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Most-cited are based on citations from 2023 ~ 2025.

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Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2020
Mee Joo Kang, Kyu-Won Jung, So Hyun Bang, Seo Hyun Choi, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo, The Community of Population-Based Regional Cancer Registries*
Cancer Res Treat. 2023;55(2):385-399.
DOI: https://doi.org/10.4143/crt.2023.447
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2020.
Materials and Methods
Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2020, with survival follow-up until December 31, 2021. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.
Results
The number of new cancer diagnoses in 2020 decreased by 9,218 cases (3.6%) compared to 2019. In 2020, newly diagnosed cancer cases and deaths from cancer were reported as 247,952 (age-standardized rate [ASR], 262.2 per 100,000) and 82,204 (ASR, 69.9 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.0% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years. The 5-year relative survival between 2016 and 2020 was 71.5%, which contributed to prevalent cases reaching over 2.2 million in 2020.
Conclusion
In 2020, the number of newly diagnosed cancer patients decreased due to the coronavirus disease 2019 pandemic, but the overall trend is on the rise. Cancer survival rates have improved over the past decades. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics. The long-term impact of the coronavirus disease 2019 pandemic on cancer statistics needs to be investigated in the future.

Citations

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Prediction of Cancer Incidence and Mortality in Korea, 2023
Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo
Cancer Res Treat. 2023;55(2):400-407.
DOI: https://doi.org/10.4143/crt.2023.448
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to report the projected cancer incidence and mortality for the year 2023 to estimate Korea’s current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2020 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2021 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2023. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend.
Results
In total, 273,076 new cancer cases and 81,818 cancer deaths are expected to occur in Korea in 2023. The most common cancer site is expected to be the lung, followed by the thyroid, breast, colon and rectum, and stomach. These five cancers are expected to represent half of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and gallbladder cancers.
Conclusion
The incidence rates for all types of cancer in Korea are estimated to gradually decrease. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.

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Original Article
Lung and Thoracic cancer
Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015
Da Som Jeon, Ho Cheol Kim, Se Hee Kim, Tae-Jung Kim, Hong Kwan Kim, Mi Hyung Moon, Kyongmin Sarah Beck, Yang-Gun Suh, Changhoon Song, Jin Seok Ahn, Jeong Eun Lee, Jeong Uk Lim, Jae Hyun Jeon, Kyu-Won Jung, Chi Young Jung, Jeong Su Cho, Yoo-Duk Choi, Seung-Sik Hwang, Chang-Min Choi, Korean Association for Lung Cancer, Korea Central Cancer Registry
Cancer Res Treat. 2023;55(1):103-111.   Published online June 20, 2022
DOI: https://doi.org/10.4143/crt.2022.264
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015.
Materials and Methods
The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020.
Results
We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non–small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%).
Conclusion
In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

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Special Article
Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2021
Eun Hye Park, Kyu-Won Jung, Nam Ju Park, Mee Joo Kang, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo, The Community of Population-Based Regional Cancer Registries
Cancer Res Treat. 2024;56(2):357-371.   Published online March 13, 2024
DOI: https://doi.org/10.4143/crt.2024.253
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021.
Materials and Methods
Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.
Results
The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per 100,000) and 82,688 (ASR, 67.6 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% from 2012 to 2015, thereafter, followed by non-significant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.8% from 2002 to 2013; 3.2% from 2013 to 2021). The 5-year relative survival between 2017 and 2021 was 72.1%, which contributed to prevalent cases reaching over 2.4 million in 2021.
Conclusion
In 2021, the number of newly diagnosed cancer patients increased as healthcare utilization recovered from the coronavirus disease 2019–related declines of 2020. Revised cancer registration guidelines expanded the registration scope, particularly for stomach and colorectal cancer. Survival rates have improved over the years, leading to a growing population of cancer survivors, necessitating a comprehensive cancer control strategy. The long-term impact of the pandemic on cancer statistics requires future investigation.

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Review Articles
Clinical Circulating Tumor DNA Testing for Precision Oncology
Hyunji Kim, Kyoung Un Park
Cancer Res Treat. 2023;55(2):351-366.
DOI: https://doi.org/10.4143/crt.2022.1026
AbstractAbstract PDFPubReaderePub
Circulating tumor DNA (ctDNA) is the portion of the cell-free DNA in the blood of cancer patients released from tumor cells via apoptosis, necrosis, or active release. From 10 mL of blood, the 4-5 mL of plasma obtained from a cancer patient contains 5-10 ng/mL of ctDNA. The plasma contains not only ctDNA of tumor origin, but also DNA from normal cells or clonal hematopoiesis. Another characteristic of ctDNA is its rapid clearance from circulation; it has a half-life of 16 minutes to 2.5 hours. Obtaining reliable results from ctDNA requires the application and approval of standardized clinical validation guidelines; however, the status of numerous ctDNA tests currently varies. The clinical use of ctDNA testing should be carefully considered based on the test’s specific needs and characteristics. Here we provide the different characteristics of ctDNA tests and information regarding their validation and approval status.

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Cellular Dormancy in Cancer: Mechanisms and Potential Targeting Strategies
Hye-Young Min, Ho-Young Lee
Cancer Res Treat. 2023;55(3):720-736.   Published online March 22, 2023
DOI: https://doi.org/10.4143/crt.2023.468
AbstractAbstract PDFPubReaderePub
Cancer is a leading cause of disease-related mortality worldwide. Drug resistance is one of the primary reasons for the failure of anticancer therapy. There are a number of underlying mechanisms for anticancer drug resistance including genetic/epigenetic modifications, microenvironmental factors, and tumor heterogeneity. In the present scenario, researchers have focused on these novel mechanisms and strategies to tackle them. Recently, researchers have recognized the ability of cancer to become dormant because of anticancer drug resistance, tumor relapse, and progression. Currently, cancer dormancy is classified into “tumor mass dormancy” and “cellular dormancy.” Tumor mass dormancy represents the equilibrium between cell proliferation and cell death under the control of blood supply and immune responses. Cellular dormancy denotes the state in which cells undergo quiescence and is characterized by autophagy, stress-tolerance signaling, microenvironmental cues, and epigenetic modifications. Cancer dormancy has been regarded as the stem of primary or distal recurrent tumor formation and poor clinical outcomes in cancer patients. Despite the insufficiency of reliable models of cellular dormancy, the mechanisms underlying the regulation of cellular dormancy have been clarified in numerous studies. A better understanding of the biology of cancer dormancy is critical for the development of effective anticancer therapeutic strategies. In this review, we summarize the characteristics and regulatory mechanisms of cellular dormancy, introduce several potential strategies for targeting cellular dormancy, and discuss future perspectives.

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Close layer
Original Articles
Head and Neck cancer
Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Hana Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn, Dongryul Oh, Myung-Ju Ahn
Cancer Res Treat. 2023;55(4):1104-1112.   Published online May 17, 2023
DOI: https://doi.org/10.4143/crt.2023.502
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect.
Results
Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1).
Conclusion
The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

Citations

Citations to this article as recorded by  
  • Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review
    Akihiro Sakai, Koji Ebisumoto, Hiroaki Iijima, Mayu Yamauchi, Daisuke Maki, Tsuyoshi Fukuzawa, Kenji Okami
    Cancer Reports.2024;[Epub]     CrossRef
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    Xiao Han, Haidong Zhang, Kai Sun, Jing Li, Wanjuan Wu, Kai Liu, Zhenkun Yu
    Frontiers in Immunology.2024;[Epub]     CrossRef
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    Marco Durante
    International Journal of Radiation Biology.2024; 100(5): 669.     CrossRef
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    Kexin Meng, Haijun Lu
    Precision Radiation Oncology.2024; 8(1): 42.     CrossRef
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    Anchi Sun, Zhiwei Xing, Rongrong Lv, Pengyuan Niu, Bao Zhao, Shiyin Ma, Hui Li
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    Rina Jiang, Mike Fritz, Syril Keena T. Que
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    Riccardo Gili, Paolo Bossi
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    Alessia Zotta, Maria Luisa Marciano, Francesco Sabbatino, Alessandro Ottaiano, Marco Cascella, Monica Pontone, Massimo Montano, Ester Calogero, Francesco Longo, Morena Fasano, Teresa Troiani, Fortunato Ciardiello, Fabiana Raffaella Rampetta, Giovanni Salz
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    Carmen Kut, Harry Quon, Xuguang Scott Chen
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Lung and Thoracic cancer
The Additive Impact of Transbronchial Cryobiopsy Using a 1.1-mm Diameter Cryoprobe on Conventional Biopsy for Peripheral Lung Nodules
Soo Han Kim, Jeongha Mok, Eun-Jung Jo, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jung Seop Eom
Cancer Res Treat. 2023;55(2):506-512.   Published online November 1, 2022
DOI: https://doi.org/10.4143/crt.2022.1008
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs).
Materials and Methods
From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022.
Results
The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm2) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm2, p < 0.001) and 1.9-mm forceps (3.7 mm2, p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications.
Conclusion
Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Citations

Citations to this article as recorded by  
  • Transbronchial lung cryobiopsy for peripheral pulmonary lesions. A narrative review
    Y. Tang, S. Tian, H. Chen, X. Li, X. Pu, X. Zhang, Y. Zheng, Y. Li, H. Huang, C. Bai
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    Mi‐Hyun Kim, Soo Han Kim, Geewon Lee, Jeongha Mok, Min Ki Lee, Ju Sun Song, Jung Seop Eom
    Respirology.2024; 29(4): 333.     CrossRef
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    Soo Han Kim, Hyun Sung Chung, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Insu Kim, Jung Seop Eom
    Cancer Research and Treatment.2024; 56(2): 464.     CrossRef
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    Ya.O. Chesalina, I.Yu. Shabalina, L.A. Semenova, I.V. Sivokozov
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    Dongil Park
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    Kazuhiro Nishiyama, Kei Morikawa, Shotaro Kaneko, Makoto Nishida, Aya Matsushima, Yoshihiro Nishi, Yu Numata, Yusuke Shinozaki, Hajime Tsuruoka, Hirotaka Kida, Hiroshi Handa, Naoki Shimada, Chie Okawa, Nobuyuki Ohike, Junki Koike, Masamichi Mineshita
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    Jung Seop Eom
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    Soo Han Kim, Jeongha Mok, Saerom Kim, Wan Ho Yoo, Eun-Jung Jo, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jung Seop Eom
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Gastrointestinal cancer
Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM/DSS-Induced Colon Cancer Mouse Model
Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Ha-Na Lee
Cancer Res Treat. 2023;55(1):196-218.   Published online July 1, 2022
DOI: https://doi.org/10.4143/crt.2022.080
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Sex hormones are known to affect the gut microbiota. Previously, we reported that endogenous and exogenous testosterone are associated with colorectal cancer (CRC) development and submucosal invasion. In the present study, we investigated whether the gut microbiota is affected by orchiectomy (ORX) and testosterone propionate (TP) administration using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model.
Materials and Methods
Gut microbiota was evaluated by means of 16S rRNA gene sequencing of stool DNA extracted from feces that were obtained at 13 weeks after AOM injection (from 22-week-old animals) and stored in a gas-generating pouch.
Results
The increase in microbial diversity (Chao1 and Phylogenetic Diversity index) and Firmicutes/Bacteroidetes (F/B) ratio upon AOM/DSS treatment in ORX mice was significantly decreased by TP supplementation. The ratio of commensal bacteria to opportunistic pathogens was lower in the TP-administered females and ORX mice than in the AOM/DSS group. Opportunistic pathogens (Mucispirillum schaedleri or Akkermansia muciniphila) were identified only in the TP group. In addition, microbial diversity and F/B ratio were higher in male controls than in female and ORX controls. Flintibacter butyricus, Ruminococcus bromii, and Romboutsia timonensis showed similar changes in the male control group as those in the female and ORX controls.
Conclusion
In conclusion, testosterone determines the dysbiosis of gut microbiota, which suggests that it plays a role in the sex-related differences in colorectal carcinogenesis.

Citations

Citations to this article as recorded by  
  • Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis
    Zihong Wu, Yuqing Huang, Renyi Zhang, Chuan Zheng, Fengming You, Min Wang, Chong Xiao, Xueke Li
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    Vineet Singh, Kanika Mahra, DaRyung Jung, Jae-Ho Shin
    Probiotics and Antimicrobial Proteins.2024; 16(5): 1744.     CrossRef
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    Jianglan Wu
    American Journal of Cancer Research.2024; 14(7): 3200.     CrossRef
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    Timur Liwinski, Matthias K. Auer, Johanna Schröder, Ina Pieknik, Christian Casar, Dorothee Schwinge, Lara Henze, Günter K. Stalla, Undine E. Lang, Alina von Klitzing, Peer Briken, Thomas Hildebrandt, Jeanne C. Desbuleux, Sarah V. Biedermann, Paul-Martin H
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    Anna Drzazga, Przemysław Bernat, Adriana Nowak, Marcin Szustak, Eliza Korkus, Edyta Gendaszewska-Darmach, Maria Koziołkiewicz
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Hematologic malignancy
Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas
Seok Jin Kim, Yeon Jeong Kim, Sang Eun Yoon, Kyung Ju Ryu, Bon Park, Donghyun Park, Duck Cho, Hyun-Young Kim, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Won Seog Kim
Cancer Res Treat. 2023;55(1):291-303.   Published online March 2, 2022
DOI: https://doi.org/10.4143/crt.2022.017
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).
Materials and Methods
After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.
Results
Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.
Conclusion
Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.

Citations

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  • Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
    Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
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    Laurence de Leval, Philippe Gaulard, Ahmet Dogan
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    Jin Ju Kim, Hyun-Young Kim, Zisun Choi, So yoon Hwang, Hansol Jeong, Jong Rak Choi, Sang Eun Yoon, Won Seog Kim, Sun-Hee Kim, Hee-Jin Kim, Sang-Yong Shin, Seung-Tae Lee, Seok Jin Kim
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    Yu-Jia Huo, Wei-Li Zhao
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    Margarita Sánchez-Beato, Miriam Méndez, María Guirado, Lucía Pedrosa, Silvia Sequero, Natalia Yanguas-Casás, Luis de la Cruz-Merino, Laura Gálvez, Marta Llanos, Juan Fernando García, Mariano Provencio
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Breast cancer
Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy
Youzhao Ma, Mingda Zhu, Jingyang Zhang, Minhao Lv, Xiuchun Chen, Zhenzhen Liu
Cancer Res Treat. 2023;55(4):1210-1221.   Published online April 4, 2023
DOI: https://doi.org/10.4143/crt.2022.1633
AbstractAbstract PDFPubReaderePub
Purpose
Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT).
Materials and Methods
The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined.
Results
Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016).
Conclusion
Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Citations

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  • Preoperative Differentiation of HER2‐Zero and HER2‐Low from HER2‐Positive Invasive Ductal Breast Cancers Using BI‐RADS MRI Features and Machine Learning Modeling
    Jiejie Zhou, Yang Zhang, Haiwei Miao, Ga Young Yoon, Jinhao Wang, Yezhi Lin, Hailing Wang, Yan‐Lin Liu, Jeon‐Hor Chen, Zhifang Pan, Min‐Ying Su, Meihao Wang
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    Mei Liu, Qin Xiang, Fengsheng Dai, Yixiao Yuan, Zhongjun Wu, Tingxiu Xiang
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    Shaorong Zhao, Yuyun Wang, Angxiao Zhou, Xu Liu, Yi Zhang, Jin Zhang
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    Sora Kang, Sung-Bae Kim
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    Neslihan Özyurt, Ali Alkan, Burcu Gülbağcı, Mustafa Seyyar, Esra Aydın, Mustafa Şahbazlar, Mehmet Türker, Oğuzcan Kınıkoğlu, Tahir Yerlikaya, Gülhan Dinç, Ali Aytaç, Ziya Kalkan, Senar Ebinç, İlkay Gültürk, Merve Keskinkılıç, Zehra Sucuoğlu İşleyen, Dilek
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    Sora Kang, So Heun Lee, Hee Jin Lee, Hyehyun Jeong, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Gyungyub Gong, Hak Hee Kim, Saebyeol Lee, Jongwon Lee, Sung-Bae Kim
    European Journal of Cancer.2023; : 112956.     CrossRef
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Special Article
Top Ten Lessons Learned from Trials in Oligometastatic Cancers
Vivian S. Tan, David A. Palma
Cancer Res Treat. 2023;55(1):5-14.   Published online December 16, 2022
DOI: https://doi.org/10.4143/crt.2022.1460
AbstractAbstract PDFPubReaderePub
Recent evidence supports the role of aggressive local treatment in the oligometastatic setting. In this review, we discuss the top 10 lessons we have learned from trials in oligometastatic cancers. Major lessons learned pertain to definitions of oligometastatic disease, outcomes, toxicity, costs, and the combination of ablative therapies with systemic therapy, including immunotherapy. Barriers to accrual for trials and upcoming phase III trials are also reviewed. These lessons may help to inform clinical practice and may be the basis for future research in the oligometastatic space.

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    Kyung Hwan Kim, Yong Chan Ahn
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    Chai Hong Rim, Won Kyung Cho, Sunmin Park, Won Sup Yoon, Dae Sik Yang
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  • Re: Toni K. Choueiri, Thomas Powles, Laurence Albiges, et al. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med 2023;388:1767–78
    Clara Cerrato, Benjamin Pradere, Maria Carmen Mir
    European Urology.2023; 84(4): e93.     CrossRef
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    Eui Kyu Chie, Chai Hong Rim, Won Kyung Cho, Yong Chan Ahn
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Original Articles
Genitourinary cancer
Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder
Hongsik Kim, Byong Chang Jeong, Joohyun Hong, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Wan Song, Hyun Hwan Sung, Jung Yong Hong, Se Hoon Park
Cancer Res Treat. 2023;55(2):636-642.   Published online October 6, 2022
DOI: https://doi.org/10.4143/crt.2022.343
AbstractAbstract PDFPubReaderePub
Purpose
The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC).
Materials and Methods
In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety.
Results
Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates.
Conclusion
Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

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  • Evaluating Neoadjuvant Immunochemotherapeutic Response for Bladder Carcinoma Using Amide Proton Transfer-Weighted MRI
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    João Queirós Coelho, Maria João Ramos, Ridhi Ranchor, Rita Pichel, Laura Guerra, Hugo Miranda, Joana Simões, Sérgio Xavier Azevedo, Joana Febra, António Araújo
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Breast cancer
PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Res Treat. 2023;55(2):531-541.   Published online September 7, 2022
DOI: https://doi.org/10.4143/crt.2022.221
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer.
Materials and Methods
We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment.
Results
Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors.
Conclusion
Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

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    Qian Ma, Bai Wei, Bi-Cheng Wang, Ganxin Wang, Xuan Zhou, Yan Wang
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    Eleonora Nicolò, Caterina Gianni, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli
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    Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
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    Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani, Monali Ray
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Sarcoma
Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single-Center Study
Xin Liu, Chengcheng Gong, Jieyun Zhang, Wanjing Feng, Yanjing Guo, Youzhou Sang, Chunmeng Wang, Yong Chen, Jian Wang, Lin Yu, Xiaowei Zhang, Zhiguo Luo
Cancer Res Treat. 2023;55(3):1001-1010.   Published online March 3, 2023
DOI: https://doi.org/10.4143/crt.2022.894
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood.
Materials and Methods
We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed.
Results
Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients.
Conclusion
Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

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  • Clinicopathological Characteristics of Inflammatory Myofibroblastic Tumor: A Single Center Retrospective Cohort Study
    Xiaoyan Si, Shafei Wu, Ruie Feng, Mengzhao Wang, Hanping Wang, Xiaotong Zhang, Li Zhang, Kaifeng Xu
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    Xingchen Li, Jie Li, Chunxiao Liang, Qing Zou
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    Jiyao Yang, Hongjin Shi, Haifeng Wang, Yidao Liu
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    Francisco Cristóbal Muñoz-Casares, Javier Martín-Broto, Pedro Cascales-Campos, Juan Torres-Melero, Irene López-Rojo, José Gómez-Barbadillo, Luis González-Bayón, Ana Sebio, César Serrano, Sara Carvalhal, Joaquim Abreu de Souza, Alexandre Souza, Guillermo F
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    Thomas Bartl, Michael Deavers, Ryan Blair Kieser, Pedro T Ramirez
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    Rafał Becht, Kajetan Kiełbowski, Justyna Żychowska, Wojciech Poncyljusz, Aleksandra Łanocha, Katarzyna Kozak, Ewa Gabrysz-Trybek, Paweł Domagała
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    Frontiers in Oncology.2024;[Epub]     CrossRef
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Gastrointestinal cancer
Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis
Ting Xu, Xicheng Wang, Ying Xin, Zhenghang Wang, Jifang Gong, Xiaotian Zhang, Yanyan Li, Congcong Ji, Yu Sun, Feilong Zhao, Depei Huang, Yuezong Bai, Jian Li, Lin Shen
Cancer Res Treat. 2023;55(2):626-635.   Published online December 23, 2022
DOI: https://doi.org/10.4143/crt.2022.1058
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC).
Materials and Methods
An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate.
Results
Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC.
Conclusion
Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

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Close layer
General
Validation and Clinical Application of ONCOaccuPanel for Targeted Next-Generation Sequencing of Solid Tumors
Moonsik Kim, Changseon Lee, Juyeon Hong, Juhee Kim, Ji Yun Jeong, Nora Jee-Young Park, Ji-Eun Kim, Ji Young Park
Cancer Res Treat. 2023;55(2):429-441.   Published online November 25, 2022
DOI: https://doi.org/10.4143/crt.2022.891
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors.
Materials and Methods
We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel.
Results
Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability–high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively.
Conclusion
ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.

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    Moonsik Kim, Jinhee Kim, An Na Seo, Ji Yun Jeong, Nora Jee-Young Park, Gun Oh Chong, Dae Gy Hong, Ji Young Park
    Pathology - Research and Practice.2023; 251: 154879.     CrossRef
  • BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy
    Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim
    Journal of Pathology and Translational Medicine.2023; 57(6): 323.     CrossRef
  • Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma
    Hyeon Yeong Jeong, Won Jun Suh, Seung Hwan Kim, Taek Min Nam, Ji Hwan Jang, Kyu Hong Kim, Seok Hyun Kim, Young Zoon Kim
    Cancers.2023; 16(1): 88.     CrossRef
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Case Report
Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient
Rui Zou, Xiao Zhou, Hailing Liu, Peng Wang, Fan Xia, Liqing Kang, Lei Yu, Depei Wu, Zhengming Jin, Changju Qu
Cancer Res Treat. 2023;55(4):1363-1368.   Published online June 14, 2023
DOI: https://doi.org/10.4143/crt.2023.371
AbstractAbstract PDFPubReaderePub
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

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    Anna Strzelec, Grzegorz Helbig
    European Journal of Haematology.2024; 112(2): 174.     CrossRef
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    Ying Zhang, Hongzhi Geng, Liangyu Zeng, Jiaqi Li, Qin Yang, Sixun Jia, Xiangping Zong, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia Li, Depei Wu
    Hematological Oncology.2024;[Epub]     CrossRef
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    Abigail V. Lee, Kevin A. Nestler, Katherine B. Chiappinelli
    Pharmacology & Therapeutics.2024; 258: 108640.     CrossRef
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    Reactions Weekly.2024; 2003(1): 302.     CrossRef
  • A systematic review of primary central nervous system lymphoma
    Lei Zhang, Qingyuan Zhang
    Holistic Integrative Oncology.2024;[Epub]     CrossRef
  • The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review
    Bibhu Prasad Satapathy, Pooja Sheoran, Rohit Yadav, Dewan Chettri, Dhruba Sonowal, Chinmayee Priyadarsini Dash, Prachi Dhaka, Vivek Uttam, Ritu Yadav, Manju Jain, Aklank Jain
    Frontiers in Immunology.2024;[Epub]     CrossRef
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    Huifang Tu, Limei Yuan, Bo Ni, Yufeng Lin, Kaiyuan Wang
    Pharmacological Research.2024; 210: 107531.     CrossRef
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Original Articles
General
Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients
Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong
Cancer Res Treat. 2023;55(4):1077-1086.   Published online June 12, 2023
DOI: https://doi.org/10.4143/crt.2022.1630
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Citations

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  • The use of patient-derived xenografts and patient-derived organoids in the search for new therapeutic regimens for pancreatic carcinoma. A review
    Emin Gayibov, Tomáš Sychra, Alžběta Spálenková, Pavel Souček, Martin Oliverius
    Biomedicine & Pharmacotherapy.2025; 182: 117750.     CrossRef
  • PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
    Bomin Ku, David Eisenbarth, Seonguk Baek, Tae-Keun Jeong, Ju-Gyeong Kang, Daehee Hwang, Myung-Giun Noh, Chan Choi, Sungwoo Choi, Taejun Seol, Hail Kim, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong, Dae-Sik Lim
    Cell Reports Medicine.2024; 5(3): 101461.     CrossRef
  • Establishment and Advancement of Pancreatic Organoids
    Dong Hyeon Lee
    Keimyung Medical Journal.2024; 43(1): 3.     CrossRef
  • Organoid as a promising tool for primary liver cancer research: a comprehensive review
    Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
    Cell & Bioscience.2024;[Epub]     CrossRef
  • The use of organoids in creating immune microenvironments and treating gynecological tumors
    Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • The pros and cons of mechanical dissociation and enzymatic digestion in patient-derived organoid cultures for solid tumor
    Jing Ren, Mengli Liu, Mingjie Rong, Xuan Zhang, Gang Wang, Yihan Liu, Haijun Li, Shichao Duan
    Cell Organoid.2024;[Epub]     CrossRef
  • Organoid: Bridging the gap between basic research and clinical practice
    Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
    Cancer Letters.2023; 572: 216353.     CrossRef
  • 5,171 View
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Lung and Thoracic cancer
Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study
Taeyun Kim, Tae Won Jang, Chang Min Choi, Mi-Hyun Kim, Sung Yong Lee, Yoon Soo Chang, Kye Young Lee, Seung Joon Kim, Sei Hoon Yang, Jeong Seon Ryu, Jeong Eun Lee, Shin Yup Lee, Chan Kwon Park, Sang Hoon Lee, Seung Hun Jang, Seong Hoon Yoon, Hyung-Joo Oh
Cancer Res Treat. 2023;55(4):1152-1170.   Published online May 19, 2023
DOI: https://doi.org/10.4143/crt.2023.493
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group).
Materials and Methods
In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes.
Results
The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5).
Conclusion
This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Citations

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  • KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer
    Jae-Sun Choi, Hye-Min Kang, Kiyong Na, Jiwon Kim, Tae-Woo Kim, Junyang Jung, Heejin Lim, Hyewon Seo, Seung Hyeun Lee
    Tuberculosis and Respiratory Diseases.2025; 88(1): 138.     CrossRef
  • A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam
    Cam Phuong Pham, Thi Thai Hoa Nguyen, Anh Tu Do, Tuan Khoi Nguyen, Thi Anh Thu Hoang, Tuan Anh Le, Dinh Thy Hao Vuong, Dac Nhan Tam Nguyen, Van Khiem Dang, Thi Oanh Nguyen, Van Luan Pham, Minh Hai Nguyen, Thi Huyen Trang Vo, Hung Kien Do, Ha Thanh Vu, Thi
    BMC Cancer.2024;[Epub]     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
  • Serum Concentrations of IGF-1R, ERK2, and EGFR and Their Clinical Significance in Patients with Neuroendocrine Tumors
    Roksana Duszkiewicz, Janusz Strzelczyk, Elżbieta Chełmecka, Joanna Katarzyna Strzelczyk
    Applied Sciences.2024; 14(16): 6998.     CrossRef
  • Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs
    Hsu-Yuan Chen, Chia-Hung Chen, Wei-Chih Liao, Yu-Chao Lin, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng, Chih-Yen Tu
    BMC Pulmonary Medicine.2024;[Epub]     CrossRef
  • Osimertinib as Second- and ≥Third-Line Treatment in Advanced and Recurrence EGFR-Mutant NSCLC Patients Harboring Acquired T790M Mutation
    Mu-Han Peng, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Gee-Chen Chang, Tsung-Ying Yang
    Cancers.2024; 16(24): 4174.     CrossRef
  • Effectiveness of first-line anticancer treatment may predict treatment response in further lines in stage III/IV patients with non-small cell lung cancer
    Monika Bratova, Jana Skrickova, Magda Matusikova, Karolina Hrabcova, Libor Havel, Leona Koubkova, Michal Hrnciarik, Jana Krejci, Ondrej Fischer, Martin Svaton, Kristian Brat
    Journal of Cancer Research and Clinical Oncology.2023; 149(19): 17123.     CrossRef
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Gastrointestinal cancer
Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer
Dae-Won Lee, Yoojoo Lim, Hwang-Phill Kim, Su Yeon Kim, Hanseong Roh, Jun-Kyu Kang, Kyung‑Hun Lee, Min Jung Kim, Seung-Bum Ryoo, Ji Won Park, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim
Cancer Res Treat. 2023;55(3):927-938.   Published online March 7, 2023
DOI: https://doi.org/10.4143/crt.2023.268
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib.
Materials and Methods
In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes.
Results
A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly.
Conclusion
Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

Citations

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  • A Systematic Review and Meta-Analysis of the Efficacy and Safety of Regorafenib in the Treatment of Metastatic Colorectal Cancer
    Bingjun Liang, Ming Tang, Chao Huang, Yidian Yang, Yue He, Shengrong Liao, Weizeng Shen
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • Adjuvant therapy for stage IIB + IIC melanoma
    Parisa Malekzadeh, Mary S. Brady
    Journal of Surgical Oncology.2024; 129(1): 91.     CrossRef
  • Variant allele frequency in circulating tumor DNA correlated with tumor disease burden and predicted outcomes in patients with advanced breast cancer
    Jianxin Zhong, Hanfang Jiang, Xiaoran Liu, Hao Liao, Feng Xie, Bin Shao, Shidong Jia, Huiping Li
    Breast Cancer Research and Treatment.2024; 204(3): 617.     CrossRef
  • Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer
    Tetsuo Ishizaki, Masahiro Sugimoto, Yu Kuboyama, Junichi Mazaki, Kenta Kasahara, Tomoya Tago, Ryutaro Udo, Kenichi Iwasaki, Yutaka Hayashi, Yuichi Nagakawa
    Journal of Clinical Medicine.2024; 13(17): 5202.     CrossRef
  • Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
    Jing Wu, Shilong Zhang, Shan Yu, Guo An, Yi Wang, Yiyi Yu, Li Liang, Yan Wang, Xiaojing Xu, YanShi Xiong, Di Shao, Zhun Shi, Nannan Li, Jingyuan Wang, Dawei Jin, Tianshu Liu, Yuehong Cui
    Nature Communications.2024;[Epub]     CrossRef
  • Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
    Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
    International Journal of Cancer.2023; 153(3): 571.     CrossRef
  • A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy
    Karen Gambaro, Maud Marques, Suzan McNamara, Mathilde Couetoux du Tertre, Cyrla Hoffert, Archana Srivastava, Anna Schab, Thierry Alcindor, Adrian Langleben, Lucas Sideris, Mahmoud Abdelsalam, Mustapha Tehfe, Felix Couture, Gerald Batist, Petr Kavan
    International Journal of Molecular Sciences.2023; 25(1): 43.     CrossRef
  • 4,897 View
  • 258 Download
  • 7 Web of Science
  • 7 Crossref
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Lung and Thoracic cancer
Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer
Jang Ho Lee, Eun Young Kim, Cheol-Kyu Park, Shin Yup Lee, Min ki Lee, Seong-Hoon Yoon, Jeong Eun Lee, Sang Hoon Lee, Seung Joon Kim, Sung Yong Lee, Jun Hyeok Lim, Tae-Won Jang, Seung Hun Jang, Kye Young Lee, Seung Hyeun Lee, Sei Hoon Yang, Dong Won Park, Chan Kwon Park, Hye Seon Kang, Chang Dong Yeo, Chang-Min Choi, Jae Cheol Lee
Cancer Res Treat. 2023;55(1):112-122.   Published online July 19, 2022
DOI: https://doi.org/10.4143/crt.2022.381
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Citations

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  • The importance of re-biopsy in the era of molecular therapy for lung cancer
    Nensi Lalic, Daliborka Bursac, Marko Bojovic, Marko Nemet, Ivan Ergelasev
    Srpski arhiv za celokupno lekarstvo.2024; 152(3-4): 209.     CrossRef
  • 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
  • Real‐world study of lazertinib as second‐line or greater treatment in advanced non‐small cell lung cancer
    Jeong Uk Lim, Kyuhwan Kim, Kyu Yean Kim, Hye Seon Kang, Ah. Young Shin, Chang Dong Yeo, Sung Kyoung Kim, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim
    Thoracic Cancer.2024; 15(19): 1513.     CrossRef
  • Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control
    Ha-Lim Jeon, Meesong Kwak, Sohee Kim, Hye-Yeon Yu, Ju-Young Shin, Hyun Ae Jung
    Scientific Reports.2024;[Epub]     CrossRef
  • A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations
    Eunbin Kwag, Soo-Dam Kim, Seong-Hoon Shin, Chulho Oak, So-Jung Park, Jun-Yong Choi, Seong Hoon Yoon, In-Cheol Kang, Mi-Kyung Jeong, Hyun Woo Lee, Sun-Hwi Bang, Ji Woong Son, Sanghun Lee, Seung Joon Kim, Hwa-Seung Yoo
    Integrative Cancer Therapies.2024;[Epub]     CrossRef
  • Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
    Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study
    Qing Zhou, He-Long Zhang, Li-Yan Jiang, Yuan-Kai Shi, Yuan Chen, Jin-Ming Yu, Cai-Cun Zhou, Yong He, Yan-Ping Hu, Zong-An Liang, Yue-Yin Pan, Wen-Lei Zhuo, Yong Song, Gang Wu, Gong-Yan Chen, You Lu, Cui-Ying Zhang, Yi-Ping Zhang, Ying Cheng, Shun Lu, Chan
    Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10771.     CrossRef
  • 6,741 View
  • 323 Download
  • 9 Web of Science
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Close layer
General
Adherence to Cancer Prevention Guidelines and Cancer Incidence and Mortality: A Population-Based Cohort Study
Jin-Kyoung Oh, Minji Han, Byungmi Kim, Eun Young Park
Cancer Res Treat. 2023;55(1):15-27.   Published online March 22, 2022
DOI: https://doi.org/10.4143/crt.2021.1031
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to estimate the risk of cancer incidence and mortality according to adherence to lifestyle-related cancer prevention guidelines.
Materials and Methods
Men and women who participated in the general health screening program in 2002 and 2003 provided by the National Health Insurance Service were included (n=8,325,492). Self-reported smoking, alcohol consumption, and physical activity habits and directly measured body mass index were collected. The participants were followed up until the date of cancer onset or death or 31 December 2018. The Cox proportional hazard model was used to evaluate the hazard ratio (HR) for cancer incidence and mortality according to different combinations of lifestyle behaviors.
Results
Only 6% of men and 15% of women engaged in healthy behavior at baseline, such as not smoking, not drinking alcohol, being moderately or highly physically active, and within a normal body mass index range. Compared to the best combination of healthy lifestyle behaviors, the weak and moderate associations with increased all cancer incidence (HR < 1.7) and mortality (HR < 2.5) were observed in those with heavy alcohol consumption and in former or current smokers. HRs of cancer mortality were significantly increased among current smokers in most combinations.
Conclusion
Compared to full adherence to cancer prevention recommendations, unhealthy behaviors increase cancer risk. As few people meet these recommendations, there is a great opportunity for cancer prevention.

Citations

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  • Increased risk of cardiovascular disease among kidney cancer survivors: a nationwide population-based cohort study
    Minji Jung, Eunjung Choo, Shufeng Li, Zhengyi Deng, Jinhui Li, Mingyi Li, Satvir Basran, Sukhyang Lee, Marvin E. Langston, Benjamin I. Chung
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Cancer survivors’ adherence to the American cancer society and American institute of cancer research dietary guidelines in Lebanon
    Jana Jabbour, Remie El Helou, Ruba Hadla, Riwa Azar, Maria Mezher, Farah Naja, Sally Temraz
    BMC Public Health.2024;[Epub]     CrossRef
  • Longitudinal Trends of Comorbidities and Survival Among Kidney Cancer Patients in Asian Population
    Minji Jung, Eunjung Choo, Jinhui Li, Zhengyi Deng, Marvin E. Langston, Sukhyang Lee, Benjamin I. Chung
    Cancer Medicine.2024;[Epub]     CrossRef
  • Combinations of lifestyle behaviors and cancer risk among Korean adults
    Ngoc Minh Luu, Thi Tra Bui, Thi Phuong Thao Tran, Thi Huyen Trang Nguyen, Jin-Kyoung Oh
    Scientific Reports.2023;[Epub]     CrossRef
  • Individual and joint effect of socioeconomic status and lifestyle factors on cancer in Korea
    Chi Lan Tran, Kui Son Choi, Sun‐Young Kim, Jin‐Kyoung Oh
    Cancer Medicine.2023; 12(16): 17389.     CrossRef
  • Tumorkachexie: die Bedeutung von Ernährung und Bewegung in der Onkologie
    Yurdagül Zopf, Hans Joachim Herrmann, Dejan Reljic, Luisa Marie Hardt
    Zeitschrift für Komplementärmedizin.2023; 15(06): 12.     CrossRef
  • Adherence to the World Cancer Research Fund/American Institute for Cancer Research and Korean Cancer Prevention Guidelines and cancer risk: a prospective cohort study from the Health Examinees-Gem study
    Jeeyoo Lee, Aesun Shin, Woo-Kyoung Shin, Ji-Yeob Choi, Daehee Kang, Jong-Koo Lee
    Epidemiology and Health.2023; 45: e2023070.     CrossRef
  • 6,425 View
  • 279 Download
  • 5 Web of Science
  • 7 Crossref
Close layer
Gastrointestinal cancer
ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer
Sung Hwan Lee, Jaekyung Cheon, Seoyoung Lee, Beodeul Kang, Chan Kim, Hyo Sup Shim, Young Nyun Park, Sanghoon Jung, Sung Hoon Choi, Hye Jin Choi, Choong-kun Lee, Hong Jae Chon
Cancer Res Treat. 2023;55(4):1291-1302.   Published online May 3, 2023
DOI: https://doi.org/10.4143/crt.2022.1450
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC.
Materials and Methods
Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines.
Results
193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells.
Conclusion
Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

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    Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
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Development and Validation of Models to Predict Lymph Node Metastasis in Early Gastric Cancer Using Logistic Regression and Gradient Boosting Machine Methods
Hae Dong Lee, Kyung Han Nam, Cheol Min Shin, Hye Seung Lee, Young Hoon Chang, Hyuk Yoon, Young Soo Park, Nayoung Kim, Dong Ho Lee, Sang-Hoon Ahn, Hyung-Ho Kim
Cancer Res Treat. 2023;55(4):1240-1249.   Published online March 21, 2023
DOI: https://doi.org/10.4143/crt.2022.1330
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
To identify important features of lymph node metastasis (LNM) and develop a prediction model for early gastric cancer (EGC) using a gradient boosting machine (GBM) method.
Materials and Methods
The clinicopathologic data of 2556 patients with EGC who underwent gastrectomy were used as training set and the internal validation set (set 1) at a ratio of 8:2. Additionally, 548 patients with EGC who underwent endoscopic submucosal dissection (ESD) as the initial treatment were included in the external validation set (set 2). The GBM model was constructed, and its performance was compared with that of the Japanese guidelines.
Results
LNM was identified in 12.6% (321/2556) of the gastrectomy group (training set & set 1) and 4.3% (24/548) of the ESD group (set 2). In the GBM analysis, the top five features that most affected LNM were lymphovascular invasion, depth, differentiation, size, and location. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristics of set 1 were 0.566, 0.922, 0.516, and 0.867, while those of set 2 were 0.810, 0.958, 0.803, and 0.944, respectively. When the sensitivity of GBM was adjusted to that of Japanese guidelines (beyond the expanded criteria in set 1 [0.922] and eCuraC-2 in set 2 [0.958]), the specificities of GBM in sets 1 and 2 were 0.516 (95% confidence interval, 0.502-0.523) and 0.803 (0.795-0.805), while those of the Japanese guidelines were 0.502 (0.488-0.509) and 0.788 (0.780-0.790), respectively.
Conclusion
The GBM model showed good performance comparable with the eCura system in predicting LNM risk in EGCs.

Citations

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  • Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach
    Y. Zou, Q. Mao, Z. Zhao, X. Zhou, Y. Pan, Z. Zuo, W. Zhang
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    Rui Morais, Diogo Libanio, João Santos-Antunes
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    Minoru Kato, Yoshito Hayashi, Ryotaro Uema, Takashi Kanesaka, Shinjiro Yamaguchi, Akira Maekawa, Takuya Yamada, Masashi Yamamoto, Shinji Kitamura, Takuya Inoue, Shunsuke Yamamoto, Takashi Kizu, Risato Takeda, Hideharu Ogiyama, Katsumi Yamamoto, Kenji Aoi,
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  • The Application of Artificial Intelligence to Cancer Research: A Comprehensive Guide
    Amin Zadeh Shirazi, Morteza Tofighi, Alireza Gharavi, Guillermo A. Gomez
    Technology in Cancer Research & Treatment.2024;[Epub]     CrossRef
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    Ahao Wu, Tengcheng Hu, Chao Lai, Qingwen Zeng, Lianghua Luo, Xufeng Shu, Pan Huang, Zhonghao Wang, Zongfeng Feng, Yanyan Zhu, Yi Cao, Zhengrong Li
    Cancer Medicine.2024;[Epub]     CrossRef
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Lung and Thoracic cancer
MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis
Yang Yang, Rongfang Qiu, Qiaoyou Weng, Ziwei Xu, Jingjing Song, Siyu Zhao, Miaomiao Meng, Dengke Zhang, Chunli Kong, Hailin Wang, Min Xu, Zhongwei Zhao, Jiansong Ji
Cancer Res Treat. 2023;55(3):778-803.   Published online January 26, 2023
DOI: https://doi.org/10.4143/crt.2022.1042
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

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  • Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer
    Linxiang Zhang, Xueying Zhang, Yan Shi, Yuhan Ni, Jiaojiao Fei, Zhixin Jin, Wenjuan Li, Xiaojing Wang, Nan Wu
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    Kiavash Hushmandi, Seyed Hassan Saadat, Seyedalireza Mirilavasani, Salman Daneshi, Amir Reza Aref, Noushin Nabavi, Rasoul Raesi, Afshin Taheriazam, Mehrdad Hashemi
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Gastrointestinal cancer
Anti–PD-L1 Antibody and/or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model
Chin-Hee Song, Nayoung Kim, Ryoung Hee Nam, Soo In Choi, Jae Young Jang, Jina Choi, Ha-Na Lee
Cancer Res Treat. 2023;55(3):894-909.   Published online January 9, 2023
DOI: https://doi.org/10.4143/crt.2022.1427
AbstractAbstract PDFPubReaderePub
Purpose
17β-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti–PD-L1 and/or estrogen treatment in MC38 colon cancer model.
Materials and Methods
A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti–PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition.
Results
At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti–PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti–PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti–PD-L1 group.
Conclusion
Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti–PD-L1 might contribute to treatment of MC38 colon cancer.

Citations

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  • Distribution and roles of Ligilactobacillus murinus in hosts
    Zhou Chuandong, Jicong Hu, Jiawen Li, Yuting Wu, Chan Wu, Guanxi Lai, Han Shen, Fenglin Wu, Changli Tao, Song Liu, Wenfeng Zhang, Hongwei Shao
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    Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
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Lung and Thoracic cancer
Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing
Beung-Chul Ahn, Ye-Jeong Han, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim
Cancer Res Treat. 2023;55(2):488-497.   Published online November 9, 2022
DOI: https://doi.org/10.4143/crt.2022.359
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents.
Materials and Methods
Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed.
Results
The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively.
Conclusion
Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

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  • Prognostic factors in non-metastatic HER2 ‘low’ and HER2 ‘negative’ breast cancer: single institute experience
    Alper Türkel, Mutlu Doğan, Elif Sertesen, Cengiz Karaçin, Sultan Çiğdem Irkkan, Öztürk Ateş
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    Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
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    David J. H. Bian, Sara F. Cohen, Anna-Maria Lazaratos, Nathaniel Bouganim, Matthew Dankner
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Gastrointestinal cancer
Universal Screening for Lynch Syndrome Compared with Pedigree-Based Screening: 10-Year Experience in a Tertiary Hospital
Min Hyun Kim, Duck-Woo Kim, Hye Seung Lee, Su Kyung Bang, Soo Hyun Seo, Kyung Un Park, Heung-Kwon Oh, Sung-Bum Kang
Cancer Res Treat. 2023;55(1):179-188.   Published online March 21, 2022
DOI: https://doi.org/10.4143/crt.2021.1512
AbstractAbstract PDFPubReaderePub
Purpose
Universal screening for Lynch syndrome (LS) refers to routine tumor testing for microsatellite instability (MSI) among all patients with colorectal cancer (CRC). Despite its widespread adoption, real-world data on the yield is lacking in Korean population. We studied the yield of adopting universal screening for LS in comparison with pedigree-based screening in a tertiary center.
Materials and Methods
CRC patients from 2007-2018 were reviewed. Family histories were obtained and were evaluated for hereditary nonpolyposis colorectal cancer (HNPCC) using Amsterdam II criteria. Tumor testing for MSI began in 2007 and genetic testing was offered using all available clinicopathologic data. Yield of genetic testing for LS was compared for each approach and step.
Results
Of the 5,520 patients, tumor testing was performed in 4,701 patients (85.2%) and family histories were obtained from 4,241 patients (76.8%). Hereditary CRC (LS or HNPCC) was present in 69 patients (1.3%). MSI-high was present in 6.9%, and 25 patients had confirmed LS. Genetic testing was performed in 41.2% (47/114) of MSI-high patients, out of which 40.4% (19/47) were diagnosed with LS. There were six additional LS patients found outside of tumor testing. For pedigree-based screening, Amsterdam II criteria diagnosed 55 patients with HNPCC. Fifteen of these patients underwent genetic testing, and 11 (73.3%) were diagnosed with LS. Two patients without prior family history were diagnosed with LS and relied solely on tumor testing results.
Conclusion
Despite widespread adoption of routine tumor testing for MSI, this is not a fail-safe approach to screen all LS patients. Obtaining a thorough family history in combination with universal screening provides a more comprehensive ‘universal’ screening method for LS.

Citations

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  • Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment
    Hyo Seon Ryu, Hyun Jung Kim, Woong Bae Ji, Byung Chang Kim, Ji Hun Kim, Sung Kyung Moon, Sung Il Kang, Han Deok Kwak, Eun Sun Kim, Chang Hyun Kim, Tae Hyung Kim, Gyoung Tae Noh, Byung-Soo Park, Hyeung-Min Park, Jeong Mo Bae, Jung Hoon Bae, Ni Eun Seo, Cha
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    Miguel Angel Trujillo-Rojas, María de la Luz Ayala-Madrigal, Melva Gutiérrez-Angulo, Anahí González-Mercado, José Miguel Moreno-Ortiz
    Hereditary Cancer in Clinical Practice.2023;[Epub]     CrossRef
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    Antonio Nolano, Alessia Medugno, Silvia Trombetti, Raffaella Liccardo, Marina De Rosa, Paola Izzo, Francesca Duraturo
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Review Article
Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers
Yongjun Cha, Sheehyun Kim, Sae-Won Han
Cancer Res Treat. 2023;55(2):367-384.
DOI: https://doi.org/10.4143/crt.2023.446
AbstractAbstract PDFPubReaderePub
Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

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    Champica Nicholas, Andrea Beharry, Anna M. Bendzsak, Kassandra R. Bisson, Keith Dadson, Shaan Dudani, Marco Iafolla, Kashif Irshad, Kirstin Perdrizet, William Raskin, Raviya Singh, David Chun Cheong Tsui, Xin Wang, Ching Yeung, Parneet K. Cheema, Brandon
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    Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
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    Isaac Garcia-Murillas, Rosalind J. Cutts, Giselle Walsh-Crestani, Edward Phillips, Sarah Hrebien, Kathryn Dunne, Kally Sidhu, Robert Daber, Benjamin Hubert, Chiharu Graybill, Peter M. DeFord, David J. Wooten, Jianhua Zhao, Rachel E. Ellsworth, Stephen R.
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