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Volume 54(2); April 2022
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Review Article
Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer
Joel Rivera-Concepcion, Dipesh Uprety, Alex A. Adjei
Cancer Res Treat. 2022;54(2):315-329.   Published online February 18, 2022
DOI: https://doi.org/10.4143/crt.2022.078
AbstractAbstract PDFPubReaderePub
Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

Citations

Citations to this article as recorded by  
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    Sara Kwon, Kyuwoong Kim, Bohyun Park, So-Jung Park, Hyun Jung Jho, Jin Young Choi
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  • Inhibition of NNMT enhances drug sensitivity in lung cancer cells through mediation of autophagy
    Jian Wang, Ming Zhang, Xin You, Yang Xu, Congcong Zhang, Ying Li, Chunhui Yang, Qi Wang
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Next-generation sequencing impact on cancer care: applications, challenges, and future directions
    Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Expression and Functional Analysis of Immuno-Micro-RNAs mir-146a and mir-326 in Colorectal Cancer
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  • Advances in Non-Small Cell Lung Cancer: Current Insights and Future Directions
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  • Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies
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  • Survival benefit of thermal ablation therapy for patients with stage II-III non-small cell lung cancer: A propensity-matched analysis
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  • CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model
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Special Articles
Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2019
Mee Joo Kang, Young-Joo Won, Jae Jun Lee, Kyu-Won Jung, Hye-Jin Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo, The Community of Population-Based Regional Cancer Registries
Cancer Res Treat. 2022;54(2):330-344.   Published online March 16, 2022
DOI: https://doi.org/10.4143/crt.2022.128
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2019.
Materials and Methods
Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2019, with survival follow-up until December 31, 2020. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.
Results
In 2019, newly diagnosed cancer cases and deaths from cancer were reported as 254,718 (ASR, 275.4 per 100,000) and 81,203 (ASR, 72.2 per 100,000), respectively. For the first time, lung cancer (n=29,960) became the most frequent cancer in Korea, excluding thyroid cancer. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. The incidence of thyroid cancer increased again from 2016 (annual percentage change, 6.2%). Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.7% from 2002 to 2013; 3.3% from 2013 to 2019). The 5-year relative survival between 2015 and 2019 was 70.7%, which contributed to prevalent cases reaching over 2 million in 2019.
Conclusion
Cancer survival rates have improved over the past decades, but the number of newly diagnosed cancers is still increasing, with some cancers showing only marginal improvement in survival outcomes. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics.

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Prediction of Cancer Incidence and Mortality in Korea, 2022
Kyu-Won Jung, Young-Joo Won, Mee Joo Kang, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo
Cancer Res Treat. 2022;54(2):345-351.   Published online March 21, 2022
DOI: https://doi.org/10.4143/crt.2022.179
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to report the projected cancer incidence and mortality for the year 2022 to estimate Korea’s current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2019 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2020 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2022. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend.
Results
In total, 274,488 new cancer cases and 81,277 cancer deaths are expected to occur in Korea in 2022. The most common cancer site is expected to be the thyroid, followed by the lung, colon and rectum, breast, and stomach. These five cancers are expected to represent half of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and gallbladder cancers.
Conclusion
The incidence rates for all types of cancer in Korea are estimated to gradually decrease. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.

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Original Articles
General
Validation of Cancer Diagnosis Based on the National Health Insurance Service Database versus the National Cancer Registry Database in Korea
Min Soo Yang, Minae Park, Joung Hwan Back, Gyeong Hyeon Lee, Ji Hye Shin, Kyuwoong Kim, Hwa Jeong Seo, Young Ae Kim
Cancer Res Treat. 2022;54(2):352-361.   Published online August 2, 2021
DOI: https://doi.org/10.4143/crt.2021.044
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to assess the feasibility of operational definitions of cancer patients in conducting cancer-related studies using the claims data from the National Health Insurance Service (NHIS).
Materials and Methods
Cancer incidence data were obtained from the Korean Central Cancer Registry, the NHIS primary diagnosis, and from the rare and intractable disease (RID) registration program.
Results
The operational definition with higher sensitivity for cancer patient verification was different by cancer type. Using primary diagnosis, the lowest sensitivity was found in colorectal cancer (91.5%; 95% confidence interval [CI], 91.7 to 92.0) and the highest sensitivity was found in breast cancer (97.9%; 95% CI, 97.8 to 98.0). With RID, sensitivity was the lowest in liver cancer (91.9%; 95% CI, 91.7 to 92.0) and highest in breast cancer (98.1%; 95% CI, 98.0 to 98.2). In terms of the difference in the date of diagnosis in the cancer registration data, > 80% of the patients showed a < 31-day difference from the RID definition.
Conclusion
Based on the NHIS data, the operational definition of cancer incidence is more accurate when using the RID registration program claims compared to using the primary diagnosis despite the relatively lower concordance by cancer type requires additional definitions such as treatment.

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    Yoon Suk Jung, Huiyeon Song, Mai Thi Xuan Tran, Boyoung Park, Chang Mo Moon
    Journal of Personalized Medicine.2022; 12(10): 1566.     CrossRef
  • The Association Between Metabolic Syndrome and Colorectal Cancer Risk by Obesity Status in Korean Women: A Nationwide Cohort Study
    Seong-geun Moon, Boyoung Park
    Journal of Preventive Medicine and Public Health.2022; 55(5): 475.     CrossRef
  • Microcalcifications, mammographic breast density, and risk of breast cancer: a cohort study
    Soyeoun Kim, Thi Xuan Mai Tran, Huiyeon Song, Boyoung Park
    Breast Cancer Research.2022;[Epub]     CrossRef
  • Association between malignancy risk and Janus kinase inhibitors versus tumour necrosis factor inhibitors in Korean patients with rheumatoid arthritis: a nationwide population-based study
    Yeo-Jin Song, Soo-Kyung Cho, Seung-Hun You, Jeong-Yeon Kim, Hyoungyoung Kim, Sun-Young Jung, Yoon-Kyoung Sung
    RMD Open.2022; 8(2): e002614.     CrossRef
  • Association Between Metabolic Syndrome and Risk of Esophageal Cancer: a Nationwide Population-Based Study
    Ji Eun Lee, Kyungdo Han, Juhwan Yoo, Yohwan Yeo, In Young Cho, Belong Cho, Jin-Ho Park, Dong Wook Shin, Jong Ho Cho, Yong-Moon Park
    Cancer Epidemiology, Biomarkers & Prevention.2022; 31(12): 2228.     CrossRef
  • Risk of non-Hodgkin lymphoma in breast cancer survivors: a nationwide cohort study
    Danbee Kang, Sang Eun Yoon, Dongwook Shin, Jin Lee, Yun Soo Hong, Se Kyung Lee, Jeong Eon Lee, Yeon Hee Park, Jin Seok Ahn, Eliseo Guallar, Won Seog Kim, Jungho Lee, Seok Jin Kim, Juhee Cho
    Blood Cancer Journal.2021;[Epub]     CrossRef
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Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy
Yilei Chen, Hongxing Huang, Yin Liu, Zhanghao Wang, Lili Wang, Quanxiao Wang, Yan Zhang, Hua Wang
Cancer Res Treat. 2022;54(2):362-374.   Published online August 3, 2021
DOI: https://doi.org/10.4143/crt.2021.424
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells.
Materials and Methods
nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro.
Results
A high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells.
Conclusion
nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

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  • A novel bispecific peptide targeting PD-1 and PD-L1 with combined antitumor activity of T-cells derived from the patients with TSCC
    Lili Wang, Junheng Zheng, Zhihao Tan, Yan Zhang, Hua Wang
    International Immunopharmacology.2024; 138: 112582.     CrossRef
  • Peptide Blockers of PD-1-PD-L1 Interaction Reinvigorate PD-1-Suppressed T Cells and Curb Tumor Growth in Mice
    Shanshan (Jenny) Zhong, Xiaoling Liu, Tomonori Kaneko, Yan Feng, Owen Hovey, Kyle Yang, Sally Ezra, Soon-Duck Ha, Sung Kim, John K. McCormick, Huadong Liu, Shawn Shun-Cheng Li
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    Xuefeng Duan, Haoyang Zou, Jiazhen Yang, Shixian Liu, Tianmin Xu, Jianxun Ding
    Journal of Controlled Release.2024; 375: 285.     CrossRef
  • Peptides as multifunctional players in cancer therapy
    Sri Murugan Poongkavithai Vadevoo, Smriti Gurung, Hyun-Su Lee, Gowri Rangaswamy Gunassekaran, Seok-Min Lee, Jae-Won Yoon, Yun-Ki Lee, Byungheon Lee
    Experimental & Molecular Medicine.2023; 55(6): 1099.     CrossRef
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    Huizhen Cao, Tianyu Wu, Xue Zhou, Shuyang Xie, Hongfang Sun, Yunxiao Sun, Youjie Li
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia
    Quanxiao Wang, Hongxing Huang, Peisheng Liang, Lili Wang, Junheng Zheng, Yan Zhang, Hua Wang
    Medical Oncology.2023;[Epub]     CrossRef
  • Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
    Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
    Journal for ImmunoTherapy of Cancer.2022; 10(6): e004799.     CrossRef
  • 10,384 View
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  • 8 Web of Science
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Attitudes toward Risk-Reducing Mastectomy and Risk-Reducing Salpingo-oophorectomy among Young, Unmarried, Healthy Women in Korea
Boyoung Park, Dongwon Kim, Jiyoung Kim, Bom Yi Lee, Junghyun Yoon, Sung-Won Kim
Cancer Res Treat. 2022;54(2):375-382.   Published online August 9, 2021
DOI: https://doi.org/10.4143/crt.2021.449
AbstractAbstract PDFPubReaderePub
Purpose
This study investigated the attitudes toward risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) as cancer prevention options for BRCA1/2 carriers in healthy, young, unmarried Korean women.
Materials and Methods
A nationally representative sample of 600 women, aged 20-39 years, completed a questionnaire on sociodemographic variables, preference for genetic testing, and intention to undergo risk-reducing surgeries after receiving information on the cancer risk of BRCA1/2 mutations and benefits of risk-reducing surgeries.
Results
A total of 54.7% and 57.7% had the intention to undergo RRM and RRSO, respectively, on the assumption that they were BRCA1/2 carriers. Older age and no intention to undergo genetic testing were associated with a reduced likelihood of undergoing RRM (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.14 to 0.61 for age 35-39 years and OR, 0.35; 95% CI, 0.20 to 0.62 for no intention for genetic testing) and RRSO (OR, 0.39; 95% CI, 0.19 to 0.79 for age 35-39 years and OR, 0.30; 95% CI, 0.17 to 0.53 for no intention for genetic testing). Women who chose to be single were likely to undergo risk-reducing surgeries (OR, 1.67; 95% CI, 1.07 to 2.60 for RRM and OR, 1.56; 95% CI, 1.00 to 2.44 for RRSO).
Conclusion
More than 50% of healthy, unmarried, young Korean women were inclined to undergo prophylactic surgeries if they were BRCA1/2 mutation carriers. Further studies on decision-making process for cancer prevention in individuals at high risk for cancer need to be conducted.

Citations

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  • Impact of graphical display on the intention to undergo risk-reducing salpingo-oophorectomy and mastectomy in individuals positive for BRCA pathogenic variant
    Yoon-Jung Choi, Younju Park, Boyoung Park, Heejung Chae, So-Youn Jung, Kum Hei Ryu, Myong Cheol Lim, Soo Jin Park, Yoon Jung Chang, Sun-Young Kong
    Scientific Reports.2024;[Epub]     CrossRef
  • 5,396 View
  • 164 Download
  • 1 Web of Science
  • 1 Crossref
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Radiation Response Prediction Model Based on Integrated Clinical and Genomic Data Analysis
Bum-Sup Jang, Ji-Hyun Chang, Seung Hyuck Jeon, Myung Geun Song, Kyung-Hun Lee, Seock-Ah Im, Jong-Il Kim, Tae-You Kim, Eui Kyu Chie
Cancer Res Treat. 2022;54(2):383-395.   Published online August 24, 2021
DOI: https://doi.org/10.4143/crt.2021.759
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings.
Materials and Methods
Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response.
Results
Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83.
Conclusion
Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

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  • Estimating the risk and benefit of radiation therapy in (y)pN1 stage breast cancer patients: A Bayesian network model incorporating expert knowledge (KROG 22–13)
    Bum-Sup Jang, Seok-Joo Chun, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
    Computer Methods and Programs in Biomedicine.2024; 245: 108049.     CrossRef
  • Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model
    Seok-Joo Chun, Bum-Sup Jang, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
    Cancers.2024; 16(8): 1494.     CrossRef
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    I-Shiow Jan, Hui Ju Ch’ang
    Radiation Oncology.2023;[Epub]     CrossRef
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    Seung Hyuck Jeon, Eui Kyu Chie
    Cancer Medicine.2023; 12(7): 8981.     CrossRef
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    Yi-Chih Tsai, Min-Chieh Hsin, Rui-Jun Liu, Ting-Wei Li, Hui-Ju Ch’ang
    Cancers.2023; 15(21): 5212.     CrossRef
  • 5,555 View
  • 181 Download
  • 5 Web of Science
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CNS cancer
Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study)
Grace S. Ahn, Kihwan Hwang, Tae Min Kim, Chul Kee Park, Jong Hee Chang, Tae-Young Jung, Jin Hee Kim, Do-Hyun Nam, Se-Hyuk Kim, Heon Yoo, Yong-Kil Hong, Eun-Young Kim, Dong-Eun Lee, Jungnam Joo, Yu Jung Kim, Gheeyoung Choe, Byung Se Choi, Seok-Gu Kang, Jeong Hoon Kim, Chae-Yong Kim
Cancer Res Treat. 2022;54(2):396-405.   Published online July 6, 2021
DOI: https://doi.org/10.4143/crt.2021.393
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).
Materials and Methods
In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B).
Results
Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33).
Conclusion
The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

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  • Achievements of international rare cancers networks and consortia in the neuro-oncology field
    Vincenzo Di Nunno, Enrico Franceschi, Ahmed Idbaih
    Current Opinion in Oncology.2024; 36(6): 554.     CrossRef
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    Jason A. Martin, Nicolas H. Hart, Natalie Bradford, Fiona Naumann, Mark B. Pinkham, Elizabeth P. Pinkham, Justin J. Holland
    Journal of Neuro-Oncology.2023; 162(1): 25.     CrossRef
  • Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats
    Anastasia Strokotova, Dmitry Sokolov, Olga Molodykh, Elena Koldysheva, Evgenii Kliver, Victor Ushakov, Maxim Politko, Nadezhda Mikhnevich, Galina Kazanskaya, Svetlana Aidagulova, Elvira Grigorieva
    Biomedical Reports.2023;[Epub]     CrossRef
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  • 162 Download
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Head and Neck cancer
Radiotherapy versus Surgery in Early-Stage HPV-Positive Oropharyngeal Cancer
Dong-Yun Kim, Hong-Gyun Wu, Jin Ho Kim, Joo Ho Lee, Soon-Hyun Ahn, Eun-Jae Chung, Keun-Yong Eom, Young Ho Jung, Woo-Jin Jeong, Tack-Kyun Kwon, Suzy Kim, Chan Woo Wee
Cancer Res Treat. 2022;54(2):406-416.   Published online June 23, 2021
DOI: https://doi.org/10.4143/crt.2021.441
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus–positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment.
Materials and Methods
This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT.
Results
With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding.
Conclusion
We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

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  • Definitive radio(chemo)therapy versus upfront surgery in the treatment of HPV-related localized or locally advanced oropharyngeal squamous cell carcinoma
    Jérémy Baude, Caroline Guigou, David Thibouw, Noémie Vulquin, Mireille Folia, Guillaume Constantin, Jihane Boustani, Christian Duvillard, Sylvain Ladoire, Gilles Truc, Aurélie Bertaut, Cédric Chevalier, Scott M. Langevin
    PLOS ONE.2024; 19(7): e0307658.     CrossRef
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    Sungryeal Kim, Hannah Park, Se Hyun Yeou, Jin Roh, Yoo Seob Shin, Chul-Ho Kim, Eun Ju Ha, Jeon Yeob Jang
    Cancers.2023; 15(13): 3276.     CrossRef
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    Chun Wei, Xiaojun Lan, Maona Qiu, Ran Cui, Qiuxia Fu, Shafiu Umar Shinge, Tobias Muluh, Ou Jiang
    Oncology Letters.2023;[Epub]     CrossRef
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  • 216 Download
  • 3 Web of Science
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Radiation-Induced Ocular Surface Disorders and Retinopathy: Ocular Structures and Radiation Dose-Volume Effect
Ozlem Ozkaya Akagunduz, Suzan Guven Yilmaz, Emin Tavlayan, Mine Esen Baris, Filiz Afrashi, Mustafa Esassolak
Cancer Res Treat. 2022;54(2):417-423.   Published online June 24, 2021
DOI: https://doi.org/10.4143/crt.2021.575
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to evaluate the radiation-induced adverse effects on ocular structures in head and neck cancer patients and investigate the radiation dose-volume effects on the cornea, lacrimal gland, retina, optic nerve and chiasm.
Materials and Methods
A total of 38 eyes of 19 patients were included in this prospective, cohort study. All patients underwent complete ophthalmological examination in addition to contrast sensitivity, visual field and visual evoked potentials (VEP) tests. Ophthalmological examinations and psychophysical tests were performed in 6th, 12th, 18th, 24th months and in the last visit. The relationship between the ophthalmologic findings, and the radiation doses below and above the cut-off values was evaluated.
Results
Contrast sensitivity decrease and visual field deterioration were observed in 42% of the patients in the last visit (median 26 months) whereas a prolonged latency and decreased amplitude of P100 wave in VEP was observed in 58% and 33% of the eyes, respectively at 24th month. Totally 16 patients (84.2%) developed dry eye disease and eight of them received radiotherapy below tolerance doses and had mild to moderate dry eye findings. Radiation-induced retinopathy was observed in three of the eyes in eight patients who received radiation above tolerance dose.
Conclusion
Head and neck cancers treated with radiotherapy, resulted in various ophthalmic complications. All patients who are treating with radiotherapy should be evaluated by an ophthalmologist in terms of anterior and posterior segment damage, even if the radiation dose is below the tolerance limit.

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    James C.H. Chow, Jason C.S. Ho, Ka Man Cheung, David Johnson, Bonaventure Y.M. Ip, Jonathan J. Beitler, Primož Strojan, Antti A. Mäkitie, Avraham Eisbruch, Sweet Ping Ng, Sandra Nuyts, William M. Mendenhall, Silvia Babighian, Alfio Ferlito
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    Jiayuan Zhuang, Yang Yang, Yuexia Liao, Chenghao Li, Wen-an Wang, Xiangxia Luo, Heng Zhou
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    Canadian Journal of Ophthalmology.2024; 59(6): e768.     CrossRef
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    Jianping Man, Yanhua Shen, Yujie Song, Kai Yang, Pei Pei, Lin Hu
    Journal of Controlled Release.2024; 370: 318.     CrossRef
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    A. Aramburu-González, J. Zarrabeitia Carrandi, C.B. Robles Elejalde, A. Quilez Larragan
    Archivos de la Sociedad Española de Oftalmología.2024; 99(8): 352.     CrossRef
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    Laura Hughes, Amy C Cohn, Neda Haghighi, Alan A McNab
    European Journal of Ophthalmology.2024; 34(5): NP53.     CrossRef
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    A. Aramburu-González, J. Zarrabeitia Carrandi, C.B. Robles Elejalde, A. Quilez Larragan
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  • Case Report: Optical coherence tomography angiography findings in radiation retinopathy
    Wafa Ammari, Asma Zaghdoudi, Olfa Berriche, Riadh Messaoud
    F1000Research.2023; 11: 968.     CrossRef
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Lung and Thoracic cancer
Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors
Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung
Cancer Res Treat. 2022;54(2):424-433.   Published online July 7, 2021
DOI: https://doi.org/10.4143/crt.2021.583
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies.

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    Wei Xu, Wenjia Zhang, Dongxu Zhao, Qi Wang, Man Zhang, Qiang Li, Wenxin Zhu, Chunfang Xu
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The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J.W. Chen, Gee-Chen Chang
Cancer Res Treat. 2022;54(2):434-444.   Published online August 2, 2021
DOI: https://doi.org/10.4143/crt.2021.671
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients.
Materials and Methods
From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.
Results
A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).
Conclusion
Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

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    Chia‐Yu Kuo, Ming‐Ju Tsai, Jen‐Yu Hung, Mei‐Hsuan Lee, Kuan‐Li Wu, Yu‐Chen Tsai, Cheng‐Hao Chuang, Chung‐Wen Huang, Chin‐Ling Chen, Chih‐Jen Yang, Inn‐Wen Chong
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    Qi-yuan Mao, Xue-qian Wang, Fei Lin, Ming-wei Yu, Hui-ting Fan, Qi Zheng, Lan-chun Liu, Chu-chu Zhang, Dao-rui Li, Hong-sheng Lin
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    Wei-Fan Ou, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Yen-Hsiang Huang, Gee-Chen Chang, Tsung-Ying Yang
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    Ruijian Li, Weiyi Li, Fang Zhang, Shanshan Li
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    Suey-Haur Lee, Yu-Ching Lin, Li-Chung Chiu, Jia-Shiuan Ju, Pi-Hung Tung, Allen Chung-Cheng Huang, Shih-Hong Li, Yueh-Fu Fang, Chih-Hung Chen, Scott Chih-Hsi Kuo, Chin-Chou Wang, Cheng-Ta Yang, Ping-Chih Hsu
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    PLOS ONE.2022; 17(10): e0275919.     CrossRef
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miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in Non-Small Cell Lung Cancer Cells by Targeting USP37
Mi Seong Kim, So Hui Kim, Sei Hoon Yang, Min Seuk Kim
Cancer Res Treat. 2022;54(2):445-457.   Published online August 3, 2021
DOI: https://doi.org/10.4143/crt.2021.622
AbstractAbstract PDFPubReaderePub
Purpose
With the identification of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) cells, EGFR–tyrosine kinase inhibitors (TKIs) are being used widely as the first-line of treatment in NSCLC. These inhibitors block auto-phosphorylation of activated EGFR by competing with ATP binding and mediate EGFR degradation independent of exogenous epidermal growth factor, which is associated with the mutation variants of EGFR. However, the precise mechanisms underlying the TKI-mediated EGFR degradation are still unclear.
Materials and Methods
To examine the physiological roles of miR-4487 and ubiquitin-specific peptidase 37 (USP37) in gefitinib-mediated EGFR degradation in NSCLC cells, multiple NSCLC cell lines were applied. The level of EGFR expression, apoptosis marker and autophagic flux were determined by western blot. Expression level of miR-4487 and cell cycle arrest was analyzed by TaqMan assay and flow cytometry respectively.
Results
We found that gefitinib mediates EGFR degradation under normal culture conditions, and is dependent on autophagic flux and the mutation variants of EGFR. Gefitinib reduced expression levels of USP37, which mediated EGFR degradation similar to gefitinib. Our results also showed a gefitinib-mediated increase in endogenous miR-4487 level and presented evidence for the direct targeting of USP37 by miR-4487, resulting in the sequential enhancement of ubiquitination, autophagy, and EGFR degradation. Thus, the depletion of USP37 and overexpression of miR-4487 led to an increase in gefitinib-mediated apoptotic cell death.
Conclusion
These data suggest that miR-4487 is a potential target for treating NSCLC, and miR-4487/USP37-regulated EGFR degradation is a determinant for developing gefitinib resistance.

Citations

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  • The significance of the crosstalk between ubiquitination or deubiquitination and ncRNAs in non-small cell lung cancer
    Yiyang Sun, Ping He, Li Li, Xue Ding
    Frontiers in Oncology.2023;[Epub]     CrossRef
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    L Xu, L Wang, R Yang, T Li, X Zhu
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    Ahmed I. Abulsoud, Shereen Saeid Elshaer, Ahmed A. El-Husseiny, Doaa Fathi, Nourhan M. Abdelmaksoud, Sherif S. Abdel Mageed, Aya Salman, Mohamed Bakr Zaki, Hesham A. El-Mahdy, Ahmed Ismail, Elsayed G.E. Elsakka, Mai A. Abd-Elmawla, Hussein M. El-Husseiny,
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Histone Deacetylase as a Valuable Predictive Biomarker and Therapeutic Target in Immunotherapy for Non-Small Cell Lung Cancer
Hyun-Seock Shin, Juwhan Choi, Jinhwan Lee, Sung Yong Lee
Cancer Res Treat. 2022;54(2):458-468.   Published online September 10, 2021
DOI: https://doi.org/10.4143/crt.2021.425
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Histone deacetylase inhibitors (HDACis) are epigenetic regulators and used clinically for hematopoietic malignancies. Recently, HDACis have received attention as a factor that modulates the immune system. In this study, the role of histone deacetylase (HDAC) expression as a predictive marker in lung cancer patients who were treated with immune checkpoint inhibitors (ICIs) and the role of HDACi and ICI combination treatment in the mouse tumor model were analyzed.
Materials and Methods
The overall response rate (ORR) and progression-free survival (PFS) were analyzed by the expression of HDAC. In vitro assay, the mRNA and protein expression levels of cytokines and programmed death-ligand 1 (PD-L1) were analyzed after HDACi treatment. In vivo assay, TC-1 tumor-bearing mice were treated with HDACi and mouse programmed cell death 1 (PD-1) inhibitor.
Results
The HDAC6 low expression group showed high ORR and prolonged PFS. When the selective HDAC6 inhibitor was administered to the A549 cell line, the levels of interleukin-1β and interleukin-6 decreased and the expression of PD-L1 was reduced. Mice that received both the mouse PD-1 inhibitor and pan-HDACi had a smaller tumor size than that of the mice from the control group. Moreover, mice treated with the mouse PD-1 inhibitor and pan-HDACi generated greater numbers of E7-specific CD8+ T cells.
Conclusion
HDAC6 expression can predict the prognosis of non–small cell lung cancerpatients who were treated with ICIs. Furthermore, co-treatment with HDACi and PD-1 inhibitor was shown to decrease the tumor growth rate and create a favorable tumor microenvironment for cytotoxic T lymphocytes in the TC-1 mouse model.

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Breast cancer
Comparison of the Effectiveness and Clinical Outcome of Everolimus Followed by CDK4/6 Inhibitors with the Opposite Treatment Sequence in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer
Hyehyun Jeong, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim
Cancer Res Treat. 2022;54(2):469-477.   Published online June 23, 2021
DOI: https://doi.org/10.4143/crt.2021.205
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In hormone receptor-positive, human epidermal growth factor receptor 2–negative metastatic breast cancer (HR+ HER2–MBC), the mainstay treatment options include cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and everolimus (EVE) in combination with endocrine treatment. This study aims to compare the outcomes of the following treatment sequences: CDK4/6i followed by EVE and EVE followed by CDK4/6i.
Materials and Methods
Data from HR+ HER2– MBC patients treated between January 2014 and November 2020 with both CDK4/6i and EVE were retrospectively analyzed.
Results
Among the 88 patients included in the study, 51 received CDK4/6i before EVE (C→E group), and 37 received EVE before CDK4/6i (E→C group) with endocrine treatment. More patients in the E→C group had endocrine resistance (13.7% vs. 40.5%), experienced palliative chemotherapy (7.8% vs. 40.5%), and were heavily treated (treated as ≥ 3rd line, 5.9% vs. 40.5%). Median overall survival was 46.8 months in the C→E group and 38.9 months in the E→C group (p=0.151). Median composite progression-free survival (PFS), defined as the time from the start of the preceding regimen to disease progression on the following regimen or death, was 24.8 months in the C→E group vs. 21.8 months in the E→C group (p=0.681). Median PFS2/PFS1 ratio did not differ significantly between groups (0.5 in the C→E group, 0.6 in the E→C group; p=0.775). Ten patients (11.4%) discontinued EVE, and two patients (2.3%) discontinued CDK4/6i during treatment.
Conclusion
Although the CDK4/6i-based regimen should be considered as an earlier line of treatment, CDK4/6i- and EVE-based treatments can be valid options in circumstances where the other treatment had been already given.

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    Yuqian Liao, Yujing Tan, Yipeng Li, Fei Ma, Jiayu Wang, Pin Zhang, Qing Li, Qiao Li, Yang Luo, Bo Lan, Shanshan Chen, Binghe Xu, Hanfang Jiang, Weihong Zhao, Ying Fan
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Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02)
Yeon Joo Kim, Yeon-Joo Kim, Yong Bae Kim, Ik Jae Lee, Jeanny Kwon, Kyubo Kim, Jihye Cha, Myungsoo Kim, In Young Jo, Jung Hoon Kim, Jaehyeon Park, Jin Hee Kim, Juree Kim, Kyung Hwan Shin, Su Ssan Kim
Cancer Res Treat. 2022;54(2):478-487.   Published online July 12, 2021
DOI: https://doi.org/10.4143/crt.2021.632
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.
Materials and Methods
This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.
Results
The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3.
Conclusion
PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

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A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer
Jung Sun Kim, Koung Jin Suh, Dae-Won Lee, Go-un Woo, Miso Kim, Se Hyun Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, So Yeon Park, In Ae Park, Jee Hyun Kim, Seock-Ah Im
Cancer Res Treat. 2022;54(2):488-496.   Published online August 13, 2021
DOI: https://doi.org/10.4143/crt.2021.394
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

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Postmastectomy Radiation Therapy for Node-Negative Breast Cancer of 5 cm or Larger Tumors: A Multicenter Retrospective Analysis (KROG 20-03)
Kyubo Kim, Jinhong Jung, Haeyoung Kim, Wonguen Jung, Kyung Hwan Shin, Ji Hyun Chang, Su Ssan Kim, Won Park, Jee Suk Chang, Yong Bae Kim, Sung Ja Ahn, Ik Jae Lee, Jong Hoon Lee, Hae Jin Park, Jihye Cha, Juree Kim, Jin Hwa Choi, Taeryool Koo, Jeanny Kwon, Jin Hee Kim, Mi Young Kim, Shin-Hyung Park, Yeon-Joo Kim
Cancer Res Treat. 2022;54(2):497-504.   Published online August 25, 2021
DOI: https://doi.org/10.4143/crt.2021.933
AbstractAbstract PDFPubReaderePub
Purpose
To evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomy
Materials and Methods
Medical records of 274 patients from 18 institutions treated with mastectomy between January 2000 and December 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p <0.001, 0.018, and <0.001, respectively). Other characteristics were not significantly different between the two groups.
Results
With a median follow-up of 95 months (range, 1-249), there were 9 locoregional recurrences, and 20 distant metastases. The 8-year locoregional recurrence-free survival rates were 98.0% with PMRT and 91.3% without PMRT (p=0.133), and the 8-year disease-free survival (DFS) rates were 91.8% with PMRT and 73.9% without PMRT (p=0.008). On multivariate analysis incorporating age, histologic grade, lymphovascular invasion, hormonal therapy, chemotherapy, and PMRT, the absence of lymphovascular invasion and the receipt of PMRT were associated with improved DFS (p=0.025 and 0.009, respectively).
Conclusion
Locoregional recurrence rate was very low in node-negative breast cancer of 5cm or larger tumors treated with mastectomy regardless of the receipt of PMRT. However, PMRT was significantly associated with improved DFS. Further investigation is needed to confirm these findings.

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    Xinxin Rao, Xuanyi Wang, Kairui Jin, Yilan Yang, Xu Zhao, Zhe Pan, Weiluo Lv, Zhen Zhang, Li Zhang, Xiaoli Yu, Xiaomao Guo
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    Yazid Belkacemi, Meena S. Moran, Burcu Celet Ozden, Yazan Masannat, Fady Geara, Mohamed Albashir, Nhu Hanh To, Kamel Debbi, Mahmoud El Tamer
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    Jessica L. Thompson, Steven G. Allen, Cecilia Pesavento, Corey W. Speers, Jacqueline S. Jeruss
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Gastrointestinal cancer
Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors
Jwa Hoon Kim, Bokyung Ahn, Seung-Mo Hong, Hwoon-Yong Jung, Do Hoon Kim, Kee Don Choi, Ji Yong Ahn, Jeong Hoon Lee, Hee Kyoung Na, Jong Hoon Kim, Yong-Hee Kim, Hyeong Ryul Kim, Hyun Joo Lee, Sung-Bae Kim, Sook Ryun Park
Cancer Res Treat. 2022;54(2):505-516.   Published online June 23, 2021
DOI: https://doi.org/10.4143/crt.2020.1198
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs.
Materials and Methods
Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included.
Results
The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS.
Conclusion
The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

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    Faizah M. Alotaibi, Ibrahim Abdullah S. Albalawi, Amna M. Anis, Hawazin Alotaibi, Seham Khashwayn, Kanan Alshammari, Jaffar A. Al-Tawfiq
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    Lilong Zhang, Wangbin Ma, Zhendong Qiu, Tianrui Kuang, Kunpeng Wang, Baohong Hu, Weixing Wang
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    Hyejee Ohm, Omar Abdel-Rahman
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    Athéna Crespin, Clément Le Bescop, Jean de Gunzburg, Fabien Vitry, Gérard Zalcman, Julie Cervesi, Pierre-Alain Bandinelli
    Frontiers in Oncology.2023;[Epub]     CrossRef
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    Lilong Zhang, Tianrui Kuang, Dongqi Chai, Wenhong Deng, Peng Wang, Weixing Wang
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    Xin-Tian Xu, Yu Qian, Meng-Xing Tian, Chen-Chen Ding, Huan Guo, Jing Tang, Guo-Liang Pi, Yuan Wu, Zhu Dai, Xin Jin
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    Ning Chen, Xiaoling Xu, Yun Fan
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    豊 木村
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    Liwei Ni, Jing Huang, Jiyuan Ding, Junyan Kou, Tingting Shao, Jun Li, Liujie Gao, Wanzhen Zheng, Zhen Wu
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    Jiaxin Zhou, Guowei Huang, Wan-Ching Wong, Da-hai Hu, Jie-wen Zhu, Ruiman Li, Hong Zhou
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    Deniz Can Guven, Taha Koray Sahin, Enes Erul, Alessandro Rizzo, Angela Dalia Ricci, Sercan Aksoy, Suayib Yalcin
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Machine Learning Model for Predicting Postoperative Survival of Patients with Colorectal Cancer
Mohamed Hosny Osman, Reham Hosny Mohamed, Hossam Mohamed Sarhan, Eun Jung Park, Seung Hyuk Baik, Kang Young Lee, Jeonghyun Kang
Cancer Res Treat. 2022;54(2):517-524.   Published online June 15, 2021
DOI: https://doi.org/10.4143/crt.2021.206
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Machine learning (ML) is a strong candidate for making accurate predictions, as we can use large amount of data with powerful computational algorithms. We developed a ML based model to predict survival of patients with colorectal cancer (CRC) using data from two independent datasets.
Materials and Methods
A total of 364,316 and 1,572 CRC patients were included from the Surveillance, Epidemiology, and End Results (SEER) and a Korean dataset, respectively. As SEER combines data from 18 cancer registries, internal validation was done using 18-Fold-Cross-Validation then external validation was performed by testing the trained model on the Korean dataset. Performance was evaluated using area under the receiver operating characteristic curve (AUROC), sensitivity and positive predictive values.
Results
Clinicopathological characteristics were significantly different between the two datasets and the SEER showed a significant lower 5-year survival rate compared to the Korean dataset (60.1% vs. 75.3%, p < 0.001). The ML-based model using the Light gradient boosting algorithm achieved a better performance in predicting 5-year-survival compared to American Joint Committee on Cancer stage (AUROC, 0.804 vs. 0.736; p < 0.001). The most important features which influenced model performance were age, number of examined lymph nodes, and tumor size. Sensitivity and positive predictive values of predicting 5-year-survival for classes including dead or alive were reported as 68.14%, 77.51% and 49.88%, 88.1% respectively in the validation set. Survival probability can be checked using the web-based survival predictor (http://colorectalcancer.pythonanywhere.com).
Conclusion
ML-based model achieved a much better performance compared to staging in individualized estimation of survival of patients with CRC.

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A Hypoxia-Induced SCFFBXL1 E3 Ligase Ubiquitinates and Degrades the MEN1 Tumor Suppressor to Promote Colorectal Cancer Tumorigenesis
Jun Zeng, Xiao-qing Xiao, Zhi-yong Zhou
Cancer Res Treat. 2022;54(2):525-540.   Published online June 29, 2021
DOI: https://doi.org/10.4143/crt.2021.373
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Emerging evidence has shown that SKP1-cullin-1-F-box-protein (SCF) E3 ligases contribute to the pathogenesis of different cancers by mediating the ubiquitination and degradation of tumor suppressors. However, the functions of SCF E3 ligases in the pathogenesis of colorectal cancer (CRC) remain obscure.
Materials and Methods
The cancerous and adjacent noncancerous tissues from CRC patients were collected, and protein levels were analyzed. Lentiviral short hairpin RNA (shRNA) and plasmid transfection were used to knock down and overexpress gene expression in CRC cell lines. Immunoprecipitation (IP), mass spectrometry, and co-IP analyses were used to determine protein interactions and the assembly of the SCF complex. Cell proliferation, migration, and tumor xenograft assays were performed to examine the effects of SCF members on CRC cell growth in vitro and in vivo.
Results
Hypoxia activated the docking of hypoxia-inducible factor 1α (HIF1α) onto the CUL1 promoter and induced CUL1 expression in CRC cells. CUL1 coupled with RBX1, SKP1, and FBXL1 to assemble the SCFFBXL1 complex in CRC biopsies and cells. The SCFFBXL1 E3 ligase specifically ubiquitinated and degraded the MEN1 tumor suppressor. Knockdown of HIF1α or SCFFBXL1 members, or blockage of SCFFBXL1 by two inhibitors (DT204 and SZLP1-41) caused the accumulation of MEN1 protein and led to a significant decrease in cell proliferation and migration in vitro and tumor growth in vivo.
Conclusion
The SCFFBXL1 E3 ligase is required for the ubiquitination of MEN1, and disruption of this complex may represent a new therapeutic strategy for the treatment of CRC.

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Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Res Treat. 2022;54(2):541-553.   Published online August 6, 2021
DOI: https://doi.org/10.4143/crt.2021.473
AbstractAbstract PDFPubReaderePub
Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

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    Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
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  • 225 Download
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Gynecologic cancer
Effectiveness of Concomitant Chemoradiotherapy with Gemcitabine in Locally Advanced Cervical Cancer Patients with Comorbidities
Hasan Brau-Figueroa, Eder Arango-Bravo, Denisse Castro-Eguiluz, Tatiana Galicia-Carmona, Leopoldo Abraham Lugo-Alferez, Ivette Cruz-Bautista, Roberto Jiménez-Lima, Lucely Cetina-Pérez
Cancer Res Treat. 2022;54(2):554-562.   Published online August 10, 2021
DOI: https://doi.org/10.4143/crt.2021.375
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy with cisplatin (CDDP) followed by brachytherapy. The presence of comorbidities are risk factors for nephrotoxicity and are associated with lower survival. Gemcitabine is a radiosensitizing drug that has shown efficacy and safety in this context. The effectiveness of concomitant chemoradiotherapy with gemcitabine was evaluated versus cisplatin in LACC patients with comorbidities and preserved renal function.
Materials and Methods
An observational, longitudinal and paired study was carried out that included patients treated between February 2003 and December 2015. The primary objectives were to evaluate response rates, progression-free survival, and overall survival; the secondary objectives were to evaluate toxicity and renal function.
Results
Sixty-three patients treated with gemcitabine at 300 mg/m2 weekly and 126 patients treated with CDDP 40 mg/m2 weekly were included. There were no significant differences in response rates and survival rates. Treatment with cisplatin presented a higher frequency of hematological toxicities, while gemcitabine presented a higher frequency of gastrointestinal toxicities. A decrease in glomerular filtration rate (GFR; baseline vs. 1-year post-treatment) was observed in the cisplatin group (p=0.002), while not in the gemcitabine group (p=0.667). In a multivariate analysis, it is observed that only CDDP correlates with the decrease in GFR (hazard ratio, 2.42; p=0.012).
Conclusion
In LACC patients with comorbidities, gemcitabine and CDDP show the same efficacy, with different toxicity profiles. Treatment with cisplatin is associated with a significant decrease in GFR during follow-up, compared to treatment with gemcitabine that does not decrease it.

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    Adane Adugna, Mamaru Getinet, Gashaw Azanaw Amare, Mohammed Jemal
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    Silvia Alarcón-Barrios, Julissa Luvián-Morales, Denisse Castro-Eguiluz, Merari Delgadillo-González, Brenda Olivia Lezcano-Velázquez, Eder Alexandro Arango-Bravo, Laura Flores-Cisneros, Sebastián Aguiar Rosas, Lucely Cetina-Pérez
    Current Problems in Cancer.2024; 48: 101041.     CrossRef
  • Association between body composition phenotypes and treatment toxicity in women with cervical cancer undergoing chemoradiotherapy
    Mariah Azevedo Aredes, Nathália Silva de Paula, Gabriela Villaça Chaves
    Nutrition.2024; 127: 112539.     CrossRef
  • Older adults with cancer and common comorbidities—challenges and opportunities in improving their cancer treatment outcomes
    Weiwei Chen, Rachel D Altshuler, Phil Daschner, Carolina Salvador Morales, Diane C St. Germain, Jennifer Guida, Pataje G S Prasanna, Jeffrey C Buchsbaum
    JNCI: Journal of the National Cancer Institute.2024; 116(11): 1730.     CrossRef
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Pediatric cancer
Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults
Hee Young Ju, Meerim Park, Jun Ah Lee, Hyeon Jin Park, Seog Yun Park, June Hyuk Kim, Hyun Guy Kang, Hee Chul Yang, Byung-Kiu Park
Cancer Res Treat. 2022;54(2):563-571.   Published online June 14, 2021
DOI: https://doi.org/10.4143/crt.2021.178
AbstractAbstract PDFPubReaderePub
Purpose
No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults.
Materials and Methods
We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m2 intravenously on day 1, irinotecan, 50 mg/m2/day intravenously on days 1-5, and temozolomide, 100 mg/m2/day orally on days 1-5.
Results
A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality.
Conclusion
The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Citations

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  • MGMT protein expression is a reliable predictive biomarker for temozolomide‐containing chemotherapy in osteosarcoma
    Yoshinori Uchihara, Katsutsugu Umeda, Yosuke Yamada, Hiroaki Ito, Keiji Tasaka, Kiyotaka Isobe, Ryo Akazawa, Naoko Kawabata, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Takashi Noguchi, Akio Sakamoto, Yoshiki Arakawa, Ayumu Arakawa, Nobuyuki Yamamoto,
    Cancer Science.2024; 115(10): 3394.     CrossRef
  • Anlotinib combined with radiotherapy and chemotherapy for recurrent pelvic osteosarcoma treatment: a case report and literature review
    Qian Chen, Kai Zheng, Ming Xu, Ning Yan, Gong Hai, Xiuchun Yu
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Irinotecan/temozolomide/vincristine

    Reactions Weekly.2022; 1910(1): 267.     CrossRef
  • Acetylenic Synthetic Betulin Derivatives Inhibit Akt and Erk Kinases Activity, Trigger Apoptosis and Suppress Proliferation of Neuroblastoma and Rhabdomyosarcoma Cell Lines
    Sylwia K. Król, Ewa Bębenek, Magdalena Dmoszyńska-Graniczka, Adrianna Sławińska-Brych, Stanisław Boryczka, Andrzej Stepulak
    International Journal of Molecular Sciences.2021; 22(22): 12299.     CrossRef
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Epidemiology of Acute Leukemia among Children with Down Syndrome in Korea
Young Bae Choi, Keon Hee Yoo
Cancer Res Treat. 2022;54(2):572-578.   Published online August 10, 2021
DOI: https://doi.org/10.4143/crt.2021.368
AbstractAbstract PDFPubReaderePub
Purpose
Children with Down syndrome (DS) show a higher risk of acute leukemia than those without DS. In this study, we investigated the nationwide incidence of acute leukemia among children with DS and compared their epidemiologic characteristics with those of children with acute leukemia but without DS.
Materials and Methods
Using the National Health Insurance Service database, we selected patients with acute leukemia aged 0–19 years at diagnosis between 2007 and 2016.
Results
Among the 4,697 children with acute leukemia, 54 (1.1%) had DS. The median incidence rate of leukemia with DS by year was 1.3% (range, 0.2%–2.0%). Sixteen patients with acute lymphoblastic leukemia (ALL; 29.6%) and 36 with acute myeloid leukemia (AML; 66.7%) had DS. The DS group showed younger age at diagnosis than the non-DS group, and diagnosis of AML was more frequent in the DS group than in the non-DS group (3 years vs. 9 years, p<0.001; 66.7% vs. 32.4%, P<0.001, respectively). The 5-year overall survival was comparable between the DS and non-DS groups (88.0% vs. 81.9%, p=0.375). Among all the Koreans born between 2007 and 2008, the incidences of acute leukemia, ALL, and AML were 49.25, 20.75, and 163.38 times higher, respectively, in the DS group than in the non-DS group.
Conclusion
Our findings support the fact that the incidence of acute leukemia is higher among patients with DS than among those without DS in Korea. However, the DS and non-DS groups in this study had a comparable overall survival rate.

Citations

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  • Cancer risks related to intellectual disabilities: A systematic review
    Amina Banda, Jenneken Naaldenberg, Aura Timen, Agnies van Eeghen, Geraline Leusink, Maarten Cuypers
    Cancer Medicine.2024;[Epub]     CrossRef
  • 5,469 View
  • 129 Download
  • 1 Web of Science
  • 1 Crossref
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Sarcoma
Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single-Center Experience over 25 Years and Evaluation of PD-L1 Expression
Heejung Chae, Jeong Eun Kim, Wanlim Kim, Jong-Seok Lee, Si Yeol Song, Min Hee Lee, Hye Won Chung, Kyung-Ja Cho, Joon Seon Song, Jin-Hee Ahn
Cancer Res Treat. 2022;54(2):579-589.   Published online July 6, 2021
DOI: https://doi.org/10.4143/crt.2021.496
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1).
Materials and Methods
We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS.
Results
The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes.
Conclusion
Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

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  • Recurrent Intrathoracic Liposarcoma: A Case Report and a Comprehensive Literature Review of a Rare Clinical Entity
    Vasileios Leivaditis , Manfred Dahm , Athanasios Papatriantafyllou, Hans-Georg Keul, Lydia Kohl, Hans-Joachim Schäfers
    Cureus.2024;[Epub]     CrossRef
  • Clinicopathological Features of Intrathoracic Liposarcoma—A Systematic Review with an Illustrative Case
    Kajetan Kiełbowski, Nikola Ruszel, Seweryn Adam Skrzyniarz, Małgorzata Edyta Wojtyś, Rafał Becht, Konrad Ptaszyński, Darko Gajić, Janusz Wójcik
    Journal of Clinical Medicine.2022; 11(24): 7353.     CrossRef
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Incidence Patterns and Outcomes of Ewing Sarcoma in South Korea (1999-2017): A Retrospective Analysis Using Korea Central Cancer Registry Data
Jun Ah Lee, Jiwon Lim, Dayeon Park, Hye Young Jin, Meerim Park, Hyeon Jin Park, Jong Woong Park, June Hyuk Kim, Hyun Guy Kang, Young-Joo Won
Cancer Res Treat. 2022;54(2):590-596.   Published online July 20, 2021
DOI: https://doi.org/10.4143/crt.2021.311
AbstractAbstract PDFPubReaderePub
Purpose
Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea.
Materials and Methods
Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups.
Results
There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors.
Conclusion
This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.

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  • Twenty‐year outcome of prevalence, incidence, mortality and survival rate in patients with malignant bone tumors
    Yao Xu, Fanqi Shi, Yanting Zhang, Mengfan Yin, Xiuxin Han, Jinyan Feng, Guowen Wang
    International Journal of Cancer.2024; 154(2): 226.     CrossRef
  • A Machine Learning-Based Predictive Model for Predicting Lymph Node Metastasis in Patients With Ewing’s Sarcoma
    Wenle Li, Qian Zhou, Wencai Liu, Chan Xu, Zhi-Ri Tang, Shengtao Dong, Haosheng Wang, Wanying Li, Kai Zhang, Rong Li, Wenshi Zhang, Zhaohui Hu, Su Shibin, Qiang Liu, Sirui Kuang, Chengliang Yin
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • TrkC, a novel prognostic marker, induces and maintains cell survival and metastatic dissemination of Ewing sarcoma by inhibiting EWSR1-FLI1 degradation
    Min Soo Kim, Won Sung Lee, Hanki Lee, Wook Jin
    Cell Death & Disease.2022;[Epub]     CrossRef
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Hematologic malignancy
Plasma Circulating Tumor DNA in Patients with Primary Central Nervous System Lymphoma
Sang Eun Yoon, Yeon Jeong Kim, Joon Ho Shim, Donghyun Park, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Yeung-Chul Mun, Kyoung Eun Lee, Duck Cho, Won Seog Kim, Seok Jin Kim
Cancer Res Treat. 2022;54(2):597-612.   Published online July 23, 2021
DOI: https://doi.org/10.4143/crt.2021.752
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL.
Materials and Methods
Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.
Results
Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment.
Conclusion
The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

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  • Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
    Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
    Annals of Laboratory Medicine.2025; 45(1): 90.     CrossRef
  • Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR
    Yujie Zhong, Geok Wee Tan, Johanna Bult, Nick Veltmaat, Wouter Plattel, Joost Kluiver, Roelien Enting, Arjan Diepstra, Anke van den Berg, Marcel Nijland
    BMC Cancer.2024;[Epub]     CrossRef
  • Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma
    Jin-Hua Liang, Yi-Fan Wu, Hao-Rui Shen, Yue Li, Jun-Heng Liang, Rui Gao, Wei Hua, Chun-Yu Shang, Kai-Xin Du, Tong-Yao Xing, Xin-Yu Zhang, Chen-Xuan Wang, Liu-Qing Zhu, Yang W. Shao, Jian-Yong Li, Jia-Zhu Wu, Hua Yin, Li Wang, Wei Xu
    Leukemia.2024; 38(7): 1541.     CrossRef
  • Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review
    Lakshmi Nayak, Chetan Bettegowda, Florian Scherer, Norbert Galldiks, Manmeet Ahluwalia, Alexander Baraniskin, Louisa von Baumgarten, Jacoline E C Bromberg, Andrés J M Ferreri, Christian Grommes, Khê Hoang-Xuan, Julia Kühn, James L Rubenstein, Roberta Rudà
    Neuro-Oncology.2024; 26(6): 993.     CrossRef
  • Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
    Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
    Cancer Research and Treatment.2024; 56(3): 920.     CrossRef
  • Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
    Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
    Blood Reviews.2024; 68: 101237.     CrossRef
  • Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas
    Jurik A. Mutter, Stefan K. Alig, Mohammad S. Esfahani, Eliza M. Lauer, Jan Mitschke, David M. Kurtz, Julia Kühn, Sabine Bleul, Mari Olsen, Chih Long Liu, Michael C. Jin, Charles W. Macaulay, Nicolas Neidert, Timo Volk, Michel Eisenblaetter, Sebastian Raue
    Journal of Clinical Oncology.2023; 41(9): 1684.     CrossRef
  • Clinical applications of circulating tumor DNA in central nervous system lymphoma
    Anna Katharina Foerster, Eliza M. Lauer, Florian Scherer
    Seminars in Hematology.2023; 60(3): 150.     CrossRef
  • Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
    Gloria Figaredo, Alejandro Martín-Muñoz, Santiago Barrio, Laura Parrilla, Yolanda Campos-Martín, María Poza, Laura Rufián, Patrocinio Algara, Marina De La Torre, Ana Jiménez Ubieto, Joaquín Martínez-López, Luis-Felipe Casado, Manuela Mollejo
    Cancers.2023; 15(16): 4022.     CrossRef
  • Asian variant intravascular large B-cell lymphoma with highly suspected central nervous system involvement: A case report
    Yong-Pyo Lee, Seung-Myoung Son, Jihyun Kwon
    World Journal of Clinical Cases.2023; 11(33): 8058.     CrossRef
  • The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies
    Rafael Colmenares, Noemí Álvarez, Santiago Barrio, Joaquín Martínez-López, Rosa Ayala
    Cancers.2022; 14(5): 1310.     CrossRef
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Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study
Yu Ri Kim, Soo-Jeong Kim, Hye Sun Lee, Soyoung Jeon, Hyunsoo Cho, Haerim Chung, Ji Eun Jang, June-Won Cheong, Yoo Hong Min, Jin Seok Kim
Cancer Res Treat. 2022;54(2):613-620.   Published online August 5, 2021
DOI: https://doi.org/10.4143/crt.2021.270
AbstractAbstract PDFPubReaderePub
Purpose
Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24.
Materials and Methods
Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24.
Results
Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001).
Conclusion
Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

Citations

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  • Clinical significance and predictive risk factors for event-free survival at 24 months in patients with PTCL, NOS
    Zheng Cao, Xiaojun Wang, Xuemin Xue, Xiaoli Feng
    Annals of Hematology.2024; 103(3): 869.     CrossRef
  • Validity of event-free survival as a surrogate endpoint in haematological malignancy: Review of the literature and health technology assessments
    Sarit Assouline, Adriana Wiesinger, Clare Spooner, Jelena Jovanović, Max Schlueter
    Critical Reviews in Oncology/Hematology.2022; 175: 103711.     CrossRef
  • 5,871 View
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Palliative medicine
A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients
Yu Jung Kim, Yusuke Hiratsuka, Sang-Yeon Suh, Beodeul Kang, Si Won Lee, Hong-Yup Ahn, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Jee Hyun Kim, Jong Seok Lee
Cancer Res Treat. 2022;54(2):621-629.   Published online July 12, 2021
DOI: https://doi.org/10.4143/crt.2021.483
AbstractAbstract PDFPubReaderePub
Purpose
We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.
Materials and Methods
In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.
Results
The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88.
Conclusion
The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.

Citations

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  • Clinicians’ Prediction of Survival Is Most Useful for Palliative Care Referral
    Eun Hee Jung, Yusuke Hiratsuka, Sang-Yeon Suh, Seok-Joon Yoon, Beodeul Kang, Si Won Lee, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Yu Jung Kim
    Palliative Medicine Reports.2024; 5(1): 365.     CrossRef
  • 7,745 View
  • 167 Download
  • 3 Web of Science
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