Cancer Research and Treatment

Original Articles

Clinical Outcomes and Histologic Subtype-Specific Patterns in Oligometastatic Soft Tissue Sarcoma of the Extremities and Trunk Wall: Implications for Curative Local Ablative Therapy: Eunkyu Yang, Han-Soo Kim, Jay Hoon Park, Yongsung Kim, Shinn Kim, Miso Kim, Jeonghwan Youk, Hak Jae Kim, Hyun-Cheol Kang, Ilkyu Han; Received September 9, 2025 Accepted October 29, 2025 Published online October 30, 2025; DOI: https://doi.org/10.4143/crt.2025.983 [Accepted]

Abstract PDF: Purpose
Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study investigated the clinical characteristics, oncologic outcomes, and histologic subtype-specific features of oligometastatic STS.
Materials and Methods
We reviewed records of 1,243 patients with extremity/trunk STS who underwent curative surgery between 2000 and 2023. Oligometastatic recurrence occurred in 170 (13.6%), 149 of whom received local ablative therapy (LAT). Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed, along with prognostic factors and subtype-specific characteristics.
Results
The median follow-up was 52.5 months. Surgery alone was the most common LAT (71.2%), followed by surgery with radiotherapy, radiotherapy alone and radiofrequency ablation. The median DSS was 50.0 months (95% confidence interval [CI], 31.5-68.5), with a 5-year DSS rate of 45.2%. The median PFS was 12.0 months (95% CI, 7.6-16.4), with a 5-year PFS of 28.1%. On multivariate analysis, LAT was independently associated with longer DSS (hazard ratio [HR], 9.629; p<0.001). Smaller oligometastatic lesion size and adequate local control of the primary tumor were also independently associated with longer DSS. Metastasis-free interval > 6 months independently predicted longer PFS. Histologic subtypes demonstrated distinct clinical behaviors; for example, myxofibrosarcoma had a lower metastatic rate but poorer DSS, whereas synovial sarcoma showed relatively favorable long-term survival.
Conclusion
Oligometastatic STS represents an intermediate disease state in which LAT can provide meaningful survival benefit. Subtype-specific differences in metastatic behavior and survival outcomes would support individualized, multimodal, and potentially curative treatment strategies.

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Preferential Sensitivity of the EGFR L858M/L861R Mutation to Second-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Chaelin Lee, Sheehyun Kim, Soyeon Kim, Taekeun Park, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jeonghwan Youk; Received March 11, 2025 Accepted August 19, 2025 Published online August 20, 2025; DOI: https://doi.org/10.4143/crt.2025.279 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Non–small cell lung cancer (NSCLC) frequently harbors targetable epidermal growth factor receptor (EGFR) mutations. However, rare variants such as EGFR L858M or L861R remain poorly characterized. This study aimed to elucidate the oncogenic potential and EGFR tyrosine kinase inhibitors (TKIs) sensitivity of the EGFR L858M/L861R mutation to inform personalized treatment strategies.
Materials and Methods
Tumor samples from an NSCLC patient were analyzed using targeted panel sequencing and confirmed with the FoundationOne Liquid CDx assay. EGFR-mutant constructs, including L858M, L858R, L861R, L861Q, L858M/L861R, and L858R/L861Q, were generated and transduced into various cell lines. Cell viability, immunoblot, and soft agar colony formation assays were conducted to assess the oncogenicity and drug sensitivity, while computational protein modeling and docking simulations evaluated the drug-binding affinities of EGFR-TKIs.
Results
Ba/F3 cells expressing the EGFR L858M/L861R mutation exhibited robust interleukin-3–independent proliferation accompanied by markedly increased EGFR phosphorylation, while NIH-3T3 cells showed anchorage-independent colony formation. Compared to other mutations, cells expressing EGFR L858M/L861R mutation were less sensitive to first-generation EGFR-TKIs (gefitinib, erlotinib) and third-generation EGFR-TKIs (osimertinib, lazertinib), whereas second-generation EGFR-TKIs (afatinib, poziotinib) demonstrated potent inhibitory effects. Computational modeling revealed a narrower drug-binding efficiency of first-generation inhibitors.
Conclusion
The EGFR L858M/L861R mutation drives strong oncogenic signaling and exhibits preferential sensitivity to second-generation EGFR-TKIs. These findings underscore the importance of accurate molecular diagnosis for guiding effective, personalized therapeutic strategies in NSCLC.

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Real-World Outcomes and Subsequent Treatment Patterns in Patients with Advanced Non-Small Cell Lung Cancer and Atypical EGFR Mutations Receiving First-Line Osimertinib Monotherapy
Jorge J. Nieva, Xuejun Wang, Deborah Doroshow, Leslie Servidio, Miranda Cooper, Yan Kwan Lau, Pritesh S. Karia, Jacqulyne Robichaux
Oncology and Therapy.2026; 14(1): 225. CrossRef

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Lung and Thoracic cancer

The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells: Songji Oh, Soyeon Kim, Bhumsuk Keam, Jeonghwan Youk, Tae Min Kim, Dong-Wan Kim, Miso Kim; Cancer Res Treat. 2025;57(4):1040-1050. Published online January 7, 2025; DOI: https://doi.org/10.4143/crt.2024.728

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study focused on combining irinotecan with poly(ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials and Methods
We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for 7 days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.
Results
We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DDR pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC₅₀ fold changes for PARP inhibitors were as follows: olaparib, 1,649±4,049; talazoparib, 25±34.21; venadaparib, 336±596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.
Conclusion
This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

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Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer: Hanbaek Yi, Jeonghwan Youk, Yoojoo Lim, Hanseong Roh, Dongsoo Kyung, Hwang-Phill Kim, Duhee Bang, Bhumsuk Keam, Tae-Min Kim, Miso Kim, Dong-Wan Kim, Tae-You Kim; Cancer Res Treat. 2024;56(3):765-773. Published online January 8, 2024; DOI: https://doi.org/10.4143/crt.2023.1294

Abstract PDF Supplementary Material PubReader ePub

Purpose
There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay.
Materials and Methods
Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results.
Results
The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R²=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations.
Conclusion
The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Citations

Citations to this article as recorded by

Trastuzumab deruxtecan in non-breast solid tumors: Expanding indications, efficacy, and future directions
A. Ghidini, R. Bukovec, L. Roncari, L. Dottorini, F. Petrelli
Critical Reviews in Oncology/Hematology.2026; 220: 105158. CrossRef
Preoperative Circulating Tumor DNA Detection and Risk Stratification in Esophageal Squamous Cell Carcinoma
Tae Hee Hong, Jun-Gi Jeong, Seong Yong Park, Byung Jo Park, Dongsoo Kyung, Hwang-Phil Kim, Jingjun Zhu, Young Ho Yang, Ha Eun Kim, Chang Young Lee, Jin Gu Lee, Yeong Jeong Jeon, Junghee Lee, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Se-Hoon Lee, Dae Joo
JAMA Surgery.2026; 161(4): 370. CrossRef
Biological basis and clinical translation prospects of circulating cell‑free DNA in precision management of breast cancer (Review)
Li-Zhuang Fan, Ai-Lan Xu, Ya-Ru Xu, Luo Yang, Fang Yuan, Xin Nie
Oncology Letters.2026; 31(6): 1. CrossRef
Reporting of molecular test results from cell-free DNA analyses: expert consensus recommendations from the 2023 European Liquid Biopsy Society ctDNA Workshop
Vincent D. de Jager, Patrizio Giacomini, Jennifer A. Fairley, Rodrigo A. Toledo, Simon J. Patton, Simon A. Joosse, Claudia Koch, Zandra C. Deans, Sofia Agelaki, Claus Lindbjerg Andersen, Daniel Andersson, Beatriz Bellosillo, Inger Riise Bergheim, Daan van
eBioMedicine.2025; 114: 105636. CrossRef
Improvement of the sensitivity of circulating tumor DNA-based liquid biopsy: current approaches and future perspectives
Ekaterina S. Kuligina, Grigoriy A. Yanus, Evgeny N. Imyanitov
Exploration of Targeted Anti-tumor Therapy.2025;[Epub] CrossRef
Next-generation sequencing impact on cancer care: applications, challenges, and future directions
Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
Frontiers in Genetics.2024;[Epub] CrossRef
Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study
Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang
Molecular Diagnosis & Therapy.2024; 28(6): 803. CrossRef
Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
Journal of Hepatology.2024;[Epub] CrossRef

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