82 results on '"Sirachainan, E."'
Search Results
2. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer
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Shitara, K., Fleitas, T., Kawakami, H., Curigliano, G., Narita, Y., Wang, F., Wardhani, S.O., Basade, M., Rha, S.Y., Wan Zamaniah, W.I., Sacdalan, D.L., Ng, M., Yeh, K.H., Sunpaweravong, P., Sirachainan, E., Chen, M.-H., Yong, W.P., Peneyra, J.L., Ibtisam, M.N., Lee, K.-W., Krishna, V., Pribadi, R.R., Li, J., Lui, A., Yoshino, T., Baba, E., Nakayama, I., Pentheroudakis, G., Shoji, H., Cervantes, A., Ishioka, C., and Smyth, E.
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- 2024
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3. Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial
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Toh, H.C., Yang, M.-H., Wang, H.-M., Hsieh, C.Y., Chitapanarux, I., Ho, K.F., Hong, R.-L., Ang, M.K., Colevas, A.D., Sirachainan, E., Lertbutsayanukul, C., Ho, G.F., Nadler, E., Algazi, A., Lulla, P., Wirth, L.J., Wirasorn, K., Liu, Y.C., Ang, S.F., Low, S.H.J., Tho, L.M., Hasbullah, H.H., Brenner, M.K., Wang, W.-W., Ong, W.S., Tan, S.H., Horak, I., Ding, C., Myo, A., and Samol, J.
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- 2024
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4. Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of Thai breast cancer patients treated with tamoxifen
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Sensorn I, Sirachainan E, Chamnanphol M, Pasomsub E, Trachu N, Supavilai P, Sukasem C, and Pinthong D
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Insee Sensorn,1 Ekaphop Sirachainan,2 Montri Chamnanphon,3 Ekawat Pasomsub,4 Narumol Trachu,5 Porntip Supavilai,1 Chonlaphat Sukasem,3 Darawan Pinthong11Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand; 2Division of Medical Oncology, Department of Medicine, 3Division for Pharmacogenomics and Personalized Medicine, 4Division for Virology, Department of Pathology, 5Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandBackground: Pharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug-metabolizing enzymes and transporters also play a role in tamoxifen metabolic pathways. The aim of this study is to investigate the impact of CYP3A4/5, ABCB1, and ABCC2 polymorphisms on the risk of recurrence in Thai patients who received tamoxifen adjuvant therapy.Methods: Patients with early-stage breast cancer who received tamoxifen adjuvant therapy were recruited in this study. All six single-nucleotide polymorphisms (SNPs), including CYP3A4*1B (-392 A>G)/*18(878 T>C), CYP3A5*3(6986 G>A), ABCB1 3435 C>T, ABCC2*1C (-24 C>T), and ABCC2 68231 A>G, were genotyped using real-time polymerase chain reaction assays. The impacts of genetic variants on disease-free survival (DFS) were analyzed using the Kaplan–Meier method and Cox regression analysis.Results: The ABCB1 3435 C>T was found to have the highest allele frequency among other variants; however, CYP3A4*1B/*18 could not be found in this study. Patients with heterozygous ABCB1 3435 CT genotype showed significantly shorter DFS than those with homozygous 3435 CC genotype (P = 0.041). In contrast, patients who carried homozygous 3435 TT genotype showed no difference in DFS from wild-type 3435 CC patients. Cox regression analysis showed that the relative risk of recurrence was increased by five times (P = 0.043; hazard ratio = 5.11; 95% confidence interval: 1.05–24.74) in those patients carrying ABCB1 3435 CT genotype compared to those with ABCB1 3435 CC.Conclusion: ABCB1 3435 C>T is likely to have a clinically significant impact on recurrence risk in Thai patients with breast cancer who receive tamoxifen adjuvant therapy.Keywords: breast cancer, CYP3A4/5, drug transporters, pharmacogenetics, disease-free survival, tamoxifen
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- 2013
5. Association of CYP2D6 and CYP2C19 polymorphisms and disease-free survival of Thai post-menopausal breast cancer patients who received adjuvant tamoxifen
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Chamnanphon M, Pechatanan K, Sirachainan E, Trachu N, Chantratita W, Pasomsub E, Noonpakdee W, Sensorn I, and Sukasem C
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Montri Chamnanphon,1 Khunthong Pechatanan,2 Ekapob Sirachainan,3 Narumol Trachu,4 Wasun Chantratita,5 Ekawat Pasomsub,5 Wilai Noonpakdee,6 Insee Sensorn,1,7 Chonlaphat Sukasem11Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 2Department of Medicine, Phramongkutklao College of Medicine, 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 4Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 5Division of Virology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 6Department of Biochemistry, Faculty of Science, Mahidol University, 7Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, ThailandPurpose: To investigate the impact of CYP2D6 and CYP2C19 polymorphisms in predicting tamoxifen efficacy and clinical outcomes in Thai breast cancer patients.Methods: Polymorphisms of CYP2D6 and CYP2C19 were genotyped by the AmpliChip™ CYP450 Test (Roche Molecular Diagnostics, Branchburg, NJ, USA) for 57 patients, who were matched as recurrent versus nonrecurrent breast cancers (n = 33 versus n = 24, respectively, with a 5-year follow-up).Results: Based on the genotype data, five CYP2D6 predicted phenotype groups were identified in this study including homozygous extensive metabolizer (13 of 57, 22.80%), extensive/intermediate metabolizer (23 of 57, 40.40%), extensive/poor metabolizer (3 of 57, 5.30%), homozygous intermediate metabolizer (14 of 57, 24.50%), and intermediate/poor metabolizer (4 of 57, 7.00%), and three CYP2C19 genotype groups including homozygous extensive metabolizer (27 of 57, 47.40%), extensive/intermediate metabolizer (27 of 57, 47.40%), and homozygous poor metabolizer (3 of 57, 5.30%). The CYP2D6 variant alleles were *10 (52 of 114, 45.60%), *5 (5 of 114, 4.40%), *41 (2 of 114, 1.80%), *4 (1 of 114, 0.90%), and *36 (1 of 114, 0.90%); the CYP2C19 variant alleles were *2 (27 of 114, 23.70%) and *3 (6 of 114, 5.30%). Kaplan–Meier estimates showed significantly shorter disease-free survival in patients with homozygous TT when compared to those with heterozygous CT or homozygous CC at nucleotides 100C>T and 1039C>T (CYP2D6*10) post-menopausal (log-rank test; P = 0.046). They also had increased risk of recurrence, but no statistically significant association was observed (hazard ratio 3.48; 95% confidence interval 0.86–14.07; P = 0.080).Conclusion: The CYP2D6 and CYP2C19 polymorphisms were not involved in tamoxifen efficacy. However, in the subgroup of post-menopausal women, the polymorphisms in CYP2D6 and CYP2C19 might be useful in predicting tamoxifen efficacy and clinical outcomes in breast cancer patients receiving adjuvant tamoxifen treatment. As the number of breast cancer patients was relatively small in this study, results should be confirmed in a larger group of prospective patients.Keywords: CYP2D6, CYP2C19, disease-free survival, tamoxifen, pharmacogenetics, breast cancer
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- 2013
6. CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients
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Sirachainan E, Jaruhathai S, Trachu N, Panvichian R, Sirisinha T, Ativitavas T, Ratanatharathorn V, Chamnanphon M, and Sukasem C
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Ekaphop Sirachainan,1 Sureerat Jaruhathai,1 Narumol Trachu,2 Ravat Panvichian,1 Thitiya Sirisinha,1 Touch Ativitavas,1 Vorachai Ratanatharathorn,1 Montri Chamnanphon,3 Chonlaphat Sukasem31Division of Medical Oncology, Department of Medicine, 2Research Center, Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 3Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAim: 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.Keywords: breast cancer, CYP2D6 polymorphism, pharmacogenetics, single-nucleotide polymorphism (SNP), tamoxifen
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- 2012
7. 652O Randomized phase III VANCE study: Gemcitabine and carboplatin (GC) followed by Epstein Barr virus-specific autologous cytotoxic T lymphocytes (EBV-CTL) versus the same chemotherapy as first-line treatment for advanced nasopharyngeal carcinoma (NPC)
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Toh, H.C., Yang, M-H., Wang, H-M., Hsieh, C-Y., Chitapanarux, I., Ho, K.F., Hong, R-L., Ang, M-K., Colevas, D., Sirachainan, E., Lertbutsayanukul, C., Ho, G.F., Samol, J., Huang, Z., Tan, C., Ding, C., and Myo, A.
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- 2022
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8. 511P Real-world survival outcomes of Asian metastatic colorectal cancer patients undergoing hepatectomy from the AsianmCRCRegistry
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Teh, C., Cai, S., Lin, J-K., Park, Y.S., Kim, T.W., Sirachainan, E., Ma, B., Wang, J-Y., Chen, W.T-L., Wang, H-M., Chen, C-C., Baek, J.Y., Zhang, S., P, S.S., Xu, J., Shrikhande, S., Lee, J-C., Jia, B., He, Y-L., and Huang, J.
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- 2020
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9. 1123P - A phase I study of the CDK4/6 inhibitor, palbociclib in combination with cetuximab and intensity modulated radiation therapy (IMRT) for locally advanced squamous cell carcinoma of the head and neck (SCCHN); A result of dose escalation cohort
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Ngamphaiboon, N., Jiarpinitnun, C., Siripoon, T., Lukerak, S., Jinawath, A., Jinawath, N., Arsa, L., Konmun, J., Kongsuphon, N., Sankaseam, N., Sirachainan, E., Witoonpanich, P., Kositwattanarerk, A., and Pattaranutaporn, P.
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- 2019
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10. 95P - Long term outcomes of preoperative concurrent CapeOx/RT in locally advanced rectal cancer
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Sirachainan, E., Sitathanee, C., Suwanthanma, W., Larbcharoensub, N., Lukrak, S., Sripaiboonkit Thokanit, N., Phongkitkarun, S., and Sumboonnanonda, K.
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- 2018
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11. 1118TiP - A phase I/II dose escalation study of the CDK4/6 inhibitor, palbociclib in combination with cetuximab and intensity modulated radiation therapy (IMRT) for locally advanced squamous cell carcinoma of the head and neck (SCCHN)
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Ngamphaiboon, N., Lukerak, S., Jiarpinitnun, C., Jinawath, A., Jinawath, N., Juengsamarn, J., Arsa, L., Konmun, J., Kongsuphon, N., Sankaseam, N., Sirachainan, E., Witoonpanich, P., Kositwattanarerk, A., and Pattaranutaporn, P.
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- 2018
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12. P3.15-24 Ramathibodi Lung Cancer Consortium (RLC) Model: Multidisciplinary Team Approach Improves Lung Cancer Patients’ Survival Outcome
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Reungwetwattana, T., Suwattanapongched, T., Sukkasem, W., Nitiwarangkul, C., Incharoen, P., Ngodngamthaweesuk, M., Leelayana, P., Cherntanomwong, P., Khajarern, S., Ativitavas, T., Chansriwong, P., Sirachainan, E., Kositwattanarerk, A., Chamroonrat, W., Ruaungkanchanasetr, R., Puataweepong, P., Swangsilpa, T., Dangprasert, S., Aulmongkon, N., Wetchaphan, B., Darayen, N., and Tangsujaritvijit, V.
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- 2018
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13. P3.09-19 Matched Thai Lung Cancer Patients Tissue and cfDNA Molecular Profile by NGS
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Trachu, N., Detarkom, S., Incharoen, P., Kamprerasart, K., Iemwimangsa, N., Arsa, L., Chantratita, W., Muntham, D., Sirachainan, E., and Reungwetwattana, T.
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- 2018
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14. P3.03-020 Unique Molecular Profile of NSCLC in Thai Population
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Trachu, N., Incharoen, P., Jinawat, A., Charoenyingwattana, A., Trachoo, O., Senson, I., Pairoj, W., Janchompoo, P., Srichunrusami, C., Detarkom, S., Lukrak, S., Sirachainan, E., Dejthevaporn, T. Sirisinha, Panvichien, R., Chantratita, W., Tienchainaanda, P., Ngodnbamthaweesuk, M., Prasongsook, N., Techasurungkul, S., Iemwimangsa, N., Klaisuban, W., and Reungwetwattana, T.
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- 2017
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15. Molecular alterations and clinical prognostic factors for cholangiocarcinoma in Thai population.
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Monnamo, N., Trachu, N., Sirachainan, E., Rattanadech, W., Detarkom, S., Reungwetwattana, T., Larbcharoensub, N., Kamprerasart, K., MunTham, D., and Sukasem, C.
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CHOLANGIOCARCINOMA ,BILIARY tract cancer ,GALLBLADDER cancer ,OPISTHORCHIS viverrini ,CLONORCHIS sinensis ,CANCER treatment - Abstract
This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months) than those with the other types of EGFR mutations (4.08 months; hazard ratio [HR]: 0.26, P=0.038) and also had a significantly lower median Ki-67 (22.5% vs 80%, P=0.025). Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P=0.043). Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR and/or PIK3CA mutations implies that targeted drugs may provide a feasible CCC treatment in the future. [ABSTRACT FROM AUTHOR]
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- 2017
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16. 998P - An optimal cumulative dose of cisplatin in chemoradiotherapy as a definitive treatment for non-metastatic nasopharyngeal carcinoma: a retrospective multicenter study
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Danchaivijitr, P., Ngamphaiboon, N., Jiarpinitnun, C., Sirachainan, E., Pattaranutaporn, P., and Setakornnukul, J.
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- 2016
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17. 426. Incidence of free colorectal cancer cells in peritoneal cavity and correlation with clinicopathologic variables: An analysis of 275 patients undergoing curative intent resection for colorectal cancer
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Suwanthanma, W., Euanorasetr, C., Lertsithichai, P., Pongtippan, A., Sirachainan, E., and Poprom, N.
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- 2014
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18. AOS17 KRAS genotypes in Thai patients with colorectal cancer
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Autkittanon, P., Reukumneuychok, B., Limsuwanachot, N., Ativitavas, T., Sirisinha, T., Panvichian, R., Ratanatharathorn, V., and Sirachainan, E.
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- 2012
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19. AOS23 O6-methylguanine-DNA-methyltransferase expression in Thai patients with malignant gliomas: Outcome and response to treatment in Ramathibodi Hospital
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Akwattanakul, W., Larbcharoensub, N., Rattanasiri, S., Sirachainan, E., Panvichian, R., Ativitavas, T., Ratanatharathorn, V., and Sirisinha, T.
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- 2012
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20. P22 Olfactory neuroblastoma – Ramathibodi Hospital experience
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Chompoonuch, S. and Sirachainan, E.
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- 2011
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21. AOSOP4 PREOPERATIVE CONCURRENT CAPOX RADIOTHERAPY IN THAI PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER.
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Sirachainan, E., Sitathanee, C., Phongkitkarun, S., Suwanthanma, W., Larbcharoensub, N., Trachu, N., Lukrak, S., and Sumboonnanonda, K.
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COMBINED modality therapy , *PREOPERATIVE care ,RECTUM tumors - Published
- 2013
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22. 124P Characteristics, prognosis and therapeutic effects of non-V600 BRAF mutated colorectal cancer.
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Arsa, L., Ngamphaiboon, N., Jinawath, A., Sripaiboonkij, N., Jinawath, N., Sirachainan, E., and Siripoon, T.
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COLORECTAL cancer , *BRAF genes , *PROGNOSIS - Published
- 2023
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23. P0080 Incidence and associated factors of cisplatin-induced chronic kidney disease after chemoradiotherapy for nasopharyngeal carcinoma.
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Mahaprom, K., Nongnuch, A., Sirachainan, E., and Ngamphaiboon, N.
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Background Cisplatin-based chemoradiotherapy (CRT) is effective and considered a standard of care for treatment of locally advanced nasopharyngeal carcinoma (NPC). Cisplatin-induced nephrotoxicity is problematic in this group of patients because they usually have poor oral intake, dehydration, and malnutrition. Acute kidney injury (AKI) during treatment is a well-known complication that leads to cisplatin discontinuation. However, cisplatin-induced chronic kidney disease (CI-CKD) may not be noticeable during CRT. Methods Patients with non-metastatic NPC who underwent cisplatin-based CRT at Ramathibodi Hospital (Nakhon Pathom, Thailand) between January 2007, and December 2012, were identified through the Ramathibodi Cancer Registry database. Patient characteristics, treatments, baseline, and post-treatment creatinine (⩽6 months after the last dose of chemotherapy) were abstracted. Estimated glomerular filtration rate (eGFR) was calculated by the CKD EPI formula. Patients with AKI were excluded. Primary endpoint was an incidence of CI-CKD, defined by the reduction of eGFR of 20 mg/dl or more from baseline. Findings 245 patients with NPC were identified. 115 eligible patients were included for analysis. All patients had an Eastern Cooperative Oncology Group status of 0–1. Median follow-up was 34.2 months. Overall, CI-CKD was observed in 36 (31%) of 115 patients. Multivariable analysis revealed being female and having a higher total dose of cisplatin during CRT were significantly associated with an increased risk of CI-CKD. Interpretation Approximately a third of patients with NPC suffered from CI-CKD after completion of treatment with cisplatin-based CRT. Total dose of cisplatin during CRT was strongly associated with CI-CKD despite patients being of a young age and with a high baseline eGFR. [ABSTRACT FROM AUTHOR]
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- 2015
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24. P0131 Factors affecting significant weight loss after concurrent chemoradiotherapy followed by adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma.
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Ngamphaiboon, N., Mahaprom, K., Jiarpinitnun, C., Sirachainan, E., and Shanatavasinkul, P.
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Background Chemoradiotherapy is regarded as the definitive treatment of locally advanced nasopharyngeal carcinoma (NPC). Treatment often leads to unintentional weight loss for many reasons such as swallowing dysfunction, mucositis, and cancer cachexia. Methods Patients with non-metastatic NPC who underwent chemoradiotherapy between January 2007, and December 2012, were identified through the Ramathibodi Cancer Registry database. Data on patient characteristics, treatment, body weight, and body mass index (BMI) were gathered. Significant weight loss was defined as ⩾10% loss from that before treatment. Factors that affected weight loss after chemoradiotherapy and within 1–3 months post-adjuvant chemotherapy were identified. Findings 245 patients with NPC were identified. 135 patients were included in this analysis. Median follow-up was 35.6 months. Overall, 28% and 39% of patients had significant weight loss after chemoradiotherapy and adjuvant chemotherapy, accordingly. The mean percent weight loss from baseline after chemoradiotherapy and adjuvant chemotherapy was −6.9% ± 6.0, and −8.5% ± 8.2, respectively. Baseline BMI ⩾23 was associated with longer overall survival ( p < 0.001). Interpretation Approximately a third of patients with NPC had significant weight loss after chemoradiotherapy and further lost weight after completion of adjuvant chemotherapy. Baseline BMI was significantly associated with weight loss after treatments. Early nutritional interventions could improve treatment outcomes. [ABSTRACT FROM AUTHOR]
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- 2015
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25. P0029 A pilot study of molecular alterations and the clinical prognostic factors of cholangiocarcinoma in the Thai population.
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Detarkom, S., Trachu, N., Larbcharoensub, N., Monnamo, N., Jinawat, A., Kamprerasart, K., MunTham, D., Sirachainan, E., and Reungwetwattana, T.
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Background Advanced cholangiocarcinoma (CCA) patients have a poor survival rate, even when receiving standard chemotherapy. No targeted therapy has been proven to benefit patients with CCA. The molecular alterations in Western and Eastern population are different. The aim of this study was to describe the natural history and clinical behaviour of the disease, including determining prognostic factors and molecular alterations of CCA in the Thai population. Methods A computerised search of a tumour registry database and tissue archive database in Ramathibodi Hospital from November 2007, to December 2011, identified 157 CCA patients who had adequate tumour tissue for DNA/RNA extraction. Data on the natural history and clinical behaviour were collected. The association and predictive ability of patient and tumour characteristics with overall survival (OS) and progression-free survival (PFS) outcomes were examined. ALK expression and ROS1 rearrangement were analysed. Findings Four significant prognostic factors for survival outcomes identified from multivariable-analysis included staging, performance status, surgical resection, and CA19-9 pre-treatment level. Median follow-up was 6.77 months. The median OS and PFS were 6.96 and 4.5 months, respectively. Advance stage disease, poor performance status, high CA19-9 level (⩾100 U/ml), and inoperability correlated with poor survival outcomes. CA19-9 ⩾100 U/ml was the optimal cut point, predicting both OS and PFS. There was a trend for better OS in patients without metastatic lymph nodes. One out of 50 patients had ALK expression, and this patient had OS of 30 months. No ROS1 gene rearrangement was found in 50 patients. Interpretation These data provided strong evidence for staging, performance status, surgical resection, and CA19-9 pre-treatment level as prognostic factors for CCA in the Thai population. Larger studies to elucidate the oncogenic drive genes of CCA are urgently needed. [ABSTRACT FROM AUTHOR]
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- 2015
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26. A new era of the Asian clinical research network: a report from the ATLAS international symposium.
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Terada M, Nakamura K, Matsuda T, Okuma HS, Sudo K, Yusof A, Imasa M, Sirachainan E, Anh PT, Fujiwara Y, Yamamoto N, Voon PJ, Chokephaibulkit K, Shibata T, Inoue M, Mano H, Shimoi T, Sriuranpong V, Yonemori K, and Shimada K
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- Humans, Thailand, Japan, Medical Oncology, Neoplasms genetics, Neoplasms therapy
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This report summarizes the presentations and discussions in the first Asian Clinical Trials Network for Cancers (ATLAS) international symposium that was held on 24 April 2022, in Bangkok, Thailand, and hosted by the National Cancer Center Hospital (NCCH), co-hosted by the Pharmaceuticals and Medical Devices Agency (PMDA), Clinical Research Malaysia (CRM) and the Thai Society of Clinical Oncology (TSCO), and supported by Embassy of Japan in Thailand. Since 2020, the NCCH has conducted the ATLAS project to enhance research environments and infrastructures to facilitate international clinical research and cancer genomic medicine in the Asian region. The purpose of the symposium was to discuss what we can achieve under the ATLAS project, to share the latest topics and common issues in cancer research and to facilitate mutual understanding. Invitees included stakeholders from academic institutions, mainly at ATLAS collaborative sites, as well as Asian regulatory authorities. The invited speakers discussed ongoing collaborative research, regulatory perspectives to improve new drug access in Asia, the status of phase I trials in Asia, the introduction of research activities at the National Cancer Center (NCC) and the implementation of genomic medicine. As the next steps after this symposium, the ATLAS project will foster increased cooperation between investigators, regulatory authorities and other stakeholders relevant to cancer research, and establish a sustainable pan-Asian cancer research group to increase the number of clinical trials and deliver novel drugs to patients with cancer in Asia., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
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- 2023
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27. Healthcare coverage affects survival of EGFR-mutant Thai lung cancer patients.
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Khiewngam K, Oranratnachai S, Kamprerasart K, Kunakorntham P, Sanvarinda P, Trachu N, Pimsa P, Wiwitkeyoonwong J, Thamrongjirapat T, Dejthevaporn T, Sirachainan E, and Reungwetwattana T
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Background: Despite significant benefits of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in patients with EGFR -mutated NSCLC, access remains limited in Thailand and elsewhere., Methods: Retrospective analysis of patients with locally advanced/recurrent NSCLC and known EGFR mutation ( EGFR m) status treated at Ramathibodi Hospital (2012-2017). Prognostic factors for overall survival (OS), including treatment type and healthcare coverage, were analyzed using Cox regression., Results: Of 750 patients, 56.3% were EGFR m-positive. After first-line therapy (n=646), 29.4% received no subsequent (second-line) treatment. EGFR-TKI-treated EGFR m-positive patients survived significantly longer than EGFR m-negative patients without EGFR-TKIs (median OS [mOS] 36.4 vs. 11.9 months; hazard ratio HR=0.38 [95%CI 0.32-0.46], P <0.001). Cox regression indicated significantly longer OS in patients with comprehensive healthcare coverage that included reimbursement of EGFR-TKIs, versus basic coverage (mOS 27.2 vs. 18.3 months; adjusted HR=0.73 [95%CI 0.59-0.90]). Compared with best supportive care (BSC; reference), EGFR-TKI-treated patients survived significantly longer (mOS 36.5 months; adjusted HR (aHR)=0.26 [95%CI 0.19-0.34]), and versus chemotherapy alone (14.5 months; aHR=0.60 [95%CI 0.47-0.78]). In EGFR m-positive patients (n=422), relative survival benefit of EGFR-TKI treatment remained highly significant (aHR[EGFR-TKI]=0.19 [95%CI 0.12-0.29]; aHR(chemotherapy only)=0.50 [95%CI 0.30-0.85]; reference:BSC), indicating that healthcare coverage (reimbursement) affected treatment choice and survival., Conclusion: Our analysis describes EGFR m prevalence and survival benefit of EGFR-TKI therapy for EGFR m-positive NSCLC patients treated from 2012-2017, one of the largest such Thai datasets. Together with research by others, these findings contributed evidence supporting the decision to broaden erlotinib access on healthcare schemes in Thailand from 2021, demonstrating the value of local real-world outcome data for healthcare policy decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khiewngam, Oranratnachai, Kamprerasart, Kunakorntham, Sanvarinda, Trachu, Pimsa, Wiwitkeyoonwong, Thamrongjirapat, Dejthevaporn, Sirachainan and Reungwetwattana.)
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- 2023
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28. Treatment outcomes of advanced hepatocellular carcinoma in real-life practice: Chemotherapy versus multikinase inhibitors.
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Oranratnachai S, Rattanasiri S, Sirachainan E, Tansawet A, Raunroadroong N, McKay GJ, Attia J, and Thakkinstian A
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- Humans, Sorafenib therapeutic use, Retrospective Studies, Leucovorin, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Treatment Outcome, Fluorouracil, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology
- Abstract
Background: Multikinase inhibitors (MKIs) represent the main treatment options for advanced hepatocellular carcinoma (aHCC). However, accessibility in developing countries is limited. A chemotherapy, Fluorouracil and Oxaliplatin (FOLFOX), offers a less expensive treatment. Therefore, this study sought to compare the clinical effectiveness of FOLFOX with Sorafenib as a first-line treatment for aHCC in real-life practice., Methods: A retrospective aHCC cohort from four Thai hospitals was investigated for patients who received FOLFOX or Sorafenib between 2013-2019. Multiple imputation by chained equations addressed missing covariate data in a treatment effect model using Weight-adjusted-censoring inverse-probability-weighted regression adjustment; overall survival (OS) and progression-free survival (PFS) were estimated., Results: A total of 504 patients were included, (Sorafenib [n = 382] and FOLFOX [n = 122]). The treatment effect model estimated a median OS for Sorafenib and FOLFOX of 11.38 and 8.22 months, representing a significantly shorter OS (95% confidence interval) of -3.16 (-6.21, -0.11) months for FOLFOX, p = 0.042. A significant shorter median PFS of FOLFOX to Sorafenib of -2.13 (-3.03, -1.24) months, p < 0.001, was reported., Conclusion: Despite significantly shorter median OS and PFS than Sorafenib, FOLFOX still extended OS by 8.22 months. This evidence may offer clinical utility to physicians considering treatment options for aHCC in low resource settings., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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29. Clinical correlations with EGFR circulating tumor DNA testing in all-stage lung adenocarcinoma.
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Incharoen P, Jinawath A, Arsa L, Kamprerasart K, Trachu N, Monnamo N, Khiewngam K, Muntham D, Chansriwong P, Sirachainan E, and Reungwetwattana T
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- Humans, ErbB Receptors genetics, Mutation, Neoplasm Recurrence, Local drug therapy, Protein Kinase Inhibitors therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Circulating Tumor DNA genetics, Antineoplastic Agents therapeutic use, Adenocarcinoma of Lung genetics
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Background: Information on genetic alterations, notably EGFR mutations, is important for guiding non-small-cell lung cancer (NSCLC) treatment. Circulating tumor DNA (ctDNA) analysis represents a less invasive alternative to tissue biopsy for analyzing mutation status, but its clinical value may vary across disease stages., Objective: To explore clinical correlates of ctDNA and tissue/plasma-based EGFR mutation (EGFRm) status across all NSCLC stages., Methods: Ninety patients were analyzed, representing three cohorts: newly-diagnosed early-stage, advanced-stage, and recurrent NSCLC. Relationships among clinical/surgical parameters, ctDNA, EGFRm status, and survival outcomes were analyzed., Results: Plasma/tissue EGFRm concordance was lower in early-stage (58.6%) than in advanced-stage patients (87.5%). In early-stage patients, ctDNA levels were variable and not significantly associated with clinical/surgical parameters. In advanced-stage patients, time to EGFR-TKI treatment failure (TTF), but not overall survival (OS), was significantly longer in EGFRm-positive vs. EGFRm-negative patients. In patients with recurrent disease, 40% of plasma samples were EGFRT790M-positive at recurrence. In T790M-positive patients, we noted slight trends toward longer OS with vs. without osimertinib treatment and longer OS and TTF with second-line vs. later-line osimertinib., Conclusions: Our results affirm the use of ctDNA testing in advanced-stage and recurrent NSCLC. Further studies on osimertinib as early-line therapy, clinical correlates and the utility of plasma-based testing in early-stage NSCLC are warranted.
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- 2023
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30. Clinical Study of Long-Term Survival in Colorectal Cancer Patients in Thailand: A 10-Year Follow-Up.
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Thokanit NS, Promchana S, Thonkamdee T, Jitkasikorn P, Siripoon T, Ngamphaiboon N, and Sirachainan E
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Background: In Thailand, data on colorectal cancer (CRC) patient characteristics and overall survival (OS) rates are limited. We aimed to describe the overall 5-year, 10-year survival and to examine factors effecting the survival outcome among patients who were diagnoses of colorectal cancer., Methods: We reviewed medical records of patients diagnosed with invasive CRC from 2007 through 2016. Demographic and clinical data were collected upon diagnosis. Kaplan-Meier method and Cox proportional hazards model to evaluate the association of overall (OS) with risk factors., Results: A total of 3,402 CRC patients (colon 59.4%, rectum 34. 5%, and rectosigmoid 6.1%) were identified. Mean (SD) and median age were 62.9 (12.7) and 63 years old (rang 14-98 years). Stages at diagnosis were I (10.1%), II (23.3), III (35.9%) and IV (30.7%). Five-year and 10-year OS of the entire cohort were 52.7% and 41.5%, respectively. Over the part 10 years, there was a trend toward improved 5-year OS in stages I, II and III. However, 3-year OS in stage IV patients remained unchanged. Confirmed poor prognostic factors included patient age ≥65 years, high grade, and advanced stage at diagnosis., Conclusion: Advanced disease was a significant prognostic factor for shorter survival. A trend toward improvement in 5-year OS in early stages over the past decade might be related to better surgical quality, improved radiation technique, and adjuvant chemotherapy. Given that patients received better systemic treatment in stage IV disease, the reason their OS was not improved should be examined., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Thokanit et al. Published by Tehran University of Medical Sciences.)
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- 2022
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31. Efficacy, Safety, and Patient-Reported Outcomes of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Thailand: A Multicenter Prospective Study.
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Charonpongsuntorn C, Tanasanvimon S, Korphaisarn K, Payapwattanawong S, Siripoon T, Pakvisal N, Juengsamarn J, Phaibulvatanapong E, Chindaprasirt J, Prasongsook N, Udomdamrongkul K, Ngamphaiboon N, and Sirachainan E
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- Humans, Quality of Life, Bevacizumab adverse effects, Prospective Studies, Thailand epidemiology, Patient Reported Outcome Measures, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
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Purpose: Atezolizumab plus bevacizumab treatment is a first-line therapy for unresectable hepatocellular carcinoma (HCC) worldwide. The efficacy, safety, and patient-reported outcomes (PROs) of HCC in Thailand have not yet been reported. This study aimed to evaluate the efficacy, safety, and PROs of atezolizumab plus bevacizumab., Materials and Methods: From September 2020 to August 2021, 30 patients with unresectable HCC who met the inclusion criteria of atezolizumab plus bevacizumab as first-line treatment were enrolled. Analysis was assessed for progression-free survival, overall survival, adverse events (AEs), and quality of life (QoL)., Results: The median progression-free survival and overall survival periods were 6.7 and 10.2 months, respectively. The disease control rate was 63.3%. The frequent AEs were proteinuria, hypertension, and hepatitis. Serious AEs included gastrointestinal bleeding, but none of the patients died from serious AEs. The discontinuation rate was 23.3%, and the median number of treatment cycles was 10.5 cycles. In total, 23.3% of the patients continued treatment after 1 year of therapy. The global health status/QoL and physical function scores showed less deterioration at baseline than at 3 and 6 months (median scores = 76.7, 71.6, and 64.1 in QoL and 84.7, 79.6, and 79.0 in physical function, respectively). The HCC18 symptom score index data showed a slow progression of symptom scores from baseline to 3 and 6 months (12.7, 19.6, and 22.3, respectively)., Conclusion: This study demonstrates that atezolizumab plus bevacizumab is effective and has a safety profile comparable with that of previous studies as first-line therapy for unresectable HCC in a real-world setting and in Thai populations. Data on PROs also demonstrate benefits in terms of patients' QoL and symptoms.
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- 2022
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32. Effects of polymorphisms in the MTHFR gene on 5-FU hematological toxicity and efficacy in Thai colorectal cancer patients.
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Atasilp C, Lenavat R, Vanwong N, Chansriwong P, Sirachainan E, Reungwetwattana T, Jinda P, Aiempradit S, Sirilerttrakul S, Chamnanphon M, Puangpetch A, Sankuntaw N, Satapornpong P, and Sukasem C
- Abstract
Background: The two common methylenetetrahydrofolate reductase ( MTHFR ) polymorphisms 677G>A and 1298A>C may have been affecting 5-FU toxicity in cancer patients for decades. Drug efficacy has also been shown by previous studies to be affected. In this study, we investigated the effects of these polymorphisms on 5-FU hematological toxicity and treatment efficacy, to provide enhanced pharmacological treatment for cancer patients., Methods: This is a retrospective study involving 52 Thai colorectal cancer patients who were treated with 5-FU based therapy, using TaqMAN real-time PCR to genotype the MTHFR polymorphisms (677G>A and 1298A>C). The toxicity and response rate were assessed using standardized measures., Results: Neutropenia was significantly more likely to be experienced ( P =0.049, OR=7.286, 95% CI=0.697-76.181) by patients with the MTHFR 677G>A polymorphism, in the same way as leukopenia ( P =0.036, OR=3.333, 95%CI=2.183-5.090) and thrombocytopenia ( P <0.001, OR=3.917, 95%CI=2.404-6.382). The MTHFR 1298A>C polymorphism had no statistical association with hematological toxicity in 5-FU treatment. The response rate to 5-FU was not significantly affected by these two polymorphisms., Conclusion: The MTHFR polymorphism 677G>A is a significant risk factor for developing leukopenia, neutropenia and thrombocytopenia as toxic effects of 5-FU therapy in cancer patients. Therefore, patients receiving 5-FU-based therapy should be aware of their polymorphisms as one risk factor for experiencing severe toxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Atasilp, Lenavat, Vanwong, Chansriwong, Sirachainan, Reungwetwattana, Jinda, Aiempradit, Sirilerttrakul, Chamnanphon, Puangpetch, Sankuntaw, Satapornpong and Sukasem.)
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- 2022
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33. Effect of Primary Tumor Location on Second- or Later-Line Treatment With Anti-Epidermal Growth Factor Receptor Antibodies in Patients With Metastatic Colorectal Cancer: A Retrospective Multi-Center Study.
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Archwamety A, Teeyapun N, Siripoon T, Poungvarin N, Tanasanvimon S, Sirachainan E, Akewanlop C, and Korphaisarn K
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Background: Current guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt ) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC., Methods: Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test., Results: Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt . Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005)., Conclusions: To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Archwamety, Teeyapun, Siripoon, Poungvarin, Tanasanvimon, Sirachainan, Akewanlop and Korphaisarn.)
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- 2022
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34. Capturing tumour heterogeneity in pre- and post-chemotherapy colorectal cancer ascites-derived cells using single-cell RNA-sequencing.
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Poonpanichakul T, Shiao MS, Jiravejchakul N, Matangkasombut P, Sirachainan E, Charoensawan V, and Jinawath N
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- Ascitic Fluid pathology, Biomarkers, Tumor metabolism, Clinical Decision-Making, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Predictive Value of Tests, RNA, Neoplasm metabolism, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Ascitic Fluid metabolism, Biomarkers, Tumor genetics, Colorectal Neoplasms drug therapy, Gene Expression Profiling, Genetic Heterogeneity, RNA, Neoplasm genetics, RNA-Seq, Single-Cell Analysis, Transcriptome
- Abstract
Malignant ascites is an abnormal accumulation of fluid within the peritoneal cavity, caused by metastasis of several types of cancers, including colorectal cancer (CRC). Cancer cells in ascites reflect poor prognosis and serve as a good specimen to study tumour heterogeneity, as they represent a collection of multiple metastatic sites in the peritoneum. In the present study, we have employed single-cell RNA-sequencing (scRNA-seq) to explore and characterise ascites-derived cells from a CRC patient. The samples were prepared using mechanical and enzymatic dissociations, and obtained before and after a chemotherapy treatment. Unbiased clustering of 19,653 cells from four samples reveals 14 subclusters with unique transcriptomic patterns in four major cell types: epithelial cells, myeloid cells, fibroblasts, and lymphocytes. Interestingly, the percentages of cells recovered from different cell types appeared to be influenced by the preparation protocols, with more than 90% reduction in the number of myeloid cells recovered by enzymatic preparation. Analysis of epithelial cell subpopulations unveiled only three out of eleven subpopulations with clear contraction after the treatment, suggesting that the majority of the heterogeneous ascites-derived cells were resistant to the treatment, potentially reflecting the poor treatment outcome observed in the patient. Overall, our study showcases highly heterogeneous cancer subpopulations at single-cell resolution, which respond differently to a particular chemotherapy treatment. All in all, this work highlights the potential benefit of single-cell analyses in planning appropriate treatments and real-time monitoring of therapeutic response in cancer patients through routinely discarded ascites samples., (© 2021 The Author(s).)
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- 2021
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35. Optimizing outcomes for patients with metastatic prostate cancer: insights from South East Asia Expert Panel.
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Schutz FAB, Sirachainan E, Kuppusamy S, Hoa NTT, Dejthevaporn T, Bahadzor B, Toan VQ, Chansriwong P, Alip A, Hue NTM, Parinyanitikul N, Tan AL, Hoang VDK, Tienchaiananda P, Chinchapattanam SND, and Garg A
- Abstract
Aims: Clinical decision making is challenging in men with metastatic prostate cancer (mPC), as heterogeneity in treatment options and patient characteristics have resulted in multiple scenarios with little or no evidence. The South East Asia Expert Panel 2019 addressed some of these challenges., Methods: Based on evidence in the literature and expert interviews, 19 statements were formulated for key challenges in the treatment of men with castration-sensitive and -resistant prostate cancer in clinical practice. A modified Delphi process was used to reach consensus among experts in the panel and develop clinical practice recommendations., Results: The majority of the panel preferred a risk-based stratification and recommended abiraterone or enzalutamide as first-line therapy for symptomatic chemotherapy naïve patients. Abiraterone is preferred over enzalutamide as a first-line treatment in these patients. However, the panel did not support the use of abiraterone in high risk lymph-node positive only (N+M0) or in non-metastatic (N0M0) patients. In select patients, low dose abiraterone with food may be used to optimize clinical outcomes. Androgen receptor gene splice variant status may be a useful guide to therapy. In addition, generic versions of approved therapies may improve access to treatment to a broader patient population. The choice of treatment, as well as sequencing are guided by both patient and disease characteristics, preferences, drug access, cost, and compliance., Conclusion: Expert recommendations are key to guidance for the optimal management of mPC. Appropriate choice, timing, and sequence of treatment options can help to tailor therapy to maximize outcomes in men with mPC., Competing Interests: Conflict of interest statement: Sai Naga Deepak Chinchapattanam is an employee of Dr Reddy’s Laboratories Ltd and Amit Garg was an employee of Dr Reddy’s Laboratories Ltd, Hyderabad at the time of meeting., (© The Author(s), 2021.)
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- 2021
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36. Effect of drug metabolizing enzymes and transporters in Thai colorectal cancer patients treated with irinotecan-based chemotherapy.
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Atasilp C, Chansriwong P, Sirachainan E, Reungwetwattana T, Sirilerttrakul S, Chamnanphon M, Puangpetch A, and Sukasem C
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- ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, ATP-Binding Cassette Transporters genetics, Adult, Aged, Alleles, Cytochrome P-450 CYP3A genetics, Female, Gene Frequency genetics, Genetic Variation genetics, Genotype, Glucuronosyltransferase genetics, Humans, Irinotecan metabolism, Irinotecan therapeutic use, Male, Membrane Transport Proteins genetics, Middle Aged, Multidrug Resistance-Associated Protein 2, Multidrug Resistance-Associated Proteins genetics, Neutropenia chemically induced, Polymorphism, Genetic genetics, Thailand epidemiology, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Irinotecan pharmacology
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Genetic polymorphisms in drug metabolizing enzymes and drug transporters may affect irinotecan toxicity. Although genetic polymorphisms have been shown to influence the irinotecan toxicity, data are limited in Thai population. Thus, the aim of this study was to assess the allele and genotype frequencies and the relationship between CYP3A4/5, DPYD, UGT1A1, ABCB1, and ABCC2 genetic variations and irinotecan-induced toxicity in Thai colorectal cancer patients. One hundred and thirty-two patients were genotyped, and the effect of genetic variations on irinotecan-induced toxicity was assessed in 66 patients who received irinotecan-based chemotherapy. Allele frequencies of ABCB1 c.1236C > T, ABCB1 c.3435C > T, ABCC2 c.3972C > T, ABCG2 c.421C > A, CYP3A4*1B, CYP3A4*18, CYP3A5*3, DPYD*5, UGT1A1*28, and UGT1A1*6 were 0.67, 0.43, 0.23, 0.27, 0.01, 0.02, 0.64, 0.19, 0.16, and 0.09, respectively. DPYD*2A and DPYD c.1774C > T variants were not detected in our study population. The ABCC2 c.3972C > T was significantly associated with grade 1-4 neutropenia (P < 0.012) at the first cycle. Patients carrying both UGT1A1*28 and *6 were significantly associated with severe neutropenia at the first (P < 0.001) and second (P = 0.017) cycles. In addition, patients carrying UG1A1*28 and *6 had significantly lower absolute neutrophil count (ANC) nadir at first (P < 0.001) and second (P = 0.001) cycles. This finding suggests that UGT1A1*28, *6, and ABCC2 c.3972C > T might be an important predictor for irinotecan-induced severe neutropenia.
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- 2020
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37. Role of BIM Deletion Polymorphism and BIM Expression as Predictive Biomarkers to Maximize the Benefit of EGFR-TKI Treatment in EGFR-Positive NSCLC.
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Incharoen P, Charonpongsuntorn C, Saowapa S, Sirachainan E, Dejthevaporn T, Kampreasart K, Trachu N, Muntham D, and Reungwetwattana T
- Subjects
- Aged, Apoptosis genetics, Bcl-2-Like Protein 11 metabolism, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung drug therapy, ErbB Receptors antagonists & inhibitors, Female, Humans, Lung Neoplasms drug therapy, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Progression-Free Survival, Retrospective Studies, Bcl-2-Like Protein 11 genetics, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics, Protein Kinase Inhibitors therapeutic use
- Abstract
Objective: BIM is a modulator of apoptosis that is triggered by EGFR-TKIs. This study evaluated the role of BIM deletion and its expression as predictor of EGFR-TKI treatment outcome., Methods: The medical record of 185 EGFR-positive advanced non-small cell lung cancer (NSCLC) patients with/ without EGFR-TKI treatment between 9/2012 and 12/2014 were retrospectively reviewed. BIM deletion polymorphism and expression were tested by RT-PCR and immunohistochemistry, respectively. Survival outcomes in EGFR-TKI-treated patients were analyzed according to treatment sequence and EGFR mutation. The correlation between BIM deletion polymorphism, expression, response rate (as a function of EGFR-TKI treatment) and schedule was also explored., Result: EGFR-TKIs were administered to 139 (75.1%) of the 185 patients: as the first-line in 52 (37.4%) patients and as later-line treatment in 87 (62.6%) patients. Median overall survival (mOS) was significantly longer in EGFR-TKIs treated patients (28.9 vs. 7.4 months, P<0.001). Among L858R-mutated patients, median progression-free survival (mPFS) was significantly longer in first-line EGFR TKI treatment than a later-line (12.6 vs. 6.3 months, P=0.03). BIM deletion polymorphism and expression was detected in 20.2% and 52.7%, respectively. Patients without BIM deletion polymorphism had a significantly longer mOS when treated with a first-line than with a later-line EGFR-TKI (28.9 vs. 20.7 months, P= 0.04). Patients without BIM expression had a significantly longer mPFS (9.6 vs. 7.3 months, P=0.01) better mOS and response rate (RR)., Conclusion: BIM deletion polymorphism and expression may predict an EGFR-TKI response in patients with EGFR-positive during therapy.
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- 2019
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38. Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma.
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Ngamphaiboon N, Chureemas T, Siripoon T, Arsa L, Trachu N, Jiarpinitnun C, Pattaranutaporn P, Sirachainan E, and Larbcharoensub N
- Subjects
- Aged, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Retrospective Studies, Smoking, B7-H1 Antigen metabolism, CD8-Positive T-Lymphocytes metabolism, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Head and Neck Neoplasms chemistry, Head and Neck Neoplasms epidemiology, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Lymphocytes, Tumor-Infiltrating metabolism, Squamous Cell Carcinoma of Head and Neck chemistry, Squamous Cell Carcinoma of Head and Neck epidemiology, Squamous Cell Carcinoma of Head and Neck mortality, Squamous Cell Carcinoma of Head and Neck pathology
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Background: No predictive biomarker of immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) has been well established. The impact of programmed death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocytes (TILs), and p16 status in HNSCC is unclear and may vary according to ethnicity., Methods: HNSCC patients treated between 2007 and 2013 were reviewed. Archival tissues were retrieved for PD-L1, CD8+ TILs, and p16 analyses. PD-L1 expression was evaluated by using the validated SP142 assay on the VENTANA platform. CD8+ TILs were defined by using semiquantitative scoring., Results: A total of 203 patients were analyzed. PD-L1 expression was observed in 80% of patients and was significantly associated with older age (P < 0.001). A high CD8+ TIL score (≥ 6) was significantly associated with never-smoking (P = 0.020), oral cavity cancer (P < 0.001), and stage M0 at presentation (P = 0.025). The p16 status was positive in 12% of patients. Patients with a high TIL score had a significantly longer OS (P = 0.032). Patients with PD-L1 expression of 1-49% and ≥ 50% were associated with a significantly shorter OS compared with those with PD-L1 < 1% (P = 0.027 and P = 0.011, respectively). Multivariate analysis showed that PD-L1 ≥ 50% was significantly associated with a poor OS. (HR 2.98 [95% CI 1.2-7.39]; P = 0.019.) CONCLUSIONS: A high prevalence of PD-L1 expression was observed in HNSCC using the validated SP142 assay. PD-L1 expression was associated with older age, while highly PD-L1 expression (≥ 50%) was an independent prognostic factor for poor OS in anti-PD1/PD-L1 untreated HNSCC patients.
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- 2019
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39. Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.
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Larbcharoensub N, Mahaprom K, Jiarpinitnun C, Trachu N, Tubthong N, Pattaranutaporn P, Sirachainan E, and Ngamphaiboon N
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- Aged, Combined Modality Therapy, Epstein-Barr Virus Infections virology, Female, Follow-Up Studies, Herpesvirus 4, Human isolation & purification, Humans, Male, Middle Aged, Nasopharyngeal Carcinoma immunology, Nasopharyngeal Carcinoma metabolism, Nasopharyngeal Carcinoma virology, Prognosis, Prospective Studies, Survival Rate, B7-H1 Antigen metabolism, Biomarkers, Tumor analysis, CD8-Positive T-Lymphocytes immunology, Epstein-Barr Virus Infections complications, Lymphocytes, Tumor-Infiltrating immunology, Nasopharyngeal Carcinoma pathology, Programmed Cell Death 1 Receptor metabolism
- Abstract
Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients., Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated., Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival., Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored.
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- 2018
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40. Determination of irinotecan, SN-38 and SN-38 glucuronide using HPLC/MS/MS: Application in a clinical pharmacokinetic and personalized medicine in colorectal cancer patients.
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Atasilp C, Chansriwong P, Sirachainan E, Reungwetwattana T, Puangpetch A, Prommas S, Sirilerttrakul S, Rerkarmnuaychoke B, Wongwaisayawan S, and Sukasem C
- Subjects
- Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacokinetics, Antineoplastic Agents, Phytogenic therapeutic use, Camptothecin blood, Camptothecin chemistry, Camptothecin pharmacokinetics, Camptothecin therapeutic use, Drug Monitoring, Glucuronides chemistry, Glucuronides pharmacokinetics, Humans, Irinotecan, Precision Medicine, Reproducibility of Results, Antineoplastic Agents, Phytogenic blood, Camptothecin analogs & derivatives, Chromatography, High Pressure Liquid methods, Colorectal Neoplasms drug therapy, Glucuronides blood, Tandem Mass Spectrometry methods
- Abstract
Background: Irinotecan (CPT-11) is chemotherapy used mainly in the metastatic colorectal cancer. The purpose of this study was to develop and validate the LC-MS/MS for the simultaneous determination of CPT-11, SN-38, and SN-38G., Methods: A 100 μL of plasma was prepared after protein precipitation and analyzed on a C18 column using 0.1% acetic acid in water and 0.1% acetic acid in acetonitrile as mobile phases. The mass spectrometer worked with multiple reaction monitoring (MRM) in positive scan mode. The standard curves were linear on a concentration range of 5-10 000 ng/mL for CPT-11, 5-1000 ng/mL for SN-38, and 8-1000 ng/mL for SN-38G., Results: In this assay, the intra and interday precision consisted of ≤9.11% and ≤11.29% for CPT-11, ≤8.70% and 8.31% for SN-38, and ≤9.90 and 9.64% for SN-38G., Conclusion: This method was successfully used to quantify CPT-11, SN-38, and SN-38G and applied to a pharmacokinetic study., (© 2017 Wiley Periodicals, Inc.)
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- 2018
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41. Molecular alterations and clinical prognostic factors for cholangiocarcinoma in Thai population.
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Trachu N, Sirachainan E, Larbcharoensub N, Rattanadech W, Detarkom S, Monnamo N, Kamprerasart K, MunTham D, Sukasem C, and Reungwetwattana T
- Abstract
This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR , KRAS , BRAF , and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR , KRAS , and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months) than those with the other types of EGFR mutations (4.08 months; hazard ratio [HR]: 0.26, P =0.038) and also had a significantly lower median Ki-67 (22.5% vs 80%, P =0.025). Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P =0.043). Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR and/or PIK3CA mutations implies that targeted drugs may provide a feasible CCC treatment in the future., Competing Interests: Disclosure The authors report no conflicts of interest in this work.
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- 2017
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42. 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.
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Cheng AL, Cornelio G, Shen L, Price T, Yang TS, Chung IJ, Dai GH, Lin JK, Sharma A, Yeh KH, Ma B, Zaatar A, Guan Z, Masood N, Srimuninnimit V, Yau T, Gibbs P, Wang X, Doval DC, Oh ST, Shim BY, Gorospe C, Wang HM, Sirachainan E, Hill A, Suh KW, Beier F, Chatterjee S, and Lim R
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Tumor metabolism, Camptothecin administration & dosage, Camptothecin adverse effects, Camptothecin analogs & derivatives, Cetuximab administration & dosage, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Disease-Free Survival, Drug Administration Schedule, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Humans, Leucovorin administration & dosage, Leucovorin adverse effects, Male, Middle Aged, Neoplasm Metastasis, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds adverse effects, Survival Rate, ras Proteins genetics, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Colorectal Neoplasms drug therapy, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
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 investigator's 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., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2017
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43. ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen.
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Sensorn I, Sukasem C, Sirachainan E, Chamnanphon M, Pasomsub E, Trachu N, Supavilai P, Pinthong D, and Wongwaisayawan S
- Abstract
Background: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim of this study is to investigate the impact of CYP3A5, CYP2D6, ABCB1, and ABCC2 polymorphisms on the risk of all distant and organ-specific metastases in Thai patients who received tamoxifen adjuvant therapy., Methods: Genomic DNA was extracted from blood samples of 73 patients with breast cancer who received tamoxifen adjuvant therapy. CYP3A5 (6986A>G), CYP2D6 (100C>T), ABCB1 (3435C>T), and ABCC2 (-24C>T) were genotyped using allelic discrimination real-time polymerase chain reaction assays. The impacts of prognostic clinical factors and genetic variants on disease-free survival were analyzed using the Kaplan-Meier method and Cox regression analysis., Results: In the univariate analysis, primary tumor size >5 cm was significantly associated with increased risk of distant metastasis (P=0.004; hazard ratio [HR] =3.05; 95% confidence interval [CI], 1.44-6.47). In the multivariate analysis, tumor size >5 cm remained predictive of distant metastasis (P<0.001; HR=5.49; 95% CI, 2.30-13.10). ABCC2 -24CC were shown to be associated with increased risk of distant metastasis (P=0.040; adjusted HR=2.34; 95% CI, 1.04-5.27). The combined genotype of ABCC2 -24CC - ABCB1 3435 CT+TT was associated with increased risk of distant and bone metastasis (P=0.020; adjusted HR=2.46; 95% CI, 1.15-5.26 and P=0.040; adjusted HR=3.70; 95% CI, 1.06-12.89, respectively)., Conclusion: This study indicates that polymorphisms of ABCC2 and ABCB1 are independently associated with bone metastasis. Further prospective studies with larger sample sizes are needed to verify this finding.
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- 2016
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44. DCE-MRI-Derived Parameters as Predictors of Response to Neo-Adjuvant Chemoradiation Treatment of Rectal Carcinoma.
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Phongkitkarun S, Tohmad U, Larbcharoensub N, Sumbunnanondha K, Swangsilpa T, and Sirachainan E
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- Adult, Aged, Female, Humans, Male, Middle Aged, Prospective Studies, Rectal Neoplasms pathology, Chemoradiotherapy, Adjuvant methods, Magnetic Resonance Imaging methods, Rectal Neoplasms therapy
- Abstract
Background: Preoperative combined chemoradiation treatment (CRT) is now accepted as the treatment of choice due to its benefits of decreasing the primary tumor volume and enhancing the sphincter preservation surgery. Determining whether a patient is responding to therapy is crucial for rectal cancer patients who may benefit from prompt treatment modifications., Objective: To evaluate the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the treatment response., Material and Method: Nineteen patients with histologically proven rectal adenocarcinoma who were candidates for neo-adjuvant CRT were prospectively included. All patients were examined by conventional and DCE-MRi at three time points (pre-, during-, and post-CRT). Surgical resection was performed after complete CRT. The pathological response and Dworak regression grade were assessed. All parameters were blindly analyzed., Results: The median pathologic response rate for all patients was 40%. Dworak regression grades of 0, 1, 2, 3, and 4 were found in 0.0%, 21.1%, 42.1%, 26.3%, and 10.5% of patients, respectively. The tumor thickness and length were 30% and 32.9% lower at during-CRT and 40.6% and 44.7% lower post-CRT and had moderate and fair negative correlations with the pathologic response rate and Dworak regression rate, respectively. Among the DCE-MRI parameters, only a change in the time to peak between pre- and during-CRT was correlated with the Dworak regression grade (p = 0.01). The percentage change in the time to peak in patients with poor regression (grades 0-1) was significantly greater than in patients with intermediate/complete regression (grades 2-4) [139.25% vs. 6.13%]., Conclusion: Changes in the tumor thickness and length evaluated by conventional MRI and the time to peak evaluated by DCE-MRI during CRT may be useful for predicting the treatment response of rectal cancer patients.
- Published
- 2016
45. Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients.
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Atasilp C, Chansriwong P, Sirachainan E, Reungwetwattana T, Chamnanphon M, Puangpetch A, Wongwaisayawan S, and Sukasem C
- Subjects
- Adult, Aged, Aged, 80 and over, Camptothecin adverse effects, Camptothecin therapeutic use, Colorectal Neoplasms drug therapy, Female, Genetic Predisposition to Disease genetics, Genotype, Humans, Irinotecan, Male, Middle Aged, Risk, Thailand, Asian People genetics, Camptothecin analogs & derivatives, Colorectal Neoplasms genetics, Glucuronosyltransferase genetics, Neutropenia chemically induced, Neutropenia genetics, Polymorphism, Genetic genetics
- Abstract
UDP-glucuronosyltransferase1A1 (UGT1A1) polymorphisms have been related with irinotecan toxicity. The purpose of this study was to determine the associations between UGT1A1(*)28 and (*)6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal cancer patients received irinotecan-based chemotherapy. Hematologic toxicities were determined in the first and second cycles of treatment. The genotypes of UGT1A1(*)28 and (*)6 were analyzed by pyrosequencing technique. The frequencies of genetic testing for UGT1A1(*)28 and (*)6 polymorphisms were 22.8% (TA6/TA7; 20.5%, TA7/TA7; 2.3%) and 15.9% (GA), respectively. No patients had the homozygous UGT1A1(*)6 (AA). Neither UGT1A1(*)28 nor UGT1A1(*)6 polymorphisms were significantly associated with severe hematologic toxicities. However, analysis of UGT1A1(*)28 and (*)6 in combination revealed an association with severe neutropenia in the first and second cycles (P = 0.044, P = 0.017, respectively). Both UGT1A1(*)28 and (*)6 polymorphisms may have an increased risk of irinotecan-induced neutropenia in Thai colorectal cancer patients., (Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
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- 2016
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46. Development of Pyrosequencing Method for Detection of UGT1A1 Polymorphisms in Thai Colorectal Cancers.
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Sukasem C, Atasilp C, Chansriwong P, Chamnanphon M, Puangpetch A, and Sirachainan E
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- Adult, Aged, Aged, 80 and over, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Sensitivity and Specificity, Software, Thailand, Colorectal Neoplasms enzymology, Colorectal Neoplasms genetics, Glucuronosyltransferase genetics, High-Throughput Nucleotide Sequencing methods, Polymorphism, Single Nucleotide genetics
- Abstract
Background: UGT1A1 is a polymorphic enzyme that has been associated with irinotecan drug metabolisms. We developed a pyrosequencing method to detect allele frequency and genotype of UGT1A1 polymorphisms (UGT1A1*28 and UGT1A1*6) in Thai colorectal cancer patients., Method: A pyrosequencing method was designed to determine UGT1A1 genetic polymorphisms including UGT1A1*28 (A[TA]7TAA) and UGT1A1*6 (211G>A) in 91 Thai colorectal cancers., Result: Genotyping by the pyrosequencing technique was 100% concordant with capillary electrophoresis sequencing. The allele frequencies for UGT1A1 genetic polymorphisms were *1/*1 (54.95%), *1/*6 (13.19%), *1/*28 (25.27%), *28/*6 (4.40%), and *28/*28 (2.20%). No homozygous mutation UGT1A1*6 was found in our population., Conclusions: We developed a rapid, reliable, more cost-effective, and simple assay to detect UGT1A1 genetic polymorphisms in routine practice before initiating irinotecan therapy. The UGT1A1*28 and UGT1A1*6 alleles were found to be similar in the Asian populations., (© 2014 Wiley Periodicals, Inc.)
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- 2016
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47. Transcriptome meta-analysis reveals dysregulated pathways in nasopharyngeal carcinoma.
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Tulalamba W, Larbcharoensub N, Sirachainan E, Tantiwetrueangdet A, and Janvilisri T
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- Biomarkers, Tumor genetics, Carcinoma, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Microarray Analysis, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms pathology, Neoplasm Proteins genetics, Prognosis, Signal Transduction, Biomarkers, Tumor biosynthesis, Gene Expression Profiling, Nasopharyngeal Neoplasms genetics, Neoplasm Proteins biosynthesis
- Abstract
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.
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- 2015
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48. Esthesioneuroblastoma metastasis to the breast: A case report and review of the literature.
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Larbcharoensub N, Kanoksil W, Cheewaruangroj W, Wiratkapun C, Sitathanee C, and Sirachainan E
- Abstract
Metastasis to the breast from an extramammary malignant neoplasm, including esthesioneuroblastoma, is uncommon. The present study describes a rare case of sinonasal esthesioneuroblastoma, Hyams' histologic grade 2, Kadish's stage C, T4N0M0, in a 30-year-old female. The patient underwent a radical ethmoidectomy with external beam radiotherapy, followed by chemotherapy including five cycles of cisplatin and etoposide. One year after the initial diagnosis, the patient presented to the hospital with the chief complaint of a rapidly enlarging lump in the right breast. A fine needle aspiration was performed and immunocytochemistry revealed a metastatic esthesioneuroblastoma. The patient received palliative chemotherapy and radiotherapy; however, the patient developed a local recurrence with systemic metastasis and succumbed to the disease seven months later.
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- 2014
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49. A call for action to improve access to care and treatment for patients with rare diseases in the Asia-Pacific region.
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Soon SS, Lopes G, Lim HY, Wong-Rieger D, Bahri S, Hickinbotham L, Jha A, Ko BS, MacDonell D, Pwu JR, Shih R, Sirachainan E, Suh DC, Wale J, Zhang X, and Wee HL
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- Asia ethnology, Humans, Pacific Ocean ethnology, Rare Diseases diagnosis, Treatment Outcome, Health Policy, Health Services Accessibility, Rare Diseases ethnology, Rare Diseases therapy
- Abstract
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.
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- 2014
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50. Treatment outcome of palliative chemotherapy in inoperable cholangiocarcinoma in Thailand.
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Butthongkomvong K, Sirachainan E, Jhankumpha S, Kumdang S, and Sukhontharot OU
- Subjects
- Adult, Aged, Aged, 80 and over, Bile Duct Neoplasms drug therapy, Bile Duct Neoplasms secondary, Capecitabine, Carboplatin administration & dosage, Cholangiocarcinoma drug therapy, Cholangiocarcinoma pathology, Cisplatin administration & dosage, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Female, Fluorouracil administration & dosage, Fluorouracil analogs & derivatives, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Prognosis, Retrospective Studies, Survival Rate, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bile Duct Neoplasms mortality, Bile Ducts, Intrahepatic drug effects, Cholangiocarcinoma mortality, Palliative Care
- Abstract
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.
- Published
- 2013
- Full Text
- View/download PDF
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