Chih-Wen Twu

Plasma EBV DNA clearance rate as a novel prognostic marker for metastatic/recurrent nasopharyngeal carcinoma.

Purpose: To investigate the prognostic effect of the concentrations and clearance rates of plasma EBV DNA in metastatic/recurrent nasopharyngeal carcinoma (NPC). Experimental Design: Thirty relapsed and four previously nontreated metastatic NPC patients were treated according to the consensus guidelines of the head and neck cancer team in our hospital (i.v. chemotherapy first, followed by local irradiation boost and oral maintenance chemotherapy where applicable). Multiple plasma samples were collected during the first month of chemotherapy. Circulating EBV DNA concentrations were measured by a real-time quantitative PCR. The half-life values (t1/2) of plasma EBV DNA clearance were calculated. The associations between clinical outcome and plasma EBV DNA assays were analyzed. Results: Tumor response evaluated after 12 weeks of treatment showed 14 complete responses (41.2%), 12 partial responses (35.3%), 7 stable diseases (20.6%), and 1 progression disease (2.9%). The plasma EBV DNA concentrations have no significant effects on outcome prediction. The t1/2 of plasma EBV DNA clearance ranged from 1.85 to 28.29 days (median, 3.99). Patients with a short t1/2 of plasma EBV DNA clearance have significantly higher complete response rate and overall survival than those with long t1/2. Multivariate analysis revealed a significant effect of the t1/2 of plasma EBV DNA clearance on survival. Conclusions: The clearance rates of plasma EBV DNA during the first month of chemotherapy can predict tumor response and patient survival. Early change of chemotherapy regimen may be considered for patients with slow plasma EBV DNA clearance rate. Clin Cancer Res; 16(3); 1016–24

Long-term survival analysis of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA levels

BACKGROUND: The objective of this study was to confirm the relation between plasma Epstein‐Barr virus (EBV) DNA (pEBV DNA) load and treatment outcomes after long‐term follow‐up in patients with nasopharyngeal carcinoma (NPC).

Plasma Epstein‐Barr virus DNA screening followed by 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography in detecting posttreatment failures of nasopharyngeal carcinoma

The authors investigated the clinical implication of plasma Epstein‐Barr virus (EBV) DNA assay and 18F‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) positron emission tomography (PET) in the detection of recurrent nasopharyngeal carcinoma (NPC).

Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

PURPOSE To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. METHODS AND MATERIALS The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. RESULTS Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). CONCLUSIONS Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

Association of p53 Codon 72 Polymorphism with Risk of Hypopharyngeal Squamous Cell Carcinoma in Taiwan

BACKGROUND p53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit. METHODS Genomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Patients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04). CONCLUSION This study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer.

The volume of retropharyngeal nodes predicts distant metastasis in patients with advanced nasopharyngeal carcinoma

We investigated the effect of retropharyngeal nodal volumes (RNV) on distant metastasis in patients with advanced nasopharyngeal carcinoma (NPC). From February 2000 to June 2006, a total of 181 patients with biopsy-proven NPC, no distant metastasis, and available pre-treatment magnetic resonance imaging (MRI) were retrospectively reviewed. Most of the patients (95.6%) had stage III/IV diseases. The contour of retropharyngeal nodes ≥5mm was delineated on the axial slides of pre-treatment T2-weighted MRI without contrast enhancement. The RNV was calculated by the Eclipse™ treatment planning software. The primary end-points were subsequent distant failure rates and distant metastasis failure-free survival (DMFFS). The pre-treatment RNV in patients who developed distant failure was higher than in those without distant failure (P=0.0536). The distant failure rates between the patients with RNV > and ≤4.68cm(3) were 33.3% and 16.0%, respectively (P=0.0112). The rates of 7-year DMFFS in patients with RNV > and ≤4.68cm(3) were 66.4% and 83.5%, respectively (P=0.0043). Multivariate Cox analysis showed N-stage (P<0.001), gender (P=0.026), and RNV (P=0.088) were important predictors for DMFFS. We conclude that the RNV measured by MRI is a potential predictor of distant metastasis in patients with advanced NPC.

Visual Screening of Oral Cavity Cancer: The Role of Otolaryngologists

Objectives: Because most screening was done by dentists, the purpose of this prospective cohort study was to evaluate the effectiveness of oral visual screening by otolaryngologists. In addition, we wanted to determine which group of enrolled patients was at potential risk of contracting oral cancer.

Long-term clinical outcome in nasopharyngeal carcinoma patients with post-radiation persistently detectable plasma EBV DNA

Purpose To investigate the long-term clinical outcome of nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma EBV (pEBV) DNA after curative radiotherapy (RT). Results The post-RT pEBV DNA levels were very lower copy number (median 21, interquartile range 8–206 copies/ml). After long-term follow-up, the relapse rate was 64.8%, the median time to progression 20 months, and 5-year overall survival (OS) 49.6%. Thirty-two of 39 (82.1%) patients with high viral load (≥ 100 copies/ml) developed tumor relapse, whereas 57.0% (49/86) patients with low viral load (< 100 copies/ml) had tumor relapse (P = 0.0065). The 5-year OS rates were 20.5% and 62.9% for patients with viral load ≥ and < 100 copies/ml (median survival, 20 vs. 100 months; P < 0.0001). Patients who received adjuvant chemotherapy (AdjCT) experienced significant reduction in distant failures (66.2% vs. 31.6%; P = 0.0001) but similar locoregional recurrences (P = 0.2337). The 5-year OS rates were 69.4% for patients who received AdjCT compared with 33.2% for those of without AdjCT (median survival, 111 vs. 32 months; P < 0.0001). Methods We screened 931 newly diagnosed NPC patients who finished curative RT and found 125 patients (13.4%) with detectable pEBV DNA one week after RT. The clinical characteristics, treatment modality, subsequent failure patterns and survivals were analyzed. Conclusions NPC patients with persistently detectable pEBV DNA after curative RT have a higher rate of treatment failure and poor survivals. Levels of the post-RT pEBV DNA and administration of AdjCT affect the final outcome significantly.

Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients

OBJECTIVES To investigate the prognostic impact of adjuvant chemotherapy (AdjCT) in patients with high-risk nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS A total 403 NPC patients with at least one of the following criteria (1) neck node>6cm; (2) supraclavicular node metastasis; (3) skull base destruction/intracranial invasion plus multiple nodes metastasis; or (4) multiple neck nodes metastasis with one of nodal size>4cm were retrospectively reviewed. All patients finished curative radiotherapy±neoadjuvant/concurrent chemotherapy. Post-radiation AdjCT consisted of tegafur-uracil (two capsules twice daily) for 12months. We analyzed the treatment outcome between patients with (n=154) and without (n=249) AdjCT. RESULTS Baseline patient characteristics at diagnosis (age, gender, pathological type, performance status, T-classification, N-classification, and overall stage) were comparable in both arms. After a median follow-up of 72months for surviving patients, 31.8% (49/154) and 42.2% (105/249) in patients with and without AdjCT developed tumor relapse respectively (P=0.0377). AdjCT improved both overall survival (HR 1.89, 95% CI 1.37-2.61, P=0.0001) and progression-free survival (HR 1.42, 95% CI 1.03-1.96, P=0.0322). There were significant reduction in distant failures (P=0.0016) but not in local (P=0.8587) or regional (P=0.8997) recurrences for patients who received AdjCT. CONCLUSION AdjCT can reduce distant failure and improve overall survival in high-risk NPC patients after curative radiotherapy±neoadjuvant/concurrent chemotherapy.

Comparison Long-term Outcome of Definitive Radiotherapy plus Different Chemotherapy Schedules in Patients with Advanced Nasopharyngeal Carcinoma.

Concurrent chemoradiotherapy (CCRT) is the current standard of care for advanced nasopharyngeal carcinoma (NPC). We hypothesize that shifting CCRT to neoadjuvant chemotherapy followed by radiotherapy (NeoCT-RT) is an alternative option. From December 2004 to January 2009, 256 NPC patients with stage II-IVB were treated by either CCRT or NeoCT-RT. All patients received the same dosage and fractionation schedule of RT. After long-term follow-up, 26.8% (34/127) and 23.3% (30/129) of patients who received CCRT and NeoCT-RT respectively, developed a tumor relapse (P = 0.6134). Overall survival (HR = 1.52, 95%CI = 0.91–2.55, P = 0.1532) and progression-free survival (HR = 1.22, 95%CI = 0.75–1.99, P = 0.4215) were similar in both groups. However, acute toxicities during RT period revealed a significant reduction of grade 3/4 vomiting (23% vs. 0%, P < 0.0001), mucositis (55% vs. 16%, P < 0.0001), and neck dermatitis (31% vs. 16%, P = 0.0041) in the NeoCT-RT group, resulting in fewer emergency room visits (10.2% vs. 1.6%, P = 0.0071). Severe treatment-related late toxicity (15% vs. 14%, P = 0.9590) and the occurrence of second malignancy (3.9% vs. 5.4%, P = 0.7887) also showed no differences. We concluded that NeoCT-RT could be an attractive alternative option of CCRT for advanced NPC.