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Volume 56(1); January 2024
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Review Article
Intensity-Modulated Radiation Therapy for Uterine Cervical Cancer to Reduce Toxicity and Enhance Efficacy – an Option or a Must?: A Narrative Review
Sea-Won Lee, Aeran Kim, Sung Jong Lee, Sung Hwan Kim, Jong Hoon Lee
Cancer Res Treat. 2024;56(1):1-17.   Published online August 30, 2023
DOI: https://doi.org/10.4143/crt.2023.562
AbstractAbstract PDFPubReaderePub
Radiotherapy (RT) is a fundamental modality in treatment of cervical cancer. With advancement of technology, conventional RT used for external beam radiotherapy (EBRT) for over half a century has been rapidly replaced with intensity-modulated radiation therapy (IMRT) especially during the last decade. This newer technique is able to differentiate the intensity of radiation within the same field, thus reduces the inevitable exposure of radiation to normal organs and enables better dose delivery to tumors. Recently, the American Society for Radiation Oncology has released a guideline for RT in cervical cancer. Although a section of the guideline recommends IMRT for the purpose of toxicity reduction, a thorough review of the literature is necessary to understand the current status of IMRT in cervical cancer. This narrative review updates the recent high-level evidences regarding the efficacy and toxicity of IMRT and provides a better understanding of the most innovative techniques currently available for EBRT enabled by IMRT.

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  • Can knowledge-based planning models validated on ethnically diverse patients lead to global standardisation of external beam radiation therapy for locally advanced cervix cancer?
    Jeevanshu Jain, Monica Serban, Marianne Sanggaard Assenholt, Varsha Hande, Jamema Swamidas, Yvette Seppenwoolde, Joanne Alfieri, Kari Tanderup, Supriya Chopra
    Radiotherapy and Oncology.2025; 204: 110694.     CrossRef
  • Long term clinical outcomes of cervical cancer patients who were recommended surgery but did not undergo it: A SEER database study
    Zhaoming Zhang, Hongfu Zhao, Guanghui Cheng
    European Journal of Surgical Oncology.2024; 50(10): 108572.     CrossRef
  • Treatment of secondary uterine malignancy following radiotherapy for cervical cancer: a study based on the SEER database
    Xiaojing Tong, Yunyun Xiao, Haozhen Li, Hang Zhang, Jiawen Li
    BMC Women's Health.2024;[Epub]     CrossRef
  • 4,634 View
  • 324 Download
  • 3 Web of Science
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Original Articles
General
Longitudinal Changes in Smoking Behaviors and Cancer-Related Mortality Risk in Middle-Aged Korean Women
Thi Xuan Mai Tran, Soyeoun Kim, Seonju Kim, Boyoung Park
Cancer Res Treat. 2024;56(1):18-26.   Published online August 2, 2023
DOI: https://doi.org/10.4143/crt.2023.341
AbstractAbstract PDFPubReaderePub
Purpose
This study investigated association between smoking habit change and cancer-related mortality risk in Korean women.
Materials and Methods
Study population were women aged ≥ 40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020. Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers. Outcomes included all-cause and cancer-related deaths. Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk.
Results
Of 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years). Compared with sustained nonsmokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups. Cancer-related risk increased 1.22-fold among sustained quitters (95% confidence interval [CI], 1.10 to 1.36), 1.56-fold (95% CI, 1.40 to 1.75) in new quitters, 1.40-fold (95% CI, 1.21 to 1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI, 1.46 to 1.78) in sustained smokers compared with sustained nonsmokers. Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of hazard ratios compared to nonsmokers (< 5 pack-years 2.12-fold, 5-10 pack-years 2.15-fold, and > 10 pack-years 2.27-fold).
Conclusion
Quitting smoking earlier is critical for preventing death from all causes and cancer among female smokers.
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Trends and Clinical Characteristics of Next-Generation Sequencing–Based Genetic Panel Tests: An Analysis of Korean Nationwide Claims Data
Mi Jang, Hae Yong Pak, Ja Yoon Heo, Hyunsun Lim, Yoon-La Choi, Hyo Sup Shim, Eun Kyung Kim
Cancer Res Treat. 2024;56(1):27-36.   Published online September 7, 2023
DOI: https://doi.org/10.4143/crt.2023.844
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea.
Materials and Methods
This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs.
Results
Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020.
Conclusion
This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.
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Head and Neck cancer
A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial
Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim
Cancer Res Treat. 2024;56(1):37-47.   Published online July 20, 2023
DOI: https://doi.org/10.4143/crt.2023.433
AbstractAbstract PDFPubReaderePub
Purpose
Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
Materials and Methods
The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Results
Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Conclusion
Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

Citations

Citations to this article as recorded by  
  • One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents
    Michael Atef Fawzy, Karim Hagag Ibrahim, Ashraf A Aly, Asmaa H Mohamed, Sara Mohamed Naguib Abdel Hafez, Walaa Yehia Abdelzaher, Eslam B Elkaeed, Aisha A Alsfouk, El-Shimaa MN Abdelhafez
    Future Medicinal Chemistry.2024; 16(21): 2211.     CrossRef
  • Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck
    Prashant Puttagunta, Saagar V. Pamulapati, James E. Bates, Jennifer H. Gross, William A. Stokes, Nicole C. Schmitt, Conor Steuer, Yong Teng, Nabil F. Saba
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • 3,959 View
  • 284 Download
  • 2 Web of Science
  • 2 Crossref
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Lung and Thoracic cancer
Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
Ki Hyeong Lee, Byoung Chul Cho, Myung-Ju Ahn, Yun-Gyoo Lee, Youngjoo Lee, Jong-Seok Lee, Joo-Hang Kim, Young Joo Min, Gyeong-Won Lee, Sung Sook Lee, Kyung-Hee Lee, Yoon Ho Ko, Byoung Yong Shim, Sang-We Kim, Sang Won Shin, Jin-Hyuk Choi, Dong-Wan Kim, Eun Kyung Cho, Keon Uk Park, Jin-Soo Kim, Sang Hoon Chun, Jangyoung Wang, SeokYoung Choi, Jin Hyoung Kang
Cancer Res Treat. 2024;56(1):48-60.   Published online June 27, 2023
DOI: https://doi.org/10.4143/crt.2023.453
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Citations

Citations to this article as recorded by  
  • First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis
    Jietao Ma, Xiaoxue Pang, Shuling Zhang, Letian Huang, Li Sun, Chengbo Han
    Scientific Reports.2024;[Epub]     CrossRef
  • 6,132 View
  • 578 Download
  • 3 Web of Science
  • 1 Crossref
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First-Line Alectinib vs. Brigatinib in Advanced Non–Small Cell Lung Cancer with ALK Rearrangement: Real-World Data
Youngkyung Jeon, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Res Treat. 2024;56(1):61-69.   Published online July 14, 2023
DOI: https://doi.org/10.4143/crt.2023.461
AbstractAbstract PDFPubReaderePub
Purpose
Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib.
Materials and Methods
Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%).
Conclusion
Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials
    D. Ross Camidge, Shunichi Sugawara, Masashi Kondo, Hye Ryun Kim, Myung-Ju Ahn, James C.H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Kentarou Kudou, Takayuki Asato, Bradley Hupf, Florin Vranceanu, Robert J. Fram, Yuichiro O
    Lung Cancer.2025; 201: 108424.     CrossRef
  • Bridging the Gap between Trial Adverse Events and Real-World Data
    Sang Hyuk Kim, Hyun Lee, Dong Won Park
    Cancer Research and Treatment.2024; 56(3): 972.     CrossRef
  • Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
    Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
    Cancer Medicine.2024;[Epub]     CrossRef
  • Cost‐Effectiveness Analysis of Adjuvant Alectinib versus Platinum‐Based Chemotherapy in Resected ALK‐Positive Non‐Small‐Cell Lung Cancer in the Chinese Health Care System
    Qiran Wei, Yifang Liang, Jiahui Mao, Xin Guan
    Cancer Medicine.2024;[Epub]     CrossRef
  • 5,181 View
  • 590 Download
  • 4 Web of Science
  • 4 Crossref
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Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non–Small Cell Lung Cancer
Beung-Chul Ahn, Charny Park, Moon Soo Kim, Jong Mog Lee, Jin Ho Choi, Hyae Young Kim, Geon Kook Lee, Namhee Yu, Youngjoo Lee, Ji-Youn Han
Cancer Res Treat. 2024;56(1):70-80.   Published online June 21, 2023
DOI: https://doi.org/10.4143/crt.2023.482
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non–small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC.
Materials and Methods
This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling.
Results
A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS.
Conclusion
NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

Citations

Citations to this article as recorded by  
  • Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication
    Jayaprakash Mandal, Tiffany Nicole Jones, Juliane Marie Liberto, Stephanie Gaillard, Tian-Li Wang, Ie-Ming Shih
    Cancer Research.2024; 84(22): 3881.     CrossRef
  • 3,698 View
  • 263 Download
  • 1 Web of Science
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Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer
Il-Hyun Park, Dae-Soon Son, Yoon-La Choi, Ji-Hyeon Choi, Ji-Eun Park, Yeong Jeong Jeon, Minseob Cho, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Jung Hee Kang, Suzy Park, Jinseon Lee, Sung-Hyun Kim, Byung-Chul Lee, Jhingook Kim
Cancer Res Treat. 2024;56(1):81-91.   Published online June 20, 2023
DOI: https://doi.org/10.4143/crt.2023.408
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens.
Materials and Methods
In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee.
Results
The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients.
Conclusion
The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Citations

Citations to this article as recorded by  
  • Highly Sensitive 3D‐Nanoplasmonic‐Based Epidermal Growth Factor Receptor Mutation Multiplex Assay Chip for Liquid Biopsy
    Ji Young Lee, Byeong‐Ho Jeong, Ho Sang Jung, Taejoon Kang, Yeonkyung Park, Jin Kyung Rho, Sung‐Gyu Park, Min‐Young Lee
    Small Science.2024;[Epub]     CrossRef
  • The Advantage of Targeted Next-Generation Sequencing over qPCR in Testing for Druggable EGFR Variants in Non-Small-Cell Lung Cancer
    Adam Szpechcinski, Joanna Moes-Sosnowska, Paulina Skronska, Urszula Lechowicz, Magdalena Pelc, Malgorzata Szolkowska, Piotr Rudzinski, Emil Wojda, Krystyna Maszkowska-Kopij, Renata Langfort, Tadeusz Orlowski, Pawel Sliwinski, Mateusz Polaczek, Joanna Chor
    International Journal of Molecular Sciences.2024; 25(14): 7908.     CrossRef
  • 4,027 View
  • 281 Download
  • 2 Web of Science
  • 2 Crossref
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Strategies to Improve Smoking Cessation for Participants in Lung Cancer Screening Program: Analysis of Factors Associated with Smoking Cessation in Korean Lung Cancer Screening Project (K-LUCAS)
Yeol Kim, Jaeho Lee, Eunju Lee, Juntae Lim, Yonghyun Kim, Choon-Taek Lee, Seung Hun Jang, Yu-Jin Paek, Won-Chul Lee, Chan Wha Lee, Hyae Young Kim, Jin Mo Goo, Kui Son Choi, Boyoung Park, Duk Hyoung Lee, Hong Gwan Seo
Cancer Res Treat. 2024;56(1):92-103.   Published online August 7, 2023
DOI: https://doi.org/10.4143/crt.2022.1598
AbstractAbstract PDFPubReaderePub
Purpose
Smoking cessation intervention is one of the key components of successful lung cancer screening program. We investigated the effectiveness and related factors of smoking cessation services provided to the participants in a population-based lung cancer screening trial.
Materials and Methods
The Korean Lung Cancer Screening Project (K-LUCAS) is a nationwide, multi-center lung cancer screening trial that evaluates the feasibility of implementing population-based lung cancer screening. All 5,144 current smokers who participated in the K-LUCAS received a mandatory smoking cessation counseling. Changes in smoking status were followed up using a telephone survey in 6 months after lung cancer screening participation. The lung cancer screening’s impact on smoking cessation is analyzed by variations in the smoking cessation interventions provided in screening units.
Results
Among 4,136 survey responders, participant’s motivation to quit smoking increased by 9.4% on average after lung cancer screening. After 6 months from the initial screening, 24.3% of participants stopped smoking, and 10.6% of participants had not smoked continuously for at least 6 months after screening. Over 80% of quitters stated that participation in lung cancer screening motivated them to quit smoking. Low-cost public smoking cessation program combined with lung cancer screening increased the abstinence rates. The smokers were three times more likely to quit smoking when the smoking cessation counseling was provided simultaneously with low-dose computed tomography screening results than when provided separately.
Conclusion
A mandatory smoking cessation intervention integrated with screening result counselling by a physician after participation in lung cancer screening could be effective for increasing smoking cessation attempts.

Citations

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  • p53 Genetics and Biology in Lung Carcinomas: Insights, Implications and Clinical Applications
    Dixan A. Benitez, Guadalupe Cumplido-Laso, Marcos Olivera-Gómez, Nuria Del Valle-Del Pino, Alba Díaz-Pizarro, Sonia Mulero-Navarro, Angel Román-García, Jose Maria Carvajal-Gonzalez
    Biomedicines.2024; 12(7): 1453.     CrossRef
  • Problems and Alternatives for Korea National Lung Cancer Screening Program for Smoking Cessation: Analysis of a Survey Involving Experts
    Cheol Min Lee, Sil Vi Han Park, Jinri Kim, Bumjo Oh, Kiheon Lee, Yeol Kim, Yu-Jin Paek
    Journal of the Korean Society for Research on Nicotine and Tobacco.2024; 15(2): 49.     CrossRef
  • The pros and cons of lung cancer screening
    Roberta Eufrasia Ledda, Georg-Christian Funk, Nicola Sverzellati
    European Radiology.2024; 35(1): 267.     CrossRef
  • Effective Smoking Cessation Counseling for Participants in a Lung Cancer Screening
    Choon-Young Kim, Yeol Kim, Cheol Min Lee
    Journal of the Korean Society for Research on Nicotine and Tobacco.2024; 15(3): 88.     CrossRef
  • 3,458 View
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Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma
Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim
Cancer Res Treat. 2024;56(1):104-114.   Published online July 24, 2023
DOI: https://doi.org/10.4143/crt.2023.728
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

Citations

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  • Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA
    Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasu
    Investigational New Drugs.2025;[Epub]     CrossRef
  • 3,130 View
  • 202 Download
  • 1 Web of Science
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Aggressive Local Ablative Radiotherapy Mitigates Progression Risk in Oligometastatic Lung Adenocarcinoma
Gowoon Yang, Kyung Hwan Kim, Chang Geol Lee, Min Hee Hong, Hye Ryun Kim, Yeona Cho, Hong In Yoon
Cancer Res Treat. 2024;56(1):115-124.   Published online August 29, 2023
DOI: https://doi.org/10.4143/crt.2023.600
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to determine the role of local ablative radiotherapy (LART) in oligometastatic/oligoprogressive lung adenocarcinoma.
Materials and Methods
Patients (n=176) with oligometastatic lung adenocarcinoma treated with LART were identified, and those treated with LART at the initial diagnosis of synchronous oligometastatic disease (OMD group) or treated with LART when they presented with repeat oligoprogression (OPD group) were included.
Results
In the OMD group (n=54), the 1- and 3-year progression-free survival (PFS) were 50.9% and 22.5%, respectively, whereas the 1- and 3-year overall survival in the OPD group were 75.9% and 58.1%, respectively. Forty-one patients (75.9%) received LART at all gross disease sites. Tyrosine kinase inhibitor (TKI) use and all-metastatic site LART were significant predictors of higher PFS (p=0.018 and p=0.046, respectively). In patients treated with TKIs at the time of LART (n=23) and those treated with all-metastatic site LART, the 1-year PFS was 86.7%, while that of patients not treated with all-metastatic site LART was 37.5% (p=0.006). In the OPD group (n=122), 67.2% of the patients (n=82) maintained a systemic therapy regimen after LART. The cumulative incidence of changing systemic therapy was 39.6%, 62.9%, and 78.5% at 6 months, 1 year, and 2 years after LART, respectively.
Conclusion
Aggressive LART can be an option to improve survival in patients with oligometastatic disease. Patients with synchronous oligometastatic disease receiving TKI and all-metastatic site LART may have improved PFS. In patients with repeat oligoprogression, LART might potentially extend survival by delaying the need to change the systemic treatment regimen.
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Breast cancer
Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study
Danbee Kang, Seri Park, Hyo Jung Kim, Seok Won Kim, Jeong Eon Lee, Jonghan Yu, Se Kyung Lee, Ji-Yeon Kim, Seok Jin Nam, Juhee Cho, Yeon Hee Park
Cancer Res Treat. 2024;56(1):125-133.   Published online September 4, 2023
DOI: https://doi.org/10.4143/crt.2023.673
AbstractAbstract PDFPubReaderePub
Purpose
We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study.
Materials and Methods
Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes.
Results
The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis.
Conclusion
In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.
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Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes
Xin Li, Zehao Li, Lin Li, Tong Liu, Cheng Qian, Yanlv Ren, Zhigao Li, Kejin Chen, Dongchen Ji, Ming Zhang, Jinsong Wang
Cancer Res Treat. 2024;56(1):134-142.   Published online August 14, 2023
DOI: https://doi.org/10.4143/crt.2023.652
AbstractAbstract PDFPubReaderePub
Purpose
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

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  • FDA-approved drugs containing dimethylamine pharmacophore: a review of the last 50 years
    Sandeep Bindra, Kuntal Bose, Amrutha Chandran Thekkantavida, Della Grace Thomas Parambi, Tariq G. Alsahli, Manu Pant, Leena K. Pappachen, Hoon Kim, Bijo Mathew
    RSC Advances.2024; 14(38): 27657.     CrossRef
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Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea
Hye Yeon Kim, Jisoo Park, Seok Joo Moon, Sohyeon Jeong, Jin Hwa Hong, Jae Kwan Lee, Geum Joon Cho, Hyun-Woong Cho
Cancer Res Treat. 2024;56(1):143-148.   Published online August 16, 2023
DOI: https://doi.org/10.4143/crt.2023.653
AbstractAbstract PDFPubReaderePub
Purpose
BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO.
Materials and Methods
A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups.
Results
There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278).
Conclusion
In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

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  • A contemporary review of breast cancer risk factors and the role of artificial intelligence
    Orietta Nicolis, Denisse De Los Angeles, Carla Taramasco
    Frontiers in Oncology.2024;[Epub]     CrossRef
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Next-Generation Sequencing in Breast Cancer Patients: Real-World Data for Precision Medicine
Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho
Cancer Res Treat. 2024;56(1):149-161.   Published online August 11, 2023
DOI: https://doi.org/10.4143/crt.2023.800
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer.
Materials and Methods
We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500.
Results
The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation.
Conclusion
NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

Citations

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  • Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
    Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
    Pathology.2024; 56(5): 653.     CrossRef
  • Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer
    Elena Guerini-Rocco, Konstantinos Venetis, Giulia Cursano, Eltjona Mane, Chiara Frascarelli, Francesco Pepe, Mariachiara Negrelli, Edoardo Olmeda, Davide Vacirca, Alberto Ranghiero, Dario Trapani, Carmen Criscitiello, Giuseppe Curigliano, Christian Rolfo,
    Critical Reviews in Oncology/Hematology.2024; 201: 104427.     CrossRef
  • An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer
    Yi Bi, Xiao Lv, Ke Wang, Jinyu Wu, Xiang Shi, Xiaodong Zheng, Xiaogang Lin
    Frontiers in Bioengineering and Biotechnology.2024;[Epub]     CrossRef
  • NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
    Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
    Romanian Journal of Morphology and Embryology.2024; 65(2): 195.     CrossRef
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Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy
Dongjin Kim, Yeuni Yu, Ki Sun Jung, Yun Hak Kim, Jae-Joon Kim
Cancer Res Treat. 2024;56(1):162-177.   Published online July 24, 2023
DOI: https://doi.org/10.4143/crt.2023.330
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy.
Materials and Methods
We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response.
Results
Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group.
Conclusion
Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.

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  • Molecular Classification of Breast Cancer Using Weakly Supervised Learning
    Wooyoung Jang, Jonghyun Lee, Kyong Hwa Park, Aeree Kim, Sung Hak Lee, Sangjeong Ahn
    Cancer Research and Treatment.2025; 57(1): 116.     CrossRef
  • Shotgun Metagenomics Reveals Minor Micro“bee”omes Diversity Defining Differences between Larvae and Pupae Brood Combs
    Daniil Smutin, Amir Taldaev, Egor Lebedev, Leonid Adonin
    International Journal of Molecular Sciences.2024; 25(2): 741.     CrossRef
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Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions
Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes
Cancer Res Treat. 2024;56(1):178-190.   Published online August 1, 2023
DOI: https://doi.org/10.4143/crt.2023.386
AbstractAbstract PDFPubReaderePub
Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.
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Gastrointestinal cancer
Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population
Hyojin Pyun, Madhawa Gunathilake, Jeonghee Lee, Il Ju Choi, Young-Il Kim, Joohon Sung, Jeongseon Kim
Cancer Res Treat. 2024;56(1):191-198.   Published online June 20, 2023
DOI: https://doi.org/10.4143/crt.2022.958
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns.
Materials and Methods
The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed.
Results
In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10–83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10–6 (0.05/13,114); DEFB108B had the lowest p=5.94×10–15, followed by FAM86C1 (p=1.74×10–14), PSCA (p=1.81×10–14), and KLHDC4 (p=5.00×10–10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway.
Conclusion
While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

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  • Investigating the Shared Genetic Architecture Between Leukocyte Telomere Length and Prostate Cancer
    Zhizhou Li, Maoyu Wang, Shuxiong Zeng, Ziwei Wang, Yidie Ying, Qing Chen, Chen Zhang, Wei He, Chaoyang Sheng, Yi Wang, Zhensheng Zhang, Chuanliang Xu, Huiqing Wang
    The World Journal of Men's Health.2024;[Epub]     CrossRef
  • A rare KLHDC4 variant Glu510Lys is associated with genetic susceptibility and promotes tumor metastasis in nasopharyngeal carcinoma
    Xi-Xi Cheng, Guo-Wang Lin, Ya-Qing Zhou, Yi-Qi Li, Shuai He, Yang Liu, Yan-Ni Zeng, Yun-Miao Guo, Shu-Qiang Liu, Wan Peng, Pan-Pan Wei, Chun-Ling Luo, Jin-Xin Bei
    Journal of Genetics and Genomics.2024;[Epub]     CrossRef
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GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment
Jaewon Hyung, Hyung-Don Kim, Min-Hee Ryu, Young Soo Park, Meesun Moon, Yoon-Koo Kang
Cancer Res Treat. 2024;56(1):199-207.   Published online June 20, 2023
DOI: https://doi.org/10.4143/crt.2023.490
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Heterogeneous human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer may lead to a misdiagnosis of HER2 status. Accurate assessment of HER2 status is essential for optimal treatment as novel HER2-directed agents are being investigated in various clinical settings. We evaluated the usefulness of HER2 re-assessment following progression on first-line treatment in initially HER2-negative advanced gastric cancer (AGC) patients.
Materials and Methods
We enrolled 177 patients with baseline HER2-negative AGC and performed HER2 re-assessment after progression on first-line treatment from February 2012 to June 2016 at Asan Medical Center, Seoul, Korea. The re-assessed HER2 status was analyzed with baseline HER2 status and clinical characteristics.
Results
The median age was 54 years (range, 24 to 80 years), and 123 patients (69.5%) were men. Seven patients (4.0%) were HER2-positive on the re-assessment. Patients with baseline HER2 negativity confirmed by a single test (n=100) had a higher HER2-positive re-assessment rate compared to those who had repeated baseline testing (n=77) (5.0% vs. 2.6%). Among the patients with single baseline HER2 testing, the rate was higher in patients with baseline HER2 immunohistochemistry (IHC) 1+ compared to those with IHC 0 (13.4% vs. 3.6%).
Conclusion
Overall, 4.0% of patients with baseline HER2-negative AGC were HER2-positive on re-assessment, and the HER2-positive re-assessment rate was higher among patients who had a single test at baseline. HER2 re assessment may be considered for initially HER2-negative patients to determine their eligibility for HER2-directed therapy, particularly if their HER2 negativity was determined by a single test, especially if they had a single baseline HER2 IHC 1+ test.

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  • Targeting HER2 in Gastroesophageal Cancer: A New Appetite for an Old Plight
    Antonella Cammarota, Rachel Woodford, Elizabeth C. Smyth
    Drugs.2025;[Epub]     CrossRef
  • 3,351 View
  • 195 Download
  • 1 Web of Science
  • 1 Crossref
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First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer
Minkyu Jung, Jii Bum Lee, Hyo Song Kim, Woo Sun Kwon, Hyun Ok Kim, Sinyoung Kim, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Hyun Cheol Chung, Sun Young Rha
Cancer Res Treat. 2024;56(1):208-218.   Published online June 28, 2023
DOI: https://doi.org/10.4143/crt.2022.1328
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials and Methods
Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses.
Results
Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients.
Conclusion
BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.

Citations

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  • Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights
    Yu Aoki, Izuma Nakayama, Kohei Shitara
    Current Oncology Reports.2025; 27(1): 15.     CrossRef
  • Nanoparticles, a promising treatment for gastric cancer
    Di Hua, Xiexing Wu, Zebin Wu, Chunyang Fan, Jiale Wang, Wei He, Yongkang Deng, Yao Zhang, Hengxiang Shu, Meng Shen, Dechun Geng, Kai Chen
    Smart Materials in Medicine.2025;[Epub]     CrossRef
  • HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments
    Magdalena K. Scheck, Ralf D. Hofheinz, Sylvie Lorenzen
    Cancers.2024; 16(7): 1336.     CrossRef
  • Comparative Analysis of ICIs, CAR-T Therapy, and Cancer Vaccines in Immunotherapy
    Junyi Chen, Ansong Liu, Yao Yao
    Transactions on Materials, Biotechnology and Life Sciences.2024; 7: 402.     CrossRef
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Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis
Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim
Cancer Res Treat. 2024;56(1):219-237.   Published online August 11, 2023
DOI: https://doi.org/10.4143/crt.2023.340
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

Citations

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  • Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness
    Liudmila V. Spirina, Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Maxim Yu. Volkov, Sergey V. Vtorushin, Irina V. Kovaleva, Tatyana S. Klyushina, Igor O. Munkuev
    Current Issues in Molecular Biology.2024; 46(2): 1281.     CrossRef
  • SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway
    Fan Li, Xiaohong Zhang, Li Feng, Xingxing Zhang
    Frontiers in Bioscience-Landmark.2024;[Epub]     CrossRef
  • Primary mucinous cystadenocarcinoma of the breast: A case report and literature review
    Xi Cao, Yongchao Luo, Songjie Shen, Xinyu Ren
    Oncology Letters.2024;[Epub]     CrossRef
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Association between Metabolically Healthy Status and Risk of Gastrointestinal Cancer
Haozhe Cui, Fei Tian, Yongliang Chen, Xiangming Ma
Cancer Res Treat. 2024;56(1):238-246.   Published online August 2, 2023
DOI: https://doi.org/10.4143/crt.2023.539
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although obesity is associated with numerous diseases, the risks of disease may depend on metabolically healthy status. Nevertheless, it is unclear to whether metabolically healthy status affects risk of gastrointestinal (GI) cancer in general Chinese population.
Materials and Methods
A total of 114,995 participants who met the criteria were included from the Kailuan Study. The study participants were divided into four groups according to body mass index (BMI)/waist circumference (WC) and metabolic status. Incident of GI cancer (esophageal cancer, gastric cancer, liver cancer, biliary cancer, pancreatic cancer, and colorectal cancer) during 2006-2020 were confirmed by review of medical records. The Cox proportional hazard regression models were used to assess the association metabolically healthy status with the risk of GI cancer by calculating the hazard ratios (HR) and 95% confidence interval (CI).
Results
During a mean 13.76 years of follow-up, we documented 2,311 GI cancers. Multivariate Cox regression analysis showed that compared with the metabolically healthy normal-weight group, metabolically healthy obese (MHO) participants demonstrated an increased risk of developing GI cancer (HR, 1.54; 95% CI, 1.11 to 2.13) by BMI categories. However, such associations were not found for WC category. These associations were moderated by age, sex, and anatomical site of the tumor. Individuals with metabolic unhealthy normal-weight or metabolic unhealthy obesity phenotype also have an increased risk of GI cancer.
Conclusion
MHO phenotype was associated with increased risk of GI cancer. Moreover, individuals who complicated by metabolic unhealthy status have an increased risk of developing GI cancer. Hence, clinicians should consider the risk of incident GI cancer in people with abnormal metabolically healthy status and counsel them about metabolic fitness and weight control.

Citations

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  • Association between transitions in metabolic health and colorectal cancer across categories of body size phenotype: a prospective cohort study
    Qian Liu, Fei Si, Yuntao Wu, Jing Yu
    Obesity.2024; 32(10): 1948.     CrossRef
  • Gastric Cancer - Epidemiology, Modifiable and Non-modifiable Risk Factors, Challenges and Opportunities: An Updated Review
    Tajul Islam Mamun, Sabrina Younus, Md. Hashibur Rahman
    Cancer Treatment and Research Communications.2024; : 100845.     CrossRef
  • Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer
    Lankang Wang, Baoyi Ni, Jia Wang, Jilai Zhou, Junyi Wang, Jiakang Jiang, Yutong Sui, Yaoyao Tian, Feng Gao, Yufeng Lyu
    Integrative Cancer Therapies.2024;[Epub]     CrossRef
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Risk Stratification of Pancreatic Ductal Adenocarcinoma Patients Undergoing Curative-Intent Surgery after Neoadjuvant Therapy
Hyun Kyung Yang, Mi-Suk Park, Kyunghwa Han, Geonsik Eom, Yong Eun Chung, Jin-Young Choi, Seungmin Bang, Chang Moo Kang, Jinsil Seong, Myeong-Jin Kim
Cancer Res Treat. 2024;56(1):247-258.   Published online August 22, 2023
DOI: https://doi.org/10.4143/crt.2023.586
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Clinical prognostic criteria using preoperative factors were not developed for post–neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria.
Materials and Methods
Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system.
Results
One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, –0.012 to 0.142).
Conclusion
“Any degree of decrease in tumor size on CT” and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.
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Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner
Pei Cao, Weigang Zhang, Junyi Qiu, Zuxiong Tang, Xiaofeng Xue, Tingting Feng
Cancer Res Treat. 2024;56(1):259-271.   Published online August 16, 2023
DOI: https://doi.org/10.4143/crt.2022.1600
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear.
Materials and Methods
We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC.
Results
Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression.
Conclusion
Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

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  • WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways
    Fan Huang, Yuchen Wang, XiaoLi Lv, Chenda Huang
    Journal of Bioenergetics and Biomembranes.2024; 56(3): 285.     CrossRef
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Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814)
Younghee Park, Tae Hyun Kim, Kyubo Kim, Jeong Il Yu, Wonguen Jung, Jinsil Seong, Woo Chul Kim, Jin Hwa Choi, Ah Ram Chang, Bae Kwon Jeong, Byoung Hyuck Kim, Tae Gyu Kim, Jin Hee Kim, Hae Jin Park, Hyun Soo Shin, Jung Ho Im, Eui Kyu Chie
Cancer Res Treat. 2024;56(1):272-279.   Published online July 31, 2023
DOI: https://doi.org/10.4143/crt.2023.616
AbstractAbstract PDFPubReaderePub
Purpose
Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.
Materials and Methods
Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.
Results
After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.
Conclusion
Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.
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Genitourinary cancer
Clear Cell Adenocarcinoma of Urethra: Clinical and Pathologic Implications and Characterization of Molecular Aberrations
Boram Song, Seok Hyun Lee, Jeong Hwan Park, Kyung Chul Moon
Cancer Res Treat. 2024;56(1):280-293.   Published online September 11, 2023
DOI: https://doi.org/10.4143/crt.2023.577
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods
We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results
All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion
Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.

Citations

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  • Urethral clear cell adenocarcinoma in an adult female: A rare case report
    Yacob Sheiferawe Seman, Michael Teklehaimanot Abera, Fadil Nuredin Abrar, Tesfaye Kebede Legesse, Mesfin Asefa Tola, Tsiyon Nigusie Alemu
    Urology Case Reports.2025; 58: 102882.     CrossRef
  • Association between CACNA1D polymorphisms and hypospadias in a southern Chinese population
    Ye He, Binyao Li, Xinying Zhao, Lingling Pan, Yanqing Liu, Chaoting Lan, Fuming Deng, Wen Fu, Yan Zhang, Xiaoyu Zuo
    Journal of Pediatric Urology.2024; 20(3): 438.e1.     CrossRef
  • The L‐type calcium channel CaV1.3: A potential target for cancer therapy
    Xuerun Liu, Boqiang Shen, Jingyi Zhou, Juan Hao, Jianliu Wang
    Journal of Cellular and Molecular Medicine.2024;[Epub]     CrossRef
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Pediatric cancer
Ten-Year Trends of Hematopoietic Stem Cell Transplantation in Korean Pediatric Cancer from the National Health Insurance Claims Data
Hyery Kim, Hwa Jung Kim, Youngjun Jo, Su Hyun Yoon, Young Kwon Koh, Sunghan Kang, Kyung-Nam Koh, Ho Joon Im
Cancer Res Treat. 2024;56(1):294-304.   Published online September 7, 2023
DOI: https://doi.org/10.4143/crt.2023.598
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to determine the current application and survival trends of hematopoietic stem cell transplantation (HSCT) among Korean children and adolescents with cancer.
Materials and Methods
Data of patients aged < 20 years with KCD-10 (Korean Classifications of Diseases, 10th revision) C codes and specific designation codes were collected from the National Health Insurance Service database. Thirty claim codes for HSCT were included, and data from 2009 to 2019 were analyzed.
Results
The operational definition of pediatric cancer yielded an annual average of 2,000, with annual cases decreasing. In 2019, 221 HSCTs were performed, a decrease from the ten-year average of 276. Allografts outnumbered autografts with a ratio of 1.5:1. The source of allograft was bone marrow in 15% of patients in 2009; however, it substantially decreased to 3.3% in 2019. Furthermore, 70.5% of allogeneic HSCT used peripheral blood stem cell (PBSC) grafts, which increased to 89.3% by 2015. Cord blood utilization markedly decreased to 2.7% in 2018. The 5-year overall survival (OS) rate of all patients was 85.1%. Overall mortality decreased among patients who underwent recent HSCT, and they exhibited a higher 5-year OS rate.
Conclusion
In Korea, the number of pediatric patients with cancer is declining; however, the ratio of transplants to all patients remains constant. Patients who recently underwent transplantation showed better survival rates, possibly due to HSCT optimization. Korea showed a substantially greater PBSC utilization in pediatric HSCT. An in-depth examination encompassing donor relations and cause of death with a prospective registry is required in future studies.
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Hematologic malignancy
Incidence and Features of Lymphoid Proliferation and Lymphomas after Solid Organ or Hematopoietic Stem Cell Transplantation in a National Database Cohort
Seung Min Hahn, Myeongjee Lee, JongHoon Hyun, Sungmin Lim, Ji-Man Kang, Jong Gyun Ahn, Dong Jin Joo, Inkyung Jung, Kyong Ihn
Cancer Res Treat. 2024;56(1):305-313.   Published online July 18, 2023
DOI: https://doi.org/10.4143/crt.2023.647
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians.
Materials and Methods
We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD.
Results
During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2).
Conclusion
We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.
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Circulating Tumor DNA Reflects Histologic and Clinical Characteristics of Various Lymphoma Subtypes
Jin Ju Kim, Hye Min Kim, Hongkyung Kim, Soo-Jeong Kim, Seung-Tae Lee, Jong Rak Choi, Saeam Shin, Doh Yu Hwang
Cancer Res Treat. 2024;56(1):314-323.   Published online July 17, 2023
DOI: https://doi.org/10.4143/crt.2023.667
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma.
Materials and Methods
Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA.
Results
Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage.
Conclusion
Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

Citations

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  • Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
    Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
    Blood Reviews.2024; 68: 101237.     CrossRef
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Impact of T-Cell Engagers on COVID-19–Related Mortality in B-Cell Lymphoma Patients Receiving B-Cell Depleting Therapy
Chan Mi Lee, Pyoeng Gyun Choe, Chang Kyung Kang, Hyeon Jae Jo, Nam Joong Kim, Sung-Soo Yoon, Tae Min Kim, Wan Beom Park, Myoung-don Oh
Cancer Res Treat. 2024;56(1):324-333.   Published online July 6, 2023
DOI: https://doi.org/10.4143/crt.2023.738
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
B-cell depleting therapies, including T-cell engager (TCE), are increasingly used for patients with hematologic malignancies, including during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the relationship between TCE therapy and COVID-19–related outcomes among patients with COVID-19 and B-cell lymphomas receiving B-cell depleting therapy.
Materials and Methods
This retrospective cohort study included patients with B-cell lymphoma, who were admitted to Seoul Natio-nal University Hospital with COVID-19 between September 2021 and February 2023, and received B-cell depleting therapy before COVID-19 diagnosis. Multivariable logistic regression was used to identify factors associated with severe to critical COVID-19 and COVID-19–related mortality.
Results
Of 54 patients with B-cell lymphomas and COVID-19 who received B-cell depleting therapy, 14 were treated with TCE (TCE group) and 40 with rituximab (RTX group). COVID-19–related mortality was higher in the TCE group than in the RTX group (57.1% vs. 12.5%, p=0.002). In multivariable analyses, TCE therapy (adjusted odds ratio [aOR], 7.08; 95% confidence interval [CI], 1.29 to 38.76; p=0.024) and older age (aOR, 1.06; 95% CI, 1.00 to 1.13; p=0.035) were associated with severe to critical COVID-19. TCE therapy (aOR, 8.98; 95% CI, 1.48 to 54.40; p=0.017), older age (aOR, 1.13; 95% CI, 1.02 to 1.26; p=0.022), and prior bendamustine therapy (aOR, 7.78; 95% CI, 1.17 to 51.65; p=0.034) were independent risk factors for COVID-19–related mortality.
Conclusion
B-cell lymphoma patients treated with TCE had significantly worse outcomes from COVID-19 than those treated with RTX. TCE therapy should be used with caution in B-cell lymphoma patients during the COVID-19 epidemic.

Citations

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  • Long-Term Outcomes of COVID-19 and Risk Factors for Prolonged or Persistent COVID-19 in Lymphoma Patients: A Multicenter, Retrospective Cohort Study
    Jung Ah Lee, Min Han, Sangmin Ahn, Yongseop Lee, Joon-Sup Yeom, Jun Yong Choi, Nam Su Ku, Su Jin Jeong, Jung Ho Kim, Jin Seok Kim, Haerim Chung, Hyunsoo Cho, Yu Ri Kim, Jin Young Ahn
    Journal of Korean Medical Science.2024;[Epub]     CrossRef
  • Features of the T-cell immune response in patients with hematological diseases after SARS-CoV-2 infection and vaccination
    K. V. Zornikova, N. O. Ivanova, O. A. Aleshina, S. A. Sheetikov, V. D. Davydova, A. V. Bogolyubova
    Russian journal of hematology and transfusiology.2024; 69(2): 200.     CrossRef
  • Call for Balancing the Risks and Benefits of Immunotherapeutic Agents for Lymphoma during the COVID-19 Pandemic
    Chan Mi Lee, Wan Beom Park
    Infection & Chemotherapy.2024; 56(3): 406.     CrossRef
  • Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial
    Catherine Thieblemont, Yasmin H. Karimi, Herve Ghesquieres, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Wojciech Jurczak, Young Rok Do, Robin Gasiorowski, David John Lewis, Tae Min Kim, Marjolein van der Poel, Michelle Limei Poon, Tatyana Feld
    Leukemia.2024; 38(12): 2653.     CrossRef
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