Cancer Research and Treatment

Original Articles

Safety and Efficacy of Combining Metastasis-Directed Stereotactic Ablative Radiation Therapy with Tyrosine Kinase Inhibitors Versus Immune Checkpoint Inhibitors in Metastatic Hepatocellular Carcinoma: Eunyeong Yang, Jeong Il Yu, Hee Chul Park, Myung Ji Goh, Byeong Geun Song, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Moon Seok Choi, Jung Yong Hong, Minsuk Kwon, Nalee Kim; Received September 5, 2025 Accepted February 1, 2026 Published online February 3, 2026; DOI: https://doi.org/10.4143/crt.2025.966 [Accepted]

Abstract PDF: Purpose
Immune checkpoint inhibitors (ICIs) have become a standard therapy for metastatic hepatocellular carcinoma (HCC), often as an alternative to tyrosine kinase inhibitors (TKIs). However, safety data combining ICIs with stereotactic ablative radiotherapy (SABR) remain limited. We compared the safety and efficacy of SABR combined with ICIs versus TKIs in patients with extrahepatic metastatic HCC.
Materials and methods
This single-center retrospective study included patients with HCC who received SABR for extrahepatic metastases combined with either TKIs or ICIs within 30 days of SABR between January 2010 and June 2024. Adverse events (AEs; CTCAE v5.0) and oncologic outcomes were evaluated using logistic regression and Cox models.
Results
Among 103 patients with 128 SABR-treated lesions, 72 patients (90 lesions) received SABR+TKI and 31 patients (38 lesions) received SABR+ICI. Acute AEs occurred only in the SABR+TKI group (8.9%), predominantly grade 1. Grade 3 late AEs were rare, occurring in one case in each group, while late AEs of lower grades were more frequent with SABR+ICI (any-grade: 57.9% vs. 25.6%, p<0.001; grade ≥2: 23.7% vs. 8.9%, p=0.024). Multivariable analysis showed borderline increased risk of grade ≥2 late AEs with SABR+ICI (p=0.052). One-year local control, progression-free survival, and overall survival were 76.6%, 35.3%, and 72.3% respectively, with no significant differences between groups.
Conclusion
Metastasis-directed SABR combined with either TKIs or ICIs was generally well tolerated in patients with extrahepatic metastatic HCC, with rare grade 3 late AEs; grade ≥2 late AEs were more frequent with SABR plus ICIs, warranting prospective evaluation.

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Immunosuppressive Tumor Microenvironment in Colorectal Cancer Lung Metastases: Implications for Recurrence After Metastasectomy: Minsuk Kwon, Min-Kyue Shin, Minae An, Yeong Jeong Jeon, Tae Hee Hong, Jung Kyong Shin, Sung Hee Lim, Yoonah Park, Yong Beom Cho, Seung Tae Kim, Yong Soo Choi, Jeeyun Lee; Received July 3, 2025 Accepted December 8, 2025 Published online December 17, 2025; DOI: https://doi.org/10.4143/crt.2025.691 [Accepted]

Abstract PDF Supplementary Material: Purpose
Colorectal cancer (CRC) lung metastases exhibit high recurrence rates after resection, underscoring the need for improved therapeutic strategies. This study aimed to characterize the tumor microenvironment (TME) of CRC lung metastases and identify the factors associated with recurrence.
Materials and Methods
Fifteen CRC patients who underwent lung metastasectomy were enrolled. Multiplex immunohistochemistry (IHC), whole exome sequencing, transcriptome profiling, and single-cell RNA sequencing (scRNA-seq) were conducted on matched tumor, adjacent and distant normal lung tissues. Immune cell populations and gene expression profiles were analyzed and correlated with clinical recurrence outcomes.
Results
Exome and transcriptome analyses revealed frequent TP53, KRAS, and APC mutations. Most tumors corresponded to consensus molecular subtypes 2 and 4, characterized by immune-depleted and fibrotic features. Tumors showed downregulation of effector T and NK cell signatures. IHC revealed reduced density and increased distance of CD8+ T cells and macrophages from the epithelial cells. scRNA-seq demonstrated increased regulatory T cells and decreased NK and effector T cells in tumor. Tumor-associated macrophages (TAMs), particularly SPP1 (osteopontin)-expressing subsets, were markedly enriched in tumor and correlated with suppressed effector T cella activity. High SPP1 expression was associated with early recurrence and poor overall survival. Patients with recurrence had higher proportion of PD-1+ CD8+ T cells in adjacent normal tissues.
Conclusion
Immunosuppressive features including enrichment of SPP1+ TAMs and depletion of effector T and NK cells contribute to recurrence after CRC lung metastasectomy. Therapeutic strategies targeting both TAMs and T cells may enhance clinical outcomes in this patient population.

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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

Citations to this article as recorded by

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

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Sarcoma

Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response: Jung Yong Hong, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Sang Kyum Kim, Yurimi Lee, Yoon-La Choi, Minsuk Kwon, Hyo Song Kim, Jeeyun Lee; Cancer Res Treat. 2023;55(2):671-683. Published online September 27, 2022; DOI: https://doi.org/10.4143/crt.2022.251

Abstract PDF Supplementary Material PubReader ePub

Purpose
Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy.
Materials and Methods
We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA.
Results
Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker.
Conclusion
Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Citations

Citations to this article as recorded by

A systematic review and meta-analysis of pazopanib efficacy and adverse effects in sarcomas
Fernanda Picozzi, Alessandro Ottaiano, Antonella Lucia Marretta, Mariachiara Santorsola, Lucia Cannella, Antonio Pizzolorusso, Francesco Caraglia, Giuseppina Della Vittoria Scarpati, Alessandra Bracigliano, Ottavia Clemente, Ines Simeone, Michele Caraglia
Journal of Translational Medicine.2026;[Epub] CrossRef
Musculoskeletal Diseases: Mechanisms and Therapeutic Advances
Xiao Ma, Eloy Yinwang, Xupeng Chai, Fangqian Wang, Zehao Chen, Shengdong Wang, Hao Zhou, Yucheng Xue, Jiangchu Lei, Fanglu Chen, Hengyuan Li, Shixin Chen, Shenzhi Zhao, Kelei Wang, Liang Chen, Junjie Gao, Zhaoming Ye, Nong Lin
MedComm.2025;[Epub] CrossRef
Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial
Hee Jin Cho, Kum-Hee Yun, Su-Jin Shin, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Hyang Joo Ryu, Joohee Lee, Iksung Cho, Heounjeong Go, Jiwon Ko, Inkyung Jung, Min Kyung Jeon, Sun Young Rha, Hyo Song Kim
Nature Communications.2024;[Epub] CrossRef
The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease
Jonathan Feicht, Ralf-Peter Jansen
RNA Biology.2024; 21(1): 312. CrossRef
Intracranial Relapse in Pediatric Sarcoma
Danielle E. Smith, Tyler Hamby, Kenneth Heym, Ashraf Mohamed, Kelly L. Vallance, Anish Ray
Journal of Pediatric Hematology/Oncology.2023; 45(7): e810. CrossRef

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