Terence Tan

Comparison of Circulating Tumour Cells and Circulating Cell-Free Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Undergoing Radiotherapy

Quantification of Epstein-Barr virus (EBV) cell-free DNA (cfDNA) is commonly used in clinical settings as a circulating biomarker in nasopharyngeal carcinoma (NPC), but there has been no comparison with circulating tumour cells (CTCs). Our study aims to compare the performance of CTC enumeration against EBV cfDNA quantitation through digital PCR (dPCR) and quantitative PCR. 74 plasma samples from 46 NPC patients at baseline and one month after radiotherapy with or without concurrent chemotherapy were analysed. CTCs were captured by microsieve technology and enumerated, while three different methods of EBV cfDNA quantification were applied, including an in-house qPCR assay for BamHI-W fragment, a CE-IVD qPCR assay (Sentosa ®) and a dPCR (Clarity™) assay for Epstein-Barr nuclear antigen 1 (EBNA1). EBV cfDNA quantitation by all workflows showed stronger correlation with clinical stage, radiological response and overall survival in comparison with CTC enumeration. The highest detection rate of EBV cfDNA in pre-treatment samples was seen with the BamHI-W qPCR assay (89%), followed by EBNA1-dPCR (85%) and EBNA1-qPCR (67%) assays. Overall, we show that EBV cfDNA outperforms CTC enumeration in correlation with clinical outcomes of NPC patients undergoing treatment. Techniques such as dPCR and target selection of BamHI-W may improve sensitivity for EBV cfDNA detection.

Asians with Localized Prostate Cancer Treated with 3-Dimensional Conformal Radiation Therapy and Adjuvant Hormonal Therapy: Comparing Phoenix and American Society of Therapeutic Radiology and Oncology (ASTRO) Definitions in an Asian Population

OBJECTIVES Conformal radiotherapy with adjuvant androgen suppression is used in our center to treat localized prostate cancer. We compare Phoenix as an alternative to American Society of Therapeutic Radiology and Oncology (ASTRO) for defining biochemical failure. Our primary aim was to assess the Phoenix and ASTRO definitions of biochemical failure in a population of mainly Asian men with early localized prostate cancer treated with conformal radiotherapy with and without androgen ablation. METHODS We retrospectively analyzed 141 patients who were treated for T1/T2 cancer of the prostate in our center from January 1997 to June 2002 with a mean duration of follow-up of 62 months. Outcomes were analyzed by using both Phoenix and ASTRO definitions of biochemical failure as well as clinical failure. RESULTS The Phoenix definition of biochemical failure was superior as measured by sensitivity, specificity, positive and negative predictive values, accuracy, and a greater concordance with clinical outcome as measured by Kappa analysis. CONCLUSIONS The ASTRO definition helped to standardize reporting of biochemical failures post-radiotherapy but inadequacies have been identified especially when adjuvant hormone therapy has been given. The Phoenix definition has been noted to be a more accurate and precise description of biochemical failure in international series, and we find this to be true in our Asian population as well.

Induction Chemotherapy plus Concurrent Chemoradiotherapy in Endemic Nasopharyngeal Carcinoma: Individual Patient Data Pooled Analysis of Four Randomized Trials

Purpose: Because of the uneven geographic distribution and small number of randomized trials available, the value of additional induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) remains controversial. This study performed an individual patient data (IPD) pooled analysis to better assess the precise role of IC + CCRT in locoregionally advanced NPC. Experimental Design: Four randomized trials in endemic areas were identified, representing 1,193 patients; updated IPD were obtained. Progression-free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. Results: Median follow-up was 5.0 years. The HR for PFS was 0.70 [95% confidence interval (CI), 0.56–0.86; P = 0.0009; 9.3% absolute benefit at 5 years] in favor of IC + CCRT versus CCRT alone. IC + CCRT also improved OS (HR = 0.75; 95% CI, 0.57–0.99; P = 0.04) and reduced distant failure (HR = 0.68; 95% CI, 0.51–0.90; P = 0.008). IC + CCRT had a tendency to improve locoregional control compared with CCRT alone (HR = 0.70; 95% CI, 0.48–1.01; P = 0.06). There was no heterogeneity between trials in any analysis. No interactions between patient characteristics and treatment effects on PFS or OS were found. After adding two supplementary trials to provide a more comprehensive overview, the conclusions remained valid and were strengthened. In a supplementary Bayesian network analysis, no statistically significant differences in survival between different IC regimens were detected. Conclusions: This IPD pooled analysis demonstrates the superiority of additional IC over CCRT alone in locoregionally advanced NPC, with the survival benefit mainly associated with improved distant control. Clin Cancer Res; 24(8); 1824–33. ©2018 AACR.

Validation of the AJCC staging system (7th edition) in Asian patients with localized prostate cancer undergoing radical radiotherapy.

112 Background: The epidemiology of prostate cancer (PCa) varies widely internationally. Although prostate cancer is usually regarded as uncommon in Asia, dramatic rises in recent years have resulted in it being ranking third by incidence in Singapore. Conventional prognostic parameters derived from Western populations have been integrated into systems such as the new AJCC seventh edition staging system, the validity of which is unclear in Asia. We thus sought to validate its performance, alongside other prognostic factors in a large Asian series of radiotherapy patients. METHODS A retrospective review of 404 consecutive Singaporean patients receiving radical radiotherapy between 1997 and 2005 at the National Cancer Centre was performed. The primary outcome was biochemical relapse free survival (BRFS), defined by the Phoenix criteria. Prognostic risk groups were defined using AJCC seventh edition. Univariate analysis (UVA) and multivariate analysis (MVA) was performed for other putative risk factors: age, race, Gleason score, prognostic risk grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy (HT) and initial PSA. RESULTS Median age was 69; median BRFS was 55 months with 71 biochemical relapses. 4 risk factors showed univariate association with BRFS: AJCC risk groups (p=0.038), T-stage (p=0.018), RT dose (p=0.025) and initial PSA value (p=0.013) with AJCC risk groups and initial PSA value remaining significant after MVA ( Table ). Harrells c-index for AJCC risk grouping was 0.56, with no significant difference seen in outcomes between AJCC risk group II and III. CONCLUSIONS Our results validate the new AJCC seventh edition prostate cancer prognostic risk grouping in an Asian radiotherapy population for the first time; the actual association however is relatively weak possibly due to differences in biology, screening or epidemiology. [Table: see text] No significant financial relationships to disclose.

Multimodality Management of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) of the endemic type (World Health Organization [WHO] type II and III) is considered separately from head and neck squamous cell cancer (HNSCC) because of certain distinctive features that confer a different biological behavior in terms of treatment responses and disease outcome. The most important feature that probably accounts for this difference is its strong association with the Epstein-Barr virus (EBV) (1–]3). This virus is probably the key etiological agent in the pathogenesis of this cancer, with genetic predisposition and other environmental factors as important cofactors (4, 5, 6, 7, 8, 9, 10, 11, 12, 13). This is in line with the peculiar geographic distribution and racial predilection of this disease.

A new prognostic index score for metastatic nasopharyngeal carcinoma: A validation study

5575 Background: Patients with metastatic undifferentiated nasopharyngeal carcinoma (mets NPC) comprise a heterogeneous group with varying survival duration. Previously, we retrospectively analyzed the factors determining survival in these patients and designed a prognostic index score (PIS). (Ong YK et al; proc ASCO 2001) We now present our analysis on a different cohort of pts to validate the PIS. METHODS The present cohort included 137 mets NPC pts. Eighty-eight percent of them received chemotherapy and this proportion is higher than that in our previous cohort. We re-analyzed the previous cohort to include only pts who received chemotherapy to derive a new PIS (nPIS) that stratified the pts into 3 prognostic groups with significantly different median survivals. The nPIS was applied to the present cohort of 118 pts who was treated with chemotherapy. Logrank test was used to compare the overall survival between the 3 groups. RESULTS The significant prognostic variables in the nPIS included poor performance status of ECOG ≥2, short disease-free interval (DFI) of < 6 mths, presence of mets at initial diagnosis, and anemia of Hb<12 g/dl. A score of 0 was assigned if the factor was absent or 1 for mets at initial diagnosis, 4 for anaemia, 5 for ECOG≥2 and 10 for short DFI. The maximum score attainable was 19 and the pts were stratified into 3 groups- good prognosis: 0-3, intermediate prognosis: 4-8, poor prognosis: ≥9. Fifty-seven pts were good prognosis, 43 intermediate prognosis and 18 poor prognosis, with median survival of 20.2 (95% CI 15.2, 25.2), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months respectively. (logrank test: p=0.003) Conclusions: The nPIS is validated in our present cohort of mets NPC pts who received chemotherapy. The factors involved are readily available in the clinics and will prove useful as a method for risk assessment and stratification of pts with mets NPC. With stratification also come uniform classification and consistent reporting in clinical trials that will help us better interpret results of any therapeutic intervention. No significant financial relationships to disclose.