ABSTRACT
BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC
Subject(s)
Chemoradiotherapy , Induction Chemotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Propensity Score , Humans , Male , Female , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/drug therapy , Middle Aged , Chemoradiotherapy/methods , Adult , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/drug therapy , Induction Chemotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Immune Checkpoint Inhibitors/therapeutic use , Aged , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Deoxycytidine/administration & dosage , Retrospective Studies , GemcitabineABSTRACT
OBJECTIVES: To compare neoadjuvant chemotherapy (NAC) plus concurrent chemoradiotherapy (CCRT) to CCRT alone in children and adolescents (age ≤ 18 years) with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC, stage III-IVA). MATERIALS AND METHODS: 195 CA-LANPC patients who were treated through CCRT with or without NAC between 2008 and 2018 were enrolled in this study. A matched cohort composed of CCRT patients and NAC-CCRT patients was generated by propensity score matching (PSM) at a 1:2 ratio. Survival outcomes and toxicities were compared between the CCRT group and NAC-CCRT group. RESULTS: Of the 195 patients, 158 (81%) received NAC plus CCRT, and 37 (19%) received CCRT alone. The NAC-CCRT group had higher EBV DNA levels (≥ 4000 copy/mL), more advanced TNM stage (stage IV disease), and lower incidence of a high radiation dose (> 6600 cGy) than the CCRT group. To avoid bias in treatment selection within retrospectively analysis, 34 patients from the CCRT group were matched with 68 patients from the NAC-CCRT group. In the matched cohort, the 5-year DMFS rate was 94.0% in the NAC-CCRT group versus 82.4% in the CCRT group, with marginal statistical significance (HR = 0.31; 95%CI 0.09-1.10; P = 0.055). During treatment, the accumulate incidence of severe acute toxicities (65.8% vs 45.9%; P = 0.037) in the NAC-CCRT group was higher than the CCRT group. However, the CCRT group had significantly higher accumulate incidence of severe late toxicities (30.3% vs 16.8%; P = 0.041) than the NAC-CCRT group. CONCLUSIONS: Addition of NAC to CCRT tended to improve long-term DMFS in CA-LANPC patients with acceptable toxicity. However, relative randomized clinical trial is still needed in the future.
Subject(s)
Nasopharyngeal Neoplasms , Neoadjuvant Therapy , Adolescent , Humans , Child , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Cohort Studies , Retrospective Studies , Propensity Score , Nasopharyngeal Neoplasms/drug therapy , Chemoradiotherapy , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
OBJECTIVES: To investigate the role of focal adhesion kinase (FAK) in the pathogenesis of cardiac hypertrophy induced by hypertension. METHODS: Using immunofluorescent labeling, confocal microscopy and Western blotting, the expression and subcellular localization of FAK in the cardiac myocytes of left ventricle were determined in 2, 6, 12, and 18 month-old rats with spontaneously hypertensive heart failure (SHHF) along with age-matched control Wistar-Kyoto (WKY) rats. RESULTS: There was no significant difference of FAK expression between 2 month-old SHHF and WKY rats (50.5+/-6.9 vs. 49.8+/-5.0, n=6, P>0.05). In contrast with the control groups, the expression of FAK significantly increased in 6, 12 and 18 month-old SHHF rats (130.6+/-3.0 vs. 47.3+/-1.3, 144.7+/-5.4 vs. 46.4+/-3.1, 141.4+/-9.8 vs. 48.5+/-2.2, each groups n=6, P<0.05) with FAK protein primarily cumulated in the intercalated disks and nuclei. CONCLUSIONS: FAK may play a role in the cell signaling transduction leading to cardiac hypertrophy, presumably through regulations of hypertrophic gene transcription and RNA processing.