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BACKGROUND: Growth differentiation factor-15 (GDF-15), a member of the TGF-ß superfamily, is overexpressed in various cancers and facilitates immune evasion by inhibiting T-cell activation. GDFATHER-TRIAL's phase 2a results demonstrated promising outcomes when combining the GDF-15 neutralizing antibody visugromab (CTL002) with nivolumab, enhancing the response to immunotherapy. This study evaluated the prognostic significance of GDF-15 expression in non-small cell lung cancer (NSCLC) tumor tissues in terms of immunotherapy response. METHODS: This retrospective study included 50 patients with metastatic NSCLC treated with nivolumab at Gazi University Hospital between January 2021 and July 2023. GDF-15 expression was evaluated using immunochemistry staining and categorized based on the intensity of cytoplasmic or membranous staining. Samples were divided into a low expression group (scores 0 and 1) and a high expression group (scores 2 and 3). The primary outcomes were progression-free survival (PFS) and overall survival (OS), which were analyzed using KaplanâMeier and Cox proportional hazards models. Objective response rates were assessed in secondary outcomes. RESULTS: Of the 50 patients, 43 were men (86%), with a median age of 63.9 years. Half of the patients exhibited low GDF-15 expression. High GDF-15 expression correlated with shorter PFS and OS. The median PFS was 7.8 months for the low-expression group versus 4.4 months for the high-expression group (HR, 0.41; 95% CI, 0.20-0.83; p = 0.013). The median OS was 18.1 months for the low-expression group compared to 11.8 months for the high-expression group (HR, 0.36; 95% CI, 0.16-0.78; p = 0.007). The objective response rate was significantly greater in the low GDF-15 group (52%) than in the high GDF-15 group (24%) (p = 0.040). CONCLUSION: Elevated GDF-15 expression in NSCLC tumor tissues is associated with poorer response to nivolumab, suggesting that GDF-15 is a potential prognostic biomarker for immunotherapy efficacy. These findings warrant further validation through prospective studies to optimize treatment strategies for NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Fator 15 de Diferenciação de Crescimento , Imunoterapia , Neoplasias Pulmonares , Humanos , Fator 15 de Diferenciação de Crescimento/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Imunoterapia/métodos , Prognóstico , Nivolumabe/uso terapêutico , Biomarcadores Tumorais/metabolismo , Adulto , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Intervalo Livre de ProgressãoRESUMO
INTRODUCTION: Locoregional gastric cancer is a still serious problem and perioperative treatments may improve success of management. Different regimens were examined. The present study purposed to compare efficacy of FLOT and DCF regimens. METHODS: Retrospective multicenter study assesed the patients with locoregional gastric cancer. There are 240 patients (137 DCF, 103 FLOT). Survival rates were compared. RESULTS: Demographic features were similar between two groups, but time period was different. FLOT group had 7.8% pathological complete response, while DCF group did not have. Disease-free survival was longer in FLOT than DCF group (median not reached-13.94 months respectively). Median overall survival was similar (30.9 vs 37.8 months) but median follow-up affected the analysis. Survival for 36 months was 63% for FLOT and 40% for DCF group (p=0.015). CONCLUSION: FLOT regimen was superior on DCF regimen for response and survival rates. DCF is historical approach. Long term follow up period needed for FLOT treatment.
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BACKGROUND: Neoadjuvant treatment is the standard treatment in locally advanced ESCC. However, the optimal chemotherapy regimen is not known. METHOD: This is a retrospective observational cohort study conducted with propensity score matching. Patients with resectable ESCC from 13 tertiary centers from Türkiye were screened between January 2011 and December 2021. We compared the efficacy and safety of neoadjuvant chemoradiotherapy with the CF and the CROSS regimens in patients with ESCC. RESULTS: Three hundred and sixty-two patients were screened. Patients who received induction chemotherapy (n = 72) and CROSS-ineligible (n = 31) were excluded. Two hundred and fifty nine patients received neoadjuvant chemoradiotherapy. After propensity score matching (n = 97 in both groups), the mPFS was 18.4 months (95% CI, 9.3-27.4) and 25.7 months (95% CI, 15.6-35.7; p = 0.974), and the mOS was 35.2 months (95% CI, 18.9-51.5) and 39.6 months (95% CI 20.1-59.2; p = 0.534), in the CF and the CROSS groups, respectively. There was no difference between subgroups regarding PFS and OS. Compared with the CF group, the CROSS group had a higher incidence of neutropenia (34.0% vs. 62.9%, p < 0.001) and anemia (54.6% vs. 75.3%, p = 0.003) in all grades. On the other hand, there was no significant difference in grade 3-4 anemia, grade 3-4 neutropenia, and febrile neutropenia between groups. There were more dose reductions and dose delays in the CROSS group than in the CF group (11.3% vs. 3.1%, p = 0.026 and 34.0% vs. 17.5%, p = 0.009, respectively). The resection rate was 52.6% in the CF-RT and 35.1% in the CROSS groups (p = 0.014). CONCLUSION: Favorable PFS and pCR rates and a comparable OS were obtained with the CROSS regimen over the CF regimen as neoadjuvant chemoradiotherapy in patients with ESCC.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fluoruracila , Terapia Neoadjuvante , Paclitaxel , Pontuação de Propensão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante/métodos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Idoso , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/mortalidade , Turquia , Quimiorradioterapia/métodos , Quimiorradioterapia/efeitos adversos , AdultoRESUMO
Introduction: The current study aims to evaluate the OX40, TIM-3, LAG-3, and PD-L1 targeted pathways in the regulation of T-cell activity in sarcoma patients to determine their relationship with overall survival (OS). Method: This study included one hundred and eleven patients with bone and soft tissue sarcoma diagnosed in two centers between 2010 and 2020. OX40, LAG-3, TIM-3 and PD-L1 expression levels were evaluated immunohistochemically from pathology preparations. Results: PD-L1 staining was detected in tumor cells, OX40, LAG-3, TIM-3 staining was detected in inflammatory cells in tumor tissue. In univariate analysis, no significant relationship was found between OX40, TIM-3, LAG-3, and PD-L1 staining and overall survival (respectively: p = 0.12, p = 0.49, p = 0.31, p = 0.95). When grade and stage at diagnosis, which were found to be significant in univariate analysis, along with OX-40, TIM-3, LAG-3, and PD-L1, were evaluated in multivariate analysis, a positive effect of OX-40 staining on overall survival was determined (p = 0.009). Considering the correlation between PDL-1 and OX40, TIM-3, and LAG-3 staining, a significant positive correlation was found between PDL-1 and TIM-3 and LAG-3 staining (respectively; p = 0.002, p = 0.001). Conclusions: There was no significant relationship between the PDL-1 staining percentage of tumor cells and OX40, TIM-3, and LAG-3 staining in inflammatory cells with the OS of sarcoma patients. However, detecting a significant positive correlation between PDL-1 staining and TIM-3 and LAG-3 staining also holds promise for finding effective targetable combination therapies that can prolong survival in sarcoma patients in the future.
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OBJECTIVE: This study aimed to assess the efficacy and safety of FOLFIRI and paclitaxel in patients with advanced gastric cancer (AGC) who were previously treated with first-line modified docetaxel, cisplatin, 5-fluorouracil (mDCF), or 5-fluorouracil, oxaliplatin, docetaxel (FLOT). METHODS: Patients who received a triplet regimen in the first line setting and were treated with FOLFIRI or paclitaxel in the second-line treatment were included. RESULTS: The study included 198 patients, with 115 receiving FOLFIRI and 83 receiving paclitaxel. The median age was 58 (range = 24-69). The median progression-free survival (mPFS) was 5.2 [95% confidence interval (CI) = 4.4-5.5] months in the FOLFIRI arm, and 4.1 (95% CI = 3.3-4.6) months in the paclitaxel arm (p = .007). The median overall survival (mOS) was 9.4 (95% CI = 7.4-10.5) months in the FOLFIRI arm and 7.2 (95% CI = 5.6-8.3) months in the paclitaxel arm (p = .008). Grade 3-4 neuropathy was higher in patients receiving paclitaxel compared to those receiving FOLFIRI (p = .04). Grade 3-4 diarrhea was 8% in the FOLFIRI arm and 2.4% in the paclitaxel arm (p = .02). CONCLUSION: Beyond progression with docetaxel-based triplet chemotherapy, FOLFIRI may be preferred as a second-line treatment over paclitaxel due to its longer mPFS and mOS.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Neoplasias Gástricas , Taxoides , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Feminino , Masculino , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Taxoides/administração & dosagem , Taxoides/uso terapêutico , Taxoides/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Fluoruracila/efeitos adversos , Turquia , Adulto Jovem , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/efeitos adversos , Resultado do Tratamento , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Camptotecina/efeitos adversosRESUMO
Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.
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Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Pancreaticoduodenectomia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Ampola Hepatopancreática/cirurgia , Ampola Hepatopancreática/patologia , Prognóstico , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias do Ducto Colédoco/patologia , Pancreaticoduodenectomia/métodos , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Análise de SobrevidaRESUMO
We investigated expressions of PD-L1, LAG-3, TIM-3, and OX40L as immune checkpoint proteins, and MSI (repetitive short-DNA-sequences due to defective DNA-repair system) status were analyzed with immunohistochemistry from tissue blocks. Of 83 patients, PD-L1 expression was observed in 18.1% (n = 15) of the patients. None of the patients exhibited LAG-3 expression. TIM-3 expression was 4.9% (n = 4), OX40L was 22.9% (n = 19), and 8.4% (n = 7) of the patients had MSI tumor. A low-to-intermediate positive correlation was observed between PD-L1 and TIM-3 expressions (rho: 0.333, p < 0.01). Although PD-L1 expression was higher in grade 3 NET/NEC, MSI status was prominent in grade 1/2 NET.
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Antígeno B7-H1 , Neoplasias Gastrointestinais , Receptor Celular 2 do Vírus da Hepatite A , Proteínas de Checkpoint Imunológico , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígeno B7-H1/análise , Antígeno B7-H1/metabolismo , Reparo do DNA , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/patologia , Receptor Celular 2 do Vírus da Hepatite A/análise , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Proteínas de Checkpoint Imunológico/análise , Proteínas de Checkpoint Imunológico/metabolismo , Proteína do Gene 3 de Ativação de Linfócitos/análise , Proteína do Gene 3 de Ativação de Linfócitos/metabolismo , Tumores Neuroendócrinos/química , Tumores Neuroendócrinos/patologia , Ligante OX40/análise , Ligante OX40/metabolismo , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Imuno-Histoquímica , Gradação de TumoresRESUMO
PURPOSE: We aimed to investigate whether visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA) index are predictive for efficacy and hematological toxicity in ER + HER2-metastatic breast cancer (BC) patients who received CDK 4/6 inhibitors. METHODS: This retrospective cohort study analyzed 52 patients who were treated with CDK 4/6 inhibitors between January 2018 and February 2021. The values of VAT, SAT, SMA indices and hematological parameters were noted before the start, at the third and sixth months of this treatment. The skeletal muscle area (SMA) and adipose tissue measurements were calculated at the level of the third lumbar vertebra. A SMA-index value of <40 cm2/m2 was accepted as the threshold value for sarcopenia. RESULTS: Patients with sarcopenia had a worse progression-free survival (PFS) compared to patients without sarcopenia (19.6 vs. 9.0 months, p = 0.005). Patients with a high-VAT-index had a better PFS (20.4 vs. 9.3 months, p = 0.033). Only the baseline low-SMA- index (HR: 3.89; 95% CI: 1.35-11.25, p = 0.012) and baseline low-VAT-index (HR: 2.15; 95% CI: 1.02-4.53, p = 0.042) had significantly related to poor PFS in univariate analyses. The low-SMA-index was the only independent factor associated with poor PFS (HR: 3.99; 95% CI: 1.38-11.54, p = 0.011). No relationship was observed between body composition parameters and grade 3-4 hematological toxicity. CONCLUSION: The present study supported the significance of sarcopenia and low visceral adipose tissue as potential early indicators of poor PFS in patients treated with CDK 4/6 inhibitors.
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Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Obesidade Abdominal , Inibidores de Proteínas Quinases , Sarcopenia , Humanos , Sarcopenia/induzido quimicamente , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Obesidade Abdominal/induzido quimicamente , Adulto , Intervalo Livre de Progressão , Gordura Intra-Abdominal/efeitos dos fármacos , Metástase Neoplásica , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Gordura Subcutânea/efeitos dos fármacosRESUMO
The aim of our study was to evaluate the association between increased splenic volume (SV) and liver fibrosis indices in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy. Patients who received adjuvant oxaliplatin-based regimens with the diagnosis of stage II and III colon cancer were evaluated. Splenic volume measurements, liver function tests, platelet count, and non-invasive liver fibrosis indices [NAFLD fibrosis score (NFS), AST to platelet ratio (APRI), and Fibrosis-4 (FIB-4)] were measured before and after treatment. A 30% increase in SV after chemotherapy compared to baseline was considered increased SV. The rate of increase in SV was 57.7% in the whole group. An increase in SV was shown at a higher rate in patients treated with capecitabine and oxaliplatin (CAPOX) than those treated with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (66.3% vs. 36.8%, p = 0.002). Furthermore, the CAPOX regimen (OR: 2.831, 95% CI: 1.125-7.121; p = 0.027), and higher post-treatment FIB-4 score (OR: 3.779; 95% CI:1.537- 9.294, p = 0.004) were determined as independent risk factors for the increased SV. Our study revealed that increased SV had a significant association with higher FIB-4 score in patients treated with oxaliplatin-based chemotherapy.
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Neoplasias do Colo , Humanos , Oxaliplatina/efeitos adversos , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Capecitabina/efeitos adversos , Fluoruracila/efeitos adversos , Cirrose Hepática , Quimioterapia Adjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucovorina/efeitos adversosRESUMO
INTRODUCTION: Niraparib, a strong poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, contributed significantly to progression-free survival as a maintenance therapy in the platinum-sensitive period in both first-line and recurrent ovarian cancer, regardless of the BRCA mutation. Grade 3-4 anemia, which has a manageable side effect profile, especially hematological, is seen in almost 1 out of every 4 patients. To the best of our knowledge, there has been no reported case of pure red cell aplasia (PRCA) induced by niraparib treatment. CASE REPORT: A 65-year-old woman diagnosed with stage 3 serous carcinoma of the tuba received niraparib front-line maintenance treatment had grade 4 anemia after 3 months of niraparib treatment. She underwent bone marrow aspiration and biopsy because of refractory anemia, which needs red blood cell (RBC) transfusions despite interruption of treatment. MANAGEMENT AND OUTCOME: The patient was treated with 1â mg/kg methyl prednisolone, after histopathological assessment was consistent with PRCA. The hemoglobin count returned to the normal range with steroid treatment. DISCUSSION: In daily practice, it should be kept in mind that in the case of refractory anemia induced by niraparib, the underlying cause might be PRCA and can be improved with steroid administration.
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Anemia Refratária , Indazóis , Neoplasias Ovarianas , Piperidinas , Aplasia Pura de Série Vermelha , Feminino , Humanos , Idoso , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Aplasia Pura de Série Vermelha/induzido quimicamente , Aplasia Pura de Série Vermelha/tratamento farmacológico , Anemia Refratária/induzido quimicamente , Anemia Refratária/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
BACKGROUND: The current study aimed to evaluate the effect of the time duration to reach the lowest prostate-specific antigen (PSA) from the onset of first-line hormonal treatment (time to nadir PSA, TTNpsa) on survival in castration-naive metastatic prostate cancer (CN-MPC) patients. METHODS: Eighty patients who had PSA response >80% with first-line hormonal therapy (luteinizing hormone-releasing hormone, LH-RH analog +/- bicalutamide) were included in this study. RESULTS: Under androgen deprivation therapy (ADT), a significant positive correlation was found between TTNpsa, nadir PSA (Npsa) duration, and progression-free survival (PFS) ( p < 0.001) and overall survival (OS) ( p < 0.001). There was no correlation between TTNpsa and Npsa duration. TTNpsa and Npsa durations were independently correlated with PFS and OS. In patients with TTNpsa value ≥19 weeks, the median PFS was 126 (95% CI, 68-184) weeks compared with TTNpsa <19-week group in which the median PFS was 44 (95% CI, 26-62) weeks ( p = 0.033). In patients with TTNpsa value ≥19 weeks, the median OS was 242 (95% CI, 169-315) weeks compared with TTNpsa <19-week group in which the OS was 156 (95% CI, 89-223) weeks ( p = 0.018). The median nadir PSA value was 1 ng/mL. The median PFS was significantly longer in the patient group with ≤1 ng/mL (137 weeks, 95% CI, 50-224) compared with the group with >1 ng/mL (41 weeks, 95% CI, 34-48) ( p < 0.001). The median OS was significantly longer in the patient group with nadir PSA ≤1 ng/mL (296 weeks, 95% CI, 220-272) compared to the group with >1 ng/mL (131 weeks, 95% CI, 84-178) ( p = 0.002). In patients with nadir PSA ≤1 ng/mL ( n = 40), there was no relationship between TTNpsa and Npsa duration with both PFS and OS. However, in patients with nadir PSA >1 ng/mL ( n = 40) subgroup, there was a significant positive correlation between TTNpsa and PFS, and OS ( p < 0.001, P = 0.016, respectively). CONCLUSION: In CN-MPC who received first-line ADT, especially in the group with the nadir PSA value >1 ng/mL, the duration of TTNpsa was positively correlated with PFS and OS.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Prognóstico , Antagonistas de Androgênios/uso terapêutico , Castração , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: Meningiomas are one of the most common intracranial tumors, accounting for 30% of the tumors of the central nervous system. MicroRNAs (miRNAs) are noncoding RNAs containing approximately 18-22 nucleotides that regulate gene expression by interfering with transcription or inhibiting translation. Recent studies have reported that miRNAs could provide information about the molecular pathogenesis of several types of tumors. This study aimed to examine the expression levels of miRNA-885 and -451 and to determine their potential roles as biomarkers in meningioma. MATERIALS AND METHODS: In total, 29 patients with meningioma (9 males and 20 females) were included in this study. The expression levels of miRNA were determined using real-time polymerase chain reaction. In addition, receiver operating characteristic curve analysis was used to analyze the predictive potential of miRNAs. RESULTS: Our results indicated a significant increase in miRNA-451 expression levels (p=0.003); however, there was no significant change in miRNA-885 expression levels (p=0.139) in patients with meningioma compared with the control group. Moreover, miRNA-885 and miRNA-451 expression levels did not differ significantly based on the histopathological grade of meningioma. CONCLUSION: miRNA-451 may be a novel potential marker for the diagnosis and prognosis, and a target for meningioma treatment.
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Neoplasias Meníngeas , Meningioma , MicroRNAs , Masculino , Feminino , Humanos , MicroRNAs/genética , Meningioma/genética , Meningioma/metabolismo , Meningioma/patologia , Prognóstico , Biomarcadores , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Perfilação da Expressão Gênica/métodosRESUMO
INTRODUCTION: Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. METHODS: We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients' body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. RESULTS: Median splenic volume change was 10% (ranging from - 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1-4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1-6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. CONCLUSION: Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Baço/patologia , Imunoterapia , Estudos Retrospectivos , Microambiente TumoralRESUMO
OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.
Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Fluoruracila , Leucovorina , Paclitaxel , Albuminas , Neoplasias PancreáticasRESUMO
AIM: To investigate the neuroprotective effect of shilajit extract in experimental head trauma. MATERIAL AND METHODS: Three groups of 33 Sprague Dawley Albino strain male rats were included in the study. Group 1 (n=11): trauma but not treated. Group 2 (n=11): trauma and treated with 0.5 mL / rat saline Group 3 (n=11): 150 mg / kg shilajit extract was administered intraperitoneally in the treatment of trauma. Following the head trauma, the indicated treatments were applied to the 2nd and 3rd groups at the first, twenty-four and forty-eighth hours. Brain tissues and blood samples were taken after the control animals were sacrificed at the 72nd hour in all groups after trauma. Sections prepared from cerebral cortex and ca1 region were examined with hematoxylin eosin and luxol fast blue staining. Total antioxidant capacity, total oxidant capacity and oxidative stress index were measured from blood samples taken after routine procedures. RESULTS: The number of red neurons and the severity of edema were significantly higher in both the cerebral cortex and the ca1 region in the group treated with trauma only and in the group administered saline after trauma compared to the group that received shilajit extract after trauma. The total antioxidant capacity increased significantly in blood samples taken only from the group treated with trauma and saline in post-trauma treatment compared to the group given post-traumatic shilajit extract, while shilajit extract given due to traumatic brain injury significantly decreased the total oxidant capacity and oxidative stress index values compared to the other groups. CONCLUSION: Shilajit extract has been shown to have a neuroprotective effect in the treatment of acute traumatic brain injury. Our study showed that shilajit may be a useful option in the treatment of secondary brain injury, in humans.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Traumatismos Craniocerebrais , Fármacos Neuroprotetores , Humanos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Antioxidantes , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Traumatismos Craniocerebrais/tratamento farmacológico , Traumatismos Craniocerebrais/complicações , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/complicações , OxidantesRESUMO
INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, Pâ =â .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, Pâ =â .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (Pâ <â .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.