Ekaphop Sirachainan

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): Validation study of the Thai version

The objective of this study was to assess the psychometric properties of the Thai version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0. The questionnaire was completed by 310 cancer patients during their follow-up at 2 teaching hospital oncology clinics. About 70% of participants had advanced stage of cancer and 72% had been receiving chemotherapy. Cronbach’s α coefficients of the six scales were above 0.7, except for cognitive and social function scales. All test–retest reliability coefficients were high. Multitrait scaling analysis showed that all item-scale correlation coefficients met the standards of convergent and discriminant validity. Most scales and items could discriminate between subgroups of patients with different clinical status assessed with the Eastern Cooperative Oncology Group (ECOG) scale. The results suggested that the EORTC QLQ-C30 and the Functional Assessment of Cancer Therapy – General (FACT-G) measured different aspects of quality of life and should be independently used. Testing psychometric properties of the EORTC QLQ-C30 in heterogeneous diagnostic group yield similar results as found in homogeneous group. These results support that the EORTC QLQ-C30 (version 3.0) has proven to be a reliable and valid measure of the quality of life in Thai patients with various types of cancer.

Association between multidrug resistance-associated protein 1 and poor prognosis in patients with nasopharyngeal carcinoma treated with radiotherapy and concurrent chemotherapy

ATP-binding cassette (ABC) multidrug transporters have been associated with chemoresistance, which is a major obstacle in attempts to improve clinical outcome of patients with nasopharyngeal carcinoma (NPC). In this study, we investigated 3 ABC multidrug transporters including MDR1, MRP1, and BCRP for their potential as prognostic indicators in patients with NPC. We examined the protein expression profiles of MDR1, MRP1, and BCRP in NPC tissues from 60 patients with advanced stages who were treated with radiotherapy and concurrent chemotherapy. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the transporter expression. Univariate analyses were performed to determine the prognostic factors that influenced treatment failure and patient survival. We found that MRP1 expression was strongly predictive of both 5-year survival (P = .025) and disease-free survival (P < .001). However, neither MDR1 nor BCRP expression was correlated with the clinicopathologic parameters. Interestingly, the incidence of recurrence and metastasis for patients in the MRP1-positive group was significantly higher than that in the MRP1-negative group (P = .003). With multivariate analysis, MRP1 expression at the time of diagnosis before the treatment was identified as an independent prognostic factor for both 5-year survival (P = .041) and disease-free survival (P = .001). MRP1 expression can therefore be used as a potent molecular risk factor and a guide for chemotherapeutic regimens in patients with advanced stages of NPC.

Impact of CYP2D6 polymorphisms on tamoxifen responses of women with breast cancer: a microarray-based study in Thailand.

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the association between genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients. We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 genetic polymorphisms using microarray-based technology. Associations between genotypes-phenotypes and disease free survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years. The 3 common allelic frequencies were 43.8% (*10), 36.5 (*1) and 10.4% (*2) which are related to extensive metabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No association between CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statistically significant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95% CI, 1.48 -31.69; P = 0.005). Furthermore, we observed statistically significant shorter DFS of homozygous CYP2D6*10 when compared with heterozygous CYP2D6*10 and other genotypes (P=0.005). CYP2D6*10 was the most common genotype in our subjects. Post-menopause patients with homozygous CYP2D6*10 and IM have shorter DFS. To confirm this relationship, larger samples and comprehensively designed trials in Thailand are required.

CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients.

Aim: We evaluated single nucleotide polymorphisms (SNPs) of CYP2D6 to identify those that influence the efficiency of tamoxifen in adjuvant treatment of breast cancer through a matched case–control study. Methods: Peripheral blood DNA was collected from 20 patients with disease recurrence during adjuvant tamoxifen treatment and from 19 patients who had completed 5 years of tamoxifen therapy without recurrence of breast cancer. CYP2D6*4 (1846G > A; rs3892097), CYP2D6*10 (100C > T, rs1065852), and CYP2D6*5 (deletion) were genotyped. The correlation between disease-free survival (DFS) and genotype and clinical outcome were assessed using Kaplan–Meier analysis and a log-rank test. Results: We found the allelic frequency of CYP2D6*10 during this study. Patients with the CYP2D6*10 homozygous variant T/T genotype had a significantly shorter median of DFS than those with C/T (P = 0.036), but DFS was not significantly different from that of patients with the C/C genotype (P = 0.316). One patient who was a carrier both of CYP2D6 G/A (1846G > A) and T/T (100C > T) had DFS of 22.7 months. Conclusions: This study demonstrated that CYP2D6*10/*10 was significantly associated with shorter DFS in Thai breast cancer patients receiving tamoxifen. This was a pilot study investigating the correlation of CYP2D6 polymorphisms and their influence on clinical outcomes in Thai estrogen receptor-positive breast cancer patients.

Treatment Outcome of Palliative Chemotherapy in Inoperable Cholangiocarcinoma in Thailand

BACKGROUND Cholangiocarcinoma is the most common cancer in males in Thailand. The outcome is poor although systemic chemotherapy has been used in attempts to improve disease control, quality of life and prolong survival in patient with unresectable and advanced disease. MATERIALS AND METHODS In this retrospective study the medical records of all patients diagnosed as having unresectable and metastatic cholangiocarcinoma and receiving systemic chemotherapy at Udonthani Cancer Hospital during January 2007 to December 2010 were reviewed. RESULTS Among the total of 105 patients, 21 received gemcitabine-based chemotherapy and 84 5FU-based chemotherapy. Most received platinum doublet regimens. 5FU-based regimens yielded an overall response rate (tumor control) of 23.8% and a median survival of 7.2 months while gemcitabine-based regimens yielded an overall response rate (tumor control) 19.1% and a median survival of 10.0 months. CONCLUSIONS Tumor control and survival of patient with advanced cholangiocarcinoma treated with gemcitabine-based and 5FU-based chemotherapy do not markedly differ.

Prognostic value of ABCG2 in moderately and poorly differentiated intrahepatic cholangiocarcinoma.

Larbcharoensub N, Sornmayura P, Sirachainan E, Wilasrusmee C, Wanmoung H & Janvilisri T 
(2011) Histopathology59, 235–246

Fractionated stereotactic radiotherapy in residual or recurrent nasopharyngeal carcinoma

The aim of this study was to evaluate results of fractionated stereotactic radiotherapy (FSRT) in patients with residual or recurrent nasopharyngeal carcinoma (NPC) in terms of local progression-free (LPFS) and overall survival (OS) rate and complications after treatment. There were 32 residual or recurrent NPC patients treated with FSRT using linac-based radiosurgery system. Time from the previous radiotherapy to FSRT was 1–165 months (median, 15). Two patients were treated for the second and one for the third recurrence. Thirteen patients (40.6%) also received chemotherapy with FSRT. Tumor volume ranged from 6.2–215 cc (median, 44.4). Average FSRT dose was 17–59.4 Gy (median, 34.6) in 4–25 fractions (median,6) in 1–5.5 weeks (median, 3). Median follow-up time was 25.5(3–67) months. LPFS rate at 1 and 3 years after FSRT was 67.8% and 37.9%. OS rate at 1 and 3 years was 89.7% and 71.2%. If all patients who had tumor progression with no further follow-up were assumed dead, the OS rate at 1 and 3 years would be 75.0% and 37.9%. Univariate analysis showed better local tumor control in patients with tumor volume ≤100 cc (p=0.04) or in those without chemotherapy (p=0.0005). Only chemotherapy retained significance in multivariate analysis (hazard ratio 5.47, 95%CI 1.86–16.04). Eight patients (25%) had complications after FSRT, all grade 2–3 except 1 grade 4 with complete recovery.

Transcriptome meta-analysis reveals dysregulated pathways in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant cancer arising from the epithelial surface of the nasopharynx that mostly appears in advanced stages of the disease, leading to a poor prognosis. To date, a number of mRNA profiling investigations on NPC have been reported in order to identify suitable biomarkers for early detection. However, the results may be specific to each study with distinct sample types. In this study, an integrative meta-analysis of NPC transcriptome data was performed to determine dysregulated pathways, potentially leading to identification of molecular markers. Ten independent NPC gene expression profiling microarray datasets, including 135 samples from NPC cell lines, primary cell lines, and tissues were assimilated into a meta-analysis and cross-validation to identify a cohort of genes that were significantly dysregulated in NPC. Bioinformatics analyses of these genes revealed the significant pathways and individual players involving in cellular metabolism, cell cycle regulation, DNA repair, as well as ErbB pathway. Altogether, we propose that dysregulation of these molecular pathways in NPC might play a role in the NPC pathogenesis, providing clues, which could eventually translate into diagnostic and therapeutic approaches.

A call for action to improve access to care and treatment for patients with rare diseases in the Asia-Pacific region

This article is a call for action to the relevant stakeholders to improve access to care and treatment for patients with rare diseases in the Asia-Pacific region by looking into three main areas: (a) developing legislative definitions to confer enforceable protection, (b) creating or strengthening policies by objectively measuring the impact brought about by rare diseases and establishing platforms to reach out to the rare disease community, and (c) fostering collaboration across sectors and countries. It is hoped that these suggested actions can catalyze discussions and progress in the region.

Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study

Micro‐Abstract The nonrandomized phase 2 APEC trial investigated first‐line once‐every‐2‐weeks cetuximab plus chemotherapy (investigators choice of FOLFOX or FOLFIRI) studied patients with KRAS/RAS wild‐type metastatic colorectal cancer. We observed an activity and safety profile similar to that reported in prior first‐line pivotal studies involving weekly cetuximab, suggesting that once‐every‐2‐weeks cetuximab is effective and tolerable as first‐line therapy. Background: In patients with KRAS wild‐type (wt) metastatic colorectal cancer (mCRC), outcomes with first‐line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first‐line once‐every‐2‐weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. Patients and Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia‐Pacific region. Patients (n = 289) received once‐every‐2‐weeks cetuximab with investigators choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression‐free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. Results: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. Conclusion: The observed activity and safety profile is similar to that reported in prior first‐line pivotal studies involving weekly cetuximab, suggesting once‐every‐2‐weeks cetuximab is effective and tolerable as first‐line therapy and may represent an alternative to weekly administration.