Cancer Research and Treatment

Original Articles

BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy: Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro; Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019; DOI: https://doi.org/10.4143/crt.2018.598

Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Citations

Citations to this article as recorded by

PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis
Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
Breast Cancer Research and Treatment.2023; 201(2): 161. CrossRef
Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
Translational Oncology.2023; 37: 101738. CrossRef
Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations
Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
JCO Precision Oncology.2022;[Epub] CrossRef
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
Ugo Testa, Germana Castelli, Elvira Pelosi
Medical Sciences.2020; 8(1): 18. CrossRef

8,259 View
190 Download
4 Web of Science
5 Crossref

Differences in Overall Survival When Colorectal Cancer Patients are Stratified into New TNM Staging Strategy: Ho-Suk Oh, Hyoung-Jung Chung, Hearn-Kook Kim, Jong-Soo Choi; Cancer Res Treat. 2007;39(2):61-64. Published online June 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.2.61

Abstract PDF PubReader ePub

Purpose

The purpose of this study is to determine whether the prognosis can be more precisely gauged by the revised 6th AJCC staging system and if this is suitable for Korean colorectal cancer patients, and especially for those patients in the Youngdong district.

Materials and Methods

Between September 1996 and December 2003, 365 patients with histologically confirmed colorectal cancer were analyzed. Kaplan-Meier analyses were used to compare the overall and stage-specific 5-year survival. All the statistical tests were two-sided.

Results

The overall 5-year survival for the entire cohort was 62%. According to the stages defined by the AJCC fifth edition system, the 5-year stage-specific survival was 91% for stage I, 82% for stage II, 51% for stage III and 4% for stage IV. According to the stages defined by the AJCC sixth edition system, the 5-year stage-specific survival was 91% for stage I, 81% for stage IIa, 83% for stage IIb, 100% for stage IIIa, 64% for stage IIIb, 37% for stage IIIc and 4% for stage IV. The 5-year survival was significantly better for the patients with stage IIIb (64%) than those patients with stage IIIc (37%) (p<.001).

Conclusion

It is widely known that the AJCC sixth edition system for colorectal cancer stratifies survival more distinctly than does the fifth edition system by providing more substages. Our study showed that stage IIIb disease had better survival than stage IIIc disease, but we couldn't confirm that this new staging system is relevant in our Korean clinical practice due to the small study population. Therefore, further study is required in a larger population.

Citations

Citations to this article as recorded by

Pathological Characteristics, Prognostic Determinants and the Outcome of Patients Diagnosed with Colorectal Adenocarcinoma at the University Teaching Hospital of Kigali
Delphine Uwamariya, Déogratias Ruhangaza, Belson Rugwizangoga, Antonio Giovanni Solimando
Canadian Journal of Gastroenterology and Hepatology.2022; 2022: 1. CrossRef
Estimating short-term and long-term survival in rectal cancer patients using cure model
Behrouz Beiranvand, Shaghayegh Kamian, Robabeh Ghodssi-Ghassemabadi
Journal of Family Medicine and Primary Care.2022; 11(9): 5615. CrossRef
Assessment of prognostic factors in long-term survival of male and female patients with colorectal cancer using non-mixture cure model based on the Weibull distribution
Mehdi Azizmohammad Looha, Elaheh Zarean, Fatemeh Masaebi, Mohamad Amin Pourhoseingholi, Mohamad Reza Zali
Surgical Oncology.2021; 38: 101562. CrossRef
The role of socioeconomic disparity in colorectal cancer stage at presentation
Aesha Patel, Owen Gantz, Pavel Zagadailov, Aziz M. Merchant
Updates in Surgery.2019; 71(3): 523. CrossRef
The effects of time valuation in cancer optimal therapies: a study of chronic myeloid leukemia
Pedro José Gutiérrez-Diez, Miguel Ángel López-Marcos, Julia Martínez-Rodríguez, Jose Russo
Theoretical Biology and Medical Modelling.2019;[Epub] CrossRef
Permanent colostomy wound: Aeromedical disposal
U Bhattacharya, A Kumar, AVK Raju
Indian Journal of Aerospace Medicine.2019; 63: 39. CrossRef
Analyzing the Long-Term Survival of Patients with Colorectal Cancer: A Study Using Parametric Non-Mixture Cure Rate Models
Mehdi Azizmohammad Looha, Elaheh Zarean , Mohamad Amin Pourhoseingholi, Seyyed Vahid Hosseini, Tara Azimi, Soheila Khodakarim
International Journal of Cancer Management.2018;[Epub] CrossRef
Colorectal Cancer in Jordan: Survival Rate and Its Related Factors
Ghazi Faisal Sharkas, Kamal H. Arqoub, Yousef S. Khader, Mohammad R. Tarawneh, Omar F. Nimri, Marwan J. Al-zaghal, Hadil S. Subih
Journal of Oncology.2017; 2017: 1. CrossRef
ROR1 expression as a biomarker for predicting prognosis in patients with colorectal cancer
Jian-Kang Zhou, Yu-Zhu Zheng, Xue-Sha Liu, Qiheng Gou, Rui Ma, Cheng-Lin Guo, Carlo M. Croce, Lunxu Liu, Yong Peng
Oncotarget.2017; 8(20): 32864. CrossRef
High expression levels of unc-51-like kinase 1 as a predictor of poor prognosis in colorectal cancer
YIFENG ZOU, ZEXIAN CHEN, XIAOWEN HE, XIAOSHENG HE, XIANRUI WU, YUFENG CHEN, XIAOJIAN WU, JIANPING WANG, PING LAN
Oncology Letters.2015; 10(3): 1583. CrossRef
Follow-up After Curative Resection of Colorectal Cancer
Bridget N. Fahy
Annals of Surgical Oncology.2014; 21(3): 738. CrossRef
An overview of colorectal cancer survival rates and prognosis in Asia
Bijan Moghimi-Dehkordi
World Journal of Gastrointestinal Oncology.2012; 4(4): 71. CrossRef

16,756 View
105 Download
12 Crossref

Phase II Study of Oxaliplatin, 5-fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as Second Line Therapy: Duk-Joo Lee, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Myung-Ju Ahn; Cancer Res Treat. 2006;38(4):201-205. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.201

Abstract PDF PubReader ePub: Purpose
The purpose of the study was to assess the efficacy and safety of biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic colorectal cancer (CRC) as a second line therapy.
Materials and Methods
Between November 2002 and October 2005, 26 patients with histologically confirmed relapsed or metastatic CRC were enrolled. All patients were previously treated with irinotecan-based combination chemotherapy. The chemotherapy regimen consisted of oxaliplatin 85 mg/m² on day 1; LV 200 mg/m² on days 1 and 2; and 5-FU 400 mg/m² bolus IV with 600 mg/m² with a 22-hour infusion on days 1 and 2 every 2 weeks.
Results
The median age of the 26 patients was 50.5 years (range, 31~72). Their metastatic sites included: the liver (42.3%), peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were evaluated for their response. Four patients achieved partial responses and 15 patients had stable disease. The overall response rate was 16% (95% confidence interval; 1.7~30.3%). The median follow-up duration for the surviving patients was 7.4 months (range, 2.08~21.2). Median overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%, respectively. The most common hematological toxicities were: NCI grade I/II leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%). The main non-hematological toxicities were: grade I/II peripheral neuropathy (16.1% and 21.5%, respectively) and nausea/vomiting (23.6%/18.5%). There was no life-threatening toxicity.
Conclusion
The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or metastatic colorectal cancer patients as second line chemotherapy.

7,301 View
26 Download

Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy: Myung-Ju Ahn, Jung-Hye Choi, Ho-Suk Oh, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Kang-Hong Lee, Kang-Won Song, Chan-Kum Park; Cancer Res Treat. 2005;37(4):216-222. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.216

Abstract PDF PubReader ePub

Purpose

In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival.

Materials and Methods

The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated.

Results

Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy.

Conclusion

These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Citations

Citations to this article as recorded by

Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
Laura Grumetti, Rita Lombardi, Federica Iannelli, Biagio Pucci, Antonio Avallone, Elena Di Gennaro, Alfredo Budillon
Cancers.2022; 14(3): 695. CrossRef
Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study
Wilson Roberto Batista, Gianni Santos, Flávia Maria Ribeiro Vital, Delcio Matos
Sao Paulo Medical Journal.2019; 137(1): 33. CrossRef
Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5‑fluorouracil‑based chemotherapy: A meta‑analysis
Jia Che, Lun Pan, Xiangling Yang, Zhiting Liu, Lanlan Huang, Chuangyu Wen, Aihua Lin, Huanliang Liu
Molecular and Clinical Oncology.2017;[Epub] CrossRef
Does anti-p53 antibody status predict for clinical outcomes in metastatic colorectal cancer patients treated with fluoropyrimidine, oxaliplatin, plus bevacizumab as first-line chemotherapy?
Hiroki Osumi, Eiji Shinozaki, Mitsukuni Suenaga, Yosuke Kumekawa, Mariko Ogura, Masato Ozaka, Satoshi Matsusaka, Keisho Chin, Noriko Yamamoto, Nobuyuki Mizunuma
BMC Cancer.2015;[Epub] CrossRef
Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
Hye Sung Won, Myung Ah Lee, Eun-Seon Chung, Dong-Goo Kim, Young Kyoung You, Tae Ho Hong, In-Seok Lee
BMC Cancer.2010;[Epub] CrossRef

9,078 View
36 Download
5 Crossref

Phase II Study of Irinotecan, 5-Fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as First-line Therapy: Young-Woong Won, Young-Hyo Lim, Ho-Yong Park, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Myung-Ju Ahn; Cancer Res Treat. 2004;36(4):235-239. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.235

Abstract PDF PubReader ePub

Background

The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer.

Materials and Methods

Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m² on days 1 and 15; 5-FU 400 mg/m² bolus IV with 600 mg/m² by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m² on days 1, 2, 15 and 16, every 4 weeks.

Results

The median age of the 24 was 57.5 years (range, 38~69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3~44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7~26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity.

Conclusion

The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.

Citations

Citations to this article as recorded by

A Phase I Study of UGT1A1 *28/*6 Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI
Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Kyun Seop Bae, Ho-Sook Kim, Jae-Gook Shin, Jung Shin Lee, Tae Won Kim
Oncology.2015; 88(3): 164. CrossRef
Effect of an Irinotencan, 5-Fluorouracil, and Leucovorin Combination Chemotherapy (FOLFIRI) in Metastatic Colorectal Cancer
Seung Hyun Lee, Byung Kwon Ahn, Sung Uhn Baek
Journal of the Korean Society of Coloproctology.2007; 23(5): 333. CrossRef
A Phase II Study of Irinotecan, 5-Fluorouracil and Leucovorin for Treatment in Patients with Previously Untreated Advanced Colorectal Cancer
Sang-Byung Bae, Nam-Su Lee, Han-Jo Kim, Kyoung-Ha Kim, Hyun-Jung Kim, Chan-Kyu Kim, Kyu-Taeg Lee, Sung-Kyu Park, Jong-Ho Won, Dae-Sik Hong, Hee-Sook Park
Cancer Research and Treatment.2006; 38(2): 72. CrossRef
Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer
Myung-Ah Lee, Jae-Ho Byun, Byoung-Young Shim, In-Sook Woo, Jin-Hyung Kang, Young Seon Hong, Kyung Shik Lee, Myung Gyu Choi, Suk Kyun Chang, Seong Taek Oh, Sung Il Choi, Doo Suk Lee
The Korean Journal of Internal Medicine.2005; 20(3): 205. CrossRef
Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer
In Ja Park, Hee Cheol Kim, Chang Sik Yu, Heung Moon Chang, Jea Hwan Lee, Jong Hoon Kim, Tae Won Kim, Jung Sun Kim, Jin Cheon Kim
Cancer Research and Treatment.2004; 36(6): 360. CrossRef

8,262 View
57 Download
5 Crossref

Radiofrequency Ablation for Metastatic Hepatic Tumor in Colorectal Carcinoma: Jung-Hye Choi, Myung-Ju Ahn, Hyunchul Rhim, Heung Woo Lee, Ho-Suk Oh, Young-Yeul Lee, Il-Young Choi, In-Soon Kim; Cancer Res Treat. 2004;36(2):128-131. Published online April 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.2.128

Abstract PDF PubReader ePub

Purpose

The purpose of this study was to assess the efficacy and safety of radiofrequency ablation (RFA) to treat hepatic metastasis in patients with colorectal carcinoma.

Materials and Methods

Between May 1999 and July 2002, a total of 45 tumors in 24 patients with colorectal cancer were treated with RFA. Thirteen patients received systemic chemotherapy after the RFA procedure. The ablation was performed percutaneously under ultrasound guidance using cool-tip or expandable electrodes and an RF generator. The medical records as well as the CT scan results taken every 3 months were retrospectively reviewed.

Results

The median follow-up duration of the surviving patients was 11.7 months (4.6~32.2 months). Complete tumor necrosis was achieved in 17 patients (70.8%) on an immediate (<24 hrs) CT scan. The median survival was 17.1 months. The 1- and 2-year survival rates were 80.5 and 25.8%, respectively. In a univariate analysis, complete necrosis, tumor size and post-RFA chemotherapy were significant factors for survival. Nineteen of the 24 patients developed a recurrence or progressed (79.2%). The median progression free survival was 5.5 months. There were no treatment related deaths or serious adverse effects, with the exception of one case of respiratory failure.

Conclusion

These results suggest that RFA is a well-tolerated and effective method to treat hepatic metastasis in colorectal carcinomas.

Citations

Citations to this article as recorded by

Single-centre survival analysis over 10 years after MR-guided radiofrequency ablation of liver metastases from different tumour entities
Susann-Cathrin Olthof, Daniel Wessling, Moritz T. Winkelmann, Hansjörg Rempp, Konstantin Nikolaou, Rüdiger Hoffmann, Stephan Clasen
Insights into Imaging.2022;[Epub] CrossRef
Prognostic factors after ultrasound‐guided percutaneous ablation of colorectal liver metastases: A systematic review
Jeanett Klubien, Andreas P. Kohl, Christian P. Nolsøe, Jacob Rosenberg, Hans‐Christian Pommergaard
Australasian Journal of Ultrasound in Medicine.2018; 21(2): 87. CrossRef
Impact of timing and cycles of systemic chemotherapy on survival outcome of colorectal liver metastases patients treated by percutaneous microwave ablation
Kai Zhang, Jie Yu, Fubo Zhou, Xiaoling Yu, Xin Li, Jianbin Wang, Zhiyu Han, Zhigang Cheng, Ping Liang
International Journal of Hyperthermia.2016; 32(5): 531. CrossRef
Efficacy and safety of thermal ablation in patients with liver metastases
Yingjun Liu, Shengping Li, Xiangbin Wan, Yi Li, Binkui Li, Yaqi Zhang, Yunfei Yuan, Yun Zheng
European Journal of Gastroenterology & Hepatology.2013; 25(4): 442. CrossRef
CT- versus coregistered FDG-PET/CT-based radiation therapy plans for conformal radiotherapy in colorectal liver metastases: a dosimetric comparison
Cem Parlak, Erkan Topkan, Serhat Sonmez, Cem Onal, Mehmet Reyhan
Japanese Journal of Radiology.2012; 30(8): 628. CrossRef

8,076 View
56 Download
5 Crossref

First
Prev
Page of 1
Next
Last

Search