Cancer Research and Treatment

Original Articles

Validating the Korean Geriatric Assessment Tool in Elderly Multiple Myeloma Patients: A Multicenter Study: Ji Yun Lee, Sang-A Kim, Youngil Koh, Ho-Young Yhim, Gyeong-Won Lee, Chang-Ki Min, Young Rok Do, Hyo Jung Kim, Sung Hwa Bae, Hyeon-Seok Eom, Sung-Hoon Jung, Hyunkyung Park, Seung-Hyun Nam, Ji Hyun Lee, Sung-Hyun Kim, Hyun Jung Lee, Young Seob Park, Soo-Mee Bang; Received January 15, 2025 Accepted February 20, 2025 Published online February 21, 2025; DOI: https://doi.org/10.4143/crt.2025.066 [Accepted]

Abstract PDF: Purpose
This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool's effectiveness in elderly multiple myeloma (MM) patients to prevent under and over-treatment.
Materials and Methods
This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022.
Results
The median age was 77 years, and 73% of patients were classified at International Staging System (ISS) stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (HR, 2.49; 95% CI, 1.09–5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03–5.86; p=0.043) had a significantly higher risk of grade 3–4 non-hematologic toxicity, whereas the IMWG definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated.
Conclusion
The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

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Associations of Financial Toxicity with Employment Concerns and Cancer-Related Distress: A Cross-Sectional Survey among Korean Working-Age Cancer Survivors: Hyun-Ju Seo, Dal-Lae Jin, Young Ae Kim, Su Jung Lee, Seok-Jun Yoon; Received January 24, 2024 Accepted December 2, 2024 Published online December 3, 2024; DOI: https://doi.org/10.4143/crt.2024.090 [Epub ahead of print]

Purpose
Although South Korea’s health insurance has a co-payment-decreasing policy for cancer survivors, information on the extent of financial toxicity and its related factors is limited. We assessed the level of financial toxicity and the association of high levels of financial toxicity with employment concerns after diagnosis and cancer-related distress in working-age cancer survivors.
Materials and Methods
A cross-sectional study was conducted. Study participants were recruited from the National Cancer Survivorship Center between November and December 2022. Financial burden was assessed using the Korean version of the Comprehensive Score for Financial Toxicity, and cancer-related distress was measured using the National Comprehensive Cancer Network Distress Thermometer. Multivariate logistic regression analyses were used to explore the associations between high financial toxicity, cancer-related distress, and changes in employment status after cancer diagnosis.
Results
Of 1,403 working-age cancer survivors, approximately 62% reported high levels of financial distress. Survivors reporting early retirement and taking time off work with the intent to return were more likely to report high financial toxicity (adjusted odds ratio [OR], 1.69; 95% confidence interval [CI], 1.14 to 2.5; and adjusted OR, 2.82; 95% CI, 1.24 to 6.43, respectively) than those with a full-time or part-time job. Moreover, cancer survivors with high distress levels were more likely to report high financial toxicity than those with low distress levels (adjusted OR, 4.36; 95% CI, 3.17 to 5.99).
Conclusion
High financial toxicity is associated with adverse employment concerns and cancer-related distress among working-age cancer survivors. Therefore, developing cancer survivorship interventions within the healthcare system is necessary to ensure improvements in financial well-being.

Citations

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Chronic Disease and Future Perceptions of Financial Control
Victoria H. Davis, Guanghao Zhang, Minal R. Patel
Medical Care.2025;[Epub] CrossRef

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Review Article

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer: Joel Rivera-Concepcion, Dipesh Uprety, Alex A. Adjei; Cancer Res Treat. 2022;54(2):315-329. Published online February 18, 2022; DOI: https://doi.org/10.4143/crt.2022.078

Abstract PDF PubReader ePub

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

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Original Articles

Pediatric cancer

Chronological Analysis of Acute Hematological Outcomes after Proton and Photon Beam Craniospinal Irradiation in Pediatric Brain Tumors: Gyu Sang Yoo, Jeong Il Yu, Sungkoo Cho, Youngyih Han, Yoonjin Oh, Do Hoon Lim, Hee Rim Nam, Ji-Won Lee, Ki-Woong Sung, Hyung Jin Shin; Cancer Res Treat. 2022;54(3):907-916. Published online October 15, 2021; DOI: https://doi.org/10.4143/crt.2021.332

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare the early hematological dynamics and acute toxicities between proton beam craniospinal irradiation (PrCSI) and photon beam craniospinal irradiation (PhCSI) for pediatric brain tumors.
Materials and Methods
We retrospectively reviewed patients with pediatric brain tumors who received craniospinal irradiation (CSI). The average change in hemoglobin levels (ΔHb_avg), absolute lymphocyte counts (ΔALC_avg), and platelet counts (ΔPLT_avg) from baseline values was evaluated and compared between the PrCSI and PhCSI groups at 1 and 2 weeks after the initiation of CSI, 1 week before and at the end of radiotherapy, and 3-4 weeks after the completion of radiotherapy using t test and mixed-model analysis.
Results
The PrCSI and PhCSI groups consisted of 36 and 30 patients, respectively. There were no significant differences in ΔHb_avg between the two groups at any timepoint. However, ΔALC_avg and ΔPLT_avg were significantly lower in the PhCSI group than in PrCSI group at every timepoint, demonstrating that PrCSI resulted in a significantly lower rate of decline and better recovery of absolute lymphocyte and platelet counts. The rate of grade 3 acute anemia was significantly lower in the PrCSI group than in in the PhCSI group.
Conclusion
PrCSI showed a lower rate of decline and better recovery of absolute lymphocyte and platelet counts than PhCSI in the CSI for pediatric brain tumors. Grade 3 acute anemia was significantly less frequent in the PrCSI group than in the PhCSI group. Further large-scale studies are warranted to confirm these results.

Citations

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Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma
Kyungmi Yang, Joong Hyun Ahn, Sook-Young Woo, Sang Hoon Jung, Ki Woong Sung, Ji Won Lee, Do Hoon Lim
BMC Pediatrics.2024;[Epub] CrossRef
Comparison of Craniospinal Irradiation Using Proton Beams According to Irradiation Method and Initial Experience Treating Pediatric Patients
Nobuyoshi Fukumitsu, Hikaru Kubota, Masayuki Mima, Yusuke Demizu, Takeshi Suzuki, Daiichiro Hasegawa, Yoshiyuki Kosaka, Atsufumi Kawamura, Toshinori Soejima
Advances in Radiation Oncology.2023; 8(5): 101251. CrossRef
Proton versus photon radiation therapy: A clinical review
Zhe Chen, Michael M. Dominello, Michael C. Joiner, Jay W. Burmeister
Frontiers in Oncology.2023;[Epub] CrossRef
Shifting Strategies in the Treatment of Pediatric Craniopharyngioma
Segev Gabay, Thomas E. Merchant, Frederick A. Boop, Jonathan Roth, Shlomi Constantini
Current Oncology Reports.2023; 25(12): 1497. CrossRef

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Gynecologic cancer

Effectiveness of Concomitant Chemoradiotherapy with Gemcitabine in Locally Advanced Cervical Cancer Patients with Comorbidities: Hasan Brau-Figueroa, Eder Arango-Bravo, Denisse Castro-Eguiluz, Tatiana Galicia-Carmona, Leopoldo Abraham Lugo-Alferez, Ivette Cruz-Bautista, Roberto Jiménez-Lima, Lucely Cetina-Pérez; Cancer Res Treat. 2022;54(2):554-562. Published online August 10, 2021; DOI: https://doi.org/10.4143/crt.2021.375

Abstract PDF Supplementary Material PubReader ePub

Purpose
The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy with cisplatin (CDDP) followed by brachytherapy. The presence of comorbidities are risk factors for nephrotoxicity and are associated with lower survival. Gemcitabine is a radiosensitizing drug that has shown efficacy and safety in this context. The effectiveness of concomitant chemoradiotherapy with gemcitabine was evaluated versus cisplatin in LACC patients with comorbidities and preserved renal function.
Materials and Methods
An observational, longitudinal and paired study was carried out that included patients treated between February 2003 and December 2015. The primary objectives were to evaluate response rates, progression-free survival, and overall survival; the secondary objectives were to evaluate toxicity and renal function.
Results
Sixty-three patients treated with gemcitabine at 300 mg/m² weekly and 126 patients treated with CDDP 40 mg/m² weekly were included. There were no significant differences in response rates and survival rates. Treatment with cisplatin presented a higher frequency of hematological toxicities, while gemcitabine presented a higher frequency of gastrointestinal toxicities. A decrease in glomerular filtration rate (GFR; baseline vs. 1-year post-treatment) was observed in the cisplatin group (p=0.002), while not in the gemcitabine group (p=0.667). In a multivariate analysis, it is observed that only CDDP correlates with the decrease in GFR (hazard ratio, 2.42; p=0.012).
Conclusion
In LACC patients with comorbidities, gemcitabine and CDDP show the same efficacy, with different toxicity profiles. Treatment with cisplatin is associated with a significant decrease in GFR during follow-up, compared to treatment with gemcitabine that does not decrease it.

Citations

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Medical nanoscale materials for virus-induced cervical cancer therapeutic modalities: For targeting delivery
Adane Adugna, Mamaru Getinet, Gashaw Azanaw Amare, Mohammed Jemal
OpenNano.2025; 21: 100221. CrossRef
Chemoradiotherapy treatment with gemcitabine improves renal function in locally advanced cervical cancer patients with renal dysfunction
Silvia Alarcón-Barrios, Julissa Luvián-Morales, Denisse Castro-Eguiluz, Merari Delgadillo-González, Brenda Olivia Lezcano-Velázquez, Eder Alexandro Arango-Bravo, Laura Flores-Cisneros, Sebastián Aguiar Rosas, Lucely Cetina-Pérez
Current Problems in Cancer.2024; 48: 101041. CrossRef
Association between body composition phenotypes and treatment toxicity in women with cervical cancer undergoing chemoradiotherapy
Mariah Azevedo Aredes, Nathália Silva de Paula, Gabriela Villaça Chaves
Nutrition.2024; 127: 112539. CrossRef
Older adults with cancer and common comorbidities—challenges and opportunities in improving their cancer treatment outcomes
Weiwei Chen, Rachel D Altshuler, Phil Daschner, Carolina Salvador Morales, Diane C St. Germain, Jennifer Guida, Pataje G S Prasanna, Jeffrey C Buchsbaum
JNCI: Journal of the National Cancer Institute.2024; 116(11): 1730. CrossRef

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3 Web of Science
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Head and Neck cancer

Radiation-Induced Ocular Surface Disorders and Retinopathy: Ocular Structures and Radiation Dose-Volume Effect: Ozlem Ozkaya Akagunduz, Suzan Guven Yilmaz, Emin Tavlayan, Mine Esen Baris, Filiz Afrashi, Mustafa Esassolak; Cancer Res Treat. 2022;54(2):417-423. Published online June 24, 2021; DOI: https://doi.org/10.4143/crt.2021.575

Abstract PDF PubReader ePub

Purpose
This study aimed to evaluate the radiation-induced adverse effects on ocular structures in head and neck cancer patients and investigate the radiation dose-volume effects on the cornea, lacrimal gland, retina, optic nerve and chiasm.
Materials and Methods
A total of 38 eyes of 19 patients were included in this prospective, cohort study. All patients underwent complete ophthalmological examination in addition to contrast sensitivity, visual field and visual evoked potentials (VEP) tests. Ophthalmological examinations and psychophysical tests were performed in 6th, 12th, 18th, 24th months and in the last visit. The relationship between the ophthalmologic findings, and the radiation doses below and above the cut-off values was evaluated.
Results
Contrast sensitivity decrease and visual field deterioration were observed in 42% of the patients in the last visit (median 26 months) whereas a prolonged latency and decreased amplitude of P100 wave in VEP was observed in 58% and 33% of the eyes, respectively at 24th month. Totally 16 patients (84.2%) developed dry eye disease and eight of them received radiotherapy below tolerance doses and had mild to moderate dry eye findings. Radiation-induced retinopathy was observed in three of the eyes in eight patients who received radiation above tolerance dose.
Conclusion
Head and neck cancers treated with radiotherapy, resulted in various ophthalmic complications. All patients who are treating with radiotherapy should be evaluated by an ophthalmologist in terms of anterior and posterior segment damage, even if the radiation dose is below the tolerance limit.

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A. Aramburu-González, J. Zarrabeitia Carrandi, C.B. Robles Elejalde, A. Quilez Larragan
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Laura Hughes, Amy C Cohn, Neda Haghighi, Alan A McNab
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A. Aramburu-González, J. Zarrabeitia Carrandi, C.B. Robles Elejalde, A. Quilez Larragan
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H Sujithra, Kannisha N Shah, R Anoop, Pushpaja K Ullattil, Gopal S Pillai, Greeshma C Ravindran, Jayesh Vazirani
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Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up: Lin Wang, Jingjing Miao, Huageng Huang, Boyu Chen, Xiao Xiao, Manyi Zhu, Yingshan Liang, Weiwei Xiao, Shaomin Huang, Yinglin Peng, Xiaowu Deng, Xing Lv, Weixiong Xia, Yanqun Xiang, Xiang Guo, Fei Han, Chong Zhao; Cancer Res Treat. 2022;54(1):118-129. Published online June 7, 2021; DOI: https://doi.org/10.4143/crt.2021.101

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.
Materials and Methods
Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.
Results
With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.
Conclusion
Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

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Genistein and chlorin E6-loaded versatile nanoformulation for remodeling the hypoxia-related tumor microenvironment and boosting photodynamic therapy in nasopharyngeal carcinoma treatment
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Peter K. M. Ku, Alexander C. Vlantis, Rita W. M. Wong, Thomas S. C. Hui, Thomas Law, Louisa K. Y. Ng, Eddy W. Y. Wong, W. T. Chang, David R. Johnson, Florence S. T. Mok, K. H. Wong, Victor Abdullah, Andrew van Hasselt, Kathy Y. S. Lee, Michael C. F. Tong
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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

Abstract PDF PubReader ePub

Purpose
We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.
Materials and Methods
Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.
Results
The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.
Conclusion
De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

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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
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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
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Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up
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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
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Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore
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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
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Factors Influencing Imatinib-Induced Hepatotoxicity: Ji Min Han, Jeong Yee, Yoon Sook Cho, Hye Sun Gwak; Cancer Res Treat. 2020;52(1):181-188. Published online June 26, 2019; DOI: https://doi.org/10.4143/crt.2019.131

Abstract PDF PubReader ePub

Purpose
Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity.
Materials and Methods
We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs.
Results
The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg.
Conclusion
The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.

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Tyrosine kinase inhibitors can activate the NLRP3 inflammasome in myeloid cells through lysosomal damage and cell lysis
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Shubhrat Purwar, Anam Fatima, Himashree Bhattacharyya, Lakshmi Venkata Simhachalam Kutikuppala, Matei-Alexandru Cozma, Bahadar Singh Srichawla, Leah Komer, Khulud Mahmood Nurani, Mihnea-Alexandru Găman
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Feng-Ru Huang, Wen-Tong Fang, Zi-Ping Cheng, Ye Shen, Dun-Jian Wang, Yong-Qing Wang, Lu-Ning Sun
Archives of Toxicology.2022; 96(4): 1075. CrossRef
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European Journal of Clinical Pharmacology.2020; 76(8): 1183. CrossRef

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Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05): Sun Hyun Bae, Hee Chul Park, Won Sup Yoon, Sang Min Yoon, In-Hye Jung, Ik Jae Lee, Jun Won Kim, Jinsil Seong, Tae Hyun Kim, Taek-Keun Nam, Youngmin Choi, Sun Young Lee, Hong Seok Jang, Dong Soo Lee, Jin Hee Kim; Cancer Res Treat. 2019;51(4):1589-1599. Published online April 10, 2019; DOI: https://doi.org/10.4143/crt.2018.687

Abstract PDF Supplementary Material PubReader ePub

Purpose
There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B.
Materials and Methods
We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy10 (α/β = 10 Gy). A total of 184 patients were included in this study.
Results
Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy10 (median, 56.0 Gy10). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD.
Conclusion
Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.

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Early Decline in Left Ventricular Ejection Fraction Can Predict Trastuzumab-Related Cardiotoxicity in Patients with Breast Cancer: A Study Using 13 Years of Registry Data: Eun Kyoung Kim, Jinhyun Cho, Ji-Yeon Kim, Sung-A Chang, Sung-Ji Park, Jin Oh Choi, Sang Chol Lee, Jin Seok Ahn, Seung Woo Park, Young-Hyuck Im, Eun Seok Jeon, Yeon Hee Park; Cancer Res Treat. 2019;51(2):727-736. Published online September 4, 2018; DOI: https://doi.org/10.4143/crt.2018.262

Abstract PDF PubReader ePub

Purpose
While concerns regarding trastuzumab-related cardiac dysfunction (TRCD) in patients with breast cancer are increasing, there is a lack of evidence supporting the current recommendations for TRCD monitoring. We aimed to investigate the clinical predictors of TRCD in the adjuvant setting of human epidermal growth factor receptor 2–positive breast cancer patients.
Materials and Methods
From August 2003 to April 2016, consecutive 998 patients who were treated with adjuvant trastuzumab for breast cancer were retrospectively evaluated. TRCD was defined as a decrease ≥10% in left ventricular ejection fraction (LVEF), with a decline below the normal limit or symptomatic heart failure.
Results
Among 787 eligible patients who had complete data sets consisting of both baseline and follow-up assessment of left ventricular systolic function by echocardiography (mean age, 49.9±9.5 years), 58 (7.4%) developed TRCD. TRCD patients had lower baseline LVEF (63% [59–66] vs. 65% [61–68], p=0.016) and more frequently administered Adriamycin (98% vs. 89%, p=0.022) than those without TRCD. On follow-up echocardiography, a drop in LVEF ≥5% within the first 3 months was more frequent in TRCD patients (78.3% vs. 38.4%, p<0.001). Regardless of baseline LVEF and Adriamycin treatment, a drop in LVEF ≥5% within the first 3 months of trastuzumab administration was strongly associated with the development of TRCD (adjusted hazard ratio, 45.1[17.0–127.6], p<0.001).
Conclusion
The overall incidence of TRCD was 7.4% in Asian breast cancer patients treated with adjuvant trastuzumab. A decline in LVEF ≥5% within the first 3 months of trastuzumab initiation was strongly associated with TRCD development in patients with breast cancer.

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Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma: Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(2):510-518. Published online June 13, 2018; DOI: https://doi.org/10.4143/crt.2018.226

Abstract PDF Supplementary Material PubReader ePub

Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

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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

Abstract PDF Supplementary Material PubReader ePub

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.

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Leukemia Research.2022; 118: 106881. CrossRef
DDGP vs. SMILE in Relapsed/Refractory Extranodal Natural Killer/T‐cell Lymphoma, Nasal Type: A Retrospective Study of 54 Patients
Xin Wang, Junxia Hu, Meng Dong, Mengjie Ding, Linan Zhu, Jingjing Wu, Zhenchang Sun, Xin Li, Lei Zhang, Ling Li, Xinhua Wang, Xiaorui Fu, Guannan Wang, Qingjiang Chen, Mingzhi Zhang, Xudong Zhang
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Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge
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Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single Institute in Korea: Tae Wan Kim, Euncheol Choi, Jeonghoon Park, Dong-ho Shin, Su Kyung Jung, Susie Seok, Kwan Ho Cho, Joo-Young Kim, Dae Yong Kim, Tae Hyun Kim, Yang Kwon Suh, Yeon Joo Kim, Sung Ho Moon; Cancer Res Treat. 2018;50(2):335-344. Published online April 19, 2017; DOI: https://doi.org/10.4143/crt.2017.070

Abstract PDF PubReader ePub

Purpose
This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI).
Materials and Methods
Twenty-four treatment-naïve patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software.
Results
The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565±0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively.
Conclusion
The local controlrate and complication profile after PBT in patientswith choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI.

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Engineering of Anti-CD133 Trispecific Molecule Capable of Inducing NK Expansion and Driving Antibody-Dependent Cell-Mediated Cytotoxicity: Jörg U. Schmohl, Martin Felices, Felix Oh, Alexander J. Lenvik, Aaron M. Lebeau, Jayanth Panyam, Jeffrey S. Miller, Daniel A. Vallera; Cancer Res Treat. 2017;49(4):1140-1152. Published online February 20, 2017; DOI: https://doi.org/10.4143/crt.2016.491

Abstract PDF PubReader ePub

Purpose
The selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 bispecific natural killer (NK) cell engager (BiKE), consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified interleukin (IL)-15 crosslinker capable of stimulating NK effector cells was introduced.
Materials and Methods
DNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE). The construct was tested for its specificity using flow cytometry, cytotoxic determinations using chromium release assays, and lytic degranulation. IL-15–mediated expansion was measured using flow-based proliferation assays. The level of interferon (IFN)-γ release was measured because of its importance in the anti-cancer response.
Results
1615133 TriKE induced NK cell–mediated cytotoxicity and NK expansion far greater than that achieved with BiKE devoid of IL-15. The drug binding and induction of cytotoxic degranulation was CD133⁺ specific and the anti-cancer activity was improved by integrating the IL-15 cross linker. The NK cell–related cytokine release measured by IFN-γ detection was higher than that of BiKE. NK cytokine release studies showed that although the IFN-γ levels were elevated, they did not approach the levels achieved with IL-12/IL-18, indicating that release was not at the supraphysiologic level.
Conclusion
1615133 TriKE enhances the NK cell anti-cancer activity and provides a self-sustaining mechanism via IL-15 signaling. By improving the NK cell performance, the new TriKE represents a highly active drug against drug refractory relapse mediated by CSCs.

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Comparison of the Clinical Outcomes of Patients with Squamous Cell Carcinoma of the Tonsil Receiving Postoperative Ipsilateral Versus Bilateral Neck Radiotherapy: A Propensity Score Matching Analysis (KROG 11-07): Youngkyong Kim, Kwan Ho Cho, Sung Ho Moon, Chang Geol Lee, Ki Chang Keum, Sang-wook Lee, Yong Chan Ahn, Dongryul Oh, Yeon-Sil Kim, Yong Kyun Won, Hong-Gyun Wu, J. Hun Hah, Young-Taek Oh; Cancer Res Treat. 2017;49(4):1097-1105. Published online February 9, 2017; DOI: https://doi.org/10.4143/crt.2016.425

Abstract PDF PubReader ePub

Purpose
The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively.
Materials and Methods
Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patientswere identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test.
Results
The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groupswere similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively.
Conclusion
INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.

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Anti-cancer Effects of a Novel Quinoline Derivative 83b1 on Human Esophageal Squamous Cell Carcinoma through Down-Regulation of COX-2 mRNA and PGE₂: Ivan Ho Yuen Pun, Dessy Chan, Sau Hing Chan, Po Yee Chung, Yuan Yuan Zhou, Simon Law, Alfred King Yin Lam, Chung Hin Chui, Albert Sun Chi Chan, Kim Hung Lam, Johnny Cheuk On Tang; Cancer Res Treat. 2017;49(1):219-229. Published online July 18, 2016; DOI: https://doi.org/10.4143/crt.2016.190

Abstract PDF Supplementary Material PubReader ePub

Purpose
83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis.
Materials and Methods
A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E2 (PGE2) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450.
Results
83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft.
Conclusion
The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.

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Downregulation of chemokine (C‑C motif) ligand 5 induced by a novel 8‑hydroxyquinoline derivative (91b1) suppresses tumor invasiveness in esophageal carcinoma
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Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer: Kyung Kee Baek, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Ho-Kyung Chun; Cancer Res Treat. 2010;42(4):185-190. Published online December 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.4.185

Abstract PDF PubReader ePub

Purpose

Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients.

Materials and Methods

This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model.

Results

Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m² (range, 85 to 1,583 mg/m²). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ≥55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN.

Conclusion

We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.

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Case Report

A Case of 5-Fluorouracil Induced Encephalopathy: Kyung A Kwon, Hyuk-Chan Kwon, Min Chan Kim, Sung-Hyun Kim, Sung Yong Oh, Suee Lee, Hyo-Jin Kim; Cancer Res Treat. 2010;42(2):118-120. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.118

Abstract PDF PubReader ePub

Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at risk for experiencing serious adverse effects following 5-fluorouracil (5-FU) based chemotherapy. Neurotoxicity is considered an extremely rare side effect of 5-FU. We report here on an unusual case of 5-FU induced encephalopathy. A 38-year-old woman with advanced gastric carcinoma was treated with adjuvant chemotherapy that consisted of infused 5-FU (1,000 mg/m²) for 5 days and cisplatin (60 mg/m²) on day 1 following total gastrectomy. Nineteen days after starting chemotherapy, the patient displayed a sudden onset of slurred speech, confusion, cognitive disturbances and paranoia. A magnetic resonance image (MRI) of the brain showed no structural abnormalities, and the other laboratory tests provided no explanations for her symptoms, other than a slightly elevated ammonia level. The patient was treated with a lactulose retention enema and thiamine infusion, the 5-FU was halted and her symptoms then recovered after 7 days.

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Original Articles

Treatment Outcomes of Sunitinib Treatment in Advanced Renal Cell Carcinoma Patients: A Single Cancer Center Experience in Korea: Min Hee Hong, Hyo Song Kim, Chan Kim, Jung Ryun Ahn, Hong Jae Chon, Sang-Joon Shin, Joong-Bae Ahn, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2009;41(2):67-72. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.67

Abstract PDF PubReader ePub

Purpose

The retrospective study was performed to assess the efficacy and toxicity profiles of sunitinib in Korean patients with metastatic renal cell carcinoma (RCC).

Materials and Methods

Between January 2005 and December 2008, 76 Korean patients with recurrent/metastatic RCC who received sunitinib were retrospectively reviewed. The primary end point was progression-free survival and the secondary end points were overall survival and response rate. We also assessed the toxicities associated with sunitinib treatment.

Results

Of the 76 patients, 69 (90.1%) were diagnosed with clear cell RCC. The median progression-free survival and overall survival were 7.2 and 22.8 months, respectively in overall patients. Sixty-two patients (81.6%) received 50 mg 4 week and 2 week off schedule, and 14 patients (18.4%) received 37.5 mg daily on a daily continuous schedule. The objective response rate and disease control rate were 27.6% and 84.2%, respectively. A dose reduction or reduction in dose due to adverse events occurred in 76% of the patients, whereas 11% of the patients had discontinued treatment. Other common laboratory abnormalities were increased serum creatinine (75.6%), elevated alanine aminotransferase (71.0%), neutropenia (61.8%), anemia (69.7%), and increased aspartate aminotrasferase (53.3%). Grade 3/4 toxicities occurred as follows: thrombocytopenia (38.2%), fatigue (10.5%), stomatitis (10.5%), and hand-foot syndrome (9.2%).

Conclusion

Our results indicate that sunitinib treatment is effective and tolerable for ecurrent/metastatic RCC patients in Korea. Further studies with prognostic or biochemical factors are needed to clarify the different toxicity profiles of this study.

Citations

Citations to this article as recorded by

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Clinical Correlation between Brain Natriutetic Peptide and Anthracyclin-induced Cardiac Toxicity: Ho Sup Lee, Chang Bae Son, Seong Hoon Shin, Yang Soo Kim; Cancer Res Treat. 2008;40(3):121-126. Published online September 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.3.121

Abstract PDF PubReader ePub

Purpose

Anthracycline can effectively treat hematologic malignancies, but has significant risk of cardiotoxicity. We measured the clinical correlation between brain natriuretic peptide (BNP) and anthracycline-induced cardiotoxicity.

Materials and Methods

Between March 2005 and March 2007, 86 patients with acute leukemia, malignant lymphoma, or multiple myeloma receiving systemic chemotherapy with anthracycline were enrolled in the Department of Hemato-oncology, Kosin University Gospel Hospital. We investigated the relationship between BNP level and cardiotoxicity through echocardiography, electrocardiography, BNP levels, and symptoms of heart failure at each chemotherapy cycle.

Results

Of the 86 participants (mean age, 48.5 years; range 20~65 years), cardiotoxicity developed in 21 patients (24.4%), with 2 patients showing arrhythmia only, 17 patients with transient aspects of heart failure, and 2 patients with chronic heart failure. Cardiotoxicity related to serum BNP level, age, cumulative dose of anthracycline, accompanying chronic disease, and elevated level of troponin-I. Heart failure was more common if BNP levels reached 100 pg/ml at least once.

Conclusions

The clinical correlation between BNP and cardiotoxicity was significant in patients with systemic anthracycline chemotherapy. A prospective clinical trial will be needed to identify the causal relationship between serum BNP level and cardiotoxicity.

Citations

Citations to this article as recorded by

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Alternative Biomarkers for Combined Biology
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Cardio-oncology: Gaps in Knowledge, Goals, Advances, and Educational Efforts
Gina Biasillo, Carlo M. Cipolla, Daniela Cardinale
Current Oncology Reports.2017;[Epub] CrossRef
Cardiovascular Complications of Cancer Therapy
Hui-Ming Chang, Rohit Moudgil, Tiziano Scarabelli, Tochukwu M. Okwuosa, Edward T.H. Yeh
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Giuseppina Novo, Christian Cadeddu, Vincenzo Sucato, Pasquale Pagliaro, Silvio Romano, Carlo G. Tocchetti, Concetta Zito, Luca Longobardo, Savina Nodari, Maria Penco
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YA-DI WANG, SU-XIAN CHEN, LI-QUN REN
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Eric S. Christenson, Theodore James, Vineet Agrawal, Ben H. Park
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The Toxicity of Cisplatin Administered by Isolated Lung Perfusion in Dogs: Ho Seok I, Kwhanmien Kim, Jhingook Kim, Young Mog Shim, Jungho Han, Sung Sae Han; J Korean Cancer Assoc. 2000;32(6):1122-1132.

Abstract PDF: PURPOSE
This research was designed to evaluate the chronic effect of isolated lung perfusion (ILP) with cisplatin on dogs.
MATERIALS AND METHODS
Fifteen dogs were divided into three groups. Group I was in ILP without cisplatin, group II with 2.5 mg/kg and group III with 5.0 mg/kg of cisplatin for 30 minutes respectively. Serial blood samples were taken before and after ILP for quantitative analysis of serum lactate dehydrogenase (LDH) and blood urea nitrogen/creatinine (BUN/Cr). The specimens from the lung were obtained 2 weeks after ILP.
RESULTS
There were no statistic significant differences in LDH concentration according to the time interval among the groups. The LDH concentration peaked at 1 week after ILP and declined thereafter to the pre-ILP concentration. The concentration of BUN/Cr was in normal range. Histologic examination showed no pathologic change. No significant histopathologic differences were found in the pulmonary parenchyme and vasculature among the groups. All of the dogs survived without complication 2 weeks after ILP.
CONCLUSION
In ILP with cisplatin of 5.0 mg/kg in normal dog, the toxicity of cisplatin itself was not observed. With further study about the technique of ILP with cisplatin it would be effective to deliver high concentration of cisplatin into the target tissue minimizing lung damage.

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Dose-Response Relationship of Radiotherapy for Locally Advanced Hepatocellular Carcinoma: Dae Yong Kim, Joon Hyoek Lee, Kwang Cheol Koh, Seung Woon Paik, Yong Chan Ahn, Seung Jae Huh, Inhwan J Yeo, Suk Won Park, Seung Hee Chang; J Korean Cancer Assoc. 2000;32(5):918-924.

Abstract PDF: PURPOSE
Recently radiotherapy is applied alone or in conjunction with transcatheter arterial chemoembolizaion (TACE) or percutaneous ethanol injection therapy (PEIT) for locally advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate dose-response relationship of radiotherapy for local control and toxicity in inoperable HCC.
MATERIALS AND METHODS
Twenty-eight patients who were not eligible for TACE and PEIT or had showed no response to these treatment were treated with a total dose of 40 Gy with 2 Gy per fraction or 30 Gy with 3 Gy per fraction (low dose group, 18 patients) or 45 Gy with 3 Gy per fraction (high dose group, 10 patients).
RESULTS
The median survival duration was 8 months and 1-year survival rate was 37%. The treatment results were as follows; partial response in 11% and 70% (p=0.001), stable disease in 56% and 30%, and progressive disease in 33% and 0% in low dose group and high dose group, respectively. The incidence of gastrointestinal (G-I) toxicity by the criteria of Southwest Oncology Group was as follows; grade 1 in 22% and 40%, grade 2 in 17% and 10%, respectively (p=0.56). There was no patient with severe G-I toxicity above grade 3. The incidence of G-I toxicity by site was as follows; grade 1 in 24% and 29%, and grade 2 in 0% and 57% in patients with right lobe and left lobe lesion, respectively (p=0.001).
CONCLUSION
This study indicates that there is clear dose-response relationship in local control. The G-I toxicity does not increase significantly with increment of radiation dose within the dose range tested in this study. And careful attention should be paid for G-I toxicity when the tumor is located in left lobe.

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Phase I Clinical Trial of Paclitaxel Plus Ifosfamide for the Patients with Refractory Ovarian Cancer: Ho Sawk Saw, Jae Kwan Lee; J Korean Cancer Assoc. 2000;32(5):895-903.

Abstract PDF: PURPOSE
Patients with advanced ovarian carcinoma and refractory to platinum based chemotherapy have a very poor prognosis and effective salvage regimens are needed. This study was conducted in order to determine the maximum tolerated dose (MTD) and dose limiting toxicity of combination with paclitaxel and ifosfamide.
MATERIALS AND METHODS
After premedication, patients received paclitaxel (110~225 mg/m2) as a 24 hour IV infusion on day 1. Ifosfamide (1,000~1,500 mg/m2) was given as a 12 hour IV infusion with standard dose of mesna on day 2~6. All patients received G-CSF (granulocyte colony stimulating factor) on day 6~15.
RESULTS
12 patients with advanced ovarian cancer entered this trial. Toxicity included bone marrow suppression, neuromuscular toxicity, urothelial toxicity, gastrointestinal toxicity, which occurred in 84.6%, 65.3%, 30.7%, 88.4% of cycles.
CONCLUSION
Neuromuscular toxicity was dose limiting toxicity. Maximum tolerated dose in com bination with paclitaxel and ifosfamide was 175 mg/m2 of paclitaxel and 1,500 mg/m2 of ifosfamide.

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Selective Cytotoxicity of the New Platnum ( 2 ) Complexes on Human Gastric Cancer Cell - lines and Normal Kidney Cells: Jee Chang Jung, Sung Goo Chang, Young Soo Rho; J Korean Cancer Assoc. 1999;31(5):1035-1043.

Abstract PDF: PURPOSE
Platinum coordination complex (cisplatin) has been currently used as one of the most effective compound in the treatment of various solid tumors. However, its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and selective cytotoxicity.
MATERIALS AND METHODS
A new series of highly water soluble platinum (II) complexes Pt (II) [1,3-Bis (phenylthio) propane) (trans-l-1,2-diaminocyclohexane) (PC-1) and Pt (II) [1,3-Bis-(phenylthio) (propane)]-1,2-diaminocyclohexane (PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (.IR), ""C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity and nephrotoxi -cities of new Pt (II) complexes were tested against MKN-45 human gastric cancer cell- lines and normal kidney cells using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5- diphenyl tetrazolium bromide] assay for cell survival and proliferation.
RESULTS
PC-1 showed activity against MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cells, and the antitumor activity of this compound was comparable or superior to that of PC-2 and cisplatin. The nephrotoxicity of PC-1 and PC-2 were found quite less than that of cisplatin using MTT, [H] thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues.
CONCLUSION
Based on these results, this novel platinum (II) complex compound (PC-1) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

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Liposomes as Acitivators of Lipophilic Platinum (2 ) Complexes: In Sook Han, Young Jae Lee; J Korean Cancer Assoc. 1999;31(1):180-187.

Abstract PDF: PURPOSE
The goal of this study is to understand the activation processes that take place within the liposomal formulation of lipophilic diaminocyclohexane platinum (DACH-Pt) complexes, to identify the activated species of this class of compounds, and to use that information to develop a reproducible liposomal formulation of DACH-Pt complexes.
MATERIALS AND METHODS
Liposomal DACH-Pt complexes were prepared by lyophilization-rehydration method using PC, PG and PA. Their intraliposomal stability and biological activity were determined by HPLC and in vitro/in vivo experiments.
RESULTS
DACH-Pt complexes in a liposomal formulation have shown significant promise in preclinical studies and clinical phase I, II trials. Interestingly, they are prodrugs which converts into one or more undetennined activated platinum species within the liposomes ex vivo. Our studies have shown that the stability of liposomal DACH-Pt complexes is inversely related with the antitumor activity of those complexes. The configuratian of leaving group in the complexes and pH of the liposome suspension affect significantly the degradation/activation process that takes place within the liposomes. DACH-Pt complexes with linear (L10) leaving groups are more stable than complexes with branched ones (B10 and NDDP), but also significantly less potent. The presence of PG and PA in the liposome is a prerequisite for the degradation/activation process of DACH-Pt complexes. As PG and PA formulation gave more dramatic changes of the original complexes than PC alone due to lower pH, the cytotoxicity and antitumor activity at those fonnulations increased against PC alone. DACH-Pt complexes are very stable in liposomes containing PC alone but inactive in vitro/in vivo experiments.
CONCLUSION
These results also support that the active species produced within the liposomal DACH-Pt complexes is DACH-Pt-Cl2.

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Toxicity of Bile Acids on Colon Cancer Cell Lines: Dong Kook Park, Ji Hyun Shin, Ho Jin Jun, Kyeong Jae Kim, Chan Young Lee; J Korean Cancer Assoc. 1999;31(1):126-133.

Abstract PDF: PURPOSE
Cytotoxicity of the bile acids on colon cancer cell lines was studied to know which bile acid was most cytotoxic to colonic mucosal epithelium. We performed agarose gel electrophoresis whether this toxicity was caused by detergent effect of the bile acids or by apoptotic pathway.
MATERIALS AND METHODS
HT29, LoVo, SW620 colon cancer cell lines were exposed to lithocholate, cholate, deoxycholate and chenodeoxycholate with 50, 100, 150, 200, 250, 300 pM as final concentration in DMEM culture media for short time (for 2 hours) and for long time (for 5 days). Agarose gel electrophoresis was performed on each colon cancer cell lines (HT29, LoVo, SW620, SW480) after 1, 2, 3, 4, 5 days exposure to deoxycholate with 150 pM concentration to detect intemucleosomal fragmentation.
RESULTS
There was no toxicity after short time exposure in all bile acids concentration and in all colon cancer cell lines. Of the bile acids, deoxycholate was most toxic for all colon cancer cell lines. And DNA fragmentation was noticed after 2 days exposure with deoxycholate. Only LoVo cell line showed apoptotic DNA pattern after 4 days of exposure with deoxycholate.
CONCLUSION
Bile acids (especially deoxycholate) are suggested to be possible agents to cause apoptosis in colonic mucosal epithelium.

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Clinical Trial

Anti-tumor Effect of the Complex of Acriflavine and Guanosine (AG60): Eun Kyung Hong, Hwan Mook Kim, Kyung Yung Lee, Young Shin Chung, Bo Im Yoo, Sang Geon Kim, E Tay Ahn, Young Bok Han; J Korean Cancer Assoc. 1997;29(1):29-37.

Abstract PDF: PURPOSE
The anti-tumor effect of the complex of acriflavine and guanosine (AG60) was investigated.
MATERIALS AND METHODS
In vitro cytotoxicity of AG60 was measured using SRB assay, and in vivo antitumor activity of AG60 was examined in CDF1 mice intraperitoneally inoculated with the P388 leukemic cells and in ICR mice inguinally implanted with S-180 cells. Tumor size and mean survival time were determined.
RESULTS
AG60 and acriflavine showed strong anti-tumor effect in vitro on lung cancer (A549), renal cancer (UO-31) and colon cancer (COLO205) cells. However, AG60 did not show the cytotoxicity against normal cell line, 3T3. The range of the IC50 of AG60 to the various tumor cell lines was 0.09 microgram/ml through 1.94 microgram/ml. The treatment of ascitic tumor bearing CDF1 mice with AG60 resulted in over 160% increases in the mean survival time. The most effective dose of AG60 was 30 mg/kg body weight in tumor implanted mice. In solid tumor bearing ICR mice tumor growth and progression were suppressed in response to the different doses at 30 days; 69.8% suppression of tumor size in response to acriflavine, 16.0% to guanosine, 87.7% to AG60 and 78.5% to doxorubicin. In addition, 35% increases were observed in the means survival time of AG60 treated group compared with control group.
CONCLUSION
The prominant anti-tumor effects of AG60 shown in this report would represent the possibility of the clinical trials.

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Original Articles

Augmentaion of Cytotoxicity of Anticancer Drugs with Biological Response Modifiers against Human Leukemia Cell Lines: Yun Young Lee, Eui Gun Chun, Jun Young Kil, Ill Kuk Yoon, Kwan Hee Yu, Byung Zun Ahn, Sam Yong Kim; J Korean Cancer Assoc. 1994;26(2):274-285.

Abstract PDF: To investigate the possibility of increased cytotoxicity of anticancer drugs, we treated human leukemia cells with combinations of anticancer drugs and biological response modifiers (BRMs). Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, we evaluated the chemosensitivity of 8 anticancer drugs(vincristine, vinblastine, adria- mycin, cisplatin, etoposide, cytosine arabinoside, bleomycin, and cyclophosphamide), and the anticancer effects of 3 BRMs(interleukin-2, alpha interferon, and gamma interferon) combined with these anticancer drugs against human leukemia HL-60 and KG-1 cells. The results were as follows; in the chemosensitivity of 8 anticancer drugs, VCR, VBL, ADR, and CPDD were effective, while VP-16, ara-C, Bleo, and CYC produced less than 50% inhibition of HL-60 and KG-1 cells lines. Among 3 BRMs investigated, all of them showed less than 20% inhibition of KG-1 cell lines and none were effective against HL-60 cells. In the anticancer effects of 3 BRMs, all of them showed about 20% inhibitory effects against KG-1 cells, but there were not any effects against HL-60 cells. All of the anticancer drugs markedly increased cytotoxic effects when they were combined with BRM. Especially, the ID values of VCR, VBL, and ADR when combined with BRMs decreased to 67~3%. These results demonstrate that some BRMs can markedly increase the cytotoxicity of VCR, VBL, ADR, CPDD, VP-16, ara-C, Bleo, and CYC and suggest possible clinical usefulwess.

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Natural Killer ( NK ) Cell cytotoxicity According to the Expression of c-erbB-2 Protein in Human Gastric Cancer Cells: Byeong Woo Park, Kang Sup Shim, Sung Hoon Noh, Coong Bai Kim, Kyung Shik Lee; J Korean Cancer Assoc. 1995;27(1):1-8.

Abstract PDF: Although there is still controversy to the relationship between c-erbB-2 protein expression and prognosis of the gastric carcinoma, there were many reports about the poor prognosis with the expression of c-erbB-2 in gastric carcinoma. The mechanisms underlying this phenomenon are not known. However several possibilities such as acquired resistance to 5-Fluorouracil(5-FU) and resistance to the host immune system were suggested. So we performed this study to evaluate whether c-erbB-2 expression can alter the natural killeriNK) cell cytotoxic activity. Using single cell suspensions from primary gastric cancer tissues and malignant ascites due to stomach cancer, the immunohistochemical reactivity to c-cerB-2 protein was examined and we performed the tests for NK cell cytotoxic activity. The c-erbB-2(+) cancer cells were significantly more resistant to NK cell cytotoxic activity than c-erbB-2( ) cancer cells. However there was no significant difference in the resiatance to NK cell cytotoxic activity according to their immunohistochemical staining intensities. These results suggest that the resistance to the NK cel1 cytotoxicity may be one of the possi- ble mechanisms of the poorer prognosis of the c-erbB-2(+ ) gastric cancers.

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