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Volume 53(4); October 2021
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Editorial
The Law Changes Behaviors: Is It Just Enough?
Dae Ho Lee
Cancer Res Treat. 2021;53(4):895-896.   Published online September 23, 2021
DOI: https://doi.org/10.4143/crt.2021.1025
PDFPubReaderePub
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  • 80 Download
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Special Articles
The Situation of Life-Sustaining Treatment One Year after Enforcement of the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life in Korea: Data of National Agency for Management of Life-Sustaining Treatment
Ha Yeon Lee, Hwa Jung Kim, Jung Hye Kwon, Sun Kyung Baek, Young-Woong Won, Yu Jung Kim, Su Jin Baik, Hyewon Ryu
Cancer Res Treat. 2021;53(4):897-907.   Published online June 2, 2021
DOI: https://doi.org/10.4143/crt.2021.327
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The “Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment for Patients at the End-of-Life” was enacted on February 3, 2016 and went into effect on February 4, 2018 in Korea. This study reviewed the first year of determination to life-sustaining treatment (LST) through data analysis of the National Agency for Management of Life-Sustaining Treatment.
Materials and Methods
The National Agency for Management of LST provided data between February 4, 2018 and January 31, 2019 anonymously from 33,549 patients. According to the forms patients were defined as either elf-determinants or family-determinants.
Results
The median age of the patient was 73 and the majority was male (59.9%). Cancer patients were 59% and self-determinants were 32.1%. Cancer patients had a higher rate of self-determinants than non-cancer (47.3% vs. 10.1%). Plan for hospice service was high in cancer patients among self-determinants (81.0% vs. 37.5%, p < 0.001). In comparison to family-determinants, self-determinants were younger (median age, 67 years vs. 75 years; p < 0.001) and had more cancer diagnosis (87.1% vs. 45.9%, p < 0.001). Decision of withholding or withdrawing of LSTs in cancer patients was higher than non-cancer patients in four items.
Conclusion
Cancer patients had a higher rate in self-determination and withholding or withdrawing of LSTs than non-cancer patients. Continued revision of the law and education of the public will be able to promote withdrawing or withholding the futile LSTs in patients at end-of-life. Further study following the revision of the law should be evaluated to change of end-of-life care.

Citations

Citations to this article as recorded by  
  • Issues and implications of the life-sustaining treatment decision act: comparing the data from the survey and clinical data of inpatients at the end-of-life process
    Eunjeong Song, Dongsoon Shin, Jooseon Lee, Seonyoung Yun, Minjeong Eom, Suhee Oh, Heejung Lee, Jiwan Lee, Rhayun Song
    BMC Medical Ethics.2024;[Epub]     CrossRef
  • Recent Trends in the Withdrawal of Life-Sustaining Treatment in Patients with Acute Cerebrovascular Disease : 2017–2021
    Seung Hwan Kim, Ji Hwan Jang, Young Zoon Kim, Kyu Hong Kim, Taek Min Nam
    Journal of Korean Neurosurgical Society.2024; 67(1): 73.     CrossRef
  • Healthcare Utilization and Supportive Care Timing in South Korean People Living With Amyotrophic Lateral Sclerosis: A Single-Center Retrospective Study
    Min Seol Jang, Shin Hye Yoo, Min Sun Kim, Belong Cho, Kyae Hyung Kim, Jeongmi Shin, Inyoung Hwang, Seok-Jin Choi, Jung-Joon Sung, Sun Young Lee
    Journal of Clinical Neurology.2024;[Epub]     CrossRef
  • Differences in end-of-life care patterns between types of hospice used for cancer patients: a retrospective cohort study
    Il Yun, Eun-Cheol Park, Chung Mo Nam, Jaeyong Shin, Suk-Yong Jang, Sung-In Jang
    BMC Palliative Care.2024;[Epub]     CrossRef
  • Validation of the Korean Version of the Clinical Frailty Scale-Adjusted Korean Triage and Acuity Scale for Older Patients in the Emergency Department
    Ho Sub Chung, Yunhyung Choi, Ji Yeon Lim, Keon Kim, Sung Jin Bae, Yoon Hee Choi, Dong Hoon Lee
    Medicina.2024; 60(6): 955.     CrossRef
  • Beyond Legal Boundaries: Public and Clinician Perspectives on Treatment Withdrawal in Infants With Poor Neurological Prognosis
    In Gyu Song, Jung Lee, Min Sun Kim, Ji Weon Lee, So Yeon Jeon, Shin Hye Yoo, Hye Yoon Park
    Journal of Korean Medical Science.2024;[Epub]     CrossRef
  • Preferred versus Actual Place of Care and Factors Associated with Home Discharge among Korean Patients with Advanced Cancer: A Retrospective Cohort Study
    In Young Hwang, Yohan Han, Min Sun Kim, Kyae Hyung Kim, Belong Cho, Wonho Choi, Yejin Kim, Shin Hye Yoo, Sun Young Lee
    Healthcare.2023; 11(13): 1939.     CrossRef
  • Comparison of the end-of-life decisions of patients with hospital-acquired pneumonia after the enforcement of the life-sustaining treatment decision act in Korea
    Ae-Rin Baek, Sang-Bum Hong, Soohyun Bae, Hye Kyeong Park, Changhwan Kim, Hyun-Kyung Lee, Woo Hyun Cho, Jin Hyoung Kim, Youjin Chang, Heung Bum Lee, Hyun-Il Gil, Beomsu Shin, Kwang Ha Yoo, Jae Young Moon, Jee Youn Oh, Kyung Hoon Min, Kyeongman Jeon, Moon S
    BMC Medical Ethics.2023;[Epub]     CrossRef
  • Problems Related to the Act on Decisions on Life-Sustaining Treatment and Directions for Improvement
    Dae Seog Heo, Shin Hye Yoo, Bhumsuk Keam, Sang Ho Yoo, Younsuck Koh
    The Korean Journal of Hospice and Palliative Care.2022; 25(1): 1.     CrossRef
  • Hospice-Palliative Medicine as a Model of Value-Based Healthcare
    Dae Seog Heo, Shin Hye Yoo, Bhumsuk Keam, Keunjoo Yoo, Insun Choi, Min-Jeong Kim
    Journal of Korean Medical Science.2022;[Epub]     CrossRef
  • Will implementation of the Life-sustaining Treatment Decisions Act reduce the incidence of cardiopulmonary resuscitation?
    In-Ae Song
    Acute and Critical Care.2022; 37(2): 256.     CrossRef
  • Aggressiveness of care in the last days of life in the emergency department of a tertiary hospital in Korea
    Jung Sun Kim, Sun Young Lee, Min Sung Lee, Shin Hye Yoo, Jeongmi Shin, Wonho Choi, Yejin Kim, Hyung Sook Han, Jinui Hong, Bhumsuk Keam, Dae Seog Heo
    BMC Palliative Care.2022;[Epub]     CrossRef
  • Hospice Care Preferences and Its Associated Factors among Community-Dwelling Residents in China
    Huijing Lin, Eunjeong Ko, Bei Wu, Ping Ni
    International Journal of Environmental Research and Public Health.2022; 19(15): 9197.     CrossRef
  • Impact of COVID-19 on the End-of-Life Care of Cancer Patients Who Died in a Korean Tertiary Hospital: A Retrospective Study
    Jeongmi Shin, Yejin Kim, Shin Hye Yoo, Jin-Ah Sim, Bhumsuk Keam
    The Korean Journal of Hospice and Palliative Care.2022; 25(4): 150.     CrossRef
  • The Law Changes Behaviors: Is It Just Enough?
    Dae Ho Lee
    Cancer Research and Treatment.2021; 53(4): 895.     CrossRef
  • 7,710 View
  • 210 Download
  • 13 Web of Science
  • 15 Crossref
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Life-Sustaining Treatment States in Korean Cancer Patients after Enforcement of Act on Decisions on Life-Sustaining Treatment for Patients at the End of Life
Young-Woong Won, Hwa Jung Kim, Jung Hye Kwon, Ha Yeon Lee, Sun Kyung Baek, Yu Jung Kim, Do Yeun Kim, Hyewon Ryu
Cancer Res Treat. 2021;53(4):908-916.   Published online June 2, 2021
DOI: https://doi.org/10.4143/crt.2021.325
AbstractAbstract PDFPubReaderePub
Purpose
In Korea, the “Act on Hospice and Palliative Care and Decisions on Life-sustaining Treatment for Patients at the End of Life” was enacted on February 4, 2018. This study was conducted to analyze the current state of life-sustaining treatment decisions based on National Health Insurance Service (NHIS) data after the law came into force.
Materials and Methods
The data of 173,028 cancer deaths were extracted from NHIS qualification data between November 2015 and January 2019.
Results
The number of cancer deaths complied with the law process was 14,438 of 54,635 cases (26.4%). The rate of patient self-determination was 49.0%. The patients complying with the law process have used a hospice center more frequently (28% vs. 14%). However, the rate of intensive care unit (ICU) admission was similar between the patients who complied with and without the law process (ICU admission, 23% vs. 21%). There was no difference in the proportion of patients who had undergone mechanical ventilation and hemodialysis in the comparative analysis before and after the enforcement of the law and the analysis according to the compliance with the law. The patients who complied with the law process received cardiopulmonary resuscitation at a lower rate.
Conclusion
The law has positive effects on the rate of life-sustaining treatment decision by patient’s determination. However, there was no sufficient effect on the withholding or withdrawing of life-sustaining treatment, which could protect the patient from unnecessary or harmful interventions.

Citations

Citations to this article as recorded by  
  • Characteristics and outcomes of patients with do-not-resuscitate and physician orders for life-sustaining treatment in a medical intensive care unit: a retrospective cohort study
    Song-I Lee, Ye-Rin Ju, Da Hyun Kang, Jeong Eun Lee
    BMC Palliative Care.2024;[Epub]     CrossRef
  • Characteristics of Life-Sustaining Treatment Decisions: National Data Analysis in South Korea
    Jiyeon Choi, Heejung Jeon, Ilhak Lee
    Asian Bioethics Review.2024; 16(1): 33.     CrossRef
  • Recent Trends in the Withdrawal of Life-Sustaining Treatment in Patients with Acute Cerebrovascular Disease : 2017–2021
    Seung Hwan Kim, Ji Hwan Jang, Young Zoon Kim, Kyu Hong Kim, Taek Min Nam
    Journal of Korean Neurosurgical Society.2024; 67(1): 73.     CrossRef
  • The Impact of Withdrawing or Withholding of Life-Sustaining Treatment: A Nationwide Case-Control Study Based on Medical Cost Analysis
    Claire Junga Kim, Do-Kyong Kim, Sookyeong Mun, Minkook Son
    Journal of Korean Medical Science.2024;[Epub]     CrossRef
  • For the Universal Right to Access Quality End-of-Life Care in Korea: Broadening Our Perspective After the 2018 Life-Sustaining Treatment Decisions Act
    Hye Yoon Park, Min Sun Kim, Shin Hye Yoo, Jung Lee, In Gyu Song, So Yeon Jeon, Eun Kyung Choi
    Journal of Korean Medical Science.2024;[Epub]     CrossRef
  • Differences in end-of-life care patterns between types of hospice used for cancer patients: a retrospective cohort study
    Il Yun, Eun-Cheol Park, Chung Mo Nam, Jaeyong Shin, Suk-Yong Jang, Sung-In Jang
    BMC Palliative Care.2024;[Epub]     CrossRef
  • Epidemiology of patients who died in the emergency departments and need of end-of-life care in Korea from 2016 to 2019
    Sun Young Lee, Young Sun Ro, Sang Do Shin, Eunsil Ko, Seong Jung Kim
    Scientific Reports.2023;[Epub]     CrossRef
  • Use of high‐flow nasal cannula oxygen therapy for patients with terminal cancer at the end of life
    Jung Sun Kim, Jeongmi Shin, Nam Hee Kim, Sun Young Lee, Shin Hye Yoo, Bhumsuk Keam, Dae Seog Heo
    Cancer Medicine.2023; 12(13): 14612.     CrossRef
  • Preferred versus Actual Place of Care and Factors Associated with Home Discharge among Korean Patients with Advanced Cancer: A Retrospective Cohort Study
    In Young Hwang, Yohan Han, Min Sun Kim, Kyae Hyung Kim, Belong Cho, Wonho Choi, Yejin Kim, Shin Hye Yoo, Sun Young Lee
    Healthcare.2023; 11(13): 1939.     CrossRef
  • Healthcare resource utilization and medical costs in patients with terminal cancer during best supportive care
    Dong-Won Kang, Yoon-Bo Shim, Eui-Kyung Lee, Mi-Hai Park, Wen-Chi Chou
    PLOS ONE.2022; 17(6): e0269565.     CrossRef
  • Aggressiveness of care in the last days of life in the emergency department of a tertiary hospital in Korea
    Jung Sun Kim, Sun Young Lee, Min Sung Lee, Shin Hye Yoo, Jeongmi Shin, Wonho Choi, Yejin Kim, Hyung Sook Han, Jinui Hong, Bhumsuk Keam, Dae Seog Heo
    BMC Palliative Care.2022;[Epub]     CrossRef
  • Effect of life-sustaining treatment decision law on pediatric in-hospital cardiopulmonary resuscitation rate: A Korean population-based study
    Jaeyoung Choi, Ah Young Choi, Esther Park, Meong Hi Son, Joongbum Cho
    Resuscitation.2022; 180: 38.     CrossRef
  • Association of perceived life satisfaction with attitudes toward life-sustaining treatment among the elderly in South Korea: a cross-sectional study
    Il Yun, Hyunkyu Kim, Eun-Cheol Park, Suk-Yong Jang
    BMC Palliative Care.2022;[Epub]     CrossRef
  • Willingness of patients with cancer pain to participate in end-of-life decisions: a multi-center cross-sectional study from three coastal provinces in southern China
    Xi Ke, Hongyu Zhu, Yu Zhang, Ling Yang, Simei Shi, Fang Zhu, Huiyu Luo
    BMC Palliative Care.2022;[Epub]     CrossRef
  • The Law Changes Behaviors: Is It Just Enough?
    Dae Ho Lee
    Cancer Research and Treatment.2021; 53(4): 895.     CrossRef
  • 5,815 View
  • 153 Download
  • 15 Web of Science
  • 15 Crossref
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Current Status and Cardinal Features of Patient Autonomy after Enactment of the Life-Sustaining Treatment Decisions Act in Korea
Hwa Jung Kim, Yu Jung Kim, Jung Hye Kwon, Young-Woong Won, Ha Yeon Lee, Sun Kyung Baek, Hyewon Ryu, Do Yeun Kim
Cancer Res Treat. 2021;53(4):917-925.   Published online June 2, 2021
DOI: https://doi.org/10.4143/crt.2021.324
AbstractAbstract PDFPubReaderePub
Purpose
The main purpose of the Life-Sustaining Treatment Decisions Act recently enacted in Korea is to respect the patient’s self-determination. We aimed to investigate the current status and features of patient self-determination after implementation of the law.
Materials and Methods
Between February 2018 and January 2019, 54,635 cancer deaths were identified from the National Health Insurance Service (NHIS) database. We analyzed the characteristics of decedents who complied with the law process by self-determination compared with decedents with family determination and with decedents who did not comply with the law process.
Results
In multivariable analysis, patients with self-determination were younger, were less likely to live in rural areas, were less likely to belong to the highest income quintile, were less likely to be treated in general hospitals, and were more likely to show a longer time from cancer diagnosis compared with patients with family determination. Compared with patients who did not comply with the law process, patients with self-determination were younger, lived in Seoul or capital area, were less likely to belong to the highest income quintile, were treated in general hospitals, were less likely to have genitourinary or hematologic malignancies, scored higher on the Charlson comorbidity index, and showed a longer time from cancer diagnosis. Patients with self-determination were more likely to use hospice and less likely to use intensive care units (ICUs) at the end-of-life (EOL).
Conclusion
Decedents with self-determination were more likely to be younger, reside in the Seoul or capital area, show a longer time from cancer diagnosis, and were less likely to belong to the highest income quintile. They utilized hospice more frequently, and received less ICU care at the EOL.

Citations

Citations to this article as recorded by  
  • The effects of hospice care on healthcare expenditure among cancer patients
    Hoyol Jhang, Wonjeong Jeong, Hyun-Soo Zhang, Dong-Woo Choi, Hyejung Kang, Sohee Park
    BMC Health Services Research.2023;[Epub]     CrossRef
  • Problems Related to the Act on Decisions on Life-Sustaining Treatment and Directions for Improvement
    Dae Seog Heo, Shin Hye Yoo, Bhumsuk Keam, Sang Ho Yoo, Younsuck Koh
    The Korean Journal of Hospice and Palliative Care.2022; 25(1): 1.     CrossRef
  • Aggressiveness of care in the last days of life in the emergency department of a tertiary hospital in Korea
    Jung Sun Kim, Sun Young Lee, Min Sung Lee, Shin Hye Yoo, Jeongmi Shin, Wonho Choi, Yejin Kim, Hyung Sook Han, Jinui Hong, Bhumsuk Keam, Dae Seog Heo
    BMC Palliative Care.2022;[Epub]     CrossRef
  • Use of antimicrobial agents in actively dying inpatients after suspension of life-sustaining treatments: Suggestion for antimicrobial stewardship
    Dayeong Kim, Subin Kim, Kyoung Hwa Lee, Sang Hoon Han
    Journal of Microbiology, Immunology and Infection.2022; 55(4): 651.     CrossRef
  • Association of perceived life satisfaction with attitudes toward life-sustaining treatment among the elderly in South Korea: a cross-sectional study
    Il Yun, Hyunkyu Kim, Eun-Cheol Park, Suk-Yong Jang
    BMC Palliative Care.2022;[Epub]     CrossRef
  • The Law Changes Behaviors: Is It Just Enough?
    Dae Ho Lee
    Cancer Research and Treatment.2021; 53(4): 895.     CrossRef
  • 6,029 View
  • 132 Download
  • 4 Web of Science
  • 6 Crossref
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Preparation and Practice of the Necessary Documents in Hospital for the “Act on Decision of Life-Sustaining Treatment for Patients at the End-of-Life”
Sun Kyung Baek, Hwa Jung Kim, Jung Hye Kwon, Ha Yeon Lee, Young-Woong Won, Yu Jung Kim, Sujin Baik, Hyewon Ryu
Cancer Res Treat. 2021;53(4):926-934.   Published online June 2, 2021
DOI: https://doi.org/10.4143/crt.2021.326
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Six forms relating to decisions on life-sustaining treatment (LST) for patients at the end-of-life (EOL) in hospital are required by the “Act on Decision of LST for Patients at the EOL.” We investigated the preparation and creation status of these documents from the database of the National Agency for Management of LST.
Materials and Methods
We analyzed the contents and details of each document necessary for decisions on LST, and the creation status of forms. We defined patients completing form 1 as “self-determined” of LST, and those whose family members had completed form 11/12 as “family decision” of LST. According to the determination subject, we compared the four items of LST on form 13 (the paper of implementation of LST) and the documentation time interval between forms.
Results
The six forms require information about the patient, doctor, specialized doctor, family members, institution, decision for LST, and intention to use hospice services. Of 44,381 who had completed at least one document, 36,693 patients had form 13. Among them, 11,531, 10,976, and 12,551 people completed forms 1, 11, and 12, respectively. The documentation time interval from forms 1, 11, or 12 to form 13 was 8.6±13.6 days, 1.0±9.5 days, and 1.5±9.7 days, respectively.
Conclusion
The self-determination rate of LST was 31% and the mean time interval from self-determination to implementation of LST was 8.6 days. The creation of these forms still takes place when the patients are close to death.

Citations

Citations to this article as recorded by  
  • Advance Care Planning in South Korea
    Yu Jung Kim, Sun-Hyun Kim
    Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen.2023; 180: 68.     CrossRef
  • Use of antimicrobial agents in actively dying inpatients after suspension of life-sustaining treatments: Suggestion for antimicrobial stewardship
    Dayeong Kim, Subin Kim, Kyoung Hwa Lee, Sang Hoon Han
    Journal of Microbiology, Immunology and Infection.2022; 55(4): 651.     CrossRef
  • The Law Changes Behaviors: Is It Just Enough?
    Dae Ho Lee
    Cancer Research and Treatment.2021; 53(4): 895.     CrossRef
  • 5,601 View
  • 131 Download
  • 3 Web of Science
  • 3 Crossref
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Original Articles
General
Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea
Sung Uk Lee, Kyungmi Yang, Sung Ho Moon, Yang-Gun Suh, Gyu Sang Yoo
Cancer Res Treat. 2021;53(4):935-943.   Published online May 17, 2021
DOI: https://doi.org/10.4143/crt.2021.409
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Proton beam therapy (PBT) is a state-of-the-art technology employed in radiotherapy (RT) for cancer patients. This study characterized how PBT has been used in clinical practice in Korea.
Materials and Methods
Patients who received any type of RT between 2007 and 2019 were identified from the radiation oncology registry of the two PBT facilities operating in Korea (National Cancer Center and Samsung Medical Center). The chi-square test was used to identify patient- and treatment-related characteristics associated with the receipt of PBT.
Results
A total of 54,035 patients had been treated with some form of RT in the two institutions, of whom 5,398 received PBT (10.0%). The number of patients who receive PBT has gradually increased since PBT first started, from 162 patients in 2007 to 1,304 patients in 2019. Among all types of cancer, PBT use in liver cancer has been steadily increasing from 20% in 2008-2009 to 32% in 2018-2019. In contrast, that in prostate cancer has been continuously decreasing from 20% in 2008-2009 to < 10% in 2018-2019. Male sex, very young or old age, stage I-II disease, residency in non-capital areas, a definitive setting, a curative treatment aim, enrollment in a clinical trial, re-irradiation and insurance coverage were significantly associated with the receipt of PBT (all p < 0.05).
Conclusion
Since PBT started in Korea, the number of patients receiving PBT has increased to more than 1,000 per year and treatment indications have expanded. Liver cancer is the most common primary tumor among all PBT cases in Korea.

Citations

Citations to this article as recorded by  
  • “Particle therapy - future for the Baltic states?” – synthesis of the expert workshop report
    Kristaps Paļskis, Erika Korobeinikova, Dace Bogorada-Saukuma, Anna Maria Camarda, Rebecca Taylor, Elena Benedetto, Edgars Mamis, Maija Radziņa, Andrejs Ērglis, Diana Adliene, Manjit Dosanjh, Maurizio Vretenar, Toms Torims
    Health and Technology.2024; 14(5): 965.     CrossRef
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    Kamila Bała, Yana Samovich, Karolina Dorobisz
    Current Oncology Reports.2024;[Epub]     CrossRef
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    J. Isabelle Choi, Camille Hardy-Abeloos, Alicia Lozano, Alexandra Hanlon, Carlos Vargas, John H. Maduro, Julie Bradley, Birgitte Offersen, Bruce Haffty, Mark Pankuch, Richard Amos, Nalee Kim, Shannon M. MacDonald, Youlia Kirova, Robert W. Mutter
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    Kyungmi Yang, Jeong Eun Lee, Won Park, Yong Chan Ahn, Seung Jae Huh
    Japanese Journal of Clinical Oncology.2023; 53(12): 1177.     CrossRef
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  • 210 Download
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  • 4 Crossref
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Correlation of NUF2 Overexpression with Poorer Patient Survival in Multiple Cancers
Xiaodan Jiang, Yan Jiang, Senbiao Luo, Karthik Sekar, Clara Kai Ting Koh, Amudha Deivasigamani, Qingzhe Dong, Niankai Zhang, Shenling Li, Fengyun Hao, Brian Kim Poh Goh, London Lucien Ooi, Yu Wang, Kam Man Hui
Cancer Res Treat. 2021;53(4):944-961.   Published online January 4, 2020
DOI: https://doi.org/10.4143/crt.2020.466
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA).
Materials and Methods
RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma (HCC) cell lines was used to evaluate NUF2’s role in HCC in vitro and in vivo.
Results
NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 μm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo.
Conclusion
NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.

Citations

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    Lisha Bao, Yingying Gong, Yulu Che, Ying Li, Tong Xu, Jinming Chen, Shanshan Wang, Zhuo Tan, Ping Huang, Zongfu Pan, Minghua Ge
    Cell Death & Disease.2024;[Epub]     CrossRef
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    Meng Ren, Hongyu Zhao, Yan Gao, Qi Chen, Xiaoting Zhao, Wentao Yue
    Journal of Ovarian Research.2023;[Epub]     CrossRef
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    Rehanguli Aimaier, Man-Hon Chung, Yihui Gu, Qingxiong Yu, Chengjiang Wei, Haibo Li, Zizhen Guo, Manmei Long, Yuehua Li, Wei Wang, Qingfeng Li, Zhichao Wang
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    Runhan Zhao, Chuang Xiong, Chao Zhang, Lin Wang, Hao Liang, Xiaoji Luo, Po-Hsiang Tsui
    Computational and Mathematical Methods in Medicine.2022; 2022: 1.     CrossRef
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    Liang Guo, Zhangyi Wu
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    Feng Jiang, Xiaolu Huang, Xiang Yang, Huixin Zhou, Yumin Wang
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Natsaranyatron Singharajkomron, Varalee Yodsurang, Suthasinee Seephan, Sakkarin Kungsukool, Supinda Petchjorm, Nara Maneeganjanasing, Warunyu Promboon, Wadsana Dangwilailuck, Varisa Pongrakhananon
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    Ruobing Leng, Yunfang Meng, Xiaomei Sun, Yingzi Zhao
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Nathan R Jacobs, Pamela A Norton
    World Journal of Hepatology.2021; 13(6): 662.     CrossRef
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Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort
Hwa Kyung Byun, Seung Yeun Chung, Kyoung-Jin Kim, Jinsil Seong
Cancer Res Treat. 2021;53(4):962-972.   Published online January 26, 2021
DOI: https://doi.org/10.4143/crt.2020.1053
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia.
Materials and Methods
A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/μL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively.
Results
Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. –0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months.
Conclusion
IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

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    Kyra M. Boorsma Bergerud, Matthew Berkseth, Drew M. Pardoll, Sudipto Ganguly, Lawrence R. Kleinberg, Jessica Lawrence, David J. Odde, David A. Largaespada, Stephanie A. Terezakis, Lindsey Sloan
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    Aleksei A. Stepanenko, Anastasiia O. Sosnovtseva, Marat P. Valikhov, Anastasia A. Chernysheva, Olga V. Abramova, Victor A. Naumenko, Vladimir P. Chekhonin
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    Yu-Chun Song, Si-Ye Chen, Xu-Ran Zhao, Hao Jing, Hui Fang, Yu Tang, Shang-Ying Hu, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Shu-Nan Qi, Guang-Yi Sun, Qiu-Zi Zhong, Xiang-Hui Du, Juan Liu, Ye-Xiong Li, Shu-Lian Wang
    Radiotherapy and Oncology.2024; 199: 110390.     CrossRef
  • Compassionate use of recombinant human IL‐7‐hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma
    Stephen Ahn, Jae‐Sung Park, Heewon Kim, Minkyu Heo, Young Chul Sung, Sin‐Soo Jeun
    Cancer Medicine.2023; 12(6): 6778.     CrossRef
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Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing
Hai-Yun Wang, Ling Deng, Ying-Qing Li, Xiao Zhang, Ya-Kang Long, Xu Zhang, Yan-Fen Feng, Yuan He, Tao Tang, Xin-Hua Yang, Fang Wang
Cancer Res Treat. 2021;53(4):973-982.   Published online February 18, 2021
DOI: https://doi.org/10.4143/crt.2020.798
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice.
Materials and Methods
TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate.
Results
The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR‒positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs.
Conclusion
Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR‒positive status could be a significant biomarker for predicting ICI response in patients.

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  • Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study
    Ling Deng, Hai‐Yun Wang, Chun‐Fang Hu, Xiao‐Yun Liu, Kuntai Jiang, Juan‐Juan Yong, Xiao‐Yan Wu, Kai‐Hua Guo, Fang Wang
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    Umer Ali, Sunitha Vungarala, Venkataswarup Tiriveedhi
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    Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
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    Zhixuan You, Meng Lv, Xuanyu He, Yingqin Pan, Junfeng Ge, Xue Hu, Yating Zheng, Mengli Huang, Chengzhi Zhou, Changxuan You
    Frontiers in Immunology.2022;[Epub]     CrossRef
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    Congqi Shi, Kaiyu Qin, Anqi Lin, Aimin Jiang, Quan Cheng, Zaoqu Liu, Jian Zhang, Peng Luo
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    P. Sean Walsh, Yangyang Hao, Jie Ding, Jianghan Qu, Jonathan Wilde, Ruochen Jiang, Richard T. Kloos, Jing Huang, Giulia C. Kennedy
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CNS cancer
Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae
Joo Ho Lee, Keun-Yong Eom, Ji Hoon Phi, Chul-Kee Park, Seung Ki Kim, Byung-Kyu Cho, Tae Min Kim, Dae Seog Heo, Kyung Taek Hong, Jung Yoon Choi, Hyoung Jin Kang, Hee Young Shin, Seung Hong Choi, Soon Tae Lee, Sung Hye Park, Kyu-Chang Wang, Il Han Kim
Cancer Res Treat. 2021;53(4):983-990.   Published online January 13, 2021
DOI: https://doi.org/10.4143/crt.2020.1052
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.
Materials and Methods
Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.
Results
The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.
Conclusion
De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

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  • NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors
    Eric Eunshik Kim, Chul-Kee Park, Seung-Ki Kim, Ji Hoon Phi, Sun Ha Paek, Jung Yoon Choi, Hyoung Jin Kang, Joo Ho Lee, Jae Kyung Won, Hongseok Yun, Sung-Hye Park
    Acta Neuropathologica Communications.2024;[Epub]     CrossRef
  • Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up
    Masayuki Kanamori, Shunji Mugikura, Osamu Iizuka, Naoko Mori, Yoshiteru Shimoda, Ichiyo Shibahara, Rei Umezawa, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Kyoko Suzuki, Hidenori Endo
    Journal of Neuro-Oncology.2024; 170(1): 173.     CrossRef
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    Hyejo Ryu, Joo Ho Lee
    Radiation Oncology Journal.2023; 41(1): 48.     CrossRef
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    Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore
    Current Oncology Reports.2023; 25(7): 765.     CrossRef
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    Adam J. Grippin, Susan L. McGovern
    Frontiers in Oncology.2023;[Epub]     CrossRef
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    Iwona Jabłońska, Marcin Goławski, Elżbieta Nowicka, Katarzyna Drosik-Rutowicz, Anna Trybus, Rafał Tarnawski, Marcin Miszczyk
    Cancers.2023; 15(10): 2789.     CrossRef
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    Kyung-Nam Koh, Ru Xin Wong, Dong-Eun Lee, Jung Woo Han, Hwa Kyung Byun, Hong In Yoon, Dong-Seok Kim, Chuhl Joo Lyu, Hyoung Jin Kang, Kyung Taek Hong, Joo Ho Lee, Il Han Kim, Ji Hoon Phi, Seung-Ki Kim, Tai-Tong Wong, Hsin-Lun Lee, I-Chun Lai, Yu-Mei Kang,
    Neuro-Oncology.2022; 24(8): 1389.     CrossRef
  • Photon versus proton whole ventricular radiotherapy for non‐germinomatous germ cell tumors: A report from the Children's Oncology Group
    David Y. Mak, Zain Siddiqui, Zhihui Amy Liu, Hitesh Dama, Shannon M. MacDonald, Shengjie Wu, Erin S. Murphy, Matthew D. Hall, Victor Malkov, Arzu Onar‐Thomas, Sameera Ahmed, Girish Dhall, Derek S. Tsang
    Pediatric Blood & Cancer.2022;[Epub]     CrossRef
  • Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission
    Takao Tsurubuchi, Kei Hara, Shingo Takano, Ai Muroi, Hiroko Fukushima, Masashi Mizumoto, Noriaki Sakamoto, Masahide Matsuda, Hiroyoshi Akutsu, Hideyuki Sakurai, Eiichi Ishikawa
    World Neurosurgery.2022; 166: e325.     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
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Head and Neck Cancer
Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma
Wan-Ru Zhang, Yu-Yun Du, Chun-Yan Guo, Han-Xing Zhou, Jie-Yi Lin, Xiao-Han Meng, Hao-Yuan Mo, Dong-Hua Luo
Cancer Res Treat. 2021;53(4):991-1003.   Published online January 13, 2021
DOI: https://doi.org/10.4143/crt.2020.1298
AbstractAbstract PDFPubReaderePub
Purpose
This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients.
Materials and Methods
Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS).
Results
Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05).
Conclusion
Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Citations

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  • Antibody Profiling of Pan-Cancer Viral Proteome Reveals Biomarkers for Nasopharyngeal Carcinoma Diagnosis and Prognosis
    Te Liang, Hao Chen, Lei Liu, Yongqiang Zheng, Zhaoen Ma, Ling Min, Jiahui Zhang, Lianfu Wu, Jie Ma, Zexian Liu, Qingfeng Zhang, Kai Luo, Di Hu, Tianxing Ji, Xiaobo Yu
    Molecular & Cellular Proteomics.2024; 23(3): 100729.     CrossRef
  • 15,257 View
  • 174 Download
  • 1 Crossref
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Recent Treatment Patterns of Oropharyngeal Cancer in Korea Based on the Expert Questionnaire Survey of the Korean Society for Head and Neck Oncology (KSHNO)
Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Ji-hoon Kim, Woo-Jin Jeong, Inn-Chul Nam, Jin Ho Kim, Hee Kyung Ahn, Sang Hoon Chun, Hyun Jun Hong, Young-Hoon Joo, Young-Gyu Eun, Sung Ho Moon, Jeongshim Lee
Cancer Res Treat. 2021;53(4):1004-1014.   Published online January 29, 2021
DOI: https://doi.org/10.4143/crt.2020.973
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea.
Materials and Methods
Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals.
Results
Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001).
Conclusion
In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

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  • Controversies in Lung Cancer: Heterogeneity in Treatment Recommendations for Stage III NSCLC According to Disease Burden and Oncogenic Driver Alterations
    Jeremy P Harris, Dylann K Fujimoto, Misako Nagasaka, Eric Ku, Garrett Harada, Hari Keshava, Ali Mahtabifard, Javier Longoria, Niral Patel, Steven Seyedin, Aaron Simon, Allen Chen
    Clinical Lung Cancer.2022; 23(4): 333.     CrossRef
  • Survey of radiation field and dose in human papillomavirus-positive oropharyngeal cancer: is de-escalation actually applied in clinical practice?
    Kyu Hye Choi, Jin Ho Song, Yeon-Sil Kim, Sung Ho Moon, Jeongshim Lee, Young-Taek Oh, Dongryul Oh, Jin Ho Kim, Jun Won Kim
    Radiation Oncology Journal.2021; 39(3): 174.     CrossRef
  • 6,038 View
  • 154 Download
  • 3 Web of Science
  • 2 Crossref
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Lung Cancer
Clinical Significance of Acute Kidney Injury in Lung Cancer Patients
Semin Cho, Eunjeong Kang, Ji Eun Kim, U Kang, Hee Gyung Kang, Minsu Park, Kwangsoo Kim, Dong Ki Kim, Kwon Wook Joo, Yon Su Kim, Hyung-Jin Yoon, Hajeong Lee
Cancer Res Treat. 2021;53(4):1015-1023.   Published online January 18, 2021
DOI: https://doi.org/10.4143/crt.2020.1010
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Acute kidney injury (AKI) in cancer patients is associated with increased morbidity and mortality. The incidence of AKI in lung cancer seems to be relatively higher compared with other solid organ malignancies, although its impact on patient outcomes remains unclear.
Materials and Methods
The patients newly diagnosed with lung cancer from 2004 to 2013 were enrolled in this retrospective cohort study. The patients were categorized according to the presence and severity of AKI. We compared all-cause mortality and long-term renal outcome according to AKI stage.
Results
A total of 3,202 patients were included in the final analysis. AKI occurred in 1,783 (55.7%) patients during the follow-up period, with the majority having mild AKI stage 1 (75.8%). During the follow-up of 2.6±2.2 years, total 1,251 patients (53.7%) were died and 5-year survival rate was 46.9%. We found that both AKI development and severity were independent risk factors for all-cause mortality in lung cancer patients, even after adjustment for lung cancer-specific variables including the stage or pathological type. In addition, patients suffered from more severe AKI tend to encounter de novo chronic kidney disease development, worsening kidney function, and end-stage kidney disease progression.
Conclusion
In this study, more than half of the lung cancer patients experienced AKI during their diagnosis and treatment period. Moreover, AKI occurrence and more advanced AKI were associated with a higher mortality risk and adverse kidney outcomes.

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  • Acute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials
    Isabela Gonçalves Lima, Isabele Benck Usiro Cabral da Silva, Vitória Carpentieri Pípolo, Vinicius Daher Alvares Delfino, Paulo Roberto Bignardi
    Immunopharmacology and Immunotoxicology.2024; 46(4): 470.     CrossRef
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    Feng Wu, Shiyuan Wang, Jialing Zhang, Peixin Wang, Aihua Zhang
    International Urology and Nephrology.2024;[Epub]     CrossRef
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    Ying Huang, Yang Li, Xialian Xu, Jie Teng, Xiaoqiang Ding, Jiarui Xu
    Renal Failure.2024;[Epub]     CrossRef
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    Huijuan Qian, Si Li, Ziyun Hu
    Oncology Letters.2024;[Epub]     CrossRef
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    Chen Gao, Longkai Peng
    Frontiers in Medicine.2023;[Epub]     CrossRef
  • Point of care ultrasonography in onco-nephrology: A stride toward better physical examination
    Bhavna Bhasin-Chhabra, Abhilash Koratala
    World Journal of Nephrology.2023; 12(2): 29.     CrossRef
  • Protocolo diagnóstico y tratamiento de la nefropatía en los pacientes con neoplasia sólida
    Rodríguez Doyágüez, M.P. Morán Magro, C.M. Durán López, P. Martínez Miguel
    Medicine - Programa de Formación Médica Continuada Acreditado.2023; 13(82): 4870.     CrossRef
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The Clinical Impact of Capmatinib in the Treatment of Advanced Non–Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification
Wonyoung Choi, Seog-Yun Park, Youngjoo Lee, Kun Young Lim, Minjoung Park, Geon Kook Lee, Ji-Youn Han
Cancer Res Treat. 2021;53(4):1024-1032.   Published online January 29, 2021
DOI: https://doi.org/10.4143/crt.2020.1331
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non–small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.
Materials and Methods
Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study. MET gene copy number (GCN), protein expression, and METex14 were analyzed and the patients’ clinical outcome were retrospectively reviewed.
Results
A total of 72 patients were included in this analysis (group A: GCN ≥ 10 or METex14, n=14; group B: others, n=58). Among them, 13 patients were treated with capmatinib (group A, n=8; group B, n=5), and the overall response rate was 50% for group A, and 0% for group B. In all patients, the median overall survival (OS) was 20.2 months (95% confidence interval [CI], 6.9 to not applicable [NA]) for group A, and 11.3 months (95% CI, 8.2 to 20.3) for group B (p=0.457). However, within group A, median OS was 21.5 months (95% CI, 20.8 to NA) for capmatinib-treated, and 7.5 months (95% CI, 3.2 to NA) for capmatinib-untreated patients (p=0.025). Among all capmatinib-untreated patients (n=59), group A showed a trend towards worse OS to group B (median OS, 7.5 months vs. 11.3 months; p=0.123).
Conclusion
Our data suggest that capmatinib is a new compelling treatment for NSCLC with MET GCN ≥ 10 or METex14 based on the improved survival within these patients.

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    Ann-Katrin Piper, Chelsea Penney, Jacqueline Holliday, Gary Tincknell, Yafeng Ma, Sarbar Napaki, Klaus Pantel, Daniel Brungs, Marie Ranson
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    Bassam Abu Thaher, Ihab Al-Masri, Kanan Wahedy, Rami Morjan, Saeb Aliwaini, Iman Mahmoud Al atter, Aayat Ahmed Elmabhouh, Areej khaled AL ibwaini, Saba Luay Alkhaldi, Basem Qeshta, Claus Jacob, Hans-Peter Deigner
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    Aref Zayed, Sana’a A. Jaber, Jomana Al Hroot, Sahar Hawamdeh, Nehad M. Ayoub, Nidal A. Qinna
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    Bo Mi Ku, Sungwon Park, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Yoon-La Choi, Myung-Ju Ahn
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    Matthew Z Guo, Kristen A Marrone, Alexander Spira, David M Waterhouse, Susan C Scott
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Prognostic Factor and Clinical Outcome in Stage III Non-Small Cell Lung Cancer: A Study Based on Real-World Clinical Data in the Korean Population
Ho Cheol Kim, Wonjun Ji, Jae Cheol Lee, Hyeong Ryul Kim, Si Yeol Song, Chang-Min Choi, Korean Association for Lung Cancer, Korea Central Cancer Registry
Cancer Res Treat. 2021;53(4):1033-1041.   Published online February 16, 2021
DOI: https://doi.org/10.4143/crt.2020.1350
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The optimal treatment for patients with stage III non-small cell lung cancer (NSCLC) remains controversial. This study aimed to investigate prognostic factors and clinical outcome in stage III NSCLC using real-world clinical data in the Korean population.
Materials and Methods
Among 8,110 patients with lung cancer selected from 52 hospitals in Korea during 2014-2016, only patients with stage III NSCLC were recruited and analyzed. A standardized protocol was used to collect clinical information and cox proportional hazards models were used to identify risk factors for mortality.
Results
A total of 1,383 patients (46.5% had squamous cell carcinoma and 40.9% had adenocarcinoma) with stage III NSCLC were enrolled, and their median age was 70 years. Regarding clinical stage, 548 patients (39.6%) had stage IIIA, 517 (37.4%) had stage IIIB, and 318 (23.0%) had stage IIIC. Pertaining to the initial treatment method, the surgery group (median survival period: 36 months) showed better survival outcomes than the non-surgical treatment group (median survival period: 18 months, p=0.001) in patients with stage IIIA. Moreover, among patients with stage IIIB and stage IIIC, those who received concurrent chemotherapy and radiation therapy (CCRT, median survival period: 24 months) showed better survival outcomes than those who received chemotherapy (median survival period: 11 months), or radiation therapy (median survival period: 10 months, p<0.001).
Conclusion
While surgery might be feasible as the initial treatment option in patients with stage IIIA NSCLC, CCRT showed a beneficial role in patients with stage IIIB and IIIC NSCLC.

Citations

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    Yu-Hung Chen, Kun-Han Lue, Sung-Chao Chu, Bee-Song Chang, Chih-Bin Lin
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    Yu-Hung Chen, Sung-Chao Chu, Ling-Yi Wang, Tso-Fu Wang, Kun-Han Lue, Chih-Bin Lin, Bee-Song Chang, Dai-Wei Liu, Shu-Hsin Liu, Sheng-Chieh Chan
    Diagnostics.2021; 11(6): 1065.     CrossRef
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Inhibition of lncRNA KCNQ1OT1 Improves Apoptosis and Chemotherapy Drug Response in Small Cell Lung Cancer by TGF-β1 Mediated Epithelial-to-Mesenchymal Transition
Deyu Li, Qin Tong, Yuane Lian, Zhizhong Chen, Yaru Zhu, Weimei Huang, Yang Wen, Qiongyao Wang, Shumei Liang, Man Li, Jianjing Zheng, Zhenhua Liu, Huanxin Liu, Linlang Guo
Cancer Res Treat. 2021;53(4):1042-1056.   Published online March 9, 2021
DOI: https://doi.org/10.4143/crt.2020.1208
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required.
Materials and Methods
In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance.
Results
The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells.
Conclusion
Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

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    Ying Liu, Wei Ding, Jianxun Wang, Xiang Ao, Junqiang Xue
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    Kai Zhan, Huafeng Pan, Zhang Zhou, Wenqian Tang, Zhining Ye, Shaogang Huang, Lei Luo
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    Patrice Cagle, Qi Qi, Suryakant Niture, Deepak Kumar
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  • 171 Download
  • 7 Web of Science
  • 8 Crossref
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Conditional Survival of Surgically Treated Patients with Lung Cancer: A Comprehensive Analyses of Overall, Recurrence-free, and Relative Survival
Dong Wook Shin, Jong Ho Cho, Jung Eun Yoo, Juhee Cho, Dong Woog Yoon, Genehee Lee, Sumin Shin, Hong Kwan Kim, Yong Soo Choi, Jhingook Kim, Jae Ill Zo, Young Mog Shim
Cancer Res Treat. 2021;53(4):1057-1071.   Published online March 9, 2021
DOI: https://doi.org/10.4143/crt.2020.1308
AbstractAbstract PDFPubReaderePub
Purpose
Survival probability changes over time in cancer survivors. This study examined conditional survival in patients undergoing curative resection for non-small cell lung cancer (NSCLC).
Materials and Methods
Five-year conditional recurrence-free survival (CRFS), conditional overall survival (COS), and conditional relative survival (CRS) up to 10 years after surgery were calculated in patients who underwent NSCLC resection from 1994 to 2016. These rates were stratified according to age, sex, year of diagnosis, pathological stage, tumor histology, smoking status, comorbidity, and lung function.
Results
Five-year CRFS increased from 65.6% at baseline to 90.9% at 10 years after surgery. Early differences in 5-year CRFS according to stratified patient characteristics disappeared, except for age: older patients exhibited persistently lower 5-year CRFS. Five-year COS increased from 72.7% to 78.3% at 8 years and then decreased to 75.4% at 10 years. Five-year CRS increased from 79.0% at baseline to 86.8% at 10 years. Older age and higher pathologic stage were associated with lower 5-year COS and CRS up to 10 years after surgery. Female patients, those with adenocarcinoma histology, non-smokers, patient without comorbidities and had good lung function showed higher COS and CRS.
Conclusion
CRFS improved over time, but significant risk remained after 5 years. CRS slightly improved over time but did not reach 90%, suggesting significant excess mortality compared to the general population. Age and stage remained significant predictors of conditional survival several years after surgery. Our conditional survival estimates should help clinicians and patients make informed treatment and personal life decisions based on survivorship status.

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    Moyan Zhang, Yicheng Liang, Peng Song
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    Jun-Peng Lin, Xiao-Feng Chen, Peiyuan Wang, Hao He, Wei-Jie Chen, Feng-Nian Zhuang, Hang Zhou, Yu-Jie Chen, Wen-Wei Wei, Shuo-Yan Liu, Feng Wang
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Breast Cancer
Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
Erwin Danil Yulian, Nurjati Chairani Siregar, Bajuadji
Cancer Res Treat. 2021;53(4):1072-1083.   Published online March 9, 2021
DOI: https://doi.org/10.4143/crt.2020.1024
AbstractAbstract PDFPubReaderePub
Purpose
The efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) is limited due to drug resistance and cardiotoxic effects. Preclinical studies have shown that statin induces apoptosis and decreases breast cancer cell growth. This study aims to evaluate the role of statin in combination with fluorouracil, adriamycin, and cyclophosphamide (FAC) therapy in LABC patients.
Materials and Methods
We undertook a randomized, double-blinded, placebo-controlled trial in two centers of Indonesia. Patients were randomly assigned to FAC plus simvastatin (40 mg/day orally) or FAC plus placebo (40 mg/day) for 21 days. The FAC regimen was repeated every 3 weeks. We evaluated the clinical response, pathological response, and toxicities.
Results
The objective response rate (ORR) for FAC plus simvastatin was 90% (95% confidence interval [CI], 0.99 to 1.67) by per-protocol analysis. No complete responses (CR) were recorded, but there were 48 partial responses. No significant difference was observed between the two groups with the ORR (p=0.103). The pathological CR rate was 6.25% (2 in simvastatin group and 1 in placebo group). Adverse events in both arms were generally mild, mainly consisted of myotoxicity. Human epidermal growth factor receptor 2 (HER2) expression was a factor related to the success of therapeutic response (odds ratio, 4.2; 95% CI, 1.121 to 15.731; p=0.033).
Conclusion
This study suggests that simvastatin combined with FAC shows improvements in ORR and pathological response in patients with LABC. Although no statistically significant difference was documented, there was a trend for better activity and tolerability. The addition of 40 mg simvastatin may improve the efficacy of FAC in LABC patients with HER2 overexpression.

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Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial
Kyung-Hun Lee, Joohyuk Sohn, Annabel Goodwin, Tiziana Usari, Silvana Lanzalone, Seock-Ah Im, Sung-Bae Kim
Cancer Res Treat. 2021;53(4):1084-1095.   Published online March 24, 2021
DOI: https://doi.org/10.4143/crt.2020.1381
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

Citations

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  • HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
    Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
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Gastrointestinal Cancer
Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer
Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha
Cancer Res Treat. 2021;53(4):1096-1103.   Published online December 30, 2020
DOI: https://doi.org/10.4143/crt.2020.928
AbstractAbstract PDFPubReaderePub
Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

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    媛媛 苏
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    Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
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Pulmonary Metastasectomy in Colorectal Cancer: A Population-Based Retrospective Cohort Study Using the Korean National Health Insurance Database
Woo Sik Yu, Mi Kyung Bae, Jung Kyu Choi, Young Ki Hong, In Kyu Park
Cancer Res Treat. 2021;53(4):1104-1112.   Published online January 15, 2021
DOI: https://doi.org/10.4143/crt.2020.1213
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The study aimed to investigate the current status and prognostic factors for overall survival in patients who had undergone pulmonary metastasectomy for colorectal cancer.
Materials and Methods
The data of 2,573 patients who had undergone pulmonary metastasectomy after surgery for colorectal cancer between January 2009 and December 2014 were extracted from the Korean National Health Insurance Service claims database. Patient-, colorectal cancer–, pulmonary metastasis–, and hospital-related factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis to identify prognostic factors for overall survival after pulmonary metastasectomy.
Results
The mean age of the patients was 60.9±10.5 years; 66.2% and 79.1% of the participants were male and had distally located colorectal cancer, respectively. Wedge resection (71.7%) was the most frequent extent of pulmonary resection; 21.8% of the patients underwent repeated pulmonary metastasectomies; 73% of pulmonary metastasectomy cases were performed in tertiary hospitals; 53.9% of patients were treated in Seoul area; 82% of patients received chemotherapy in conjunction with pulmonary metastasectomy. The median survival duration was 51.8 months. The 3- and 5-year overall survival rates were 67.7% and 39.4%, respectively. In multivariate analysis, female sex, distally located colorectal cancer, pulmonary metastasectomy-only treatment, and high hospital volume (> 10 pulmonary metastasectomy cases/yr) were positive prognostic factors for survival.
Conclusion
Pulmonary metastasectomy seemed to provide long-term survival of patients with colorectal cancer. The female sex, presence of distally located colorectal cancer, and performance of pulmonary metastasectomy in high-volume centers were positive prognostic factors for survival.

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    Matthias Grott, Hauke Winter, Martin Eichhorn
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    Panxin Peng, Yusong Luan, Peng Sun, Liming Wang, Xufeng Zeng, Yangyang Wang, Xuhao Cai, Peide Ren, Yonggang Yu, Qi Liu, Haoyue Ma, Huijing Chang, Bolun Song, Xiaohua Fan, Yinggang Chen
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    Jeong Il Yu, Gyu Sang Yoo, Hee Chul Park, Doo Ho Choi, Woo Yong Lee, Seong Hyeon Yun, Hee Cheol Kim, Yong Beom Cho, Jung Wook Huh, Yoon Ah Park, Jung Kyong Shin, Joon Oh Park, Seung Tae Kim, Young Suk Park, Jeeyun Lee, Won Ki Kang, Ho Yeong Lim, Jung Yong
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    Hong Yang, Lei Chen, Xiuxiu Wu, Chenghai Zhang, Zhendan Yao, Jiadi Xing, Ming Cui, Beihai Jiang, Xiangqian Su
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Fasting Blood Glucose, Cholesterol, and Risk of Primary Liver Cancer: The Kailuan Study
Xiangming Ma, Haozhe Cui, Miaomiao Sun, Qian Liu, Xining Liu, Guangjian Li, Yaochen Wei, Qingjiang Fu, Siqing Liu, Liying Cao
Cancer Res Treat. 2021;53(4):1113-1122.   Published online January 19, 2021
DOI: https://doi.org/10.4143/crt.2020.817
AbstractAbstract PDFPubReaderePub
Purpose
The influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in china was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated.
Materials and Methods
Overall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or TC with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/ non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBG/non-hypocholesterolemia, elevated FBG/hypocholesterolemia and normal FBG/ non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model.
Results
During 1,134,843.68 person*years follow up, a total of 388 PLC cases occured. We found the elevated FBG and hypocholesterolemia increases the risk for PLC, respectively. Compared with the non-hypocholesterolemia/normal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (HR=1.19,95%CI 0.88–1.62) and hypocholesterolemia/normal FBG group (HR=1.53,95%CI 1.19–1.97), and in the hypocholesterolemia/elevated FBG group (HR=3.16 95%CI2.13-4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease.
Conclusion
Elevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated.

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Effect of Preoperative Tumor Under-Staging on the Long-term Survival of Patients Undergoing Radical Gastrectomy for Gastric Cancer
Mi Lin, Qi-Yue Chen, Chao-Hui Zheng, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Chang-Ming Huang
Cancer Res Treat. 2021;53(4):1123-1133.   Published online March 5, 2021
DOI: https://doi.org/10.4143/crt.2020.651
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the effect of preoperative tumor staging deviation (PTSD) on the long-term survival of patients undergoing radical gastrectomy for gastric cancer (RGGC).
Materials and Methods
Clinicopathological data of 2,346 patients who underwent RGGC were retrospectively analyzed. The preoperative tumor-lymph node-metastasis (TNM) under-staging group (uTNM) comprised patients who had earlier preoperative TNM than postoperative TNM, and the no preoperative under-staging group (nTNM) comprised the remaining patients.
Results
There were 1,031 uTNM (44.0%) and 1,315 nTNM cases (56.0%). Cox prognostic analysis revealed that PTSD independently affected the overall survival (OS) after surgery. The 5-year OS was lower in the uTNM group (41.8%) than in the nTNM group (71.6%). The patients less than 65 years old, with lower American Society of Anaesthesiologists score, 2-5 cm tumor located at the lower stomach, and cT1 or cN0 preoperative staging would more likely undergo D1+ lymph node dissection (LND) in uTNM (p < 0.05). Logistic analyses revealed that tumor size > 2 cm and body mass index ≤ 22.72 kg/m2 were independent risk factors of preoperative TNM tumor under-staging in patients with cT1N0M0 staging (p < 0.05).
Conclusion
Underestimated tumor staging is not rare, which possibly results in inadequate LND and affects the long-term survival for patients undergoing RGGC. D2 LND should be carefully performed in patients who are predisposed to this underestimation.

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Neurocognitive Effects of Chemotherapy for Colorectal Cancer: A Systematic Review and a Meta-Analysis of 11 Studies
Soo Young Hwang, Kwanghyun Kim, Byeonggwan Ha, Dongkyu Lee, Seonung Kim, Seongjun Ryu, Jisu Yang, Sun Jae Jung
Cancer Res Treat. 2021;53(4):1134-1147.   Published online March 17, 2021
DOI: https://doi.org/10.4143/crt.2020.1191
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Chemotherapy-related cognitive impairment (CRCI) is a controversial concept not much explored on colorectal cancer patients.
Materials and Methods
We identified 11 prospective studies: eight studies on 696 colorectal cancer patients who received chemotherapy and three studies on 346 rectal cancer patients who received neoadjuvant chemoradiotherapy. Standardized mean differences (SMDs) of neuropsychological test results and the cognitive quality-of-life scale were calculated using random effect models. A meta-regression was conducted to investigate the association between mean study population age and effect sizes.
Results
The association between chemotherapy and cognitive impairment was not clear in colorectal cancer patients (SMD, 0.003; 95% confidence interval, ‒0.080 to 0.086). However, a meta-regression showed that older patients are more vulnerable to CRCI than younger patients (β=‒0.016, p < 0.001).
Conclusion
Chemotherapy has an overall positive negligible effect size on the cognitive function of colorectal patients. Age is a significant moderator of CRCI.

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Genitourinary Cancer
A Predictive Model Based on Bi-parametric Magnetic Resonance Imaging and Clinical Parameters for Clinically Significant Prostate Cancer in the Korean Population
Tae Il Noh, Chang Wan Hyun, Ha Eun Kang, Hyun Jung Jin, Jong Hyun Tae, Ji Sung Shim, Sung Gu Kang, Deuk Jae Sung, Jun Cheon, Jeong Gu Lee, Seok Ho Kang
Cancer Res Treat. 2021;53(4):1148-1155.   Published online December 31, 2020
DOI: https://doi.org/10.4143/crt.2020.1068
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to develop and validate a predictive model for the assessment of clinically significant prostate cancer (csPCa) in men, prior to prostate biopsies, based on bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters.
Materials and Methods
We retrospectively analyzed 300 men with clinical suspicion of prostate cancer (prostate-specific antigen [PSA] ≥ 4.0 ng/mL and/or abnormal findings in a digital rectal examination), who underwent bpMRI-ultrasound fusion transperineal targeted and systematic biopsies in the same session, at a Korean university hospital. Predictive models, based on Prostate Imaging Reporting and Data Systems scores of bpMRI and clinical parameters, were developed to detect csPCa (intermediate/high grade [Gleason score ≥ 3+4]) and compared by analyzing the areas under the curves and decision curves.
Results
A predictive model defined by the combination of bpMRI and clinical parameters (age, PSA density) showed high discriminatory power (area under the curve, 0.861) and resulted in a significant net benefit on decision curve analysis. Applying a probability threshold of 7.5%, 21.6% of men could avoid unnecessary prostate biopsy, while only 1.0% of significant prostate cancers were missed.
Conclusion
This predictive model provided a reliable and measurable means of risk stratification of csPCa, with high discriminatory power and great net benefit. It could be a useful tool for clinical decision-making prior to prostate biopsies.

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    Kristina I. Ringe, Jin Wang, Ying Deng, Shan Pi, Amine Geahchan, Bachir Taouli, Mustafa R. Bashir
    Journal of Magnetic Resonance Imaging.2024; 59(1): 58.     CrossRef
  • Magnetic Resonance Imaging, Clinical, and Biopsy Findings in Suspected Prostate Cancer
    Arya Haj-Mirzaian, Kristine S. Burk, Ronilda Lacson, Daniel I. Glazer, Sanjay Saini, Adam S. Kibel, Ramin Khorasani
    JAMA Network Open.2024; 7(3): e244258.     CrossRef
  • The Barcelona Predictive Model of Clinically Significant Prostate Cancer
    Juan Morote, Angel Borque-Fernando, Marina Triquell, Anna Celma, Lucas Regis, Manel Escobar, Richard Mast, Inés M. de Torres, María E. Semidey, José M. Abascal, Carles Sola, Pol Servian, Daniel Salvador, Anna Santamaría, Jacques Planas, Luis M. Esteban, E
    Cancers.2022; 14(6): 1589.     CrossRef
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    Tae Il Noh, Ji Sung Shim, Sung Gu Kang, Jun Cheon, Jeong Gu Lee, Seok Ho Kang
    Sexual Medicine.2022; 10(3): 1.     CrossRef
  • Comparative Analysis of PSA Density and an MRI-Based Predictive Model to Improve the Selection of Candidates for Prostate Biopsy
    Juan Morote, Angel Borque-Fernando, Marina Triquell, Anna Celma, Lucas Regis, Richard Mast, Inés M. de Torres, María E. Semidey, José M. Abascal, Pol Servian, Anna Santamaría, Jacques Planas, Luis M. Esteban, Enrique Trilla
    Cancers.2022; 14(10): 2374.     CrossRef
  • Magnetic Resonance Imaging-Based Predictive Models for Clinically Significant Prostate Cancer: A Systematic Review
    Marina Triquell, Miriam Campistol, Ana Celma, Lucas Regis, Mercè Cuadras, Jacques Planas, Enrique Trilla, Juan Morote
    Cancers.2022; 14(19): 4747.     CrossRef
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Neoadjuvant Chemotherapy–Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study
Hongzhe Shi, Wen Zhang, Xingang Bi, Dong Wang, Zejun Xiao, Youyan Guan, Kaopeng Guan, Jun Tian, Hongsong Bai, Linjun Hu, Chuanzhen Cao, Weixing Jiang, Zhilong Hu, Jin Zhang, Yan Chen, Shan Zheng, Xiaoli Feng, Changling Li, Yexiong Li, Jianhui Ma, Yueping Liu, Aiping Zhou, Jianzhong Shou
Cancer Res Treat. 2021;53(4):1156-1165.   Published online February 10, 2021
DOI: https://doi.org/10.4143/crt.2020.1356
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy.
Materials and Methods
Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate.
Results
Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory.
Conclusion
After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

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  • Does Bladder Cancer Subtype Influence Pathologic Complete Response (pCR) and Pelvic Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response Evaluation After Neoadjuvant Chemotherapy? Pathological Perspective
    Ji Min Kim, Euno Choi, Sun Hee Sung, Jungmin Jo, Dong-Hyeon Lee, Sanghui Park
    Clinical Genitourinary Cancer.2024; 22(2): 224.     CrossRef
  • A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3)
    Harshit Garg, Mukund Bhandari, Furkan Dursun, Michael A. Liss, Dharam Kaushik, Robert S. Svatek, Ahmed M. Mansour
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Clinical efficacy analysis of partial cystectomy and radical cystectomy in the treatment of muscle-invasive sarcomatoid carcinoma of the urinary bladder
    Jiansheng Xiao, Hua Chen, Jiaqi Ge, Tairong Liu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Downstaging guided neoadjuvant strategy shift and bladder preservation in locally advanced bladder cancer: A case report
    Gan Du, Zhichao Jiang, Wang Qu, Jin Zhang, Shan Zheng, Yueping Liu, Aiping Zhou, Hongzhe Shi, Jianzhong Shou
    Heliyon.2024; 10(6): e27685.     CrossRef
  • Editorial: Organ-sparing surgery for genitourinary cancers
    Gongwei Long, Xingyuan Xiao, Haoran Liu, Yucong Zhang, Chunguang Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?
    Olivier Riou, Christophe Hennequin, Jonathan Khalifa, Paul Sargos
    Cancer/Radiothérapie.2024; 28(6-7): 623.     CrossRef
  • Health-related quality of life after curative treatment for muscle-invasive bladder cancer
    Elisabeth Grobet-Jeandin, Ugo Pinar, Jérôme Parra, Morgan Rouprêt, Thomas Seisen
    Nature Reviews Urology.2023; 20(5): 279.     CrossRef
  • Combined Modality Bladder-Sparing Therapy for Muscle-Invasive Bladder Cancer: How (Should) We Do It? A Narrative Review
    Artur Lemiński, Wojciech Michalski, Bartłomiej Masojć, Krystian Kaczmarek, Bartosz Małkiewicz, Jakub Kienitz, Barbara Zawisza-Lemińska, Michał Falco, Marcin Słojewski
    Journal of Clinical Medicine.2023; 12(4): 1560.     CrossRef
  • Survival after sequential neoadjuvant chemotherapy followed by trimodal treatment or radical cystectomy for muscle-invasive bladder cancer
    Pierre-Louis Reignier, Hélène Gauthier, Christophe Hennequin, Quiterie Aussedat, Evanguelos Xylinas, François Desgrandchamps, Stéphane Culine, Alexandra Masson-Lecomte, Clément Dumont
    World Journal of Urology.2023; 41(11): 3249.     CrossRef
  • Neoadjuvant chemotherapy with gemcitabine and cisplatin followed by selective bladder preservation chemoradiotherapy in muscle-invasive urothelial carcinoma of bladder
    Hyun Hwan Sung, Hana Kim, Ryul Kim, Chan Kyo Kim, Ghee Young Kwon, Won Park, Wan Song, Byong Chang Jeong, Se Hoon Park
    Investigative and Clinical Urology.2022; 63(2): 168.     CrossRef
  • Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature
    Jie Wu, Rui-Yang Xie, Chuan-Zhen Cao, Bing-Qing Shang, Hong-Zhe Shi, Jian-Zhong Shou
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Contemporary Staging for Muscle-Invasive Bladder Cancer: Accuracy and Limitations
    Patrick J. Hensley, Valeria Panebianco, Eugene Pietzak, Alexander Kutikov, Raghu Vikram, Matthew D. Galsky, Shahrokh F. Shariat, Morgan Roupret, Ashish M. Kamat
    European Urology Oncology.2022; 5(4): 403.     CrossRef
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Use of Gemcitabine plus Carboplatin is Associated with Poor Outcomes in Urothelial Carcinoma Patients with Chronic Kidney Disease Stage 4-5
Hyung-Don Kim, Hyeon-Su Im, Jwa Hoon Kim, Hyehyun Jeong, Shin Kyo Yoon, Inkeun Park, Jae Lyun Lee
Cancer Res Treat. 2021;53(4):1166-1173.   Published online March 4, 2021
DOI: https://doi.org/10.4143/crt.2021.091
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the clinical outcomes with gemcitabine-carboplatin (GCb), the standard treatment for patients with advanced urothelial carcinoma (UC) who are ineligible for cisplatin-based regimens, in advanced UC patients with a glomerular filtration rate (GFR) < 30 mL/min.
Materials and Methods
A retrospective cohort study involving GCb-treated advanced UC patients with GFR < 60 mL/min (n=89) was performed. Clinical outcomes were compared between subgroups with GFR < 30 mL/min and GFR ≥ 30 mL/min but < 60 mL/min.
Results
Most baseline characteristics were comparable between the two subgroups. Patients with GFR < 30 mL/min had a significantly lower objective response rate (12.5%) compared to those with higher GFR levels (56.7%) (p=0.004). The number of GCb cycles was significantly lower in patients with GFR < 30 mL/min (median 2 cycles) than in those with higher GFR levels (median 6 cycles) (p=0.002). Compared to those with GFR ≥ 30 mL/min but < 60 mL/min, patients with GFR < 30 mL/min showed significantly worse progression-free survival (PFS) and overall survival (OS) (p < 0.001 for both). Further stratification of patient subgroups according to their GFR (i.e., GFR ≥ 45 mL/min but < 60 mL/min vs. GFR ≥ 30 mL/min but < 45 mL/min vs. GFR < 30 mL/min) revealed significantly different PFS and OS (p < 0.001 for both).
Conclusion
The use of GCb is discouraged in advanced UC patients with GFR < 30 mL/min. Alternative therapeutic approaches with better efficacy are warranted for these patients.

Citations

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  • Onconephrology: mitigation of renal injury in chemotherapy administration
    Umut Selamet, Rebecca S. Ahdoot, Reed Salasnek, Lama Abdelnour, Ramy M. Hanna
    Current Opinion in Nephrology & Hypertension.2024; 33(2): 257.     CrossRef
  • Management of bladder cancer in older patients
    Shingo Hatakeyama, Shintaro Narita, Kazutaka Okita, Takuma Narita, Hiromichi Iwamura, Naoki Fujita, Junichi Inokuchi, Yoshiyuki Matsui, Hiroshi Kitamura, Chikara Ohyama
    Japanese Journal of Clinical Oncology.2022; 52(3): 203.     CrossRef
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Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
Cancer Res Treat. 2021;53(4):1174-1183.   Published online March 17, 2021
DOI: https://doi.org/10.4143/crt.2021.031
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs.
Materials and Methods
All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation.
Results
FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cutoff value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low expression of FBXL5 (hazard ratio, 2.001; p=0.034) was significantly associated with shorter overall survival.
Conclusion
FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

Citations

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  • Differences in genomic profile of high-grade urothelial carcinoma according to tumor location
    Cheol Keun Park, Nam Hoon Cho
    Urologic Oncology: Seminars and Original Investigations.2022; 40(3): 109.e1.     CrossRef
  • The Role of Iron in Cancer Progression
    Qianqian Guo, Liwen Li, Shanshan Hou, Ziqiao Yuan, Chenhui Li, Wenzhou Zhang, Lufeng Zheng, Xiaoman Li
    Frontiers in Oncology.2021;[Epub]     CrossRef
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  • 137 Download
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Pediatric cancer
Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea
Jung Yoon Choi, Che Ry Hong, Kyung Taek Hong, Hyoung Jin Kang, Seongkoo Kim, Jae Wook Lee, Pil Sang Jang, Nack-Gyun Chung, Bin Cho, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Jong Jin Seo, Seung Min Hahn, Jung Woo Han, Chuhl Joo Lyu, Eu Jeen Yang, Young Tak Lim, Keon Hee Yoo, Hong Hoe Koo, Hoon Kook, In Sang Jeon, Hana Cho, Hee Young Shin
Cancer Res Treat. 2021;53(4):1184-1194.   Published online January 4, 2021
DOI: https://doi.org/10.4143/crt.2020.289
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development.
Materials and Methods
In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed.
Results
Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events.
Conclusion
Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

Citations

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  • Clofarabine

    Reactions Weekly.2023; 1958(1): 155.     CrossRef
  • Patient-Level Meta-analysis of Clofarabine in Acute Lymphoblastic Leukemia
    Sima Jeha, Hiroaki Goto, André Baruchel, Emmanuelle Boëlle-Le Corfec, Christine Geffriaud-Ricouard, Rob Pieters, Hee Young Shin
    Advances in Therapy.2023; 40(12): 5447.     CrossRef
  • Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era
    Shang Mengxuan, Zhou Fen, Jin Runming
    Frontiers in Pediatrics.2022;[Epub]     CrossRef
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  • 195 Download
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Sarcoma
Real-World Clinical Outcomes and Prognostic Factors for Patients with Advanced Angiosarcoma who Received Systemic Treatment
Changhee Park, Miso Kim, Yoonjin Kwak, Kyung Chul Moon, Se Hyun Kim, Bhumsuk Keam, Yu Jung Kim, Tae Min Kim, Dong-Wan Kim
Cancer Res Treat. 2021;53(4):1195-1203.   Published online February 1, 2021
DOI: https://doi.org/10.4143/crt.2020.1337
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated.
Materials and Methods
We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions.
Results
Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0–6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0–14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8–4.3) and a mOS of 5.4 months (95% CI 3.5–NA).
Conclusion
Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.

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  • Hepatic Angiosarcoma with Peliosis Hepatis
    Kensuke Kitsugi, Kazuhito Kawata, Moe Matsumoto, Masahiro Umemura, Tomohiko Hanaoka, Maho Yamashita, Shingo Takatori, Jun Ito, Kazuyoshi Ohta, Takeshi Chida, Hidenao Noritake, Takafumi Suda
    Internal Medicine.2023; 62(8): 1157.     CrossRef
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    Yuta Ushida, Takafumi Sato, Tomotaka Kato, Yasuyuki Shigematsu, Hiromichi Ito, Takeshi Suzuki, Yosuke Inoue, Yoshihiro Ono, Atsushi Oba, Yu Takahashi
    Clinical Journal of Gastroenterology.2022; 15(2): 427.     CrossRef
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    Siwei Bi, Ai Zhong, Xiya Yin, Jingyi Li, Ying Cen, Junjie Chen
    Current Treatment Options in Oncology.2022; 23(2): 137.     CrossRef
  • Results of NC-6300 (Nanoparticle Epirubicin) in an Expansion Cohort of Patients with Angiosarcoma
    Richard F Riedel, Victoria Chua, Ania Moradkhani, Natalie Krkyan, Amir Ahari, Atsushi Osada, Sant P Chawla
    The Oncologist.2022; 27(10): 809.     CrossRef
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