repeated for a total of 6 cycles or until the occurrence of unacceptable toxicity, loss to follow up, confirmation of disease progression or death. All the patients underwent Contrast enhanced CT scan along with markers NLR, PLR, carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9) at the baseline and at the end of 3 and 6 cycles of chemotherapy and the tumour response was assessed based on Response Evaluation Criteria in Solid Tumours RECIST 1.1 criteria. Progression free survival was calculated from the date of documentation of best response. The response was correlated with markers CEA, CA19.9, NLR and PLR. OBSERVATION: At a cut-off of NLR (>3 ng/ml) and PLR (>190) predicts progression with a sensitivity of 91% and 100% respectively and both with a specificity of 100%. Out of 30 participants 11 (36.7%) had disease progression (p<0.001). Disease progression noted in 8 participants (26.7%) after 3 cycles (P<0.001) and in 3 participants (13.6%) after 6 cycles of chemotherapy (p <0.001). Disease control rate was 63.33%: 01(3.3%) patient with complete response, 07(23.3%) patients with partial response, 11(36.7%) patients with stable disease. Mean progression free survival in participants associated with progressive disease was 11.45±5.54 weeks (p <0.001). Neutrophil to lymphocyte ratio (NLR) >3 (95%CI 7.6-13.6; log rank test P<0.01) and Platelet to lymphocyte ratio (PLR) >190 (95%CI 7.67-8.83; log rank test p<0.001) were significantly associated with worse progression free survival. CONCLUSION: Increased levels of NLR (>3) and PLR (>190) have prognostic value to predict progression free survival (PFS) in advanced gallbladder carcinoma patients on palliative chemotherapy. NLR and PLR can be used as prognostic markers in advanced gallbladder carcinoma.


Assuntos
Carcinoma , Neoplasias da Vesícula Biliar , Adolescente , Plaquetas , Antígeno CA-19-9 , Antígeno Carcinoembrionário , Cisplatino/uso terapêutico , Progressão da Doença , Neoplasias da Vesícula Biliar/tratamento farmacológico , Humanos , Linfócitos , Neutrófilos/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
11.
Curr Oncol ; 29(4): 2174-2184, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35448150

RESUMO

Oesophagogastric (OG) cancer is a highly lethal disease requiring novel treatment options. c-MYC and/or HER-2 amplified oesophageal cancer models have demonstrated sensitivity to BTK inhibition with ibrutinib. We evaluated the safety and efficacy of ibrutinib in patients with c-MYC and/or HER2 amplified pre-treated advanced OG cancer. c-MYC and HER2 amplification status were determined by FISH. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DC) at 8 weeks, safety, progression-free survival (PFS) and overall survival (OS). Eleven patients were enrolled. Eight patients had c-MYC amplified tumours, six were HER2 amplified and three were c-MYC and HER2 co-amplified. Grade ≥ 3 adverse events were fever, neutropenia, and vomiting. Grade ≥ 3 gastrointestinal haemorrhage occurred in three patients and was fatal in two cases. Among seven evaluable patients, three patients (43%) achieved a best response of SD at 8 weeks. No PR or CR was observed. Disease control was achieved for 32 weeks in one patient with a dual c-MYC and HER2 highly co-amplified tumour. The median PFS and OS were 1.5 (95% CI: 0.8-5.1) and 5.1 (95% CI: 0.8-14.5) months, respectively. Ibrutinib had limited clinical efficacy in patients with c-MYC and/or HER2 amplified OG cancer. Unexpected gastrointestinal bleeding was observed in 3 out of 8 treated patients which was considered a new safety finding for ibrutinib in this population.


Assuntos
Neoplasias Esofágicas , Piperidinas , Adenina/análogos & derivados , Adenina/uso terapêutico , Humanos , Piperidinas/uso terapêutico , Intervalo Livre de Progressão
12.
Gan To Kagaku Ryoho ; 49(4): 371-380, 2022 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-35444117

RESUMO

Like most complex(or multifactorial)diseases, cancer results not from a single factor, but rather from the interaction of multiple genes and environmental factors. Thus patients can experience different signs and symptoms that reflect more than one consequence of suffering the disease. When evaluating the effects of new treatments in cancer clinical trials, the multidimensional assessment using multiple outcomes to measure improvements in the patients' signs and symptoms associated with treatments would be preferred. Most cancer clinical trials use more than one clinical outcome as multiple primary, or primary and(key)secondary endpoints, such as overall survival, endpoints based on tumor assessments(e.g., disease-free survival, event-free survival, objective response rate, time to progression, progression-free survival), and endpoints involving symptom assessment. Utilizing multiple endpoints may provide the opportunity for characterizing the intervention's multidimensional effects, but also creates challenges, specifically controlling the Type Ⅰ and/or Type Ⅱ errors in hypotheses testing and trial designs associated with multiple endpoints. In this article, we review issues in design, monitoring, analysis and reporting of clinical trials with multiple endpoints, with illustrating examples in oncology disease settings. We outline several methods for controlling the Type Ⅰ error associated multiple tests, which have been commonly used in clinical trials. We also briefly discuss issues in interim analyses and group sequential designs for clinical trials with multiple endpoints.


Assuntos
Ensaios Clínicos como Assunto , Neoplasias , Intervalo Livre de Doença , Humanos , Neoplasias/tratamento farmacológico , Intervalo Livre de Progressão , Projetos de Pesquisa
13.
Clin Epigenetics ; 14(1): 50, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410311

RESUMO

BACKGROUND: TIGIT is an immune checkpoint under investigation as therapeutic target. Understanding the regulation of TIGIT on an epigenetic level might support the development of companion biomarkers. METHODS: We correlated TIGIT DNA methylation of single CpG sites with gene expression, signatures of immune infiltrates and interferon-γ, and survival in melanoma. We further analyzed methylation levels in immune cell subsets, melanocyte and melanoma cell lines. TIGIT expression patterns within components of the melanoma microenvironment were analyzed by single cell sequencing. We used quantitative methylation-specific PCR, flow cytometry, and immunohistochemistry for correlations between expression and methylation and to assess the effect of pharmacological demethylation of melanoma cells treated with 5-aza-2-deoxycytidine (decitabine). Finally, we investigated the association of patients' survival with TIGIT mRNA and methylation. RESULTS: Depending on the sequence context of the analyzed CpG site, we found a cell type-specific TIGIT gene locus methylation pattern and significant correlations of TIGIT methylation with mRNA expression, an interferon γ signature, and distinct immune cell infiltrates, including TIGIT+ lymphocytes. We detected a melanoma cell-intrinsic TIGIT protein expression. Pharmacological demethylation of the A375 melanoma cell line led to a constitutive TIGIT expression. Low promoter flank methylation and high mRNA expression was associated with patients' prognosis and predicted progression-free survival in patients treated with anti-PD-1 immunotherapy. A high TIGIT+ lymphocyte score was associated with better progression-free survival under anti-PD-1 immunotherapy. CONCLUSIONS: Our data demonstrate an epigenetic regulation of TIGIT expression via DNA methylation within the melanoma microenvironment. TIGIT DNA methylation and expression may serve as predictive biomarkers in the context of immunotherapies in melanoma.


Assuntos
Metilação de DNA , Melanoma , Epigênese Genética , Humanos , Imunoterapia , Melanoma/tratamento farmacológico , Melanoma/genética , Prognóstico , Intervalo Livre de Progressão , RNA Mensageiro/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Microambiente Tumoral
14.
BMC Med ; 20(1): 120, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35410334

RESUMO

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Ensaios Clínicos como Assunto , Humanos , Imunoterapia , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão
15.
Int Urol Nephrol ; 54(6): 1187-1192, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35384583

RESUMO

PURPOSE: Advanced prostate cancer does not respond to traditional androgen deprivation therapy (ADT) at some point in the treatment. The development of new hormonal agents demonstrated clear efficacy and changed the treatment scenario. OBJECTIVES: To evaluate the use of new antiandrogens alone versus their use in combination with maintenance ADT in patients with advanced castration-resistant prostate cancer. METHODS: A literature systematic review of randomized clinical trials, cohorts, and real-life studies including patients who received the new antiandrogens with or without ADT due to histologic confirmed advanced castration-resistant prostate adenocarcinoma was carried out. RESULTS: 2181 articles were identified and three studies were included with a total of 246 patients. Two studies were randomized clinical trials, and the third was a retrospective study, which showed similar results for both arms, in relation to PSA response, radiological progression-free survival, and testosterone levels, in addition to cost analysis with savings avoided in the ADT maintenance-free arm. Despite the positive data, it is still not possible to categorically state whether there is a statistical benefit in suspending the ADT during the use of new antiandrogens, due to the heterogeneity of the studies. CONCLUSION: The literature is limited on the issue. Available data are still immature with no clear benefit of the use of newer antiandrogens alone in the setting of advanced castration-resistant prostate cancer.


Assuntos
Antagonistas de Androgênios , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
16.
Oncoimmunology ; 11(1): 2066609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35481285

RESUMO

In patients with melanoma brain metastases (MBM), a combination of radiotherapy (RT) with immune checkpoint inhibitors (ICI) is routinely used. However, the best sequence of radio-immunotherapy (RIT) remains unclear. In an exploratory phase 2 trial, MBM patients received RT (stereotactic or whole-brain radiotherapy depending on the number of MBM) combined with ipilimumab (ipi) ± nivolumab (nivo) in different sequencing (Rad-ICI or ICI-Rad). Comparators arms included patients treated with ipi-free systemic treatment or without RT (in MBM-free patients). The primary endpoints were radiological and immunological responses in the peripheral blood. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Of 106 screened, 92 patients were included in the study. Multivariate analysis revealed an advantage for patients starting with RT (Rad-ICI) for overall response rate (RR: p = .007; HR: 7.88 (95%CI: 1.76-35.27)) and disease control rate (DCR: p = .036; HR: 6.26 (95%CI: 1.13-34.71)) with a trend for a better PFS (p = .162; HR: 1.64 (95%CI: 0.8-3.3)). After RT plus two cycles of ipi-based ICI in both RIT sequences, increased frequencies of activated CD4, CD8 T cells and an increase in melanoma-specific T cell responses were observed in the peripheral blood. Lasso regression analysis revealed a significant clinical benefit for patients treated with Rad-ICI sequence and immunological features, including high frequencies of memory T cells and activated CD8 T cells in the blood. This study supports increasing evidence that sequencing RT followed by ICI treatment may have better effects on the immunological responses and clinical outcomes in MBM patients.


Assuntos
Neoplasias Encefálicas , Melanoma , Neoplasias Encefálicas/radioterapia , Humanos , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Intervalo Livre de Progressão , Radioimunoterapia
17.
Sci Rep ; 12(1): 6352, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428842

RESUMO

Disease-free survival (DFS) comprises both breast cancer and non-breast cancer events. DFS has not been validated as a surrogate endpoint for overall survival (OS) in most breast cancer subtypes. We assessed changes to the type of events contributing to DFS over time. We identified adjuvant studies in breast cancer (BC) from 2000 to 2020 where the endpoint was DFS. We examined change in distant DFS events and the BC-related DFS using univariable and multivariable linear regression. Data were reported quantitatively using the Burnand criteria irrespective of statistical significance. We included 84 studies (88 cohorts), comprising 212,191 participants, 41,604 DFS events and 23,205 distant DFS events. The DFS event rate/100 participants/year has declined modestly over time (ß - 0.34, p = 0.001). Start year was negatively associated with distant DFS events (ß - 0.58, p < 0.0001); however, the effect was lost after adjusting for follow-up time (ß - 0.18, p = 0.096). The average number of BC-related events/100 participants/year also declined over time (ß - 0.28, p = 0.009). In multivariable analysis, start year and ER expression were quantitatively associated with distant DFS events and BC-related DFS events. DFS events have declined over time driven by a reduction in BC related events. As DFS events are increasingly defined by non-BC events, there will be limited surrogacy between DFS and OS.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Intervalo Livre de Progressão , Estudos Retrospectivos
18.
Front Immunol ; 13: 840207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432362

RESUMO

Background: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. Methods: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. Results: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21- B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). Conclusion: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Linfócitos B , Estudos de Coortes , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Intervalo Livre de Progressão , Estudos Prospectivos
19.
BMC Cancer ; 22(1): 364, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379201

RESUMO

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Intervalo Livre de Progressão , Estudos Retrospectivos
20.
Zhonghua Yi Xue Za Zhi ; 102(14): 1000-1006, 2022 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-35399019

RESUMO

Objective: To determinate the value of tumor growth rate (TGR) in evaluating the efficacy of early drug treatment for neuroendocrine neoplasm (NEN). Methods: Patients with NEN who treated at Chinese Academy of Medical Sciences Cancer Hospital from January 2010 to December 2018 were retrospectively enrolled. A total of 30 patients (16 males and 14 females, aged from 26 to 73 (53±11) years) were enrolled. The sum of largest diameter of target lesions and the interval time were measured, TGR of 3 months after the first treatment was calculated using a formula. Intraclass correlation coefficient (ICC) were used to test the repeatability of TGR. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cut-off values of TGR for predicting progression-free survival (PFS). Overall patients and SD patients assessed by RECIST were grouped by the optimal cut-off values of TGR. Kaplan-Meier method was used to estimate PFS rates and plot patient survival curves of patients at different group of TGR. Cox risk proportional hazard model was used to assess the effect of TGR on the prognosis. Results: The optimal cut-off value of TGR was -5.8(%/m), the area under the curve was 0.921 (95%CI: 0.824-0.999, P<0.001). Interobserver ICC was 0.955 (95%CI: 0.907-0.978,P<0.001). Multivariate Cox analysis showed that compared with the patients with TGR<-5.8, the patients with TGR ≥-5.8 had a higher risk of progression in either overall population (HR: 10.906, 95%CI: 1.953-60.898, P=0.006) or the SD population (HR: 14.354, 95%CI: 1.602-128.627, P=0.017); TGR ≥-5.8 was an independent risk factor affecting the prognosis of NEN. Conclusions: TGR can evaluate the efficacy of NEN's early anti-tumor drug treatment, and associate with prognosis.


Assuntos
Tumores Neuroendócrinos , Feminino , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Curva ROC , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...