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BACKGROUND: Links have been reported between the airflow limitation and both metabolic syndrome (MetS) and fatty liver (FL). Additionally, associations between genetic factors and risks of MetS, FL, and airflow limitation have been identified separately in different studies. Our study aims to simultaneously explore the association between specific single nucleotide polymorphisms (SNPs) of certain genes and the risk of the three associated diseases. METHODS: In this retrospective cross-sectional nationwide study, 150,709 participants from the Taiwan Biobank (TWB) were enrolled. We conducted a genotype-phenotype association analysis of nine SNPs on seven genes (ApoE-rs429358, MBOAT7-rs641738, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, TM6SF2-rs58542926, and IFNL4-rs368234815) using data from the TWB1.0 and TWB2.0 genotype dataset. Participants underwent a series of assessments including questionnaires, blood examinations, abdominal ultrasounds, and spirometry examinations. RESULTS: MetS was associated with FL and airflow limitation. ApoE-rs429358, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, and TM6SF2-rs58542926 were significantly associated with the risk of MetS. The cumulative impact of T alleles of ApoE-rs429358 and TM6SF2-rs58542926 on the risk of FL was observed (p-value for trend < 0.001). Individuals without MetS and airflow limitation carrying LEPR-rs1805096 G_G genotype exhibited a reduction in the forced expiratory volume in 1 s percentage prediction (Coefficient -35, 95 % confidence interval (CI) -69.7- -0.4), low forced vital capacity percentage prediction (Coefficient -41.6, 95 % CI -82.6- -0.6), and low vital capacity percentage prediction (Coefficient -42.2, 95 % CI -84.2- -0.1). CONCLUSIONS: MetS significantly correlated with FL and airflow limitation. Multiple SNPs were notably associated with MetS. Specifically, T alleles of ApoE-rs429358 and TM6SF2-rs58542926 cumulatively increased the risk of FL. LEPR-rs1805096 shows a trend-wise association with pulmonary function, which is significant in patients without MetS or airflow limitation.
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Hígado Graso , Predisposición Genética a la Enfermedad , Síndrome Metabólico , Polimorfismo de Nucleótido Simple , Humanos , Síndrome Metabólico/genética , Masculino , Taiwán/epidemiología , Femenino , Persona de Mediana Edad , Estudios Transversales , Estudios Retrospectivos , Anciano , Hígado Graso/genética , Estudios de Asociación Genética , Adulto , Receptores de Leptina/genética , Bancos de Muestras Biológicas , Apolipoproteínas E/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Proteínas de la Membrana/genética , Factores de RiesgoRESUMEN
Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.
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OBJECTIVES: This study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population. METHODS: Patients with SLE (n=2782) and matched non-SLE controls (n=11 128) were genotyped using Genome-Wide TWB 2.0 single-nucleotide polymorphism (SNP) array. PRS models (C+T, LDpred2, Lassosum, PRSice-2, PRS-continuous shrinkage (CS)) were constructed for predicting SLE susceptibility. Logistic regression was assessed for C+T-based PRS association with renal involvement in patients with SLE. RESULTS: In the training set, C+T-based SLE-PRS, only incorporating 27 SNPs, outperformed other models with area under the curve (AUC) values of 0.629, surpassing Lassosum (AUC=0.621), PRSice-2 (AUC=0.615), LDpred2 (AUC=0.609) and PRS-CS (AUC=0.602). Additionally, C+T-based SLE-PRS demonstrated consistent predictive capacity in the testing set (AUC=0.620). Individuals in the highest quartile exhibited earlier SLE onset (39.06 vs 44.22 years, p<0.01), higher Systemic Lupus Erythematosus Disease Activity Index scores (3.00 vs 2.37, p=0.04), elevated risks of renal involvement within the first year of SLE diagnosis, including WHO class III-IV lupus nephritis (OR 2.36, 95% CI 1.47 to 3.80, p<0.01), estimated glomerular filtration rate <60 mL/min/1.73m2 (OR 1.49, 95% CI 1.18 to 1.89, p<0.01) and urine protein-to-creatinine ratio >150 mg/day (OR 2.07, 95% CI 1.49 to 2.89, p<0.01), along with increased seropositivity risks, compared with those in the lowest quartile. Furthermore, among patients with SLE with onset before 50 years, the highest PRS quartile was significantly associated with more serious renal diseases within the first year of SLE diagnosis. CONCLUSIONS: PRS of SLE is associated with earlier onset, renal involvement within the first year of SLE diagnosis and seropositivity in Taiwanese patients. Integrating PRS with clinical decision-making may enhance lupus nephritis screening and early treatment to improve renal outcomes in patients with SLE.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Adulto , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/epidemiología , Nefritis Lúpica/genética , Puntuación de Riesgo Genético , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Riñón , GenotipoRESUMEN
Purpose: This research aimed to analyze electron stream effect (ESE) during magnetic resonance image guided radiotherapy (MRgRT) for breast cancer patients on a MR-Linac (0.35 Tesla, 6MV), with a focus on the prevention of redundant radiation exposure. Materials and methods: RANDO phantom was used with and without the breast attachment in order to represent the patients after breast conserving surgery (BCS) and those received modified radical mastectomy (MRM). The prescription dose is 40.05 Gy in fifteen fractions for whole breast irradiation (WBI) or 20 Gy single shot for partial breast irradiation (PBI). Thirteen different portals of intensity-modulated radiation therapy were created. And then we evaluated dose distribution in five areas (on the skin of the tip of the nose, the chin, the neck, the abdomen and the thyroid.) outside of the irradiated field with and without 0.35 Tesla. In addition, we added a piece of bolus with the thickness of 1cm on the skin in order to compare the ESE difference with and without a bolus. Lastly, we loaded two patients' images for PBI comparison. Results: We found that 0.35 Tesla caused redundant doses to the skin of the chin and the neck as high as 9.79% and 5.59% of the prescription dose in the BCS RANDO model, respectively. For RANDO phantom without the breast accessory (simulating MRM), the maximal dose increase were 8.71% and 4.67% of the prescription dose to the skin of the chin and the neck, respectively. Furthermore, the bolus we added efficiently decrease the unnecessary dose caused by ESE up to 59.8%. Conclusion: We report the first physical investigation on successful avoidance of superfluous doses on a 0.35T MR-Linac for breast cancer patients. Future studies of MRgRT on the individual body shape and its association with ESE influence is warranted.
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Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Quimioradioterapia , Biomarcadores de Tumor/genética , Mutación , GenómicaRESUMEN
RATIONALE: Lung cancer is 1 of the most prevalent cancers globally. Definitive stereotactic ablative radiotherapy (SABR) is suggested for those who are unfit for or refuse surgical intervention. Here we present a patient with 2 lung cancer lesions who received SABR simultaneously with magnetic resonance Linear accelerator (Linac)-magnetic resonance (MR). PATIENT CONCERNS: A 46-years-old man had history of left lower lung cancer post lobectomy in 2018. Two recurrent tumors were found 2 years following, then became enlarged 4 months later. DIAGNOSES: The recurrent tumors were found by computed tomography. INTERVENTIONS: SABR was indicated due to inoperability and small size. Simulation was done both by computed tomography and MR scan with ViewRay MRIdian Linac, with the prescription dose being 50 gray in 4 fractions performed every other day within 2 weeks. The 2 lesions were irradiated at the same time with a single isocenter with mean treatment time was 78 minutes. OUTCOMES: No acute side effect was noted. Follow-up chest computed tomography scan 14 months after SABR showed mild consolidation and pneumonitis over the upper irradiated site favoring radiation-related reasons, while pneumonitis was resolved over the lower irradiated site. Positron emission tomography showed no definite evidence of FDG-avid recurrence. The patient has survived over 18 months following SABR and more than 4 years from the first diagnosis of lung cancer without significant adverse effects. LESSONS: Simultaneous SABR for multiple lung lesions is quite challenging because tumor motion by breathing can increase the risk of missing the target. With help by MR-Linac, simultaneous SABR to multiple lung lesions can be performed safely with efficacy.
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Neoplasias Pulmonares , Radiocirugia , Masculino , Humanos , Persona de Mediana Edad , Planificación de la Radioterapia Asistida por Computador/métodos , Recurrencia Local de Neoplasia/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Tomografía de Emisión de Positrones , Radiocirugia/métodosRESUMEN
BACKGROUND: The optimal radiotherapy dose for locally advanced esophageal squamous cell carcinoma in endemic areas treated with neoadjuvant concurrent chemoradiotherapy is unclear. METHODS: Eligible patients diagnosed between 2010 and 2019 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders. The hazard ratio (HR) of death was compared between high dose (50-50.4 Gy) and low dose (40-41.4 Gy) radiotherapy. We also evaluated other outcomes and performed supplementary analyses via an alternative approach. RESULTS: Our study population consisted of 644 patients. The PS weight-adjusted HR of death was 0.92 (95% confidence interval: 0.7-1.19, p = 0.51). There were no statistically significant differences for other outcomes or supplementary analyses. CONCLUSIONS: In this population-based study from an endemic area, we found no significant difference in overall survival between high vs. low radiotherapy doses.
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BACKGROUND: Keloid is a benign tumor with high recurrence rate; accordingly, complete surgical excision with adjuvant radiotherapy is one of the most effective treatments. This study reviewed outcomes of keloid patients receiving surgery and adjuvant radiotherapy in Kaohsiung Medical University Hospital. MATERIALS AND METHODS: All patients received radiation dose with 15 Gy, with their first radiotherapy within 24 hours after surgical excision. The end points were recurrence rate and local recurrence-free interval (LRFI), defined clinically as palpable gross tumor over the treatment site and duration from the last day of radiotherapy to disease recurrence. RESULTS: From May 2017 to July 2020, 32 patients with 40 keloid lesions were included. The mean age for these patients was 37.6 years, and the median follow-up time was 15.3 months. The overall recurrence rate was 52.5%, and the median LRFI was 9.7 months. Recurrence rates for males and females were 46.7% and 56% ( P = 0.567), respectively; for head and ear, chest, shoulder and upper extremities, and abdomen and back were 12.5%, 61.5%, 63.6%, and 62.5% ( P = 0.093); for lesions over 20 cm 2 and below 20 cm 2 were 62.5% and 50% ( P = 0.527); and for megavoltage electron beam and kilovoltage photon beam were 56.7% and 40% ( P = 0.361), respectively. Patients were further classified into 2 groups by lesion sites, which showed lower recurrence rate ( P = 0.011) and longer LRFI ( P = 0.028) with lesions over the head and ear than other sites. CONCLUSIONS: We found that lesion site might be a prognostic factor for keloid recurrence. Adjuvant radiation dose escalation for high-recurrence risk areas (other than the head and ear) might be required.
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Queloide , Adulto , Femenino , Humanos , Masculino , Queloide/radioterapia , Queloide/cirugía , Queloide/patología , Pronóstico , Radioterapia Adyuvante , RecurrenciaRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study's purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE. METHODS: A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package. RESULTS: Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA. CONCLUSIONS: We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.
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Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that α2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and α2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant [KD]: 1.95 × 10-10 ± 0.21 × 10-10 M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via α2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in CD14+ cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.
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Presentación de Antígeno , Carcinoma Hepatocelular/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Neoplasias Hepáticas/inmunología , Células Mieloides/inmunología , Proteínas de Neoplasias/inmunología , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Femenino , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Lectina 3 Similar a Ig de Unión al Ácido Siálico/genéticaRESUMEN
BACKGROUND: The optimal radiotherapy dose for locally advanced cervical esophageal squamous cell carcinoma (C-ESqCC) treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. Here, we aimed to compare the survival of those treated with high dose versus standard dose via a population based approach. METHODS: Eligible C-ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between high (60-70 Gy) and standard dose (50-50.4 Gy). We also evaluated the outcome in supplementary analyses via alternative approaches. RESULTS: Our primary analysis consisted of 141 patients in whom covariates were well balanced after PS weighting. The HR of death when high dose was compared with standard dose was 0.65 (95% confidence interval [CI]: 0.4-1.03, p = 0.07). The HR of IECM was 0.74 (p = 0.45). The HR of OS remained similarly insignificant in supplementary analyses. CONCLUSIONS: We observed a trend in favor of high radiotherapy dose versus standard dose for C-ESqCC treated with dCCRT in this population-based nonrandomized study. Further studies are needed to confirm the findings of the study.
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Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , CuelloRESUMEN
MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Desoxirribonucleasas/metabolismo , Factor Nuclear 3-beta del Hepatocito/metabolismo , Proteína Homóloga de MRE11/metabolismo , Neoplasias de la Boca/metabolismo , Receptores CXCR4/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Femenino , Xenoinjertos , Humanos , Proteína Homóloga de MRE11/genética , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/radioterapia , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tolerancia a Radiación , Transducción de Señal , Tasa de Supervivencia , Pez CebraRESUMEN
BACKGROUND: Diversity in the HLA genes might be associated with disease outcomes-the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). METHODS: We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus. RESULTS: Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend = 1.18â ×â 10-7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratioâ =â 1.40; 95% confidence interval, 1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control. CONCLUSIONS: Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Alelos , Carcinoma Hepatocelular/genética , Hepatitis B/complicaciones , Hepatitis B/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/genética , Humanos , Neoplasias Hepáticas/genéticaRESUMEN
BACKGROUND: The role of radiotherapy for cT4bNanyM0 esophageal squamous cell carcinoma (ESqCC) is relatively unclear, with both chemotherapy (C/T) alone and definitive concurrent chemoradiotherapy (dCCRT) being treatment options in the current guidelines. We aimed to compare the survival of dCCRT versus C/T for these patients via a population-based approach. METHODS: Eligible cT4b ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance the observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between dCCRT and C/T. We also evaluated OS in subgroups of either low or standard radiotherapy doses. RESULTS: Our primary analysis consisted of 247 patients in whom covariates were well balanced after PS weighing. The HR for death when dCCRT was compared with C/T was 0.36 (95% confidence interval 0.24-0.53, P < 0.001). Similar results were found for IECM. Statistical significance was only observed in the standard RT dose but not in the low dose in subgroup analyses. CONCLUSIONS: In this population-based nonrandomized study of cT4bNanyM0 ESqCC patients from Asia (Taiwan), we found that the use of radiotherapy with chemotherapy was associated with better overall survival than chemotherapy alone. Further studies (especially RCTs) are needed to confirm our findings.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Quimioradioterapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Humanos , Puntaje de Propensión , Taiwán/epidemiologíaRESUMEN
Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur-uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur-uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur-uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur-uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur-uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events.
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HYPOTHESIS: Whereas autophagy has been linked to various human diseases, whether it also plays a role in cholesteatoma is virtually unknown. This study aimed to investigate the activity and regulation of autophagy in cholesteatoma. BACKGROUND: The treatment of middle ear cholesteatoma has been challenging due to an insufficient understanding of the underlying disease mechanism. METHODS: Expression of microtubule-associated protein 1A/1B-light chain 3 (LC3), the autophagy protein marker, and phosphorylated Akt (p-Akt), and mammalian target of rapamycin (p-mTOR), the known autophagy regulators, in fresh retroauricular skin and cholesteatoma tissue samples was analyzed by immunoblotting. The results were further confirmed by immunohistochemistry and statistical analyses. Cell proliferation of primary retroauricular skin- and cholesteatoma-derived fibroblasts was evaluated by methyl thiazol tetrazolium (MTT) assay. Ectopic expression of serine proteinase inhibitor, clade B, member 3 (SERPINB3) in the fibroblasts was achieved by electroporation and the expression was detected by immunoblotting. RESULTS: LC3 expression was significantly decreased in cholesteatoma in most of the 15 paired retroauricular skin/cholesteatoma tissue samples. However, p-Akt and p-mTOR expression in the cholesteatoma samples was not significantly different from that in the control subjects. Immunohistochemical studies further demonstrated an inverse correlation between LC3 expression and cholesteatoma. The cholesteatoma fibroblasts proliferated faster than the retroauricular skin fibroblasts, and had higher SERPINB3 but lower LC3 expression. Furthermore, overexpression of SERPINB3 in the retroauricular skin fibroblasts enhanced cell proliferation and downregulated LC3 expression. CONCLUSION: Autophagy is significantly suppressed in cholesteatoma tissues, which may not involve the Akt/mTOR signaling pathway. More importantly, SERPINB3 may promote cell proliferation and negatively regulate autophagy in cholesteatoma fibroblasts. Together, these findings warrant further investigation into the pathogenic mechanism of cholesteatoma.
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Colesteatoma del Oído Medio , Autofagia , Fibroblastos/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVES: In current guidelines, early tongue cancer status post partial glossectomy without adverse risk features do not require adjuvant treatment. However, many of these patients developed recurrence with neck metastases soon. The objectives of this study were to investigate the potential risk factors in early tongue cancer that prophylactic management of neck may be considered. MATERIALS AND METHODS: From January 2010 to September 2015, this retrospective study enrolled 102 patients with T1-2N0 primary oral tongue squamous cell carcinoma according to AJCC 8th edition Cancer Staging System. All patients underwent partial glossectomy with or without selective neck dissection, and did not receive any adjuvant treatment. Patients with any adverse risk features were excluded. We have studied the 4-year cancer-specific survival and neck recurrence rate, and analyzed the relevance between pathologic tumor classification, tumor depth, tumor histologic grade, and measured surgical margin of primary tumor. RESULTS: The median follow up duration was 47â¯months (range 6-93â¯months) with the median recurrence interval was 13â¯months. Histologic grade ≥2 of primary tumor was significantly associated with increased risk of neck recurrence and disease-specific mortality in both univariate and multivariate analysis. CONCLUSION: Histologic grade ≥2 was an adverse prognostic factor of neck recurrence and was significantly associated with poor cancer-specific survival in T1-2N0 early oral tongue cancer patients. Therefore, prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck may be considered in T1-2N0 early oral tongue cancer with histologic grade ≥2 of primary tumor.
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Neoplasias de la Lengua/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) reduces overall treatment duration and results in less radiotherapy (RT)-induced dermatitis. However, the use of traditional sequential approach or IMRT-SIB is still under debate since there is not enough evidence of long-term clinical outcomes. The present study investigated 216 patients who underwent breast conserving surgery (BCS) between 2010 and 2013. The median age was 51 years (range, 21-81 years). All patients received IMRT-SIB, 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Among 216 patients, 175 patients received post-operative RT with forward IMRT and 41 patients had Tomotherapy. The median follow-up was 6.4 years. Forty patients (97.6%) in the Tomotherapy arm and 147 patients (84%) in the IMRT arm developed grade 0-1 skin toxicity (P = 0.021). For the entire cohort, the 5-year and 7-year overall survival (OS) rates were 94.4% and 93.1% respectively. The 7-year distant metastasis-free survival rates were 100% vs 89.1% in the Tomotherapy and IMRT arm respectively (P = 0.028). In conclusion, Tomotherapy improved acute skin toxicity compared with forward IMRT-SIB. Chronic skin complication was 1.9%. IMRT-SIB resulted in good long-term survival.
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Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Planificación de la Radioterapia Asistida por Computador , Radioterapia Guiada por Imagen , Radioterapia de Intensidad Modulada , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Mastectomía Segmentaria , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Tomografía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: This study investigated the impact of post-radiation sinusitis on the prognosis of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT). METHODS: Two hundred and thirty patients with non-metastatic NPC were analyzed in terms of freedom from local failure (FFLF), freedom from distant failure (FFDF), overall survival (OS), and disease-free survival (DFS). For each patient, the status of the sinus mucosa was flexibly assessed by documenting mucosal changes as indicated by differences between images obtained before radiotherapy and more than 6 months post-radiation. RESULTS: With a median follow-up of 39.7 months (8 to 81 months), 19 (8.26%) patients relapsed locally, 13 (5.65%) patients failed in the neck, and 26 (11.3%) patients developed distant metastases. The presence of sinusitis noted in images post-radiation was a significant predictor for DFS (p = 0.001), FFLF (p = 0.004), and FFDF (p = 0.015), in addition to having high negative predictive value for local relapse (97.5%). CONCLUSIONS: This is the first study to investigate the prognostic value of post-radiation sinusitis in NPC patients treated with IMRT. Post-radiation sinusitis was found to be a significant predictor for DFS, FFLF, and FFDF, and was also found to have high negative predictive value for local recurrence (97.5%). It may thus be used as an additional tool for clinicians to determine the possibility of recurrence.
Asunto(s)
Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/epidemiología , Traumatismos por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Sinusitis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Órganos en Riesgo/efectos de la radiación , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Glutamine is the primary fuel for the gastrointestinal epithelium and maintains the mucosal structure. Oncologists frequently encounter oral mucositis, which can cause unplanned breaks in radiotherapy (RT). OBJECTIVES: The aim of this study was to explore the association between oral glutamine and acute toxicities in patients with head and neck cancer undergoing RT. METHODS: This was a parallel, double-blind, randomized, placebo-controlled Phase III trial conducted in a university hospital. A central randomization center used computer-generated tables to allocate interventions to 71 patients with stages I-IV head and neck cancers. The patients, care providers, and investigators were blinded to the group assignment. Eligible patients received either oral glutamine (5 g glutamine and 10 g maltodextrin) or placebo (15 g maltodextrin) 3 times daily from 7 d before RT to 14 d after RT. The primary and secondary endpoints were radiation-induced oral mucositis and neck dermatitis, respectively. These were documented in agreement with the National Cancer Institute Common Terminology Criteria for Adverse Events version 3. RESULTS: The study included 64 patients (placebo n = 33; glutamine n = 31) who completed RT for the completers' analysis. Based on multivariate analysis, glutamine had no significant effect on the severity of oral mucositis (OR: 0.3; 95% CI: 0.05, 1.67; P = 0.169). Only the change in body mass index (BMI) was significant in both multivariate completers (OR: 0.41; 95% CI: 0.20, 0.84; P = 0.015) and per-protocol analysis (OR: 0.40; 95% CI: 0.20, 0.83; P = 0.014). No difference was found in the incidence and severity of neck dermatitis between the two arms. CONCLUSIONS: The decrease in BMI was strongly related to the severity of oral mucositis in the head and neck cancer patients under RT, but not to the use of glutamine. This trial was registered at clinicaltrials.gov as NCT03015077.