Cancer Research and Treatment

Original Articles

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Received March 23, 2024 Accepted August 18, 2024 Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Breast cancer

A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer: Jung Sun Kim, Koung Jin Suh, Dae-Won Lee, Go-un Woo, Miso Kim, Se Hyun Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, So Yeon Park, In Ae Park, Jee Hyun Kim, Seock-Ah Im; Cancer Res Treat. 2022;54(2):488-496. Published online August 13, 2021; DOI: https://doi.org/10.4143/crt.2021.394

Abstract PDF PubReader ePub

Purpose
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m² on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m² every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

Citations

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Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE)
P. Meyer-Wilmes, J. Huober, M. Untch, J.-U. Blohmer, W. Janni, C. Denkert, P. Klare, T. Link, K. Rhiem, C. Bayer, M. Reinisch, V. Bjelic-Radisic, D.M. Zahm, C. Hanusch, C. Solbach, G. Heinrich, A.D. Hartkopf, A. Schneeweiss, P. Fasching, N. Filmann, V. Ne
ESMO Open.2024; 9(5): 103009. CrossRef
Real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and laboratory parameters in patients across metastatic tumor sites
Vikas Talreja, Sangeeta Khetwani, Ethirajan Nanadagopal, Nilesh Eknath Borkar, Kunal Khobragade
International Journal of Molecular and Immuno Oncology.2024; 9: 46. CrossRef
Safety and efficacy of generic nab-paclitaxel-based therapy in Chinese patients with malignant tumors in a real-world setting: a multicenter prospective observational study
Fei He, Yancai Sun, Wenzhou Zhang, Qiongshi Wu, Donghang Xu, Zaixian Bai, Zhiying Hao, Weiyi Feng, Kanghuai Zhang, Jiang Liu, Mei Dong, Guangxuan Liu, Guohui Li
Discover Oncology.2024;[Epub] CrossRef
Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study
Zhichao Tian, Shuping Dong, Yang Yang, Shilei Gao, Yonghao Yang, Jinpo Yang, Peng Zhang, Xin Wang, Weitao Yao
BMC Cancer.2022;[Epub] CrossRef
Paclitaxel

Reactions Weekly.2022; 1926(1): 383. CrossRef
Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity
Ľuboš Nižnanský, Denisa Osinová, Roman Kuruc, Alexandra Hengerics Szabó, Andrea Szórádová, Marián Masár, Žofia Nižnanská
International Journal of Molecular Sciences.2022; 23(24): 15619. CrossRef
A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma
Hua Yang, Mu-Zi-he Zhang, Hui-wei Sun, Yan-tao Chai, Xiaojuan Li, Qiyu Jiang, Jun Hou
Frontiers in Oncology.2021;[Epub] CrossRef

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Gastrointestinal cancer

Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer: Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2022;54(2):541-553. Published online August 6, 2021; DOI: https://doi.org/10.4143/crt.2021.473

Abstract PDF PubReader ePub

Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

Citations

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Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
Cancers.2024; 16(9): 1690. CrossRef
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Update on Combination Strategies of PARP Inhibitors
Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
Cancer Control.2024;[Epub] CrossRef
The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
Cells.2022; 11(9): 1463. CrossRef
Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
Viruses.2022; 14(7): 1372. CrossRef
Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited
Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Tina Dalianis
Cancers.2022; 15(1): 93. CrossRef

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Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients: Woochan Park, Ju-Hee Bang, Ah-Rong Nam, Mei Hua Jin, Hyerim Seo, Jae-Min Kim, Kyoung Seok Oh, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2021;53(1):199-206. Published online October 6, 2020; DOI: https://doi.org/10.4143/crt.2020.497

Abstract PDF Supplementary Material PubReader ePub

Purpose
The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC).
Materials and Methods
We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics.
Results
The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline.
Conclusion
sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.

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Laccase-inspired bi-amino acid MOFs with high substrate affinity: Catalytic deposition induced “signal-down” electrochemical response towards PD-L1
Ruhui Hu, Suyun Zhong, Hezhen Liu, Yawen Liu, Hongxia Chen, Xiaojun Hu
Sensors and Actuators B: Chemical.2024; 399: 134773. CrossRef
Prognostic significance of soluble PD-L1 in prostate cancer
Margarita Zvirble, Zilvinas Survila, Paulius Bosas, Neringa Dobrovolskiene, Agata Mlynska, Gintaras Zaleskis, Jurgita Jursenaite, Dainius Characiejus, Vita Pasukoniene
Frontiers in Immunology.2024;[Epub] CrossRef
CRP and soluble CTLA4 are determinants of anti-PD1 resistance in gastrointestinal cancer
Kotoe Oshima
American Journal of Cancer Research.2024; 14(3): 1174. CrossRef
Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications
Lin Chen, Yuqing Chao, Wenjing Li, Zhixia Wu, Qinchuan Wang
Biomarker Research.2024;[Epub] CrossRef
Myeloid subsets impede the efficacy of anti-PD1 therapy in patients with advanced gastric cancer (WJOG10417GTR study)
Hirokazu Shoji, Chie Kudo-Saito, Kengo Nagashima, Hiroshi Imazeki, Kai Tsugaru, Naoki Takahashi, Takeshi Kawakami, Yusuke Amanuma, Takeru Wakatsuki, Naohiro Okano, Yukiya Narita, Yoshiyuki Yamamoto, Rika Kizawa, Kei Muro, Kazunori Aoki, Narikazu Boku
Journal for ImmunoTherapy of Cancer.2024; 12(11): e010174. CrossRef
Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy
Xiao-Peng Duan, Ke Liu, Xiao-Dong Jiao, Bao-Dong Qin, Bing Li, Xi He, Yan Ling, Ying Wu, Shi-Qi Chen, Yuan-Sheng Zang
Frontiers in Oncology.2023;[Epub] CrossRef
Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy
Kabsoo Shin, Joori Kim, Se Jun Park, Myung Ah Lee, Jae Myung Park, Myung-Gyu Choi, Donghoon Kang, Kyo Young Song, Han Hong Lee, Ho Seok Seo, Sung Hak Lee, Bohyun Kim, Okran Kim, Juyeon Park, Nahyeon Kang, In-Ho Kim
Scientific Reports.2023;[Epub] CrossRef
Site-specific protein biomarkers in gastric cancer: a comprehensive review of novel biomarkers and clinical applications
Takahiro Shinozuka, Mitsuro Kanda, Yasuhiro Kodera
Expert Review of Molecular Diagnostics.2023; 23(8): 701. CrossRef
The predictive role of soluble programmed death ligand 1 in digestive system cancers
Jian Ruan, Zhihong Zhao, Yuting Qian, Ruilian Xu, Guixiang Liao, Feng-Ming (Spring) Kong
Frontiers in Oncology.2023;[Epub] CrossRef
Does Elevated Pre-Treatment Plasma PD-L1 Level Indicate an Increased Tumor Burden and Worse Prognosis in Metastatic Colorectal Cancer?
Magdolna Dank, Dorottya Mühl, Magdolna Herold, Lilla Hornyák, Attila Marcell Szasz, Zoltan Herold
Journal of Clinical Medicine.2022; 11(16): 4815. CrossRef
How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches
Michele Ghidini, Angelica Petrillo, Andrea Botticelli, Dario Trapani, Alessandro Parisi, Anna La Salvia, Elham Sajjadi, Roberto Piciotti, Nicola Fusco, Shelize Khakoo
Journal of Clinical Medicine.2021; 10(7): 1412. CrossRef

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Breast cancer

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients: Mihong Choi, Jiyeon Han, Bo Ram Yang, Myoung-jin Jang, Miso Kim, Dae-Won Lee, Tae-Yong Kim, Seock-Ah Im, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee; Cancer Res Treat. 2021;53(1):65-76. Published online September 23, 2020; DOI: https://doi.org/10.4143/crt.2020.430

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
Materials and Methods
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Results
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Conclusion
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

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Santosh Kumar Maurya, Smriti Chaudhri, Shashank Kumar, Sanjay Gupta
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Are statins onco- suppressive agents for every type of tumor? A systematic review of literature
Luca Filaferro, Fabiana Zaccarelli, Giovanni Francesco Niccolini, Andrea Colizza, Federica Zoccali, Michele Grasso, Massimo Fusconi
Expert Review of Anticancer Therapy.2024; 24(6): 435. CrossRef
Investigating the relationship between insulin use and all-cause mortality, breast cancer mortality, and recurrence risk in diabetic patients with breast cancer: A comprehensive systematic review and meta-analysis
Marina V. Loktionova, Mahdi Mohammadian, Roya Choopani, Soleiman Kheiri, Abdollah Mohammadian-Hafshejani, Kathleen Bennett
PLOS ONE.2024; 19(12): e0314565. CrossRef
Impact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis
Xiaolin Jia, Ye Lu, Zili Xu, Qingqing Mu
Frontiers in Oncology.2023;[Epub] CrossRef
Effect of statins use on risk and prognosis of breast cancer: a meta-analysis
Guodong Zhao, Yanjun Ji, Qing Ye, Xin Ye, Guanqun Wo, Xi Chen, Xinyi Shao, Jinhai Tang
Anti-Cancer Drugs.2022; 33(1): e507. CrossRef
Studying the Cytotoxic Activity of Newly Designed and Synthesized HDAC Inhibitors Derivatives of Pentanoyl Anilide‐5‐Biguanide
Othman Makki Sagheer, Mohammed Hassan Mohammed, Jaafar S. Wadi, Zaid O. Ibraheem
Macromolecular Symposia.2022;[Epub] CrossRef
Metformin and Breast Cancer: Where Are We Now?
Mónica Cejuela, Begoña Martin-Castillo, Javier A. Menendez, Sonia Pernas
International Journal of Molecular Sciences.2022; 23(5): 2705. CrossRef
Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression
Giorgia Centonze, Dora Natalini, Alessio Piccolantonio, Vincenzo Salemme, Alessandro Morellato, Pietro Arina, Chiara Riganti, Paola Defilippi
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Synthesis of gamma biguanides butyric acid analogues as HDAC inhibitors and studying their cytotoxic activity
Othman Makki Sagheer, Mohammed Hassan Mohammed, Zaid O. Ibraheem, Jaafar S. Wadi, Mustafa F. Tawfeeq
Materials Today: Proceedings.2021; 47: 5983. CrossRef
Statins: a repurposed drug to fight cancer
Wen Jiang, Jin-Wei Hu, Xu-Ran He, Wei-Lin Jin, Xin-Yang He
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef
Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study
Byoung Hyuck Kim, Moon-June Cho, Jeanny Kwon
International Journal of Clinical Oncology.2021; 26(11): 2004. CrossRef

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Gastrointestinal cancer

Adjuvant Chemotherapy in Microsatellite Instability–High Gastric Cancer: Jin Won Kim, Sung-Yup Cho, Jeesoo Chae, Ji-Won Kim, Tae-Yong Kim, Keun-Wook Lee, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2020;52(4):1178-1187. Published online June 11, 2020; DOI: https://doi.org/10.4143/crt.2020.313

Abstract PDF Supplementary Material PubReader ePub

Purpose
Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Material and Methods This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.
Results
Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).
Conclusion
MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

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Satya Das, Taymeyah Al-Toubah, Jonathan Strosberg
Cancers.2021; 13(19): 4872. CrossRef

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Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy: Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, In Gyu Hwang, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, In Sook Woo, Soojung Hong, Tae-Yong Kim, Ji Yeon Baek, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Hun-Mo Ryoo, Kyung Hee Lee, Jee Hyun Kim; Cancer Res Treat. 2019;51(3):1249-1256. Published online January 2, 2019; DOI: https://doi.org/10.4143/crt.2018.451

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
Materials and Methods
Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
Results
The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
Conclusion
KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

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Han Zhao, Xinlin Lu, Senshuang Zheng, Danmei Wei, Lizhong Zhao, Yuan Wang, Geertruida H. de Bock, Wenli Lu
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Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study
In Gyu Hwang, Minsuk Kwon, Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, Soojung Hong, Tae-Yong Kim, Sun Young Kim, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Kyung Hee Lee,
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Koung Jin Suh, Seonghae Yoon, Jin Won Kim, Seo Hyun Yoon, Ji-Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jee Hyun Kim
Journal of Geriatric Oncology.2021; 12(6): 922. CrossRef
Predictive Value of Geriatric Oncology Screening and Geriatric Assessment in Older Patients with Solid Cancers: Protocol for a Danish prospective cohort study (PROGNOSIS-G8)
Helena Møgelbjerg Ditzel, Ann-Kristine Weber Giger, Cecilia Margareta Lund, Henrik Jørn Ditzel, Afsaneh Mohammadnejad, Per Pfeiffer, Jesper Ryg, Trine Lembrecht Jørgensen, Marianne Ewertz
Journal of Geriatric Oncology.2021; 12(8): 1270. CrossRef
The Globalization of Geriatric Oncology: From Data to Practice
Ravindran Kanesvaran, Supriya Mohile, Enrique Soto-Perez-de-Celis, Harpreet Singh
American Society of Clinical Oncology Educational Book.2020; (40): e107. CrossRef

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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01): In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro; Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018; DOI: https://doi.org/10.4143/crt.2017.562

Abstract PDF PubReader ePub

Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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The Impact of Skin Problems on the Quality of Life in Patients Treated with Anticancer Agents: A Cross-Sectional Study: Jaewon Lee, Jin Lim, Jong Seo Park, Miso Kim, Tae-Yong Kim, Tae Min Kim, Kyung-Hun Lee, Bhumsuk Keam, Sae-Won Han, Je-Ho Mun, Kwang Hyun Cho, Seong Jin Jo; Cancer Res Treat. 2018;50(4):1186-1193. Published online December 14, 2017; DOI: https://doi.org/10.4143/crt.2017.435

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patients treated with anticancer agents often experience a variety of treatment-related skin problems, which can impair their quality of life.
Materials and Methods
In this cross-sectional study, Dermatology Life Quality Index (DLQI) and clinical information were evaluated in patients under active anticancer treatment using a questionnaire survey and their medical records review.
Results
Of 375 evaluated subjects with anticancer therapy, 136 (36.27%) and 114 (30.40%) were treated for breast cancer and colorectal cancer, respectively. We found that women, breast cancer, targeted agent use, and longer duration of anticancer therapy were associated with higher dermatology-specific quality of life distraction. In addition, itching, dry skin, easy bruising, pigmentation, papulopustules on face, periungual inflammation, nail changes, and palmoplantar lesions were associated with significantly higher DLQI scores. Periungual inflammation and palmoplantar lesions scored the highest DLQI.
Conclusion
We believe our findings can be helpful to clinicians in counseling and managing the patients undergoing anticancer therapy.

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Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate: Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(4):1033-1043. Published online April 7, 2017; DOI: https://doi.org/10.4143/crt.2016.413

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

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Jamie C. Brehaut, Kelly Carroll, Justin Presseau, Dawn P. Richards, Jenn Gordon, Angèle Bénard, Natasha Hudek, Ian D. Graham, Dean A. Fergusson, Susan Marlin
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Jamie C. Brehaut, Kelly Carroll, Jenn Gordon, Justin Presseau, Dawn P. Richards, Dean A. Fergusson, Ian D. Graham, Susan Marlin
Current Oncology.2021; 28(3): 2014. CrossRef
Regional Differences in Access to Clinical Trials for Cancer in Korea
Woorim Kim, Seongkyeong Jang, Yoon Jung Chang
Quality Improvement in Health Care.2021; 27(1): 20. CrossRef
How Cancer Patients Perceive Clinical Trials (CTs) in the Era of CTs: Current Perception and Its Differences Between Common and Rare Cancers
Ji Hyun Park, Ji Sung Lee, HaYeong Koo, Jeong Eun Kim, Jin-Hee Ahn, Min-Hee Ryu, Sook-ryun Park, Shin-kyo Yoon, Jae Cheol Lee, Yong-Sang Hong, Sun Young Kim, Kyo-Pyo Kim, Chang-Hoon Yoo, Jung Yong Hong, Jae Lyun Lee, Kyung Hae Jung, Baek-Yeol Rhyoo, Tae W
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Colorectal cancer survivors’ willingness to participate in a hypothetical clinical trial of Korean medicine: A cross-sectional study
Yown Hwangbo, Gyung Mo Son, Kyung Hee Kim, Myeong Sook Kwon, Kun Hyung Kim
European Journal of Integrative Medicine.2020; 33: 101033. CrossRef
Perception and Satisfaction of Anticancer Drug Clinical Trials in Cancer Patients
Ju Kyung Jeon, Jeong Hye Kim
Asian Oncology Nursing.2019; 19(1): 18. CrossRef
Challenges in informed consent decision-making in Korean clinical research: A participant perspective
Im-Soon Choi, Eun Young Choi, Iyn-Hyang Lee, Dermot Cox
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Clinical Trials: What, Where, When?
Olga S. Kobyakova, Ivan A. Deev, Evgeny S. Kulikov, Roman I. Shtykh, Igor D. Pimenov, Olga I. Zvonareva, Igor V. Mareev
Annals of the Russian academy of medical sciences.2018; 73(5): 314. CrossRef

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S-1–Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study: Namju Kim, Jin Won Kim, Je-Hyun Baek, Jin-Soo Kim, Ho-Kyung Choung, Tae-Yong Kim, Kyung-Hun Lee, Yung-Jue Bang, Sang In Khwarg, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Jae-Yong Chung, Soyeon Ahn, Keun-Wook Lee; Cancer Res Treat. 2018;50(1):30-39. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.569

Abstract PDF Supplementary Material PubReader ePub

Purpose
This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.
Materials and Methods
A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.
Results
Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1–related non-hematologic toxicity more frequently than those without LDO (p=0.016).
Conclusion
LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

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Influenza A Virus Utilizes the Nasolacrimal System to Establish Respiratory Infection after Ocular Exposure in the Swine Model
Shubin Li, Xuebin Peng, MinJie Wang, Wenqian Wang, Yuye Liu, Qian Yang, Makoto Ozawa
Transboundary and Emerging Diseases.2024;[Epub] CrossRef
Nasolacrimal Duct Obstruction in the Patients Receiving Treatment for Cancer
Vasily D. Yartsev, Eugenia L. Atkova
International Ophthalmology Clinics.2023; 63(3): 137. CrossRef
Obstrução lacrimal pós-tratamento oncológico: revisão de literatura
Camilla Duarte Silva, Fabricio Lopes da Fonseca, Juliana Mika Kato, Suzana Matayoshi
Revista Brasileira de Oftalmologia.2022;[Epub] CrossRef
A Case of Nasolacrimal Duct Obstruction During S-1 Treatment For Breast Cancer
Hisataka Ominato, Michihisa Kono, Hidekiyo Yamaki, Takumi Kumai, Miki Takahara, Akihiro Katada, Tatsuya Hayashi
Practica Oto-Rhino-Laryngologica.2022; 115(6): 503. CrossRef
Corneal nerve changes following treatment with neurotoxic anticancer drugs
Jeremy Chung Bo Chiang, David Goldstein, Susanna B. Park, Arun V. Krishnan, Maria Markoulli
The Ocular Surface.2021; 21: 221. CrossRef
The impact of anticancer drugs on the ocular surface
Jeremy Chung Bo Chiang, Ilyanoon Zahari, Maria Markoulli, Arun V. Krishnan, Susanna B. Park, Annalese Semmler, David Goldstein, Katie Edwards
The Ocular Surface.2020; 18(3): 403. CrossRef
Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients
Hirofumi Yasui, Takeshi Kawakami, Hiroya Kashiwagi, Keita Mori, Katsuhiro Omae, Jun Kasai, Kunihiro Yoshisue, Masahiro Kawahira, Takahiro Tsushima, Nozomu Machida, Akira Fukutomi, Ken Yamaguchi
International Journal of Clinical Oncology.2019; 24(6): 660. CrossRef

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Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor–Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors: Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Tae-Yong Kim, Yu Jung Kim, Sae-Won Han, Eunyoung Kang, Eun-Kyu Kim, Kidong Kim, Jae Hong No, Wonshik Han, Dong-Young Noh, Maria Lee, Hee Seung Kim, Seock-Ah Im, Jee Hyun Kim; Cancer Res Treat. 2017;49(4):1153-1163. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.463

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO).
Materials and Methods
We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015.
Results
The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL.
Conclusion
Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.

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Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists
Jinna Lin, Shuqi Zheng, Qiang Liu
Cancer Treatment Reviews.2025; 133: 102879. CrossRef
Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study
Yifei Chen, Ruyan Zhang, Ying Yan, Huiping Li, Guohong Song
Breast Cancer Research and Treatment.2024; 206(3): 543. CrossRef
Oophorectomy in Premenopausal Patients with Estrogen Receptor-Positive Breast Cancer: New Insights into Long-Term Effects
Fatima Khan, Kristin Rojas, Matthew Schlumbrecht, Patricia Jeudin
Current Oncology.2023; 30(2): 1794. CrossRef
Comparison of outcomes in patients with luminal type breast cancer treated with a gonadotropin-releasing hormone analog or bilateral salpingo-oophorectomy: A cohort retrospective study
Dwi Ris Andriyanto, Prihantono, Salman Ardi Syamsu, Muhammad Ihwan Kusuma, Joko Hendarto, Indra, Nilam Smaradania, Elridho Sampepajung, Asrul Mappiwali, Muhammad Faruk
Annals of Medicine & Surgery.2022;[Epub] CrossRef
Awareness of the Causes Leading to Surgical Ablation of Ovarian Function in Premenopausal Breast Cancer—A Single-Center Analysis
Joana Correia Oliveira, Filipa Costa Sousa, Inês Gante, Margarida Figueiredo Dias
Medicina.2021; 57(4): 385. CrossRef
Long-term effect of repeated deslorelin acetate treatment in bitches for reproduction control
Brändli SP, Palm J, Kowalewski MP, Reichler IM
Theriogenology.2021; 173: 73. CrossRef
Prognostic Factors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2–) Advanced Breast Cancer: A Systematic Literature Review
Gebra Cuyún Carter, Maitreyee Mohanty, Keri Stenger, Claudia Morato Guimaraes, Shivaprasad Singuru, Pradeep Basa, Sheena Singh, Vanita Tongbram, Sherko Kuemmel, Valentina Guarneri, Sara M Tolaney
Cancer Management and Research.2021; Volume 13: 6537. CrossRef
Oophorectomy as a Hormonal Ablation Therapy in Metastatic and Recurrent Breast Cancer: Current Indications and Results
Islam H. Metwally, Omar Hamdy, Saleh S. Elbalka, Mohamed Elbadrawy, Dina M. Elsaid
Indian Journal of Surgical Oncology.2019; 10(3): 542. CrossRef
Targeted Therapy for Premenopausal Women with HR+, HER2− Advanced Breast Cancer: Focus on Special Considerations and Latest Advances
Aditya Bardia, Sara Hurvitz
Clinical Cancer Research.2018; 24(21): 5206. CrossRef

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CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy: Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2017;49(3):807-815. Published online January 18, 2017; DOI: https://doi.org/10.4143/crt.2016.326

Abstract PDF PubReader ePub

Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

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Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
Cancer Treatment and Research Communications.2021; 28: 100431. CrossRef
Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei—A Novel Treatment Approach
Aruna Prabhu, Andreas Brandl, Satoshi Wakama, Shouzou Sako, Haruaki Ishibashi, Akiyoshi Mizumoto, Nobuyuki Takao, Kousuke Noguchi, Shunsuke Motoi, Masumi Ichinose, Yang Liu, Yutaka Yonemura
Cancers.2020; 12(8): 2212. CrossRef
Clinical and Translational Research Challenges in Biliary Tract Cancers
Angela Lamarca, Melissa Frizziero, Mairéad G. McNamara, Juan W. Valle
Current Medicinal Chemistry.2020; 27(29): 4756. CrossRef
Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin
Min su You, Ji Kon Ryu, Young Hoon Choi, Jin Ho Choi, Gunn Huh, Woo Hyun Paik, Sang Hyub Lee, Yong-Tae Kim
BMC Cancer.2019;[Epub] CrossRef
Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy
Puzhao Wu, Jing Wang
Oncology Letters.2019;[Epub] CrossRef
CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer
Naminatsu Takahara, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kei Saito, Kensaku Noguchi, Tatsunori Suzuki, Tomoka Nakamura, Tatsuya Sato, Kazunaga Ishigaki, Ryunosuke Hakuta, Tsuyoshi Takeda, Rie Uchino, Suguru Mizuno, Hirofumi Kogure, Minoru Tada
Cancer Chemotherapy and Pharmacology.2017; 80(6): 1105. CrossRef

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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis: Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(3):643-655. Published online October 6, 2016; DOI: https://doi.org/10.4143/crt.2016.168

Abstract PDF Supplementary Material PubReader ePub

Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.
Materials and Methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.
Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho- Src and proliferative-signaling molecules were down-regulated in KX-01–sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01– induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01–sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.
Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

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Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization
Viola K. DeTemple, Antje Walter, Sabine Bredemeier, Ralf Gutzmer, Katrin Schaper-Gerhardt
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Stephen Moore, Veda Kulkarni, Angela Moore, Jennifer R. Landes, Rebecca Simonette, Qin He, Peter L. Rady, Stephen K. Tyring
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Mario Valenti, Matteo Bianco, Alessandra Narcisi, Antonio Costanzo, Riccardo Borroni, Marco Ardigò
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Angela Moore, Kara Hurley, Stephen A. Moore, Luke Moore
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Jaebeom Park, Minji Kang, Ahyoung Lim, Kyung-Jin Cho, Chong Hak Chae, Byumseok Koh, Hongjun Jeon
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Y. Gilaberte, M.T. Fernández-Figueras
Actas Dermo-Sifiliográficas.2022; 113(1): 58. CrossRef
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Maan T. Khayat, Abdelsattar M. Omar, Farid Ahmed, Mohammad I. Khan, Sara M. Ibrahim, Yosra A. Muhammad, Azizah M. Malebari, Thikryat Neamatallah, Moustafa E. El-Araby
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Cancers.2022; 14(6): 1575. CrossRef
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Minru Liao, Rui Qin, Wei Huang, Hong-Ping Zhu, Fu Peng, Bo Han, Bo Liu
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SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases
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Y. Gilaberte, M.T. Fernández-Figueras
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Kinsie E Arnst, Souvik Banerjee, Hao Chen, Shanshan Deng, Dong‐Jin Hwang, Wei Li, Duane D Miller
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Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity
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Michael J. Ciesielski, Yahao Bu, Stephan A. Munich, Paola Teegarden, Michael P. Smolinski, James L. Clements, Johnson Y. N. Lau, David G. Hangauer, Robert A. Fenstermaker
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Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea: Seung Hoon Beom, Jisu Oh, Tae-Yong Kim, Kyung-Hun Lee, Yaewon Yang, Koung Jin Suh, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, Tae-You Kim, Dong-Young Noh, Seock-Ah Im; Cancer Res Treat. 2017;49(2):454-463. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.259

Abstract PDF PubReader ePub

Purpose
Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients.
Materials and Methods
This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment historywere extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity.
Results
The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated.
Conclusion
Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

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Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis
Josee-Lyne Ethier, Danielle N. Desautels, Eitan Amir, Helen MacKay
Gynecologic Oncology.2017; 147(1): 158. CrossRef

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Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program: Myoung Kyun Son, Min-Hee Ryu, Joon Oh Park, Seock-Ah Im, Tae-Yong Kim, Su Jin Lee, Baek-Yeol Ryoo, Sook Ryun Park, Yoon-Koo Kang; Cancer Res Treat. 2017;49(2):350-357. Published online July 19, 2016; DOI: https://doi.org/10.4143/crt.2016.067

Abstract PDF PubReader ePub

Purpose
The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.
Materials and Methods
Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on /1 week off).
Results
None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a handfoot skin reaction (n=31).
Conclusion
This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

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English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology
Seiichi Hirota, Ukihide Tateishi, Yuji Nakamoto, Hidetaka Yamamoto, Shinji Sakurai, Hirotoshi Kikuchi, Tatsuo Kanda, Yukinori Kurokawa, Haruhiko Cho, Toshirou Nishida, Akira Sawaki, Masato Ozaka, Yoshito Komatsu, Yoichi Naito, Yoshitaka Honma, Fumiaki Tak
International Journal of Clinical Oncology.2024; 29(6): 647. CrossRef
A randomised phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumours
Hyung-Don Kim, Changhoon Yoo, Min-Hee Ryu, Yoon-Koo Kang
British Journal of Cancer.2023; 129(2): 275. CrossRef
Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule
Maria Susanna Grimaudo, Alice Laffi, Nicolò Gennaro, Roberta Fazio, Federico D’Orazio, Laura Samà, Licia Vanessa Siracusano, Federico Sicoli, Salvatore Lorenzo Renne, Armando Santoro, Alexia Francesca Bertuzzi
Frontiers in Oncology.2023;[Epub] CrossRef
Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours
Marin Golčić, Robin L. Jones, Paul Huang, Andrea Napolitano
Cancers.2023; 15(16): 4081. CrossRef
Medical oncological treatment for patients with Gastrointestinal Stromal Tumor (GIST) – A systematic review
Charlotte Margareta Brinch, Ninna Aggerholm-Pedersen, Estrid Hogdall, Anders Krarup-Hansen
Critical Reviews in Oncology/Hematology.2022; 172: 103650. CrossRef
Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature
Deborah van de Wal, Mai Elie, Axel Le Cesne, Elena Fumagalli, Dide den Hollander, Robin L. Jones, Gloria Marquina, Neeltje Steeghs, Winette T. A. van der Graaf, Olga Husson
Cancers.2022; 14(7): 1832. CrossRef
Efficacy and safety of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors
Ryugo Teranishi, Tsuyoshi Takahashi, Toshirou Nishida, Seiichi Hirota, Yukinori Kurokawa, Takuro Saito, Kazuyoshi Yamamoto, Kotaro Yamashita, Koji Tanaka, Tomoki Makino, Masaaki Motoori, Takeshi Omori, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki
International Journal of Clinical Oncology.2022; 27(7): 1164. CrossRef
The Role of Regorafenib in the Management of Advanced Gastrointestinal Stromal Tumors: A Systematic Review
Vahe Khachatryan, Asmaa Muazzam, Chandani Hamal, Lakshmi Sai Deepak Reddy Velugoti, Godfrey Tabowei, Greeshma N Gaddipati, Maria Mukhtar, Mohammed J Alzubaidee, Raga Sruthi Dwarampudi, Sheena Mathew, Sumahitha Bichenapally, Lubna Mohammed
Cureus.2022;[Epub] CrossRef
CT Image Examination Based on Virtual Reality Analysis in Clinical Diagnosis of Gastrointestinal Stromal Tumors
Zhiying Wang, Qiaoyan Qu, Ke Cai, Ting Xu, Zhihan Lv
Journal of Healthcare Engineering.2021; 2021: 1. CrossRef
The Use of Inhibitors of Tyrosine Kinase in Paediatric Haemato-Oncology—When and Why?
Agnieszka Kaczmarska, Patrycja Śliwa, Monika Lejman, Joanna Zawitkowska
International Journal of Molecular Sciences.2021; 22(21): 12089. CrossRef
Molecular Modeling Study of c-KIT/PDGFRα Dual Inhibitors for the Treatment of Gastrointestinal Stromal Tumors
Seketoulie Keretsu, Suparna Ghosh, Seung Joo Cho
International Journal of Molecular Sciences.2020; 21(21): 8232. CrossRef
Regorafenib treatment outcome for Taiwanese patients with metastatic gastrointestinal stromal tumors after failure of imatinib and sunitinib: A prospective, non‑randomized, single‑center study
Chia‑Hsiang Hu, Chun‑Nan Yeh, Jen‑Shi Chen, Chun‑Yi Tsai, Shang‑Yu Wang, Chi‑Tung Cheng, Ta‑Sen Yeh
Oncology Letters.2020; 20(3): 2131. CrossRef
Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers
Ganfeng Xie, Yuzhu Gong, Shuang Wu, Chong Li, Songtao Yu, Zhe Wang, Jianfang Chen, Quanfeng Zhao, Jianjun Li, Houjie Liang
Advances in Therapy.2019; 36(8): 1986. CrossRef
Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib
Jae-Joon Kim, Min-Hee Ryu, Changhoon Yoo, Mo Youl Beck, Jung Eun Ma, Yoon-Koo Kang
The Oncologist.2019; 24(11): e1212. CrossRef
Growing Role of Regorafenib in the Treatment of Patients with Sarcoma
Mark Agulnik, Steven Attia
Targeted Oncology.2018; 13(4): 417. CrossRef
Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients
Gustavo Schvartsman, Michael J. Wagner, Behrang Amini, Chrystia M. Zobniw, Van Anh Trinh, Andrea G. Barbo, Heather Y. Lin, Wei-Lien Wang, Anthony Paul Conley, Vinod Ravi, Dejka M. Araujo, Maria Alejandra Zarzour, Robert S. Benjamin, Shreyaskumar Patel, Ne
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Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib
Bin Zhao, Hong Zhao
Oncotarget.2017; 8(55): 93813. CrossRef

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Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study: Se Hyun Kim, Kyung Hae Jung, Tae-Yong Kim, Seock-Ah Im, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, Sarah Park, In Hae Park, Keun Seok Lee, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Jee Hyun Kim; Cancer Res Treat. 2016;48(4):1373-1381. Published online March 23, 2016; DOI: https://doi.org/10.4143/crt.2015.475

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy.
Materials and Methods
This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model.
Results
A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2– subtype.
Conclusion
LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2– patients is notable and worthy of further investigation.

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Breast Cancer Patients With Positive Apical or Infraclavicular/Ipsilateral Supraclavicular Lymph Nodes Should Be Excluded in the Application of the Lymph Node Ratio System
Zhe Wang, Wei Chong, Huikun Zhang, Xiaoli Liu, Yawen Zhao, Zhifang Guo, Li Fu, Yongjie Ma, Feng Gu
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: A dose-response meta-analysis
Jinzhao Liu, Yifei Li, Weifang Zhang, Chenhui Yang, Chao Yang, Liang Chen, Mingjian Ding, Liang Zhang, Xiaojun Liu, Guozhong Cui, Yunjiang Liu
Frontiers in Surgery.2022;[Epub] CrossRef
Prognostic implications of regression of metastatic axillary lymph nodes after neoadjuvant chemotherapy in patients with breast cancer
Yul Ri Chung, Ji Won Woo, Soomin Ahn, Eunyoung Kang, Eun-Kyu Kim, Mijung Jang, Sun Mi Kim, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
Scientific Reports.2021;[Epub] CrossRef
Using a novel T-lymph node ratio model to evaluate the prognosis of nonmetastatic breast cancer patients who received preoperative radiotherapy followed by mastectomy
Yang Wang, Yuanyuan Zhao, Song Liu, Weifang Tang, Hong Gao, Xucai Zheng, Shikai Hong, Shengying Wang
Medicine.2017; 96(42): e8203. CrossRef
The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and CE(A)F chemotherapy response to breast cancer and clinical outcomes
Xiang Li, Ruishan Zhang, Zhuangkai Liu, Shuang Li, Hong Xu
Oncotarget.2017; 8(12): 20252. CrossRef
Prognostic Significance of Inner Quadrant Involvement in Breast Cancer Treated with Neoadjuvant Chemotherapy
Ji Hyun Chang, Wan Jeon, Kyubo Kim, Kyung Hwan Shin, Wonshik Han, Dong-Young Noh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal of Breast Cancer.2016; 19(4): 394. CrossRef

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Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX: Mi-Jung Kim, Sae-Won Han, Dae-Won Lee, Yongjun Cha, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Se Hyung Kim, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim; Cancer Res Treat. 2016;48(3):990-997. Published online January 14, 2016; DOI: https://doi.org/10.4143/crt.2015.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients.
Materials and Methods
Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells.
Results
Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly.
Conclusion
Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

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Deepanshi Mahajan, Vasudha Sambyal, Kamlesh Guleria
Egyptian Journal of Medical Human Genetics.2025;[Epub] CrossRef
Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy
Kadriye Bir Yücel, Atiye Cenay Karabörk Kilic, Osman Sütcüoglu, Ozan Yazıcı, Koray Kilic, Gözde Savaş, Aytug Uner, Nazan Günel, Ahmet Özet, Nuriye Özdemir
Journal of Chemotherapy.2024; 36(3): 249. CrossRef
Effects of methanolic leaf extract and fractions of Irvingia gabonensis on hematological parameters in Wistar rats with splenomegaly
Fidelia Okoben, InnocentMary Ejiofor, Ikechukwu Mbagwu, Daniel Ajaghaku, Fredrick Anowi
Sciences of Pharmacy.2024; 3(1): 11. CrossRef
Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure
A. Puente, J.I. Fortea, C. Del Pozo, M. Serrano, M. Alonso-Peña, A. Giráldez, L. Tellez, J. Martinez, M. Magaz, L. Ibañez, J. Garcia, E. Llop, C. Alvarez-Navascues, M. Romero, E. Rodriguez, M.T. Arias Loste, A. Antón, V. Echavarria, C. López, A. Albillos,
Digestive and Liver Disease.2024; 56(10): 1721. CrossRef
The “appearing” and “disappearing” ascites in the treatment of colorectal cancer: a case report
Hong-Ming Cui, Xin-Peng Shu, Zheng-Qiang Wei, Xing-Ye Wu
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A contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of oxaliplatin-related thrombocytopenia in patients with gastrointestinal malignancies: a retrospective study
Yuhong Dai, Yiqi Cheng, Ziling Zhou, Zhen Li, Yan Luo, Hong Qiu
PeerJ.2023; 11: e16230. CrossRef
Natural Language Processing of Large-Scale Structured Radiology Reports to Identify Oncologic Patients With or Without Splenomegaly Over a 10-Year Period
Simon Sun, Kaelan Lupton, Karen Batch, Huy Nguyen, Lior Gazit, Natalie Gangai, Jessica Cho, Kevin Nicholas, Farhana Zulkernine, Varadan Sevilimedu, Amber Simpson, Richard K. G. Do
JCO Clinical Cancer Informatics.2022;[Epub] CrossRef
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Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
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Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
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Ryo Ohta, Takeshi Yamada, Keisuke Hara, Takuma Iwai, Kohji Tanakaya, Keiichiro Ishibashi, Kazuhiko Yoshimatsu, Chihiro Kosugi, Masahiro Tsubaki, Hideo Nakajima, Masatoshi Oya, Hiroshi Yoshida, Keiji Koda, Hideyuki Ishida
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N. Sanoj Rejinold, Kondareddy Cherukula, Jong Hoon Ha, In‐Kyu Park, Yeu‐Chun Kim
Advanced Therapeutics.2019;[Epub] CrossRef
Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer
Jeonghyun Kang, Joon Seong Park, Sung Gwe Ahn, Jin Hong Lim, Seung Hyuk Baik, Dong Sup Yoon, Kang Young Lee, Joon Jeong
Annals of Surgical Treatment and Research.2018; 95(3): 161. CrossRef
Automatized spleen segmentation in non-contrast-enhanced MR volume data using subject-specific shape priors
Oliver Gloger, Klaus Tönnies, Robin Bülow, Henry Völzke
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Cancer Chemotherapy and Pharmacology.2016; 78(1): 119. CrossRef

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Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study: Younak Choi, Do-Youn Oh, Kyubo Kim, Eui Kyu Chie, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Sung Whan Ha, Yung-Jue Bang; Cancer Res Treat. 2016;48(3):1045-1055. Published online October 16, 2015; DOI: https://doi.org/10.4143/crt.2015.226

Abstract PDF PubReader ePub

Purpose
The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. Materials and Methods Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively.
Results
Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. Conclusion In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

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Dose-Escalated SBRT for Borderline and Locally Advanced Pancreatic Cancer: Resectability Rate and Pathological Results of a Multicenter Prospective Study
Barbara Salas-Salas, Laura Ferrera-Alayon, Alberto Espinosa-Lopez, Maria Luisa Perez-Rodriguez, Antonio Alayón Afonso, Andres Vera-Rosas, Gabriel Garcia-Plaza, Rodolfo Chicas-Sett, Maria Soledad Martinez-Martin, Elisa Salcedo, Andrea Kannemann, Marta Llor
Cancers.2025; 17(2): 191. CrossRef
Dose-escalated SBRT for borderline and locally advanced pancreatic cancer. Feasibility, safety and preliminary clinical results of a multicenter study
B. Salas, L. Ferrera-Alayón, A. Espinosa-López, A. Vera-Rosas, E. Salcedo, A. Kannemann, A. Alayon, R. Chicas-Sett, M. LLoret, P.C. Lara
Clinical and Translational Radiation Oncology.2024; 45: 100753. CrossRef
Survival benefits of radiotherapy in locally advanced unresectable and metastatic pancreatic cancer: a single-institution cohort and SEER database analysis
Bi-Yang Cao, Le-Tian Zhang, Chen-Chen Wu, Jing Wang, Lin Yang
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Comparing concurrent chemoradiotherapy, 125I seed implantation combined with chemotherapy, and chemotherapy alone efficacy in treating unresectable locally advanced pancreatic cancer
Yanfen Zheng, Rui Huang, Wenxue Zou, Chao Liu, Hongxin Niu, Jinbo Yue
Precision Radiation Oncology.2022; 6(2): 144. CrossRef
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American Journal of Clinical Oncology.2021; 44(9): 469. CrossRef
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Toshimichi ASANO, Satoshi HIRANO, Toru NAKAMURA, Takehiro NOJI, Keisuke OKAMURA, Takahiro TSUCHIKAWA, Yuma EBIHARA, Toshiaki SHICHINOHE
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Sophie Otter, Irene Chong, Ria Kalaitzaki, Diana Tait
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International Journal of Clinical Oncology.2017; 22(6): 1069. CrossRef
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The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy: Younak Choi, Tae-Yong Kim, Do-Youn Oh, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2016;48(1):171-179. Published online March 13, 2015; DOI: https://doi.org/10.4143/crt.2014.292

Abstract PDF Supplementary Material PubReader ePub

Purpose
A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear. Materials and Methods We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years’ duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset).
Results
Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). Conclusion For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.

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Dooyeon Lee, Mun Sem Liew, Spiros Fourlanos, Julian Choi
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Jing Yang, Hang Yang, Ling Cao, Yuzhen Yin, Ying Shen, Wei Zhu
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Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy: Min Kyoon Kim, Wonshik Han, Hyeong-Gon Moon, Soo Kyung Ahn, Jisun Kim, Jun Woo Lee, Ju-Yeon Kim, Taeryung Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Seock-Ah Im, Tae-You Kim, In Ae Park, Dong-Young Noh; Cancer Res Treat. 2015;47(2):197-207. Published online September 4, 2014; DOI: https://doi.org/10.4143/crt.2013.247

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Purpose
The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. Materials and Methods We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort. Results BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. Conclusion We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

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Risk scoring system for predicting breast conservation after neoadjuvant chemotherapy
Lobna Ouldamer, Sofiane Bendifallah, Joseph Pilloy, Flavie Arbion, Gilles Body, Caroline Brisson, Vincent Lavoué, Jean Lévêque, Emile Daraï
The Breast Journal.2019; 25(4): 696. CrossRef
Score for the Survival Probability in Metastasis Breast Cancer: A Nomogram-Based Risk Assessment Model
Zhenchong Xiong, Guangzheng Deng, Xinjian Huang, Xing Li, Xinhua Xie, Jin Wang, Zeyu Shuang, Xi Wang
Cancer Research and Treatment.2018; 50(4): 1260. CrossRef
Development of Nomogram to Predict the Best Military Category Using Physical Fitness Variables: A Model Development in Navy Trainees
Milad Nazarzadeh, Ali Reza Khoshdel, Abolfazl Goodarzi, Alireza Mosavi Jarrahi
Journal of Archives in Military Medicine.2018;[Epub] CrossRef
Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer
Chang Seok Ko, Kyu Min Kim, Jong Won Lee, Han Shin Lee, Sae Byul Lee, Guiyun Sohn, Jisun Kim, Hee Jeong Kim, Il Yong Chung, Beom Seok Ko, Byung Ho Son, Seung Do Ahn, Sung-Bae Kim, Hak Hee Kim, Sei Hyun Ahn
Journal of Breast Disease.2018; 6(2): 52. CrossRef
External validation of a published nomogram for prediction of brain metastasis in patients with extra-cerebral metastatic breast cancer and risk regression analysis
Ludivine Genre, Henri Roché, Léonel Varela, Dorra Kanoun, Monia Ouali, Thomas Filleron, Florence Dalenc
European Journal of Cancer.2017; 72: 200. CrossRef
Facteurs prédictifs de traitement conservateur après chimiothérapie néo-adjuvante dans le cancer du sein
J. Pilloy, C. Fleurier, M. Chas, L. Bédouet, M.L. Jourdan, F. Arbion, G. Body, L. Ouldamer
Gynécologie Obstétrique Fertilité & Sénologie .2017; 45(9): 466. CrossRef
Actual Conversion Rate from Total Mastectomy to Breast Conservation after Neoadjuvant Chemotherapy for Stages II–III Breast Cancer Patients
Hyejin Mo, Yumi Kim, Jiyoung Rhu, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im, Eun-Shin Lee, Han-Byoel Lee, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han
Journal of Breast Disease.2017; 5(2): 51. CrossRef

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A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions: Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Wonshik Han, Kyubo Kim, Eui Kyu Chie, In-Ae Park, Young Tae Kim, Dong-Young Noh, Sung Whan Ha, Yung-Jue Bang; Cancer Res Treat. 2014;46(3):280-287. Published online July 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.3.280

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Purpose
A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. Materials and Methods We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. Results A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). Conclusion Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.

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Unusual metastases of breast cancer: a single-center retrospective study
Pınar ÖZDEMİR AKDUR, Nazan ÇİLEDAĞ
The European Research Journal.2023; 9(6): 1444. CrossRef
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Lei Zhu, Haiman Bian, Lieming Yang, Jianjing Liu, Wei Chen, Xiaofeng Li, Jian Wang, Xiuyu Song, Dong Dai, Zhaoxiang Ye, Wengui Xu, Xiaozhou Yu
Thoracic Cancer.2019; 10(5): 1086. CrossRef

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