Cancer Research and Treatment

Original Articles

Pediatric cancer

Malignant Hepatocellular Neoplasm, Not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis Than Hepatoblastoma: In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh; Cancer Res Treat. 2026;58(2):642-655. Published online May 12, 2025; DOI: https://doi.org/10.4143/crt.2025.117

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Purpose
Malignant hepatocellular neoplasm, not otherwise specified (HCN-NOS) is a provisional diagnostic entity, characterised by intermediate or a combination of hepatoblastoma and pediatric hepatocellular carcinoma (p-HCC) features. We compared the characteristics of HCN-NOS with hepatoblastoma and p-HCC.
Materials and Methods
The records of 148 pediatric patients diagnosed with hepatocellular malignancy after resection were retrieved from the institutional database. Clinical parameters and histopathology slides were reviewed to re-establish each patient’s diagnosis. Molecular analyses were conducted in 37 patients.
Results
Patients were profiled as 21 (14.2%) with HCN-NOS, 109 (73.6%) with hepatoblastoma, and 18 (12.2%) with p-HCC. The median age was 8.6 years in HCN-NOS, 1.2 years in hepatoblastoma, and 7.9 years in p-HCC. Background liver disease was frequently observed in p-HCC (11/18, 61%) but infrequent in HCN-NOS (4/21, 19%) and hepatoblastoma (4/109, 3.7%). HCN-NOS presented with a more advanced PRETEXT stage (p=0.012), metastasis (p < 0.001), and lymphovascular invasion (p < 0.001) than hepatoblastoma and p-HCC. Patients with HCN-NOS received longer cycles of preoperative chemotherapy; however, they reported a lower decrease in serum alpha-fetoprotein and tumor size than hepatoblastoma (p=0.043, p=0.004, and p=0.044, respectively). HCN-NOS was an independent poor prognostic factor for event-free survival (hazard ratio, 4.968; 95% confidence interval, 2.004 to 12.32; p < 0.001).
Conclusion
The possibility of HCN-NOS should be considered in pediatric patients with liver cancer, especially those ≥ 5 years old with no background liver disease. Because HCN-NOS exhibits poor chemoresponsiveness and unfavourable postoperative prognosis, liver transplantation should be strongly considered.

Citations

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Conversion Hepatectomy After New FP Therapy for Malignant Hepatocellular Neoplasm, Not Otherwise Specified: A Case Report
Etsuko Moriyama, Hironori Koga, Takashi Niizeki, Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Takahiko Tokushige, Masahito Nakano, Ryoko Kuromatsu, Toru Goto, Masaki Honda, Taizo Hibi, Yoshiki Mikami, Reiichiro Kondo, Jun Akiba, Takumi Kawaguchi
Hepatology Research.2026; 56(6): 1047. CrossRef

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Gastrointestinal cancer

Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma: In Hye Song, Bokyung Ahn, Young Soo Park, Deok Hoon Kim, Seung-Mo Hong; Cancer Res Treat. 2025;57(2):492-506. Published online September 27, 2024; DOI: https://doi.org/10.4143/crt.2024.667

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Purpose
Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs).
Materials and Methods
Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed.
Results
Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS.
Conclusion
We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Citations

Citations to this article as recorded by

Malignant Hepatocellular Neoplasm, Not Otherwise Specified, Displays Poorer Chemoresponsiveness and Postoperative Prognosis Than Hepatoblastoma
In Hye Song, Sujin Gang, Hee Mang Yoon, Pyeong Hwa Kim, Bokyung Ahn, Jihun Kim, Deok Hoon Kim, Jung-Man Namgoong, Kyung-Nam Koh
Cancer Research and Treatment.2026; 58(2): 642. CrossRef
Intraductal Papillary Squamous Neoplasm (IPSN) of the Pancreas: Histological and Molecular Characterization of a Novel and Distinct Intraductal Cancer Precursor
Michele Bevere, Antonio Pea, Volkan Adsay, Olca Basturk, Lodewijk A. Brosens, Irene Esposito, Ralph H. Hruban, David Klimstra, Seung-Mo Hong, Aatur D. Singhi, Seung Soo Lee, Paola Mattiolo, Davide Pasini, Andrea Mafficini, Paola Piccoli, Serena Pedron, Ca
Modern Pathology.2026; 39(7): 101011. CrossRef
Mixed adenoneuroendocrine carcinoma of the gallbladder: a case report and literature review
Zhenghui Sui, Wei Wang, De Zhang, Yifan Sun, Jiajing Li, Xingwei Gu, Ganggang Miao
Frontiers in Oncology.2026;[Epub] CrossRef
Hepatoid adenocarcinoma of the stomach and non-hepatoid alpha-fetoprotein-producing gastric cancer exhibit a high degree of molecular similarity
Liqiao Chen, Xuesong Yang, Peiyu Zhu, Han Bao, Yan Wu, Ke Ji, Ji Zhang, Xiaojiang Wu, Kai Zhou, Jieli Xu, Jiatian Tang, Anqiang Wang, Zhaode Bu
Cellular Oncology.2025;[Epub] CrossRef

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Lung and Thoracic cancer

Comparison of Clinicopathogenomic Features and Treatment Outcomes of EGFR and HER2 Exon 20 Insertion Mutations in Non–Small Cell Lung Cancer: Single-Institution Experience: So Heun Lee, Hyehyun Jeong, Deok Hoon Kim, Se Jin Jang, Sang-We Kim, Shinkyo Yoon, Dae Ho Lee; Cancer Res Treat. 2024;56(3):774-784. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1177

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Purpose
Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non–small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins.
Materials and Methods
Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only.
Results
Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months.
Conclusion
Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.

Citations

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Andamertinib in Advanced NSCLC With EGFR Exon 20 Insertions After Platinum-Based Chemotherapy or Immunotherapy: Results From the Phase 2 KANNON Study
Jin-Ji Yang, Yu Mu, Zhe-Hai Wang, Jian-Chun Duan, Yan Zhang, Lin Wu, Hua Zhong, Jun Zhao, Yu Yao, Ping Wang, Xiao-Ling Li, Run-Xiang Yang, Xu-Hong Min, Dong-Qing Lv, Hai-Peng Xu, Zhen-Ming Fu, Bo Shen, Long-Hua Sun, Chang-Li Wang, Jian-Ya Zhou, Rui-Lian X
Journal of Thoracic Oncology.2026; 21(3): 103518. CrossRef
Epidemiology and Real-World Outcomes in Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Mutant Non-small Cell Lung Cancer by Region: A Targeted Literature Review
Koichi Goto, Hidetoshi Hayashi, Sonia S. Maruti, Heiko Zettl, Lalith Mittal, Smit Pathak, Xiuning Le
Targeted Oncology.2026; 21(3): 337. CrossRef
New Treatment Strategies for Rare Genomic Alterations: EGFR Exon 20 Insertions and HER2-Deregulated Lung Cancer
Lodovica Zullo, Jordi Remon
Cancers.2026; 18(14): 2334. CrossRef
Advancements in Gene Therapy for Non-Small Cell Lung Cancer: Current Approaches and Future Prospects
Iwona Ziółkowska-Suchanek, Natalia Rozwadowska
Genes.2025; 16(5): 569. CrossRef
Real-World Outcomes and Biomarker Analysis Based on Routine Clinical, Laboratory, and Pathologic Parameters in Metastatic or Unresectable Esophageal Cancer Treated with First-Line Anti-PD-1 Plus Fluoropyrimidine and Platinum
Jiyun Jeong, Seyoung Seo, Sung-Bae Kim, Joon Seon Song, Hye Ryun Kim, Byoung Chul Cho, Minkyu Jung, Chang Gon Kim, Moonki Hong, Min Hee Hong, Sook Ryun Park
Cancers.2025; 17(19): 3149. CrossRef

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