Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer: Seong-Eun Kim, Hyehyun Jeong, Sun Young Kim, Jeong Eun Kim, Yong Sang Hong, Deokhoon Kim, Jihun Kim, Ji Sung Lee, Tae Won Kim; Cancer Res Treat. 2025;57(4):1104-1114. Published online January 10, 2025; DOI: https://doi.org/10.4143/crt.2024.569

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on epidermal growth factor receptor (EGFR) amplification status.
Materials and Methods
Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least five copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥ 6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp–).
Results
Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp– patients (median OS [mOS], 76 vs. 37 months; p=0.145). Among 572 patients who received anti-EGFR antibody–based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp– patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp– patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344).
Conclusion
This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

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Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials: Jaewon Hyung, Minsu Kang, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jaekyung Cheon, Hyewon Ryu, Ji Sung Lee, Ji-Won Kim, In Sil Choi, Jin Hyun Park, Ghassan K. Abou-Alfa, Jin Won Kim, Changhoon Yoo; Cancer Res Treat. 2025;57(2):519-527. Published online October 17, 2024; DOI: https://doi.org/10.4143/crt.2024.652

Abstract PDF Supplementary Material PubReader ePub

Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

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Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials
Changhoon Yoo, Anna Saborowski, Jaewon Hyung, Patrick Wenzel, Ilhwan Kim, Henning Wege, Kyu-pyo Kim, Gunnar Folprecht, Baek-Yeol Ryoo, Phillip Schütt, Jaekyung Cheon, Thorsten Götze, Hyewon Ryu, Ji Sung Lee, Arndt Vogel
Journal of Hepatology.2025;[Epub] CrossRef

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Breast cancer

Epidemiology of Second Non-breast Primary Cancers among Survivors of Breast Cancer: A Korean Population–Based Study by the SMARTSHIP Group: Haeyoung Kim, Su SSan Kim, Ji Sung Lee, Jae Sun Yoon, Hyun Jo Youn, Hyukjai Shin, Jeong Eon Lee, Se Kyung Lee, Il Yong Chung, So-Youn Jung, Young Jin Choi, Jihyoung Cho, Sang Uk Woo, Korean Breast Cancer Society; Cancer Res Treat. 2023;55(2):580-591. Published online December 27, 2022; DOI: https://doi.org/10.4143/crt.2022.410

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer.
Materials and Methods
Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis.
Results
The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02).
Conclusion
Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient’s age at IBC diagnosis, income level, and a receipt of systemic treatments.

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Development of a risk prediction model for second primary thyroid cancer in female breast cancer patients based on machine learning algorithms
Qianqian Yang, Zhihong Li, Yunfei Zhang, Roza Doktorzhan, Xiuhua Zhang, Wenjia Guo
Scientific Reports.2026;[Epub] CrossRef
Risk of second primary cancer in young breast cancer survivors: an important yet overlooked issue
Xinyi Liang, Yiwei Qin, Pengwei Li, You Mo, Dawei Chen
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Molecule subtypes play important roles for second primary malignancies development based on 324,661 breast cancer survivors
Jin Shi, Jian Liu, Guo Tian, Daojuan Li, Di Liang, Yutong He
Scientific Reports.2025;[Epub] CrossRef
Comorbidity burden and risk of second primary non-breast cancer in breast cancer survivors
Amrita Mukherjee, Zheng Gu, Lie Hong Chen, Rowan T. Chlebowski, Arnold L. Potosky, Reina Haque
Cancer Epidemiology.2025; 97: 102867. CrossRef
Association of radiotherapy for stage I–III breast cancer survivors and second primary malignant cancers: a population-based study
Jin Shi, Jian Liu, Guo Tian, Daojuan Li, Di Liang, Jun Wang, Yutong He
European Journal of Cancer Prevention.2024; 33(2): 115. 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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Prognostic Impact of Reactive Oxygen Species Modulator 1 in Surgically Resected Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinomas
Tae-Woo Kim, Kiyong Na, Junyang Jung, Heejin Lim, Hyewon Seo, Seung Hyeun Lee
Oncology.2024; 102(11): 969. CrossRef
ROMO1 – a potential immunohistochemical prognostic marker for cancer development
Eva Tsoneva, Mariela B. Vasileva-Slaveva, Stoyan G. Kostov, Angel D. Yordanov
Oncologie.2023; 25(6): 753. CrossRef
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
OncoTargets and Therapy.2021; Volume 14: 5097. CrossRef
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
Frontiers in Oncology.2021;[Epub] CrossRef
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
OncoTargets and Therapy.2020; Volume 13: 8173. CrossRef
Reactive oxygen species modulator 1 expression predicts lymph node metastasis and survival in early-stage non-small cell lung cancer
Taehee Kim, Yoon Jin Cha, Ji Hyun Park, Arum Kim, Yong Jun Choi, Hye Jung Park, Jung Weon Lee
PLOS ONE.2020; 15(12): e0239670. CrossRef
Reactive Oxygen Species Modulator 1 (ROMO1), a New Potential Target for Cancer Diagnosis and Treatment
Mohammad Amin Amini, Seyed Saman Talebi, Jamshid Karimi
Chonnam Medical Journal.2019; 55(3): 136. CrossRef
Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion
Seung Hyeun Lee, Myung Jae Park, Sue In Choi, Eun Joo Lee, Sang Yeub Lee, Kwang Ho In
Medicine.2017; 96(4): e5975. CrossRef

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