Prognostic nutritional score based on pretreatment lymphocyte, platelet, and prealbumin predicts prognosis in patients with pancreatic cancer.

BACKGROUND AND OBJECTIVES: Pretreatment immunological indicators and nutritional factors are associated with survival of many malignancies. This study aims to develop a prognostic nutritional score based on a combination of pretreatment lymphocyte, platelet, and prealbumin (Co-LPPa) in patients with pancreatic cancer (PC) and to investigate the prognostic significance of this score. METHODS: Patients who underwent pancreatectomy with a curative intent for PC were retrospectively enrolled. A pretreatment prognostic score was established by immunological indicators and nutritional factors that were independently associated with survival. RESULTS: Pretreatment lymphocyte (<1.6 × 109 /L), platelet (<160 × 109 /L) and prealbumin (<0.23 g/L) were independently associated with poorer overall survival (OS) and recurrence-free survival (RFS), and were used to create the Co-LPPa score. The Co-LPPa scores were inversely related to OS and RFS, and were able to stratify survival into four groups. The survival differences among the four groups were all significant. Besides, the Co-LPPa scores could stratify survival independently of pathological prognostic factors. The Co-LPPa score was superior to prognostic nutritional index and carbohydrate antigen 19-9 in predicting OS and RFS. CONCLUSION: The Co-LPPa score could accurately predict the prognosis of PC patients who underwent curative resection. The score may be helpful for preoperative therapeutic strategies.

Endoscopic ultrasound-guided gallbladder endoscopic mucosal resection: a pilot porcine study.

INTRODUCTION: Endoscopic ultrasound (EUS)-guided natural orifice transluminal gallbladder polypectomy provides a minimally invasive alternative to cholecystectomy. The study aimed to investigate the feasibility and safety of protocol for gallbladder endoscopic mucosal resection (gEMR) under EUS guidance using a porcine model. MATERIAL AND METHODS: Fifteen Bama mini pigs were randomly divided into the control (CG, n = 3) and experimental (EG, n = 12) groups. EUS-guided fine needle aspiration was performed in the CG and used to establish a gallbladder pathway for polyp resection under EUS guidance in the EG. Procedural safety was evaluated using routine blood and biochemical tests, microbial bile cultures, histopathological tests, and enzyme-linked immunosorbent assays for inflammatory adhesion factors. RESULTS: EUS-guided metal stents were successfully deployed in all 12 pigs. Two cases of stent displacement occurred postoperatively, and one pig died of infectious peritonitis on the first day after stent implantation. In 11 surviving experimental animals, mature gallbladder paths were formed at 7-14 days after gastro-cholecystostomy, through which gEMR of gallbladder polyps was successfully performed. There were no significant changes in levels of inflammatory and adhesion factors during the postoperative process. CONCLUSIONS: EUS-gEMR may be a safe and effective minimally invasive treatment approach for gallbladder polyps.

Activin A induces growth arrest through a SMAD- dependent pathway in hepatic progenitor cells.

BACKGROUND: Activin A, an important member of transforming growth factor-ß superfamily, is reported to inhibit proliferation of mature hepatocyte. However, the effect of activin A on growth of hepatic progenitor cells is not fully understood. To that end, we attempted to evaluate the potential role of activin A in the regulation of hepatic progenitor cell proliferation. RESULTS: Using the 2-acetaminofluorene/partial hepatectomy model, activin A expression decreased immediately after partial hepatectomy and then increased from the 9th to 15th day post surgery, which is associated with the attenuation of oval cell proliferation. Activin A inhibited oval cell line LE6 growth via activating the SMAD signaling pathway, which manifested as the phosphorylation of SMAD2/3, the inhibition of Rb phosphorylation, the suppression of cyclinD1 and cyclinE, and the promotion of p21WAF1/Cip1 and p15INK4B expression. Treatment with activin A antagonist follistatin or blocking SMAD signaling could diminish the anti-proliferative effect of activin A. By contrast, inhibition of the MAPK pathway did not contribute to this effect. Antagonizing activin A activity by follistatin administration enhanced oval cell proliferation in the 2-acetylaminofluorene/partial hepatectomy model. CONCLUSION: Activin A, acting through the SMAD pathway, negatively regulates the proliferation of hepatic progenitor cells.

Nomogram model for predicting early recurrence for resectable pancreatic cancer: A multicenter study.

Pancreatic cancer is a highly aggressive malignancy that is characterized by early metastasis, high recurrence, and therapy resistance. Early recurrence after surgery is one of the important reasons affecting the prognosis of pancreatic cancer. This study aimed to establish an accurate preoperative nomogram model for predicting early recurrence (ER) for resectable pancreatic adenocarcinoma. We retrospectively analyzed patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2011 and December 2020. The training set consisted of 604 patients, while the validation set included 222 patients. Survival was estimated using Kaplan-Meier curves. The factors influencing early recurrence of resectable pancreatic cancer after surgery were investigated, then the predictive model for early recurrence was established, and subsequently the predictive model was validated based on the data of the validation group. The preoperative risk factors for ER included a Charlson age-comorbidity index ≥ 4 (odds ratio [OR]: 0.628), tumor size > 3.0 cm on computed tomography (OR: 0.628), presence of clinical symptoms (OR: 0.515), carbohydrate antigen 19-9 > 181.3 U/mL (OR 0.396), and carcinoembryonic antigen > 6.01 (OR: 0.440). The area under the curve (AUC) of the predictive model in the training group was 0.711 (95% confidence interval: 0.669-0.752), while it reached 0.730 (95% CI: 0.663-0.797) in the validation group. The predictive model may enable the prediction of the risk of postoperative ER in patients with resectable pancreatic ductal adenocarcinoma, thereby optimizing preoperative decision-making for effective treatment.

EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells.

Epidermal growth factor receptor substrate 15 (EPS15) is part of the EGFR pathway and has been implicated in various tumorigenesis. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an essential role in liver hepatocellular carcinoma (LIHC) by regulating the expression of proteins and genes. Through analysis of the cancer genome atlas (TCGA) database, we found that EPS15 is highly expressed in LIHC tissue, and lncRNA EPS15-antisense1 (EPS15-AS1) decreased in LIHC cell lines. However, the function of EPS15-AS1 in LIHC is still unknown. When EPS15-AS1 was overexpressed in HepG2 cell lines, the expression of EPS15 was reduced and cell activity and invasiveness were inhibited. In addition, we observed an increase in Fe2+ ion and lipid peroxidation after overexpression of EPS15-AS1, and further analysis showed that the susceptibility to ferroptosis increased. Aldo-keto reductase family 1 member B 1 (AKR1B1) belongs to the aldo/keto reductase superfamily and is involved in maintaining the cellular redox balance. Survival analysis revealed that patients with a higher level of AKR1B1 have a lower survival rate in the TCGA database. We also found that EPS15 enhanced the AKR1B1 expression in LIHC, and AKR1B1 had the ability to promote cell invasiveness. Moreover, overexpression of AKR1B1 alleviated the promoting effect of EPS15-AS1 on ferroptosis. Therefore, EPS15-AS1 can induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of EPS15 and AKR1B1 and disrupting the redox balance. EPS15 and AKR1B1 may serve as biomarkers for diagnosis and lncRNA EPS15-AS1 potential drug for LIHC.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma.

OBJECTIVE: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains uncertain. METHODS: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy (GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated. RESULTS: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival (OS) and recurrence-free survival (RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-node-metastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS. CONCLUSIONS: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Presence of tumor deposits is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma.

Tumor deposits (TDs) are associated with poor prognosis in several malignancies and have been incorporated into the tumor-node-metastasis (TNM) staging system for colorectal cancer. This study aims to explore the significance of TDs in pancreatic ductal adenocarcinoma (PDAC). All patients who underwent pancreatectomy with a curative intent for PDAC were retrospectively enrolled. Patients were categorized into 2 groups according to the status of TDs: the positive group, in which TDs were present, and the negative group, in which TDs were absent. The prognostic significance of TDs was evaluated. In addition, a modified staging system was developed by incorporating TDs into the eighth edition of the TNM staging system. One hundred nine (17.8%) patients had TDs. Patients with TDs demonstrated significantly lower 5-year overall survival (OS) and recurrence-free survival (RFS) rates than those without TDs (OS: 9.1% vs. 21.5%, P=0.001; RFS: 6.1% vs. 16.7%, P<0.001). Even after matching, patients with TDs still had significantly worse OS and RFS than those without TDs. In the multivariate analysis, the presence of TDs was an independent prognostic factor in patients with PDAC. The survival of patients with TDs was similar to that of patients with N2 stage disease. The modified staging system had a greater Harrell's C-index than the TNM staging system, which indicates better performance in predicting survival. The presence of TDs was an independent prognostic factor for PDAC. Categorizing patients with TDs into N2 stage improved the accuracy of the TNM staging system in predicting prognosis.

Biological risk based on preoperative serum CA19-9 and histological grade predicts prognosis and improves accuracy of classification in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Carbohydrate antigen (CA) 19-9 and histological grade can serve as indicators of the biological characteristics of pancreatic ductal adenocarcinoma (PDAC). AIMS: The aim of this study was to investigate the combined impact of preoperative CA19-9 levels and histological grade on prognosis and classification accuracy in PDAC patients. METHODS AND RESULTS: A retrospective cohort study was conducted on 612 patients with PDAC who underwent curative pancreatectomy, and a biological risk model based on preoperative CA19-9 levels and histology grade was established. The prognostic importance of the biological risk model was evaluated, and its validity was confirmed through a validation cohort of 218 patients. The survival of patients with PDAC was independently associated with preoperative CA19-9 levels and histology grade, indicating a biological risk. This biological risk was incorporated into the eighth edition of the TNM staging system, leading to the development of a modified TNM (mTNM) staging system. Receiver operating characteristic (ROC) curves demonstrated that the mTNM staging system had a significantly larger area under the curve (AUC) than the TNM staging system. The discriminatory capacity of the mTNM staging system was further validated in an independent cohort. CONCLUSION: Biological risk based on preoperative CA19-9 and histological grade could predict the survival of patients with PDAC. The incorporation of biological risk into the TNM staging system has the potential to enhance the accuracy of patient classification in PDAC, predicting patient survival and enabling the development of individualized treatment plans.

Artificial intelligence-based comprehensive analysis of immune-stemness-tumor budding profile to predict survival of patients with pancreatic adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. CD8+ T cells, cancer stem cells (CSCs), and tumor budding (TB) have been significantly correlated with the outcome of patients with PDAC, but the correlations have been independently reported. In addition, no integrated immune-CSC-TB profile for predicting survival in patients with PDAC has been established. METHODS: Multiplexed immunofluorescence and artificial intelligence (AI)-based comprehensive analyses were used for quantification and spatial distribution analysis of CD8+ T cells, CD133+ CSCs, and TB. In vivo humanized patient-derived xenograft (PDX) models were established. Nomogram analysis, calibration curve, time-dependent receiver operating characteristic curve, and decision curve analyses were performed using R software. RESULTS: The established 'anti-/pro-tumor' models showed that the CD8+ T cell/TB, CD8+ T cell/CD133+ CSC, TB-adjacent CD8+ T cell, and CD133+ CSC-adjacent CD8+ T cell indices were positively associated with survival of patients with PDAC. These findings were validated using PDX-transplanted humanized mouse models. An integrated nomogram-based immune-CSC-TB profile that included the CD8+ T cell/TB and CD8+ T cell/CD133+ CSC indices was established and shown to be superior to the tumor-node-metastasis stage model in predicting survival of patients with PDAC. CONCLUSIONS: 'Anti-/pro-tumor' models and the spatial relationship among CD8+ T cells, CSCs, and TB within the tumor microenvironment were investigated. Novel strategies to predict the prognosis of patients with PDAC were established using AI-based comprehensive analysis and machine learning workflow. The nomogram-based immune-CSC-TB profile can provide accurate prognosis prediction for patients with PDAC.

A new staging system for postoperative prognostication in pancreatic ductal adenocarcinoma.

The current TNM staging system for pancreatic ductal adenocarcinoma (PDAC) has revised the definitions of T and N categories as well as stage groups. However, studies validating these modifications have yielded inconsistent results. The existing TNM staging system in prognostic prediction remains unsatisfactory. The prognosis of PDAC is closely associated with pathological and biological factors. Herein, we propose a new staging system incorporating distant metastasis, postoperative serum levels of CA19-9 and CEA, tumor size, lymph node metastasis, lymphovascular involvement, and perineural invasion to enhance the accuracy of prognosis assessment. The proposed staging system exhibited a strong correlation with both overall survival and recurrence-free survival, effectively stratifying survival into five distinct tiers. Additionally, it had favorable discrimination and calibration. Thus, the proposed staging system demonstrates superior prognostic performance compared to the TNM staging system, and can serve as a valuable complementary tool to address the limitations of TNM staging in prognostication.

Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis.

BACKGROUND: Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance. METHODS: We established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editing, sphere formation assays, iron assays and luciferase assays were conducted to elucidate the mechanism. RESULTS: High-throughput drug screening of chemotherapy-resistant PDOs identified irbesartan, an angiotensin ‖ type 1 (AT1) receptor antagonist, which could synergistically enhance the ability of chemotherapy to kill PDAC cells. In vitro and in vivo validation using PDO, PDX and KPC mouse models showed that irbesartan efficiently sensitized PDAC tumors to chemotherapy. Mechanistically, we found that irbesartan decreased c-Jun expression by inhibiting the Hippo/YAP1 pathway and further overcame chemotherapy resistance in PDAC. We also explored c-Jun, a potential target of irbesartan, which can transcriptionally upregulate the expression of key genes involved in stemness maintenance (SOX9/SOX2/OCT4) and iron metabolism (FTH1/FTL/TFRC). More importantly, we observed that PDAC patients with high levels of c-Jun expression demonstrated poor responses to the current standard chemotherapy regimen (gemcitabine plus nab-paclitaxel). Moreover, patients with PDAC had significant survival benefits from treatment with irbesartan plus a standard chemotherapy regimen in two-center retrospective clinical cohorts and patients with high c-Jun expression exhibited a better response to combination chemotherapy. CONCLUSIONS: Irbesartan could be used in combination with chemotherapy to improve the therapeutic efficacy in PDAC patients with high levels of c-Jun expression. Irbesartan effectively inhibited chemotherapy resistance by suppressing the Hippo/YAP1/c-Jun/stemness/iron metabolism axis. Based on our findings, we are designing an investigator-initiated phase II clinical trial on the efficacy and safety of irbesartan plus a standard gemcitabine/nab-paclitaxel regimen in the treatment of patients with advanced III/IV staged PDAC and are hopeful that we will observe patient benefits.

Salvage endoscopic nasopharyngectomy and intensity-modulated radiotherapy versus conventional radiotherapy in treating locally recurrent nasopharyngeal carcinoma.

BACKGROUND: Although endoscopic nasopharyngectomy and intensity-modulated radiotherapy (IMRT) have been reported to be useful in treating isolated local recurrent nasopharyngeal carcinoma (NPC), their efficacy needs to be revaluated with comparison to 2D conventional radiotherapy (RT). METHODS: Four hundred ten patients with recurrent NPC were retrospectively analyzed, among whom the patients underwent IMRT, endoscopic nasopharyngectomy, and 2D conventional RT. RESULTS: The 5-year overall survival (OS) and distant metastasis-free survival were significantly higher in endoscopic nasopharyngectomy and IMRT groups than in 2D conventional RT group both in the entire series and in the subgroup of patients with recurrent T1 to 2 NPC (p < .05), except in the subgroup of recurrent T3 to 4 stratifications (IMRT vs 2D conventional RT; 28.8% vs 16.8%; p = .351). Furthermore, endoscopic nasopharyngectomy was associated with better OS than IMRT in the recurrent T1 to 2 subgroup (79.2% vs 62.1%; p = .007). Multivariate analysis indicated therapeutic modality was an independent predictor of OS and distant metastasis-free survival (p < .001). CONCLUSION: Endoscopic nasopharyngectomy and IMRT are associated with an improved OS and distant metastasis-free survival of patients with recurrent NPC compared to 2D conventional RT in early recurrent disease.

[Synthesis and radiopharmacology of S-(2-18F-fluoroethyl)-L-methionine for tumor imaging].

AIM: To develop S-(2-18F-fluoroethyl)-L-methionine (18FEMET) as an amino acid positron emission tomography (PET) tracer for tumors, and to evaluate the value of 18FEMET in the differentiation of experimental tumor and experimental inflammation. METHODS: 18FEMET was prepared by nucleophilic fluorination reaction via a two-step procedure. Biodistribution of 18FEMET in normal mice, carcinoma-bearing mice and inflammatory mice, and 18FEMET PET imaging for carcinoma-bearing mice and inflammatory mice were performed compared with 2-[18F] fluoro-2-deoxy-D-glucose (FDG) and O-(2-[18F] fluoroethyl)-L-tyrosine (FET). RESULTS: The overall radiochemical yield with no decay correction was 15%-25%, the whole synthesis time was about 70 min by manual operation, and the radiochemical purity was above 95%. High uptake and long retention of 18FEMET in pancreas, kidney, colon, liver and heart were observed. But low uptakes in brain and blood were found. Furthermore, high uptake of 18FEMET, FDG and FET in tumor, high uptake of FDG in inflammatory tissue, and almost no uptake of 18FEMET and FET in inflammatory tissue were also observed. CONCLUSION: 18FEMET is easy to prepare and can be used to differentiate between tumor and inflammatory tissue. It seems to be a potential amino acid tracer for tumors with PET imaging.

A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

The aim of this randomized study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) for patients with locoregionally advanced nasopharyngeal carcinoma. From August 2002 to April 2005, 408 patients were randomly divided into two groups: an IC+CCRT group and an IC+RT group. Patients in both groups received the same induction chemotherapy: two cycles of floxuridine (FuDR)+carboplatin (FuDR, 750 mg/m(2), d1-5; carboplatin, area under the curve [AUC]=6). The patients received radiotherapy 1 week after they finished the induction chemotherapy. The patients in the IC+CCRT group also received carboplatin (AUC=6) on days 7, 28, and 49 of radiotherapy. Eight patients did not meet the inclusion criteria, and the remaining 400 cases were analyzed. Grade III or IV toxicity was found in 28.4% of the patients in the IC+CCRT group and 13.1% of those in the IC+RT group (P<.001). Five-year overall survival rates were 70.3% and 71.7% (P=0.734) in the IC+CCRT and IC+RT groups, respectively. No significant differences in failure-free survival, locoregional control, and distant control were found between the two groups. Compared with the IC+RT program, the IC+CCRT program used in the present study did not improve the overall survival and failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma. Using carboplatin in the concurrent chemoradiotherapy was not suitable for nasopharyngeal carcinoma.

Polymorphisms in the endothelin-1 and endothelin a receptor genes and survival in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: We aimed to investigate the prognostic role of endothelin-1 (EDN1) and endothelin A receptor (EDNRA) gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). EXPERIMENTAL DESIGN: Two hundred three consecutive patients with locoregionally advanced NPC were enrolled. Seven potentially functional polymorphisms in the EDN1 and EDNRA genes were determined by ligase detection reaction-PCR method from prospectively collected blood samples. The influence of the genetic polymorphisms on patient overall survival (OS) was analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test. RESULTS: The 5-year OS in patients with EDNRA/H323H TT, TC, and CC genotypes were 81.3%, 62.1%, and 75.0%, respectively (P = 0.004). Patients carrying the heterozygous (TC) or homozygous variant (CC) genotype in EDNRA/H323H were combined for analysis, which revealed that the 5-year OS in patients with TC/CC genotypes was significantly lower than those with the wild-type TT genotype (63.2% vs. 81.3%; P = 0.002). Multivariate analysis showed that EDNRA/H323H polymorphism (HR: 1.95; 95% CI: 1.18-3.23; P = 0.009) and N classification (HR: 1.35; 95% CI: 1.03-1.79; P = 0.03) were independent significant prognostic factors for OS in patients with locoregionally advanced NPC. In contrast, the EDN1 polymorphisms revealed no prognostic value. CONCLUSIONS: The EDNRA/H323H polymorphism was a novel and independent prognostic marker for patients with locoregionally advanced NPC. The analysis of EDNRA/H323H polymorphism may help identify patient subgroups at high risk for poor disease outcome.

Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown. METHODS: Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m(2) on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to-treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the χ(2) test. All statistical tests were two-sided. RESULTS: With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly. CONCLUSION: Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC.

Prognostic implication of pretreatment titer of serum immunoglobulin A against Epstein-Barr virus capsid antigen in nasopharyngeal carcinoma patients in Sihui, Guangdong.

BACKGROUND AND OBJECTIVE: Currently, the serum immunoglobulin A against Epstein-Barr virus capsid antigen (EBV-VCA/IgA) is one of the most commonly used markers for diagnosis of nasopharyngeal carcinoma (NPC). However, its value for prognostic implication in NPC patients is unclear. This study was to evaluate the relationship between pretreatment titers of EBV-VCA/IgA and NPC patients' survival. METHODS: The clinicopathologic data of 317 NPC patients treated in Sun Yat-sen University Cancer Center between 1990 and 2003 were retrieved from the registration system of cancer incidence and mortality of Sihui city, Guangdong province. The correlation of pretreatment EBV-VCA/IgA titers to the survival of these patients was analyzed. RESULTS: Pretreatment VCA/IgA titer was significantly higher in stage III-IV NPC patients than in stage I-II patients (p = 0.01). The survival time was significantly shorter in the 170 patients with higher EBV-VCA/IgA titers (>or= 1:160) than in the 147 patients with lower EBV-VCA/IgA titers ( < 1:160). The 5-year survival rate was 65% in low EBV-VCA/IgA titer group and 43% in high titer group (p = 0.01). Multivariate analyses showed that clinical stage, sex, the year of treatment, and pretreatment serum EBV-VCA/IgA titer were all independent prognostic factors of NPC. CONCLUSION: Pretreatment serum EBV-VCA/IgA titer may be used as an independent prognostic marker of NPC.

Endoscopic microwave coagulation therapy for early recurrent T1 nasopharyngeal carcinoma.

The result of reirradiation in recurrent T1 (rT1) nasopharyngeal carcinoma (NPC) is unsatisfactory. We sought to study the efficacy and complications of endoscopic microwave coagulation therapy (MCT) in salvaging rT1 NPC after primary radiotherapy. Between August 1994 and April 2005, 55 patients with rT1 NPC were treated with endoscopic MCT. With a median follow-up of 102.1 months, 52 of 55 patients are still alive. Five patients had local failure after retreatment. The overall survival and local progression-free survival were 100% (95% CI, 99.4% to 100%) and 94.5% (95% CI, 94.1% to 94.9%) at 2 years, respectively, and 93.6% (95% CI, 93.5% to 94.4%) and 90.7% (95% CI, 90.2% to 91.2%) at 5 years. The common complications of endoscopic MCT were mild postoperative pain and headache. Nasopharyngeal necrosis was transient in one patient and subsided in 1 month. Endoscopic MCT achieved significant survival and tumour control without severe complications in selective rT1 NPC.

Induction-concurrent chemoradiotherapy versus induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: Induction chemotherapy and radiotherapy or concurrent chemoradiotherapy are the most two effective treatments for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to compare the efficacy of induction-concurrent chemoradiotherapy versus induction chemotherapy and radiotherapy for patients with locoregionally advanced NPC. METHODS: From August 2002 to April 2005, 408 patients were randomly divided into the induction-concurrent chemoradiotherapy (IC/CCRT) group and the induction chemotherapy and radiotherapy (IC/RT) group. Patients in both groups received the same induction chemotherapy, including two cycles of floxuridine (FuDR) plus carboplatin (FuDR750 mg/m2, d1-5; carboplatin AUC=6). All the patients underwent radiotherapy one week after completing the induction chemotherapy. The patients in the IC/CCRT group also received carboplatin (AUC=6) on day 7, 28, and 49 during radiotherapy. Eight patients did not meet the inclusion criteria and were excluded. The remaining 400 cases were analyzed. RESULTS: Grade III/IV toxicity was found in 28.4% of the patients in the IC/CCRT group and 13.1% in the IC/RT group (P < 0.001). After a median follow up time of 3.9 years, the three-year overall survival was 75.9% and 83.4% (P = 0.12) in the IC/CCRT and IC/RT groups, respectively. No significant differences in the failure-free survival rate, the locoregional control rate, and the distant control rate were found between the two groups. CONCLUSION: The IC/CCRT program does not improve the overall survival rate in patients with locoregionally advanced NPC compared with the IC/RT program.

[Endoscopic microwave coagulation therapy for locally recurrent nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Management of locally recurrent nasopharyngeal carcinoma (NPC) is difficult. External beam re-irradiation could cure some patients but might cause severe radiation injury. This study was to evaluate the clinical value of endoscopic microwave coagulation therapy as salvage treatment for locally recurrent NPC. METHODS: Between Aug. 1994 and Apr. 2005, 55 patients with locally recurrent NPC (stage rT1) were treated with endoscopic microwave coagulation therapy. Local progression-free and overall survival were observed. RESULTS: The median follow-up was 102.1 months (range, 22.4-153.9 months). The median time from last irradiation to recurrence was 22.1 months (range, 6.5-125.6 months). Five patients had local failure. The 5-year local progression-free and overall survival rates were 90.7% and 93.6%, respectively. No patient had intraoperative complications. One patient had nasopharyngeal necrosis after operation, and was healed after one month. CONCLUSIONS: Endoscopic microwave coagulation therapy is effective without severe complications in locally recurrent NPC patients. It is a minimally invasive therapy for recurrent NPC.