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Volume 55(3); July 2023
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Review Articles
Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy
Gyu Sang Yoo, Chai Hong Rim, Won Kyung Cho, Jae-Uk Jeong, Eui Kyu Chie, Hyeon-Min Cho, Jun Won Um, Yong Chan Ahn, Jong Hoon Lee, on behalf of Korean Cancer Association Oligometastasis Working Group
Cancer Res Treat. 2023;55(3):707-719.   Published online March 15, 2023
DOI: https://doi.org/10.4143/crt.2022.1599
AbstractAbstract PDFPubReaderePub
Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist’s and surgeon’s perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.
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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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  • Design, synthesis and antitumor activity of 4-arylamine substituted pyrimidine derivatives as noncovalent EGFR inhibitors overcoming C797S mutation
    Yaqing Zuo, Zhiwu Long, Rongrong Li, Yi Le, Silong Zhang, Huan He, Longjia Yan
    European Journal of Medicinal Chemistry.2024; 265: 116106.     CrossRef
  • Unveiling the role of cellular dormancy in cancer progression and recurrence
    Evelyne Collignon
    Current Opinion in Oncology.2024; 36(2): 74.     CrossRef
  • Mitophagy-Mediated Tumor Dormancy Protects Cancer Cells from Chemotherapy
    Yunqing Sun, Yang Chen, Zhenan Liu, Jingjing Wang, Junqiang Bai, Ruixue Du, Mingshu Long, Zhengjun Shang
    Biomedicines.2024; 12(2): 305.     CrossRef
  • Survival strategies: How tumor hypoxia microenvironment orchestrates angiogenesis
    Mengrui Yang, Yufeng Mu, Xiaoyun Yu, Dandan Gao, Wenfeng Zhang, Ye Li, Jingyang Liu, Changgang Sun, Jing Zhuang
    Biomedicine & Pharmacotherapy.2024; 176: 116783.     CrossRef
  • Colorectal cancer and dormant metastases: Put to sleep or destroy?
    Marina A Senchukova
    World Journal of Gastrointestinal Oncology.2024; 16(6): 2304.     CrossRef
  • Tumor Dormancy and Reactivation: The Role of Heat Shock Proteins
    Haneef Ahmed Amissah, Stephanie E. Combs, Maxim Shevtsov
    Cells.2024; 13(13): 1087.     CrossRef
  • Advancements in Understanding the Hide-and-Seek Strategy of Hibernating Breast Cancer Cells and Their Implications in Oncology from a Broader Perspective: A Comprehensive Overview
    Aiman Al-Ruwishan, Bushra Amer, Ahmed Salem, Ahmed Abdi, Namoonga Chimpandu, Abdelmonem Esa, Alexandros Melemenis, Muhammad Zubair Saleem, Roselit Mathew, Yaser Gamallat
    Current Issues in Molecular Biology.2024; 46(8): 8340.     CrossRef
  • Prospects of compounds of herbal plants as anticancer agents: a comprehensive review from molecular pathways
    Putri Cahaya Situmorang, Syafruddin Ilyas, Sony Eka Nugraha, Rony Abdi Syahputra, Nik Mohd Afizan Nik Abd Rahman
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Deciphering genetic and nongenetic factors underlying tumour dormancy: insights from multiomics analysis of two syngeneic MRD models of melanoma and leukemia
    Marie-Océane Laguillaumie, Sofia Titah, Aurélie Guillemette, Bernadette Neve, Frederic Leprêtre, Pascaline Ségard, Faruk Azam Shaik, Dominique Collard, Jean-Claude Gerbedoen, Léa Fléchon, Lama Hasan Bou Issa, Audrey Vincent, Martin Figeac, Shéhérazade Seb
    Biological Research.2024;[Epub]     CrossRef
  • Deciphering Dormant Cells of Lung Adenocarcinoma: Prognostic Insights from O-glycosylation-Related Tumor Dormancy Genes Using Machine Learning
    Chenfei Dong, Yang Liu, Suli Chong, Jiayue Zeng, Ziming Bian, Xiaoming Chen, Sairong Fan
    International Journal of Molecular Sciences.2024; 25(17): 9502.     CrossRef
  • Outcomes in ischemic and hemorrhagic stroke patients with cancer: The Japan Stroke Data Bank
    Takeshi Yoshimoto, Kazunori Toyoda, Sohei Yoshimura, Shinichi Wada, Masafumi Ihara, Junji Miyazaki, Kaori Miwa, Tomohide Yoshie, Yoshihiro Miyamoto, Shotai Kobayashi, Kazuo Minematsu, Masatoshi Koga
    Journal of the Neurological Sciences.2024; 466: 123234.     CrossRef
  • Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer – a systematic review and meta-analysis
    Longlan Zhou, Lin Zhang
    Journal of Chemotherapy.2024; : 1.     CrossRef
  • Apolipoproteins have a major role in cellular tumor dormancy in triple negative breast cancer: In-silico study
    Zaynab El-Gammal, Usama Bakry, Ahmed F. El-Sayed, Toka A. Ahmed, Gehad Atef Oura, Shimaa E. Elshenawy, Nagwa El-Badri, Amin F. Romany, Khaled Amer, Tarek Elnagdy, Osama Mahmoud Azmy, Tarek Taha Ahmed Ali
    Scientific Reports.2024;[Epub]     CrossRef
  • Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
    Wurood A. Shihab, Ammar A. Razzak Kubba, Lubna H. Tahtamouni, Khaled M. Saleh, Mai F. AlSakhen, Sana I. Kanaan, Abdulrahman M. Saleh, Salem R. Yasin
    Current Medicinal Chemistry.2024; 31(38): 6336.     CrossRef
  • Navigating the Complexity of Resistance in Lung Cancer Therapy: Mechanisms, Organoid Models, and Strategies for Overcoming Treatment Failure
    Da Hyun Kang, Jisoo Lee, Subin Im, Chaeuk Chung
    Cancers.2024; 16(23): 3996.     CrossRef
  • The changing treatment landscape of EGFR-mutant non-small-cell lung cancer
    Fei Zhou, Haoyue Guo, Yang Xia, Xiuning Le, Daniel S. W. Tan, Suresh S. Ramalingam, Caicun Zhou
    Nature Reviews Clinical Oncology.2024;[Epub]     CrossRef
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Original Articles
General
Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers
Jae Sik Kim, Joo Ho Lee, Sang-Rok Jeon, Yongsub Kim, Seung Hyuck Jeon, Hong-Gyun Wu
Cancer Res Treat. 2023;55(3):737-745.   Published online January 4, 2023
DOI: https://doi.org/10.4143/crt.2022.1414
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)–overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen.
Materials and Methods
Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription–quantitative polymerase chain reaction.
Results
We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1, and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment.
Conclusion
The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Citations

Citations to this article as recorded by  
  • Uncovering the bookshelves of CRISPR-based libraries: Advances and applications in cancer studies
    Nathalia Quintero-Ruiz, Wesley de Lima Oliveira, Marcos Vinicius Esteca, Daniela Campos Granato, Fernando Moreira Simabuco
    Critical Reviews in Oncology/Hematology.2024; 196: 104287.     CrossRef
  • CRISPR-Cas and CRISPR-based screening system for precise gene editing and targeted cancer therapy
    Mingming Qin, Chunhao Deng, Liewei Wen, Guoqun Luo, Ya Meng
    Journal of Translational Medicine.2024;[Epub]     CrossRef
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Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study
Yae Jee Baek, Youn-Jung Lee, So Ra Park, Kyoo Hyun Kim, Seung-Hoon Beom, Choong-kun Lee, Sang Joon Shin, Sun Young Rha, Sinyoung Kim, Kyoung Hwa Lee, Jung Ho Kim, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Minkyu Jung, Jin Young Ahn
Cancer Res Treat. 2023;55(3):746-757.   Published online February 9, 2023
DOI: https://doi.org/10.4143/crt.2022.1541
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs).
Materials and Methods
Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer.
Results
Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs.
Conclusion
CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Citations

Citations to this article as recorded by  
  • Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study
    Hong-Hong Liu, Yunbo Xie, Bao-Peng Yang, Huan-Yue Wen, Peng-Hui Yang, Jin-E Lu, Yan Liu, Xi Chen, Meng-Meng Qu, Yang Zhang, Wei-Guo Hong, Yong-Gang Li, Junliang Fu, Fu-Sheng Wang
    Signal Transduction and Targeted Therapy.2024;[Epub]     CrossRef
  • Immune response of COVID-19 vaccines in solid cancer patients: A meta-analysis
    Tiantian Hua, Ru Fan, Yang Fan, Feng Chen
    Human Vaccines & Immunotherapeutics.2024;[Epub]     CrossRef
  • A Three-Dose mRNA COVID-19 Vaccine Regime Produces Both Suitable Immunogenicity and Satisfactory Efficacy in Patients with Solid Cancers
    Urska Janzic, Urska Bidovec-Stojkovic, Peter Korosec, Katja Mohorcic, Loredana Mrak, Marina Caks, Maja Ravnik, Erik Skof, Matija Rijavec
    Vaccines.2023; 11(6): 1017.     CrossRef
  • Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients
    Christopher W. Dukes, Marine Potez, Jeffrey Lancet, Barbara J. Kuter, Junmin Whiting, Qianxing Mo, Brett Leav, Haixing Wang, Julie S. Vanas, Christopher L. Cubitt, Kimberly Isaacs-Soriano, Kayoko Kennedy, Julie Rathwell, Julian Diaz Cobo, Wesley O’Nan, Br
    Vaccines.2023; 12(1): 13.     CrossRef
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Recent Trends of Medical Expenses Associated with Radiation Therapy in Korea Based on HIRA Big Data
Jeong Eun Lee, Kyungmi Yang, Yong Chan Ahn, Won Park, Seung Jae Huh
Cancer Res Treat. 2023;55(3):758-765.   Published online January 30, 2023
DOI: https://doi.org/10.4143/crt.2022.389
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to determine the trends in the use of radiotherapy (RT) and the expenses associated with it in South Korea.
Materials and Methods
The statistical data of the claims and reimbursement records provided on the Health and Insurance Review and Assessment Service website were utilized. This included information such as the number of patients, fractions, medical expenses according to treatment codes, in/outpatient, sex, age, and regions of hospitals. We analyzed data from 2016 to 2020.
Results
With a growing RT infrastructure and an increase in the number of radiation oncologists, the expenses for RT were 605.5 million USD in 2020, which had increased 1.5 times from 394.7 million USD in 2016. This growth was mainly because of the increased usage of advanced RT techniques. Furthermore, the proportion of intensity-modulated radiation therapy (IMRT) expenses in the total expenses increased by 1.6 times from 48.8% in 2016 to 76.9% in 2020. Advanced techniques were used more commonly in older individuals or children. However, the proportion of IMRT expenses increased mostly in young women. Additionally, geographical differences in RT use and expense were observed, although the gap in the IMRT fractions decreased among the regions.
Conclusion
Recent medical expenses associated with RT in Korea have increased in tandem with technological advances and changes in demographics.

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  • Large institutional experience of early outcomes and dosimetric findings with postoperative stereotactic partial breast irradiation in breast cancer
    Jee Suk Chang, Jeongshim Lee, Frank A. Vicini, Jin Sung Kim, Jihun Kim, Seo Hee Choi, Ik Jae Lee, Yong Bae Kim
    Radiotherapy and Oncology.2024; 191: 110066.     CrossRef
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Breast cancer
Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies
Yong Wha Moon, Seung Ki Kim, Keun Seok Lee, Moon Hee Lee, Yeon Hee Park, Kyong Hwa Park, Gun Min Kim, Seungtaek Lim, Seung Ah Lee, Jae Duk Choi, Eunhye Baek, Hyesun Han, Seungjae Baek, Seock-Ah Im
Cancer Res Treat. 2023;55(3):766-777.   Published online January 19, 2023
DOI: https://doi.org/10.4143/crt.2022.987
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
Materials and Methods
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
Results
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
Conclusion
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

Citations

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  • Comparison of Prophylactic Efficacy of Eflapegrastim and Pegteograstim for Chemotherapy-induced Neutropenia in Pancreatic Cancer Patients Receiving FOLFIRINOX/mFOLFIRINOX
    Eui Seon Lee, Min Jung Geum, Jong Hee Ko, Jae Song Kim, Eun Sun Son, Yun Mi Yu
    Journal of Korean Society of Health-System Pharmacists.2024; 41(3): 253.     CrossRef
  • 4,490 View
  • 266 Download
  • 1 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.

Citations

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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
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • The multifaceted role of SOX2 in breast and lung cancer dynamics
    Kiavash Hushmandi, Seyed Hassan Saadat, Seyedalireza Mirilavasani, Salman Daneshi, Amir Reza Aref, Noushin Nabavi, Rasoul Raesi, Afshin Taheriazam, Mehrdad Hashemi
    Pathology - Research and Practice.2024; 260: 155386.     CrossRef
  • PIK3IP1: structure, aberration, function, and regulation in diseases
    Yingjie Jia, Pengxing He, Xubin Ma, Kaili Lv, Ying Liu, Yichao Xu
    European Journal of Pharmacology.2024; 977: 176753.     CrossRef
  • UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
    Li He, Heng Chen, Bin Ruan, Li He, Ming Luo, Yulun Fu, Rui Zou
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling
    Zhichun Zhang, Yanyan Guo, Xuejun Gao, Xiaoyan Wang, Chanyuan Jin
    Regenerative Therapy.2024; 26: 775.     CrossRef
  • Landscape of targeted therapies for lung squamous cell carcinoma
    Qiuxuan Chen, Xiaoshuo Zheng, Weiting Cheng, Jian Li
    Frontiers in Oncology.2024;[Epub]     CrossRef
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The Incidence and Risk Factors of Chronic Pulmonary Infection after Radiotherapy in Patients with Lung Cancer
Yeonseok Choi, Jae Myoung Noh, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Hongryull Pyo, Yong Chan Ahn, Byeong-Ho Jeong
Cancer Res Treat. 2023;55(3):804-813.   Published online January 3, 2023
DOI: https://doi.org/10.4143/crt.2022.1305
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate cumulative incidence and risk factors associated with chronic pulmonary infection (CPI) development after radiotherapy for lung cancer.
Materials and Methods
We retrospectively analyzed 1,872 patients with lung cancer who received radiotherapy for lung cancer from 2010-2014, had a follow-up period of ≥ 3 months after radiotherapy, and did not have CPI at the time of radiotherapy. CPI was defined as pulmonary tuberculosis, non-tuberculous mycobacterial pulmonary disease, chronic pulmonary aspergillosis, or pulmonary actinomycosis. The cumulative incidence of CPI and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards analysis was performed to identify risk factors associated with CPI development.
Results
The median follow-up period was 2.3 years with OS rates of 55.6% and 37.6% at 2 and 5 years, respectively. CPI developed in 59 patients at a median of 1.8 years after radiotherapy, with cumulative incidence rates of 1.1%, 3.4%, 5.0%, and 6.8% at 1, 3, 5, and 7 years, respectively. A lower body mass index, interstitial lung disease, prior pulmonary tuberculosis, larger clinical target volume, history of lung cancer surgery or radiation pneumonitis, and use of inhaled corticosteroids were independent risk factors for CPI development.
Conclusion
The long-term survival rate of lung cancer patients receiving radiotherapy was not low, but the cumulative incidence of CPI gradually increased to 6.8% at 7 years after radiotherapy. Therefore, close monitoring of CPI development is required in surviving patients with risk factors.

Citations

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  • Invasive aspergillosis complicated in a patient with non-small cell lung cancer harboring RET fusion during treatment with RET-TKIs: a case report and literature review
    Kaidiriye Setiwalidi, Yimeng Li, Yuyan Ma, Zhanpeng Hao, Yujia Zhao, Yuxin Zhang, Xuan Liang, Tao Tian, Zhiping Ruan, Yu Yao, Xiao Fu
    Frontiers in Oncology.2024;[Epub]     CrossRef
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Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non–Small Cell Lung Cancer
Rongxin Liao, Kehong Chen, Jinjin Li, Hengqiu He, Guangming Yi, Mingfeng Huang, Rongrong Chen, Lu Shen, Xiaoyue Zhang, Zaicheng Xu, Zhenzhou Yang, Yuan Peng
Cancer Res Treat. 2023;55(3):814-831.   Published online January 12, 2023
DOI: https://doi.org/10.4143/crt.2022.1315
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.
Materials and Methods
We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.
Results
We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation.
Conclusion
Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Citations

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  • Prognostic and Predictive Biomarkers of Oligometastatic NSCLC: New Insights and Clinical Applications
    Mandy Jongbloed, Martina Bortolot, Leonard Wee, Jarno W.J. Huijs, Murillo Bellezo, Rianne D.W. Vaes, Frank Aboubakar Nana, Koen J. Hartemink, Dirk K.M. De Ruysscher, Lizza E.L. Hendriks
    JTO Clinical and Research Reports.2024; 5(12): 100740.     CrossRef
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Diagnostic Performance of Endosonography to Detect Mediastinal Lymph Node Metastasis in Patients with Radiological N1 Non–Small Cell Lung Cancer
Bo-Guen Kim, Jong Ho Cho, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jhingook Kim, Young Mog Shim, Byeong-Ho Jeong
Cancer Res Treat. 2023;55(3):832-840.   Published online March 2, 2023
DOI: https://doi.org/10.4143/crt.2022.1428
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Guidelines recommend that non–small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1.
Materials and Methods
Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed.
Results
The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15 to 3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32 to 79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63 to 5.55; p < 0.001) were related to OMM in radiological N1 NSCLC patients.
Conclusion
Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

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  • EBUS‐TBNA for mediastinal staging of centrally located T1N0M0 non‐small cell lung cancer clinically staged with PET/CT
    Pere Serra Mitjà, Bruno García‐Cabo, Ignasi Garcia‐Olivé, Joaquim Radua, Ramón Rami‐Porta, Lluís Esteban, Bienvenido Barreiro, Sergi Call, Carmen Centeno, Felipe Andreo, Carme Obiols, Juan Manuel Ochoa, Mireia Martínez‐Palau, Nina Reig, Mireia Serra, José
    Respirology.2024; 29(2): 158.     CrossRef
  • Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non–Small Cell Lung Cancer
    Bo-Guen Kim, Byeong-Ho Jeong, Goeun Park, Hong Kwan Kim, Young Mog Shim, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Jong Ho Cho
    Cancer Research and Treatment.2024; 56(2): 502.     CrossRef
  • Clinical utility of artificial intelligence–augmented endobronchial ultrasound elastography in lymph node staging for lung cancer
    Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
    JTCVS Techniques.2024; 27: 158.     CrossRef
  • Artificial Intelligence Algorithm Can Predict Lymph Node Malignancy from Endobronchial Ultrasound Transbronchial Needle Aspiration Images for Non-Small Cell Lung Cancer
    Yogita S. Patel, Anthony A. Gatti, Forough Farrokhyar, Feng Xie, Waël C. Hanna
    Respiration.2024; : 1.     CrossRef
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EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study
Weiguang Gu, Hua Zhang, Yiyu Lu, Minjing Li, Shuang Yang, Jianmiao Liang, Zhijian Ye, Zhihua Li, Minhong He, Xiaoliang Shi, Fei Wang, Dong You, Weiquan Gu, Weineng Feng
Cancer Res Treat. 2023;55(3):841-850.   Published online February 13, 2023
DOI: https://doi.org/10.4143/crt.2022.1438
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods
This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results
The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion
EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

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  • SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells
    Ping Tian, Dajun Du, Li Yang, Nan Zhou, Ling Tao, Divijendra Natha Reddy Sirigiri
    PLOS ONE.2024; 19(2): e0298295.     CrossRef
  • PIK3CA mutation as an acquired resistance driver to EGFR-TKIs in non-small cell lung cancer: Clinical challenges and opportunities
    Xiaohong Liu, Wuxuan Mei, Pengfei Zhang, Changchun Zeng
    Pharmacological Research.2024; 202: 107123.     CrossRef
  • Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis
    Yosuke Fukuda, Yoshitaka Uchida, Koichi Ando, Ryo Manabe, Akihiko Tanaka, Hironori Sagara
    Respiratory Investigation.2024; 62(3): 481.     CrossRef
  • Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer
    Xiao Liang, Jiali Xu, Yuqin Jiang, Yuqian Yan, Hongshuai Wu, Jiali Dai, Yanan Cui, Chen Zhang, Wei Chen, Zhihong Zhang, Renhua Guo
    Molecular Carcinogenesis.2024; 63(9): 1643.     CrossRef
  • Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review
    Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios, Yamil Liscano
    Cancers.2024; 16(13): 2338.     CrossRef
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Combination of the LARS1 Inhibitor, BC-LI-0186 with a MEK1/2 Inhibitor Enhances the Anti-Tumor Effect in Non–Small Cell Lung Cancer
Sang Hoon Lee, Eun Young Kim, Jung Min Han, Gyoonhee Han, Yoon Soo Chang
Cancer Res Treat. 2023;55(3):851-864.   Published online March 20, 2023
DOI: https://doi.org/10.4143/crt.2022.1527
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC).
Materials and Methods
Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model.
Results
LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model.
Conclusion
The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.

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  • LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma
    Longfei Fan, Zhongqiang Qin, Di Wu, Yunchuan Yang, Yigang Zhang, Bo Xie, Jingyu Qian, Jianzhu Wei, Zhaoying Wang, Peipei Yang, Zhen Qian, Mu Yuan, Ziyi Zhu, Yulin Tan, Yi Tan
    International Journal of General Medicine.2024; Volume 17: 2203.     CrossRef
  • Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer
    Hasan Alsharoh, Paul Chiroi, Ekaterina Isachesku, Radu Andrei Tanasa, Ovidiu-Laurean Pop, Radu Pirlog, Ioana Berindan-Neagoe
    Biomedicines.2024; 12(7): 1489.     CrossRef
  • UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer
    Chi Young Kim, Eun Hye Lee, Se Hyun Kwak, Sang Hoon Lee, Eun Young Kim, Min Kyoung Park, Yoon Jin Cha, Yoon Soo Chang
    Tuberculosis and Respiratory Diseases.2024; 87(4): 494.     CrossRef
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Predictors of Post-chemoradiotherapy Pulmonary Complication in Locally Advanced Non–Small Cell Lung Cancer
Tae Hoon Lee, Byung-Hee Kang, Hak Jae Kim, Hong-Gyun Wu, Joo Ho Lee
Cancer Res Treat. 2023;55(3):865-874.   Published online January 19, 2023
DOI: https://doi.org/10.4143/crt.2022.1538
AbstractAbstract PDFPubReaderePub
Purpose
We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non–small cell lung cancer (LA-NSCLC).
Materials and Methods
Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS).
Results
PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001).
Conclusion
PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.

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  • Pneumonitis Risk After Chemoradiotherapy With and Without Immunotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
    Chong Han, Jingping Qiu, Lu Bai, Tingting Liu, Jun Chen, He Wang, Jun Dang
    International Journal of Radiation Oncology*Biology*Physics.2024; 119(4): 1179.     CrossRef
  • Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities
    Mark Stares, Leo R. Brown, Dhruv Abhi, Iain Phillips
    Cancers.2024; 16(8): 1508.     CrossRef
  • Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis
    Tingting Liu, Sihan Li, Silu Ding, Jingping Qiu, Chengbo Ren, Jun Chen, He Wang, Xiaoling Wang, Guang Li, Zheng He, Jun Dang
    eClinicalMedicine.2023; 64: 102246.     CrossRef
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Efficacy of Prophylactic Cranial Irradiation According to the Risk of Extracranial Recurrence in Limited-Stage Small Cell Lung Cancer
Tae Hoon Lee, Joo-Hyun Chung, Hong-Gyun Wu, Suzy Kim, Joo Ho Lee, Bhumsuk Keam, Jin-Soo Kim, Ki Hwan Kim, Byoung Hyuck Kim, Hak Jae Kim
Cancer Res Treat. 2023;55(3):875-884.   Published online February 24, 2023
DOI: https://doi.org/10.4143/crt.2022.1583
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for “early brain metastasis”, which occurs before extracranial recurrence (ECR), and “late brain metastasis”, which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC).
Materials and Methods
We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors.
Results
The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026).
Conclusion
PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.
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A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer
Youngjoo Lee, Soo-Hyun Lee, Geon Kook Lee, Eun Jin Lim, Ji-Youn Han
Cancer Res Treat. 2023;55(3):885-893.   Published online March 20, 2023
DOI: https://doi.org/10.4143/crt.2023.283
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC).
Materials and Methods
This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate.
Results
Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046).
Conclusion
Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

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  • Cardiovascular/anti‐inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta‐analysis of randomized trials
    David J. Benjamin, Alyson Haslam, Vinay Prasad
    Cancer Medicine.2024;[Epub]     CrossRef
  • Repurposing simvastatin in cancer treatment: an updated review on pharmacological and nanotechnological aspects
    Nargis Ara, Abdul Hafeez, Shom Prakash Kushwaha
    Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(10): 7377.     CrossRef
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    Tony Yu, Benjamin H. Lok
    Cancers.2024; 16(20): 3438.     CrossRef
  • β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers
    Pedro Gabriel Senger Braga, Janaína da Silva Vieira, Aline Rachel Bezerra Gurgel, Patricia Chakur Brum
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Statins—From Fungi to Pharmacy
    Anna Sadowska, Patryk Osiński, Alicja Roztocka, Karolina Kaczmarz-Chojnacka, Ewa Zapora, Diana Sawicka, Halina Car
    International Journal of Molecular Sciences.2023; 25(1): 466.     CrossRef
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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.

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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
    Microbiological Research.2024; 282: 127648.     CrossRef
  • 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
    Cell Communication and Signaling.2024;[Epub]     CrossRef
  • 17β-estradiol in colorectal cancer: friend or foe?
    Zihong Wu, Chong Xiao, Jiamei Wang, Min Zhou, Fengming You, Xueke Li
    Cell Communication and Signaling.2024;[Epub]     CrossRef
  • Sexual dimorphism of gut microbiota in colorectal cancer
    Zihong Wu, Ziming Wang, Jiamei Wang, Chong Xiao, Fengming You, Xueke Li
    Chinese Science Bulletin.2024;[Epub]     CrossRef
  • Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer
    Zihong Wu, Yi Sun, Wenbo Huang, Zhenzhen Jin, Fengming You, Xueke Li, Chong Xiao
    Frontiers in Cellular and Infection Microbiology.2024;[Epub]     CrossRef
  • Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes
    Zhihui Song, An Yan, Zehui Guo, Yuhang Zhang, Tao Wen, Zhenzhen Li, Zhihua Yang, Rui Chen, Yi Wang
    Frontiers in Cellular and Infection Microbiology.2023;[Epub]     CrossRef
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Overview of the National Cancer Screening Program for Colorectal Cancer in Korea over 14 Years (2004-2017)
Bomi Park, Eun Young Her, Kyeongmin Lee, Fatima Nari, Jae Kwan Jun, Kui Son Choi, Mina Suh
Cancer Res Treat. 2023;55(3):910-917.   Published online March 8, 2023
DOI: https://doi.org/10.4143/crt.2022.1432
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the participation and follow-up test compliance rates and key performance indicators of the National Cancer Screening Program (NCSP) for colorectal cancer (CRC) from 2004 to 2017.
Materials and Methods
The overall outcomes of the NCSP for CRC were analyzed using the NCSP data collected from 2004 to 2017 and the Korean Central Cancer Registry for CRC from 2005 to 2017. We cross-sectionally analyzed the participation and follow-up test compliance rates and performance indicators for each year. The trend of participation rates as an annual percentage change was assessed, and other statistical analyses were performed.
Results
The screening participation rates increased from 7.3% in 2004 to 30.5% in 2017. Additionally, the screening rates were higher among individuals aged 60-69 years and National Health Insurance Service beneficiaries of low-income status. However, the adherence to the follow-up test decreased from 63% in 2004 to 32% in 2017. The follow-up tests using the double-contrast barium enema method decreased from 42.2% in 2004 to 0.3% in 2017. However, follow-up tests by colonoscopy increased from 21.0% in 2004 to 31.8% in 2017. Furthermore, the positivity, false-positive, and interval CRC rates decreased, whereas the specificity increased from 2004 to 2016, indicating improved performance of CRC.
Conclusion
The participation rates and performance of the NCSP for CRC have steadily improved, whereas adherence to follow-up tests has decreased. Additionally, there is a rapid growth in colonoscopy volume as a follow-up test. Continued efforts are required to improve the follow-up rates.

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  • Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study
    Hwayoung Noh, Jeeyoo Lee, Nazlisadat Seyed Khoei, Laia Peruchet-Noray, Daehee Kang, Beatrice Fervers, Karl-Heinz Wagner, Aesun Shin, Heinz Freisling
    British Journal of Cancer.2024; 131(10): 1635.     CrossRef
  • Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea
    Dong Jun Kim, Nan-He Yoon, Jae Kwan Jun, Mina Suh, Sunhwa Lee, Seongju Kim, Ji Eun Kim, Hooyeon Lee
    Cancer Research and Treatment.2024; 56(4): 1164.     CrossRef
  • National cancer screening program for colorectal cancer in Korea
    Seung Min Baik, Ryung-Ah Lee
    Annals of Surgical Treatment and Research.2023; 105(6): 333.     CrossRef
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One-Week versus Two-Week Chemoradiotherapy Followed by Curative Surgery in Rectal Cancer: Long-Term Comparative Pooled Analysis of Two Prospective Multicenter Phase II Trials
Soo-Yoon Sung, Dae Yong Kim, Hong Seok Jang, Tae Hyun Kim, Hee Chul Park, Eui Kyu Chie, Taek-Keun Nam, Sung Hwan Kim, Jong Hoon Lee
Cancer Res Treat. 2023;55(3):918-926.   Published online February 27, 2023
DOI: https://doi.org/10.4143/crt.2022.1646
AbstractAbstract PDFPubReaderePub
Purpose
The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of 1- and 2-week chemoradiotherapy (CRT), respectively.
Materials and Methods
Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during 1 week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions for 2 weeks with oral capecitabine.
Results
A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival rate was 86.5% in 1-week CRT and 85.3% in 2-week CRT (p=0.841). The 5-year recurrence-free survival rate was 83.5% in 1-week CRT and 77.1% in 2-week CRT (p=0.448). One patient (1.4%) in 1-week CRT and 11 patients (13.8%) in 2-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy (p=0.006). One-week CRT had significantly higher acute hematologic (12.8% vs. 3.8%, p=0.040) and nonhematologic (38.6% vs. 16.3%, p=0.002) toxicity than 2-week CRT.
Conclusion
Both 1- and 2-week schedules of CRT showed favorable survival outcomes after 7 years of follow-up. But, 2-week course achieved more increased tumor response and decreased acute toxicity than 1-week course.
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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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  • 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
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Intraindividual Comparison of MRIs with Extracellular and Hepatobiliary Contrast Agents for the Noninvasive Diagnosis of Hepatocellular Carcinoma Using the Korean Liver Cancer Association–National Cancer Center 2022 Criteria
Ja Kyung Yoon, Dai Hoon Han, Sunyoung Lee, Jin-Young Choi, Gi Hong Choi, Do Young Kim, Myeong-Jin Kim
Cancer Res Treat. 2023;55(3):939-947.   Published online February 10, 2023
DOI: https://doi.org/10.4143/crt.2022.1645
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The aim of the present study was to evaluate the per-lesion sensitivity and specificity of the Korean Liver Cancer Association–National Cancer Center (KLCA-NCC) 2022 criteria for the noninvasive diagnosis of hepatocellular carcinoma (HCC), with intraindividual comparison of the diagnostic performance of magnetic resonance imaging with extracellular agents (ECA-MRI) and hepatobiliary agents (HBA-MRI).
Materials and Methods
Patients at high risk for HCC who were referred to a tertiary academic institution for hepatic lesions with size ≥ 10 mm between July 2019 and June 2022 were enrolled. A total of 91 patients (mean age, 58.1 years; 76 men and 15 women) with 118 lesions who underwent both ECA-MRI and HBA-MRI were eligible for final analysis. The per-lesion sensitivities and specificities of the KLCA-NCC 2022 criteria using ECA-MRI and HBA-MRI were compared using McNemar’s test.
Results
The 118 lesions were 93 HCCs, 4 non-HCC malignancies, and 21 benign lesions. On HBA-MRI, the “definite” HCC category showed significantly higher sensitivity than ECA-MRI (78.5% vs. 58.1%, p < 0.001), with identical specificity (92.0% vs. 92.0%, p > 0.999). For “probable” or “definite” HCC categories, there were no differences in the sensitivity (84.9% vs. 84.9%, p > 0.999) and specificity (84.0% vs. 84.0%, p > 0.999) between ECA-MRI and HBA-MRI.
Conclusion
The “definite” HCC category of the KLCA-NCC 2022 criteria showed higher sensitivity in diagnosing HCC on HBA-MRI compared with ECA-MRI, without compromising specificity. There were no significant differences in the sensitivity and specificity of “probable” or “definite” HCC categories according to ECA-MRI and HBA-MRI.

Citations

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  • Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents
    Ja Kyung Yoon, Dai Hoon Han, Sunyoung Lee, Jin‐Young Choi, Gi Hong Choi, Do Young Kim, Myeong‐Jin Kim
    Liver International.2024; 44(10): 2847.     CrossRef
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The Oncologic Implications of Tumor Multiplicity in Intrahepatic Cholangiocarcinoma: Its Prognostic Value Might Be Underestimated
So Jeong Yoon, Sunghae Park, Hongbeom Kim, Sang Hyun Shin, Jin Seok Heo, Jinsoo Rhu, Gyu-Seong Choi, Jong Man Kim, Jae-Won Joh, In Woong Han
Cancer Res Treat. 2023;55(3):948-955.   Published online February 27, 2023
DOI: https://doi.org/10.4143/crt.2023.290
AbstractAbstract PDFPubReaderePub
Purpose
In the latest staging system of the American Joint Committee on Cancer for intrahepatic cholangiocarcinoma (IHCCC), solitary tumors with vascular invasion and multiple tumors are grouped together as T2. However, recent studies report that multifocal IHCCC has a worse prognosis than a single lesion. This study aimed to investigate the risk factors for IHCCC and explore the prognostic significance of multiplicity after surgical resection.
Materials and Methods
A total of 257 patients underwent surgery for IHCCC from 2010 to 2019 and the clinicopathological data were retrospectively reviewed. Risk factor analysis was performed to identify variables associated with survival after resection. Survival outcomes were compared between patients with solitary and multiple tumors.
Results
In multivariable analysis, the presence of preoperative symptoms, tumor size, lymph node ratio, multiplicity, and tumor differentiation were identified as risk factors for survival. Among 82 patients with T2, overall survival was significantly longer in patients with solitary tumors (sT2) than in those with multiple tumors (mT2) (p=0.017). Survival was compared among patients with stage II-sT2, stage II-mT2, and stage III. The stage II-sT2 group showed prolonged survival when compared with stage II-mT2 or stage III. Survivals of stage II-mT2 and stage III patients were not statistically different.
Conclusion
Tumor multiplicity was an independent risk factor for overall survival of IHCCC after surgical resection. Patients with multiple tumors showed poorer survival than patients with a single tumor. The oncologic significance of multiplicity in IHCCC should be reappraised and reflected in the next staging system update.
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Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX
So Heun Lee, Dae Wook Hwang, Changhoon Yoo, Kyu-pyo Kim, Sora Kang, Jae Ho Jeong, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Yejong Park, Bong Jun Kwak, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim
Cancer Res Treat. 2023;55(3):956-968.   Published online February 27, 2023
DOI: https://doi.org/10.4143/crt.2022.409
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

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  • The survival effect of neoadjuvant therapy and neoadjuvant plus adjuvant therapy on pancreatic ductal adenocarcinoma patients with different TNM stages: a propensity score matching analysis based on the SEER database
    Hao Hu, Yang Xu, Qiang Zhang, Yuan Gao, Zhenyu Wu
    Expert Review of Anticancer Therapy.2024; 24(6): 467.     CrossRef
  • Neoadjuvant treatment of pancreatic ductal adenocarcinoma: Whom, when and how
    Nebojsa Manojlovic, Goran Savic, Stevan Manojlovic
    World Journal of Gastrointestinal Surgery.2024; 16(5): 1223.     CrossRef
  • Case Study on Analysing the Early Disease Detection of Pancreatic Ductal Adenocarcinoma in Korean Association for Clinical Oncology
    Sijithra Ponnarassery Chandran, N. Santhi
    American Journal of Clinical Oncology.2024; 47(10): 475.     CrossRef
  • Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy—a systematic review and meta-analysis
    Jiahao Wu, Yike Zhang, Haodong Wang, Wenyi Guo, Chengqing Li, Yichen Yu, Han Liu, Feng Li, Lei Wang, Jianwei Xu
    Frontiers in Oncology.2024;[Epub]     CrossRef
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Genitourinary cancer
Early Plasma Circulating Tumor DNA as a Potential Biomarker of Disease Recurrence in Non-metastatic Prostate Cancer
Xiaochen Fei, Xinxing Du, Yiming Gong, Jiazhou Liu, Liancheng Fan, Jiayi Wang, Yanqing Wang, Yinjie Zhu, Jiahua Pan, Baijun Dong, Wei Xue
Cancer Res Treat. 2023;55(3):969-977.   Published online March 2, 2023
DOI: https://doi.org/10.4143/crt.2022.1557
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.
Materials and Methods
This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression.
Results
Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence.
Conclusion
Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Citations

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  • Role of Liquid Biopsy in Progressive PSA Patients after Radical Prostatectomy
    Marcel Figueras, Lourdes Mengual, Mercedes Ingelmo-Torres, Fiorella L. Roldán, Bernat Padullés, Héctor Alfambra, Sandra Herranz, Pilar Paredes, Gary Amseian, Joel Mases, Maria J. Ribal, Laura Izquierdo, Antonio Alcaraz
    Diagnostics.2024; 14(20): 2293.     CrossRef
  • Circulating Tumor DNA Is a Variant of Liquid Biopsy with Predictive and Prognostic Clinical Value in Breast Cancer Patients
    Tatiana M. Zavarykina, Polina K. Lomskova, Irina V. Pronina, Svetlana V. Khokhlova, Marina B. Stenina, Gennady T. Sukhikh
    International Journal of Molecular Sciences.2023; 24(23): 17073.     CrossRef
  • 3,432 View
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Gynecologic cancer
Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma
Nan Kang, Yinli Zhang, Shichao Guo, Ran Chen, Fangzhou Kong, Shuchun Wang, Mingming Yuan, Rongrong Chen, Danhua Shen, Jianliu Wang
Cancer Res Treat. 2023;55(3):978-991.   Published online February 2, 2023
DOI: https://doi.org/10.4143/crt.2022.1647
AbstractAbstract PDFPubReaderePub
Purpose
The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients.
Materials and Methods
A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored.
Results
TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion.
Conclusion
This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

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  • Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival
    Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai
    Thoracic Cancer.2024; 15(19): 1502.     CrossRef
  • High-Grade Endometrial Mesenchymal Sarcoma: Current Status and Future Trends
    Zhang Lushuang, Zhao Liubiqi
    Clinical Journal of Obstetrics and Gynecology.2023; 6(3): 132.     CrossRef
  • 4,037 View
  • 185 Download
  • 1 Web of Science
  • 2 Crossref
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Pediatric cancer
Gonadal Function in Female Adolescent and Young Adult Survivors of Childhood Cancer
Hye Young Jin, Jun Ah Lee, Meerim Park, Hyeon Jin Park
Cancer Res Treat. 2023;55(3):992-1000.   Published online January 31, 2023
DOI: https://doi.org/10.4143/crt.2022.1518
AbstractAbstract PDFPubReaderePub
Purpose
Childhood cancer survivors (CCSs) are at risk for premature ovarian insufficiency (POI). The aim of this study is to evaluate ovarian function and associated health outcomes in female adolescent and young adult survivors of childhood cancer.
Materials and Methods
Sixty-nine female CCSs were enrolled. Medical records of CCSs were retrospectively reviewed. The subjects were categorized into three groups according to follicular stimulating hormone (FSH) levels (cutoff, 12, 40 IU/L). Anti-müllerian hormone (AMH) level less than 1 ng/mL was considered low AMH level.
Results
Of 69 subjects, 14 (20.3%) had POI and 14 (20.3%) had FSH levels between 12 and 40 IU/L. Forty-one of 69 (59.4%) had normal FSH levels. Pelvic irradiation and stem cell transplantation (SCT) were more frequently performed in subjects with POI (p=0.001 and p < 0.001). AMH levels were remarkably low when FSH levels were over 12 IU/L (p < 0.001). In multivariate analysis, cyclophosphamide equivalent dose and SCT were significant treatment factors for developing low AMH levels (p=0.005 and p=0.002, respectively). Total, low-density lipoprotein cholesterol and triglyceride were significantly different in three groups according to FSH levels (p=0.047, p=0.030, and p=0.045). Z-score of femur neck bone mineral density was significantly reduced when FSH levels were increased (p=0.011).
Conclusion
Gonadal dysfunction is common in CCSs. Gonadal function was associated with a few treatment factors known to increase the risk of POI. Regular monitoring of gonadal function is needed for better health outcomes.

Citations

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  • Systematic Review of the Gonadotoxicity and Risk of Infertility of Soft Tissue Sarcoma Chemotherapies in Pre- and Postpubertal Females and Males
    Marcel Steinmann, Anita Rietschin, Flavia Pagano, Tanya Karrer, Attila Kollár, Susanna Weidlinger, Michael von Wolff
    Journal of Adolescent and Young Adult Oncology.2024;[Epub]     CrossRef
  • Bone Mineral Density in Survivors of Childhood Cancer: A Meta-Analysis
    Lilly Velentza, Panagiotis Filis, Mari Wilhelmsson, Per Kogner, Nikolas Herold, Lars Sävendahl
    Pediatrics.2024;[Epub]     CrossRef
  • 3,164 View
  • 160 Download
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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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  • Inflammatory myofibroblastic tumor of the adrenal gland: A case report
    Jiyao Yang, Hongjin Shi, Haifeng Wang, Yidao Liu
    Urology Case Reports.2024; 55: 102763.     CrossRef
  • Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations
    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
    Cancers.2024; 16(15): 2646.     CrossRef
  • Thoracic epithelioid inflammatory myofibroblastic sarcoma: a rare and aggressive disease with case report and literature review
    Linke Yang, Pei Li, Runze Liu, Baomin Feng, Huiqing Mao, Xiaoyong Tang, Guangjian Yang
    Discover Oncology.2024;[Epub]     CrossRef
  • Metastasized inflammatory myofibroblastic tumor of uterine origin
    Thomas Bartl, Michael Deavers, Ryan Blair Kieser, Pedro T Ramirez
    International Journal of Gynecologic Cancer.2024; 34(10): 1643.     CrossRef
  • Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib—a case report
    Rafał Becht, Kajetan Kiełbowski, Justyna Żychowska, Wojciech Poncyljusz, Aleksandra Łanocha, Katarzyna Kozak, Ewa Gabrysz-Trybek, Paweł Domagała
    Therapeutic Advances in Medical Oncology.2024;[Epub]     CrossRef
  • 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
    Thoracic Cancer.2024;[Epub]     CrossRef
  • Rare giant epithelioid inflammatory myofibroblastic sarcoma of the abdominal cavity in a child: a case report and review of the literature
    Jinzhou Li, Haixing Su, Sheng Zhang, Xianyun Chen, Chongzhi Hou, Tao Cheng
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • 3,239 View
  • 136 Download
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Close layer
Hematologic malignancy
Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
Seo-Yeon Ahn, TaeHyung Kim, Mihee Kim, Ga-Young Song, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim
Cancer Res Treat. 2023;55(3):1011-1022.   Published online January 26, 2023
DOI: https://doi.org/10.4143/crt.2022.1407
AbstractAbstract PDFPubReaderePub
Purpose
We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype.
Materials and Methods
Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.
Results
Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).
Conclusion
Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.

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  • CEBPA double mutations associated with ABO antigen weakness in hematologic diseases
    Seung Jun Choi, Hyun Kyung Kim, Eun Jung Suh, Soon Sung Kwon, Saeam Shin, Seung-Tae Lee, Sinyoung Kim
    Blood Advances.2024; 8(6): 1487.     CrossRef
  • CEBPA bZIP in-frame mutations in acute myeloid leukemia: prognostic and therapeutic implications
    Fenghong Zhang, Zhen Shen, Jundan Xie, Jingren Zhang, Qian Wu, Rui Jiang, Xiangyu Zhao, Xiaofei Yang, Suning Chen
    Blood Cancer Journal.2024;[Epub]     CrossRef
  • Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia
    Juan Carlos Rivera, Daniel Nuñez, Elizabet Millar, Kimberly Ramirez, Mauricio Chandía, Claudio Aguayo
    International Journal of Laboratory Hematology.2023; 45(6): 833.     CrossRef
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Close layer
Clinical Impact of Drug Adherence of Tyrosine Kinase Inhibitors in Children with Ph-Positive Acute Lymphoblastic Leukemia
Jun-Xia Wang, Miao-Miao Yang, Li-Peng Liu, Hui-Min Zhang, Meng-Chuan Wang, Yu-Wen Chen, Xiao-Ying Zang, Fang Hu
Cancer Res Treat. 2023;55(3):1023-1030.   Published online February 6, 2023
DOI: https://doi.org/10.4143/crt.2022.1618
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to explore the impact of ABL1–tyrosine kinase inhibitors (TKIs) adherence on the survival of chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) children and clarify the potential predictors of patients’ prognosis from TKIs intake practices.
Materials and Methods
Ninety newly diagnosed Ph+ ALL patients who received TKIs were enrolled. We collected the baseline characteristics and adverse events in all children; moreover, TKIs adherence was measured by an eight-item Morisky medication adherence scale (MMAS-8). Progression-free survival (PFS) and overall survival (OS) analysis were performed, and risk factors for PFS and OS were evaluated.
Results
Among all patients, 69 cases were regarded as adherers, while 21 were non-adherers. The median duration of TKIs interruption was significantly prolonged in the non-adherence group than in the adherence group (13 [0-101] vs. 56 [11-128], p < 0.001). Additionally, dose reduction occurred in 55.2% of non-adherers versus 23.0% of adherers (p=0.002). The PFS and OS in adherers were significantly higher versus non-adherers (p=0.020 and p=0.039). MMAS-8 score was an independent risk factor for PFS (p=0.010) and OS (p=0.031). Among non-adherers, the median OS was only 23.1% (4.2%-42%) in patients aged ≤ 10 years versus 54.4% (38.8%-70%) in adolescents. Most of the patients who experienced TKIs non-adherence suffered pancytopenia.
Conclusion
TKIs adherence during treatment significantly influenced the survival of pediatric Ph+ ALL patients, and non-adherers with age ≤ 10 years were more vulnerable to TKIs disruption. The cumulative TKIs dose should be especially emphasized to patients with age ≤ 10 years, which may result in an inferior achievement of relevant treatment milestones.
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Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis
Jinchul Kim, Jinhyun Cho, Sang Eun Yoon, Won Seog Kim, Seok Jin Kim
Cancer Res Treat. 2023;55(3):1031-1047.   Published online March 13, 2023
DOI: https://doi.org/10.4143/crt.2022.1658
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
Materials and Methods
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
Results
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
Conclusion
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.

Citations

Citations to this article as recorded by  
  • Polatuzumab vedotin combined with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma: A systematic review protocol
    Mohammadreza Eslami, Mahdi Mehrabi, Mehrdad Payandeh, Fakhredin Saba, Chen Li
    PLOS ONE.2024; 19(8): e0308247.     CrossRef
  • Targeting CD22 for B-cell hematologic malignancies
    Jia Xu, Wenjing Luo, Chenggong Li, Heng Mei
    Experimental Hematology & Oncology.2023;[Epub]     CrossRef
  • 6,758 View
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Case Report
Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA
Jung-Ki Yoon, Jongseong Ahn, Sheehyun Kim, Hwang-Phil Kim, Jun-kyu Kang, Duhee Bang, Yoojoo Lim, Tae-You Kim
Cancer Res Treat. 2023;55(3):1048-1052.   Published online January 31, 2023
DOI: https://doi.org/10.4143/crt.2022.1529
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

Citations

Citations to this article as recorded by  
  • Circulating tumor DNA validity and potential uses in metastatic breast cancer
    Ottavia Amato, Nefeli Giannopoulou, Michail Ignatiadis
    npj Breast Cancer.2024;[Epub]     CrossRef
  • DNA damage targeted therapy for advanced breast cancer
    Vanessa Patel, Sandra Casimiro, Catarina Abreu, Tiago Barroso, Rita Teixeira de Sousa, Sofia Torres, Leonor Abreu Ribeiro, Gonçalo Nogueira-Costa, Helena Luna Pais, Conceição Pinto, Leila Costa, Luís Costa
    Exploration of Targeted Anti-tumor Therapy.2024; 5(3): 678.     CrossRef
  • Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer
    Seung-Hwan Jeong, Dongsoo Kyung, Hyeong Dong Yuk, Chang Wook Jeong, Wookjae Lee, Jung-Ki Yoon, Hwang-Phill Kim, Duhee Bang, Tae-You Kim, Yoojoo Lim, Cheol Kwak
    Cancers.2023; 15(10): 2847.     CrossRef
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Cancer Res Treat : Cancer Research and Treatment
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