ABSTRACT
Approximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Metastasis , RNA Stability , RNA, Messenger , Receptor, Notch1 , Humans , Receptor, Notch1/metabolism , Receptor, Notch1/genetics , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/metabolism , Cell Line, Tumor , RNA, Messenger/metabolism , RNA, Messenger/genetics , Animals , Gene Expression Regulation, Neoplastic , Mice, Nude , Male , Female , Mice , Signal Transduction , Mice, Inbred BALB C , Up-Regulation/genetics , Carcinoma/metabolism , Carcinoma/genetics , Carcinoma/pathology , Middle AgedABSTRACT
There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.
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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
BACKGROUND: Identifying the target of natural killer (NK) cells in colorectal cancer (CRC) is critical for optimising the clinical use of NK cell-mediated immunotherapy. Mismatch repair deficiency (dMMR) is associated with high immune cell infiltration and MHC Class I defects. Whether dMMR CRC responses to NK cell therapy remains unclear. METHODS: MLH1, DR4, and DR5 knockout cell lines were established using CRISPR-Cas9 system. NK92-MI or NK cell isolated from BABL/C mice were used as effector cells against tumour cells. Inflammatory cytokines secretion by CRC cells was assessed via cytokine analysis. NK-cell-deficient/proficient animal models were used to validate the NK cell sensitivity. RESULTS: We observed that dMMR CRC cells were more sensitive to NK cell-mediated cytotoxicity than were mismatch-repair-proficient (pMMR) CRC cells. In dMMR CRC, Death receptor (DR)4/5 was upregulated and mediated sensitivity to NK cell-mediated cytotoxicity. DR4/5-mediated secretion of interleukin -12 sustained NK cell viability in dMMR CRC. NK cell depletion induced dMMR CRC tumour growth, and NK cell transfer inhibited lung metastasis of dMMR CRC with DR4/5 expression in vivo. TP53 upregulated DR4/DR5 expression in dMMR CRC. CONCLUSIONS: dMMR associated with increased sensitivity to NK cell-mediated cytotoxicity in CRC. DR4/DR5 sensitise dMMR CRC to NK cell-mediated cytotoxicity.
Subject(s)
Colorectal Neoplasms , Killer Cells, Natural , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Animals , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/immunology , Mice , Humans , Cell Line, Tumor , DNA Mismatch Repair , Cytotoxicity, Immunologic , Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics , Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism , MutL Protein Homolog 1/genetics , MutL Protein Homolog 1/deficiency , MutL Protein Homolog 1/metabolism , Mice, Inbred BALB C , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/immunology , Neoplastic Syndromes, Hereditary/pathology , Brain NeoplasmsSubject(s)
Acute Kidney Injury , Biomarkers , Cardiac Surgical Procedures , Postoperative Complications , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/blood , Humans , Biomarkers/blood , Cardiac Surgical Procedures/adverse effects , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Lipocalin-2/bloodABSTRACT
PURPOSE: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa). METHODS AND MATERIALS: Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/- NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein-Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS). RESULTS: Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. CONCLUSIONS: The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.
Subject(s)
Chemoradiotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoadjuvant Therapy , Neoplasm Staging , Humans , Male , Female , Aged , Chemoradiotherapy/methods , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Retrospective Studies , Disease-Free Survival , Comorbidity , Aged, 80 and over , Chemotherapy, AdjuvantABSTRACT
PURPOSE: PIK3CA mutation or overexpression is associated with immunotherapy resistance in multiple cancer types, but is also paradoxically associated with benefit of COX-2 inhibition on patient survival of colorectal cancer (CRC) with mismatch repair deficiency (dMMR). This study examined whether and how PIK3CA status affected COX-2-mediated tumor inflammation and immunotherapy response of dMMR CRC. METHODS: Murine colon cancer cells MC38, CT26, and CT26-Mlh1-KO were used to construct PIK3CA knockdown and overexpression models to mimic dMMR CRC with PIK3CA dysregulation, and xenograft models were used to evaluate how PIK3CA regulate COX-2 expression, CD8+ T cells infiltration, tumor growth, and therapy response to anti-PD-L1 treatment using immunocompetent mice. Western blot was carried out to delineate the signaling pathways in human and mouse cancer cells, and immunohistochemical analysis together with bioinformatics analysis using human patient samples. RESULTS: PIK3CA upregulates COX-2 expression through MEK/ERK signaling pathway independent of AKT signaling to promote tumor inflammation and immunosuppression. PIK3CA knockdown profoundly reduced CT26 tumor growth in a CD8+ T cell-dependent manner, while PIK3CA overexpression significantly inhibited CD8+ T cells infiltration and promoted tumor growth. Furthermore, MEK or COX-2 inhibition augmented the anti-tumor activity of anti-PD-L1 immunotherapy on dMMR CRC mouse models, accompanied with increased CD8+ T cells infiltration and activated tumor microenvironment. CONCLUSION: Our results identified that the PIK3CA hyperactivation in dMMR CRC upregulated COX-2 through MEK signaling, which inhibited CD8+ T cells infiltration and promoted tumor growth, together led to immunotherapy resistance. COX-2 or MEK inhibition may relieve therapy resistance and promote therapy efficacy of anti-PD-1/PD-L1 immunotherapy for treating dMMR CRC with PIK3CA overexpression or activating mutation.
Subject(s)
CD8-Positive T-Lymphocytes , Class I Phosphatidylinositol 3-Kinases , Colorectal Neoplasms , Cyclooxygenase 2 , Immunotherapy , Animals , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/therapy , Cyclooxygenase 2/metabolism , Humans , Cell Line, Tumor , Immunotherapy/methods , Mice , CD8-Positive T-Lymphocytes/immunology , B7-H1 Antigen/metabolism , DNA Mismatch Repair , Mice, Inbred BALB C , Female , Gene Expression Regulation, Neoplastic , MAP Kinase Signaling System , Signal Transduction , Brain Neoplasms , Neoplastic Syndromes, HereditarySubject(s)
Coronary Artery Bypass , Patient Discharge , Aged , Middle Aged , Humans , Follow-Up Studies , Arteries , Treatment Outcome , Postoperative ComplicationsABSTRACT
Background: Ovarian endometriomas, resulting from the invasion of endometriosis into ovarian tissue, can significantly affect ovarian reserve, potentially leading to infertility. When conservative treatments fail, it may further aggravate ovarian reserve decline by invading the ovarian cortex and, in severe cases, result in premature ovarian failure and infertility. Objective: This study aimed to investigate the impact of various hemostasis methods on ovarian reserve function in cases of laparoscopic cystectomy for ovarian endometriomas. Methods: We conducted a systematic review and meta-analysis to assess the effects of different hemostasis techniques used during laparoscopic cystectomy for ovarian endometriomas. A comprehensive analysis of relevant literature was performed, focusing on the impact of bipolar electrocoagulation, ultrasonic scalpel, and suture hemostasis on ovarian reserve function. The evaluation criteria included Anti-Müllerian hormone levels and antral follicle counts. Results: Our analysis revealed significant variations in the impact of hemostasis methods on ovarian reserve function. While all methods aimed to stop bleeding during surgery, the thermal damage to surrounding tissues differed. Bipolar electrocoagulation, ultrasonic scalpel, and suture hemostasis showed varying effects on ovarian reserve, with implications for post-operative fertility. Conclusions: The choice of the hemostasis method in laparoscopic cystectomy for ovarian endometriomas has a crucial influence on ovarian reserve function. Our findings emphasize the need to consider the potential consequences of thermal damage when selecting a hemostasis technique. Clinicians should weigh the benefits and risks of each method to protect ovarian reserve function effectively. This study offers valuable insights for guiding clinical practice, ensuring optimal outcomes for patients facing endometrioma-related fertility challenges.
ABSTRACT
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
BACKGROUND: Although the use of regorafenib plus nivolumab demonstrates promising outcomes in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC), this effect has not been substantiated in other studies. Moreover, a comparison between the outcomes of regorafenib and programmed cell death protein 1 (PD-1) antibody combination therapy and regorafenib monotherapy remains unexplored. In this study, we aimed to assess whether regorafenib and PD-1 antibody combination therapy is superior to regorafenib monotherapy as a third-line treatment for MSS mCRC. METHODS: Patients with MSS mCRC who received regorafenib and PD-1 antibody or regorafenib monotherapy as third-line treatment were eligible for inclusion. RESULTS: In total, 179 patients were enrolled, of which 84 were administered regorafenib combined with a PD-1 antibody and 95 were administered regorafenib monotherapy. Patients administered regorafenib combined with a PD-1 antibody had similar progression-free survival (PFS) as those on regorafenib monotherapy (median PFS was 2.4 months and 1.9 months, respectively, p = 0.086). The administration of regorafenib combined with a PD-1 antibody resulted in significantly longer PFS than that seen with regorafenib monotherapy in both male (5.2 months vs. 2.4 months, p = 0.001) and female (3.9 months vs. 1.8 months, p = 0.037) patients without liver metastasis. Female patients with liver metastasis who were administered regorafenib combined with a PD-1 antibody had shorter PFS than those administered regorafenib monotherapy (1.8 months vs. 2.0 months, p = 0.030). CONCLUSION: Liver metastasis and sex are predictors of survival benefit following the addition of a PD-1 antibody to regorafenib in patients with MSS mCRC.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Male , Female , Programmed Cell Death 1 Receptor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Phenylurea Compounds/therapeutic use , Liver Neoplasms/secondary , Microsatellite RepeatsABSTRACT
BACKGROUND: To assess the feasibility of adjusting radiation dose (RD) in childhood NPC with favorable tumor response after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Using an NPC-specific database, children and adolescents (≤18 years) with locoregionally advanced NPC (CA-LANPC) were retrospectively analyzed. Enrolled patients were those who received favorable tumor response after 2-4 cycles of NAC followed by concurrent chemoradiotherapy. Survival outcomes and treatment-related toxicities were compared for the standard RD on primary tumors (PT-RDstandard, 66-72 Gy) and the reduced RD on primary tumors (PT-RDreduced, 60-65.9 Gy). RESULTS: A total of 132 patients were included, and the median follow-up time was 75.2 months (IQR, 53.2-98.7 months) for the entire cohort. The PT-RDreduced group had a significantly decreased incidence of severe mucositis (51.3 % vs 32.1 %; P = 0.034) when compared to the PT-RDstandard group. The total incidence of severe sequela in the PT-RDstandard group were significantly higher than those in the PT-RDreduced group (31.8 % vs 13.7 %; P = 0.029). In the propensity-matched analysis, the PT-RDreduced group resulted in parallel 5-year survival with the PT-RDstandard group from the matched cohort (disease-free survival, 82.7 % vs 80.3 %, P = 0.841; overall survival, 91.7 % vs 91.3 %, P = 0.582; distant metastasis-free survival, 87.5 % vs 82.8 %, P = 0.573; and locoregional relapse-free survival, 95.6 % vs 97.3 %, P = 0.836). In multivariate analysis, the impact of PT-RDreduced on all survival end points remained insignificant. CONCLUSIONS: Chemoradiotherapy with RD at levels of 60-65.9 Gy may be a reasonable strategy for CA-LANPC with favorable tumor response after NAC.
Subject(s)
Nasopharyngeal Neoplasms , Neoadjuvant Therapy , Adolescent , Child , Humans , Nasopharyngeal Carcinoma/pathology , Neoadjuvant Therapy/adverse effects , Retrospective Studies , Feasibility Studies , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CisplatinABSTRACT
It is well known that plant growth, development, survival and geographical distribution are constrained by extreme climatic conditions, especially extreme low temperature. Under cold stress, cold-inducible promoters were identified as important molecular switches to transcriptionally regulate the initiation of genes associated with cold acclimation processes and enhance the adaptability of plants to cold stimulation. Wheat (Triticum aestivum L.) is one of the most dominating food crops in the world, and wheat crops are generally overwintering with strong cold resistance. Our previous study already proved that heterologous expression of wheat ice recrystallization inhibition (IRI) genes enhanced freezing tolerance in tobacco. However, the upstream regulatory mechanisms of TaIRI are ambiguous. In this study, the space-time specific expression of TaIRI genes in wheat was analyzed by quantitative real-time PCR (qRT-PCR), and results showed that the expression of TaIRI in all tissues was cold-induced and accelerate by exogenous methyl jasmonate (MeJA). Three promoters of TaIRI genes were isolated from wheat genome, and various 5'-deletion fragments of TaIRIp were integrated into ß-glucuronidase (GUS) within vector pCAMBIA1301. The promoter activity of TaIRI genes was determined through transient expression system of tobacco and stable expression of Arabidopsis thaliana. Results revealed that the GUS activity were significantly strengthened by cold and MeJA treatments. This study will provide insights into elucidating the transcription-regulatory mechanism of IRI proteins responding to low temperature.
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Allium mongolicum Regel is a wild and sandy vegetable with unique flavours. In this study, a complete chloroplast (cp) genome of A. mongolicum was obtained (Genbank accession number: OM630416), and contained 153,609 base pairs with the GC ratio as 36.8%. 130 genes were annotated including 84 protein-coding genes, 38 tRNA, and 8 rRNA genes. The large single-copy (LSC) region was 82,644 bp, and a small single-copy (SSC) region was 18,049 bp, which were separated by two inverted repeats (IRs, including IRa and IRb) of 26,458 bp. Comparative genome analyses of 55 Allium species suggested that genomic structure of genus Allium was conserved, and LSC and SSC regions were outstanding with high variability. Among them, more divergent loci were in the SSC region covering ycf1-rrn4.5 and ndhF-ccsA. Phylogenetic analysis on cp genomes of 55 Allium determined that all members were clustered into 13 clades, and A. mongolicum had close relationship with A. senescens. Corresponding analyses of four protein-coding genes (ycf1, ndhF, rpl32, and ccsA) in aforementioned divergent loci confirmed that ycf1 was finally chosen as the candidate gene for species identification and evolutionary classification of genus Allium. These data provide valuable genetic resources for future research on Allium.
Subject(s)
Allium , Genome, Chloroplast , Phylogeny , Allium/genetics , Chloroplasts/genetics , GenomicsABSTRACT
PURPOSE: To determine the sensitivity of a noncontrast T1 dispersion cardiovascular magnetic resonance technique for detecting diffuse fibrosis in hypertrophic cardiomyopathy (HCM). METHODS: Thirty-two adult HCM patients and ten age- and gender-matched healthy volunteers were prospectively included in this study. Patients and controls underwent cine, T1ρ-mapping, and pre- and post-contrast T1-mapping imaging using a 3-T magnetic resonance system. Myocardial extracellular volume fraction (ECV) maps were obtained using pre- and post-contrast T1 maps to determine reference values for diffuse fibrosis. Myocardial T1ρ and T1ρ dispersion maps called myocardial fibrosis index (mFI) maps provided 570 myocardial segments for Pearson or Spearman correlation analysis. The left ventricle myocardia of the HCM patients were divided into 16 segments that were further classified as either normal-thickness myocardium (<15 mm) (HCM-N) or hypertrophic myocardium (≥15 mm) (HCM-H). RESULTS: ECV and mFI values increased progressively on a per-segment basis from healthy controls to the HCM-N group and then to the HCM-H group (ECV: 27.4 ± 2.8% vs. 31.1 ± 4.2% vs. 37.6 ± 6.9%, respectively [P < 0.0001]; mFI: 6.1 ± 0.9 ms vs. 8 ± 1.9 ms vs. 11 ± 3.3 ms, respectively [P < 0.0001]). There was a strong positive correlation between the segmented ECV and the mFI (r = 0.878). The mFI was equally or significantly better than the ECV for differentiating fibrosis content in HCM-N and HCM-H according to their receiver operating characteristic curves. CONCLUSION: A T1ρ dispersion imaging mFI can sensitively detect diffuse myocardial fibrosis in HCM, even in HCM-N.
Subject(s)
Cardiomyopathies , Cardiomyopathy, Hypertrophic , Adult , Cardiomyopathies/pathology , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/pathology , Contrast Media , Fibrosis , Humans , Magnetic Resonance Imaging , Magnetic Resonance Imaging, Cine/methods , Magnetic Resonance Spectroscopy , Myocardium/pathology , Predictive Value of TestsABSTRACT
BACKGROUND: We aim to investigate the prognostic value of weight loss during radiotherapy (RT) among patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1149 NPC patients who received radical RT were retrospectively analyzed. Patients' weight were measured at initiation of RT (WPre-RT) and every week during RT (WRT1,2,3,4,5,6,7). Percentage of weight loss (PWL) at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT (RT-PWL1,2,3,4,5,6,7) were calculated using the following equation: (WPre-RT -WRT1,2,3,4,5,6,7)/WPre-RT × 100%. The optimal threshold of RT-PWL7 was determined by recursive partitioning analyses (RPAs). Our endpoints included disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS). RESULTS: The median RT-PWLs were 0, 0, 1.5, 2.9, 4.1, 5.5, 6.6% at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT, respectively. RT-PWL7 optimal threshold with respect to DFS was 5.3% based on RPAs. Therefore, a consistent threshold of 5% (<5% vs > ≥5%) was selected to classify NPC patients into low RT-PWL7 and high RT-PWL7 groups for survival analysis. Compared to high RT-PWL7 (≥5%), patients with low RT-PWL7 (< 5%) had significantly better ten-year DFS (61.2% vs 78.8%; P < 0.001), OS (70.1% vs 86.6%; P < 0.001), and DMFS (80.2% vs 88.5%; P = 0.007). However, no difference was observed between LRRFS groups (91.7% vs 94.3%; P = 0.173). In multivariate analysis, high RT-PWL7 was an independent risk factor for DFS (HR, 1.56; 95%CI, 1.19-2.03; P = 0.001), OS (HR, 1.54; 95%CI, 1.11-2.15; P = 0.011), and DMFS (HR, 1.47; 95%CI, 1.03-2.10; P = 0.033) in patients with NPC. In addition, treatment strategy, plasma Epstein-Barr virus DNA, and N stage were associated with weight loss. CONCLUSIONS: High RT-PWL7 was significantly associated with decreased DFS, OS, and DMFS for NPC patients. Clinicians should continuously inform patients on the health impact of minimizing RT-PWL7 under 5% during radiotherapy.
Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Cohort Studies , Disease-Free Survival , Herpesvirus 4, Human/genetics , Humans , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local/complications , Prognosis , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Weight LossABSTRACT
BACKGROUND: To assess the prognostic value of the systemic inflammation response index (SIRI) combined with plasma load of Epstein-Barr virus (EBV) DNA in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC). METHODS: A total of 205 consecutive patients with CALANPC were enrolled. We used recursive partitioning analysis (RPA) to classify patients into various risk groups, with a primary endpoint of overall survival (OS). RESULTS: Elevated SIRI (≥1.53) and EBV DNA (≥4000 copy/ml) were significantly associated with inferior OS in CALANPC. RPA categorized patients into low- and high-risk groups based on prognostic factors. Survival curves showed excellent discrimination in OS (95.3% vs 77.6%; p < 0.001) between the low- and high-risk groups. A significant improvement was confirmed using the prognostic methods for conventional TNM staging systems (p < 0.05). CONCLUSIONS: The combination of SIRI with EBV DNA provided a more detailed understanding of patient risks, and enhanced risk discrimination in CALANPC.
Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Adolescent , Child , DNA, Viral , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/genetics , Humans , Inflammation , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/pathology , PrognosisABSTRACT
PURPOSE: To quantify and predict the survival benefits of cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC). MATERIALS AND METHODS: Patients with CA-LANPC who received first-line neoadjuvant chemotherapy (NAC) followed by concurrent chemoradiotherapy (CCRT) between September 2007 and April 2018 were evaluated. Recursive partitioning analyses (RPAs) helped identify the ideal thresholds of CC-CCD on disease-free survival (DFS). We then developed a web-based predictive model to quantify the survival benefit of CC-CCD for CA-LANPC. RESULTS: In total, 139 patients were eligible for the analysis. The median CC-CCD was 162 mg/m2 (IQR, 138-192 mg/m2). The optimum cut-off point of CC-CCD was 160 mg/m2 for DFS. Hence, we selected 160 mg/m2 as the cut-off to classify CA-LANPC into either high or low CC-CCD groups for survival analysis. The 5-year DFS rates were 91.6% in the high (≥160 mg/m2) CC-CCD group and 77.8% in the low (<160 mg/m2) CC-CCD group (P = 0.011). Multivariate analysis indicated CC-CCD (HR, 0.34; 95%CI, 0.13-0.87; P = 0.024), T stage (HR, 3.72; 95%CI, 1.35-10.22; P = 0.011), and EBV DNA (HR, 3.00; 95%CI, 1.00-8.97; P = 0.049) were independent prognostic factors and were incorporated into the prognostic model. N stage was also included due to its clinical importance. The predictive model was demonstrably accurate (C-index, 0.741) when predicting 5-year DFS rates. CONCLUSIONS: We built a predictive model to quantify the survival benefit of CC-CCD for CA-LANPC treated with NAC plus CCRT. This tool may improve individual treatment consultations and facilitate evidence-based decision-making.