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Original Articles
Phase II Trial of Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Combined with Pegteograstim for Unresectable, Locally Advanced Sinonasal Squamous Cell Carcinoma: KCSG HN18-07
Bhumsuk Keam, Ho Jung An, Seong Hoon Shin, Min Kyoung Kim, Jung Hae Cho, Seyoung Seo, Sung-Bae Kim
Received October 24, 2024  Accepted December 13, 2024  Published online December 16, 2024  
DOI: https://doi.org/10.4143/crt.2024.1025    [Accepted]
AbstractAbstract PDF
Purpose
The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population.
Materials and Methods
Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 stage or potential compromise of critical organ function on surgery. Three TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1, 5-fluorouracil 1,000 mg/m2 on days 1–4 every 3 weeks) cycles were administered with prophylactic pegteograstim. The primary outcome was the overall response rate (ORR); the secondary outcomes included 2-year progression-free survival (PFS), eyeball preservation rate, and safety.
Results
Among 28 patients screened, 25 were evaluable for efficacy (one screen-failure; two evaluable for safety only). The confirmed ORR was 72.0%. The definitive post-NAC treatment comprised chemoradiotherapy (n=15) and surgery (n=10). With a median follow-up of 25.5 months, median PFS was not reached and the 2-year PFS rate was 60.4%. Response to NAC was related to prolonged PFS (p=0.038). No patient underwent eyeball exenteration at the data cutoff point. Treatment-related adverse events of grade ≥3 were neutropenia (48.1%) including febrile neutropenia (14.8%), followed by acute kidney injury (22.2%), nausea/vomiting (11.1%), anemia (7.4%), thrombocytopenia (7.4%), and enterocolitis (3.7%).
Conclusion
TPF NAC showed a promising efficacy and might help preserve critical structures in this population, which needs to be validated in a large prospective trial (KCT0003377).
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Palliative medicine
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 Res Treat. 2025;57(1):280-288.   Published online July 1, 2024
DOI: https://doi.org/10.4143/crt.2024.360
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
In Korea, the Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment (LST) was implemented on February 4, 2018. We aimed to investigate relevant factors and clinical changes associated with LST decisions after law enforcement.
Materials and Methods
This single-center retrospective study included patients who completed LST documents using legal forms at Asan Medical Center from February 5, 2018, to June 30, 2020.
Results
5,896 patients completed LST documents, of which 2,704 (45.8%) signed the documents in person, while family members of 3,192 (54%) wrote the documents on behalf of the patients. Comparing first year and following year of implementation of the act, the self-documentation rate increased (43.9% to 47.2%, p=0.014). Moreover, the number of LST decisions made during or after intensive care unit admission decreased (37.8% vs. 35.2%, p=0.045), and the completion rate of LST documents during chemotherapy increased (6.6% vs. 8.9%, p=0.001). In multivariate analysis, age < 65 (odds ratio [OR], 1.724; 95% confidence interval [CI], 1.538 to 1.933; p < 0.001), unmarried status (OR, 1.309; 95% CI, 1.097 to 1.561; p=0.003), palliative care consultation (OR, 1.538; 95% CI, 1.340 to 1.765; p < 0.001), malignancy (OR, 1.864; 95% CI, 1.628 to 2.133; p < 0.001), and changes in timing on the first year versus following year (OR, 1.124; 95% CI, 1.003 to 1.260; p=0.045) were related to a higher self-documentation rate.
Conclusion
Age < 65 years, unmarried status, malignancy, and referral to a palliative care team were associated with patients making LST decisions themselves. Furthermore, the subject and timing of LST decisions have changed with the LST act.
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General
Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study
Songji Choi, Seyoung Seo, Ju Hyun Lee, Koung Jin Suh, Ji-Won Kim, Jin Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jwa Hoon Kim, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Sang-We Kim, Dae Ho Lee, Jae Cheol Lee, Chang-Min Choi, Shinkyo Yoon, Su-Jin Koh, Young Joo Min, Yongchel Ahn, Hwa Jung Kim, Jin Ho Baek, Sook Ryun Park, Jee Hyun Kim
Cancer Res Treat. 2024;56(2):404-413.   Published online November 7, 2023
DOI: https://doi.org/10.4143/crt.2023.784
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex.
Materials and Methods
This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea.
Results
A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits.
Conclusion
Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Citations

Citations to this article as recorded by  
  • Cancer care for transgender and gender‐diverse people: Practical, literature‐driven recommendations from the Multinational Association of Supportive Care in Cancer
    Elizabeth J. Cathcart‐Rake, Alexandre Chan, Alvaro Menendez, Denise Markstrom, Carla Schnitzlein, Yee Won Chong, Don S. Dizon
    CA: A Cancer Journal for Clinicians.2025; 75(1): 68.     CrossRef
  • Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats
    Chiara Di Marino, Álvaro Llorente-Berzal, Alba M. Diego, Ariadni Bella, Laura Boullon, Esther Berrocoso, Michelle Roche, David P. Finn
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
  • [Translated article] Toxicity of the FOLFOX-6 regimen, with or without 5-fluorouracil bolus, in metastatic colorectal cancer
    María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
    Farmacia Hospitalaria.2025;[Epub]     CrossRef
  • The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma
    Jun Kawashima, Yutaka Endo, Selamawit Woldesenbet, Mujtaba Khalil, Miho Akabane, François Cauchy, Feng Shen, Shishir Maithel, Irinel Popescu, Minoru Kitago, Matthew J. Weiss, Guillaume Martel, Carlo Pulitano, Luca Aldrighetti, George Poultsides, Andrea Ru
    Annals of Surgical Oncology.2025;[Epub]     CrossRef
  • Toxicidad del esquema FOLFOX-6, asociado o no a bolo de 5-fluorouracilo, en cáncer colorrectal metastásico
    María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
    Farmacia Hospitalaria.2024;[Epub]     CrossRef
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Lung and Thoracic cancer
Integrin αvβ3 Induces HSP90 Inhibitor Resistance via FAK Activation in KRAS-Mutant Non-Small Cell Lung Cancer
Shinkyo Yoon, Hannah Yang, Hyun-Min Ryu, Eunjin Lee, Yujin Jo, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Wanlim Kim, Kyung Hae Jung, Sook Ryun Park, Eun Kyung Choi, Sang-We Kim, Kang-Seo Park, Dae Ho Lee
Cancer Res Treat. 2022;54(3):767-781.   Published online September 30, 2021
DOI: https://doi.org/10.4143/crt.2021.651
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Heat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non–small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors.
Materials and Methods
We established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker.
Results
We identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and β3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both in vitro and in vivo xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922.
Conclusion
The synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC.

Citations

Citations to this article as recorded by  
  • Triiodothyronine promotes the proliferation and chemoresistance of cholangiocarcinoma cells via HIF-1α/Glut1-stimulated glycolysis
    Dihua Huang, Feng Xu, Luohang Xu, Zekai Tang, Yanxin Hu, Jiandong Li, Jianhua Yu
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(5): 167814.     CrossRef
  • Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications
    Yoshinobu Kariya, Michiru Nishita
    International Journal of Molecular Sciences.2025; 26(7): 3143.     CrossRef
  • Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR‐Mutated Lung Cancer Cells Resistant to Osimertinib
    Yu‐Ting Kang, Hui‐Yi Chang, Ya‐Chu Hsieh, Chia‐Hsuan Chou, I‐Lun Hsin, Jiunn‐Liang Ko
    Environmental Toxicology.2024; 39(12): 5238.     CrossRef
  • Junctional adhesion molecular 3 (JAM3) is a novel tumor suppressor and improves the prognosis in breast cancer brain metastases via the TGF-β/Smad signal pathway
    Kaitao Zhu, Shiwei Li, Hongru Yao, Jilong Hei, WenGuo Jiang, Tracey Martin, Shanyi Zhang
    Journal of Neuro-Oncology.2024; 170(2): 331.     CrossRef
  • Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence
    Bashar Alhasan, Marina Mikeladze, Irina Guzhova, Boris Margulis
    Cancer and Metastasis Reviews.2023; 42(1): 217.     CrossRef
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General
Functional Impairments in the Mental Health, Depression and Anxiety Related to the Viral Epidemic, and Disruption in Healthcare Service Utilization among Cancer Patients in the COVID-19 Pandemic Era
Kyumin Kim, Harin Kim, Joohee Lee, Inn-Kyu Cho, Myung Hee Ahn, Ki Young Son, Jeong Eun Kim, Hee Jeong Kim, Sang Min Yoon, So Hee Kim, Moon Jung Kwon, Hwa Jung Kim, Su-Jin Koh, Seyoung Seo, Seockhoon Chung
Cancer Res Treat. 2022;54(3):671-679.   Published online September 17, 2021
DOI: https://doi.org/10.4143/crt.2021.585
AbstractAbstract PDFPubReaderePub
Purpose
Literature is scarce regarding cancer care utilization during the massive outbreak of coronavirus disease 2019 (COVID-19) in the Republic of Korea. We investigated functional impairments in mental health and their relationships with depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization among cancer patients in the COVID-19 pandemic era.
Materials and Methods
We used an online survey with questions related to the disturbances faced by patients with cancer in utilizing healthcare services in the pandemic era. Current mental health status was assessed using the Work and Social Adjustment Scale (WSAS), Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale, Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI), Brief Resilience Scale (BRS), Cancer-Related Dysfunctional Beliefs about Sleep Scale (C-DBS), and Fear of COVID-19 over Cancer (FCC).
Results
Among the 221 responders, 95 (43.0%) reported disruptions in healthcare service utilization during the COVID-19 pandemic. Logistic regression analysis revealed that functional impairment in the mental health of these patients was expected due to disruptions in healthcare service utilization, high levels of depression, anxiety regarding the viral epidemic, fear of COVID over cancer, and low resilience. Mediation analysis showed that patient resilience and cancer-related dysfunctional beliefs about sleep partially mediated the effects of viral anxiety on functional impairment.
Conclusion
In this pandemic era, patients with cancer experience depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization, which may influence their functional impairments in mental health.

Citations

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    Amanda L King, Kayla N Roche, Elizabeth Vera, Valentina Pillai, Lily Polskin, Alvina A Acquaye-Mallory, Lisa Boris, Eric Burton, Anna Choi, Ewa Grajkowska, Heather E Leeper, Marissa Panzer, Marta Penas-Prado, Jennifer Reyes, Solmaz Sahebjam, Brett J Theel
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    Yash B. Shah, Stephanie Kjelstrom, Diana Martinez, Adam Leitenberger, Donna‐Marie Manasseh, Melissa Bollmann‐Jenkins, Ann Partridge, Virginia Kaklamani, Rowen Chlebowski, Sharon Larson, Marisa Weiss
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  • Discrepancy between desired time in bed and desired total sleep time in patients with cancer: The DBST index and its relationship with insomnia severity and sleep onset latency
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    Frontiers in Psychiatry.2023;[Epub]     CrossRef
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    Hyuk Joo Lee, Cheolkyung Sin, Hyeyeong Kim, Hyeon-Su Im, Jae-Cheol Jo, Yoo Jin Lee, Youjin Kim, Junseok Ahn, Soyoung Yoo, Su-Jin Koh, Seockhoon Chung
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    Harin Kim, Inn-Kyu Cho, Dongin Lee, Kyumin Kim, Joohee Lee, Eulah Cho, C. Hyung Keun Park, Seockhoon Chung
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    Eulah Cho, Dongin Lee, Inn-Kyu Cho, Joohee Lee, Junseok Ahn, Young Rong Bang
    Sleep Medicine Research.2022; 13(2): 68.     CrossRef
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  • 10,143 View
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  • 18 Web of Science
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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
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    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
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  • 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
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    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
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