Cancer Research and Treatment

Original Article

Biomarker Testing Practices for Non–Small Cell Lung Cancer: Survey Insights from South Korean Pathology Laboratories: Sehui Kim, Dajeong Kim, Lucia Kim, Wan-Seop Kim; Received September 29, 2025 Accepted January 28, 2026 Published online January 30, 2026; DOI: https://doi.org/10.4143/crt.2025.927 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Molecular biomarker testing is essential for lung cancer management and precision medicine. This study evaluated biomarker testing practices for non–small cell lung cancer (NSCLC) across pathology laboratories in South Korea.
Materials and Methods
A nationwide survey of 30 pathology laboratories assessed testing policies, biomarker adoption, testing platforms, next-generation sequencing (NGS) implementation, reporting practices, turnaround times (TATs), and perceived challenges.
Results
All institutions routinely performed biomarker testing; 20 (66.7%) employed reflex testing at least in part. Tissue was the primary specimen type, and cytology and liquid biopsy specimens were accepted by 90.0% and 46.7% of institutions, respectively. For non-squamous NSCLC, all institutions tested epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, and programmed cell death ligand 1 (PD-L1), with additional testing for BRAF (86.7%) and KRAS (80.0%); other actionable targets were rarely tested outside NGS. In squamous NSCLC, PD-L1 was routinely assessed, whereas other drivers were tested less frequently. All institutions performed tissue-based NGS using companion diagnostic (CDx) and/or non-CDx platforms, and liquid biopsy–based NGS was available in 46.7% of institutions. Median TATs were 2-3, 5, 9, 19, and 15 days for immunohistochemistry, polymerase chain reaction, fluorescence in situ hybridization, tissue-based NGS, and liquid biopsy–based NGS, respectively. Reported barriers included limited sample availability, workforce shortages, prolonged TATs, regulatory restrictions, and lack of standardization.
Conclusion
Biomarker testing is widely implemented in South Korea, with increasing integration of NGS. Despite alignment with international recommendations, systemic and policy reforms are needed to harmonize workflows, reduce variability, and optimize precision oncology.

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Review Article

The Current Evidence and Future Direction of Adjuvant Treatment for Gastric Cancer in the Era of Precision Medicine: Jong Hyuk Yun, Yoon Young Choi, Jae-Ho Cheong; Cancer Res Treat. 2025;57(3):621-634. Published online January 23, 2025; DOI: https://doi.org/10.4143/crt.2024.1222

Abstract PDF PubReader ePub

Although gastric cancer remains a significant global health burden, its treatment strategies vary across different geographical regions, leading to distinct guidelines. In Asia, particularly in Korea, D2 gastrectomy followed by adjuvant chemotherapy has been established as the standard treatment for stage II/III gastric cancer based on landmark clinical trials. However, this “one-size-fits-all” approach requires refinement as emerging evidence suggests heterogeneous outcomes even within the same stage. This review discusses the evolving landscape of adjuvant treatment in gastric cancer, emphasizing the transition towards precision medicine. Recent molecular characterization of gastric cancer has revealed distinct subtypes with varying prognoses and chemotherapy responses, exemplified by the favorable outcomes of microsatellite instability–high tumors without adjuvant chemotherapy. Additionally, clinical factors including sub-stages within stage II/III, patient performance status, comorbidities, and personal preferences should be considered in treatment decisions. The integration of these molecular and clinical factors, along with shared decision-making between physicians and patients, represents a crucial step toward personalized treatment approaches. Looking ahead, the field is poised for further evolution with the emergence of immune checkpoint inhibitors, growing evidence for neoadjuvant chemotherapy in selected cases, and the potential of circulating tumor DNA as a biomarker for minimal residual disease. This comprehensive approach to treatment decision-making, considering both tumor biology and patient factors, will be essential for realizing precision medicine in gastric cancer care.

Citations

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From Control to Conversion: Optimizing Systemic Therapy for Curative-Intent Conversion Surgery in Metastatic Gastric Cancer
Hye Sook Han, Sun Young Rha
Journal of Gastric Cancer.2026; 26(1): 146. CrossRef
Advances in Nano-Enabled Biosensing Technology for Gastric Cancer Diagnosis: Mechanistic Insights and Translational Perspectives
Anjali Yadav, Arzoo Saini, Neeraj Dilbaghi, Neelam Yadav
Critical Reviews in Analytical Chemistry.2026; : 1. CrossRef
A Nomogram Integrating HOXA9 Expression and Clinicopathological Factors for Predicting Postoperative Recurrence in Gastric Cancer: A Single-Center Retrospective Study
Jianze Weng, Jingwen Ying, Minming Xia, Yijie Xie
OncoTargets and Therapy.2026; Volume 19: 1. CrossRef
Precision oncology in gastric cancer: navigating molecular subtypes, therapeutic targets, and future horizons
Yanyun Hong, Xiaodong Wang, Hang Yu, Xiaosun Liu, Chao Tang
Cellular Oncology.2026;[Epub] CrossRef
Preoperative albumin-bilirubin grade combined with sarcopenia predicts long-term outcomes after laparoscopic gastrectomy for advanced gastric cancer
Shuangshuang Hou, Yang Yu, Nanbo Li, Wenjing Yu, Zhiyuan Dai, He Li, Lianyi Guo, Jiajun Yin, Ju Wu
BMC Gastroenterology.2025;[Epub] CrossRef
Dynamic postoperative prognosis and follow-up optimization for gastric cancer patients after neoadjuvant therapy: a multicenter retrospective study
Qing Zhong, Zhi-Quan Zhang, Kai-Ning Ye, Min-Xian Zhuang, Yu-Qin Sun, Zhi-Xin Shang-Guan, Dong Wu, Cai-Ming Weng, Meng-Qi Xue, Tao-Yuan Qiu, Yi Li, Yu-Bin Ma, Fang-Hui Ding, Yong-Hong Wang, Shi-Chao Wu, Bao-Long Li, Wei Zhao, Ji-Yun Zhu, Jun-Hua Yu, Ju Wu
Gastric Cancer.2025; 28(6): 1260. CrossRef

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Original Articles

General

Target-Enhanced Whole-Genome Sequencing Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel: Sangmoon Lee, Jin Roh, Jun Sung Park, Islam Oguz Tuncay, Wonchul Lee, Jung-Ah Kim, Brian Baek-Lok Oh, Jong-Yeon Shin, Jeong Seok Lee, Young Seok Ju, Ryul Kim, Seongyeol Park, Jaemo Koo, Hansol Park, Joonoh Lim, Erin Connolly-Strong, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn, Hyun Woo Lee, Seokhwi Kim, Jang-Hee Kim, Minsuk Kwon; Cancer Res Treat. 2025;57(2):350-361. Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.114

Abstract PDF Supplementary Material PubReader ePub

Purpose
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS.
Materials and Methods
This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches.
Results
TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making.
Conclusion
TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Citations

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Whole-genome landscapes of 1,364 breast cancers
Ryul Kim, Jonghan Yu, Joonoh Lim, Brian Baek-Lok Oh, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung Joo Chae, Ji-Yeon Kim, Ga Eun Park, Bong Joo Kang, Pill Sun Paik, Soo Yeon Bae, Chang Ik Yoon, Young Joo Lee, Dooreh Kim, Kabsoo Shin, Ji Eun Lee, Jun Ka
Nature.2026; 649(8099): 1282. CrossRef
Pan-Cancer Targeted Sequencing Reveals Genomic Heterogeneity and Prognostic Subgroups in Urothelial Bladder Cancer
Dimitar Ugrinovski, Skender Saidi, Viktor Stankov, Martina Ambardjieva, Slavica Josifovska, Anne-Katrin Koehler, Joerg Gabert, Sasho Panov
Cancers.2026; 18(6): 1026. CrossRef

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Breast cancer

A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong; Cancer Res Treat. 2024;56(4):1113-1125. Published online May 10, 2024; DOI: https://doi.org/10.4143/crt.2024.100

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

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Revolutionizing early detection of TNBC: The rise of non-invasive biomarkers and next-gen diagnostic strategies
Aqsa Ashraf, Syeda Zainab Amir, Laiba Jahangir, Emma Daniel, Muhammad Mustafa
Critical Reviews in Oncology/Hematology.2026; 218: 105107. CrossRef
Artificial Intelligence in Triple-Negative Breast Cancer: Applications in Diagnosis, Treatment Response, and Prognosis
Ziyu Fu, Xiaofei Huo, Andrew B. Jing, Jingfei Ma, Gaiane M. Rauch
Diagnostics.2026; 16(5): 671. CrossRef
Integrating multi-omics and artificial intelligence for personalized breast cancer management: A guide to clinicians
Hussein Sabit, Amit K. Yadav, Siamak Salimy, Amr Sakr, Shaimaa Abdel-Ghany, Alhassan Soliman Wadan, Amany I. Alqosaibi, Rawan Rashwan, Yara Saad AlGosaibi, Mashael Mashal Alnamshan, Jawaher Almulhim, Nouf K. Alaqeel, Borros Arneth
Cancer Letters.2026; 649: 218468. CrossRef
Development of predictive models for the prognosis of triple-negative breast cancer using multiple transcriptomic analyses
Suhyun Hwangbo, Yoojin Choi, Jae Yong Ryu, Julie Decock
PLOS One.2026; 21(5): e0348414. CrossRef
A 20-feature radiomic signature of triple-negative breast cancer identifies patients at high risk of death
Humaira Noor, Yuanning Zheng, Adam B. Mantz, Ryle Zhou, Andrew Kozlov, Wendy B. DeMartini, Shu-Tian Chen, Satoko Okamoto, Debra M. Ikeda, Melinda L. Telli, Allison W. Kurian, James M. Ford, Shaveta Vinayak, Mina Satoyoshi, Vishal Joshi, Sarah A. Mattonen,
npj Breast Cancer.2025;[Epub] CrossRef
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Shan Jiang, Zhiwen Hong, Qianjiang Wu, Rouhan A, Zhaobo Wang, Xue Guan, Xinghua Wang, Ari A. Kassardjian, Yali Cui, Tengchuang Ma
Cancers.2025; 17(19): 3201. CrossRef
A systems biology approach to unveil shared therapeutic targets and pathological pathways across major human cancers
Aftab Alam, Mohd Faizan Siddiqui, Rifat Hamoudi, Uday Kishore, Maria J. Fernandez-Cabezudo, Basel K. Al-Ramadi
Computational and Structural Biotechnology Journal.2025; 27: 5459. CrossRef
Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database
Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan, Masakazu Yashiro
Genes.2024; 15(6): 792. CrossRef

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Review Article

Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design: Hyerim Ha, Hee Yeon Lee, Jee Hyun Kim, Do Yeun Kim, Ho Jung An, SeungJin Bae, Hye-sung Park, Jin Hyoung Kang; Cancer Res Treat. 2024;56(4):991-1013. Published online May 7, 2024; DOI: https://doi.org/10.4143/crt.2024.128

Abstract PDF Supplementary Material PubReader ePub

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

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Original Articles

Genitourinary cancer

Early Plasma Circulating Tumor DNA as a Potential Biomarker of Disease Recurrence in Non-metastatic Prostate Cancer: Xiaochen Fei, Xinxing Du, Yiming Gong, Jiazhou Liu, Liancheng Fan, Jiayi Wang, Yanqing Wang, Yinjie Zhu, Jiahua Pan, Baijun Dong, Wei Xue; Cancer Res Treat. 2023;55(3):969-977. Published online March 2, 2023; DOI: https://doi.org/10.4143/crt.2022.1557

Abstract PDF Supplementary Material PubReader ePub

Purpose
In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.
Materials and Methods
This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression.
Results
Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence.
Conclusion
Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

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Liquid Biopsy in Non-Metastatic Prostate Cancer: Clinical Evidence and Future Directions
Maria Chiara Sighinolfi, Giuseppe Pallotta, Marzia Del Re, Koosha Moosavi, Or Schubert, Francesco Rossi, Filippo Gavi, Simone Assumma, Enrico Panio, Angelo Totaro, Filippo Turri, Mauro Ragonese, Nazario Foschi, Pierluigi Russo, Ela Patel, Carlo Gandi, Giu
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Lei Tang
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Rajvi Goradia, Taylor Goodstein, Debasish Sundi, Akshay Sood, Shawn Dason, Eric A. Singer
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Method development for pancreatic and ovarian cancer baseline ctDNA detection and measurable residual disease monitoring
Tim Alexander Steiert, Philipp M. Altrock, Axel Künstner, Vishal Dixit, Burkhard Brandt, Pamela Pinzani, Hauke Busch, Andre Franke, Michael Forster
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Method development for pancreatic and ovarian cancer baseline ctDNA detection and measurable residual disease monitoring
Tim Alexander Steiert, Philipp M. Altrock, Axel Künstner, Vishal Dixit, Burkhard Brandt, Pamela Pinzani, Hauke Busch, Andre Franke, Michael Forster
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Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer
Angela Yee, Jim Smith, Rajiv Kumar, Akash Sali, Euan J. Rodger, Aniruddha Chatterjee
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Minimal residual disease as a target for liquid biopsy in patients with solid tumours
Klaus Pantel, Catherine Alix-Panabières
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Marius E. Mayerhoefer, Andreas Kienzle, Sungmin Woo, Hebert Alberto Vargas
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Stepan A. Kopytov, Guzel R. Sagitova, Dmitry Y. Guschin, Vera S. Egorova, Andrei V. Zvyagin, Alexey S. Rzhevskiy
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Taigo Kato, Shugo Yajima, Yoshiaki Nakamura, Shin Kobayashi, Hideaki Miyake
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Circulating Tumor DNA as a Biomarker for Precision Medicine in Prostate Cancer: A Systematic Review
Nouhaila Chanhih, Abdelilah Laraqui, Salma Hassine, Ahmed Ameur, Larbi Hamedoun, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Idriss Lahlou Amine, Khalid Ennibi, Abdelaziz Benjouad, Lamiae Belayachi
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Next-generation Proteomics-Based Discovery, Verification, and Validation of Urine Biomarkers for Bladder Cancer Diagnosis: Jungyo Suh, Dohyun Han, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak, Chang Wook Jeong; Cancer Res Treat. 2022;54(3):882-893. Published online October 9, 2021; DOI: https://doi.org/10.4143/crt.2021.642

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to identify, verify, and validate a multiplex urinary biomarker-based prediction model for diagnosis and surveillance of urothelial carcinoma of bladder, using high-throughput proteomics methods.
Materials and Methods
Label-free quantification of data-dependent and data-independent acquisition of 12 and 24 individuals was performed in each of the discovery and verification phases using mass spectrometry, simultaneously using urinary exosome and proteins. Based on five scoring system based on proteomics data and statistical methods, we selected eight proteins. Enzyme-linked immunosorbent assay on urine from 120 patients with bladder mass lesions used for validation. Using multivariable logistic regression, we selected final candidate models for predicting bladder cancer.
Results
Comparing the discovery and verification cohorts, 38% (50/132 exosomal differentially expressed proteins [DEPs]) and 44% (109/248 urinary DEPs) are consistent at statistically significance, respectively. The 20 out of 50 exosome proteins and 27 out of 109 urinary proteins were upregulated in cancer patients. From eight selected proteins, we developed two diagnostic models for bladder cancer. The area under the receiver operating characteristic curve (AUROC) of two models were 0.845 and 0.842, which outperformed AUROC of urine cytology.
Conclusion
The results showed that the two diagnostic models developed here were more accurate than urine cytology. We successfully developed and validated a multiplex urinary protein-based prediction, which will have wide applications for the rapid diagnosis of urothelial carcinoma of the bladder. External validation for this biomarker panel in large population is required.

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Huan Liu, Dong Niu, Tong-Yao Yu, Yu-Hua Wang, Kun-Lin Ran, Yan-Hua Liu, Da-Chuan Yin, Chen-Yan Zhang
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Divya Pandey, Vineeta Tiwari, Dipanjana Ghosh
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Bogdan Budnik, Hossein Amirkhani, Klaus Weinberger, Saharnaz Nedjat, Mohammad H. Forouzanfar, Ashkan Afshin, Qi Wu
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Head and Neck Cancer

Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12: Yun-Gyoo Lee, Hyun Chang, Bhumsuk Keam, Sang Hoon Chun, Jihyun Park, Keon Uk Park, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, Keun-Wook Lee, Hye Ryun Kim, Sung-Bae Kim, Myung-Ju Ahn, In Gyu Hwang; Cancer Res Treat. 2021;53(3):671-677. Published online December 7, 2020; DOI: https://doi.org/10.4143/crt.2020.824

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.

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Seo Yoon Jang, Yun‐Gyoo Lee, Sang Hoon Chun, Ji Hyun Park, Keon Uk Park, Hyun Chang, Keun‐Wook Lee, Hye Ryun Kim, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, In Gyu Hwang, Myung‐Ju Ahn, Sung‐Bae Kim, Bhumsuk Keam
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Kazufumi Obata, Satoshi Kano, Akira Ohkoshi, Akito Kakiuchi, Takahiro Inoue, Jun Taguchi, Ai Tagawa, Daisuke Matsushita, Jun Miyaguchi, Tentaro Endo, Ryo Ishii, Kazue Ito, Eiichi Ishida, Takahiro Suzuki, Naoto Araki, Tomotaka Kawase, Kenichi Takano
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BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy: Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro; Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019; DOI: https://doi.org/10.4143/crt.2018.598

Abstract PDF PubReader ePub

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

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

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Dynamics of Soluble Programmed Death-Ligand 1 (sPDL1) during Chemotherapy and Its Prognostic Implications in Cancer Patients: Biomarker Development in Immuno-oncology: Hyerim Ha, Ju-Hee Bang, Ah-Rong Nam, Ji-Eun Park, Mei Hua Jin, Yung-Jue Bang, Do-Youn Oh; Cancer Res Treat. 2019;51(2):832-840. Published online October 5, 2018; DOI: https://doi.org/10.4143/crt.2018.311

Abstract PDF PubReader ePub

Purpose
The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients.
Materials and Methods
From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed.
Results
The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003).
Conclusion
The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.

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Chemotherapy driven alterations in NK cell receptors and ligands in high grade serous ovarian cancer
Pavan Kumar, Samruddhi Ranmale, Sanket Mehta, Hemant Tongaonkar, Vashishth Maniar, Jayanti Mania-Pramanik
Frontiers in Immunology.2026;[Epub] CrossRef
Electrochemical sensors for the detection of immune checkpoint related proteins and their role in cancer companion diagnostics
Louise Barnaby, Andrew G. Watts, Pedro Estrela
Biosensors and Bioelectronics: X.2025; 22: 100561. CrossRef
Soluble sFas, sFasL, sPD1, and sPDL1 Analyses in the Peripheral Blood of Locally Advanced Breast Cancer Patients Before and After Neoadjuvant Chemotherapy
Carolina de Souza Vasconcelos, Marcelo Ramos Tejo Salgado, Mario Rino Martins, Carlos Eduardo Caiado Anunciação, Denise Viana Sobral, Leuridan Cavalcante Torres
Journal of Surgical Oncology.2025; 132(5): 817. CrossRef
Identification of serum proteins associated with response of triple-negative breast cancer to neoadjuvant chemotherapy: preliminary results from the INSTIGO trial
Celeste Pinard, Angeline Ginzac, Ioana Molnar, Hugo Veyssiere, Yannick Bidet, Vincent Sapin, Julie Durif, Catherine Abrial, Frederique Penault-Llorca, Xavier Durando, Nina Radosevic-Robin
Clinical Proteomics.2025;[Epub] 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
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
Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC
Ling Yi, Xiaojue Wang, Siyun Fu, Zhuohong Yan, Tianyu Ma, Siqi Li, Panjian Wei, Hongtao Zhang, Jinghui Wang
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Prognostic value of soluble programmed cell death ligand-1 (sPD-L1) in lymphoma: a systematic review and meta-analysis
Yangyang Ding, Cheng Sun, Linhui Hu, Shudao Xiong, Zhimin Zhai
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Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
Targeted Oncology.2023; 18(6): 837. 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
The prognostic role of soluble transforming growth factor‐β and its correlation with soluble programmed death‐ligand 1 in biliary tract cancer
Jin Won Kim, Kyung‐Hun Lee, Ji‐Won Kim, Koung Jin Suh, Ah‐Rong Nam, Ju‐Hee Bang, Mei Hua Jin, Kyoung‐Seok Oh, Jae‐Min Kim, Tae‐Yong Kim, Do‐Youn Oh
Liver International.2021; 41(2): 388. CrossRef
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 Research and Treatment.2021; 53(1): 199. CrossRef
The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas
Shujun Liu, Yadi Zhu, Chenxi Zhang, Xiangrui Meng, Bo Sun, Guojun Zhang, Yubo Fan, Xixiong Kang
Frontiers in Oncology.2020;[Epub] CrossRef
The prognostic role of soluble TGF‐beta and its dynamics in unresectable pancreatic cancer treated with chemotherapy
Hyunkyung Park, Ju‐Hee Bang, Ah‐Rong Nam, Ji Eun Park, Mei Hua Jin, Yung‐Jue Bang, Do‐Youn Oh
Cancer Medicine.2020; 9(1): 43. CrossRef
Soluble programmed death-1 (sPD-1) and programmed death ligand 1 (sPD-L1) as potential biomarkers for the diagnosis and prognosis of glioma patients
Shujun Liu, Yadi Zhu, Chenxi Zhang, Jiajia Liu, Hong Lv, Guojun Zhang, Xixiong Kang
Journal of Medical Biochemistry.2020; 39(4): 444. CrossRef
Soluble PD-1: Predictive, Prognostic, and Therapeutic Value for Cancer Immunotherapy
Muhammad Khan, Zhihong Zhao, Sumbal Arooj, Yuxiang Fu, Guixiang Liao
Frontiers in Immunology.2020;[Epub] CrossRef

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15 Web of Science
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Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial: Min Hwan Kim, Xianglan Zhang, Minkyu Jung, Inkyung Jung, Hyung Soon Park, Seung-Hoon Beom, Hyo Song Kim, Sun Young Rha, Hyunki Kim, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung; Cancer Res Treat. 2019;51(2):819-831. Published online September 27, 2018; DOI: https://doi.org/10.4143/crt.2018.331

Abstract PDF Supplementary Material PubReader ePub

Purpose
Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection.
Materials and Methods
This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomy with or without adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values.
Results
Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis.
Conclusion
This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

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Plasma Macrophage Migration Inhibitory Factor and CCL3 as Potential Biomarkers for Distinguishing Patients with Nasopharyngeal Carcinoma from High-Risk Individuals Who Have Positive Epstein-Barr Virus Capsid Antigen-Specific IgA: Ning Xue, Jian-Hua Lin, Shan Xing, Dan Liu, Shi-Bing Li, Yan-Zhen Lai, Xue-Ping Wang, Min-Jie Mao, Qian Zhong, Mu-Sheng Zeng, Wan-Li Liu; Cancer Res Treat. 2019;51(1):378-390. Published online May 29, 2018; DOI: https://doi.org/10.4143/crt.2018.070

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to identify novel plasma biomarkers for distinguishing nasopharyngeal carcinoma (NPC) patients from healthy individuals who have positive Epstein-Barr virus (EBV) viral capsid antigen (VCA-IgA).
Materials and Methods
One hundred seventy-four plasma cytokines were analyzed by a Cytokine Array in eight healthy individuals with positive EBV VCA-IgA and eight patients with NPC. Real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry were employed to detect the expression levels of macrophage migration inhibitory factor (MIF) and CC chemokine ligand 3 (CCL3) in NPC cell lines and tumor tissues. Plasma MIF and CCL3 were measured by ELISA in 138 NPC patients, 127 EBV VCA-IgA negative (VN) and 100 EBV VCA-IgA positive healthy donors (VP). Plasma EBV VCA-IgA was determined by immunoenzymatic techniques.
Results
Thirty-four of the 174 cytokines varied significantly between the VP and NPC group. Plasma MIF and CCL3 were significantly elevated in NPC patients compared with VN and VP. Combination of MIF and CCL3 could be used for the differential diagnosis of NPC from VN cohort (area under the curve [AUC], 0.913; sensitivity, 90.00%; specificity, 80.30%), and combination of MIF, CCL3, and VCA-IgA could be used for the differential diagnosis of NPC from VP cohort (AUC, 0.920; sensitivity, 90.00%; specificity, 84.00%), from (VN+VP) cohort (AUC, 0.961; sensitivity, 90.00%; specificity, 92.00%). Overexpressions of MIF and CCL3 were observed in NPC plasma, NPC cell lines and NPC tissues.
Conclusion
Plasma MIF, CCL3, and VCA-IgA combination significantly improves the diagnostic specificity of NPC in high-risk individuals.

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Serum Chemokines CCL3 and CCL7 as Complementary Diagnostic Biomarkers Across Tumor Grades in Clear Cell Renal Cell Carcinoma
Weronika Sokólska, Monika Zajkowska, Agnieszka Kulczyńska-Przybik, Tadeusz Werel, Karolina Orywal
International Journal of Molecular Sciences.2026; 27(5): 2490. CrossRef
Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis
Vikrant Kumar, Nawaid Hussain Khan, Shashi Nandar Kumar, Neeraj Mahajan, Wafa Aziz, Vinay Kumar, Chaitenya Verma, Harleen Khatra
Biochemistry Research International.2026;[Epub] CrossRef
Roles of Macrophage Migration Inhibitory Factor (MIF) Signaling Pathway in Oncovirus Infection and Virus-Associated Cancers
Jiaojiao Fan, Victor Ryu, Zhiqiang Qin, Lu Dai
Viruses.2025; 17(12): 1582. CrossRef
Nasopharyngeal carcinoma-associated inflammatory cytokines: ongoing biomarkers
Chuwen Liang, Jun Kan, Jingli Wang, Wei Lu, Xiaoyan Mo, Bei Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Genetic Variants of the MIF Gene and Susceptibility of Rectal Cancer
Dongyu Chuo, Dapeng Lin, Mingdi Yin, Yuze Chen
Pharmacogenomics and Personalized Medicine.2021; Volume 14: 55. CrossRef
microRNA-451 (miR-451) Regulates the Apoptosis of Non-Small Cell Lung Cancer Cells by Targeting Macrophage Migration Promoting Factors
Caihong Wei, Dan Guo, Huayun Pu
Journal of Biomaterials and Tissue Engineering.2021; 11(7): 1388. CrossRef

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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma: Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim; Cancer Res Treat. 2019;51(1):300-312. Published online May 9, 2018; DOI: https://doi.org/10.4143/crt.2018.012

Abstract PDF Supplementary Material PubReader ePub

Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

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19,468 View
662 Download
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Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer: Soomin Ahn, Hyun Jeong Kim, Milim Kim, Yul Ri Chung, Eunyoung Kang, Eun-Kyu Kim, Se Hyun Kim, Yu Jung Kim, Jee Hyun Kim, In Ah Kim, So Yeon Park; Cancer Res Treat. 2018;50(4):1418-1432. Published online January 24, 2018; DOI: https://doi.org/10.4143/crt.2017.552

Abstract PDF PubReader ePub

Purpose
Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST.
Materials and Methods
The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed.
Results
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup.
Conclusion
ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

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Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05): Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park; Cancer Res Treat. 2018;50(4):1252-1259. Published online January 2, 2018; DOI: https://doi.org/10.4143/crt.2017.438

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).
Materials and Methods
This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed.
Results
Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
Conclusion
Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.

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Inter-alpha Inhibitor H4 as a Potential Biomarker Predicting the Treatment Outcomes in Patients with Hepatocellular Carcinoma: Eun-Jung Lee, Seung-Hyun Yang, Kyoung-Jin Kim, Hyejung Cha, Seo Jin Lee, Ji-Hye Kim, Junkyu Song, Kyung-Hee Chun, Jinsil Seong; Cancer Res Treat. 2018;50(3):646-657. Published online July 17, 2017; DOI: https://doi.org/10.4143/crt.2016.550

Abstract PDF Supplementary Material PubReader ePub

Purpose
Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins.
Materials and Methods
2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrixassisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells.
Results
Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis.
Conclusion
Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.

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Yu Liu, Yan-Qing Li, Shi-Hao Huang, Yong-Long Li, Jia-Wei Xia, Jun-Shuang Jia, Fang Wei, Jia-Hong Wang, Guan-Qi Dai, Yu-Cai Wang, Xiao-Yan Li, Liu-Xin Han, Xiao-Ling Zhang, Xu-Dong Xiang, Wen-Tao Zhao, Dong Xiao, Xiao-Lin Lin
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Yingying Sun, Jie Jin, Hongyan Jing, Yingying Lu, Qingqing Zhu, Changjuan Shu, Qinghua Zhang, Dadao Jing
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Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy: Lingyun Liu, Wei Wang, Yi Zhang, Jianting Long, Zhaohui Zhang, Qiao Li, Bin Chen, Shaoqiang Li, Yunpeng Hua, Shunli Shen, Baogang Peng; Cancer Res Treat. 2018;50(2):538-550. Published online June 1, 2017; DOI: https://doi.org/10.4143/crt.2017.106

Abstract PDF PubReader ePub

Purpose
Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection.
Materials and Methods
Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses.
Results
The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients.
Conclusion
Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.

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Meta-Analysis

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis: Chiara Cremolini, Carlotta Antoniotti, Filippo Pietrantonio, Rosa Berenato, Marco Tampellini, Chiara Baratelli, Lisa Salvatore, Federica Marmorino, Beatrice Borelli, Federico Nichetti, Paolo Bironzo, Cristina Sonetto, Maria Di Bartolomeo, Filippo de Braud, Fotios Loupakis, Alfredo Falcone, Massimo Di Maio; Cancer Res Treat. 2017;49(3):834-845. Published online November 15, 2016; DOI: https://doi.org/10.4143/crt.2016.249

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).
Materials and Methods
A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson’s correlation coefficient (R) and the coefficient of determination (R²).
Results
Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R²=0.539, p < 0.001) and poor correlation (R=0.169, R²=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident.
Conclusion
Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

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Original Articles

FGFR4 Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition: Sang Hee Cho, Chang Soo Hong, Hee Nam Kim, Min Ho Shin, Ka Rham Kim, Hyun Jeong Shim, Jun Eul Hwang, Woo Kyun Bae, Ik Joo Chung; Cancer Res Treat. 2017;49(3):766-777. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.457

Abstract PDF PubReader ePub

Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patientswith resected colon cancer, including the underlying mechanism.
Materials and Methods
FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.
Results
Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.
Conclusion
The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.

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Targeting Colorectal Cancer Stem Cells Through Inhibition of the Fibroblast Growth Factor Receptor 4 Pathway with a Novel Antibody
Gessica Filocamo, Mariachiara Buccarelli, Armin Lahm, Mirko Brunetti, Chantal Paolini, Gabriele De Luca, Michele Signore, Giorgia Castellani, Alessandra Boe, Romina Alfonsi, Mauro Biffoni, Ruggero De Maria, Lucia Ricci-Vitiani, Christian Steinkühler, Paol
Cancers.2026; 18(3): 418. CrossRef
The FGF–FGFR axis as an immune–metabolic rheostat in gastrointestinal inflammation and cancer
Khamis Salem Saeed Saad, Chunfang Zhou, Guangxin Lu, Gang Wei, Huolong Cha, Ezzaddin Alwabri, Zhifang Zhang, Zequn Sun, Yingying Liao
Frontiers in Immunology.2026;[Epub] CrossRef
FGFR4 promotes CAF activation through the CXCL10-CXCR3 axis in colon cancer
Eun-Gene Sun, Ji-Na Choi, Mi-Ra Park, Dae-Hwan Kim, MinJeong Sung, Hyun-Jeong Shim, Jun-Eul Hwang, Woo-Kyun Bae, Chaeyong Jung, Young-Kook Kim, Ik-Joo Chung, Sang-Hee Cho
Cell Death & Disease.2025;[Epub] CrossRef
Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment
Alessandro Ottaiano, Mariachiara Santorsola, Monica Ianniello, Anna Ceccarelli, Marika Casillo, Francesco Sabbatino, Nadia Petrillo, Marco Cascella, Francesco Caraglia, Carmine Picone, Francesco Perri, Roberto Sirica, Silvia Zappavigna, Guglielmo Nasti, G
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Chengcheng Yang, Dingli Song, Fengyu Zhao, Jie Wu, Boxiang Zhang, Hong Ren, Qi Sun, Sida Qin
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Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
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Fibroblast growth factor receptor 4 increases epidermal growth factor receptor (EGFR) signaling by inducing amphiregulin expression and attenuates response to EGFR inhibitors in colon cancer
Chang‐Soo Hong, Eun‐Gene Sun, Ji‐Na Choi, Dae‐Hwan Kim, Jo‐Heon Kim, Kyung‐Hyun Ryu, Hyun‐Jeong Shim, Jun‐Eul Hwang, Woo‐Kyun Bae, Hyeong‐Rok Kim, Kyung Keun Kim, Chaeyong Jung, Ik‐Joo Chung, Sang‐Hee Cho
Cancer Science.2020; 111(9): 3268. CrossRef
Mahanine induces apoptosis, cell cycle arrest, inhibition of cell migration, invasion and PI3K/AKT/mTOR signalling pathway in glioma cells and inhibits tumor growth in vivo
Maohua Chen, Xiangqian Yin, Chuan Lu, Xiandong Chen, Huajun Ba, Jianyong Cai, Jun Sun
Chemico-Biological Interactions.2019; 299: 1. CrossRef
Fibroblast growth factor receptor 4 (FGFR4) as detected by immunohistochemistry is associated with postoperative residual disease in ovarian cancer
Sabine Heublein, Michael S. Anglesio, Frederik Marmé, Stefan Kommoss
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TAp73 inhibits cell invasion and migration by directly activating KAI1 expression in colorectal carcinoma
Woo-Kyun Bae, Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Ji-Hee Lee, Keunsoo Kang, Kyung-Hyun Ryu, Hyun-Jeong Shim, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung
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The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction
Álvaro Quintanal-Villalonga, Laura Ojeda-Márquez, Ángela Marrugal, Patricia Yagüe, Santiago Ponce-Aix, Ana Salinas, Amancio Carnero, Irene Ferrer, Sonia Molina-Pinelo, Luis Paz-Ares
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Effects of FGFR gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-docetaxel-based chemotherapy in breast cancer patients
Lu Chen, Huijie Qi, Liudi Zhang, Haixia Li, Jie Shao, Haifei Chen, Mingkang Zhong, Xiaojin Shi, Ting Ye, Qunyi Li
BMC Cancer.2018;[Epub] CrossRef

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Blocking Interleukin-4 Receptor α Using Polyethylene Glycol Functionalized Superparamagnetic Iron Oxide Nanocarriers to Inhibit Breast Cancer Cell Proliferation: Abjal Pasha Shaik, Asma Sultana Shaik, Ali Al Majwal, Achraf Al Faraj; Cancer Res Treat. 2017;49(2):322-329. Published online July 12, 2016; DOI: https://doi.org/10.4143/crt.2016.091

Abstract PDF PubReader ePub

Purpose
The specific targeting of interleukin-4 receptor α (IL4Rα) receptor offers a promising therapeutic approach for inhibition of tumor cell progression in breast cancer patients. In the current study, the in vitro efficacy of superparamagnetic iron oxide nanoparticles conjugated with anti-IL4Rα blocking antibodies (SPION-IL4Rα) via polyethylene glycol polymers was evaluated in 4T1 breast cancer cells.
Materials and Methods
Cell viability, reactive oxygen species generation, and apoptosis frequency were assessed in vitro in 4T1 cancer cell lines following exposure to SPION-IL4Rα alone or combined with doxorubicin. In addition, immunofluorescence assessments and fluorimetrywere performed to confirm the specific targeting and interaction of the developed nanocarriers with IL4Rα receptors in breast cancer cells.
Results
Blocking of IL4Rα receptors caused a significant decrease in cell viability and induced apoptosis in 4T1 cells. In addition, combined treatment with SPION-IL4Rα+doxorubicin caused significant increases in cell death, apoptosis, and oxidative stress compared to either SPION-IL4Rα or doxorubicin alone, indicating the enhanced therapeutic efficacy of this combination. The decrease in fluorescence intensity upon immunofluorescence and fluorimetry assays combined with increased viability and decreased apoptosis following the blocking of IL4Rα receptors confirmed the successful binding of the synthesized nanocarriers to the target sites on murine 4T1 breast cancerous cells.
Conclusion
These results suggest that SPION-IL4Rα nanocarriers might be used for successfulreduction of tumor growth and inhibition of progression of metastasis in vivo.

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Application of nanoparticles in antibody drug delivery
Wumiti Xiefukaiti, Qingmei Zhu, Nadira Dolkun, XueJun Xiao
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Jiasheng Xu, Lei Ding, Jianfeng Mei, Yeting Hu, Xiangxing Kong, Siqi Dai, Tongtong Bu, Qian Xiao, Kefeng Ding
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Sruthi Laakshmi Mugundhan, Mothilal Mohan
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Jaishree S., Kousalya Selvaraj, Prakash S., Vineesh D.
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Naseem Akhtar, Hamdoon A. Mohammed, Mohammed Yusuf, Amal Al-Subaiyel, Ghassan M. Sulaiman, Riaz A. Khan
Nanomaterials.2022; 12(20): 3686. CrossRef
Expression of IL4Rα and IL13Rα1 are associated with poor prognosis of soft-tissue sarcoma of the extremities, superficial trunk, and retroperitoneum
Kyoung Min Kim, Usama Khamis Hussein, See-Hyoung Park, Young Jae Moon, Zhongkai Zhang, Asmaa Gamal Ahmed, Ae-Ri Ahn, Ho Sung Park, Jung Ryul Kim, Kyu Yun Jang
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Veronica Manescu (Paltanea), Gheorghe Paltanea, Iulian Antoniac, Marius Vasilescu
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Recent Progress in Iron Oxide Nanoparticles as Therapeutic Magnetic Agents for Cancer Treatment and Tissue Engineering
Mahboubeh Nabavinia, Juan Beltran-Huarac
ACS Applied Bio Materials.2020; 3(12): 8172. CrossRef
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Mi-Ae Kang, Jongsung Lee, Sang Ha, Chang Lee, Kyoung Kim, Kyu Jang, See-Hyoung Park
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Cari L. Meisel, Polly Bainbridge, Dimitrios Mitsouras, Joyce Y. Wong
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Current aspects in treatment of breast cancer based of nanodrug delivery systems and future prospects
Adil M. Allahverdiyev, Etkin Parlar, Sahar Dinparvar, Melahat Bagirova, Emrah Şefik Abamor
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Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer
Jörgen Elgqvist
International Journal of Molecular Sciences.2017; 18(5): 1102. CrossRef

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Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy: Seung Hyeun Lee, Sue In Choi, Ji Sung Lee, Chul Hwan Kim, Won Jai Jung, Eun Joo Lee, Kyung Hoon Min, Gyu Young Hur, Seung Heon Lee, Sung Yong Lee, Je Hyeong Kim, Sang Yeub Lee, Chol Shin, Jae Jeong Shim, Kyung Ho Kang, Kwang Ho In; Cancer Res Treat. 2017;49(1):141-149. Published online May 18, 2016; DOI: https://doi.org/10.4143/crt.2016.133

Abstract PDF PubReader ePub

Purpose
Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
Materials and Methods
Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated.
Results
A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology.
Conclusion
Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

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ROMO1 – a potential immunohistochemical prognostic marker for cancer development
Eva Tsoneva, Mariela B. Vasileva-Slaveva, Stoyan G. Kostov, Angel D. Yordanov
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Serum Reactive Oxygen Species Modulator 1 as a Novel Predictive Biomarker for Resected Lung Adenocarcinoma: A Retrospective Pilot Study
Boksoon Chang, In Kyung Hwang, Seung Hyeun Lee
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Overexpression of Reactive Oxygen Species Modulator 1 Predicts Unfavorable Clinical Outcome in EGFR-Mutant Lung Adenocarcinomas Treated With Targeted Therapy
Won Gun Kwack, Ji-Youn Sung, Seung Hyeun Lee
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Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer
Hadi Ghasemi, Mohammad Amin Amini, Atefeh Pegah, Ebrahim Azizi, Heidar Tayebinia, Shima Khanverdilou, Seyed Habibollah Mousavibahar, Aida Alizamir
Molecular Biology Reports.2020; 47(9): 6497. CrossRef
Reactive Oxygen Species Modulator 1 is Associated with Poor Survival in Patients with Non-Small Cell Lung Cancer After Stereotactic Fractionated Radiosurgery: A Retrospective Pilot Study

Moonkyoo Kong, Ji-Youn Sung, Seung Hyeun Lee
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Ipilimumab Real-World Efficacy and Safety in Korean Melanoma Patients from the Korean Named-Patient Program Cohort: Minkyu Jung, Jeeyun Lee, Tae Min Kim, Dae Ho Lee, Jin Hyung Kang, Sung Young Oh, Soo Jung Lee, Sang Joon Shin; Cancer Res Treat. 2017;49(1):44-53. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.024

Abstract PDF PubReader ePub

Purpose
Ipilimumab improves survival in advanced melanoma patients. However, the efficacy and safety of ipilimumab has not been evaluated in Asian melanoma patients with a high frequency of mucosal and acral melanoma subtypes.
Materials and Methods
Advanced melanoma patients treated with 3 mg/kg ipilimumab in a Korean multicenter named-patient program (NPP) were evaluated between September 2014 and July 2015. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes.
Results
A total of 104 advanced melanoma patients were treated. The primary sites were acral (31.7%), mucosal (26%), cutaneous (26%), uveal (9.6%), and unknown (6.7%). Sixty-eight patients (65.4%) experienced adverse events, and the most common toxicity was skin rash (22.1%), 10 patients (9.6%) experienced adverse events of grade 3 or higher. The median progression-free survival (PFS) was 2.73 months (95% confidence interval, 2.67 to 2.85), and there was no difference in PFS according to subtypes. Poor performance status, liver metastasis, and NLR (≥5) were independent poor prognostic factors by multivariate analysis.
Conclusion
In the Korean NPP cohort, ipilimumab showed similar efficacy and tolerability compared to Western patients, regardless of subtypes. All subtypes should benefit from ipilimumab with consideration of performance status, liver metastasis, and NLR.

Citations

Citations to this article as recorded by

Acral lentiginous melanoma. Part II. Staging, surgical management, the role of systemic therapy, shortcomings, and future directions
Daniella Jaguan, Sach Thakker, Micah Belzberg, Nina Gulati, Janeth R. Campbell, Brittney K. DeClerck, Vishal A. Patel, Gino K. In
Journal of the American Academy of Dermatology.2026; 94(2): 435. CrossRef
Pretreatment neutrophil-to-lymphocyte ratio is associated with immunotherapy efficacy in patients with advanced cancer: a systematic review and meta-analysis
Jialin Su, Yuning Li, Shuhua Tan, Tianli Cheng, Yongzhong Luo, Lemeng Zhang
Scientific Reports.2025;[Epub] CrossRef
Real‑world efficacy and safety data of immune checkpoint inhibitors in Turkish patients with metastatic melanoma: A Turkish oncology group retrospective study
Alpaslan Ozgun, Fatma Mustafayev, Izzet Dogan, Sezai Vatansever, Melek Eryilmaz, Atike Erdogan, Gamze Ozturk, Murat Ayhan, Merve Turan, Mahmut Yildirim, Emre Hafizoglu, Oznur Bal, Pinar Tolunay, Ahmet Demirkazik, Eyyup Cavdar, Selcuk Seber, Gokcen Cevik,
Molecular and Clinical Oncology.2025; 22(6): 1. CrossRef
Baseline neutrophil-to- ratio combined with the change during treatment provides risk stratification for metastatic malignant melanoma patients treated with PD-1 inhibitors in a Chinese population
Chen Wang, Shengyan Liu, Xin Li, Kang Cui, Weijie Zhang, Yabing Du
Frontiers in Oncology.2023;[Epub] CrossRef
Effect of liver metastasis on the efficacy of immune checkpoint inhibitors in cancer patients: a systemic review and meta-analysis
Bao-Wen Tian, Cheng-Long Han, Han-Chao Wang, Lun-Jie Yan, Zi-Niu Ding, Hui Liu, Xin-Cheng Mao, Jin-Cheng Tian, Jun-Shuai Xue, Long-Shan Yang, Si-Yu Tan, Zhao-Ru Dong, Yu-Chuan Yan, Dong-Xu Wang, Tao Li
Clinical & Experimental Metastasis.2023; 40(4): 255. CrossRef
MelRisk: Using neutrophil-to-lymphocyte ratio to improve risk prediction models for metastatic cutaneous melanoma in the sentinel lymph node
Ryckie G. Wade, Samuel Bailey, Alyss V. Robinson, Michelle C.I. Lo, Howard Peach, Marc D.S. Moncrieff, James Martin
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The Prognostic Significance of Baseline Neutrophil-to-Lymphocyte Ratio in Melanoma Patients Receiving Immunotherapy
Yayun Li, Yu Meng, Huiyan Sun, Lin Ye, Furong Zeng, Xiang Chen, Guangtong Deng
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Julianne M. Falotico, Shari R. Lipner
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Prognostic value of neutrophil-lymphocyte ratio and lactate dehydrogenase in melanoma patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis
Yongchao Zhang, Bozhi Liu, Sergei Kotenko, Wei Li
Medicine.2022; 101(32): e29536. CrossRef
Real‐world, population‐based cohort study of toxicity and resource utilization of second‐line ipilimumab for metastatic melanoma in Ontario, Canada
Wei Fang Dai, Jaclyn Beca, Ruth Croxford, Wanrudee Isaranuwatchai, Ines B. Menjak, Teresa M. Petrella, Nicole Mittmann, Craig C. Earle, Scott Gavura, Rebecca E. Mercer, Timothy P. Hanna, Kelvin K. W. Chan
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Náthali Felícia Mineiro dos Santos Garrett, Ana Cristina Carvalho da Costa, Elaine Barros Ferreira, Giovanni Damiani, Paula Elaine Diniz dos Reis, Christiane Inocêncio Vasques, Gayle E. Woloschak
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Malgorzata Gajdzis, Radoslaw Kaczmarek, Pawel Gajdzis
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Anja Wessely, Theresa Steeb, Michael Erdmann, Lucie Heinzerling, Julio Vera, Max Schlaak, Carola Berking, Markus Vincent Heppt
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Sebastien Jaillon, Andrea Ponzetta, Diletta Di Mitri, Angela Santoni, Raffaella Bonecchi, Alberto Mantovani
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Kelcie Witges, Leigh Anne Shafer, Ryan Zarychanski, Ahmed M. Abou-Setta, Rasheda Rabbani, Orvie Dingwall, Charles N. Bernstein
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Fausto Petrelli, Raffaele Ardito, Barbara Merelli, Veronica Lonati, Mary Cabiddu, Silvia Seghezzi, Sandro Barni, Antonio Ghidini
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Wungki Park, Gilberto Lopes
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Xianhe Xie, Junjin Liu, Haitao Yang, Huijuan Chen, Sijing Zhou, Heng Lin, Ziyuan Liao, Yin Ding, Liting Ling, Xuewen Wang
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Immunological Backbone of Uveal Melanoma: Is There a Rationale for Immunotherapy?
Ernesto Rossi, Giovanni Schinzari, Ilaria Grazia Zizzari, Brigida Anna Maiorano, Monica Maria Pagliara, Maria Grazia Sammarco, Vincenzo Fiorentino, Gianluigi Petrone, Alessandra Cassano, Guido Rindi, Emilio Bria, Maria Antonietta Blasi, Marianna Nuti, Gia
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Lucy T. Xu, Pauline F. Funchain, James F. Bena, Manshi Li, Ahmad Tarhini, Eren Berber, Arun D. Singh
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Tao Jiang, Meng Qiao, Chao Zhao, Xuefei Li, Guanghui Gao, Chunxia Su, Shengxiang Ren, Caicun Zhou
Cancer Immunology, Immunotherapy.2018; 67(5): 713. CrossRef
Prognostic value of neutrophil-to-lymphocyte ratio in melanoma
Yingguo Ding, Shan Zhang, Jianjun Qiao
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Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study
Tony Ibrahim, Christine Mateus, Maria Baz, Caroline Robert
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Qiaoyun Tan, Shuxia Liu, Caixia Liang, Xiaohong Han, Yuankai Shi
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A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a predictor of poor progression-free survival in patients with metastatic melanoma
Antoine Finon, Julia Zaragoza, Hervé Maillard, Nathalie Beneton, Guido Bens, Mahtab Samimi, Agnès Caille, Laurent Machet
European Journal of Dermatology.2018; 28(1): 38. CrossRef
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Markus V. Heppt, Theresa Steeb, Justin Gabriel Schlager, Stefanie Rosumeck, Corinna Dressler, Thomas Ruzicka, Alexander Nast, Carola Berking
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Frontiers in Oncology.2017;[Epub] CrossRef

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The Usefulness of Procalcitonin and C-Reactive Protein as Early Diagnostic Markers of Bacteremia in Cancer Patients with Febrile Neutropenia: Dae Yong Kim, Yoon-Seon Lee, Shin Ahn, Yeon Hee Chun, Kyung Soo Lim; Cancer Res Treat. 2011;43(3):176-180. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.176

Abstract PDF PubReader ePub

PURPOSE
Procalcitonin (PCT) and C-reactive protein (CRP) are well known inflammatory markers. This study was designed to determine whether PCT and CRP are useful as early diagnostic markers for bacteremia in cancer patients with febrile neutropenia (FN) in the emergency department (ED).
MATERIALS AND METHODS
In this retrospective study, 286 episodes of FN in the ED were consecutively included between June 2009 and August 2010. From medical records, clinical characteristics including PCT and CRP were extracted and analyzed.
RESULTS
Bacteremia was identified in 38 (13.3%) of the 286 episodes. The median values of PCT (2.8 ng/mL vs. 0.0 ng/mL, p=0.000) and CRP (15.9 mg/dL vs. 5.6 mg/dL, p=0.002) were significantly higher in the group with bacteremia compared to the group without bacteremia. In univariate analysis, elevated PCT (>0.5 ng/mL) and CRP (>10 mg/dL) as well as older age, hypotension, tachycardia, tachypnea, and high body temperature were significantly associated with bacteremia. On multivariate analysis, elevated PCT (>0.5 ng/mL) (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4 to 9.2; p<0.01) and tachypnea (OR, 3.4; 95% CI, 1.4 to 8.5; p<0.01) were independent early diagnostic markers for bacteremia in FN patients. The area under the curve of PCT was 74.8% (95% CI, 65.1 to 84.6%) and that of CRP was 65.5% (95% CI, 54.8 to 76.1%). With a PCT cut-off value of 0.5 ng/mL, sensitivity and specificity were 60.5% and 82.3%, respectively, while the sensitivity and specificity were 57.6% and 67.3%, respectively, with a CRP cutoff of 10 mg/dL.
CONCLUSION
These findings suggest that PCT is a useful early diagnostic marker for the detection of bacteremia in FN at the ED and has better diagnostic value than CRP.

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