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OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.
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Anticuerpos Monoclonales , Neoplasias de Cabeza y Cuello , Humanos , Ciclo Celular , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
PURPOSE: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. MATERIALS AND METHODS: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. RESULTS: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020). CONCLUSIONS: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02289547.
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BACKGROUND: We sought to investigate whether serum immune and inflammatory parameters can help to predict distant metastasis (DM) in patients with unresectable hepatocellular carcinoma (HCC) undergoing curative radiation therapy (RT). METHODS: A total of 76 RT courses were analyzed. The following variables were included in the analysis: systemic inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), absolute lymphocyte count, lymphocyte-to-monocyte ratio, albumin, albumin-to-alkaline phosphatase ratio, RT-related parameters, and levels of total protein, hemoglobin, α-fetoprotein, and PIVKA-II. Distant control (DC) and overall survival (OS) rates were calculated and compared. RESULTS: The mean age was 61.4 years, and most patients were men (n = 62, 81.6%). The median RT fraction number and fractional doses were 12 (range, 4-30) and 5 (range, 2-12) Gy, respectively. With a median follow-up of 12 (range, 3.1-56.7) months, the 1-year DC and OS rates were 64.4% and 55.2%, respectively. The development of DM significantly deteriorated OS (p = 0.013). In the multivariate analysis, significant independent prognostic indicators for DC and OS rates were the highest posttreatment PLR (≤235.7 vs. >235.7, p = 0.006) and the lowest posttreatment PNI (≤25.4 vs. >25.4, p < 0.001), respectively. CONCLUSIONS: Posttreatment serum PLR might be helpfully used as a predictive biomarker of DM in unresectable HCC patients undergoing RT. Future research is necessary to confirm our findings.
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BACKGROUND/AIMS: We compared the efficacy of the granisetron transdermal system (GTS) with that of ondansetron for controlling chemotherapy-induced nausea and vomiting (CINV) in patients treated with highly emetogenic chemotherapy (HEC). METHODS: We randomized a total of 389 patients to groups treated by GTS and ondansetron before HEC. The primary endpoint was the percentage of patients achieving complete response (CR; no retching/vomiting/rescue medication) of CINV from the time of chemotherapy initiation to 24 hours after the last administration of chemotherapy (prespecified non-inferiority margin of 15%). Quality of life (QoL) was also assessed using the Functional Living Index-Emesis (FLIE). RESULTS: The per protocol analysis included 152 (47.80%) and 166 patients (52.20%) in the GTS and ondansetron groups, respectively. In the full analysis set, the most common diagnosis, regimen, and period of chemotherapy were lung cancer (149 patients, 40.27%), cisplatin-based regimen (297 patients, 80.27%), and 1 day chemotherapy (221 patients, 59.73%). The CR rates were 86.84% and 90.36% in the GTS and ondansetron groups, respectively; the treatment difference was -3.52% (95% confidence interval, -10.52 to 3.48) and met the primary endpoint, indicating that GTS was not inferior to ondansetron. Patient satisfaction, assessed on the FLIE, showed significantly higher scores in the GTS group compared to the ondansetron group (mean ± standard deviation, 1,547.38 ± 306.00 and 1,494.07 ± 312.05 mm, respectively; p = 0.0449). CONCLUSION: GTS provided effective, safe, and well-tolerated control of CINV and improved the QoL in HEC.
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Antieméticos , Antineoplásicos , Humanos , Granisetrón/efectos adversos , Antieméticos/uso terapéutico , Antieméticos/efectos adversos , Ondansetrón/efectos adversos , Calidad de Vida , Antineoplásicos/efectos adversos , Náusea/inducido químicamente , Náusea/prevención & control , Náusea/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control , Método Doble CiegoRESUMEN
We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies' nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP, and EREG, and two genes were downregulated, including CXCL9 and GNLY. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.
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Background and Objectives: The prediction of the prognosis and effect of neoadjuvant therapy is vital for patients with advanced or unresectable colorectal carcinoma (CRC). Materials and Methods: We investigated several tumor microenvironment factors, such as intratumoral budding (ITB), desmoplastic reaction (DR), and Klintrup-Mäkinen (KM) inflammation grade, and the tumor-stroma ratio (TSR) in pretreatment biopsy samples (PBSs) collected from patients with advanced or unresectable CRC. A total of 85 patients with 74 rectal carcinomas and 11 colon cancers treated at our hospital were enrolled; 66 patients had curative surgery and 19 patients received palliative treatment. Results: High-grade ITB was associated with recurrence (p = 0.002), death (p = 0.034), and cancer-specific death (p = 0.034). Immature DR was associated with a higher grade of clinical tumor-node-metastasis stage (cTNM) (p = 0.045), cN category (p = 0.045), and cM category (p = 0.046). The KM grade and TSR were not related to any clinicopathological factors. High-grade ITB had a significant relationship with tumor regression in patients who received curative surgery (p = 0.049). Conclusions: High-grade ITB in PBSs is a potential unfavorable prognostic factor for patients with advanced CRC. Immature DR, TSR, and KM grade could not predict prognosis or therapy response in PBSs.
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Adenocarcinoma , Neoplasias Colorrectales , Adenocarcinoma/patología , Adenocarcinoma/terapia , Biopsia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Humanos , Terapia Neoadyuvante , Pronóstico , Estudios Retrospectivos , Microambiente TumoralRESUMEN
The role of ß-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC). We aimed to analyze the role of DKK1 or ß-catenin as a prognostic factor in BTC, and determine the clinical associations of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocytes (TIL). We used data from The Cancer Genome Atlas Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. CD8+ TIL expression was a significant predictor of favorable overall survival (OS) and relapse-free survival (RFS) (median OS, 34.9 months in high-TIL, 16.7 months in low-TIL, P < 0.0001 respectively; median RFS, 27.1 months in high-TIL, 10.0 months in low-TIL, P < 0.0001 respectively). In the high-CD8+ TIL BTC group, the tumor expression of ß-catenin and DKK1 had a significant negative impact on either OS or RFS. In the low-TIL BTC group, there were no differences according to ß-catenin and DKK1 expression. Cox regression multivariate analysis demonstrated that CD8+ TIL and ß-catenin retained significant association with OS. Among patients with resected BTC, the ß-catenin and DKK1 protein and high CD8+ TIL levels were associated with poor and good clinical outcomes, respectively.
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Neoplasias del Sistema Biliar/química , Biomarcadores de Tumor/análisis , Linfocitos T CD8-positivos/inmunología , Péptidos y Proteínas de Señalización Intercelular/análisis , Linfocitos Infiltrantes de Tumor/inmunología , beta Catenina/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/inmunología , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/cirugía , Bases de Datos Genéticas , Femenino , Humanos , Inmunohistoquímica , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Tiempo , Microambiente TumoralRESUMEN
BACKGROUND: Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. METHODS: A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. RESULTS: RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P < 0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P < 0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35-0.97, P < 0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81-2.26, P = 0.251). CONCLUSIONS: Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.
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Proteínas Portadoras/metabolismo , Gastrectomía , Recurrencia Local de Neoplasia/epidemiología , Proteínas de Unión al ARN/metabolismo , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Proteínas Portadoras/análisis , Supervivencia sin Enfermedad , Mucosa Gástrica/patología , Mucosa Gástrica/cirugía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores Protectores , Proteínas de Unión al ARN/análisis , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Análisis de Matrices TisularesRESUMEN
Chemotherapy-induced nausea and vomiting (CINV) is an unbearable side effect. Identifying high emetic risk patients and providing more active antiemetics strategies are mandatory to improve the tolerability of chemotherapy. In this prospective cohort study, leptin, ghrelin, and substance P were measured at baseline, day 3, and day 14 during the first cycle of chemotherapy. Nausea and vomiting were measured each day for the first 4 days of the first cycle of chemotherapy. Eighty-two patients were enrolled. Colorectal cancer (61%) and gastric cancer (35.4%) were common cancer types. All patients received moderate emetic risk chemotherapy. Forty-five (54.9%) patients had nausea, and 15 (18.3%) patients experienced vomiting. In univariate analysis, a higher level of baseline substance P, which is a target of NK1-RA (Neurokinin 1 receptor antagonist), was a significant predictive marker for chemotherapy-induced nausea [odds ratio (OR): 2.6, 95% confidence interval (CI): 1.02-6.62, p = 0.046]. Regarding chemotherapy-induced vomiting, patients with higher levels of substance P had a greater chance of vomiting [OR: 1.72, 95% CI: 0.49-5.99, p = 0.395] than those with lower levels of substance P. In patients receiving moderate emetic risk chemotherapy, active antiemetics, including NK1-RA, could be considered for those with high levels of substance P.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Eméticos/efectos adversos , Náusea/diagnóstico , Neoplasias/tratamiento farmacológico , Sustancia P/sangre , Vómitos/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Náusea/sangre , Náusea/inducido químicamente , Neoplasias/patología , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Vómitos/sangre , Vómitos/inducido químicamenteRESUMEN
CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs (p = 0.027) but not of Foxp3+ TILs (p = 0.455) and CD20+ TILs (p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis (p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) (p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC (p = 0.011; hazard ratio (HR) = 0.435; 95% confidence interval (CI) = 0.245-0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.
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BACKGROUND: We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA, and germline APOBEC3A/B deletion polymorphism in patients with breast cancers and to investigate the correlation between their expressions and clinicopathological characteristics. METHODS: RNA and DNA samples were extracted from 138 breast cancer tissues and adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using quantitative real-time polymerase chain reaction. Insertion and deletion PCR assays were performed to detect the A3B deletion allele. The serum concentrations of soluble programmed death-ligand 1 (sPD-L1) and interferon gamma were determined using enzyme-linked immunosorbent assays. RESULTS: A3B mRNA expression levels were significantly higher in triple-negative breast cancers compared to hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancers. Older age of the patient and high ki-67 expression were associated with increased expression levels of A3A and A3B mRNA. Advanced tumor stage, presence of lymph node involvement, and high histological grade were associated with increased expression levels of A3A mRNA. The APOBEC3A/B deletion allele was found in 77 (55.8%) patients. TP53 and PIK3CA mutations were detected in 62 (44.9%) and 31 (22.5%) patients, respectively. The presence of a PIK3CA mutation was associated with lower A3A mRNA expression levels. There was a weak positive relationship between A3A mRNA expression levels and serum sPD-L1 levels. CONCLUSIONS: There was a difference in A3B mRNA expression levels according to breast cancer subtypes, and high levels of A3A and A3B mRNA expressions were associated with an aggressive phenotype. There was a high incidence of APOBEC3A/B deletion allele. Further studies are needed to identify the clinical significance of APOBEC in Asian patients with breast cancer.
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Neoplasias de la Mama/genética , Citidina Desaminasa/genética , Regulación Neoplásica de la Expresión Génica , Antígenos de Histocompatibilidad Menor/genética , Proteínas/genética , Antígeno B7-H1/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/clasificación , Fosfatidilinositol 3-Quinasa Clase I/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Interferón gamma/sangre , Persona de Mediana Edad , Polimorfismo Genético , ARN Mensajero/genética , ARN Mensajero/metabolismo , Eliminación de Secuencia , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND/AIMS: Hyaluronic acid (HA) regulates cell adhesion, migration and proliferation in various cancers. The clinical implications of HA in resected head and neck squamous cell carcinoma have not been elucidated. We investigated the clinical significance and prognostic value of the expression of tumoral and stromal HA and its related proteins in oropharyngeal and oral cavity cancer. METHODS: Resected tissues from oropharyngeal or oral cavity cancer patients undergoing surgery were analysed in tissue microarrays divided into stroma and cancer panels. The expression levels of HA, HA synthases and hyaluronidases were also assessed by immunohistochemistry. RESULTS: A total of 160 resected oropharyngeal or oral cavity cancer tissues were analysed. Stromal HA expression was observed more frequently in human papilloma virus (HPV)-negative tumors, but other clinicopathological characteristics did not differ. In patients with HPV-negative oral cavity cancers, high stromal HA expression was associated with significantly shorter recurrence-free survival and overall survival compared with low stromal HA expression. The expression of HA in both tumors and stroma was significantly correlated with poorer outcomes than other combinations in patients with HPV-negative oral cavity cancers. However, these prognostic roles of HA were not observed in patients with HPV-negative oropharyngeal cancers. In the HPV-stratified multivariate analysis, high stromal HA expression remained an independent indicator of poor prognosis in terms of recurrence-free survival. CONCLUSION: High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas/cirugía , Humanos , Ácido Hialurónico , Boca , PronósticoRESUMEN
PURPOSE: The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage. MATERIALS AND METHODS: Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. RESULTS: Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. CONCLUSION: Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.
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Adenocarcinoma de Células Claras/diagnóstico , Neoplasias Ováricas/diagnóstico , Adenocarcinoma de Células Claras/etiología , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/etiología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Pronóstico , República de Corea , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
To compare the incidence of brain metastases of advanced non-small cell lung cancer (NSCLC) treated with systemic cytotoxic chemotherapy (CC) and targeted therapy (TT), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011, to November 30, 2016. Of the 29,174 patients newly diagnosed with stage IIIB or IV NSCLC who received systemic treatment, we investigated the initial and subsequent incidence of brain metastases. Besides, among 22,458 patients without initial brain metastasis, the overall cumulative incidence of subsequent brain metastases was compared according to systemic treatment administered. In total, 1,126 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7% vs. 3.8%; 3-year: 17.2% vs. 5.0%; P < 0.001). Younger age, female sex, and first-line TT were significant risk factors for subsequent brain metastasis. In conclusion, the overall cumulative incidence of brain metastasis was significantly higher in patients received TT as the first-line treatment than in those received CC.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Anciano , Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Cuidados Paliativos , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy. MATERIALS AND METHODS: Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined. RESULTS: Serum samples from 138 patients (median age: 75â¯years, range: 70-92â¯years) were collected from February 2014 to December 2016. During a median follow up time of 13.8â¯months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, Pâ¯=â¯0.009), activin A (Pâ¯=â¯0.007), and myostatin (Pâ¯=â¯0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32-3.72; Pâ¯=â¯0.003) and myostatin (HR 3.02, 95% CI 1.39-6.57; Pâ¯=â¯0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model. CONCLUSION: In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation.
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Activinas/sangre , Proteína C-Reactiva/metabolismo , Interleucina-6/sangre , Mortalidad , Miostatina/sangre , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias/sangre , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias del Sistema Biliar/sangre , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/patología , Biomarcadores/sangre , Quimiocina CXCL10/sangre , Colágeno Tipo I/sangre , Neoplasias del Colon/sangre , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Árboles de Decisión , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Fibronectinas/sangre , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Péptidos/sangre , Pronóstico , República de Corea , Sirtuina 1/sangre , Neoplasias Gástricas/sangre , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/sangre , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
The microRNA-200 (miR-200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well-known regulators of the epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR-200 family members control RNA-binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR-200a and miR-200b could recognize QKI 3'-UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR-200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR-200 overexpression, and the 3'-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR-200 form a negative feedback loop to maintain homeostatic responses to EMT-inducing signals.
Asunto(s)
Carcinoma de Células Escamosas/patología , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , MicroARNs/genética , Neoplasias de la Boca/patología , Proteínas de Unión al ARN/genética , Regiones no Traducidas 3' , Animales , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Femenino , Expresión Génica , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Neoplasias de la Boca/genética , PronósticoRESUMEN
BACKGROUND/AIMS: The purpose of the study is to investigate the associations between sarcopenia and health-related quality of life in elderly men and women in Korea. METHODS: In a cross-sectional study using data from 2008 to 2011 Korean National Health and Nutrition Examination Survey, 4,937 adults aged 60 years and older who underwent a dual-energy X-ray absorptiometry scan were included in the study. Sarcopenia is defined as an appendicular skeletal muscle index of two standard deviations or more below the mean for young, healthy reference populations. The health-related quality of life was measured using the EuroQol-5 dimension questionnaire. RESULTS: The overall prevalence of sarcopenia was 6.6% in these Korean people over the age of 60 years: 11.1% for men and 3.2% for women. Sarcopenic men tended to have lower income, lower physical activity, lower body mass index, and smaller waist circumference compared with nonsarcopenic men. Sarcopenic women tended to have higher body mass index and larger waist circumference compared with nonsarcopenic women. Sarcopenic men showed higher impairments in mobility, self-care, usual activities, and pain/discomfort compared with nonsarcopenic men. Women with sarcopenia also showed higher impairments in mobility, self-care, usual activities, and anxiety/depression compared with nonsarcopenic women. Sarcopenia showed an association with impairments in selfcare for men, and with impairments in self-care, usual activities, and anxiety/depression for women, after adjusting for other confounding factors. CONCLUSION: There is a significant association between sarcopenia and impaired health-related quality of life in this elderly Korean population, and these results differ between men and women.
Asunto(s)
Calidad de Vida , Sarcopenia/psicología , Absorciometría de Fotón , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Prevalencia , República de Corea/epidemiología , Factores de Riesgo , Sarcopenia/diagnóstico por imagen , Sarcopenia/epidemiología , Factores Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND/AIMS: This study was conducted to identify risk factors that predict vulnerability to cancer therapy on the basis of the clinical, geriatric, and quality of life assessment before starting treatment in elderly patients. METHODS: Seventy-five patients aged 65 years and over with newly diagnosed stage IV solid cancer receiving chemotherapy were analyzed. Clinical and laboratory data were collected. The geriatric assessment was performed using the Korean versions of the Modified Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, and Geriatric Depression Scale. The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC-QLQ-C30) was also performed. RESULTS: Forty-one patients stopped cancer treatment during or after the end of first-line therapy and were classified as the treatment interruption group. By univariate analysis, treatment interruption was associated with metastases to ≥ 2 distant sites, lower albumin level, lower EORTC-QLQ-C30 physical and role functioning scores, and higher EORTC-QLQ-C30 fatigue and appetite loss symptom scores. By multivariate analysis, treatment interruption was significantly associated with low score for the EORTC-QLQ-C30 physical functioning scale (odds ratio [OR], 1.020; 95% confidence interval [CI], 1.002 to 1.039; p = 0.030), and ≥ 2 sites of distant metastases (OR, 2.965; 95% CI, 1.012 to 8.681; p = 0.047). CONCLUSION: The EORTC-QLQ-C30 physical functioning score and metastases to ≥ 2 organs, which indicate a poor physical functional status and metastatic high tumor burden, were significantly associated with interruption of first-line treatment in elderly patients with cancer.