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1.
BMC Cancer ; 24(1): 954, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103762

RESUMEN

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 Kaplan‒Meier 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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Factor 15 de Diferenciación de Crecimiento , Inmunoterapia , Neoplasias Pulmonares , Humanos , Factor 15 de Diferenciación de Crecimiento/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Masculino , Femenino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Inmunoterapia/métodos , Pronóstico , Nivolumab/uso terapéutico , Biomarcadores de Tumor/metabolismo , Adulto , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/uso terapéutico , Supervivencia sin Progresión
2.
Medicine (Baltimore) ; 103(30): e38828, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058877

RESUMEN

The fact that the human epidermal growth factor receptor 2 (HER2)-low group, historically classified as HER2 negative in breast cancer histology, benefited from HER2-targeted treatments similarly to the HER2-positive group indicates that this group has a distinct histology from the HER2-0 group. The effectiveness of cyclin-dependent kinase 4/6 inhibitors, which are the standard first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer, in this newly defined histological subgroup remains a topic of debate. In our study, we examined the impact of HER2 status on the efficacy of CDK4/6 inhibitors. Our study is a retrospective, multicenter, real-world data analysis. One hundred sixty patients were included in the study. The relationship between HER2 status and other clinical-pathological features, as well as progression-free survival, was examined. Median follow-up was 20.33 ±â€…0.98 months. The mPFS could not be reached. All patients exhibited positive estrogen receptor expression. Among the patients, 111 (69.4%) were categorized as HER2-0, and 49 (30.6%) as HER2-low. The 24-month progression-free survival rates were similar between HER2-0 and HER2-low patients (60.6% vs 65.3%, hormone receptor: 1.18, CI: 0.67-2.20, P = .554). We established that the mPFS achieved with cyclin-dependent kinase 4/6 inhibitors as a first-line therapy for patients with advanced breast cancer is unaffected by HER2 status.


Asunto(s)
Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Estudios Retrospectivos , Persona de Mediana Edad , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Adulto , Supervivencia sin Progresión , Receptores de Estrógenos/metabolismo
3.
Cancer Med ; 13(14): e70002, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39030808

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Fluorouracilo , Terapia Neoadyuvante , Paclitaxel , Puntaje de Propensión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Neoadyuvante/métodos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Anciano , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Turquía , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Adulto
4.
Curr Med Res Opin ; 40(7): 1137-1143, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38857167

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Neoplasias Gástricas , Taxoides , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Femenino , Masculino , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Taxoides/administración & dosificación , Taxoides/uso terapéutico , Taxoides/efectos adversos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Fluorouracilo/efectos adversos , Turquía , Adulto Joven , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Resultado del Tratamiento , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Hidrocarburos Aromáticos con Puentes/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/administración & dosificación , Camptotecina/uso terapéutico , Camptotecina/efectos adversos
5.
J Clin Med ; 13(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38930150

RESUMEN

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.

6.
Cancer Chemother Pharmacol ; 93(5): 497-507, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38436714

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Obesidad Abdominal , Inhibidores de Proteínas Quinasas , Sarcopenia , Humanos , Sarcopenia/inducido químicamente , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Estudios Retrospectivos , Persona de Mediana Edad , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Obesidad Abdominal/inducido químicamente , Adulto , Supervivencia sin Progresión , Grasa Intraabdominal/efectos de los fármacos , Metástasis de la Neoplasia , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Grasa Subcutánea/efectos de los fármacos
7.
Indian J Cancer ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38451840

RESUMEN

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.

8.
Cancer Invest ; 42(2): 141-154, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38486421

RESUMEN

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.


Asunto(s)
Antígeno B7-H1 , Neoplasias Gastrointestinales , Receptor 2 Celular del Virus de la Hepatitis A , Proteínas de Punto de Control Inmunitario , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Reparación del ADN , Neoplasias Gastrointestinales/química , Neoplasias Gastrointestinales/patología , Receptor 2 Celular del Virus de la Hepatitis A/análisis , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Proteínas de Punto de Control Inmunitario/análisis , Proteínas de Punto de Control Inmunitario/metabolismo , Proteína del Gen 3 de Activación de Linfocitos/análisis , Proteína del Gen 3 de Activación de Linfocitos/metabolismo , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/patología , Ligando OX40/análisis , Ligando OX40/metabolismo , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Inmunohistoquímica , Clasificación del Tumor
9.
J Clin Med ; 13(3)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38337537

RESUMEN

Background: Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce electrocardiographic changes. This study examined the effect of anti-emetic medications on arrhythmogenic potential and hemodynamic alterations. Methods: We considered patients aged 18 or above receiving chemotherapy between June 2013 and December 2013. Patients were grouped by anti-emetic medication: intravenous granisetron (Group G), oral aprepitant plus IV granisetron (Group AG), IV palonosetron (Group P), and oral aprepitant plus IV palonosetron (Group AP). We recorded blood pressure and electrocardiography initially and at the thirtieth minute post-medication, focusing on P dispersion, QTc dispersion, and systolic/diastolic blood pressure alterations. Results: The study included 80 patients (20 per group). Baseline systolic/diastolic blood pressure and P dispersion showed no significant variance. However, the baseline QTc dispersion was significantly lower in Groups P and AP than G and AG. The thirtieth-minute systolic/diastolic blood pressures were significantly lower than the baseline for Groups AG and AP, and the heart rates decreased in all groups. Group P showed significantly fewer blood pressure changes. Conclusions: We found no arrhythmogenic potential linked to granisetron, palonosetron, and aprepitant. Hypotension was more frequent at 30 min post-medication in granisetron or aprepitant recipients. Considering no hypotension occurred when using palonosetron alone, this treatment was deemed safer.

11.
J Chemother ; 36(3): 249-257, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37578138

RESUMEN

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.


Asunto(s)
Neoplasias del Colon , Humanos , Oxaliplatino/efectos adversos , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Capecitabina/efectos adversos , Fluorouracilo/efectos adversos , Cirrosis Hepática , Quimioterapia Adyuvante/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucovorina/efectos adversos
12.
J Oncol Pharm Pract ; 30(1): 210-214, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37642988

RESUMEN

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.


Asunto(s)
Anemia Refractaria , Indazoles , Neoplasias Ováricas , Piperidinas , Aplasia Pura de Células Rojas , Femenino , Humanos , Anciano , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Aplasia Pura de Células Rojas/inducido químicamente , Aplasia Pura de Células Rojas/tratamiento farmacológico , Anemia Refractaria/inducido químicamente , Anemia Refractaria/tratamiento farmacológico , Esteroides/uso terapéutico
13.
J Cancer Res Ther ; 19(Suppl 2): S845-S850, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38102905

RESUMEN

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.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Pronóstico , Antagonistas de Andrógenos/uso terapéutico , Castración , Estudios Retrospectivos
14.
Cureus ; 15(10): e47324, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38021491

RESUMEN

OBJECTIVE: The ATM gene is one of the most common breast cancer (BC) susceptibility genes after BRCA1/2 and has been shown to be a moderate BC susceptibility gene. The association between ATM germline mutation and clinical features of BC is now unknown. In this article, clinicopathological features of BC patients with ATM germline heterozygous mutation were investigated. MATERIALS AND METHODS: Patients admitted to the Medical Genetics department of a tertiary hospital between January 2020 and December 2022 were examined. Only invasive BC patients with pathogenic mutation, likely pathogenic mutation, or variants of uncertain significance (VUS) were included in the study. RESULTS: In all, 121 patients were included in the study. The median age at the first cancer diagnosis of the patients was 44 years. Of the total number of patients, 75.2% (91) had the histological subtype of infiltrating ductal carcinoma, and 43% (52) had Luminal B molecular subtype features. At a median follow-up of 16 months, 5.8% (7) of patients developed cancer in the contralateral breast. In addition, 7.4% (9) of the patients developed a second primary cancer during follow-up. When the patients were compared according to ATM variant classification, the localization, histologic types, and molecular subtypes of the BC were not different between all groups (respectively; p=0.68, p=0.65, p=0.32). CONCLUSIONS: To the best of our knowledge, this is the first publication that evaluates the clinical and pathological characteristics of BC patients with germline heterozygous ATM mutations in the Turkish population. When patients were compared according to variant classifications of ATM mutation, patients' histological and molecular subtypes were similar.

15.
BMC Cancer ; 23(1): 1045, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37904131

RESUMEN

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.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Nivolumab/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Bazo/patología , Inmunoterapia , Estudios Retrospectivos , Microambiente Tumoral
17.
Pancreas ; 52(4): e235-e240, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37816170

RESUMEN

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.


Asunto(s)
Gemcitabina , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Fluorouracilo , Leucovorina , Paclitaxel , Albúminas , Neoplasias Pancreáticas
19.
J Oncol Pharm Pract ; 29(6): 1537-1540, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37524106

RESUMEN

INTRODUCTION: Breast cancer is the most common cancer in women worldwide. One of the treatment choices used in hormone receptor positive and HER2 expression negative metastatic breast cancer is cyclin dependent kinase 4/6 (CDK) inhibitors. There are differences between the effects and adverse events of all CDK4/6 inhibitors. In this report, we describe a 48-year-old female patient with breast cancer who developed pulmonary infiltrates secondary to drug in the second year of follow-up with Ribociclib therapy. CASE REPORT: The patient who used ribociclib for metastatic breast cancer was admitted to hospital for routine controls. The patient, in the eighth month of ribociclib treatment, had no active complaints. In the patient's imaging, pulmonary infiltrates were detected in the lower lobe of the right lung. MANAGEMENT AND OUTCOME: The drug was continued in the patient who was asymptomatic and had no infectious signs. Pneumonitis, interstitial lung disease, tuberculosis, COVID-19 and other viral agents were excluded in the patient. A minimal increase in pulmonary infiltrates was observed in the follow-up. However, the patient who does not have any complaints is currently continuing ribociclib at 600 mg/day. DISCUSSION: The pulmonary infiltrates that developed in the patient increased with continued use of ribociclib, suggesting that this was due to ribociclib. The Naranjo Adverse Drug Reaction Probability Scale also indicates probable relationship.

20.
Turk J Med Sci ; 53(1): 413-419, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36945944

RESUMEN

BACKGROUND: The optimal sarcopenia measurement method in patients with a diagnosis of glioblastoma multiforme (GBM) is unknown. It has been found that temporal muscle thickness (TMT) may reflect sarcopenia and be associated with survival, but the relationship between temporal muscle area (TMA) and GBM prognosis has never been evaluated before. The primary outcome of the study was to evaluate the relationship between TMA/TMT and overall survival (OS) time in newly diagnosed GBM patients. METHODS: The data of patients who presented at the university hospital between January 2009 and January 2019 with a confirmed diagnosis of glioblastoma multiforme at the time of diagnosis were analyzed retrospectively. Temporal muscle thickness and TMA were measured retrospectively from preoperative MRIs of patients diagnosed with GBM. Due to the small number of patients and the failure to determine a cut-off value with acceptable sensitivity and specificity using ROC analysis, the median values were chosen as the cut-off value. The patients were basically divided into two according to their median TMT (6.6 mm) or TMA (452 mm2 ) values, and survival analysis was performed with the Kaplan-Meier analysis. RESULTS: The median TMT value was 6.6 mm, and the median TMA value was 452 mm2 . The median overall survival (OS) was calculated as 25.8 months in patients with TMT < 6.6 mm, and 15.8 months in patients with TMT ≥ 6.6 mm (p = 0.29). The median overall survival (OS) of patients with TMA < 452mm2 was 26.3 months, and the group with TMA ≥ 452mm2 was 14.6 months (p = 0.06). The median disease-free survival was 18.3 months (%95 CI: 13.2-23.4) in patients with TMT < 6.6mm, while mDFS was 10.9 (%95 CI: 8.0-13.8) months in patients with TMT ≥ 6.6mm (p = 0.21). The median disease-free survival was found to be 21.0 months (%95 CI: 15.8-26.1) in patients with TMA < 452 mm2 and 10.5 months (%95 CI: 7.8-13.2) in patients with TMA ≥ 452 mm2 (p = 0.018). DISCUSSION: No association could be demonstrated between TMT or TMA and OS of GBM patients. In addition, the median DFS was found to be longer in patients with low TMA. There is an unmet need to determine the optimal method of sarcopenia in GBM patients.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Sarcopenia , Humanos , Glioblastoma/complicaciones , Glioblastoma/diagnóstico por imagen , Músculo Temporal/patología , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Pronóstico
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