[Show abstract][Hide abstract] ABSTRACT: Purpose/Objective(s): Distant metastasis represents a significant source
of treatment failure in patients with locally advanced nasopharyngeal
carcinoma (NPC) who are treated with concurrent cisplatin and radiation
therapy (RT). A recent randomized trial investigating the efficacy of
adding induction chemotherapy (gemcitabine, carboplatin, and paclitaxel,
GCP) to the current standard regime of concurrent cisplatin and RT, failed
to indicate further improvement in survival outcomes with the experimental
strategy. In this secondary analysis, we test the hypothesis that
raised plasma EBV DNA levels measured pre-treatment predicts for a
therapeutic benefit with induction GCP.
Materials/Methods: Patients with biopsy-proven stage 3/4 NPC with no
evidence of distant metastasis were eligible. All patients underwent intensity
modulated RT, delivered to a dose of 69.96 and 60 Gy in 33
fractions to the gross tumor and high risk subclinical and nodal regions,
respectively. Cisplatin, at a dose of 40 mg/m2, was administered concurrently
once a week with RT. In the experimental arm, the 3-weekly GCP
combination regime comprised of gemcitabine, 1 gm/m2, carboplatin,
AUC 2.5, paclitaxel, 70 mg/m2, given at days 1 and 8 for a total of 3
cycles. Plasma EBV DNA levels were quantified using real-time quantitative
polymerase chain reaction assay.
Results: A total of 172 patients were accrued for the primary randomized
study. Median follow-up of all patients was 3.25 (range, 1.07-8.42)
and 2.69 years (range, 0.11 - 8.32) in the GCP and control arms,
respectively. Overall survival (OS), disease-free survival (DFS), anddistant metastasis-free survival (DMFS) were comparable between both
treatment arms (HR: OS Z 1.05, 95% CI Z 0.44-2.53, p Z 0.915; DFS
Z 0.77, 95% CI Z 0.44-1.35, p Z 0.362; DMFS Z 0.81, 95% CI Z
0.39-1.71, p Z 0.585). One hundred twelve patients had EBV DNA
analysis pre-treatment (N Z 56, GCP and control). Of this group of
patients, 37 (66.1%) and 41 (73.2%) in the control and GCP arms,
respectively, had detectable levels of EBV DNA pre-treatment. For
patients with detectable EBV DNA levels, induction GCP seems to
confer a favorable DFS and DMFS (HR: DFS Z 0.39, 95% CI Z 0.14-
1.11, p Z 0.056; DMFS Z 0.45, 95% CI Z 0.13-1.49, p Z 0.166). In
contrast, DFS and DMFS were comparable between both treatment arms
in patients with undetectable EBV DNA levels at baseline (HR: DFS Z
0.74, 95% CI Z 0.18-2.97, p Z 0.617; DMFS Z 0.80, 95% CI Z 0.11-
5.69, p Z 0.864). Local regional failure rates were comparable between
both arms, independent of baseline EBV DNA levels.
Conclusions: The addition of induction chemotherapy to concurrent
chemoradiation therapy in locally advanced NPC remains controversial.
Nonetheless, patients with detectable EBV DNA levels pre-treatment
appear to benefit from induction GCP, both in terms of DFS and
DMFS. Baseline EBV DNA level potentially has a role as a predictive
marker in stratifying patients with stage 3/4 NPC for induction
[Show abstract][Hide abstract] ABSTRACT: Objective: To determine the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on caries progression in nasopharyngeal carcinoma patients treated with radiotherapy.
Methods: 24 patients were randomized into two groups before starting intensity-modulated radiotherapy. Subjects had at least eight remaining teeth after oral health clearance and gave informed consent. Individuals with previous history of head and neck radiotherapy or with known milk allergy were excluded. The test group used 0.4% stannous fluoride gel in a custom tray and a crème containing 10% CPP-ACP daily; the placebo group used a similar crème without CPP-ACP and otherwise identical care. Subjects were instructed to apply the crème three-times-daily and fluoride gel once daily throughout the radiotherapy period and thereafter. Tooth surface caries status according to the ICDAS II criteria, saliva and plaque parameters were measured before radiotherapy, and at 2-weeks and 3-months post-radiotherapy.
Results: 21 males and three females with a median age of 50 years (IQR: 45~59) were recruited. 22 patients returned for the 3-month post-radiotherapy review, at which time reduced plaque pH, salivary flow rates, pH and buffering capacity were observed. 9 subjects in the intervention group and 8 subjects in the placebo group developed 32 and 59 new caries lesions respectively. The intervention group showed a lower rate of caries progression as compared to the placebo group for all tooth surfaces (OR: 0.51, 95% CI: 0.17 to 1.59) with the occlusal surfaces showing lower caries progression (OR: 0.20, 95% CI: 0.03 to 1.29) as compared to smooth surfaces (OR: 0.61, 95% CI: 0.16 to 2.38).
Conclusion: Within the limitations of this study, CPP-ACP use reduced the rate of caries progression in nasopharyngeal carcinoma patients in the first three months after radiotherapy.
IADR Asia/Pacific Region (APR) Regional Meeting and Co-Annual Scientific Meeting of IADR Divisions 2013; 08/2013
[Show abstract][Hide abstract] ABSTRACT: There are at least five cancers with uniquely high incidence amongst East and Southeast Asian ethnic groups - namely nasopharyngeal carcinoma (NPC); gastric carcinoma; hepatocellular carcinoma (HCC); adeno-carcinoma of the lung in female non-smokers and nasal NK/T-cell lymphomas. They all appear to be related to an infective cause (Epstein Barr Virus, Helicobacter pylori, hepatitis B virus). We hypothesize that a genetic bottleneck 30,000years ago at the Last Glacial Maximum could have resulted in unique genetic polymorphisms in Toll-like receptor 8, making East Asians more vulnerable to these infective associated cancers. This bottleneck could have been caused by the presence of malaria in the southern Himalayan conduit between central and East Asia; and only those with an attenuated innate immune response to the malarial parasite (perhaps reflected by the TLR8 polymorphism) were spared the ravages of cerebral malaria; allowing these people to cross into east Asia, but then rendering them susceptible to later endemic infections and their associated cancers.
[Show abstract][Hide abstract] ABSTRACT: We sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone.
Seven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria.
Median follow-up was 7.2years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermitte's syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%).
While radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques.
Radiotherapy and Oncology 01/2012; 104(3):305-11. · 4.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is essential to determine local tumour extent in patients with nasopharyngeal carcinoma (NPC), as it affects prognosis and accuracy of primary target delineation during radiotherapy treatment planning. This study aims to evaluate the efficacy of three imaging modalities (MRI, CT and 18F-FDG-PET/CT) in detecting intracranial extension of NPC.
The study population comprised of 78 patients with histologically proven NPC. Cancer staging was performed with MRI of the neck, whole body 18F-FDGPET/ CT and contrast-enhanced CT of the neck, thorax, abdomen and pelvis.
MRI detected 14 patients with intracranial extension of disease, constituting a detection rate of 17.9%. CT identified 5 out of these 14 patients (detection rate of 6.4%) while 18F-FDG-PET/CT identified 6 out of these 14 patients (detection rate of 7.7%). Using MRI as the reference imaging modality, the sensitivity and specificity of CT was 35.7% and 100% while the sensitivity and specificity of 18F-FDG-PET/CT was 42.9% and 100%.
MRI remains the modality of choice for detecting intracranial disease extension of NPC.
Head & Neck Oncology 01/2012; 4(2):49. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal cancer (NPC) is endemic in Southern China, with Guandong province and Hong Kong reporting some of the highest incidences in the world. The journal Science has called it a "Cantonese cancer". We propose that in fact NPC is a cancer that originated in the Bai Yue ("proto Tai Kadai" or "proto Austronesian" or "proto Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage. However, the work by John Ho raised the profile of NPC, and because of the high incidence of NPC in Hong Kong and Guangzhou, NPC became known as a Cantonese cancer. We searched historical articles, articles cited in PubMed, Google, monographs, books and Internet articles relating to genetics of the peoples with high populations of NPC. The migration history of these various peoples was extensively researched, and where possible, their genetic fingerprint identified to corroborate with historical accounts. Genetic and anthropological evidence suggest there are a lot of similarities between the Bai Yue and the aboriginal peoples of Borneo and Northeast India; between Inuit of Greenland, Austronesian Mayalo Polynesians of Southeast Asia and Polynesians of Oceania, suggesting some common ancestry. Genetic studies also suggest the present Cantonese, Minnans and Hakkas are probably an admixture of northern Han and southern Bai Yue. All these populations have a high incidence of NPC. Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.
[Show abstract][Hide abstract] ABSTRACT: Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.
58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.
58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.
Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients.
[Show abstract][Hide abstract] ABSTRACT: Human Vgamma2Vdelta2 T cells play important role in immunity to infection and cancer by monitoring self and foreign isoprenoid metabolites with their gammadelta T cell antigen receptors. Like CD4 and CD8 alphabeta T cells, adult peripheral Vgamma2Vdelta2 T cells represent a pool of heterogeneous cells with distinct functional capabilities.
The aim of this study was to characterize the phenotypes and functions of various Vgamma2Vdelta2 T cell subsets in patients with nasopharyngeal carcinoma (NPC). We sought to develop a better understanding of the role of these cells during the course of disease and to facilitate the development of immunotherapeutic strategies against NPC.
Although similar total percentages of peripheral blood Vgamma2Vdelta2 T cells were found in both NPC patients and normal donors, Vgamma2Vdelta2 T cells from NPC patients showed decreased cytotoxicity against tumor cells whereas Vgamma2Vdelta2 T cells from normal donors showed potent cytotoxicity. To investigate further, we compared the phenotypic characteristics of Vgamma2Vdelta2 T cells from 96 patients with NPC and 54 healthy controls. The fraction of late effector memory Vgamma2Vdelta2 T cells (T(EM RA)) was significantly increased in NPC patients with corresponding decreases in the fraction of early memory Vgamma2Vdelta2 T cells (T(CM)) compared with those in healthy controls. Moreover, T(EM RA) and T(CM) Vgamma2Vdelta2 cells from NPC patients produced significantly less IFN-gamma and TNF-alpha, potentially contributing to their impaired cytotoxicity. Radiotherapy or concurrent chemo-radiotherapy further increased the T(EM RA) Vgamma2Vdelta2 T cell population but did not correct the impaired production of IFN-gamma and TNF-alpha observed for T(EM RA) Vgamma2Vdelta2 T cells.
We have identified distinct alterations in the Vgamma2Vdelta2 T cell subsets of patients with NPC. Moreover, the overall cellular effector function of gammadelta T cells is compromised in these patients. Our data suggest that the contribution of Vgamma2Vdelta2 T cells to control NPC may depend on the activation state and differentiation of these cells.
Cancer Immunology and Immunotherapy 12/2008; 58(7):1095-107. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endemic nasopharyngeal carcinoma (NPC) commonly metastasizes to the lungs, liver, and bones. This study aims to assess the efficacy of 4 distant metastasis staging modalities, namely (1) conventional work-up comprising chest X-ray, liver ultrasound, and skeletal scintigraphy, (2) CT of the thorax, abdomen, and skeletal scintigraphy, (3) (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), and (4) integrated FDG-PET/CT.
Seventy-eight consecutive patients diagnosed with NPC were enrolled and followed up for a minimum of 6 months to confirm the staging at diagnosis.
Six patients (7.7%) had distant metastases at diagnosis. The sensitivities and specificities of conventional work-up, combined CT and skeletal scintigraphy, FDG-PET, and FDG-PET/CT were 33.3%, 66.7%, 83.3%, and 83.3%; and 90.3%, 91.7%, 94.4%, and 97.2%, respectively. The corresponding accuracies were 85.9%, 89.7%, 93.6%, and 96.2%.
FDG-PET/CT is the most sensitive, specific, and accurate modality for distant metastasis staging of endemic NPC.
Head & Neck 11/2008; 31(3):346-54. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess toxicity and response in the sequential administration of gemcitabine followed by cisplatin in unresectable or metastatic non-small cell lung cancer.
Twenty-three patients were enrolled in this study. Gemcitabine was given at 1,250 mg/m2 on days 1 and 8, for four 21-day cycles.
There were 4 patients with partial responses. 5 patients with stable disease and 10 patients with progressive disease, giving a response rate of 21%. The median time to disease progression was 3.3 months. The median overall survival was 14.6 months. Toxicities graded 3 or 4 included anaemia (13.0%), neutropaenia (13.0%), supraventricular tachycardia (4.3%), and nausea and vomiting (4.3%).
Although these results show similar efficacy to single-agent treatment regimens, the low toxicity profile and promising survival outcome with this regimen are important points for consideration.
Annals of the Academy of Medicine, Singapore 01/2006; 35(1):33-7. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m(-2) day(-1) and i.v. 5-fluorouracil 1000 mg m(-2) day(-1), both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites.
British Journal of Cancer 09/2005; 93(3):279-86. · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data on combined modality treatment for locally advanced squamous cell carcinoma of the oesophagus involving Asian patients are limited.
A retrospective study of 56 consecutive patients with this condition treated with concurrent chemoradiotherapy followed by surgery in a single tertiary institution in Singapore was performed.
The median overall survival of the entire cohort was 14.1 months [95% confidence interval (CI); range, 8.6 to 19.6 months]. In patients who underwent successful oesophagectomy after chemoradiotherapy (n = 17), the median survival was 27.8 months compared to 9.8 months for those who did not have surgery (n = 39) (P = 0.046, log-rank test). The median time to first relapse for the entire cohort was 16.1 months (95% CI, 7.7 to 24.5 months). The time to first relapse was 23.9 months in the subgroup of patients with successful surgery and 12.1 months in the group which did not (P = 0.147, log-rank test). The high proportion of patients who were medically unfit for surgery or declined surgery may have conferred a selection bias.
Concurrent chemoradiotherapy followed by surgery is feasible in selected patients. The benefit of adding of surgery to chemoradiotherapy is still controversial and we await the results of randomised controlled trials comparing chemoradiotherapy with surgery versus chemoradiotherapy alone.
Annals of the Academy of Medicine, Singapore 07/2005; 34(5):369-75. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin < 12 g dl(-1) (score 4) and disease-free interval (DFI) (DFI < or = 6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0-3; intermediate, 4-8; poor, > or = 9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P = 0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials.
British Journal of Cancer 04/2005; 92(8):1382-7. · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A useful measure of quality of life should be easy and quick to complete. Recently, we reported the development and validation of a shortened Chinese version of the Functional Living Index-Cancer (FLIC), which we called the Quick-FLIC. In the present study of 327 English-speaking and 221 Chinese-speaking cancer patients, we validated the English version of the Quick-FLIC and further assessed the Chinese version. The 11 Quick-FLIC items were administered alongside the 11 remaining items of the full FLIC, but there appeared to be little context effect. Validity of the English version of the Quick-FLIC was attested by its strong correlation with two other measures of quality of life, and its ability to detect differences between patients with different performance status and treatment status (each P<0.001). Its internal consistency (alpha=0.86) and test-retest reliability (intraclass correlation=0.76) were also satisfactory. The measure was responsive to changes in performance status (P<0.001). The Chinese version showed similar characteristics. The Quick-FLIC behaved in ways that are highly comparable with the FLIC, even though the Quick-FLIC comprised only 11 items whereas the FLIC comprised 22. Further research is required to see whether the use of shorter instruments can improve data quality and response rates, but the fact that shorter instruments place less burden on the patients is itself inherently important.
British Journal of Cancer 02/2005; 92(4):668-72. · 4.82 Impact Factor