Hai-Yang Chen

Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma

BackgroundTo evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC).MethodsThree hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD.ResultsMedian follow-up was 66 months (range, 2–82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30–50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30–50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172).ConclusionsOur data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging.

Development and External Validation of Nomograms for Predicting Survival in Nasopharyngeal Carcinoma Patients after Definitive Radiotherapy.

The distant metastasis free survival (DMFS) and overall survival (OS) differ significantly among individuals even within the same clinical stages. The purpose of this retrospective study was to build nomograms incorporating plasma EBV DNA for predicting DMFS and OS of nasopharyngeal carcinoma (NPC) patients after definitive radiotherapy. A total of 1168 non-metastatic NPC patients from two institutions were included to develop the nomograms. Seven and six independent prognostic factors were identified to build the nomograms for OS and DMFS, respectively. The models were externally validated by a separate cohort of 756 NPC patients from the third institutions. For predicting OS, the c-index of the nomogram was significantly better than that of the TNM staging system (Training cohort, P = 0.005; validation cohort, P = 0.03). The c-index of nomogram for DMFS in the training and validation set were both higher than that of TNM classification with marginal significance (P = 0.048 and P = 0.057, respectively). The probability of 1-, 3-, and 5-year OS and DMFS showed optimal agreement between nomogram prediction and actual observation. The proposed stratification of risk groups based on the nomograms allowed significant distinction between Kaplan-Meier curves for survival outcomes. The prognostic nomograms could better stratify patients into different risk groups.

Low Prognostic Nutritional Index (PNI) Predicts Unfavorable Distant Metastasis-Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis

Background Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). Methods A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. Results The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001) as well as multivariate analysis (P<0.001) before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001). The PNI consistently showed a higher AUC value at 1-year (0.780), 3-year (0.793) and 5-year (0.812) in comparison with other prognostic scores. Conclusion PNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients with non-metastatic NPC.

A novel prognostic score model incorporating CDGSH iron sulfur domain2 (CISD2) predicts risk of disease progression in laryngeal squamous cell carcinoma

Background The role of CDGSH iron sulfur domain 2 (CISD2) in laryngeal squamous cell carcinoma (LSCC) remains unclear. Results CISD2 were up-regulated in LSCC tissues compared with adjacent noncancerous tissues both at mRNA and protein levels. CISD2 was significantly correlated with T stage, lymph node metastasis, clinical stage and disease progression. A prognostic model (C-N model) for PFS was subsequently constructed based on independent prognostic factors including CISD2 and N classification. This model significantly divided LSCC patients into three risk subgroups and was more accurate than the prediction efficacy of TNM classification in the training cohort (C-index, 0.710 vs 0.602, P = 0.027) and validation cohort (C-index, 0.719 vs 0.578, P = 0.014). Methods Real-time PCR and Western blotting were employed to examine the expression of CISD2 in eight fresh paired LSCC samples. Immunohistochemistry was performed to assess CISD2 expression in 490 paraffin-embedded archived LSCC samples. A prognostic model for progression-free survival (PFS) was built using independent factors. The concordance index (C-Index) was used to evaluate the prognostic ability of the model. Conclusions CISD2 was up-regulated in LSCC. The novel C-N model, which includes CISD2 levels and N classification, is more accurate than conventional TNM classification for predicting PFS in LSCC.

C-Reactive Protein/Albumin Ratio (CAR) as a Prognostic Factor in Patients with Non-Metastatic Nasopharyngeal Carcinoma.

Background: The C-reactive protein/albumin (CRP/ALB) ratio has recently been associated with clinical outcomes in patients suffering various types of cancer. In this retrospective study, we investigated the prognostic value of the pre-treatment CRP/ALB ratio (CAR) in non-metastatic nasopharyngeal carcinoma (NPC) patients. Methods: The cohort included 2685 patients with non-metastatic NPC. Univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of CAR with overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and locoregional recurrence-free survival (LRRFS) in patients with NPC. Kaplan-Meier survival analyses was used to compare groups classified by CAR. Results: Patients were categorised by the CAR using a cut-off value of 0.064. Multivariate Cox proportional hazard analysis verified that high CAR level was a significant predictor for inferior OS (P = 0.003), DMFS (P = 0.035), and LRRFS (P = 0.024), but not for DFS (P = 0.093). CAR was also an independent prognostic factor for OS when stratified by Epstein-Barr virus DNA level ( ≥ 2560 or < 2560 copies ml-1). Conclusions: High CAR provides prognostication regarding OS, DMFS, DFS, and LRRFS in patients with NPC. CAR is a valuable coadjutant for Epstein-Barr virus DNA levels for identifying survival differences.

Plasma Fibrinogen Correlates with Metastasis and is Associated with Prognosis in Human Nasopharyngeal Carcinoma

Background: The purpose of this observational study was to evaluate the prognostic significance of the pre-treatment plasma fibrinogen level for survival outcomes in nasopharyngeal carcinoma (NPC). Methods: A total of 998 patients with NPC treated at a single centre in China were retrospectively enrolled, of whom 182 (18.2%) developed distant metastasis during follow-up. Survival analyses were performed by the Kaplan-Meier method and Cox regression modelling to measure 3-year overall survival (OS) and distant metastasis-free survival (DMFS). Results: Median OS for the entire cohort was 37.8 months. Using the cut-off value of 3.345 g/L identified in receiver operating curve analysis for fibrinogen, a high pre-treatment plasma fibrinogen level were associated with older age (P = 0.034), advanced TNM stage (P = 0.004) and development of distant metastasis (P < 0.001; Chi-square test). Multivariate Cox proportional hazard analysis demonstrated the pre-treatment plasma fibrinogen level was an independent significant prognostic factor for OS and DMFS in both the entire cohort and also among patients who developed distant metastasis during follow-up. Conclusions: This study suggests the pre-treatment plasma fibrinogen level may serve as an independent prognostic marker to predict the survival outcomes of patients with NPC, including patients with metastatic disease.

Prostate tumor overexpressed-1, in conjunction with human papillomavirus status, predicts outcome in early-stage human laryngeal squamous cell carcinoma

In human cancer, molecular markers combined with clinical characteristics are used increasingly to predict prognosis. Prostate tumor overexpressed-1 (PTOV1), first identified in prostate cancer, is a key factor in tumor progression and correlates with unfavorable clinical outcomes. HPV infection status was tested by HPV E6-targeted multiplex real-time PCR and p16 immunohistochemistry (IHC). Real-time PCR and western blotting analyses were used to examine the mRNA and protein expression levels of PTOV1 in eight paired LSCC samples. IHC was performed to assess PTOV1 protein expression in 196 paraffin-embedded, archived LSCC samples. PTOV1 protein and mRNA expression was increased in LSCC tissues compared with adjacent noncancerous tissue samples. High expression of PTOV1was significantly associated with advanced TNM stage by the X2 test. Multivariate analysis revealed that PTOV1 and HPV status were independent prognostic indicators of overall survival (OS) and progression-free survival (PFS) (P = 0.001, P = 0.009 for OS, P = 0.005, P = 0.012 for PFS, respectively). Our study provides the first evidence that the combination of PTOV1 expression level and HPV status provides more prognostic information compared with HPV status alone with the significance still exists in the HPV negative subgroup.

Additional Cervical Lymph Node Biopsy is Not a Significant Prognostic Factor for Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era: A Propensity Score-matched Analysis from an Epidemic Area

Introduction: This study aimed to evaluate the prognostic value of cervical lymph node biopsy and whether different biopsy methods would lead different outcomes in NPC in the intensity-modulated radiotherapy (IMRT) era. Material and Methods: 1492 patients with biopsy-proven, non-metastatic NPC, and treated by IMRT with or without chemotherapy were retrospectively reviewed. Cervical lymph node biopsy was performed in 183 (12.3%) patients: 61(4.1%) by needle puncture and 118(7.9%) by excision biopsy. Propensity-score matching was used to match patients in both arms at an equal ratio. Overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and nodal relapse-free survival (NRFS) were assessed using the Kaplan-Meier method and compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. Results: In the original cohort of 1492 patients, patients receiving cervical lymph node biopsy had comparable survival (OS: P = 0.736, DMFS: P = 0.749, LRFS: P = 0.538, NRFS: P = 0.093,) with patients receiving isolated napharynx biopsy. The results for the propensity-match cohort of 316 patients were similar. Interestingly, compared with the control group and needle puncture biopsy group, a slightly lower nodal recurrence rate was observed in the excision biopsy group (P = 0.082 and P = 0.072, respectively). Adjusting for the known prognostic factors in multivariate analysis, cervical biopsy did not cause a higher risk of death, distant metastasis, or nodal relapse. Conclusions: Pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, suggesting the resist of the biopsy and more aggressive treatment after the biopsy may be unnecessary.

The Novel Prognostic Score Combining Red Blood Cell Distribution Width and Body Mass Index (COR-BMI) Has Prognostic Impact for Survival Outcomes in Nasopharyngeal Carcinoma

Background: A novel inflammation-and nutrition-based scoring system based on red blood cell distribution width and body mass index (COR-BMI) has prognostic value in nasopharyngeal carcinoma (NPC). Here, we assessed the prognostic value of COR-BMI in NPC. Methods: Retrospective study of 2,318 patients with non-metastatic NPC treated at Sun Yat-sen University Cancer Center was conducted. Patients were stratified into three groups using the COR-BMI score, which is based on two objective and easily measurable parameters: red blood cell distribution width (RDW) and body mass index (BMI). Kaplan-Meier survival analyses were used to compare groups; multivariate Cox proportional models were used to calculate overall survival (OS) and disease-free survival (DFS). Results: Four-year overall survival (OS) rates were 88.7%, 84.5%, and 71.4% for patients with COR-BMI scores of 0, 1, and 2 respectively (P = 0.006). Multivariate Cox proportional hazard analysis revealed COR-BMI was an independent predictor of OS (HR for COR-BMI 1: 1.239, 95% CI: 1.012-1.590; HR for COR-BMI 2: 2.367, 95% CI: 1.311-4.274, P = 0.013), but not DFS (P = 0.482). In subgroup analysis of metastatic NPC, OS rates decreased as COR-BMI increased. In patients with a COR-BMI score of 1, radiotherapy plus chemotherapy led to better OS than radiotherapy alone. Conclusions: COR-BMI may serve as an indicator of poor prognosis in both NPC and metastatic NPC. Radiotherapy plus chemotherapy may benefit patients with a COR-BMI score of 1.

Cervical lymph node carcinoma metastasis from unknown primary site: a retrospective analysis of 154 patients

Despite advances in diagnosis and treatment, the existence of cervical lymph node carcinoma of unknown primary site (CCUP) has always been an urgent problem worldwide. There is still no consensus on the optimal management for CCUP. In this retrospective review, we analyze the clinical characteristics of CCUP patients treated at our institution and examine how these characteristics and treatments were associated with survival. Clinicopathologic features, treatments, and survival outcomes of 154 CCUP patients were collected from the hospital records and analyzed. Survival was estimated by Kaplan–Meier methods and compared by the log‐rank test. Cox proportional hazards regression analysis was used to assess the factors independently associated with overall survival (OS) and progression‐free survival (PFS). Median follow‐up period was 26.44 months (range, 0.53–146.53 months). Multivariate analysis showed N stage, pathologic type, and lymph node extranodal extension (ENE) to be independent prognostic factors for OS in CCUP patients, but not PFS. Subgroup analysis of patients who received radiotherapy showed that radiotherapy to the pharyngeal mucosa was associated with better OS (P = 0.045), but not with better PFS. Advanced N stage, nonsquamous cell carcinoma, and lymph node ENE predict poor prognosis in patients with CCUP. In addition, radiotherapy to suspicious mucosa is accompanied by better OS. These study findings should be useful to clinicians when selecting the treatment approach.