Qi Zeng

A Matched Cohort Study of Standard Chemo-Radiotherapy versus Radiotherapy Alone in Elderly Nasopharyngeal Carcinoma Patients

The impact of standard chemo-radiotherapy (CRT) as preferred therapy for elderly patients (age≥60 years) with nasopharyngeal carcinoma (NPC) remains unclear. Therefore, a strict matched cohort study was conducted to compare the survival and treatment toxicity of standard chemo-radiotherapy in the elderly NPC patients with those of radiotherapy (RT) alone. From 1998 to 2003, total 498 newly diagnosed elderly non-metastatic NPC patients were abstracted and classified into two groups by the treatments they received. For each patient in the CRT group, a matched pair in RT group was identified by matching for gender, age, histological type, T and N classifications, RT dose to primary tumor and neck nodes, and days of radiotherapy. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared between the two groups. Two groups were well balanced in clinical characteristics because of the strict matching conditions. Totally 87 pairs can be assessed according to the criteria. The 5-year OS, CSS, FFS, and LR-FFS for CRT and RT groups were 62% versus 40% (P=0.013), 67% versus 47% (P=0.018), 65% versus 53% (log-rank: P=0.064, Breslow: P=0.048), and 88% versus 72%, (P=0.019), respectively. There was no significant difference in 5-year D-FFS between the two groups (75% vs. 73%, P=0.456). The CRT group experienced significantly more Grade ≥3 acute mucositis (46.0% vs. 28.7%, P= 0.019). We concluded that standard chemo-radiotherapy can achieve a reasonable local and regional control in elderly NPC patients with acceptable and reversible acute toxicity. However, distant metastasis remains the dominant failure pattern. When the elderly NPC patients are in good performance status following a complete evaluation of overall functional status and comorbidity conditions, standard chemo-radiotherapy is worthy of recommendation.

Ten-year outcomes of a randomised trial for locoregionally advanced nasopharyngeal carcinoma: A single-institution experience from an endemic area

OBJECTIVE We previously reported the five-year results of a randomised trial that compared induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) with induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was to report the ten-year results and to explore potential prognostic factors. METHODS From August 2002 to April 2005, 408 patients with locoregionally advanced NPC were randomly assigned to receive either IC (carboplatin and floxuridine)+CCRT (carboplatin) or IC+RT. The survival rates were analysed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. RESULTS The ten-year overall survival, failure-free survival, locoregional failure-free survival and distant failure-free survival rates for the entire patient cohort were 49.5%, 48.0%, 80.8% and 66.9%, respectively. No significant survival differences were found between the IC+CCRT and IC+RT arms. By 3 years from the date of randomisation, 62.5% of the relapses had been detected; no recurrence occurred after 8 years. Within 3 years after randomisation, 77.0% of the metastases were detected; 0.8% was identified after 8 years. Age, Union for International Cancer Control (UICC) N-stage, serum lactate dehydrogenase (LDH) and body mass index (BMI) were independent prognostic factors that predicted death. Smoking status and total radiotherapy dose were independent prognostic factors that predicted locoregional recurrence. UICC N-stage, LDH and BMI were independent prognostic factors that predicted distant metastasis. CONCLUSIONS Concurrent carboplatin chemotherapy did not significantly improve the long-term survival after inductive carboplatin and floxuridine chemotherapy in locoregionally advanced nasopharyngeal carcinoma. In addition to patient and tumour characteristics, LDH, BMI and smoking status were important baseline prognostic factors for tumour recurrence or distant metastasis; these are worthy of further prognostic investigation in future studies.

Nomograms for predicting long-term survival in patients with non-metastatic nasopharyngeal carcinoma in an endemic area

Purpose Nomogram for predicting more than a 5-year survival for non-metastatic nasopharyngeal carcinoma (NPC) was lacking. This study aimed to develop the new nomograms to predict long-term survival in these patients. Results The median follow-up time for training set and test set was 95.2 months and 133.3 months, respectively. The significant predictors for death were age, gender, body mass index (BMI), T stage, N stage, lactate dehydrogenase (LDH), and radiotherapy techniques. For predicting recurrence, age, gender, T stage, LDH, and radiotherapy techniques were significant predictors, whereas age, gender, BMI, T stage, N stage and LDH were significant predictors for distant metastasis. The calibration curves showed the good agreements between nomogram-predicted and actual survival. The c-indices for predicting death, recurrence, and distant metastases between nomograms and the TNM staging system were 0.767 VS.0.686 (P<0.001), 0.655 VS.0.585 (P<0.001), and 0.881 VS.0.754 (P<0.001), respectively. These results were further confirmed in the test set. Methods On the basis of a retrospective study of 1593 patients (training set) who received radiotherapy alone or concurrent chemoradiotherapy from 2000 to 2004, significant predictors were identified and incorporated to build the nomograms. The calibration curves of nomogram-predicted survival versus the actual survival were plotted and reviewed. Bootstrap validation was performed to calculate the concordance index (c-index). These models were further validated in an independent prospective trial (test set, n=400). Conclusion The established nomograms suggest more-accurate long-term prediction for patients with non-metastatic NPC.

Image-based Multilevel Subdivision of M1 Category in TNM Staging System for Metastatic Nasopharyngeal Carcinoma

Purpose To establish an image-based M1 category subdivision system for personalized prognosis prediction and treatment planning in patients with metastatic nasopharyngeal carcinoma (NPC). Materials and Methods A total of 1172 patients with metachronous metastasic NPC were retrospectively enrolled (the dataset is from Sun Yat-sen University Cancer Center for derivation, and the combined datasets are from Guangzhou Medical University Cancer Center and the Fifth Affiliated Hospital of Sun Yat-sen University for validation). The Ethics Committee of the three centers approved this study. A general subdivision system of the M1 category was established on the basis of the most influential metastatic features for overall survival (OS). The following multilevel subdivision system for precise subdivision of the M1 category was designed: M [number of locations]-Location [number of lesions], with B indicating bone, L indicating the lung, H indicating the liver, and N indicating a node. The correlation of the M1 subdivisions with OS was determined with Cox regression. The best treatment response was assessed with Response Evaluation Criteria in Solid Tumors 1.1 guidelines and modified Response Evaluation Criteria in Solid Tumors criteria. Results Multivariate analysis in the derivation cohort showed that the number of metastatic lesions (multiple or single), the number of metastatic locations (multiple or single), liver involvement, and bone involvement were independent prognostic factors for OS. In general, subdividing the cohort by the number of metastatic lesions and the number of metastatic locations resulted in three subcategories of differential OS: M1a, a single lesion in a single organ or location; M1b, multiple lesions in a single organ or location; and M1c, metastases in multiple locations (for M1b vs M1a, hazard ratio [HR] = 2.28, 95% confidence interval [CI]: 1.71, 3.05; for M1c vs M1a, HR = 3.65, 95% CI: 2.75, 4.85); these subdivisions were externally validated. The multilevel subdivision system could be further used to discriminate among subgroups of differential OS under the M1b subcategory. Findings from analysis of multilevel subgroups suggested that patients with a single metastatic lesion (M1-B1, M1-L1, M1-H1, M1-N1) or two lesions in the liver only (M1-H2) had high rates of complete response (CR) or complete surgical resection (CSR) and 3-year OS after treatment (CR plus CSR rates >30%, and 3-year OS rates >50%); there were high 3-year OS rates (>50%) in patients with stage M1-B2, M1-L2, or M1-H3 disease but relatively low rates of CR or CSR. Conclusion Use of the multilevel M1 subdivision system in patients with NPC could facilitate more precise prognosis prediction and better identification of patients who will respond well to treatment than the conventional subdivision strategy. (©) RSNA, 2016 Online supplemental material is available for this article.

The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients

There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log‐rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure‐free survival (FFS) (HR=0.811; P = 0.010), and loco‐regional failure‐free survival (LR‐FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack‐years was also an independent predictor of OS (HR = 0.673; P < 0.001) and FFS (HR = 0.681; P < 0.001), LR‐FFS (HR = 0.663; P = 0.001). A significant positive additive effect was found for the interaction between low post‐RT Hb and high SI on OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post‐RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco‐regional recurrence compared with light smokers with high post‐RT Hb levels, and post‐RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post‐RT Hb level and pack‐years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post‐RT Hb levels in the future.

Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

Objective Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5%) was higher than in the FC group (10.7%). Neutropenia and leukopenia were the most common grade 3–4 adverse events in the TC group, and mucositis was the most common in the FC group. Conclusion These data indicate that TC and FC therapies have similar efficacy in treating locally advanced NPC and both are well tolerated.

CT-Guided Percutaneous Step-by-Step Radiofrequency Ablation for the Treatment of Carcinoma in the Caudate Lobe.

AbstractThe location of the caudate lobe and its complex anatomy make caudate lobectomy and radiofrequency ablation (RFA) under ultrasound guidance technically challenging. The objective of the exploratory study was to introduce a novel modality of treatment of lesions in caudate lobe and discuss all details with our experiences to make this novel treatment modality repeatable and educational.The study enrolled 39 patients with liver caudate lobe tumor first diagnosed by computerized tomography (CT) or magnetic resonance imaging (MRI). After consultation of multi-disciplinary team, 7 patients with hepatic caudate lobe lesions were enrolled and accepted CT-guided percutaneous step-by-step RFA treatment.A total of 8 caudate lobe lesions of the 7 patients were treated by RFA in 6 cases and RFA combined with percutaneous ethanol injection (PEI) in 1 case. Median tumor diameter was 29 mm (range, 18–69 mm). A right approach was selected for 6 patients and a dorsal approach for 1 patient. Median operative time was 64 min (range, 59–102 min). Median blood loss was 10 mL (range, 8-16 mL) and mainly due to puncture injury. Median hospitalization time was 4 days (range, 2–5 days). All lesions were completely ablated (8/8; 100%) and no recurrence at the site of previous RFA was observed during median 8 months follow-up (range 3–11 months). No major or life-threatening complications or deaths occurred.In conclusion, percutaneous step-by-step RFA under CT guidance is a novel and effective minimally invasive therapy for hepatic caudate lobe lesions with well repeatability.

Dynamically prognosticating patients with hepatocellular carcinoma through survival paths mapping based on time-series data

Patients with hepatocellular carcinoma (HCC) always require routine surveillance and repeated treatment, which leads to accumulation of huge amount of clinical data. A predictive model utilizes the time-series data to facilitate dynamic prognosis prediction and treatment planning is warranted. Here we introduced an analytical approach, which converts the time-series data into a cascading survival map, in which each survival path bifurcates at fixed time interval depending on selected prognostic features by the Cox-based feature selection. We apply this approach in an intermediate-scale database of patients with BCLC stage B HCC and get a survival map consisting of 13 different survival paths, which is demonstrated to have superior or equal value than conventional staging systems in dynamic prognosis prediction from 3 to 12 months after initial diagnosis in derivation, internal testing, and multicentric testing cohorts. This methodology/model could facilitate dynamic prognosis prediction and treatment planning for patients with HCC in the future.Patients with hepatocellular carcinoma require regular follow-up. Here, using Cox-based feature selection to identify key prognostic features, the authors convert time-series follow-up data into a cascading survival map, and show that the approach improves dynamic prognosis prediction for patients.