Cancer Research and Treatment

Original Articles

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

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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

Citations to this article as recorded by

Liquid Biopsy in Non-Metastatic Prostate Cancer: Clinical Evidence and Future Directions
Maria Chiara Sighinolfi, Giuseppe Pallotta, Marzia Del Re, Koosha Moosavi, Or Schubert, Francesco Rossi, Filippo Gavi, Simone Assumma, Enrico Panio, Angelo Totaro, Filippo Turri, Mauro Ragonese, Nazario Foschi, Pierluigi Russo, Ela Patel, Carlo Gandi, Giu
Cancers.2026; 18(5): 800. CrossRef
Letter to the Editor: “Dynamic risk stratification - guided management of medullary thyroid carcinoma: integrating surgical precision with RET-targeted therapies and molecular surveillance”
Lei Tang
International Journal of Surgery.2026; 112(2): 5424. CrossRef
Using ctDNA to Inform Adjuvant Therapy for Urologic Malignancies
Rajvi Goradia, Taylor Goodstein, Debasish Sundi, Akshay Sood, Shawn Dason, Eric A. Singer
Cancers.2026; 18(7): 1121. CrossRef
Method development for pancreatic and ovarian cancer baseline ctDNA detection and measurable residual disease monitoring
Tim Alexander Steiert, Philipp M. Altrock, Axel Künstner, Vishal Dixit, Burkhard Brandt, Pamela Pinzani, Hauke Busch, Andre Franke, Michael Forster
Open Research Europe.2026; 6: 87. CrossRef
Minimal residual disease as a target for liquid biopsy in patients with solid tumours
Klaus Pantel, Catherine Alix-Panabières
Nature Reviews Clinical Oncology.2025; 22(1): 65. CrossRef
Update on Liquid Biopsy
Marius E. Mayerhoefer, Andreas Kienzle, Sungmin Woo, Hebert Alberto Vargas
Radiology.2025;[Epub] CrossRef
The Evolving Landscape of Novel and Old Biomarkers in Localized High-Risk Prostate Cancer: State of the Art, Clinical Utility, and Limitations Toward Precision Oncology
Lilia Bardoscia, Angela Sardaro, Mariagrazia Quattrocchi, Paola Cocuzza, Elisa Ciurlia, Ilaria Furfaro, Maria Antonietta Gilio, Marcello Mignogna, Beatrice Detti, Gianluca Ingrosso
Journal of Personalized Medicine.2025; 15(8): 367. CrossRef
Circulating Tumor DNA in Prostate Cancer: A Dual Perspective on Early Detection and Advanced Disease Management
Stepan A. Kopytov, Guzel R. Sagitova, Dmitry Y. Guschin, Vera S. Egorova, Andrei V. Zvyagin, Alexey S. Rzhevskiy
Cancers.2025; 17(15): 2589. CrossRef
Current Status and Future Perspectives of Molecular Residual Disease Testing in Genitourinary Cancers
Taigo Kato, Shugo Yajima, Yoshiaki Nakamura, Shin Kobayashi, Hideaki Miyake
International Journal of Urology.2025; 32(12): 1735. CrossRef
Circulating Tumor DNA as a Biomarker for Precision Medicine in Prostate Cancer: A Systematic Review
Nouhaila Chanhih, Abdelilah Laraqui, Salma Hassine, Ahmed Ameur, Larbi Hamedoun, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Idriss Lahlou Amine, Khalid Ennibi, Abdelaziz Benjouad, Lamiae Belayachi
International Journal of Molecular Sciences.2025; 26(22): 11049. CrossRef
Circulating Tumor DNA And Its Potential Applications for Assessing Effectiveness of Neoadjuvant Drug Therapy in the Breast Cancer Patients
Tatiana M. Zavarykina, Irina V. Pronina, Polina S. Mazina, Svetlana V. Khokhlova, Gennady T. Sukhikh
Biochemistry (Moscow).2025; 90(11): 1484. CrossRef
Emerging biomarkers in prostate cancer diagnosis and treatment: Insights into genetic, RNA and metabolic markers (Review)
Yuanshe Huang, Jingxin Mao, Xiaobing Li
International Journal of Oncology.2025; 68(2): 1. CrossRef
Liquid biopsy in genitourinary cancers: Diagnostic and prognostic implications
Joe Youssef, Amani Yehya, Zahraa Salhab, Ricardo Bitar, Fatima Ghamlouche, Hisham F Bahmad, Wassim Abou-Kheir
World Journal of Clinical Oncology.2025;[Epub] CrossRef
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

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Pediatric cancer

Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse: Xinyu Wan, Xiaomin Yang, Fan Yang, Tianyi Wang, Lixia Ding, Lili Song, Yan Miao, Xiang Wang, Yani Ma, Chengjuan Luo, Jingyan Tang, Longjun Gu, Jing Chen, Yanjing Tang, Jun Lu, Benshang Li; Cancer Res Treat. 2022;54(3):917-925. Published online September 17, 2021; DOI: https://doi.org/10.4143/crt.2021.399

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Purpose
Anti-CD19 chimeric antigen receptor T-cell immunotherapy (19CAR-T) has achieved impressive clinical results in adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement.
Materials and Methods
CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry.
Results
Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%.
Conclusion
19CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.

Citations

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CAR-T Cell Exhaustion in Cancer over the Past Decade: Mitochondrial Metabolism as a Target for Counteraction
Lingling Si, Di Wei, Jinghao Pan, Renato B. Baleeiro, Louisa S. Chard Dunmall, Yaohe Wang
Cancer Letters.2026; 639: 218240. CrossRef
Expression of the CXCR4 S338X Variant Improves Anti‐Leukemia Efficacy of Anti‐CD19 CAR‐T Cells
Yushu Mao, Xiaodan Wang, Chun‐Hui Jin, Zhifeng Wei, Qinghao Ding, Ke‐Ke Zhang, Bo‐Wen Dong, Kai‐Wen Zheng, Yufei Hou, Tao Zhang, Wen‐Jie Zhao, Zheng Hu, Yong‐Guang Yang
Cancer Science.2026; 117(3): 613. CrossRef
Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia
Tingting Yang, Yetian Dong, Mingming Zhang, Jingjing Feng, Shan Fu, Pingnan Xiao, Ruimin Hong, Huijun Xu, Jiazhen Cui, Simao Huang, Guoqing Wei, Delin Kong, Jia Geng, Alex H. Chang, He Huang, Yongxian Hu
Experimental Hematology & Oncology.2025;[Epub] CrossRef
Efficacy and safety of tocilizumab in managing cytokine release syndrome after CD19 CAR-T therapy for relapsed or refractory B-cell acute lymphoblastic leukemia
Qianyi Zhou, Yuxin An, Xiaomei Zhang, Xia Xiao, Xue Bai, Pengjiang Liu, Yedi Pu, Juanxia Meng, Haibo Zhu, Cuicui Lyu, Huan Zhang, Yu Zhang, Tianle Xie, Haotian Meng, Hairong Lyu
Frontiers in Immunology.2025;[Epub] CrossRef
Extramedullary relapse of acute lymphoblastic leukemia treated with a CAR-T cell therapy bridge to unrelated cord blood transplantation: a case report and review of the literature
Huibo Li, Jie Liu, Dan Guo, Yanqiu Zhao, Qi Li, Sen Qi, Jinxiao Hou, Jianping Zhang, Shengjin Fan
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Safety and efficacy of CD19-targeted CAR-T-cell therapy for patients with relapsed or refractory TCF3-PBX1 fusion gene-positive B-ALL
Can Huang, Yuanyin Teng, Tingting Yang, Mingming Zhang, Yinghui Yu, Shan Fu, Jingjing Feng, He Huang, Yongxian Hu
Hematology.2025;[Epub] CrossRef
Overcoming the challenges of primary resistance and relapse after CAR-T cell therapy
Alexandra Dreyzin, Alexander W. Rankin, Katia Luciani, Tatyana Gavrilova, Nirali N. Shah
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Difference in Efficacy and Safety of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Containing 4-1BB and CD28 Co-Stimulatory Domains for B-Cell Acute Lymphoblastic Leukemia
Lijuan Wu, Junchao Chen, Ruifen Cai, Xinrui Wang, Yixiao Liu, Qingshan Zheng, Lujin Li
Cancers.2023; 15(10): 2767. CrossRef
Incidence of CD19-negative relapse after CD19-targeted immunotherapy in R/R BCP acute lymphoblastic leukemia: a review
Franco Locatelli, Bijal Shah, Tracy Thomas, Kelly Velasco, Babatunde Adedokun, Ibrahim Aldoss, Lia Gore, Dieter Hoelzer, Renato Bassan, Jae H. Park, Nicolas Boissel, Hagop Kantarjian
Leukemia & Lymphoma.2023; 64(10): 1615. CrossRef
Using the Power of Junctional Adhesion Molecules Combined with the Target of CAR-T to Inhibit Cancer Proliferation, Metastasis and Eradicate Tumors
Christopher Mendoza, Dario Mizrachi
Biomedicines.2022; 10(2): 381. CrossRef
Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy
Elizabeth M. Holland, Bonnie Yates, Alex Ling, Constance M. Yuan, Hao-Wei Wang, Maryalice Stetler-Stevenson, Michael LaLoggia, John C. Molina, Daniel A. Lichtenstein, Daniel W. Lee, John A. Ligon, Haneen Shalabi, Mark A. Ahlman, Nirali N. Shah
Blood Advances.2022; 6(7): 2167. CrossRef
Efficacy and safety of CD19 CAR-T cell therapy for patients with B cell acute lymphoblastic leukemia involving extramedullary relapse
Luo HUANG, Mingming ZHANG, Guoqing WEI, Houli ZHAO, Yongxian HU, He HUANG
Journal of Zhejiang University (Medical Sciences).2022; 51(2): 151. CrossRef
Results of ARI‐0001 CART19 cell therapy in patients with relapsed/refractory CD19‐positive acute lymphoblastic leukemia with isolated extramedullary disease
Valentín Ortiz‐Maldonado, Anna Alonso‐Saladrigues, Marta Español‐Rego, Nuria Martínez‐Cibrián, Anna Faura, Laura Magnano, Albert Català, Daniel Benítez‐Ribas, Eva Giné, Marina Díaz‐Beyá, Juan Gonzalo Correa, Montserrat Rovira, Mercedes Montoro‐Lorite, Ale
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Dian-Dian Liu, Wei-Cong Hong, Kun-Yin Qiu, Xin-Yu Li, Yong Liu, Li-Wen Zhu, Wei-Xin Lai, Han- Chen, Hua-Qing Yang, Lu-Hong Xu, Jian-Pei Fang
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Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and BCR-ABL-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin
Sabine Kayser, Chiara Sartor, Marlise R. Luskin, Jonathan Webster, Fabio Giglio, Nydia Panitz, Andrew M. Brunner, Matthias Fante, Christoph Lutz, Daniel Wolff, Anthony D. Ho, Mark J. Levis, Richard F. Schlenk, Cristina Papayannidis
Haematologica.2022; 107(9): 2064. CrossRef

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Erratum

ERRATUM: Comparison between Craniospinal Irradiation and Limited-Field Radiation in Patients with Non-metastatic Bifocal Germinoma: Bo Li, Wenyi Lv, Chunde Li, Jiongxian Yang, Jiajia Chen, Jin Feng, Li Chen, Zhenyu Ma, Youqi Li, Jiayi Wang, Yanwei Liu, Yanong Li, Shuai Liu, Shiqi Luo, Xiaoguang Qiu; Cancer Res Treat. 2021;53(2):607. Published online March 9, 2021; DOI: https://doi.org/10.4143/crt.2020.437.E; Corrects: Cancer Res Treat 2020;52(4):1050

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Original Articles

Central nervous system

Comparison between Craniospinal Irradiation and Limited-Field Radiation in Patients with Non-metastatic Bifocal Germinoma: Bo Li, Wenyi Lv, Chunde Li, Jiongxian Yang, Jiajia Chen, Jin Feng, Li Chen, Zhenyu Ma, Youqi Li, Jiayi Wang, Yanwei Liu, Yanong Li, Shuai Liu, Shiqi Luo, Xiaoguang Qiu; Cancer Res Treat. 2020;52(4):1050-1058. Published online July 9, 2020; DOI: https://doi.org/10.4143/crt.2020.437; Correction in: Cancer Res Treat 2021;53(2):607

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Purpose
Whether craniospinal irradiation (CSI) could be replaced by limited-field radiation in non-metastatic bifocal germinoma remains controversial. We addressed the issue based on the data from our series and the literature.
Methods
Data from 49 patients diagnosed with non-metastatic bifocal germinoma at our hospital during the last 10 years were collected. The Pediatric Quality of Life Inventory 4.0 was used to evaluate health-related quality of life (HRQOL). Additionally, 81 patients identified from the literature were also analyzed independently.
Results
In our cohort, 34 patients had tumors in the sellar/suprasellar (S/SS) plus pineal gland (PG) regions and 15 in the S/SS plus basal ganglia/thalamus (BG/T) regions. The median follow-up period was 52 months (range, 10 to 134 months). Our survival analysis showed that patients treated with CSI (n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS; p=0.540), but better DFS than those treated with focal radiotherapy (FR; n=3, p=0.016). All 81 patients from the literature had tumors in the S/SS+PG regions. Relapses were documented in 4/45 patients treated with FR, 2/17 treated with whole-ventricle irradiation, 0/4 treated with WBRT, and 1/15 treated with CSI. Survival analysis did not reveal DFS differences between the types of radiation field (p=0.785). HRQOL analysis (n=44) in our cohort found that, compared with S/SS+PG germinoma, patients with BG/T involvement had significantly lower scores in social and school domains. However, HRQOL difference between patients treated with CSI and those not treated with CSI was not significant.
Conclusion
In patients with non-metastatic bifocal germinoma, it is rational that CSI could be replaced by limited-field radiation. HRQOL in patients with BG/T involvement was poorer.

Citations

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Long-term intelligence after high-dose radiotherapy to the primary site versus chemotherapy and whole-ventricle radiotherapy in patients with germinoma
Masayuki Kanamori, Yumi Sugawara, Yoshiteru Shimoda, Osamu Iizuka, Yoshinari Osada, Shota Yamashita, Ichiyo Shibahara, Rei Umezawa, Naoko Mori, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Keiichi Jingu, Shunji Mugikura, Kyoko Suzuki, Hidenori Endo
International Journal of Clinical Oncology.2026; 31(4): 649. CrossRef
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International Journal of Clinical Oncology.2025; 30(10): 1906. CrossRef
Retrospective investigation of hereditary syndromes in patients with medulloblastoma in a single institution
Ying Wang, Jingchuan Wu, Wei Li, Jiankang Li, Raynald Liu, Bao Yang, Chunde Li, Tao Jiang
Child's Nervous System.2021; 37(2): 411. CrossRef
Pineal Gland Tumors: A Review
Gaia Favero, Francesca Bonomini, Rita Rezzani
Cancers.2021; 13(7): 1547. CrossRef
Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma
Cristina Ilcus, Horatiu Silaghi, Carmen Emanuela Georgescu, Carmen Georgiu, Anca Ileana Ciurea, Simona Delia Nicoara, Cristina Alina Silaghi
Journal of Personalized Medicine.2021; 11(7): 661. CrossRef
Basal Ganglia Germ Cell Tumors With or Without Sellar Involvement: A Long-Term Follow-Up in a Single Medical Center and a Systematic Literature Review
Yi Zhang, Li Wang, Wenbin Ma, Hui Pan, Renzhi Wang, Huijuan Zhu, Yong Yao
Frontiers in Endocrinology.2021;[Epub] CrossRef

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Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18: Xiaohui Xu, Cheng Song, Zhihua Chen, Chenxiao Yu, Yi Wang, Yiting Tang, Judong Luo; Cancer Res Treat. 2018;50(1):71-87. Published online February 24, 2017; DOI: https://doi.org/10.4143/crt.2017.013

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Purpose
The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC).
Materials and Methods
In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3’-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used.
Results
In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay.
Conclusion
HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.

Citations

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Man Wang, Shuai Jiang, Yinfeng Zhang, Peifeng Li, Kun Wang
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