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Original Articles
General
Association between Tumor Size at the Time of Disease Progression and Survival Outcomes
Chi Hoon Maeng, Bum Jun Kim, Myung-Ju Ahn, In Sil Choi, Dae Young Zang, Bo-Hyung Kim, Minji Kwon, Dae Seog Heo, Bhumsuk Keam
Cancer Res Treat. 2025;57(2):362-368.   Published online October 22, 2024
DOI: https://doi.org/10.4143/crt.2024.690
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study evaluates the prognostic significance of tumor size at disease progression (PD) and depth of response (DOR) in cancer patients.
Materials and Methods
We performed post hoc analysis using data from six prospective clinical trials conducted by the Korean Cancer Study Group. Patients with tumor size at PD was categorized into ‘Mild PD’ and ‘Significant PD’ based on the cutoff values of relative change from baseline using maximally selected rank statistics. The overall survival (OS) and progression-free survival (PFS) were compared between PD and DOR categories.
Results
Among the 194 evaluable patients, 130 experienced PD. A 35.48% decrease from baseline in tumor size at PD was chosen for the cutoff between mild and significant PD for OS (mild PD: tumor size from the baseline ≤ −35.48%; significant PD > −35.48%). The mild PD had superior OS compared to the significant PD (25.8 vs. 12.8 months; Hazard ratio [HR] 0.47, 95% CI 0.266-0.843, p=0.009). When using an exploratory cutoff based on whether the tumor size was below vs. exceeded from the baseline (mild PD: tumor size from the baseline ≤ 0%; significant PD > 0%), OS remained significantly longer in the mild PD (17.1 vs. 11.8 months; HR 0.60, 95% CI 0.392-0.932, p=0.021). The greatest DOR was associated with the longest OS and PFS (p<0.001 for both).
Conclusion
Tumor size at PD and DOR were significant prognostic factors for progressive disease. Maintaining a sufficiently reduced tumor size even during PD was associated with better survival outcomes.
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The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group
Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yun, Byung-Ho Nam, Dae Young Zang
Cancer Res Treat. 2025;57(1):39-46.   Published online July 10, 2024
DOI: https://doi.org/10.4143/crt.2024.421
AbstractAbstract PDFPubReaderePub
Purpose
The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients.
Materials and Methods
We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided.
Results
From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient.
Conclusion
Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.
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Lung and Thoracic cancer
Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2023;55(4):1134-1143.   Published online May 23, 2023
DOI: https://doi.org/10.4143/crt.2023.311
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs.
Materials and Methods
We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed.
Results
High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI.
Conclusion
High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

Citations

Citations to this article as recorded by  
  • Simultaneous blockade of the CD73/EGFR axis inhibits tumor growth
    Keivan Ardeshiri, Hadi Hassannia, Ghasem Ghalamfarsa, Hanieh Jafary, Farhad Jadidi
    IUBMB Life.2025;[Epub]     CrossRef
  • Exploring the Expression of CD73 in Lung Adenocarcinoma with EGFR Genomic Alterations
    Elodie Long-Mira, Christophe Bontoux, Guylène Rignol, Véronique Hofman, Sandra Lassalle, Jonathan Benzaquen, Jacques Boutros, Salomé Lalvée-Moret, Katia Zahaf, Virginie Lespinet-Fabre, Olivier Bordone, Sophia Maistre, Christelle Bonnetaud, Charlotte Cohen
    Cancers.2025; 17(6): 1034.     CrossRef
  • Comprehensive pan-cancer analysis of CD73: Explore its association with prognosis and tumor immune microenvironment
    Chen Chen, Sasa Liu, Yanfen Ma
    Heliyon.2024; 10(22): e40329.     CrossRef
  • 3,802 View
  • 282 Download
  • 3 Web of Science
  • 3 Crossref
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Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non–Small Cell Lung Cancer
Chaelin Lee, Miso Kim, Dong-Wan Kim, Tae Min Kim, Soyeon Kim, Sun-Wha Im, Yoon Kyung Jeon, Bhumsuk Keam, Ja-Lok Ku, Dae Seog Heo
Cancer Res Treat. 2022;54(1):140-149.   Published online May 3, 2021
DOI: https://doi.org/10.4143/crt.2021.385
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs.
Materials and Methods
We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening.
Results
In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs.
Conclusion
Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Citations

Citations to this article as recorded by  
  • Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors
    Tomohiro Kondo, Osamu Kikuchi, Yoshihiro Yamamoto, Tomohiko Sunami, Yafeng Wang, Keita Fukuyama, Tomoki Saito, Hideto Nakahara, Sachiko Minamiguchi, Masashi Kanai, Atsushi Sueyoshi, Manabu Muto
    The Oncologist.2025;[Epub]     CrossRef
  • A Constitutive EGFR Kinase Dimer to Study Inhibitor Pharmacology
    Justin J. Kim, Ilse K. Schaeffner, David E. Heppner, Ciric To, Pasi A. Jänne, Tyler S. Beyett, Michael J. Eck
    Molecular Pharmacology.2024; 105(2): 97.     CrossRef
  • Tumor-associated Macrophages Mediate Gefitinib Resistance in Lung Cancer through HGF/c-met Signaling Pathway
    Xiali Tang, Yu Chen, Demin Jiao, Xiang Liu, Jun Chen, Yongyang Liu, Chunyan Jiang, Qingyong Chen
    Anti-Cancer Agents in Medicinal Chemistry.2024; 24(1): 30.     CrossRef
  • Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer
    Ziyang Jiang, Zhihan Gu, Xiaomin Yu, Tao Cheng, Bofu Liu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Molecular Targets and Mechanisms of Casein-Derived Tripeptides Ile-Pro-Pro and Val-Pro-Pro on Hepatic Glucose Metabolism
    Chenyang Wang, Lin Zheng, Mouming Zhao
    Journal of Agricultural and Food Chemistry.2023; 71(48): 18802.     CrossRef
  • Erlotinib

    Reactions Weekly.2022; 1907(1): 208.     CrossRef
  • 9,449 View
  • 339 Download
  • 5 Web of Science
  • 6 Crossref
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General
Analysis of Cancer Patient Decision-Making and Health Service Utilization after Enforcement of the Life-Sustaining Treatment Decision-Making Act in Korea
Dalyong Kim, Shin Hye Yoo, Seyoung Seo, Hyun Jung Lee, Min Sun Kim, Sung Joon Shin, Chi-Yeon Lim, Do Yeun Kim, Dae Seog Heo, Chae-Man Lim
Cancer Res Treat. 2022;54(1):20-29.   Published online April 12, 2021
DOI: https://doi.org/10.4143/crt.2021.131
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to confirm the decision-making patterns for life-sustaining treatment (LST) and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act.
Materials and Methods
Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the LST form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data.
Results
The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient’s intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient’s intention).
Conclusion
The cancer patient’s own decision-making rather than the family’s decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs.

Citations

Citations to this article as recorded by  
  • Factors Affecting Life-Sustaining Treatment Decisions and Changes in Clinical Practice after Enforcement of the Life-Sustaining Treatment (LST) Decision Act: A Tertiary Hospital Experience in Korea
    Yoon Jung Jang, Yun Jung Yang, Hoi Jung Koo, Hye Won Yoon, Seongbeom Uhm, Sun Young Kim, Jeong Eun Kim, Jin Won Huh, Tae Won Kim, Seyoung Seo
    Cancer Research and Treatment.2025; 57(1): 280.     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
  • 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
  • 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
  • Comparison of factors influencing the decision to withdraw life-sustaining treatment in intensive care unit patients after implementation of the Life-Sustaining Treatment Act in Korea
    Claire Junga Kim, Kyung Sook Hong, Sooyoung Cho, Jin Park
    Acute and Critical Care.2024; 39(2): 294.     CrossRef
  • Nurses' engagement in advance care planning practices: A descriptive cross‐sectional study
    Sangmin Lee, Naixue Cui, Hyejin Kim
    Journal of Clinical Nursing.2024;[Epub]     CrossRef
  • 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
  • Development and Feasibility Evaluation of Smart Cancer Care 2.0 Based on Patient-Reported Outcomes for Post-Discharge Management of Patients with Cancer
    Jin Ah Kwon, Songsoo Yang, Su-Jin Koh, Young Ju Noh, Dong Yoon Kang, Sol Bin Yang, Eun Ji Kwon, Jeong-Wook Seo, Jin sung Kim, Minsu Ock
    Cancer Research and Treatment.2024; 56(4): 1040.     CrossRef
  • Advance Care Planning in South Korea
    Yu Jung Kim, Sun-Hyun Kim
    Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen.2023; 180: 68.     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
  • 7,748 View
  • 205 Download
  • 11 Web of Science
  • 10 Crossref
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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.

Citations

Citations to this article as recorded by  
  • Optimal treatment approach for intracranial germinoma: a systematic review and meta-analysis
    Zhirui Zhou, Jiabing Liu, Qi Yue, Lingxiao Chen, Xiwei Zhang, Xin Lin, Lin Zheng, Enmin Wang, Yang Wang, Ying Mao
    BMC Cancer.2025;[Epub]     CrossRef
  • Distribution and failure patterns of primary central nervous system lymphoma related to the hippocampus: implications for hippocampal avoidance irradiation
    Hyejo Ryu, Xue Li, Tae Hoon Lee, Tae Min Kim, Seung Hong Choi, Chul-Kee Park, Soon Tae Lee, Sung-Hye Park, Jae-Kyung Won, Bum-Sup Jang, Il Han Kim, Joo Ho Lee
    Journal of Neuro-Oncology.2025;[Epub]     CrossRef
  • 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
  • Excluding prepontine cistern from whole ventricle radiotherapy target volume in localized germinoma
    Hyejo Ryu, Joo Ho Lee
    Radiation Oncology Journal.2023; 41(1): 48.     CrossRef
  • Intracranial Germinomas: Diagnosis, Pathogenesis, Clinical Presentation, and Management
    Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore
    Current Oncology Reports.2023; 25(7): 765.     CrossRef
  • Proton therapy for pediatric diencephalic tumors
    Adam J. Grippin, Susan L. McGovern
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Intracranial Germinoma—Association between Delayed Diagnosis, Altered Clinical Manifestations, and Prognosis
    Iwona Jabłońska, Marcin Goławski, Elżbieta Nowicka, Katarzyna Drosik-Rutowicz, Anna Trybus, Rafał Tarnawski, Marcin Miszczyk
    Cancers.2023; 15(10): 2789.     CrossRef
  • Outcomes of intracranial germinoma—A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies
    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
  • 11,246 View
  • 359 Download
  • 13 Web of Science
  • 12 Crossref
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Palliative medicine
Difficulties Doctors Experience during Life-Sustaining Treatment Discussion after Enactment of the Life-Sustaining Treatment Decisions Act: A Cross-Sectional Study
Shin Hye Yoo, Wonho Choi, Yejin Kim, Min Sun Kim, Hye Yoon Park, Bhumsuk Keam, Dae Seog Heo
Cancer Res Treat. 2021;53(2):584-592.   Published online November 19, 2020
DOI: https://doi.org/10.4143/crt.2020.735
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to investigate difficulties doctors experience during life-sustaining treatment (LST) discussion with seriously ill patients and their families after enactment of the LST Decisions Act in February 2018.
Materials and Methods
A cross-sectional survey was conducted in a tertiary hospital in the Republic of Korea in August 2019. Six hundred eighty-six doctors who care for seriously ill patients were given a structured questionnaire, and difficulties during the discussion were examined.
Results
One hundred thirty-two doctors completed the questionnaire. Eighty-five percent answered they treat cancer patients. Most (86.4%) experienced considerable difficulties during LST discussions (mean score, 7.4±1.6/10). The two most common difficulties were communication with patients and family and determining when to discuss LST. Two-thirds of doctors found direct discussions with the patient difficult and said they would initiate LST discussions only with family. LST discussions were actually initiated later than considered appropriate. When medically assessing whether the patient is imminently dying, 56% of doctors experienced disagreements with other doctors, which could affect their decisions.
Conclusion
This study found that most doctors experienced serious difficulties regarding communication with patients and family and medical assessment of dying process during LST discussions. To alleviate these difficulties, further institutional support is needed to improve the LST discussion between doctors, patients, and family.

Citations

Citations to this article as recorded by  
  • Nurses' engagement in advance care planning practices: A descriptive cross‐sectional study
    Sangmin Lee, Naixue Cui, Hyejin Kim
    Journal of Clinical Nursing.2024;[Epub]     CrossRef
  • Navigating shared decision-making after the Life-Sustaining Treatment Decision Act: a qualitative study of in-depth interviews with terminal cancer patients, families, and healthcare professionals
    Soo-Young Yu, Yu-eun Lee, Sung Joon Shin, Go-un Woo, Dalyong Kim, Jung Hye Kwon, Do Yeun Kim, Eunyoung Eunice Suh
    Supportive Care in Cancer.2024;[Epub]     CrossRef
  • Advance Care Planning in Palliative Care in Asia: Barriers and Implications
    Yoo Jeong Lee, Sun-Hyun Kim, Shin Hye Yoo, A-Sol Kim, Cheng-Pei Lin, Diah Martina, Masanori Mori, Sang-Yeon Suh
    Journal of Hospice and Palliative Care.2024; 27(4): 107.     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
  • Ethical Issues Referred to Clinical Ethics Support at a University Hospital in Korea: Three-Year Experience After Enforcement of Life-Sustaining Treatment Decisions Act
    Shin Hye Yoo, Yejin Kim, Wonho Choi, Jeongmi Shin, Min Sun Kim, Hye Yoon Park, Bhumsuk Keam, Jae-Joon Yim
    Journal of Korean Medical Science.2023;[Epub]     CrossRef
  • Advance Care Planning in South Korea
    Yu Jung Kim, Sun-Hyun Kim
    Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen.2023; 180: 68.     CrossRef
  • Physicians’ attitudes and experiences about withholding/withdrawing life-sustaining treatments in pediatrics: a systematic review of quantitative evidence
    Yajing Zhong, Alice Cavolo, Veerle Labarque, Chris Gastmans
    BMC Palliative Care.2023;[Epub]     CrossRef
  • Public awareness of advance care planning and hospice palliative care: a nationwide cross-sectional study in Korea
    Boram Kim, Junyong Lee, Youn Seon Choi
    BMC Palliative Care.2023;[Epub]     CrossRef
  • Analysis of Cancer Patient Decision-Making and Health Service Utilization after Enforcement of the Life-Sustaining Treatment Decision-Making Act in Korea
    Dalyong Kim, Shin Hye Yoo, Seyoung Seo, Hyun Jung Lee, Min Sun Kim, Sung Joon Shin, Chi-Yeon Lim, Do Yeun Kim, Dae Seog Heo, Chae-Man Lim
    Cancer Research and Treatment.2022; 54(1): 20.     CrossRef
  • Physician decision-making process about withholding/withdrawing life-sustaining treatments in paediatric patients: a systematic review of qualitative evidence
    Yajing Zhong, Alice Cavolo, Veerle Labarque, Chris Gastmans
    BMC Palliative Care.2022;[Epub]     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
  • Awareness of Doctors’ Shared Decision-Making in Life-Sustaining Care Decisions
    Dalyong Kim, Hyun Jung Lee, Soo-Young Yu, Jung Hye Kwon, Hee Kyung Ahn, Jee Hyun Kim, Seyoung Seo, Chi Hoon Maeng, Seungtaek Lim, Do Yeun Kim, Sung Joon Shin
    The Korean Journal of Hospice and Palliative Care.2021; 24(4): 204.     CrossRef
  • 6,991 View
  • 111 Download
  • 9 Web of Science
  • 12 Crossref
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Implication of the Life-Sustaining Treatment Decisions Act on End-of-Life Care for Korean Terminal Patients
Jung Sun Kim, Shin Hye Yoo, Wonho Choi, Yejin Kim, Jinui Hong, Min Sun Kim, Hye Yoon Park, Bhumsuk Keam, Dae Seog Heo
Cancer Res Treat. 2020;52(3):917-924.   Published online March 23, 2020
DOI: https://doi.org/10.4143/crt.2019.740
AbstractAbstract PDFPubReaderePub
Purpose
Life-sustaining treatment (LST) decisions for patients and caregivers at the end-of-life (EOL) process are supported by the “Act on Hospice and Palliative Care and Decisions on LST for Patients at the EOL,” enforced in February 2018. Itremains unclear whether the act changes EOL decisions and LST implementation in clinical practice. For this study, we investigated patients’ decision-making regarding LSTs during the EOL process since the act’s enforcement.
Materials and Methods
Retrospective reviews were conducted on adult patients who were able to decide to terminate LST and died at Seoul National University Hospital between February 5, 2018, and February 5, 2019. We examined demographics, who made the decisions, the type and date of documentation confirming patient's LST, and whether the LST was withheld or withdrawn.
Results
Of 809 patients who were enrolled, 29% (n=231) completed forms regarding LST themselves, and 71% (n=578) needed family members to decide. The median time from confirmation of the EOL process to death and from the Advance Statement to death were 2 and 5 days, respectively (both ranges, 0 to 244). In total, 90% (n=727) of patients withheld treatment, and 10% (n=82)withdrew it. We found a higher withdrawal rate when family members made the decisions (13.3% vs. 1.7%, p < 0.001).
Conclusion
After the act’s enforcement, withdrawing LSTs became lawful and self-determination rates increased. Family members still make 71% of decisions regarding LSTs, but these are often inconsistent with the patients’ wishes; thus, further efforts are needed to integrate the new act into clinical practice.

Citations

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The Prognostic Value of Albumin-to-Alkaline Phosphatase Ratio before Radical Radiotherapy in Patients with Non-metastatic Nasopharyngeal Carcinoma: A Propensity Score Matching Analysis
Jae Sik Kim, Bhumsuk Keam, Dae Seog Heo, Doo Hee Han, Chae-Seo Rhee, Ji-hoon Kim, Kyeong Cheon Jung, Hong-Gyun Wu
Cancer Res Treat. 2019;51(4):1313-1323.   Published online January 29, 2019
DOI: https://doi.org/10.4143/crt.2018.503
AbstractAbstract PDFPubReaderePub
Purpose
We first analyzed the prognostic power of albumin-to-alkaline phosphatase ratio (AAPR) before radical radiotherapy (RT) in non-metastatic nasopharyngeal carcinoma (NPC) patients.
Materials and Methods
The records of 170 patients with biopsy-proven, non-metastatic NPC treated by radical RT between 1998 and 2016 at our institution were retrospectively reviewed. Median follow-up duration was 50.6 months. All patients received intensity-modulated RT and cisplatin based chemotherapy before, during, or after RT. The major treatment of patients was based on concurrent chemoradiotherapy (92.4%). The AAPR was calculated by the last value of both albumin and alkaline phosphatase within 1 month immediately preceding RT. The optimal cut-off level of AAPR was determined by using Cutoff Finder, a web-based system. Propensity score matching (PSM) analysis was performed.
Results
The optimal cut-off level of AAPR was 0.4876. After PSM analysis of whole cohort, an AAPR was not related to survival outcomes. In PSM analysis for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC), an AAPR ≥ 0.4876 was related to better overall survival (OS), progression-free survival (PFS), and locoregional relapse–free survival (LRRFS) (OS: hazard ratio [HR], 0.341; 95% confidence interval [CI], 0.144 to 0.805; p=0.014; PFS: HR, 0.416; 95% CI, 0.189 to 0.914; p=0.029; and LRRFS: HR, 0.243; 95% CI, 0.077 to 0.769; p=0.016, respectively).
Conclusion
The AAPR, inexpensive and readily derived from a routine blood test, could be an independent prognostic factor for patients with LA-NPC. And it might help physicians determine treatment plans by identifying the patient's current status. Future prospective clinical trials to validate its prognostic value are needed.

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Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer
Su-Jung Kim, Soyeon Kim, Dong-Wan Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yusoo Lee, Jaemoon Koh, Yoon Kyung Jeon, Dae Seog Heo
Cancer Res Treat. 2019;51(3):1231-1240.   Published online December 31, 2018
DOI: https://doi.org/10.4143/crt.2018.486
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer.
Materials and Methods
We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed.
Results
PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163).
Conclusion
PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.

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Acquired Resistance of MET-Amplified Non-small Cell Lung Cancer Cells to the MET Inhibitor Capmatinib
Seulki Kim, Tae Min Kim, Dong-Wan Kim, Soyeon Kim, Miso Kim, Yong-Oon Ahn, Bhumsuk Keam, Dae Seog Heo
Cancer Res Treat. 2019;51(3):951-962.   Published online October 10, 2018
DOI: https://doi.org/10.4143/crt.2018.052
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1.
Materials and Methods
We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines.
Results
We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor.
Conclusion
Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.

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The Risk of Herpes Zoster in Patients with Non-small Cell Lung Cancer according to Chemotherapy Regimens: Tyrosine Kinase Inhibitors versus Cytotoxic Chemotherapy
Ji Young Choi, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Seong Jin Jo
Cancer Res Treat. 2019;51(1):169-177.   Published online April 5, 2018
DOI: https://doi.org/10.4143/crt.2017.491
AbstractAbstract PDFPubReaderePub
Purpose
Despite the successful use of tyrosine kinase inhibitors (TKIs) in cancer patients, their effect on herpes zoster development has not been studied. The aim of this study was to evaluate and compare the effects of epidermal growth factor receptor (EGFR) TKI and cytotoxic chemotherapy on the risk of herpes zoster development in non-small cell lung cancer (NSCLC) patients.
Materials and Methods
We conducted a medical review of all eligible NSCLC patients in Seoul National University hospital between 2002 and 2015. We classified patients based on whether they previously underwent EGFR TKI therapy into either the TKI group or the cytotoxic group. We compared the incidence rates of herpes zoster during TKI therapy and cytotoxic chemotherapy. Additionally, the longitudinal risk of herpes zoster from TKIs was analyzed using the incidence rate ratio (IRR) of the TKI group to the cytotoxic group and the log-rank test of the Kaplan-Meier method.
Results
Of the 2,981 NSCLC patients, 54 patients (1.54%) developed herpes zoster. In the TKI group (2,002 patients), the IRR of herpes zoster during TKI therapy compared to that during cytotoxic chemotherapy was 1.05 (95% confidence interval [CI], 0.53 to 2.09). The IRR of the TKI group compared to the cytotoxic group was 1.33 (95% CI, 0.64 to 2.76). The Kaplan-Meier cumulative risk of both groups was not significantly different.
Conclusion
Our results show that the incidence rate of herpes zoster in the TKI group was not statistically different from the incidence in the cytotoxic group during and after chemotherapy in NSCLC patients.

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Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer
Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo
Cancer Res Treat. 2019;51(1):119-127.   Published online March 12, 2018
DOI: https://doi.org/10.4143/crt.2018.019
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This randomized phase III study was designed to compare the efficacy and safety of irinote-can plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC).
Materials and Methods
Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival.
Results
A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP.
Conclusion
The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.

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The Effect of Hospice Consultation on Aggressive Treatment of Lung Cancer
Shin Hye Yoo, Bhumsuk Keam, Miso Kim, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2018;50(3):720-728.   Published online July 14, 2017
DOI: https://doi.org/10.4143/crt.2017.169
AbstractAbstract PDFPubReaderePub
Purpose
The aims of this study were to investigate trends of aggressive treatment of non-small cell lung cancer (NSCLC) patients at the end-of-life (EOL) during the recent 5 years and examine the relationship between hospice consultation (HC) and aggressive care.
Materials and Methods
The medical records of 789 patients with stage IIIB-IV NSCLC at Seoul National University Hospital (SNUH) who received palliative chemotherapy and died from 2010 to 2014 were retrospectively reviewed. Indicators of aggressive treatment were evaluated, and the association of HC with these indicators was analyzed.
Results
During the last 5 years, the frequency of HC increased from 26.7% to 43.6%. The time interval from last chemotherapy to death increased, and the proportion of patients who received palliative chemotherapy, visited an emergency room, were admitted to intensive care unit, during the last month of life, and died in SNUH significantly decreased over time. Referral to HC was significantly associated with lower intensive care unit admission rates, lower out-of-hospital death rates, and less use of the chemotherapy within 1 month prior to death. Overall survival did not differ by HC.
Conclusion
The pattern of cancer care nearthe EOL has become less aggressivewhen HCwas provided. The positive association of HCwith better EOL care suggests that providing HC at the optimal time might help to avoid futile aggressive treatment.

Citations

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    Wei-Shu Lai, I-Ting Liu, Jui-Hung Tsai, Pei-Fang Su, Pin-Hsuan Chiu, Ying-Tzu Huang, Ge-Lin Chiu, Yu-Yeh Chen, Peng-Chan Lin
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    Jeong-Han Kim, Shin Hye Yoo, Bhumsuk Keam, Dae Seog Heo
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Comparison of Native Escherichia coli L-Asparaginase versus Pegylated Asparaginase, in Combination with Ifosfamide, Methotrexate, Etoposide, and Prednisolone, in Extranodal NK/T-Cell Lymphoma, Nasal Type
Hyun Jee Kim, Chan-Young Ock, Tae Min Kim, Sung Hee Lee, Ju-Yeun Lee, Sun hoi Jung, Yoon Sook Cho, Miso Kim, Bhumsuk Keam, Dong-Wan Kim, Il Han Kim, Dae Seog Heo
Cancer Res Treat. 2018;50(3):670-680.   Published online July 3, 2017
DOI: https://doi.org/10.4143/crt.2017.051
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The aim of this study was to compare asparaginase-related toxicities in two asparaginase preparations, namely native Escherichia coli L-asparaginase (L-ASP) and pegylated asparaginase (PEG-ASP) in combination with ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) in natural killer (NK)/T-cell lymphoma (NTCL).
Materials and Methods
A total of 41 NTCL patients who received IMEP plus native E. coli L-ASP or PEG-ASP at Seoul National University Hospital were included in this study between January 2013 and March 2016. IMEP/ASP treatment consisted of ifosfamide, methotrexate, etoposide, plus native E. coli L-ASP (6,000 IU/m2 on days 1, 3, 5, 7, 9, and 11) or PEG-ASP (2,500 IU/m2 on day 1) every 3 weeks. ASP-related toxicities, toxicity patterns, length of hospital stay, and clinical outcomes were compared between the different treatment groups.
Results
The frequency of ASP-related toxicities was similar between the IMEP plus native E. coli L-ASP group and the PEG-ASP group apart from hypofibrinogenemia (native E. coli L-ASP vs. PEG-ASP group, 86.4% vs. 36.8%; p=0.001). Although post-treatment transaminase and albumin levels were significantly high and low, respectively, hepatotoxicity gradients before and after treatment did not differ significantly between the groups. Since PEG-ASP was given at an outpatient clinic in some patients, length of hospital stay was significantly shorter in the IMEP plus PEG-ASP group (median, 4.0 vs. 6.0 days; p=0.002). A favorable tendency of clinical outcomes was observed in NTCL patients treated with IMEP plus PEG-ASP (complete remission rate, 73.7% vs. 45.5%; p=0.067).
Conclusion
IMEP plus PEG-ASP showed similar ASP-related toxicities, shorter length of hospital stay, and a trend towards improved clinical outcomes compared with IMEP plus native E. coli L-ASP in NTCL.

Citations

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Experiences and Opinions Related to End-of-Life Discussion: From Oncologists' and Resident Physicians' Perspectives
Su-Jin Koh, Shinmi Kim, JinShil Kim, Bhumsuk Keam, Dae Seog Heo, Kyung Hee Lee, Bong-Seog Kim, Jee Hyun Kim, Hye Jung Chang, Sun Kyung Baek
Cancer Res Treat. 2018;50(2):614-623.   Published online July 3, 2017
DOI: https://doi.org/10.4143/crt.2016.446
AbstractAbstract PDFPubReaderePub
Purpose
The aims of this study were to explore how oncologists and resident physicians practice end-of-life (EOL) discussions and to solicit their opinions on EOL discussions as a means to improve the quality of EOL care.
Materials and Methods
A survey questionnaire was developed to explore the experiences and opinions about EOL discussions among oncologists and residents. Descriptive statistics, the t test, and the chisquare test were performed for the analyses.
Results
A total of 147 oncologists and 229 residents participated in this study. The study respondents reported diverse definitions of “terminal state,” and mostrespondents tried to disclose the patient’s condition to the patient and/or family members. Both groups were involved in EOL care discussions, with a rather low satisfaction level (57.82/100). The best timing to initiate discussionwas consideredwhen metastasis or disease recurrence occurred orwhen withdrawal of chemotherapy was anticipated. Furthermore, the study respondents suggested that patients and their family members should be included in the EOL discussion. Medical, legal, and ethical knowledge and communication difficulties along with practical issues were revealed as barriers and facilitators for EOL discussion.
Conclusion
This study explored various perspectives of oncologists and resident physicians for EOL discussion. Since the Life-Sustaining-Treatment Decision-Making Act will be implemented shortly in Korea, now is the time for oncologists and residents to prepare themselves by acquiring legal knowledge and communication skills. To achieve this, education, training, and clinical tools for healthcare professionals are required.

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Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate
Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im
Cancer Res Treat. 2017;49(4):1033-1043.   Published online April 7, 2017
DOI: https://doi.org/10.4143/crt.2016.413
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

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    Teck Long King, Shirin Hui Tan, Shirley Siang Ning Tan, Wei Hong Lai, Mohamad Adam Bujang, Pei Jye Voon
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The Association between End-of-Life Care and the Time Interval between Provision of a Do-Not-Resuscitate Consent and Death in Cancer Patients in Korea
Sun Kyung Baek, Hye Jung Chang, Ja Min Byun, Jae Joon Han, Dae Seog Heo
Cancer Res Treat. 2017;49(2):502-508.   Published online September 1, 2016
DOI: https://doi.org/10.4143/crt.2016.073
AbstractAbstract PDFPubReaderePub
Purpose
We explored the relationship between the use of each medical intervention and the length of time between do-not-resuscitate (DNR) consent and death in Korea.
Materials and Methods
A total of 295 terminal cancer patients participated in this retrospective study. Invasive interventions (e.g., cardiopulmonary resuscitation, intubation, and hemodialysis), less invasive interventions (e.g., transfusion, antibiotic use, inotropic use, and laboratory tests), and the time interval between the DNR order and death were evaluated. The subjects were divided into three groups based on the amount of time between DNR consent and death (G1, time interval ≤ 1 day; G2, time interval > 1 day to ≤ 3 days; and G3, time interval > 3 days).
Results
In general, there were fewer transfusions and laboratory tests near death. Invasive interventions tended to be implemented only in the G1 group. There was also less inotrope use and fewerlaboratory tests in the G3 group than G1 and G2. Moreover, the G3 group received fewer less invasive interventions than those in G1 (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03 to 0.84; 3 days before death, and OR, 0.16; 95% CI, 0.04 to 0.59; the day before death). The frequency of less invasive interventions both 1 and 3 days before death was significantly lower for the G3 group than the G1 (p ≤ 0.001) and G2 group compared to G1 (p=0.001).
Conclusion
Earlier attainment of DNR permission was associated with reduced use of medical intervention. Thus, physicians should discuss death with terminal cancer patients at the earliest practical time to prevent unnecessary and uncomfortable procedures and reduce health care costs.

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Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer
Miso Kim, Bhumsuk Keam, Tae-Min Kim, Hoon-Gu Kim, Jin-Soo Kim, Sung Sook Lee, Seong Hoon Shin, Min Kyoung Kim, Keon Uk Park, Dong-Wan Kim, Hwan Jung Yun, Jong Seok Lee, Dae Seog Heo
Cancer Res Treat. 2017;49(2):416-422.   Published online July 28, 2016
DOI: https://doi.org/10.4143/crt.2016.121
AbstractAbstract PDFPubReaderePub
Purpose
The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer.
Materials and Methods
Patients were treated with irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity.
Results
A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the perprotocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%).
Conclusion
Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

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Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma
Yongjun Cha, Yu Jung Kim, Se-Hoon Lee, Tae-Min Kim, Seung Hong Choi, Dong-Wan Kim, Chul-Kee Park, Il Han Kim, Jee Hyun Kim, Eunhee Kim, Byungse Choi, Chae-Yong Kim, In Ah Kim, Dae Seog Heo
Cancer Res Treat. 2017;49(1):129-140.   Published online May 18, 2016
DOI: https://doi.org/10.4143/crt.2015.466
AbstractAbstract PDFPubReaderePub
Purpose
Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established.
Materials and Methods
Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups.
Results
Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups.
Conclusion
In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.

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The Effect of Induction Chemotherapy Using Docetaxel, Cisplatin, and Fluorouracil on Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Meta-Analysis
Ryul Kim, Seokyung Hahn, Junghoon Shin, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2016;48(3):907-916.   Published online November 17, 2015
DOI: https://doi.org/10.4143/crt.2015.359
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to compare the survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) undergoing concurrent chemoradiotherapy (CRT) alone with that of patients undergoing induction chemotherapy (IC) using docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by CRT.
Materials and Methods
A search of the PubMed, EMBASE, and Cochrane Library databases was performed in April 2015 and abstracts from the American Society of Clinical Oncology meetings (2008-2014) were reviewed. Summaries of the results were pooled using a fixed-effect model, and the risk of bias was evaluated using the Cochrane tool.
Results
A total of six relevant trials comprising 1,280 patients were identified. There was no statistically significant overall survival (OS) advantage for TPF prior to CRT (TPF/CRT) over CRT alone (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.79 to 1.09; p=0.339). Progression- free survival (PFS) was significantly longer in the TPF/CRT arms (HR, 0.82; 95% CI, 0.70 to 0.95; p=0.009). Patients with non-oropharyngeal LA-HNSCC obtained the greatest OS and PFS benefits from TPF (HR, 0.68; 95% CI, 0.47 to 0.99; p=0.043 and HR, 0.67; 95% CI, 0.48 to 0.94; p=0.022, respectively). The complete response rate was significantly increased (risk ratio [RR], 1.34; 95% CI, 1.14 to 1.56; p < 0.001), and the distant metastasis rate tended to decrease (RR, 0.65; 95% CI, 0.40 to 1.04; p=0.071) in the TPF/CRT arms.
Conclusion
IC with TPF followed by CRT is not superior to CRT alone for OS. However, PFS and the complete response rate were significantly improved in the TPF/CRT arms. TPF/CRT for patients with nonoropharyngeal LA-HNSCC provided clear survival advantages.

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VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma
Seongyeol Park, Soo Jeong Nam, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, J. Hun Hah, Tack-Kyun Kwon, Dong-Wan Kim, Myung-Whun Sung, Dae Seog Heo, Yung-Jue Bang
Cancer Res Treat. 2016;48(2):518-526.   Published online July 14, 2015
DOI: https://doi.org/10.4143/crt.2015.093
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). Materials and Methods A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS).
Results
In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. Conclusion High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.

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Reduced Dose Intensities of Doxorubicin in Elderly Patients with DLBCL in Rituximab Era
Hyerim Ha, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, Dong-Wan Kim, Chul Woo Kim, Dae Seog Heo
Cancer Res Treat. 2016;48(1):304-311.   Published online April 9, 2015
DOI: https://doi.org/10.4143/crt.2014.339
AbstractAbstract PDFPubReaderePub
Purpose
The dose intensity of doxorubicin (DID) is important to the survival of diffuse large B cell lymphoma (DLBCL) patients. However, due to expected toxicities, most elderly patients cannot receive full doses of anthracyclines. The purpose of this study was to evaluate the effect of DID on the survival of elderly DLBCL patients (age ≥ 70 years) in the rituximab era.
Materials and Methods
We analyzed 433 DLBCL patients who were treated with R-CHOP between December 2003 and October 2011 at the Seoul National University Hospital. Of these patients, 19.2% were aged ≥ 70 years. We analyzed the survival outcomes according to DID.
Results
Significantly poorer overall survival (OS) was observed for patients aged ≥ 70 years (2-year OS rate: 59.9% vs. 84.2%; p < 0.001). DID ≤ 10 mg/m2/wk had a significant effect on the OS and progression-free survival (PFS) in elderly patients (2-year OS rate: 40.0% in DID ≤ 10 mg/m2/wk vs. 62.6% in DID > 10 mg/m2/wk; p=0.031; 2-year PFS: 35.0% vs. 65.7%; p=0.036). The OS on each 1.7 mg/m2/wk doxorubicin increment above 10 mg/m2/wk in elderly patients was not significant among the groups (2-year OS rate: 75.0% in DID 10.0- 11.7 mg/m2/wk vs. 66.7% in DID 15.0-16.7 mg/m2/wk; p=0.859). Treatment related mortality was not related to DID.
Conclusion
DID can be reduced up to 10 mg/m2/wk in elderly DLBCL patients in the rituximab era. Maintenance of DID > 10 mg/m2/wk and judicious selection of elderly patients who are tolerant to DID is necessary.

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Gefitinib-Induced Interstitial Lung Disease in Korean Lung Cancer Patients
Seung-Hoon Beom, Dong-Wan Kim, Sung Hoon Sim, Bhumsuk Keam, Jin Hyun Park, Jeong-Ok Lee, Tae Min Kim, Se-Hoon Lee, Dae Seog Heo
Cancer Res Treat. 2016;48(1):88-97.   Published online March 3, 2015
DOI: https://doi.org/10.4143/crt.2014.201
AbstractAbstract PDFPubReaderePub
Purpose
Interstitial lung disease (ILD) is a serious adverse effect of gefitinib. We examined the incidence and clinical characteristics of drug-induced ILD in Korean non-small cell lung carcinoma patients treated with gefitinib. Materials and Methods A retrospective cohort study was performed in non-small cell lung cancer (NSCLC) patients who started gefitinib treatment at Seoul National University Hospital from January 2002 through December 2011. Patients who developed new abnormal radiologic findings with respiratory symptoms after gefitinib treatment were defined as having possible adverse pulmonary reactions. The patients’ medical records were reviewed independently by investigators to identify the causes of pulmonary toxicities. Results Among the 1,114 patients evaluated, 128 patients (11.5%) developed pulmonary adverse reactions after taking gefitinib. An infectious complication occurred in 98 patients (8.8%) and 15 patients (1.3%) developed ILD. Nine of the 15 patients (60.0%) with gefitinib-induced ILD experienced a fatal clinical course that met either the Common Terminology Criteria for Adverse Events grade 4 (n=3) or grade 5 (n=6). In the multivariate analysis, a lower serum albumin level (≤ 3.0 g/dL) at baseline was significantly associated with the development of gefitinib-induced ILD (odds ratio, 3.91; 95% confidence interval, 1.20 to 12.71). Conclusion The incidence of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported worldwide, but lower than values reported for Japanese population. ILD was usually a lifethreatening adverse effect of gefitinib, and the development of ILD was significantly associated with a lower baseline serum albumin level.

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Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors
Do-Youn Oh, Se-Hoon Lee, Sae-Won Han, Mi-Jung Kim, Tae-Min Kim, Tae-You Kim, Dae Seog Heo, Miyuki Yuasa, Yasuo Yanagihara, Yung-Jue Bang
Cancer Res Treat. 2015;47(4):607-615.   Published online February 26, 2015
DOI: https://doi.org/10.4143/crt.2014.249
AbstractAbstract PDFPubReaderePub
Purpose
OPB-31121 is an oral STAT3 inhibitor with a good preclinical antitumor activity. This phase I dose-escalation study of OPB-31121 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. Materials and Methods Patients received OPB-31121 once daily for 28 days of each cycle followed by 2 weeks rest. A standard 3+3 design was used for dose-escalation. Safety and response were evaluated by the National Cancer Institute–Common Terminology Criteria for Adverse Events (NCICTCAE) ver. 3.0 and Response Evaluation Criteria in Solid Tumor (RECIST) ver. 1.0, respectively.
Results
Twenty-five patients were treated with OPB-31121 at five dose levels: 100 mg (n=4), 200 mg (n=3), 400 mg (n=3), 600 mg (n=7), and 800 mg (n=8). Seven patients discontinued treatment during cycle 1 for various reasons other than study drug-related adverse events. Among 18 patients who were evaluable for dose-limiting toxicity (DLT), three DLTs were observed: one DLT (grade 3 vomiting) at 600 mg and two DLTs (grade 3 vomiting, grade 3 diarrhea) at 800 mg. The MTD was determined as 800 mg/day. Common adverse events were gastrointestinal adverse event including nausea (84%), vomiting (80%), and diarrhea (72%). Pharmacokinetics did not demonstrate dose-proportionality of OPB-31121. Eight patients had stable disease and 10 patients had disease progression. Two patients (1 colon cancer, 1 rectal cancer) showed tumor shrinkage. One gastric cancer patient continued treatment up to cycle 13 before disease progression. Conclusion This study demonstrates feasibility of STAT3 inhibition in patients with advanced solid tumor. OPB-31121, at the MTD of 800 mg/day, was safe and relatively well tolerated, and has a preliminary antitumor activity.

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Pemetrexed Singlet Versus Nonpemetrexed-Based Platinum Doublet as Second-Line Chemotherapy after First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Failure in Non-small Cell Lung Cancer Patients with EGFR Mutations
Sehhoon Park, Bhumsuk Keam, Se Hyun Kim, Ki Hwan Kim, Yu Jung Kim, Jin-Soo Kim, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Jong Seok Lee, Dae Seog Heo
Cancer Res Treat. 2015;47(4):630-637.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.244
AbstractAbstract PDFPubReaderePub
Purpose
Platinum-based doublet chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC); however, the role of a platinum-based doublet as second-line therapy after failure of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC patients has not yet been elucidated. The purpose of this study was to compare the clinical efficacy of pemetrexed versus a platinum-based doublet as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations. Materials and Methods We designed a multicenter retrospective cohort study of 314 NSCLC patients with EGFR mutations who received an EGFR TKI as first-line palliative chemotherapy. Our analysis included 83 patients who failed EGFR TKI therapy and received second-line cytotoxic chemotherapy.
Results
Forty-six patients were treated using a platinum-based doublet and 37 patients were treated using singlet pemetrexed. The overall response rates of patients receiving a platinum-based doublet and patients receiving pemetrexed were17.4% and 32.4%, respectively (p=0.111). The median progression-free survival (PFS) of patients receiving pemetrexed was significantly longer than that of patients receiving a platinum-based doublet (4.2 months vs. 2.7 months, respectively; p=0.008). The hazard ratio was 0.54 (95% confidence interval, 0.34 to 0.86; p=0.009). Conclusion Our retrospective analysis found that second-line pemetrexed singlet therapy provided significantly prolonged PFS compared to second-line platinum-based doublet chemotherapy for NSCLC patients with EGFRmutations who failed first-line EGFR TKI. Conduct of prospective studies for confirmation of our results is warranted.

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  • Real-world osimertinib pretreatment experience in patients with epidermal growth factor receptor T790M mutation-positive locally advanced or metastatic non-small cell lung cancer
    Gee-Chen Chang, Jin-Yuan Shih, Chong-Jen Yu, Heng-Sheng Chao, Cheng-Ta Yang, Chien-Chung Lin, Jen-Yu Hung, Sheng-Yen Hsiao, Chin-Chou Wang, Chih-Feng Chian, Te-Chun Hsia, Yuh-Min Chen, Chien-Feng Li
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    Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo
    Cancer Research and Treatment.2023; 55(4): 1134.     CrossRef
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  • A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line
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Cancer Treatment near the End-of-Life Becomes More Aggressive: Changes in Trend during 10 Years at a Single Institute
Younak Choi, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2015;47(4):555-563.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.200
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate and compare cancer treatment near the end-of-life (EOL) over a 10-year period. Materials and Methods Patients with advanced solid cancer at Seoul National University Hospital who received palliative chemotherapy and had died were enrolled. We categorized the consecutive patients according to two time periods: 2002 (n=57) and 2012 (n=206). Aggressiveness of cancer treatment near the EOL was evaluated.
Results
The median patient age was 62, and 65.4% of patients (n=172) were male. Time from the last chemotherapy to death (TCD) was found to have been significantly shortened, from 66.0 days to 34.0 days during 10 years (p < 0.001); 17% of patients received molecular targeted agents as the last chemotherapy regimen in 2012. The proportion of patients who received intensive care unit care within the last month increased from 1.8% in 2002 to 19.9% in 2012 (p < 0.001), and emergency room visits within the last month also increased from 22.8% to 74.8% (p < 0.001). Although hospice referral increased from 9.1% to 37.4% (p < 0.001), timing of referral was delayed from median 53 days to 8 days before death (p=0.004). Use of targeted agents as the last chemotherapy for over-two-regimen users was associated with shortened TCD (hazard ratio, 2.564; p=0.002). Conclusion Cancer treatment near the EOL became more aggressive over 10 years.

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Cisplatin-Based Chemotherapy Is a Strong Risk Factor for Thromboembolic Events in Small-Cell Lung Cancer
Yun-Gyoo Lee, Eunyoung Lee, Inho Kim, Keun-Wook Lee, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Dae Seog Heo
Cancer Res Treat. 2015;47(4):670-675.   Published online January 2, 2015
DOI: https://doi.org/10.4143/crt.2014.045
AbstractAbstract PDFPubReaderePub
Purpose
Cisplatin-associated arterial and venous thromboembolic events (TEEs) are becoming an increasing concern. In patients with small-cell lung cancer (SCLC) who are treated using cisplatin-based chemotherapy, we assume that the overall risk of TEEs is high. However, cisplatin-associated vascular toxicity in patients with SCLC has been overlooked to date. The aim of this study was to determine the incidence of TEEs in patients with SCLC and to analyze the predictors for TEE occurrence. Materials and Methods We retrospectively analyzed 277 patients who received chemotherapy for SCLC between 2006 and 2012. As the influence of chemotherapy on TEE occurrence developed after its initiation, a time-dependent Cox regression analysis was used to estimate the significant predictors for TEE. Results Among the 277 patients, 30 patients (11%) developed a TEE. The 3-month, 6-month, and 1-year cumulative incidences of TEEs were 5.0%, 9.1%, and 10.2%, respectively. Of 30 total TEEs, 22 (73%) occurred between the time of initiation and 4 weeks after the last dose of platinum-based chemotherapy. Approximately 218 patients (79%) received cisplatin-based chemotherapy. In multivariate analysis, cisplatin-based chemotherapy was an independent risk factor for TEE occurrence (hazard ratio [HR], 4.36; p=0.05). Variables including smoking status (common HR, 2.14; p=0.01) and comorbidity index (common HR, 1.60; p=0.05) also showed significant association with TEE occurrence. Conclusion The 1-year cumulative incidence of TEE is 10.2% in Asian patients with SCLC. Cisplatinbased chemotherapy in SCLC might be a strong predictor for the risk of TEE.

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The Impact of Molecularly Targeted Treatment on Direct Medical Costs in Patients with Advanced Non-small Cell Lung Cancer
June-Koo Lee, Dong-Wan Kim, Bhumsuk Keam, Tae Min Kim, Se-Hoon Lee, Young-Joo Kim, Dae Seog Heo
Cancer Res Treat. 2015;47(2):182-188.   Published online September 12, 2014
DOI: https://doi.org/10.4143/crt.2013.227
AbstractAbstract PDFPubReaderePub
Purpose
To investigate the impact of targeted treatment on direct medical costs of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Medical records of 108 stage IIIB/IV NSCLC patients treated in Seoul National University Hospital between 2003 and 2009, were reviewed to collect medical resources utilization data from the diagnosis of stage IIIB/IV NSCLC to the end of active anti-cancer treatment. The direct medical costs were calculated by multiplying the number of medical resources used by the unit price. All costs were expressed in US dollars for each patient. Results The mean total direct medical costs were $34,732 (standard deviation, 21,168) in the study cohort. The mean total direct medical costs were higher in epidermal growth factor receptor (EGFR) mutation (EGFR MT)–positive patients than EGFR wild-type (EGFR WT) patients ($41,403 vs. $30,146, p=0.005). However, the mean monthly direct medical costs did not differ significantly between EGFR MT–positive patients and EGFR WT patients ($2,120 vs. $2,702, p=0.119) because of the longer duration of active anti-cancer treatment in EGFR MT–positive patients. This discrepancy was mainly attributable to EGFR MT–positive patients’ lower non-chemotherapy costs ($948 vs. $1,522, p=0.007). The total and monthly direct medical costs of ALK fusion–positive patients who did not receive ALK inhibitors did not differ from WT/WT patients. Conclusion This study suggests that the availability of targeted agents for EGFR MT–positive patients lowers the mean monthly medical costs by prolonging survival and diminishing the use of other medical resources, despite the considerable drug costs.

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Low-Dose Whole Brain Radiotherapy with Tumor Bed Boost after Methotrexate-Based Chemotherapy for Primary Central Nervous System Lymphoma
Byoung Hyuck Kim, Il Han Kim, Sung-Hye Park, Chul Kee Park, Hee Won Jung, Tae Min Kim, Se-Hoon Lee, Dae Seog Heo
Cancer Res Treat. 2014;46(3):261-269.   Published online July 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.3.261
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to evaluate the outcome of low-dose whole brain radiotherapy (WBRT) with tumor bed boost after methotrexate-based chemotherapy in the management of primary central nervous system lymphoma (PCNSL). Materials and Methods We retrospectively analyzed 64 patients with pathologically proven PCNSL between 2000 and 2011. Methotrexate-based chemotherapy with a median of five cycles was followed by radiotherapy to the whole brain and to the initial tumor bed. The median dose to the whole brain and to the tumor bed was 27 Gy (range, 18 to 36 Gy) and 50.4 Gy (range, 45 to 54 Gy), respectively. Results With a median follow-up period of 27 months, 55 patients (85.9%) achieved complete response (CR). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 52.6% and 39.3%, respectively. In univariate analysis, factors associated with OS were age, performance status, involvement of deep structure, and CR to sequential chemoradiotherapy (CRT). These variables remained as significant factors for OS in multivariate analysis. CR to sequential CRT was the only positive factor associated with PFS (p=0.009). Neurologic toxicity was more common in elderly patients older than 60 years (p=0.025). Conclusion Low-dose WBRT with tumor bed boost after methotrexate-based chemotherapy might be an effective method for management of PCNSL.

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