Cancer Research and Treatment

Original Articles

Long-Term Survival Outcomes of Surgical Resection for Lung Adenocarcinoma with Intraoperatively Diagnosed Pleural Metastasis: Target Treatment Era: Yelee Kwon, Jae Kwang Yun, Geun Dong Lee, Se Hoon Choi, Yong-Hee Kim, Hyeong Ryul Kim; Received October 15, 2024 Accepted December 27, 2024 Published online December 30, 2024; DOI: https://doi.org/10.4143/crt.2024.993 [Accepted]

Abstract PDF: Purpose
This study aimed to evaluate the clinical impact of main tumor resection on long-term survival compared with pleural biopsy alone in patients with lung adenocarcinoma who were intraoperatively diagnosed with pleural metastasis.
Materials and Methods
A total of 176 patients with adenocarcinoma who had unexpected pleural metastasis detected during surgery from 2002 to 2021 were retrospectively analyzed. Each surgeon decided whether to perform main tumor resection or pleural biopsy alone.
Results
The patients were grouped based on the surgical approaches: main tumor resection (Resection group; n=83) and pleural biopsy only (O&C group; n=93). The Resection group had better overall survival (OS, 10-year survival: 27.9% vs. 9.4%; median survival: 68.3 vs. 36.6 months; p<0.01) and locoregional progression-free survival (10-year survival: 12.5% vs. 7.1%; median survival: 19.6 vs. 10.6 months; p<0.01) than the O&C group. Similar results were found for OS in patients who received tyrosine kinase inhibitors (TKIs) as first-line therapy (10-year survival: 49.2% vs. 15.0%; median survival: 72.2 vs. 45.4 months; p=0.03), patients who did not undergo TKIs treatment (10-year survival: 29.4% vs. 9.2%; median survival: 82.4 vs. 23.8 months; p<0.01), and patients with positive target gene mutation (10-year survival: 31.7% vs. 10.1%; median survival: 72.2 vs. 33.7 months; p<0.01). In multivariate analysis, pleural biopsy only (hazard ratio, 1.73; p=0.04) was a significant predictor of OS.
Conclusion
Main tumor resection can improve survival in patients with lung adenocarcinoma who had unexpected pleural metastasis during operation.

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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.

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Lung and Thoracic cancer

Recurrence Dynamics of Pathological N2 Non–Small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor: In Ha Kim, Geun Dong Lee, Sehoon Choi, Hyeong Ryul Kim, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Jae Kwang Yun; Cancer Res Treat. 2025;57(1):105-115. Published online July 23, 2024; DOI: https://doi.org/10.4143/crt.2024.150

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC).
Materials and Methods
From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared.
Results
In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96–1.46) and 1.58 (1.31–1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease.
Conclusion
The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

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Evaluation of Uncertain Resection for Localized Non-small Cell Lung Cancer: The Crucial Prognosis of Suboptimal Lymph Node Assessment
Romain Vergé, Axel Rouch, Pierre Rabinel, Claire Renaud, Mathilde Cazaux, Laurent Brouchet
The Annals of Thoracic Surgery.2025;[Epub] CrossRef

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Differences in the Prognostic Impact between Single-Zone and Multi-Zone N2 Node Metastasis in Patients with Station-Based Multiple N2 Non–Small Cell Lung Cancer: Shia Kim, Geun Dong Lee, SeHoon Choi, Hyeong Ryul Kim, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Jae Kwang Yun; Cancer Res Treat. 2025;57(1):95-104. Published online July 22, 2024; DOI: https://doi.org/10.4143/crt.2024.120

Abstract PDF Supplementary Material PubReader ePub: Purpose
The International Association for the Study of Lung Cancer suggests further subdivision of pathologic N (pN) category in non–small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups.
Materials and Methods
This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal.
Results
Among 996 eligible patients, 211 (21.2%), 394 (39.6%), and 391 (39.3%) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT category, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.49 to 0.90; p=0.009) and was comparable to that of N2a2 disease (HR, 1.12; 95% CI, 0.83 to 1.49; p=0.46).
Conclusion
Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

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The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study: Seong Yong Park, Samina Park, Geun Dong Lee, Hong Kwan Kim, Sehoon Choi, Hyeong Ryul Kim, Yong-Hee Kim, Dong Kwan Kim, Seung-Il Park, Tae Hee Hong, Yong Soo Choi, Jhingook Kim, Jong Ho Cho, Young Mog Shim, Jae Ill Zo, Kwon Joong Na, In Kyu Park, Chang Hyun Kang, Young-Tae Kim, Byung Jo Park, Chang Young Lee, Jin Gu Lee, Dae Joon Kim, Hyo Chae Paik; Cancer Res Treat. 2023;55(1):94-102. Published online June 9, 2022; DOI: https://doi.org/10.4143/crt.2022.290

Abstract PDF Supplementary Material PubReader ePub

Purpose
This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery.
Materials and Methods
The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded.
Results
The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS.
Conclusion
Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

Citations

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Application of postoperative adjuvant radiotherapy in limited-stage small cell lung cancer: A systematic review and meta-analysis
Chuanhao Zhang, Genghao Zhao, Huajian Wu, Jianing Jiang, Wenyue Duan, Zhijun Fan, Zhe Wang, Ruoyu Wang
Radiotherapy and Oncology.2024; 193: 110123. CrossRef
A 15-Gene-Based Risk Signature for Predicting Overall Survival in SCLC Patients Who Have Undergone Surgical Resection
Sevcan Atay
Cancers.2023; 15(21): 5219. CrossRef

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2 Crossref

Gastrointestinal cancer

Role of Esophagectomy after Chemoradiation Therapy in Patients with Locally Advanced Squamous Cell Carcinoma: A Comparative Analysis Stratified by Clinical Response to Chemoradiation Therapy: Jesang Yu, Jong Hoon Kim, Sung-Bae Kim, Sook Ryun Park, Young-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Ho June Song, Kye Jin Song, Jeong Yun Jang, Yoon Young Jo, Ye Jin Yoo; Cancer Res Treat. 2022;54(4):1148-1156. Published online December 20, 2021; DOI: https://doi.org/10.4143/crt.2021.885

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the long-term effect of esophagectomy in patients with esophageal squamous cell carcinoma (ESCC) by comparing the chemoradiotherapy (CRT)-only group and the trimodality treatment (TMT) group who received concurrent CRT followed by surgery.
Materials and Methods
We included 412 operable ESCC patients treated with TMT or CRT between January 2005 and December 2015. The oncological outcomes of the two groups were compared using a weighted Cox proportional-hazards model with inverse probability of treatment weighting (IPTW).
Results
The median survival time was 64 and 32 months in the TMT (n=270) and CRT (n=142) groups, respectively (p < 0.001). After IPTW, the median overall survival (OS) remained significantly higher in the TMT group than in the CRT group (61 months vs. 32 months, p=0.016). Moreover, the TMT group showed a better local recurrence-free rate (LRFR, p < 0.001) and distant metastasis-free rate (p=0.007). In the subgroup of patients with clinical complete response (cCR), the OS was not significantly different between the two groups, both before and after IPTW adjustment (p=0.35 and p=0.93). However, among non-cCR patients, the OS was significantly higher in the TMT group (64% vs. 45%, p < 0.001).
Conclusion
In patients with locally advanced ESCC, TMT was superior to CRT in terms of OS and LRFR. Such difference was more prominent in the non-cCR subgroup. In patients who achieved cCR, esophagectomy was effective in improving LRFR but not OS, suggesting that esophagectomy may be omitted in complete responders.

Citations

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Diagnosing Complete Response to Preoperative Chemoradiation in Esophageal Cancer Using Dynamic Contrast-Enhanced MRI Response Criteria
Yura Ahn, Jooae Choe, Hyun Joo Lee, Sook Ryun Park, Jong-Hoon Kim, Ho June Song, Min-Ju Kim, Yong-Hee Kim
Korean Journal of Radiology.2025; 26(3): 269. CrossRef
Comparison of esophageal cancer survival after neoadjuvant chemoradiotherapy plus surgery versus definitive chemoradiotherapy: A systematic review and meta-analysis
Junli Ke, Yujie Xie, Shenyang Huang, Wei Wang, Zhengang Zhao, Wanli Lin
Asian Journal of Surgery.2024; 47(9): 3827. CrossRef
Multi-disciplinary management of esophageal carcinoma: Current practices and future directions
Chanyoot Bandidwattanawong
Critical Reviews in Oncology/Hematology.2024; 197: 104315. CrossRef
Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma
Tae Hee Hong, Tae Ho Kim, Genehee Lee, Jeonghee Yun, Yeong Jeong Jeon, Junghee Lee, Sumin Shin, Seong Yong Park, Jong Ho Cho, Yong Soo Choi, Young Mog Shim, Jong-Mu Sun, Dongryul Oh, Hong Kwan Kim
European Journal of Cardio-Thoracic Surgery.2024;[Epub] CrossRef
Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study
Tongpeng Xu, Jianan Bai, Kun Zhao, Xiaofeng Chen, Shuhui Wang, Shusheng Zhu, Chongqi Sun, Chenhui Zhao, Ting Wang, Ling Zhu, Meizhen Hu, Fei Pang, Junling Zhang, Wei Wang, Yongqian Shu, Fang Li, Yue Zhou
Annals of Surgical Oncology.2024; 31(13): 9321. CrossRef
Unveiling Therapeutic Targets for Esophageal Cancer: A Comprehensive Review
Rakesh Acharya, Ananya Mahapatra, Henu Kumar Verma, L. V. K. S. Bhaskar
Current Oncology.2023; 30(11): 9542. CrossRef
Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma
Young Seob Shin, Jeong Yun Jang, Ye Jin Yoo, Jesang Yu, Kye Jin Song, Yoon Young Jo, Sung-Bae Kim, Sook Ryun Park, Ho June Song, Yong-Hee Kim, Hyeong Ryul Kim, Jong Hoon Kim
Gastroenterology Report.2023;[Epub] CrossRef

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Genitourinary cancer

Genomic Sequencing for Bladder Urothelial Carcinoma and Its Clinical Implications for Immunotherapy: Ryul Kim, Jung Yong Hong, Jeeyun Lee, Ghee Young Kwon, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2022;54(3):894-906. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.854

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to explore the genomic and transcriptomic landscape of bladder cancer (BC) and its implication for treatment with an immune checkpoint inhibitor (ICI).
Materials and Methods
We analyzed whole-exome and -transcriptome sequences of tumor samples from 64 BC patients who underwent surgical resection with either transurethral resection or radical cystectomy. For exploratory purposes, programmed death-ligand 1 (PD-L1) expression was evaluated in a subset of patients (n=57) including those treated with ICI (n=8).
Results
We identified frequent molecular dysregulations in chromatin regulatory genes (KDM6A, ARID1A, MLL2, and STAG2) and recurrent copy number alterations. Thirty-five samples (54.7%) were PD-L1–positive (PD-L1 combined positive score ≥ 1) with a significantly higher exonic tumor mutational burden (TMB) compared to PD-L1–negative BC samples (p=0.010). We observed that various immune-responsive pathways, including the PD-L1 signaling pathway, were enriched significantly in PD-L1–positive BCs. Interestingly, genes in the CTLA4 pathway were enriched significantly in PD-L1–positive BC as well. Among eight patients who received ICI, progressive disease was confirmed in one patient, whose tumor had low exonic TMB, negative PD-L1 status, and a relatively colder microenvironment.
Conclusion
Gaining new insights into the molecular landscape of BC will improve treatment strategies. Our analysis suggests a rationale for studying dual checkpoint inhibition against BC.

Citations

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Targeting the PD-1/PD-L1 Signaling Pathway for Cancer Therapy: Focus on Biomarkers
Areti Strati, Christos Adamopoulos, Ioannis Kotsantis, Amanda Psyrri, Evi Lianidou, Athanasios G. Papavassiliou
International Journal of Molecular Sciences.2025; 26(3): 1235. CrossRef
Development of a Technique for Diagnosis and Screening of Superficial Bladder Cancer by Cell-Pellet DNA From Urine Sample
Jaekwon Seok, Hee Jeong Kwak, Chan-Koo Kang, Ah Ram Kim, Woo Suk Choi, Hyoung Keun Park, Sung Hyun Paick, Hyeong Gon Kim, Yeonjoo Kwak, Tak-Il Jeon, Kyung Min Lim, Baeckseung Lee, Aram Kim, Ssang-Goo Cho
Laboratory Investigation.2025; 105(6): 104124. CrossRef
The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy
Li-Juan Chen, Xin-Yang Xu, Xiao-Dan Zhong, Yan-Jun Liu, Ming-Hui Zhu, Fan Tao, Chang-Yun Li, Qiu-Sheng She, Guan-Jun Yang, Jiong Chen
Bioorganic Chemistry.2023; 133: 106409. CrossRef
A novel cuproptosis-related lncRNAs signature predicts prognostic and immune of bladder urothelial carcinoma
Zheng Zhou, Yusong Zhou, Wei Liu, Jing Dai
Frontiers in Genetics.2023;[Epub] CrossRef
Implication of KDM6A in Bladder Cancer
Marianne Matar, Gilles Prince, Ibrahim Hamati, Maria Baalbaky, Jonas Fares, Marc Aoude, Charbel Matar, Hampig Raphael Kourie
Pharmacogenomics.2023; 24(9): 509. CrossRef
Subsequent Systemic Therapy following Platinum and Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma
Joohyun Hong, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park
Biomedicines.2022; 10(8): 2005. CrossRef
Antineoplastics

Reactions Weekly.2022; 1933(1): 61. CrossRef
Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma
Tongjin Xie, Bin Liu, Dongbo Liu, Yusong Zhou, Qingping Yang, Dai Wang, Mengjie Tang, Wei Liu
Frontiers in Pharmacology.2022;[Epub] CrossRef

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Gastrointestinal cancer

Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors: Jwa Hoon Kim, Bokyung Ahn, Seung-Mo Hong, Hwoon-Yong Jung, Do Hoon Kim, Kee Don Choi, Ji Yong Ahn, Jeong Hoon Lee, Hee Kyoung Na, Jong Hoon Kim, Yong-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Sung-Bae Kim, Sook Ryun Park; Cancer Res Treat. 2022;54(2):505-516. Published online June 23, 2021; DOI: https://doi.org/10.4143/crt.2020.1198

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.
Materials and Methods
Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.
Results
The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.
Conclusion
The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

Citations

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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
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Ryuichi Morita, Takeshi Ishikawa, Toshifumi Doi, Junichiro Itani, Daiki Sone, Naoto Iwai, Ken Inoue, Hirotaka Konishi, Osamu Dohi, Naohisa Yoshida, Atsushi Shiozaki, Kazuhiko Uchiyama, Tomohisa Takagi, Hitoshi Fujiwara, Hideyuki Konishi, Yoshito Itoh
Oncology Letters.2025;[Epub] CrossRef
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Yinfang Gu, Xiaofang Zou, Junlin Zhu, Guowu Wu
World Journal of Surgical Oncology.2025;[Epub] CrossRef
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Min Deng, Yun Qing, Dan Qiu, Ya Sheng, Juan Zhou, Lan Sun
Frontiers in Oncology.2025;[Epub] CrossRef
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Cancer Immunology, Immunotherapy.2025;[Epub] CrossRef
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Yutaka Kimura, Atsushi Gakuhara, Shuichi Fukuda, Yasunari Fukuda, Terukazu Yoshihara, Chikato Koga, Naotsugu Haraguchi, Jin-ichi Hida
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Yi Yu, Tao Wu, Wei Gan, Can Liu, Ran Zhang, Jinxiu Zheng, Jianping Xiong, Jun Chen, Junhe Li
Clinical and Translational Oncology.2024; 26(9): 2360. CrossRef
Pembrolizumab for recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus: a drug safety evaluation
Kazumasa Yamamoto, Shun Yamamoto, Ken Kato
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Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort
Tomoki Makino, Shigeto Nakai, Kota Momose, Kotaro Yamashita, Koji Tanaka, Hiroshi Miyata, Sachiko Yamamoto, Masaaki Motoori, Yutaka Kimura, Yuki Ushimaru, Motohiro Hirao, Jin Matsuyama, Yusuke Akamaru, Yukinori Kurokawa, Hidetoshi Eguchi, Yuichiro Doki
Esophagus.2024; 21(3): 319. CrossRef
The impact of antibiotic use in gastrointestinal tumors treated with immune checkpoint inhibitors: systematic review and meta-analysis
Faizah M. Alotaibi, Ibrahim Abdullah S. Albalawi, Amna M. Anis, Hawazin Alotaibi, Seham Khashwayn, Kanan Alshammari, Jaffar A. Al-Tawfiq
Frontiers in Medicine.2024;[Epub] CrossRef
Prognostic factors of second-line nivolumab monotherapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study for 184 cases
Sho Sato, Takashi Suzuki, Takashi Chinen, Hironori Yamaguchi, Yusuke Suzuki, Nobukazu Hokamura, Zenichiro Saze, Koji Kono, Keita Takahashi, Fumiaki Yano, Tsutomu Sato, Takashi Kosaka, Itaru Endo, Yasushi Ichikawa, Yutaka Miyawaki, Hiroshi Sato, Hideaki Sh
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Xu Tong, Meiyuan Jin, Lulu Wang, Dongli Zhang, Yuping Yin, Qian Shen
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Prognostic nutritional index as a prognostic biomarker for gastrointestinal cancer patients treated with immune checkpoint inhibitors
Lilong Zhang, Wangbin Ma, Zhendong Qiu, Tianrui Kuang, Kunpeng Wang, Baohong Hu, Weixing Wang
Frontiers in Immunology.2023;[Epub] CrossRef
Impact of Patient Characteristics on the Outcomes of Patients with Gastrointestinal Cancers Treated with Immune Checkpoint Inhibitors
Hyejee Ohm, Omar Abdel-Rahman
Current Oncology.2023; 30(1): 786. CrossRef
A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors
Athéna Crespin, Clément Le Bescop, Jean de Gunzburg, Fabien Vitry, Gérard Zalcman, Julie Cervesi, Pierre-Alain Bandinelli
Frontiers in Oncology.2023;[Epub] CrossRef
The Use of Antibiotics During Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Advanced Esophagogastric Cancer
Lilong Zhang, Tianrui Kuang, Dongqi Chai, Wenhong Deng, Peng Wang, Weixing Wang
International Immunopharmacology.2023; 119: 110200. CrossRef
Predictive Impact of Prognostic Nutritional Index in Patients with Cancer Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Xin-Tian Xu, Yu Qian, Meng-Xing Tian, Chen-Chen Ding, Huan Guo, Jing Tang, Guo-Liang Pi, Yuan Wu, Zhu Dai, Xin Jin
Nutrition and Cancer.2023; 75(6): 1413. CrossRef
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Ning Chen, Xiaoling Xu, Yun Fan
Therapeutic Advances in Medical Oncology.2023;[Epub] CrossRef
進行食道癌に対する化学療法，化学放射線療法における栄養管理
豊木村
The Japanese Journal of SURGICAL METABOLISM and NUTRITION.2023; 57(6): 183. CrossRef
Prognostic and predictive impact of neutrophil‐to‐lymphocyte ratio and HLA‐I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy
Lin Wang, Yanrong Zhu, Bo Zhang, Xi Wang, Hongnan Mo, Yuchen Jiao, Jiachen Xu, Jing Huang
Thoracic Cancer.2022; 13(11): 1631. CrossRef
Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Liwei Ni, Jing Huang, Jiyuan Ding, Junyan Kou, Tingting Shao, Jun Li, Liujie Gao, Wanzhen Zheng, Zhen Wu
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Lung Cancer

Prognostic Factor and Clinical Outcome in Stage III Non-Small Cell Lung Cancer: A Study Based on Real-World Clinical Data in the Korean Population: Ho Cheol Kim, Wonjun Ji, Jae Cheol Lee, Hyeong Ryul Kim, Si Yeol Song, Chang-Min Choi, Korean Association for Lung Cancer, Korea Central Cancer Registry; Cancer Res Treat. 2021;53(4):1033-1041. Published online February 16, 2021; DOI: https://doi.org/10.4143/crt.2020.1350

Abstract PDF Supplementary Material PubReader ePub

Purpose
The optimal treatment for patients with stage III non-small cell lung cancer (NSCLC) remains controversial. This study aimed to investigate prognostic factors and clinical outcome in stage III NSCLC using real-world clinical data in the Korean population.
Materials and Methods
Among 8,110 patients with lung cancer selected from 52 hospitals in Korea during 2014-2016, only patients with stage III NSCLC were recruited and analyzed. A standardized protocol was used to collect clinical information and cox proportional hazards models were used to identify risk factors for mortality.
Results
A total of 1,383 patients (46.5% had squamous cell carcinoma and 40.9% had adenocarcinoma) with stage III NSCLC were enrolled, and their median age was 70 years. Regarding clinical stage, 548 patients (39.6%) had stage IIIA, 517 (37.4%) had stage IIIB, and 318 (23.0%) had stage IIIC. Pertaining to the initial treatment method, the surgery group (median survival period: 36 months) showed better survival outcomes than the non-surgical treatment group (median survival period: 18 months, p=0.001) in patients with stage IIIA. Moreover, among patients with stage IIIB and stage IIIC, those who received concurrent chemotherapy and radiation therapy (CCRT, median survival period: 24 months) showed better survival outcomes than those who received chemotherapy (median survival period: 11 months), or radiation therapy (median survival period: 10 months, p<0.001).
Conclusion
While surgery might be feasible as the initial treatment option in patients with stage IIIA NSCLC, CCRT showed a beneficial role in patients with stage IIIB and IIIC NSCLC.

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The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis: Ryul Kim, Seokyung Hahn, Junghoon Shin, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo; Cancer Res Treat. 2016;48(3):907-916. Published online November 17, 2015; DOI: https://doi.org/10.4143/crt.2015.359

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT.
Materials and Methods
A search of the PubMed, EMBASE, and Cochrane Library databases was performed in April 2015 and abstracts from the American Society of Clinical Oncology meetings (2008-2014) were reviewed. Summaries of the results were pooled using a fixed-effect model, and the risk of bias was evaluated using the Cochrane tool.
Results
A total of six relevant trials comprising 1,280 patients were identified. There was no statistically significant overall survival (OS) advantage for TPF prior to CRT (TPF/CRT) over CRT alone (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.79 to 1.09; p=0.339). Progression- free survival (PFS) was significantly longer in the TPF/CRT arms (HR, 0.82; 95% CI, 0.70 to 0.95; p=0.009). Patients with non-oropharyngeal LA-HNSCC obtained the greatest OS and PFS benefits from TPF (HR, 0.68; 95% CI, 0.47 to 0.99; p=0.043 and HR, 0.67; 95% CI, 0.48 to 0.94; p=0.022, respectively). The complete response rate was significantly increased (risk ratio [RR], 1.34; 95% CI, 1.14 to 1.56; p < 0.001), and the distant metastasis rate tended to decrease (RR, 0.65; 95% CI, 0.40 to 1.04; p=0.071) in the TPF/CRT arms.
Conclusion
IC with TPF followed by CRT is not superior to CRT alone for OS. However, PFS and the complete response rate were significantly improved in the TPF/CRT arms. TPF/CRT for patients with nonoropharyngeal LA-HNSCC provided clear survival advantages.

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Synergistic Effect of Sulindac and Simvastatin on Apoptosis in Lung Cancer A549 Cells through AKT-Dependent Downregulation of Survivin: Young-Suk Kim, Chang-Hwan Seol, Jae-Wan Jung, Su-Jin Oh, Ki-Eun Hwang, Hwi-Jung Kim, Eun-Taik Jeong, Hak-Ryul Kim; Cancer Res Treat. 2015;47(1):90-100. Published online October 27, 2014; DOI: https://doi.org/10.4143/crt.2013.194

Abstract PDF PubReader ePub

Purpose
Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventive or chemotherapeutic agents. The mechanism underlying the deregulation of survivin by NSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. In this study, we investigated the synergistic interaction of sulindac and simvastatin in lung cancer A549 cells.
Materials and Methods
Cell viability was measured by an MTT assay, while the expression of apoptotic markers, AKT, and survivin in response to sulindac and simvastatin was examined by Western blotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells. Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDA and MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. The effects of AKT on survivin expression in sulindac- and simvastatin-treated cells were assessed. Survivin was knocked down or overexpressed to determine its role in apoptosis induced by sulindac and simvastatin.
Results
Sulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROS production in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, while AKT overexpression markedly increased survivin expression, even in the presence of sulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininduced apoptosis. In contrast, survivin upregulation protected against sulindac- and simvastatin-induced apoptosis.
Conclusion
Combined treatment with sulindac and simvastatin augmented their apoptotic potential in lung cancer cells through AKT signaling-dependent downregulation of survivin. These results indicate that sulindac and simvastatin may be clinically promising therapies for the prevention of lung cancer.

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Case Report

Pseudoaneurysm Due to Squamous Cell Carcinoma of the Lung: Two Cases of Spontaneous Resolution after Chemotherapy: So-Young Kim, Hak-Ryul Kim, Jung-Sub Song, Ki-Eun Hwang, Jeong-Hyun Shin, Seoung-Nam Shin, Dong Kim, Seong-Hoon Park, Sei-Hoon Yang, Eun-Taik Jeong; Cancer Res Treat. 2009;41(4):237-240. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.237

Abstract PDF PubReader ePub

Pseudoaneurysm due to cancer is uncommon generally and is extremely rare in lung cancer. We report two cases of false aneurysms due to lung cancer that spontaneously regressed upon chemotherapy without intervention. Both patients had squamous cell carcinoma of the lung and the diagnosis of a pseudoaneurysm was made using computed tomography. There was no evidence of severe bronchial hemorrhage and the psuedoaneurysms were small and well-encased. Chemotherapy was performed and the pseudoaneurysms resolved.

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Original Articles

Arsenic Trioxide Induces Apoptosis of HL-60 Cells via Activation of Intrinsic Caspase Protease with Mitochondrial Dysfunction: Byung Hak Jung, Channy Park, Hak Ryul Kim, Moo Rim Park; Cancer Res Treat. 2002;34(4):308-315. Published online August 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.4.308

Abstract PDF

Arsenic trioxide (As2O3) was introduced into the treatment of refractory or relapsed acute promyelocytic leukemia and showed a striking effectiveness in China and United States multicenter study. However, the mechanistic basis for the carcinogenic or therapeutic effects of arsenics is still poorly understood. So, this study is performed to determine whether As2O3 induces apoptosis through intrinsic caspase cascades in acute promyelocytic leukemia HL-60 cells.
MATERIALS AND METHODS
HL-60 cells were treated with As2O3 to investigate apoptosis through signaling of caspase cascades and mitochondrial dysfunction.
RESULTS
As2O3 (>0.5 uM) decreased the viability of HL-60 cells in a dose-dependent manner, which was revealed as apoptosis shown chromatin condensation and ladder pattern DNA fragmentation. As2O3 increased the catalytic activity of caspase family cysteine proteases including caspase-3 and -9 proteases. Consistently, PARP, an intracellular biosubstrate of caspase-3 protease, was cleaved from 116 kDa to 85 kDa fragments. It also induced the change of mitochondrial membrane potential. Morever, As2O3 resulted in the increase of Bak.
CONCLUSION
These data suggest that As2O3 induces apoptosis of HL-60 cells through activation of intrinsic caspase protease with mitochondrial dysfunction.

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The Time‐Dependent Serial Gene Response to Zeocin Treatment Involves Caspase‐Dependent Apoptosis in HeLa Cells
Jooyeon Hwang, Young‐Youl Kim, Sungjin Huh, Junghee Shim, Chan Park, Kuchan Kimm, Dong Kug Choi, Tae‐Kyu Park, Soonhag Kim
Microbiology and Immunology.2005; 49(4): 331. CrossRef

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The Expression of a Novel 90 kDa Stress Protein in Human Malignant Neoplasms: Hong Rae Cho, Gyu Yeol Kim, Chan Jin Park, Byung Kyun Ko, Chang Woo Nam, Sung Sook Kim, Hae Who Park, Do Ha Kim, Sung Ryul Kim, Jeong Woo Park, Won Joon Yoon, Jeong Min Park, Seung Ju Cha, Wha Ja Cho, Dae Hwa Choi; J Korean Cancer Assoc. 1999;31(4):793-801.

Abstract PDF: PURPOSE
When cells are subjected to stressful stimuli such as, heat shock, toxic metal, nutrient deprivation, and metabolic disruption, they increase production of specific stress proteins that buffer them from harm. We reported that the expression of a navel 90 kDa cellular protein was increased by the infection of a fish rhabdovirus and heat shock in a fish cell. This new 90 kDa protein is not expressed in normal animal tissues but is highly induced in progressively transforming tissues or cells. That gives us some ideas tl at it is possible for this stress protein to be expressed in specific human cancer tissues.
MATERIALS AND METHODS
Commercialized checkerboard multi-tumor block (DAKO Co. Carpinteria, CA) was used for immunohistochemical analysis. The samples of human gastric cancer, colon cancer and breast cancer tissues were evaluated by Western blot and Northern blot for overexpression of the novel 90 kDa stress protein. Sera of those patients were analyzed by ELISA for the presence of antibody against the novel 90 kDa stress protein.
RESULTS
Immunohistochemical staining of human tumor tissue blocks showed significant immunostaining of novel 90 kDa stress protein in carcinomas such as colon cancer, breast cancer and stomach cancer but no apparent immunostaining in sarcomas. Coinciding with the immunohistochemical result, Western blotting and Northern blotting analyses indicate that the expression of the novel 90 kDa stress protein was increased in carcinomas. In addition, the antibody titer against the novel 90 kDa stress protein was found to be elevated in the sera of cancer patients.
CONCLUSIONS
The novel 90 kDa stress protein gene expression was elevated in carcinomas such as gastric cancer, breast cancer and colon cancer. These findings suggest that this new stress protein can be used as a tumor marker and may function as a chaperone in tumor growth.

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Acinar Cell Carcinoma in a Pancreas : Report of a recurrent case: Eun Sook Lee, Ki Hoon Jung, Nam Ryul Kim, Seon Hahn Kim, Sae Min Kim, Chul Hwan Kim; J Korean Cancer Assoc. 1996;28(4):782-787.

Abstract PDF: Acinar cell carcinoma of the pancreas is a rare neoplasm arising from the exocrine cells of the pancreas, comprising no more than 1 to 2% of all pancreatic cancers. CT appearence of pancreatic acinar carcinoma has been described as a sharply circumscribed mass with central necrosis. We report a case of recurrent acinar cell carcinoma of the pancreas in a 41-year-old man who had distal pancreatectomy three years ago for primary acinar cell carcinoma.

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