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1.
J Clin Med ; 13(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38930150

RESUMO

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.

2.
Curr Med Res Opin ; 40(7): 1137-1143, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38857167

RESUMO

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.


Assuntos
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 adversos
3.
N Engl J Med ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924756

RESUMO

BACKGROUND: Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

4.
Artigo em Inglês | MEDLINE | ID: mdl-38795147

RESUMO

OBJECTIVES: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. DESIGN: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. RESULTS: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.

5.
Medicine (Baltimore) ; 103(21): e37972, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787994

RESUMO

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.


Assuntos
Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas , Crizotinibe , Neoplasias Pulmonares , Humanos , Crizotinibe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Quinase do Linfoma Anaplásico/genética , Adulto , Idoso , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Resultado do Tratamento
6.
Clin Transl Oncol ; 26(8): 1878-1885, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38451412

RESUMO

AIM: HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer. METHODS: A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed. RESULTS: The median age was 64 (24-83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36-27.58), and in the low ratio group was 16.17 months (95% CI: 10.95-21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02-28.37) in the high HER2 gene copy number group and 10.13 months (5.55-14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55-14.33) in the group with high HER2 gene copy number and 7.56 months (4.62-10.49) in the low copy number group (p = 0.06). CONCLUSION: Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.


Assuntos
Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Receptor ErbB-2/metabolismo , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Prognóstico , Taxa de Sobrevida , Turquia/epidemiologia , Cromossomos Humanos Par 17/genética , Hibridização in Situ Fluorescente
7.
Cancer Chemother Pharmacol ; 93(5): 497-507, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38436714

RESUMO

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.


Assuntos
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 fármacos
8.
Indian J Cancer ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38451840

RESUMO

BACKGROUND: In metastatic colorectal cancer (mCRC), the genetic structure and cell metabolism of the primary tumor lesion might be different from metastatic lesions. It is thought that cell-level glucose metabolism may differ due to the difference in RAS wild and mutant mCRC patients' prognosis. In this study, we aimed to compare 2-deoxy-2-[fluorine-18]-fluoro-D-glucose Positron Emission Tomography (18F-FDG PET/CT) uptake levels for KRAS mutation status and primary-metastatic tumor localization. METHODS: Our study is a retrospective cohort analysis that included RAS mutation status study and staging-oriented 18F-FDG PET/CT conducted on mCRC patients. RESULTS: There was no significant relationship between metastasis and primary tumor maximum Standardized uptake value (SUVmax) values according to the KRAS mutational status (P > 0.05). Patients with liver metastasis along with mutant BRAF mutation status had significantly higher SUVmax values in PET-CT scans (P = 0.04). There was a negative correlation between SUVmax values of lung metastases and overall survival (r = -0.35, P = 0.04). Patients with high carcinoembryonic antigen (CEA) levels had significantly higher SUVmax values of lung metastasis than patients with normal CEA levels (P = 0.009). Patients with high CA19-9 levels had significantly higher SUVmax values of liver, peritoneal, and bone metastasis than patients with normal CA19-9 levels (P = 0.002, P = 0.001, P = 0.004, respectively). There was no significant correlation between SUVmax values of metastasis and Lactate dehydrogenase (LDH) values. Liver metastasis of right-sided mCRCs had significantly higher SUVmax values (P = 0.03). CONCLUSION: We could not demonstrate a significant association between KRAS mutation and SUVmax values of PET scan in primary or metastatic tumor sites in advanced CRC.

9.
Cancer Invest ; 42(2): 141-154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38486421

RESUMO

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.


Assuntos
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 Tumores
11.
J Oncol Pharm Pract ; 30(1): 210-214, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37642988

RESUMO

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 1 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.


Assuntos
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 terapêutico
12.
J Chemother ; 36(3): 249-257, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37578138

RESUMO

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.


Assuntos
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 adversos
13.
J Cancer Res Ther ; 19(Suppl 2): S845-S850, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38102905

RESUMO

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.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Prognóstico , Antagonistas de Androgênios/uso terapêutico , Castração , Estudos Retrospectivos
15.
BMC Cancer ; 23(1): 1045, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904131

RESUMO

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.


Assuntos
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 Tumoral
16.
Pancreas ; 52(4): e235-e240, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37816170

RESUMO

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 Pancreáticas
17.
Oncologist ; 28(10): 875-884, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37676712

RESUMO

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, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .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 (P < .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.


Assuntos
Tumores Neuroendócrinos , Humanos , Pessoa de Meia-Idade , Capecitabina/efeitos adversos , Temozolomida/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Turquia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento
20.
Head Neck ; 45(7): 1643-1653, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37084179

RESUMO

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.


Assuntos
Recidiva Local de Neoplasia , Neoplasias das Glândulas Salivares , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/terapia , Glândulas Salivares Menores/patologia
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