Cancer Research and Treatment

Original Articles

Novel Breast Cancer Risk Assessment Tools for Pre- and Post-Menopausal Asian Women: Development and Validation in a Nationwide Mammographic Screening Cohort: Wonyoung Jung, Yong-Moon Mark Park, Sang Hyun Park, Kyungdo Han, Junhee Park, Yohwan Yeo, Jung Kwon Lee, Dale P. Sandler, Dong Wook Shin; Received September 4, 2024 Accepted January 30, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.861 [Accepted]

Abstract PDF: Purpose
Widely used breast cancer risk-prediction tools are based on data from Western countries, but risk factors may differ for Asian women. Hence, we aimed to develop a risk assessment tool for breast cancer in Asian women using a nationwide, population-based mammographic screening cohort.
Materials and Methods
Women aged ≥40 years who underwent breast cancer screening and general health examination in 2009 were included. Age, body mass index (BMI), breast density, lifestyle and reproductive factors, and comorbidities were used to develop 5-year breast cancer risk-prediction models for premenopausal (n=771,856) and postmenopausal (n=1,108,047) women at baseline. The best-fit risk prediction model was constructed using backward stepwise selection in a Cox proportional hazards model and was transformed into a risk score nomogram. The performance was assessed by discrimination and calibration.
Results
In premenopausal women, high BMI, low parity, short breastfeeding period, early age at menarche, high breast density, a history of benign breast masses, and family history of breast cancer contributed to the risk prediction of breast cancer. In postmenopausal women, age, diabetes mellitus, dyslipidemia, late-onset menopause, and hormone replacement therapy use were additional risk predictors of breast cancer. Our risk-prediction model showed a concordant statistic of 0.58 (0.57–0.59) for premenopausal women and 0.64 (0.63–0.65) for postmenopausal women. The calibration plot demonstrated good correlations for both models.
Conclusion
Our breast cancer risk-prediction model demonstrated performance comparable to that of Western countries, especially among postmenopausal women. This provides a foundation for implementing risk-based screening recommendations in Asian women.

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Genitourinary cancer

Physical Activity and Bladder Cancer Risk: Findings of the Japan Collaborative Cohort Study: Hang An, Keyang Liu, Kokoro Shirai, Ryo Kawasaki, Akiko Tamakoshi, Hiroyasu Iso; Cancer Res Treat. 2024;56(2):616-623. Published online October 6, 2023; DOI: https://doi.org/10.4143/crt.2023.962

Abstract PDF Supplementary Material PubReader ePub: Purpose
The association of physical activity with the risk of bladder cancer remains inconsistent among Asian populations. We aimed to examine the association in a large Japanese cohort.
Materials and Methods
In a population-based prospective cohort study, a total of 50,374 Japanese adults aged 40-79 years without a history of cancer or cardiovascular disease who had information on physical activity from self-administrated questionnaires were used for analysis. We performed Cox proportional hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident bladder cancer after adjusting for several potential confounders.
Results
During the median 17.5 years of follow-up, 153 incident bladder cancers (116 men and 37 women) were identified. After the multivariable adjustment, HRs (95% CI) of bladder cancer concerning those with recreational sports participation of 1-2 hr/wk, 3-4 hr/wk, and 5 hr/wk and more were 0.67 (0.38-1.20), 0.79 (0.36-1.74), and 0.28 (0.09-0.89), respectively (p for trend=0.017). Compared with mostly sitting at the workplace, occupational physical activity of standing and walking were associated with a lower risk of bladder cancer (HR, 0.53 [95% CI, 0.32 to 0.85]). Hours of daily walking were not associated with the risk. The lower risk of bladder cancer was more evident for recreational sports (HR, 0.33 [95% CI, 0.10 to 1.00]), and for occupational standing and walking activity at work (HR, 0.57 [95% CI, 0.33 to 0.98]) among men.
Conclusion
Recreational sports participation and occupational physical activity were inversely associated with the risk of bladder cancer among Japanese, especially in men.

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Breast cancer

Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies: Yong Wha Moon, Seung Ki Kim, Keun Seok Lee, Moon Hee Lee, Yeon Hee Park, Kyong Hwa Park, Gun Min Kim, Seungtaek Lim, Seung Ah Lee, Jae Duk Choi, Eunhye Baek, Hyesun Han, Seungjae Baek, Seock-Ah Im; Cancer Res Treat. 2023;55(3):766-777. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.987

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
Materials and Methods
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
Results
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
Conclusion
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

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Comparison of Prophylactic Efficacy of Eflapegrastim and Pegteograstim for Chemotherapy-induced Neutropenia in Pancreatic Cancer Patients Receiving FOLFIRINOX/mFOLFIRINOX
Eui Seon Lee, Min Jung Geum, Jong Hee Ko, Jae Song Kim, Eun Sun Son, Yun Mi Yu
Journal of Korean Society of Health-System Pharmacists.2024; 41(3): 253. CrossRef

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Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09): Jieun Lee, Keun Seok Lee, Sung Hoon Sim, Heejung Chae, Joohyuk Sohn, Gun Min Kim, Kyung-Hee Lee, Su Hwan Kang, Kyung Hae Jung, Jae-ho Jeong, Jae Ho Byun, Su-Jin Koh, Kyoung Eun Lee, Seungtaek Lim, Hee Jun Kim, Hye Sung Won, Hyung Soon Park, Guk Jin Lee, Soojung Hong, Sun Kyung Baek, Soon Il Lee, Moon Young Choi, In Sook Woo; Cancer Res Treat. 2023;55(1):123-135. Published online March 24, 2022; DOI: https://doi.org/10.4143/crt.2021.1561

Abstract PDF Supplementary Material PubReader ePub

Purpose
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Citations

Citations to this article as recorded by

HER2 expression and pathway status in male breast cancer patients: results of an integrated analysis among 6,150 patients
Boqiang Lyu, Shidi Zhao, Hui Wang, Shouping Gong, Biyuan Wang
Scientific Reports.2025;[Epub] CrossRef
Male breast cancer - a single center experience
Igor Djurisic, Milan Zegarac, Milan Kocic, Vladimir Jokic, Nikola Vucic, Ognjen Petrovic, Nada Santrac, Jovana Koncar, Andjela Ivezic, Srdjan Nikolic
Srpski arhiv za celokupno lekarstvo.2025; 153(1-2): 53. CrossRef
Clinicopathologic Features and Prognoses of Male Patients With Breast Cancer
Meiling Huang, Jingjing Xiao, Changjiao Yan, Rui Ling, Ting Wang
American Journal of Men's Health.2024;[Epub] CrossRef

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3 Crossref

Breast Cancer

Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial: Kyung-Hun Lee, Joohyuk Sohn, Annabel Goodwin, Tiziana Usari, Silvana Lanzalone, Seock-Ah Im, Sung-Bae Kim; Cancer Res Treat. 2021;53(4):1084-1095. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2020.1381

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

Citations

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HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Detection and analysis of the safety profile of talazoparib based on FAERS database
Mufei Tang, Peiyan Liu, Linzhe Du, Yuanyuan Li, Jinjin Chen, Yang Li
Expert Opinion on Drug Safety.2024; : 1. CrossRef
Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment
Haixia Liu, Xiaohui Chen, Yimin Jia, Hengyi Chen, Xiaohui Wang, Guoxiang Liu, Yang Luo
Interdisciplinary Medicine.2023;[Epub] CrossRef
Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer
Shicheng Yang, Allen Green, Needa Brown, Alexis Robinson, Merline Senat, Bryanna Testino, Daniela M. Dinulescu, Srinivas Sridhar
Frontiers in Oncology.2023;[Epub] CrossRef
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
S.-A. Im, A. Gennari, Y.H. Park, J.H. Kim, Z.-F. Jiang, S. Gupta, T.H. Fadjari, K. Tamura, M.Y. Mastura, M.L.T. Abesamis-Tiambeng, E.H. Lim, C.-H. Lin, A. Sookprasert, N. Parinyanitikul, L.-M. Tseng, S.-C. Lee, P. Caguioa, M. Singh, Y. Naito, R.A. Hukom,
ESMO Open.2023; 8(3): 101541. CrossRef
Molecular Biology Mechanisms and Emerging Therapeutics of Triple-Negative Breast Cancer
Zhiying Zhang, Rui Zhang, Donghai Li
Biologics: Targets and Therapy.2023; Volume 17: 113. CrossRef
Development of the PARP inhibitor talazoparib for the treatment of advanced BRCA1 and BRCA2 mutated breast cancer
Evthokia A. Hobbs, Jennifer K. Litton, Timothy A. Yap
Expert Opinion on Pharmacotherapy.2021; : 1. CrossRef

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Gynecologic Cancer

Performance and Diagnostic Accuracy of Human Papillomavirus Testing on Self-Collected Urine and Vaginal Samples in a Referral Population: Hyun-Woong Cho, Jin Hwa Hong, Kyung Jin Min, Yung-Taek Ouh, Seok Ju Seong, Jun Hye Moon, Seong Hwan Cho, Jae Kwan Lee; Cancer Res Treat. 2021;53(3):829-836. Published online December 24, 2020; DOI: https://doi.org/10.4143/crt.2020.1165

Abstract PDF PubReader ePub

Purpose
The study aimed to evaluate the diagnostic accuracy of polymerase chain reaction ‒based high-risk human papillomavirus (HPV) assays on self-collected vaginal and urine samples for detection of precancerous cervical lesions in referral population.
Materials and Methods
Women referred for colposcopy following abnormal cytology, were included this study. A total of 314 matched urine, vaginal, and cervical samples were collected. All samples were tested for HPV DNA using the RealTime HR-S HPV and Anyplex II HPV 28 assays. Primary endpoints were sensitivity for cervical intraepithelial neoplasia (CIN) 2+/CIN3+ and specificity for Result
The sensitivity of Realtime HR-S and Anyplex HPV assay was 93.13% (95% confidence interval [CI], 87.36 to 96.81) and 90.08% (95% CI, 83.63 to 94.61) for CIN2+ (n=130); specificity for Conclusion
The detection performance for hrHPV and CIN2+ on self-collected vaginal samples was comparable to that of clinician-collected cervical samples. On the other hand, HPV tests using urine were inferior to those using clinician-collected cervical samples in terms of detecting hrHPV and CIN2+.

Citations

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Diagnostic accuracy of human papillomavirus testing on self-collected samples among women referred for colposcopy
ChunX Yan, Jiong Ma, Xia Zheng, Jing Shu, XiaoJ Wang, XiaoY Chen, Feng Gao, XiaoQ Li, ShanQ M, LongM Huang, XiaoT Yu, XueJ Chen
Scientific Reports.2025;[Epub] CrossRef
Accuracy of real-time PCR assays for human papillomavirus using urine samples: a systematic review and meta-analysis
Byeong-Min Park, Soohyun Kim, Jieun Choi, Yoonkyung Song, Seungman Park, Randall Hayden
Journal of Clinical Microbiology.2025;[Epub] CrossRef
Variables that impact HPV test accuracy during vaginal self collection workflow for cervical cancer screening
Laurence Vaughan, Devin Gary, Millie Shah, Lyndsay Lewellen, Laura Galbraith, Valentin Parvu
Gynecologic Oncology Reports.2024; 54: 101421. CrossRef
Clinical performance of a newly developed domestic urine‐based HPV test for cervical cancer screening in China
Hui‐Fang Xu, Xue‐Lian Zhao, Shuang Zhao, Shang‐Ying Hu, Xun Zhang, Fang‐Hui Zhao, You‐Lin Qiao
Journal of Medical Virology.2023;[Epub] CrossRef
Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?
Yu-Hsiang Shih, Lou Sun, Shih-Tien Hsu, Ming-Jer Chen, Chien-Hsing Lu
International Journal of Women's Health.2023; Volume 15: 1421. CrossRef
Preliminary Results of Feasibility and Acceptability of Self-Collection for Cervical Screening in Italian Women
Illari Sechi, Narcisa Muresu, Mariangela V. Puci, Laura Saderi, Arcadia Del Rio, Andrea Cossu, Maria R. Muroni, Santina Castriciano, Marianna Martinelli, Clementina E. Cocuzza, Giovanni Sotgiu, Andrea Piana
Pathogens.2023; 12(9): 1169. CrossRef
Human papillomavirus testing using HPV APTIMA® assay and an external cellularity control in self‐collected samples
Christophe Pasquier, Stéphanie Raymond, Delphine Duchanois, Karine Sauné, Kevin Oliveira‐Mendes, Christophe Vayssiere, Jacques Izopet
Journal of Medical Virology.2023;[Epub] CrossRef
Comparison of Different Self-Sampling Devices for Molecular Detection of Human Papillomavirus (HPV) and Other Sexually Transmitted Infections (STIs): A Pilot Study
Illari Sechi, Clementina Cocuzza, Marianna Martinelli, Narcisa Muresu, Santina Castriciano, Giovanni Sotgiu, Andrea Piana
Healthcare.2022; 10(3): 459. CrossRef
The Potential of Urine for Human papillomavirus-related Cervical Cancer Prevention
Maryame Lamsisi, Guorong Li, Celine Chauleur, Moulay Mustapha Ennaji, Thomas Bourlet
Future Virology.2022; 17(7): 495. CrossRef
Evaluation of BD Onclarity™ HPV Assay on Self-Collected Vaginal and First-Void Urine Samples as Compared to Clinician-Collected Cervical Samples: A Pilot Study
Marianna Martinelli, Chiara Giubbi, Illari Sechi, Fabio Bottari, Anna Daniela Iacobone, Rosario Musumeci, Federica Perdoni, Narcisa Muresu, Andrea Piana, Robert Fruscio, Fabio Landoni, Clementina Elvezia Cocuzza
Diagnostics.2022; 12(12): 3075. CrossRef
Urine HPV in the Context of Genital and Cervical Cancer Screening—An Update of Current Literature
Alexandros Daponte, George Michail, Athina-Ioanna Daponte, Nikoletta Daponte, George Valasoulis
Cancers.2021; 13(7): 1640. CrossRef
Diagnostic Test Accuracy of First-Void Urine Human Papillomaviruses for Presence Cervical HPV in Women: Systematic Review and Meta-Analysis
Peter Bober, Peter Firment, Ján Sabo
International Journal of Environmental Research and Public Health.2021; 18(24): 13314. CrossRef

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Central nervous system

Mutant IDH1 Enhances Temozolomide Sensitivity via Regulation of the ATM/CHK2 Pathway in Glioma: Lin Lin, Jinquan Cai, Zixiao Tan, Xiangqi Meng, Ruiyan Li, Yang Li, Chuanlu Jiang; Cancer Res Treat. 2021;53(2):367-377. Published online October 13, 2020; DOI: https://doi.org/10.4143/crt.2020.506

Abstract PDF PubReader ePub

Purpose
Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate.
Materials and Methods
IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation.
Results
We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC₅₀ of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment.
Conclusion
These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

Citations

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Impact of NQO1 dysregulation in CNS disorders
Li Yuhan, Maryam Khaleghi Ghadiri, Ali Gorji
Journal of Translational Medicine.2024;[Epub] CrossRef
Expression of molecular markers and synergistic anticancer effects of chemotherapy with antimicrobial peptides on glioblastoma cells
Alexandr N. Chernov, Alexandr V. Kim, Sofia S. Skliar, Evgeniy V. Fedorov, Anna N. Tsapieva, Tatiana A. Filatenkova, Aleksei L. Chutko, Marina V. Matsko, Elvira. S. Galimova, Olga V. Shamova
Cancer Chemotherapy and Pharmacology.2024; 93(5): 455. CrossRef
Factors related to tumor response rate from TCGA three omics data—variants, expression, methylation
Hyung-Min Ahn, Insu Park, Chang Geun Kim, Young Kyung Ko, Jeong-An Gim
Journal of Environmental Science and Health, Part C.2024; 42(3): 173. CrossRef
Comparison of MRI Sequences to Predict IDH Mutation Status in Gliomas Using Radiomics-Based Machine Learning
Dilek N. G. Kasap, Nabila Gala Nacul Mora, David A. Blömer, Burak Han Akkurt, Walter Leonhard Heindel, Manoj Mannil, Manfred Musigmann
Biomedicines.2024; 12(4): 725. CrossRef
Oncometabolite 2-hydroxyglutarate suppresses basal protein levels of DNA polymerase beta that enhances alkylating agent and PARG inhibition induced cytotoxicity
Kate M. Saville, Rasha Q. Al-Rahahleh, Aisha H. Siddiqui, Morgan E. Andrews, Wynand P. Roos, Christopher A. Koczor, Joel F. Andrews, Faisal Hayat, Marie E. Migaud, Robert W. Sobol
DNA Repair.2024; 140: 103700. CrossRef
Enhancing Therapeutic Approaches in Glioblastoma with Pro-Oxidant Treatments and Synergistic Combinations: In Vitro Experience of Doxorubicin and Photodynamic Therapy
Bruno Agustín Cesca, Matías Daniel Caverzan, María Julia Lamberti, Luis Exequiel Ibarra
International Journal of Molecular Sciences.2024; 25(14): 7525. CrossRef
Tricarboxylic Acid Cycle Relationships with Non-Metabolic Processes: A Short Story with DNA Repair and Its Consequences on Cancer Therapy Resistance
Enol Álvarez-González, Luisa María Sierra
International Journal of Molecular Sciences.2024; 25(16): 9054. CrossRef
IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications
Kristian A. Choate, Evan P. S. Pratt, Matthew J. Jennings, Robert J. Winn, Paul B. Mann
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The theory of massively repeated evolution and full identifications of cancer-driving nucleotides (CDNs)
Lingjie Zhang, Tong Deng, Zhongqi Liufu, Xueyu Liu, Bingjie Chen, Zheng Hu, Chenli Liu, Miles E Tracy, Xuemei Lu, Hai-Jun Wen, Chung-I Wu
eLife.2024;[Epub] CrossRef
Oncometabolites as Regulators of DNA Damage Response and Repair
Susan E. Gueble, Ranjit S. Bindra
Seminars in Radiation Oncology.2022; 32(1): 82. CrossRef
Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma
Liesbeth Everix, Shankari Nair, Cathryn H. S. Driver, Ingeborg Goethals, Mike M. Sathekge, Thomas Ebenhan, Charlot Vandevoorde, Julie Bolcaen
Cancers.2022; 14(7): 1821. CrossRef
Chk1/2 inhibitor AZD7762 enhances the susceptibility of IDH-mutant brain cancer cells to temozolomide
Erkin Ozgiray, Fatma Sogutlu, Cigir Biray Avci
Medical Oncology.2022;[Epub] CrossRef
From Laboratory Studies to Clinical Trials: Temozolomide Use in IDH-Mutant Gliomas
Xueyuan Sun, Sevin Turcan
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Emanuela Di Gregorio, Gianmaria Miolo, Asia Saorin, Agostino Steffan, Giuseppe Corona
International Journal of Molecular Sciences.2021; 22(11): 5574. CrossRef
The function and mechanism of the JARID2/CCND1 axis in modulating glioma cell growth and sensitivity to temozolomide (TMZ)
Weilu Kuang, Wuzhong Jiang, Yinyun Chen, Yifu Tian, Zhengzheng Liu
Cancer Biology & Therapy.2021; 22(5-6): 392. CrossRef
Valproic Acid Enhanced Temozolomide-Induced Anticancer Activity in Human Glioma Through the p53–PUMA Apoptosis Pathway
Hong-Chieh Tsai, Kuo-Chen Wei, Pin-Yuan Chen, Chiung-Yin Huang, Ko-Ting Chen, Ya-Jui Lin, Hsiao-Wei Cheng, Yi-Rou Chen, Hsiang-Tsui Wang
Frontiers in Oncology.2021;[Epub] CrossRef

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Lung cancer

Genetic Alterations in Preinvasive Lung Synchronous Lesions: Soyeon Ahn, Jisun Lim, Soo Young Park, Hyojin Kim, Hyun Jung Kwon, Yeon Bi Han, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung; Cancer Res Treat. 2020;52(4):1120-1134. Published online June 5, 2020; DOI: https://doi.org/10.4143/crt.2020.307

Abstract PDF Supplementary Material PubReader ePub

Purpose
Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD)
Materials and Methods
We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing.
Results
Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions.
Conclusion
Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

Citations

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Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma
Jisun Lim, Yeon Bi Han, Soo Young Park, Soyeon Ahn, Hyojin Kim, Hyun Jung Kwon, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung
Cells.2021; 10(12): 3484. CrossRef

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154 Download
2 Web of Science
1 Crossref

Clinical Outcomes of Immune Checkpoint Blocker Therapy for Malignant Melanoma in Korean Patients: Potential Clinical Implications for a Combination Strategy Involving Radiotherapy: Jeongshim Lee, Jee Suk Chang, Mi Ryung Roh, Minkyu Jung, Choong-Kun Lee, Byung Ho Oh, Kee Yang Chung, Woong Sub Koom, Sang Joon Shin; Cancer Res Treat. 2020;52(3):730-738. Published online February 13, 2020; DOI: https://doi.org/10.4143/crt.2019.598

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the clinical efficacy of immune checkpoint blocker (ICB) therapy for metastatic or advanced melanoma in Korean patients. As well, we assessed whether the effects of ICBs can be enhanced by combination therapy with palliative radiotherapy (RT).
Materials and Methods
We retrospectively reviewed the records of 127 patients with metastatic melanoma who received ICB with or without palliative RT between 2014 and 2018. The melanoma subtypes were classified as follows: chronic sun-damaged (CSD), acral, mucosal, and uveal. The primary endpoint was the objective response rate (ORR).
Results
The overall ORR was 15%, with 11 complete and eight partial responses. ORRs for CSD, acral/mucosal, and uveal melanomas were 50%, 16.5%, and 0%, respectively (p=0.009). In addition to the subtype, stage at treatment, total tumor burden at treatment, and ICB type were significantly associated with ORR (all p < 0.05). Palliative RT was administered in 44% of patients during the treatment, and it did not affect ORR. Clinical responders to ICB therapy exhibited significantly higher 1-year progression-free and overall survival rates than nonresponders.
Conclusion
ORR for ICB monotherapy in Korean patients with melanoma is relatively modest compared with that in Western patients because the non-CSD subtypes are predominant in the Korean population. Our findings regarding combination therapy with ICB provided a rationale for the initiation of our phase II study (NCT04017897).

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Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications
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Gaofei Yin, Wei Guo, Zhigang Huang, Xiaohong Chen
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The pharmacotherapeutic management of nail unit and acral melanomas
Julianne M. Falotico, Shari R. Lipner
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A Comparison of 2 Disease Burden Assessment Methods (3D Volume Versus the Number of Lesions) for Prognostication of Survival in Metastatic Melanoma: Implications for the Characterization of Oligometastatic Disease
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Prediction of Immune-Checkpoint Blockade Monotherapy Response in Patients With Melanoma Based on Easily Accessible Clinical Indicators
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Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review
Jennifer Ben Shimol, Yuli Guzman-Prado, Maria Karlinskaya, Tima Davidson
Critical Reviews in Oncology/Hematology.2021; 167: 103499. CrossRef

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Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma: Jii Bum Lee, Hyung Soon Park, Sejung Park, Hyo Jin Lee, Kyung A Kwon, Young Jin Choi, Yu Jung Kim, Chung Mo Nam, Nam Hoon Cho, Beodeul Kang, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2019;51(4):1578-1588. Published online April 16, 2019; DOI: https://doi.org/10.4143/crt.2018.671

Abstract PDF PubReader ePub

Purpose
Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC.
Materials and Methods
From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus.
Results
Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]).
Conclusion
Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

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A perspective on the application of macrocyclic design strategies in antitumor drugs
Yan-Hong Li, Yu-Kang Lin, Jian-Fan Cai, Zhong-Kai Zou, Pei-Liang Zhao
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Zebularine showed anti-tumor efficacy in clear cell renal cell carcinoma
Haoyu Xu, Senlin Peng, Junwu Li, Yuanyuan Bai, Guozhi Zhao, Simin Liang, Wei Tang
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Advances in non‐clear cell renal cell carcinoma management: From heterogeneous biology to treatment options
Nathaniel R. Wilson, Yusuf Acikgoz, Elshad Hasanov
International Journal of Cancer.2024; 154(6): 947. CrossRef
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Yanru Yang, Jingyu Guo, Mingyang Li, Guangxin Chu, Hai Jin, Jing Ma, Qingge Jia
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Yaping Zhang, Jian Chen, Xiaoyan Wang, Hui Wang, Xiaoli Chen, Jianfeng Hong, Hongming Fang
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Cost-effectiveness analysis of anlotinib versus sunitinib as first-line treatment for metastatic renal cell carcinoma in China
Jingyang Lin, Qingxia Fang, Xiaochun Zheng, Meng Li
PLOS ONE.2023; 18(2): e0281402. CrossRef
Targeted Literature Review of Outcomes to Initial Systemic Therapy for Advanced/Metastatic Non-Clear Cell Renal Cell Carcinoma in Observational Studies
Shawna R. Calhoun, Manish Sharma, Chung-Han Lee
Kidney Cancer.2023; 7(1): 123. CrossRef

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Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study: Joon Mee Kim, Jin Hee Sohn, Mee-Yon Cho, Woo Ho Kim, Hee Kyung Chang, Eun Sun Jung, Myeong-Cherl Kook, So-Young Jin, Yang Seok Chae, Young Soo Park, Mi Seon Kang, Hyunki Kim, Jae Hyuk Lee, Do Youn Park, Kyoung Mee Kim, Hoguen Kim, Young Ju Suh, Sang Yong Seol, Hwoon-Yong Jung, Deuck–Hwa Kim, Na Rae Lee, Seung-Hee Park, Ji Hye You; Cancer Res Treat. 2019;51(4):1568-1577. Published online April 1, 2019; DOI: https://doi.org/10.4143/crt.2019.019

Abstract PDF PubReader ePub

Purpose
The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance.
Materials and Methods
We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions.
Results
The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important.
Conclusion
The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

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Poor agreement between biopsies and endoscopic submucosal dissection specimens of Esophageal and Gastric Epithelial Lesions in a western setting
Elisa Cantú-Germano, Glòria Fernández-Esparrach, Alberto Herreros De Tejada, José Carlos Marín-Gabriel, Hugo Uchima, Felipe Ramos-Zabala, Eduardo Albéniz, José Santiago, Oscar Nogales, Enrique Rodríguez De Santiago, Joan B Gornals, Beatriz Peñas, Joaquín
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Chang Zhao, Bo-Jin Su, Wei-Zhen Lin, An-Fang He, Da-Yang Hui, Hai-Ling Liu, Hui Chen, Ming-Ya Xiao, Jian-Ning Chen, Hai-Feng Li, Jin-Yue Zheng, Wei-Jia Wang, Yan Huang, Chun-Kui Shao
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Ricardo Gonzalez, Ashirbani Saha, Clinton J.V. Campbell, Peyman Nejat, Cynthia Lokker, Andrew P. Norgan
Journal of Pathology Informatics.2024; 15: 100347. CrossRef
A new, simplified endoscopic scoring system for predicting clinical outcome in gastric low-grade intraepithelial neoplasia: the “e-cout system”
Nanjun Wang, Xiaotong Niu, Longsong Li, Jing Tang, Yawei Bi, Shengzhen Liu, Ke Han, Yaxuan Cheng, Zhaobei Cai, Ningli Chai, Enqiang Linghu
Neoplasia.2024; 56: 101030. CrossRef
A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy
Yu Han Zhao, Yu Zheng, Jie Sha, Hong Jin Hua, Ke Dong Li, Yu Lu, Yi Ni Dang, Guo Xin Zhang
Gut and Liver.2023; 17(1): 78. CrossRef
A standardized pathology report for gastric cancer: 2nd edition
Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
Journal of Pathology and Translational Medicine.2023; 57(1): 1. CrossRef
Tumor heterogeneity and carcinoma in resected specimens of gastric low-grade dysplasia: A retrospective single center study
Ga-Yeong Shin, Jun Young Park, Sung Hak Lee, Yu Kyung Cho, Myung-Gyu Choi, Jae Myung Park, Alessandro Rizzo
PLOS ONE.2023; 18(1): e0280735. CrossRef
A Standardized Pathology Report for Gastric Cancer: 2nd Edition
Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
Journal of Gastric Cancer.2023; 23(1): 107. CrossRef
Accuracy of administrative claim data for gastric adenoma after endoscopic resection
Ga-Yeong Shin, Hyun Ho Choi, Jae Myung Park, Sang Yoon Kim, Jun Young Park, Donghoon Kang, Yu Kyung Cho, Sung Soo Kim, Myung-Gyu Choi
Clinical Endoscopy.2023; 56(3): 325. CrossRef
Artificial Intelligence in the Pathology of Gastric Cancer
Sangjoon Choi, Seokhwi Kim
Journal of Gastric Cancer.2023; 23(3): 410. CrossRef
Establishment and validation of a clinical diagnostic model for gastric low-grade intraepithelial neoplasia
Ting Sun, Xi-quan Ke, Meng Wang, Qi-zhi Wang
Medicine.2023; 102(46): e35515. CrossRef
Assessment of deep learning assistance for the pathological diagnosis of gastric cancer
Wei Ba, Shuhao Wang, Meixia Shang, Ziyan Zhang, Huan Wu, Chunkai Yu, Ranran Xing, Wenjuan Wang, Lang Wang, Cancheng Liu, Huaiyin Shi, Zhigang Song
Modern Pathology.2022; 35(9): 1262. CrossRef
Deep learning for automatic diagnosis of gastric dysplasia using whole-slide histopathology images in endoscopic specimens
Zhongyue Shi, Chuang Zhu, Yu Zhang, Yakun Wang, Weihua Hou, Xue Li, Jun Lu, Xinmeng Guo, Feng Xu, Xingran Jiang, Ying Wang, Jun Liu, Mulan Jin
Gastric Cancer.2022; 25(4): 751. CrossRef
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Joaquín Cubiella, Ángeles Pérez Aisa, Miriam Cuatrecasas, Pilar Díez Redondo, Gloria Fernández Esparrach, José Carlos Marín-Gabriel, Leticia Moreira, Henar Núñez, M. Luisa Pardo López, Enrique Rodríguez de Santiago, Pedro Rosón, José Miguel Sanz Anquela,
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Gastroenterología y Hepatología (English Edition).2021; 44(1): 67. CrossRef

9,662 View
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Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer: Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J. Solomon, Alice T. Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D. Wilner, Tony Mok; Cancer Res Treat. 2018;50(3):691-700. Published online July 6, 2017; DOI: https://doi.org/10.4143/crt.2017.280

Abstract PDF Supplementary Material PubReader ePub

Purpose
Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials.
Materials and Methods
This analysis evaluated previously treated and untreated patients in two randomized, openlabel phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and “as-treated” populations for efficacy and safety endpoints, respectively.
Results
In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity.
Conclusion
These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.

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Yan Yang, Caiyu Jiang, Yang Yang, Lu Guo, Jiang Huang, Xingren Liu, Chi Wu, Jun Zou
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Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices
Claudio Martín, Andrés F. Cardona, Zyanya Lucia Zatarain-Barrón, Alejandro Ruiz-Patiño, Omar Castillo, George Oblitas, Luis Corrales, Lorena Lupinacci, María Angelina Pérez, Leonardo Rojas, Lisde González, Luis Chirinos, Carlos Ortíz, Mauricio Lema, Carlo
Oncology.2018; 94(5): 297. CrossRef
CRISPR therapeutic tools for complex genetic disorders and cancer (Review)
Stella Baliou, Maria Adamaki, Anthony Kyriakopoulos, Demetrios Spandidos, Michalis Panagiotidis, Ioannis Christodoulou, Vassilis Zoumpourlis
International Journal of Oncology.2018;[Epub] CrossRef

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Efficacy and Safety of First-Line Necitumumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in East Asian Patients with Stage IV Squamous Non-small Cell Lung Cancer: A Subgroup Analysis of the Phase 3, Open-Label, Randomized SQUIRE Study: Keunchil Park, Eun Kyung Cho, Maximino Bello, Myung-Ju Ahn, Sumitra Thongprasert, Eun-Kee Song, Victoria Soldatenkova, Henrik Depenbrock, Tarun Puri, Mauro Orlando; Cancer Res Treat. 2017;49(4):937-946. Published online January 6, 2017; DOI: https://doi.org/10.4143/crt.2016.423

Abstract PDF PubReader ePub

Purpose
The phase 3 randomized SQUIRE study revealed significantly longer overall survival (OS) and progression-free survival (PFS) for necitumumab plus gemcitabine and cisplatin (neci+GC) than for gemcitabine and cisplatin alone (GC) in 1,093 patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC). This post hoc subgroup analysis assessed the efficacy and safety of neci+GC among East Asian (EA) patients enrolled in the study.
Materials and Methods
All patients received up to six 3-week cycles of gemcitabine (days 1 and 8, 1,250 mg/m²) and cisplatin (day 1, 75 mg/m²). Patients in the neci+GC arm also received necitumumab (days 1 and 8, 800 mg) until disease progression or unacceptable toxicity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from stratified Cox proportional hazards models.
Results
In EA patients, there were improvements for neci+GC (n=43) versus GC (n=41) in OS (HR, 0.805; 95% CI, 0.484 to 1.341) and PFS (HR, 0.720; 95% CI, 0.439 to 1.180), consistent with the results for non-EA patients observed in the present study. The overall safety data were consistent between EA and non-EA patients. A numerically higher proportion of patients experienced serious adverse events (AEs), grade ≥ 3 AEs, and AEs with an outcome of death for neci+GC versus GC in EA patients and EA patients versus non-EA patients for neci+GC.
Conclusion
Although limited by the small sample size and post hoc nature of the analysis, these findings are consistent with those of the overall study and suggest that neci+GC offers a survival advantage and favorable benefit/risk for EA patients with advanced squamous NSCLC.

Citations

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Phytochemicals intended for anticancer effects at preclinical levels to clinical practice: Assessment of formulations at nanoscale for non-small cell lung cancer (NSCLC) therapy
The Hong Phong Nguyen, V. Bharath Kumar, Vinoth Kumar Ponnusamy, Thi Thu Thao Mai, Phuong Tran Nhat, Kathirvel Brindhadevi, Arivalagan Pugazhendhi
Process Biochemistry.2021; 104: 55. CrossRef
Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis
Irena Ilic, Sandra Sipetic, Jovan Grujicic, Milena Ilic
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Jeffrey W. Clark, Dan L. Longo
Current Opinion in Pulmonary Medicine.2018; 24(4): 355. CrossRef
Necitumumab in the treatment of non-small-cell lung cancer: clinical controversies
Vincenzo di Noia, Ettore D’Argento, Sara Pilotto, Giulia Grizzi, Mario Caccese, Roberto Iacovelli, Giampaolo Tortora, Emilio Bria
Expert Opinion on Biological Therapy.2018; 18(9): 937. CrossRef
SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting
Alastair Greystoke, Nicola Steele, Hendrik-Tobias Arkenau, Fiona Blackhall, Noor Md Haris, Colin R Lindsay, Raffaele Califano, Mark Voskoboynik, Yvonne Summers, Karen So, Dana Ghiorghiu, Angela W Dymond, Stuart Hossack, Ruth Plummer, Emma Dean
British Journal of Cancer.2017; 117(7): 938. CrossRef

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East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL): Keunchil Park, Joo-Hang Kim, Eun Kyung Cho, Jin-Hyoung Kang, Jin-Yuan Shih, Annamaria Hayden Zimmermann, Pablo Lee, Ekaterine Alexandris, Tarun Puri, Mauro Orlando; Cancer Res Treat. 2016;48(4):1177-1186. Published online February 22, 2016; DOI: https://doi.org/10.4143/crt.2015.401

Abstract PDF PubReader ePub

Purpose
REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported.
Materials and Methods
Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate.
Results
In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2).
Conclusion

Results
of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

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Efficacy and outcomes of ramucirumab and docetaxel in patients with metastatic non-small cell lung cancer after disease progression on immune checkpoint inhibitor therapy: Results of a monocentric, retrospective analysis
Samuel A. Kareff, Kunal Gawri, Khadeja Khan, Deukwoo Kwon, Estelamari Rodriguez, Gilberto de Lima Lopes, Richa Dawar
Frontiers in Oncology.2023;[Epub] CrossRef
Clinical Trial and Real-World Outcomes of Patients With Metastatic NSCLC in the Post-Platinum–Based Chemotherapy Failure Setting
Yu Yang Soon, Wesley Furnback, Jin Kim, Po-Ya Chuang, Gordon Chavez, Christina Proescholdt, Cloe Ying Chee Koh
JTO Clinical and Research Reports.2023; 4(11): 100579. CrossRef
Safety and effectiveness of ramucirumab and docetaxel: a single-arm, prospective, multicenter, non-interventional, observational, post-marketing safety study of NSCLC in Japan
Yucherng Chen, Soshi Nagaoka, Taeko Katayose, Nobuyuki Sekine
Expert Opinion on Drug Safety.2022; 21(5): 691. CrossRef
Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients
Hirotaka Suto, Yumiko Inui, Atsuo Okamura
Cancers.2022; 14(9): 2075. CrossRef
Cost-effectiveness analysis of pegfilgrastim in patients with non-small cell lung cancer receiving ramucirumab plus docetaxel in Japan
Yu Kondo, Tomoya Tachi, Takayoshi Sakakibara, Jun Kato, Aki Kato, Takahito Mizuno, Yoshio Miyake, Hitomi Teramachi
Supportive Care in Cancer.2022; 30(8): 6775. CrossRef
Sintilimab versus docetaxel as second‐line treatment in advanced or metastatic squamous non‐small‐cell lung cancer: an open‐label, randomized controlled phase 3 trial (ORIENT‐3)
Yuankai Shi, Lin Wu, Xinmin Yu, Puyuan Xing, Yan Wang, Jianying Zhou, Airong Wang, Jianhua Shi, Yi Hu, Ziping Wang, Guangyu An, Yong Fang, Sanyuan Sun, Caicun Zhou, Changli Wang, Feng Ye, Xingya Li, Junye Wang, Mengzhao Wang, Yunpeng Liu, Yanqiu Zhao, Yin
Cancer Communications.2022; 42(12): 1314. CrossRef
The Relevance of Docetaxel-related Febrile Neutropenia to Patient-reported Symptoms and the Quality of Life in Japanese, East Asian (Korean, Taiwanese), and Non-East Asian Patients Based on Post-hoc Analyses of Two Randomized Clinical Trials of Docetaxel
Yukie Omori, Sotaro Enatsu, Alan J.M. Brnabic, Narayan Rajan, Jin-Yuan Shih, Joo-Hang Kim, Keunchil Park, Akira Inoue
Haigan.2019; 59(7): 1140. CrossRef
Current and Emergent Therapy Options for Advanced Squamous Cell Lung Cancer
Mark A. Socinski, Coleman Obasaju, David Gandara, Fred R. Hirsch, Philip Bonomi, Paul A. Bunn, Edward S. Kim, Corey J. Langer, Ronald B. Natale, Silvia Novello, Luis Paz-Ares, Maurice Pérol, Martin Reck, Suresh S. Ramalingam, Craig H. Reynolds, David R. S
Journal of Thoracic Oncology.2018; 13(2): 165. CrossRef
Therapeutic perspectives for brain metastases in non-oncogene addicted non-small cell lung cancer (NSCLC): Towards a less dismal future?
Stefano Frega, Laura Bonanno, Valentina Guarneri, Pierfranco Conte, Giulia Pasello
Critical Reviews in Oncology/Hematology.2018; 128: 19. CrossRef
Ramucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials
Chia-Jui Yen, Kei Muro, Tae-Won Kim, Masatoshi Kudo, Jin-Yuan Shih, Keun-Wook Lee, Yee Chao, Sang-We Kim, Kentaro Yamazaki, JooHyuk Sohn, Rebecca Cheng, Yawei Zhang, Polina Binder, Gu Mi, Mauro Orlando, Hyun Cheol Chung
Journal of Global Oncology.2018; (4): 1. CrossRef
Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer
Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J. Solomon, Alice T. Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D. Wilner, Tony Mok
Cancer Research and Treatment.2018; 50(3): 691. CrossRef
The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum
Takumi Fujiwara, Hirotsugu Kenmotsu, Tateaki Naito, Takahisa Kawamura, Nobuaki Mamesaya, Mie Kotake, Haruki Kobayashi, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Tetsuhiko Taira, Haruyasu Murakami, Katsuhiro Omae, Keita Mori, Masahiro E
Cancer Chemotherapy and Pharmacology.2017; 79(6): 1229. CrossRef
The safety and efficacy of ramucirumab in combination with docetaxel in the treatment of lung cancer
Valérie Paulus, Virginie Avrillon, Maurice Pérol
Expert Review of Anticancer Therapy.2016; 16(11): 1119. CrossRef
Recommendations of the Austrian Working Group on Pulmonary Pathology and Oncology for predictive molecular and immunohistochemical testing in non-small cell lung cancer
Helmut H. Popper, Ulrike Gruber-Mösenbacher, Georg Hutarew, Maximilian Hochmair, Gudrun Absenger, Luka Brcic, Leonhard Müllauer, Gerhard Dekan, Ulrike Setinek, Dagmar Krenbek, Michael Vesely, Robert Pirker, Wolfgang Hilbe, Rainer Kolb, Gerald Webersinke,
memo - Magazine of European Medical Oncology.2016; 9(4): 191. CrossRef

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Pemetrexed-Erlotinib, Pemetrexed Alone, or Erlotinib Alone as Second-Line Treatment for East Asian and Non-East Asian Never-Smokers with Locally Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer: Exploratory Subgroup Analysis of a Phase II Trial: Dae Ho Lee, Jung Shin Lee, Jie Wang, Te-Chun Hsia, Xin Wang, Jongseok Kim, Mauro Orlando; Cancer Res Treat. 2015;47(4):616-629. Published online November 24, 2014; DOI: https://doi.org/10.4143/crt.2014.051

Abstract PDF PubReader ePub

Purpose
This subgroup analysis of a phase II trial was conducted to assess possible ethnicity-based trends in efficacy and safety in East Asian (EA) and non-EA populations with nonsquamous non-small cell lung cancer (NSCLC).
Materials and Methods
Never-smoker patients (n=240) with locally advanced or metastatic nonsquamous NSCLC included 133 EA patients randomized to pemetrexed supplemented with dexamethasone, folic acid, and vitamin B12 plus erlotinib (pemetrexed-erlotinib) (n=41), erlotinib (n=49), or pemetrexed (n=43), and 107 non-EA patients randomized to pemetrexed-erlotinib (n=37), erlotinib (n=33), or pemetrexed (n=37). The primary endpoint, progression-free survival (PFS), was analyzed using a multivariate Cox model.
Results
Consistent with the results of the overall study, a statistically significant difference in PFS among the three arms was noted in the EA population favoring pemetrexed-erlotinib (overall p=0.003) as compared with either single-agent arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29 to 0.79; p=0.004 vs. erlotinib; HR, 0.40; 95% CI, 0.23 to 0.70; p=0.001 vs. pemetrexed). The EA patients treated with pemetrexed-erlotinib achieved a longer median PFS (7.4 months) compared with erlotinib (4.5 months) and pemetrexed (4.0 months). The PFS results also numerically favored pemetrexed-erlotinib in the non-EA population (overall p=0.210) (HR, 0.62; 95% CI, 0.37 to 1.05; p=0.078 vs. erlotinib; HR, 0.75; 95% CI, 0.42 to 1.32; p=0.320 vs. pemetrexed) (median PFS: pemetrexed-erlotinib, 6.7 months; erlotinib, 3.0 months; pemetrexed, 4.4 months).
Conclusion
The PFS results from this subset analysis in both EA and non-EA populations are consistent with the results in the overall population. The PFS advantage for pemetrexed-erlotinib is significant compared with the single agents in EA patients.

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Association of Hypokalemia Incidence and Better Treatment Response in NSCLC Patients: A Meta-Analysis and Systematic Review on Anti-EGFR Targeted Therapy Clinical Trials
Jiawei Zhou, Jianling Bai, Yuanping Yue, Xin Chen, Theis Lange, Dongfang You, Yang Zhao
Frontiers in Oncology.2022;[Epub] CrossRef
Non-Smoking-Associated Lung Cancer: A distinct Entity in Terms of Tumor Biology, Patient Characteristics and Impact of Hereditary Cancer Predisposition
Elisabeth Smolle, Martin Pichler
Cancers.2019; 11(2): 204. CrossRef
Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials
Huiyu Wang, Zunjing Zhang, Feng Liu, Miaoying Zhou, Handi Lv
Pteridines.2019; 30(1): 171. CrossRef
A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non–Small-Cell Lung Cancer
James Chih-Hsin Yang, Tony Mok, Baohui Han, Mauro Orlando, Tarun Puri, Keunchil Park
Clinical Lung Cancer.2018; 19(1): 27. CrossRef
Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non–small-cell Lung Cancer
Tianhong Li, Bilal Piperdi, William V. Walsh, Mimi Kim, Laurel A. Beckett, Rasim Gucalp, Missak Haigentz, Venu G. Bathini, Huiyu Wen, Kaili Zhou, Patricia B. Pasquinelli, Srikanth Gajavelli, Meera Sreedhara, Xianhong Xie, Primo N. Lara, David R. Gandara,
Clinical Lung Cancer.2017; 18(1): 60. CrossRef
Erlotinib intercalating pemetrexed/cisplatin versus erlotinib alone in Chinese patients with brain metastases from lung adenocarcinoma: a prospective, non-randomised, concurrent controlled trial (NCT01578668)
Haihong Yang, Qiuhua Deng, Yuan Qiu, Jun Huang, Yubao Guan, Fengnan Wang, Xin Xu, Xinyun Yang
ESMO Open.2017; 2: e000112. CrossRef
Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure
Jung Ran Choi, Seong Yong Park, O Kyu Noh, Young Wha Koh, Dae Ryong Kang
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Epidermal Growth Factor Receptor Mutation Status in the Treatment of Non-small Cell Lung Cancer: Lessons Learned
Dae Ho Lee, Vichien Srimuninnimit, Rebecca Cheng, Xin Wang, Mauro Orlando
Cancer Research and Treatment.2015; 47(4): 549. CrossRef

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Case Reports

A Case of Pure Red Cell Aplasia Associated with Angioimmunoblastic T-cell Lymphoma: Jung-Hye Choi, Young-Ha Oh, Ile-Kyu Park; Cancer Res Treat. 2010;42(2):115-117. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.115

Abstract PDF PubReader ePub

Pure red cell aplasia is a bone marrow failure characterized by a progressive normocytic anemia and reticulocytopenia without leucopenia and thrombocytopenia. It is associated with various hematologic diseases. However, pure red cell aplasia with angioimmunoblastic T cell lymphoma has rarely been reported. Here we describe a 43-year-old woman with pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma. She had severe anemia (hemoglobin 6.9 g/dL) and a low reticulocyte count (0.2%). Direct and indirect Coombs' tests were positive. A CT scan of the abdomen revealed marked hepatosplenomegaly and small multiple lymphadenopathies. A bone marrow biopsy revealed focal infiltration of abnormal lymphoid cells and absence of red cell precursors. Splenic biopsy was compatible with angioimmunoblastic T-cell lymphoma. Ultimately, diagnosis of pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma was made. After initiating CHOP therapy, the patient achieved complete remission, which was accompanied, shortly thereafter, by a rise in hemoglobin levels which finally returned to normal.

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Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma
Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P. Quick
The American Journal of the Medical Sciences.2021; 361(3): 375. CrossRef
Angioimmunoblastic T-cell lymphoma accompanied by pure red cell aplasia: A case report
Teiko Kawahigashi, Izumi Kitagawa, Eri Tanaka
World Journal of Clinical Oncology.2020; 11(6): 405. CrossRef
EXPERIENCE OF MANAGING ANEMIA IN ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA
Hiromi Hashimoto, Shinya Ohata, Takako Tomita, Kazuko Konishi, Yoshinori Kubota, Maki Kanzawa, Yosuke Minami, Takeshi Sugimoto
Japanese Journal of Transfusion and Cell Therapy.2017; 63(1): 30. CrossRef
Angioimmunoblastic T-Cell Lymphoma Presenting with an Acute Serologic Epstein-Barr Virus Profile
Timothy Beer, Patrick Dorion
Hematology Reports.2015; 7(2): 5893. CrossRef
B-Cell Prolymphocytic Leukemia Carrying t(8;14)(q24;q32), Associated with Both Autoimmune Hemolytic Anemia and Pure Red Cell Aplasia
Futoshi Iioka, Takashi Akasaka, Masahiko Hayashida, Atsuko Okumura, Hitoshi Ohno
Journal of Clinical and Experimental Hematopathology.2014; 54(3): 219. CrossRef
Angioimmunoblastic T-cell lymphoma-associated pure red cell aplasia with abdominal pain
Jin Tao
World Journal of Clinical Oncology.2013; 4(3): 75. CrossRef
Pure Red Cell Aplasia and Lymphoproliferative Disorders: An Infrequent Association
Efthymia Vlachaki, Michael D. Diamantidis, Philippos Klonizakis, Styliani Haralambidou-Vranitsa, Elizabeth Ioannidou-Papagiannaki, Ioannis Klonizakis
The Scientific World Journal.2012; 2012: 1. CrossRef

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F-18 FDG PET-positive Fibrous Dysplasia in a Patient with Intestinal Non-Hodgkin's Lymphoma: Mi Kim, Hyeong Su Kim, Jung Han Kim, Joo Hyun Jang, Kook Jin Chung, Mi Kyung Shin, Hee Sung Hwang, Byung Chun Kim, So Young Jung; Cancer Res Treat. 2009;41(3):171-174. Published online September 28, 2009; DOI: https://doi.org/10.4143/crt.2009.41.3.171

Abstract PDF PubReader ePub

Fibrous dysplasia (FD) is a common benign bone disorder of an unclear etiology. It is known that FD can appear without an increased FDG uptake on F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). However, there are also several reports that FD showed increased FDG uptake and this mimicked malignant bone involvement on FDG-PET. Herein we describe a case of biopsy-proven FDG-PET positive FD in a patient with intestinal non-Hodgkin's lymphoma (NHL). A 45-year-old woman was diagnosed with intestinal NHL, which was removed by right hemicolectomy. After the operation, the FDG-PET/CT scan showed hypermetabolic activity in the right transverse process of the T10 vertebra. The patient then received a total of 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy every 3 weeks. After completion of the planned chemotherapy, the 2^nd FDG-PET/CT showed increased FDG uptake (SUVmax=6.0 g/mL) of the previous bone lesion. The MR images revealed a T1-hypointense lesion with sharp borders in the same region, and this showed homogenous contrast enhancement on the fat-suppressed T1-weighted images. After the radiologic studies were carefully reviewed, the bone lesion was assumed to be benign such as FD. We performed bone biopsy and the histological examination confirmed the diagnosis of FD. In conclusion, bone lesions with FDG uptake need to be carefully interpreted when evaluating patients with known malignancy.

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Polyostotic Fibrous Dysplasia Mimicking Bone Involvement in Hodgkin Lymphoma: A Pediatric Case and Literature Review
Gianfranco Lapietra, Maria Luisa Moleti, Fiorina Giona, Arianna Turchetti, Mauro Celli, Alessandro Corsi, Anna Zambrano, Miriam D'Avanzo, Luca Celli, Anna Maria Testi
Acta Haematologica.2021; 144(2): 212. CrossRef
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Maria Kalemaki, Apostolos Karantanas, Dimitris Exarchos, Efstathios Detorakis, Odysseas Zoras, Kostas Marias, Corina Millo, Ulas Bagci, Ioannis Pallikaris, Andreas Stratis, Ioannis Karatzanis, Kostas Perisinakis, Pavlos Koutentakis, Georgios Kontadakis, D
International Journal of Oncology.2020;[Epub] CrossRef
Extensive polyostotic fibrous dysplasia evaluated for malignant transformation with99mTc-MDP bone scan and18F-FDG PET/CT
William Makis, Stephan Probst
BJR|case reports.2016; 2(3): 20150440. CrossRef
FDG Uptake in Liposclerosing Myxofibrous Tumor Causes Upstaging of Hodgkin Lymphoma
Jongho Kim, Wengen Chen, Charles Resnik, Vasken Dilsizian, Qing Chen, Amy S. Kimball
Clinical Nuclear Medicine.2015; 40(4): 325. CrossRef
Fibrous dysplasia mimicking vertebral bone metastasis on 18F-FDG PET/computed tomography in a patient with tongue cancer
Ibrahim Guler, Alaaddin Nayman, Gonca Kara Gedik, Mustafa Koplay, Oktay Sari
The Spine Journal.2015; 15(6): 1501. CrossRef
Fibrous Dysplasia Mimicking Bone Metastasis on Both Bone Scintigraphy and 18F-FDG PET-CT: Diagnostic Dilemma in a Patient with Breast Cancer
Sudhir Suman KC, Punit Sharma, Harmandeep Singh, Chandrasekhar Bal, Rakesh Kumar
Nuclear Medicine and Molecular Imaging.2012; 46(4): 318. CrossRef

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Original Articles

Hydrogen Peroxide Producing Lactobacilli in Women with Cervical Neoplasia: Ho Sun Choi, Ki Min Kim, Chol Hong Kim, Seok Mo Kim, Jong Seok Oh; Cancer Res Treat. 2006;38(2):108-111. Published online April 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.2.108

Abstract PDF PubReader ePub

Purpose

It is well known that human papillomavirus (HPV) is the main cause of cervical neoplasia, and hydrogen peroxide-producing lactobacilli are the most important microorganisms for maintaining the balance of the vaginal ecosystem. The purpose of our study was to investigate the relationship of hydrogen peroxide-producing lactobacilli, cervical neoplasia and high-risk HPV.

Materials and Methods

We enrolled 1138 women with abnormal cervical smears or cervicograms who were referred to the department of Obstetrics and Gynecology at Chonnam National University Medical School. In all of them, 1,138 vaginal swabs were collected for the qualitative assay of hydrogen peroxide producing lactobacilli and 150 cervical swabs were used for the HPV hybrid capture II test without regard to the subjects' pregnancy status. In the non-pregnant women, 880 cervical biopsies and/or loop electrosurgical excision procedures were performed for making the histological diagnosis.

Results

There was no significant difference not only between the distribution of H₂O₂ producing lactobacilli and the cervical histology, but also between the distribution of H₂O₂ producing lactobacilli and the positivity for high-risk HPV.

Conclusions

Both cervical neoplasia and high-risk HPV may not be influenced by the existence of hydrogen peroxide producing lactobacilli in the vagina.

Citations

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Unravelling the Biological Interplay Between Genital HPV Infection and Cervicovaginal Microbiota in Sub-Saharan Africa: Implications for Cervical (Pre)cancer Prevention
Harris Onywera, Zizipho Z. A. Mbulawa, Adrian Brink, Anna-Lise Williamson, Lamech M. Mwapagha
Venereology.2024; 3(4): 211. CrossRef
Antimicrobial activity of Lactobacillus against microbial flora of cervicovaginal infections
Subramanyam Dasari, Raju Naidu Devanaboyaina Shouri, Rajendra Wudayagiri, Lokanatha Valluru
Asian Pacific Journal of Tropical Disease.2014; 4(1): 18. CrossRef
PCR‐based identification of eight lactobacillus species and 18 hr‐HPV genotypes in fixed cervical samples of south african women at risk of HIV and BV
Joke A.M. Dols, Gregor Reid, Remco Kort, Frank H.J. Schuren, Hugo Tempelman, Tj. Romke Bontekoe, Hans Korporaal, E.M. Van der Veer, Pieter W. Smit, Mathilde E. Boon
Diagnostic Cytopathology.2012; 40(6): 472. CrossRef

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Polymorphisms of p53, p21 and IRF-1 and Cervical Cancer Susceptibility in Korean Women: Sung Jong Lee, Sung Eun Namkoong, Won Chul Lee, Jae Woong Sul, Sun Ha Jee, Youn Kyoung You, Jong Eun Lee, Jong Sup Park; Cancer Res Treat. 2002;34(5):357-364. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.357

Abstract PDF

PURPOSE
The aim of this study was to identify gene- gene and gene-environmental factor on cervical carcinogenesis in Korean women.
MATERIALS AND METHODS
We evaluated 185 women patients who had cervical cancer with 345 normal control healthy women. The single nucleotide polymorphisms (SNPs) of the p53 codon 72, the p21 codon 31 and the IRF-1 intron 6 were evaluated from extracted DNA of peripheral blood with an automatic DNA sequencer. The difference of each SNP, gene-gene and gene-environmental interaction between normal controls and patients, were evaluated in an adjusted environmental background.
RESULTS
With regard to environmental factors, the cervical cancer increased in the women with a lower level of education, a younger age at first sexual intercourse and with the increased number of children borne. The women who had p53 (Arg/Arg), IRF-1 (T/T) and an education of less than 6 years showed a 14.7 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and an education of more than 15 years. The women who had p53 (Arg/Arg), p21 (Ser/Ser) and more than 3 children showed a 6.4 fold increased risk of cervical cancer than those women who had p53 (~Pro), p21 (~Arg) and had borne no child. The women who had p53 (Arg/Arg), IRF-1 (T/T) and had experience of first sexual intercourse before the age of 22-years showed a 5.5 fold increased risk of cervical cancer than those women who had p53 (~Pro), IRF-1 (~C) and had experience of first sexual intercourse after the age of 26-years.
CONCLUSION
We found that the level of education, the age at first intercourse, and the number of children borne, were independent risk factors in cervical carcinogenesis. The specific combination of p53, p21 and IRF-1 gene-gene and gene-environmental interactions were significantly noted in the cervical carcinogenesis of Korean women.

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Distinctive cell cycle regulatory protein profiles by adenovirus delivery of p53 in human papillomavirus-associated cancer cells
H.-S. JIN, S.-M. BAE, Y.-W. KIM, J.-M. LEE, S.-E. NAMKOONG, B.-D. HAN, Y.-J. LEE, C.-K. KIM, H.-J. CHUN, W.-S. AHN
International Journal of Gynecological Cancer.2006; 16(2): 698. CrossRef
Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells
Yong-Seok Lee, Su-Mi Bae, Sun-Young Kwak, Dong-Chun Park, Yong-Wook Kim, Soo-Young Hur, Eun-Kyung Park, Byoung-Don Han, Young-Joo Lee, Chong-Kook Kim, Do Kang Kim, Woong-Shick Ahn
Cancer Research and Treatment.2006; 38(3): 168. CrossRef
Cellular process classification of human papillomavirus-16-positive SiHa cervical carcinoma cell using Gene Ontology
W. S. Ahn, M.-J. Seo, S. M. Bae, J. M. Lee, S. E. Namkoong, C. K. Kim, Y.-W. Kim
International Journal of Gynecological Cancer.2005; 15(1): 94. CrossRef

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Discrepancies of the Values on the Withholding Futile Interventions between Physician and Family Members of Terminal Cancer Patients: Do Youn Oh, Mi Ra Kim, In Sil Choi, Yo Han Joh, Byung Su Kim, Do Yeun Kim, Jee Hyun Kim, Se Hoon Lee, Tae You Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; Cancer Res Treat. 2001;33(4):350-356. Published online August 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.4.350

Abstract PDF: PURPOSE
To analyze the controversies surrounding therapeutic decision-making and the withholding of life- sustaining treatments, values held concerning therapeutic interventions of terminal cancer patients are compared between physicians and family members.
MATERIALS AND METHODS
42 advanced or terminal stage cancer patients were enrolled for the study. The questionnaires were administered to the duty doctor and the family of the patients. Questions included whether to use new agents with a 15% partial efficacy and whether to use opioid analgesics, intravenous nutrition, a feeding tube, antibiotics, and hemodialysis. Additionally, we asked about the administration of CPR, ventilator application, and euthanasia. If the family permitted, the same questionnaires were given to the patients.
RESULTS
Of the 42 cases, 5 families refused to answer the questionnaire. Of the available 37 families, only 5 families permitted access to the patients. Of the 5 patients, 2 patients refused the questionnaire. Only 67.6% and 8.1% of families and the patients clearly understood the stage of cancer. The use of a new agent was accepted by 45.2% of the physicians and 45.9% of the families. The rankings of the acceptance of treatment in the physicians and in the families were similar. The concordance rate between the physicians and the families was lowest on ventilator application and CPR. 31% of the physicians and 43.2% of the families agreed on the issue of euthanasia.
CONCLUSION
Values held on issues like therapeutic decision-making and the withholding of life-sustaining treatments in terminal cancer patients are discordant between physicians and family members. In order to resolve controversies on the role of physicians in end-of-life decisions, the values of physicians as well as patients and their family members should be considered in the final decision-making process.

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Frequency of bcl-2/JH Rearrangement in Benign Lymphoid Hyperplasia: Young A Yoo, Seung Ho Lee, Mi Na Son, Zeung Kun Cho, Kun Choi, Jong Wook Choi, Sang Won Shin, Byung Soo Kim, Jun Suk Kim, In Sun Kim, Yeul Hong Kim; J Korean Cancer Assoc. 2000;32(3):587-594.

Abstract PDF: No abstract available.

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Expression of Prostatic Carcinoma Oncogene PTI - 1 in Prostatic Carcinoma , Prostatic Intraepithelial Neoplasia and Benign Prostatic Hyperplasia Using in situ PCR: Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; J Korean Cancer Assoc. 2000;32(1):136-147.

Abstract PDF: PURPOSE
Prostatic tumor induced gene-1 (PTI-1) is a mutated human EF-la and putative prostatic carcinoma tumor-inducing oncogene, that is differently expressed in prostatic cancer and benign prostatic hyperplasia. And, it is more sensitive marker than prostate- specific antigen (PSA) for detecting human prostate cancer in the bloodstream. This study invastigated the expression of PTI-1 in paraffin embedded tissue of prostatic carcinoma, prostatic intraepithelial neoplasia, and benign prostatic hyperplasia using in situ PCR.
MATERIALS AND METHODS
we evaluated expression of PTI-1 in prostatic carcinoma with prostatic intraepithelial neoplasia (PIN) of 32 cases, benign hyperplasia of 20 cases, high grade transitional cell carcinoma of 10 cases and colon cancer of 10 cases for control group. Also, the immunohistochemical staining for PSA was performed to comparison with clinical value of PSA.
RESULTS
The serum level of PSA was closely related to stage and Gleason score (p < 0.05). However, the results of immunohistochemical stains were variable to stage and Gleason score. PTI-1 using in situ PCR expressed in 50% of prostatic carcinoma, 41% of prostatic intraepithelial neoplasia, 10% of benign hyperplasia and colon cancer (p < 0.05). No expression is observed in transitional cell carcinoma. In prostatic carcinoma, PTI-1 expressed in 43.8% (7/16) of stage II, 50.0% (5/10) of stage III, and 66.7% (4/6) of stage IV (p<0.05). In PIN, expression of PTI-1 was similar to prostatic carcinoma (p<0.05).
CONCLUSION
PTI-1 represented a relatively sensitive marker for prostatic carcinoma and PIN, indicator of prostatic carcinoma progression.

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The Clinical Values of Metaplasia, p 53, c - erbB2 and CEA Expression in Gallbladder Carcinoma: Seok Mo Kim, Seong Hwan Kim, Jeong Hwan Chang, Sung chul Lim, Chae Hong Suh; J Korean Cancer Assoc. 1999;31(6):1261-1270.

Abstract PDF: PURPOSE
We evaluated the correlation between the carcinogenesis of gallbladder and the expression of lysozyme, p53, c-erbB2 and CEA in gallbladder lesions.
MATERIALS AND METHODS
Thirty cases of gallbladder lesions (containing 17 cases of GB carcinoma) were examined. We analyzed the clinicopathologic findings of the early (stage I & II) and advanced carcinoma (stage III, IV & V) and those of carcinoma with or without metaplasia in the tumor. We performed p53, c-erbB2 and CEA immunohistochemical staining and compared their findings with those of normal mucosa and preneoplastic lesions. We also performed lysozyme immunohistochemical staining and compared its finding with metaplastic and non-metaplastic lesions.
RESULTS
There are two distinct genetic pathways in gallbladder cacinogenesis and metaplastic carcinoma was more frequent than non-metaplastic carcinoma. Metaplasia of gallbladder did not reveal any difference of the clinicopathologic findings and depth of invasion (Nevin stage). Lysozyme expression was found in all metaplastic lesions but non-expression did not indicate non-metaplastic lesions. p53 mutations and c-erbB2 alterations may have a role in the carcinogenesis of gallbladder carcinomas, especially, in a late event, and in an early and late events, respectively. The correlation of p53 and c-erbB2 expressions was found but which did not indicate that the co-expression was needed in the carcinogenesis. CEA immunohistochemical staining may be helpful in the differential diagnosis of benign lesions and precancerous and cancerous lesions of the gallbladder.
CONCLUSION
These results suggest that p53 mutations and c-erbB2 alterations may have a role in the carcinogenesis of gallbladder carcinomas, especially, in a late event, and in an early and late events, respectively.

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Survival, Differentiation and ATM Phenotype of PC-12 Cells by Down - regulation of AT Gene: Ho Keun Yi, Soo Hee Chang, Dae Yeol Lee, Jung Soo Kim, Pyoung Han Hwang; J Korean Cancer Assoc. 1999;31(5):1065-1073.

Abstract PDF: PURPOSE
Ataxia Telangiectasia (AT) is a hereditary multi-systemic disease resulting from mutations of AT gene and is characterized by progressive neurodegeneration, cancer, immune system defects, and hypersensitivity to ionizing radiation. AT gene has a homologue sequence of PI3-kinase. The activity and cellular function of PI3-kinase in AT gene remains unclear. This study was undertaken to evaluate the function of AT gene through the effect on cell survival and differentiation by the inhibition of AT gene expression.
MATERIALS AND METHODS
NH2-terminal portion of AT gene was isolated from MCF-7 cells by RT-PCR. The isolated DNA fragment was ligated in reverse orientation in pcDNA3. This antisense ATM expression vector was transfected to PC-12 cells by calcium phosphate method, and the transformed cells were selected using G418 and immunohisto- chemistry. To analyze the cell survival and differentiation, cells were cultured in serum free medium supplemented with/without NGF. We performed the immunoprecipitation for the p53 induction of cells after ionizing radiation, and the FACS for the apoptosis of cells after the exposure of wortmanin.
RESULTS
PC-12 cells which down-regulated AT gene (like ATM, AT mutated) showed decreased survival and ceased differentiation with NGF. Also, PC-12 (ATM) cells showed increased apoptosis with wortmanin and reduced or delayed p53 induction after ionizingradiation.
CONCLUSION
Results obtained from these studies suggest that AT gene regulates survival and differentiation of PC-12 cells through PI3-kinase activity. It seems that apoptosis is induced by the inhibition of AT gene expression.

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Type of Intestinal Metaplasia in the Surrounding Mucosa of Gastric Carcinoma and Expression of bcl-2, p53 and c-erbB-2 Prtein in Gastric Carcinoma: Seung Che Cho, Kun Young Kwon; J Korean Cancer Assoc. 1999;31(5):898-911.

Abstract PDF: PURPOSE
This study was carried out to clarify significance of types of intestinal metaplasia and roles of bcl-2, p53 and c-erbB-2 protein in the development of gastric carcinoma.
MATERIALS AND METHODS
Total one hundred fifty nine cases of surgically resected stomachs with benign ulcer (n=21), dysplasia (n=18) and gastric carcinoma (n=120) were studied histologically, histochemically and immunohistochemically.
RESULTS
Type III intestinal metaplasia was significantly more common in the carcinoma patients in older age group. Bcl-2 expression was found in 94.4% cases of dysplasia and 75.0% cases of carcinoma. Positivity for bcl-2 protein was significantly higher in intestinal type carcinomas than in diffuse type carcinomas (p=0.000). The expression of p53 protein showed 50.0% cases of dysplasia and 49.2% cases of carcinoma. The expression of p53 protein was significantly correlated with depth of invasion (p=0.000), regional lymph node metastasis (p=0.001), and tumor size (p=0.001). C-erbB-2 protein was only expressed in 15.0% cases of carcinoma. The expression of c-erbB-2 protein was found more often in advanced carcinomas (p=0.001) and carcinomas with regional lymph node metastasis (p=0.003).
CONCLUSION
Type III intestinal metaplasia was associated with age, but not with types of gastric carcinoma. Bcl-2 protein is probably involved in dysplastic lesion of gastric carcinogenic sequence and associated with intestinal type carcinoma, and p53 protein is also involved in dysplasia. p53 protein and c-erbB-2 protein may have a role of tumor invasion and nodal metastasis as poor prognostic factors.

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Clinico-pathologic Study on Multiple Squamous Epithelial Neoplasia of the Esophagus: Kyung Ja Cho, Seung Sook Lee, Jae Soo Koh, Jae Ill Zo, Ja June Jang; J Korean Cancer Assoc. 1999;31(3):598-606.

Abstract PDF: PURPOSE
Multicentric occurrence of esophageal squamous neoplasm has been known to be significant in terms of its pathogenesis and production of detectable early lesions. This study was performed to establish the incidence, pattem and clinico-pathologic features of multiple squamous epithelial neoplasia of the esophagus in Korea.
MATERIALS AND METHODS
Forty-two consecutive cases of esophageal squamous cell carcinoma surgically treated at Korea Cancer Center Hospital in 1991 were studied. For pathological analysis, whole esophagectomy specimens were sectioned, micrascopically examined, and reconstructed. Age, sex, alcohol and smoking history, tumor location, stage, lymph node metastasis and survival were compared among different neoplastic conditions.
RESULT
Fifteen cases (35.7%) showed multiple squamous lesions, 6 (14.3%) with multiple carcinomas and dysplasias, and 9 (21.4%) with single carcinomas with separate dysplasias. Intraepithelial lesions contiguous to main tumors were commonly observed (61.9%). Lugol`s solution staining pattern was compatible with epithelial pathology. Lymph node metastasis rate was significantly higher in cases with multiple carcinomas. Smoking history was significantly more common in patients with solitary catcinomas only.
CONCLUSION
The multicentric occurrence of squamous epithelial dysplasia and carcinoma in the esophagus was confirmed in Korean patients, supporting the concept of field carcinogenesis at this region. However, lack of evidence for strong environmental influence in the patients with multiple lesions suggests yet another risk factor.

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Correlation of Breast Cancer with Atypical Ductal Hyperplasia on Fine-needle Aspiration Cytology Speciemens: Lee Su Kim, Jin Hee Sohn, Jeong Jin Kim, Jong Hyun Kim, Kyung Ho Cha, Song Kim, Chang Sig Choi, Bong Hwa Lee; J Korean Cancer Assoc. 1999;31(3):517-522.

Abstract PDF: PURPOSE
Atypical ductal hyperplasia (ADH) is a lesion with significant malignant potential We evaluated the prevalence of breast carcinoma in surgical breast biopsies performed on palpable breast lesions diagnosed initially as ADH by fine needle aspiration cytology (FNAC).
MATERIALS AND METHODS
Between January 1, 1996 and December 31, 1997, 942 patients who underwent FNAC at the Department of Surgery and Pathology, College of Medicine, Hallym University and Department of Surgery, Central Gil Hospital were analyzed. ADH was found in 46 (4.9%) of 942 patients, and surgica1 excision subsequently was performed in 39 of these cases. In these 39 cases, cytologic and histopathologic results from FNAC and surgical biopsies were reviewed and correlated.
RESULTS
Histopathologic study of the 39 surgically excised lesions diagnosed as ADH in their FNAC specimens showed breast cancer in 15 cases (38.5%), ADH in 11 cases (28.2%) and benign disease in 13 cases (33.3%).
CONCLUSION
In our patient populatian, 15 cases (38.5%) of 39 patients with ADH at FNAC had a breast cancer. Therefore, the FNAC finding of ADH may warrant a recommendation for an excisional biopsy.

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Bcl-2 Expression in Endometrial Hyperplasia and Carcinoma: Jong Hyeok Kim, Chang Won Koh, Joor Yung Huh, Bong Hee Kim, Hun Sik Kong, Jun Hee Na, Yong Nam Kim, Young Tak Kim, Joo Hyun Nam; J Korean Cancer Assoc. 1998;30(6):1207-1218.

Abstract PDF: PURPOSE
To speculate the role of bcl-2 protooncogene in endometrial carcinogenesis by determination of the expression of bcl-2 in endometrial hyperplasia and carcinoma.
MATERIALS AND METHODS
We studied bcl-2 expression by an immunohistochemical method in the paraffin-embedded blocks of 78 patients with endometrial hyperplasia, 64 with simple hyperpasia, 9 with complex hyperplasia and 5 with atypical hyperplasia respectively, and 33 endometrial carcinoma treated at Asan Medical Center from June, 1989 to May, 1997. Intensity of bcl-2 staining was scored on a scale of 0 to 4, calibrated by comparison with stromal lymphocytes, which always received a score of 4.
RESULTS
The results of this study showed that bcl-2 was relatively highly expressed in simple (n= 64), complex (n=9) and atypical hyperplasias (n=5) with mean staining scores of 2.95+/-1.09 (Mean+Standard Deviation), 2.78+/-1.20 and 3.60+/-0.89 respectively, which showed no difference among histologic types. In endometrial carcinoma, the expression of bcl-2 was significantly down regulated (mean score=1.76+/-1.35) compared with that of hyperplasia, and did not conelate with FIGO surgical stage. However, grade III tumor showed significantly lower expression that grade I or II tumor.
CONCLUSION
Bcl-2 expression is down regulated in endometrial carcinoma than endo- metrial hyperplasia, and correlates with tumor grade, which suggest that bcl-2 expression might be the result of carcinogenesis or bcl-2 plays only an adjunctive role in the endometrial carcinogenesis.

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DNA Content and Ki - 67 Antibody Expression by Means of Image Analyzer for Laryngeal Lesions: Hyung Ro Chu, Sun Hee Lee, Jong Ouck Choi, In Sun Kim; J Korean Cancer Assoc. 1994;26(3):466-474.

Abstract PDF: The laryngeal epithelial cell kinetics of 26 laryngeal lesions(invasive squamous cell carcinoma 14, epithelial hyperplasia 5, laryngeal nodule 7) were studied by immunohistochemical analysis with the monoclonal antibody Ki-67, which reacts with a nuclear antigen in proliferating cells using paraffin embedded tissue. For DNA analysis, touch imprint with fresh biopsy specimens were stained with Feulgen and analyzed by image analyzer in 22 cases. 1) The positive nuclear area of Ki-67 were 32.65+-11.59% in invasive squamous cell carcino- ma, 20.14 +- 3.38% in epithelial hyperplasia and 11.66+ 3.02% in laryngeal nodule. 2) DNA aneuploidy was found in 7 cases of 10(70%) invasive squamous cell carcinomas, 2 cases of 5(40%) epithelial hyperplasia and none of laryngeal nodules. 3) Average proliferative index(S phasa+ G2/M phase) was 24.32+- 1l.33% in spuamous cell carcinama, 13.09 +- 10.90% in epithelia1 hyperplasia and 4.50 +- 1.19% in laryngeal nodule. As the results, the measurement of the DNA content and Ki-67 positive nuclear area on the small biopsy obtained by microscopic surgery used as effective factors predicting prognosis.

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A case of Multicentric Castleman's Disease: Yong Ho Song, Seon Ho Hwang, Jae Woong Lee, In Soon Kim, You Hern Ahn, Ho Joong Kim, Young Hyeh Ko; J Korean Cancer Assoc. 1995;27(4):696-703.

Abstract PDF: Multicentric Castleman's disease is a systemic lymphoproliferative disorder, characterized by generalized lymphadenopathe, multisystem involvement, disordered immunity and an in- creased incidence of malignant tumors, particularly Kaposis sarcoma and lymphoid neoplasia. The clinical presentation and laboratory features of this syndrome are similar to those of an- other atypical lymphorliferative disorder, angioimmunoblastic lymphadenopathy with dysproteinemia, although this is histologically different from Castleman's disease. A 21-year old male presented ta us with complaints of arthralgia and myalgia of 4 months duration, followed by 2weeks of high fever. Initial physical findings showed small, generalized lymphadenopathies in cervical, axillary and inguinal areas. He developed hepatosplenomegaly and pleuropericardial effusions rapidly. Lymph node biopsy from left inguinal area was consistent with angiofollicular lymph node hyperplasia, plasma cell type.

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