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41 "Se-Hoon Lee"
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Original Articles
Lung and Thoracic cancer
Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non–Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial
Junghoon Shin, Sehhoon Park, Kyung Hwan Kim, Eui-Cheol Shin, Hyun Ae Jung, Jong Ho Cho, Jong-Mu Sun, Se-Hoon Lee, Yong Soo Choi, Jin Seok Ahn, Jhingook Kim, Keunchil Park, Young Mog Shim, Hong Kwan Kim, Jae Myoung Noh, Yong Chan Ahn, Hongryull Pyo, Myung-Ju Ahn
Cancer Res Treat. 2024;56(4):1084-1095.   Published online April 30, 2024
DOI: https://doi.org/10.4143/crt.2024.084
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods
In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1).
Results
Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion
Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.
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Endocrine cancer
Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAFV600E-Mutated Thyroid Cancer
Youngkyung Jeon, Sehhoon Park, Se-Hoon Lee, Tae Hyuk Kim, Sun Wook Kim, Myung-Ju Ahn, Hyun Ae Jung, Jae Hoon Chung
Cancer Res Treat. 2024;56(4):1270-1276.   Published online March 6, 2024
DOI: https://doi.org/10.4143/crt.2023.1278
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
BRAF mutations are detected in 30%-80% of papillary thyroid cancer (PTC) cases. DaBRAFenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non–small cell lung cancer. This study aimed to evaluate the efficacy and safety of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer.
Materials and Methods
This was a retrospective study to evaluate the efficacy of daBRAFenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received daBRAFenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of daBRAFenib and trametinib.
Results
Between December 2019 and January 2022, 27 PTC patients including eight patients with poorly differentiated or anaplastic transformation, received daBRAFenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients.
Conclusion
DaBRAFenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction.

Citations

Citations to this article as recorded by  
  • Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2
    Dong Yeob Shin, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim
    International Journal of Thyroidology.2024; 17(1): 168.     CrossRef
  • Antineoplastic Effect of ALK Inhibitor Crizotinib in Primary Human Anaplastic Thyroid Cancer Cells with STRN–ALK Fusion In Vitro
    Silvia Martina Ferrari, Francesca Ragusa, Giusy Elia, Valeria Mazzi, Eugenia Balestri, Chiara Botrini, Licia Rugani, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Camilla Virili, Alessandro Antonelli, Poupak Fallahi
    International Journal of Molecular Sciences.2024; 25(12): 6734.     CrossRef
  • The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review
    Odysseas Violetis, Panagiota Konstantakou, Ariadni Spyroglou, Antonios Xydakis, Panagiotis B. Kekis, Sofia Tseleni, Denise Kolomodi, Manousos Konstadoulakis, George Mastorakos, Maria Theochari, Javier Aller, Krystallenia I. Alexandraki
    Journal of Personalized Medicine.2024; 14(6): 654.     CrossRef
  • Treatment of Unresectable BRAF V600E, TERT-Mutated Differentiated Papillary Thyroid Cancer With Dabrafenib and Trametinib
    Neha Bapat, Tatiana Ferraro, Layal Esper, Arjun S Joshi, Faysal Haroun, Chelsey K Baldwin
    JCEM Case Reports.2024;[Epub]     CrossRef
  • Trametinib

    Reactions Weekly.2024; 2035(1): 467.     CrossRef
  • 2,594 View
  • 378 Download
  • 2 Web of Science
  • 5 Crossref
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Lung and Thoracic cancer
First-Line Alectinib vs. Brigatinib in Advanced Non–Small Cell Lung Cancer with ALK Rearrangement: Real-World Data
Youngkyung Jeon, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Res Treat. 2024;56(1):61-69.   Published online July 14, 2023
DOI: https://doi.org/10.4143/crt.2023.461
AbstractAbstract PDFPubReaderePub
Purpose
Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib.
Materials and Methods
Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%).
Conclusion
Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Citations

Citations to this article as recorded by  
  • Bridging the Gap between Trial Adverse Events and Real-World Data
    Sang Hyuk Kim, Hyun Lee, Dong Won Park
    Cancer Research and Treatment.2024; 56(3): 972.     CrossRef
  • Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
    Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
    Cancer Medicine.2024;[Epub]     CrossRef
  • Cost‐Effectiveness Analysis of Adjuvant Alectinib versus Platinum‐Based Chemotherapy in Resected ALK‐Positive Non‐Small‐Cell Lung Cancer in the Chinese Health Care System
    Qiran Wei, Yifang Liang, Jiahui Mao, Xin Guan
    Cancer Medicine.2024;[Epub]     CrossRef
  • 5,083 View
  • 585 Download
  • 4 Web of Science
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Expanded Access Program Pralsetinib in Advanced Non–Small Cell Lung Cancer with Rearranged during Transfection (RET) Gene Rearrangement
Youngkyung Jeon, Hyun Ae Jung, Sehhoon Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Se-Hoon Lee
Cancer Res Treat. 2023;55(4):1144-1151.   Published online May 22, 2023
DOI: https://doi.org/10.4143/crt.2023.403
AbstractAbstract PDFPubReaderePub
Purpose
Rearranged during transfection (RET) gene rearrangement is a well-known driver event in non–small cell lung cancer (NSCLC). Pralsetinib is a selective inhibitor of RET kinase and has shown efficacy in oncogenic RET-altered tumors. This study evaluated the efficacy and safety of expanded access program (EAP) use of pralsetinib in pretreated, advanced NSCLC patients with RET rearrangement.
Materials and Methods
Patients who received pralsetinib as part of the EAP at Samsung Medical Center were evaluated through a retrospective chart review. The primary endpoint was overall response rate (ORR) per the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 guidelines. Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Between April 2020 and September 2021, 23 of 27 patients were enrolled in the EAP study. Two patients who were not analyzed due to brain metastasis and two patients whose expected survival was within 1 month were excluded from the analysis. After a median follow-up period of 15.6 months (95% confidence interval [CI], 10.0 to 21.2), ORR was 56.5%, the median PFS was 12.1 months (95% CI, 3.3 to 20.9), and the 12-month OS rate was 69.6%. The most frequent treatment-related adverse events (TRAEs) were edema (43.5%) and pneumonitis (39.1%). A total of 8.7% of patients experienced extra-pulmonary tuberculosis. TRAEs with a common grade of three or worse were neutropenia (43.5%) and anemia (34.8%). Dose reduction was required in nine patients (39.1%).
Conclusion
Pralsetinib presents a clinical benefit when used in patients with RET-rearranged NSCLC, consistent with a pivotal study.

Citations

Citations to this article as recorded by  
  • Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC
    Francesca Lucibello, Valérie Gounant, Mihaela Aldea, Michaël Duruisseaux, Maurice Perol, Christos Chouaid, Jaafar Bennouna, Vincent Fallet, Aldo Renault, Florian Guisier, Etienne Giroux-Leprieur, Marie Wislez, Anne-Claire Toffart, Julien Mazieres, Clémenc
    JTO Clinical and Research Reports.2025; 6(1): 100743.     CrossRef
  • Clinical evidence and adverse event management update of patients with RET- rearranged advanced non-small-cell lung cancer (NSCLC) treated with pralsetinib
    Giuseppe Lo Russo, Paolo Bironzo, Chiara Bennati, Laura Bonanno, Annamaria Catino, Giulio Metro, Iacopo Petrini, Marco Russano, Antonio Passaro
    Critical Reviews in Oncology/Hematology.2024; 194: 104243.     CrossRef
  • RET Fusion Testing in Patients With NSCLC: The RETING Study
    Esther Conde, Susana Hernandez, Jose Luis Rodriguez Carrillo, Rebeca Martinez, Marta Alonso, Daniel Curto, Beatriz Jimenez, Alejandra Caminoa, Amparo Benito, Pilar Garrido, Sergi Clave, Edurne Arriola, Isabel Esteban-Rodriguez, Javier De Castro, Irene San
    JTO Clinical and Research Reports.2024; 5(4): 100653.     CrossRef
  • Efficacy and safety of pralsetinib in patients with RET fusion positive non–small cell lung cancer: An observational real world study
    Dehua Liao, Minghui Long, Jiwen Zhang, Xingyu Wei, Fei Li, Ting Yan, Desong Yang
    Lung Cancer.2024; 196: 107936.     CrossRef
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  • 213 Download
  • 5 Web of Science
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Head and Neck cancer
Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Hana Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn, Dongryul Oh, Myung-Ju Ahn
Cancer Res Treat. 2023;55(4):1104-1112.   Published online May 17, 2023
DOI: https://doi.org/10.4143/crt.2023.502
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect.
Results
Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1).
Conclusion
The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

Citations

Citations to this article as recorded by  
  • Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review
    Akihiro Sakai, Koji Ebisumoto, Hiroaki Iijima, Mayu Yamauchi, Daisuke Maki, Tsuyoshi Fukuzawa, Kenji Okami
    Cancer Reports.2024;[Epub]     CrossRef
  • Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects
    Makoto Ito, Souichiro Abe, Sou Adachi, Yukihiko Oshima, Arisa Takeuchi, Wataru Ohashi, Takashi Iwata, Tetsuya Ogawa, Akiko Ota, Yasuaki Kubota, Takahito Okuda, Kojiro Suzuki
    Japanese Journal of Radiology.2024; 42(4): 424.     CrossRef
  • Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis
    Xiao Han, Haidong Zhang, Kai Sun, Jing Li, Wanjuan Wu, Kai Liu, Zhenkun Yu
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Kaplan lecture 2023: lymphopenia in particle therapy
    Marco Durante
    International Journal of Radiation Biology.2024; 100(5): 669.     CrossRef
  • Clinical application of high‐LET radiotherapy combined with immunotherapy in malignant tumors
    Kexin Meng, Haijun Lu
    Precision Radiation Oncology.2024; 8(1): 42.     CrossRef
  • Research progress of immunotherapy for advanced head and neck cancer
    Anchi Sun, Zhiwei Xing, Rongrong Lv, Pengyuan Niu, Bao Zhao, Shiyin Ma, Hui Li
    Medical Oncology.2024;[Epub]     CrossRef
  • A review and bibliometric analysis of global research on proton radiotherapy
    Ge Song, Zhi Zheng, Yingming Zhu, Yaoting Wang, Song Xue
    Medicine.2024; 103(19): e38089.     CrossRef
  • Cutaneous Squamous Cell Carcinoma: An Updated Review
    Rina Jiang, Mike Fritz, Syril Keena T. Que
    Cancers.2024; 16(10): 1800.     CrossRef
  • Radiotherapy and immunology
    Liangliang Wang, Connor Lynch, Sean P. Pitroda, András Piffkó, Kaiting Yang, Amy K. Huser, Hua Laura Liang, Ralph R. Weichselbaum
    Journal of Experimental Medicine.2024;[Epub]     CrossRef
  • The Evolving Paradigm of Immunotherapy in Head-and-neck Squamous Cell Cancers
    Riccardo Gili, Paolo Bossi
    Journal of Head & Neck Physicians and Surgeons.2024; 12(1): 13.     CrossRef
  • Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach
    Alessia Zotta, Maria Luisa Marciano, Francesco Sabbatino, Alessandro Ottaiano, Marco Cascella, Monica Pontone, Massimo Montano, Ester Calogero, Francesco Longo, Morena Fasano, Teresa Troiani, Fortunato Ciardiello, Fabiana Raffaella Rampetta, Giovanni Salz
    Biomedicines.2024; 12(10): 2337.     CrossRef
  • Emerging Radiotherapy Technologies for Head and Neck Squamous Cell Carcinoma: Challenges and Opportunities in the Era of Immunotherapy
    Carmen Kut, Harry Quon, Xuguang Scott Chen
    Cancers.2024; 16(24): 4150.     CrossRef
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  • 12 Web of Science
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Lung and Thoracic cancer
The Role of Brain Radiotherapy before First-Line Afatinib Therapy, Compared to Gefitinib or Erlotinib, in Patients with EGFR-Mutant Non–Small Cell Lung Cancer
Hyun Ae Jung, Sehhoon Park, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun
Cancer Res Treat. 2023;55(2):479-487.   Published online December 27, 2022
DOI: https://doi.org/10.4143/crt.2022.1344
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Brain metastasis is common in patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer (NSCLC) at initial presentation. A previous study showed that brain radiotherapy (RT) before first-generation (first-G) EGFR–tyrosine kinase inhibitor (TKI) therapy is associated with longer overall survival than TKI therapy alone. However, there is no data regarding the role of additional brain RT before afatinib therapy.
Materials and Methods
Between October 2014 and June 2019, EGFR-mutant NSCLC patients with brain metastases who started first-G EGFR-TKIs (gefitinib or erlotinib) or afatinib as first-line therapy were retrospectively analyzed. This study compared overall survival and intracranial progression-free survival (PFS) between patients who received EGFR-TKIs alone and EGFR-TKIs with brain RT and either a first-G EGFR-TKI or afatinib, respectively.
Results
The median follow-up duration was 29.6 months (range, 1.5 to 116.9 months). In the first-G EGFR-TKI group (n=155), 94 patients (60.6%) received the first-G EGFR-TKI alone and 61 patients (39.4%) received brain RT prior to their first-G EGFR-TKI. In the afatinib group (n=204), 126 patients (61.8%) received afatinib alone and 78 patients (38.2%) received brain RT prior to afatinib. There was no difference in overall survival rates between the groups with RT (35.6 months: 95% confidence interval [CI], 27.9 to 43.3) and without RT (31.4 months: 95% CI, 23.9 to 38.9) in the afatinib group (p=0.58), but there was a significant difference in overall survival in the first-G EGFR-TKI group in a manner favoring additional brain RT (41.1 months: 95% CI, 30.5 to 51.7 vs. 25.8 months: 95% CI, 20.1 to 31.5; p=0.02). Meanwhile, median intracranial PFS was not different between patients who received EGFR-TKI therapy alone vs. EGFR-TKI therapy with brain RT in both the first-G EGFR-TKI (p=0.39) and afatinib (p=0.24) groups.
Conclusion
Afatinib therapy alone showed comparable survival outcomes to those of afatinib with brain RT. The current study suggests that brain RT could be an optional, not mandatory, treatment modality when afatinib therapy is considered in patients with EGFR-mutant NSCLC.

Citations

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  • Radiation Recall Pneumonitis: The Open Challenge in Differential Diagnosis of Pneumonia Induced by Oncological Treatments
    Francesca Grassi, Vincenza Granata, Roberta Fusco, Federica De Muzio, Carmen Cutolo, Michela Gabelloni, Alessandra Borgheresi, Ginevra Danti, Carmine Picone, Andrea Giovagnoni, Vittorio Miele, Nicoletta Gandolfo, Antonio Barile, Valerio Nardone, Roberta G
    Journal of Clinical Medicine.2023; 12(4): 1442.     CrossRef
  • Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study
    H.A. Jung, S. Park, S.-H. Lee, J.S. Ahn, M.-J. Ahn, J.-M. Sun
    ESMO Open.2023; 8(6): 102068.     CrossRef
  • Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review
    Jiamin Xu, Zhongming Wang
    Frontiers in Oncology.2023;[Epub]     CrossRef
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  • 3 Web of Science
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Cancer-Specific Sequences in the Diagnosis and Treatment of NUT Carcinoma
Mi-Sook Lee, Sungbin An, Ji-Young Song, Minjung Sung, Kyungsoo Jung, Eun Sol Chang, Juyoung Choi, Doo-Yi Oh, Yoon Kyung Jeon, Hobin Yang, Chaithanya Lakshmi, Sehhoon Park, Joungho Han, Se-Hoon Lee, Yoon-La Choi
Cancer Res Treat. 2023;55(2):452-467.   Published online October 14, 2022
DOI: https://doi.org/10.4143/crt.2022.910
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC.
Materials and Methods
We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts.
Results
As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness.
Conclusion
This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Citations

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  • Indirect targeting of MYC and direct targeting in combination with chemotherapies are more effective than direct mono-targeting in triple negative breast cancer
    Negesse Mekonnen, Hobin Yang, Nirmal Rajasekaran, Kyoung Song, Yoon-La Choi, Young Kee Shin
    Translational Oncology.2025; 51: 102204.     CrossRef
  • NUT-midline carcinoma of the lung with rare BRD3-NUTM1 fusion
    Prerana Jha, Vaishakhi Trivedi, Nandini Menon, Minit Shah, Irene A George, Rohit Mishra, Trupti Pai, Fuzail Ahmad, Venkataramanan Ramachandran, Vanita Noronha, Kumar Prabhash, Prashant Kumar
    Cancer Research, Statistics, and Treatment.2024; 7(1): 110.     CrossRef
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  • 2 Web of Science
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EGFR Mutation–Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis
Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Cancer Res Treat. 2023;55(2):498-505.   Published online October 4, 2022
DOI: https://doi.org/10.4143/crt.2022.388
AbstractAbstract PDFPubReaderePub
Purpose
The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non–small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemoradiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status.
Materials and Methods
We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern.
Results
Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation.
Conclusion
Patients with EGFR mutation–positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.

Citations

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  • Prognostic Factors in Postoperative Brain Metastases Derive From Non-small Cell Lung Cancer: A Retrospective Analysis
    Haibin Chen, Liang Sun, Zhi Yang, Yuanyuan Qu, Nanyang Tong, Caixing Sun, Liang Xia
    Clinical Medicine Insights: Oncology.2024;[Epub]     CrossRef
  • Brain metastasis screening in the molecular age
    Joanna K Tabor, Amanda Onoichenco, Vinayak Narayan, A Gabriella Wernicke, Randy S D’Amico, Morana Vojnic
    Neuro-Oncology Advances.2023;[Epub]     CrossRef
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  • 3 Web of Science
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Case Report
Osimertinib Combined with Systemic Chemotherapy for EGFR Mutant, T790M-Negative, Non–Small Cell Lung Cancer Patients Who Develop Leptomeningeal Metastases with Extracranial Progression to Prior EGFR TKI
Hye Ryeon Kim, Hyunji Jo, Hongsik Kim, Joohyun Hong, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin-Seok Ahn, Myung-Ju Ahn
Cancer Res Treat. 2023;55(1):344-349.   Published online March 26, 2022
DOI: https://doi.org/10.4143/crt.2021.1603
AbstractAbstract PDFPubReaderePub
Leptomeningeal metastasis (LM) is a rare but fatal clinical condition with a short survival time. The incidence of LM from epidermal growth factor receptor mutant (EGFRm) non–small cell lung cancer (NSCLC) has increased due to the limited efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the central nervous system (CNS). Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean overall survival from LM diagnosis was 14.7 months (95% confidence interval, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.

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Original Articles
Head and Neck cancer
A Single-Arm, Prospective, Phase II Study of Cisplatin Plus Weekly Docetaxel as First-Line Therapy in Patients with Metastatic or Recurrent Salivary Gland Cancer
Hye Ryeon Kim, Su Jin Lee, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Han-Sin Jeong, Man Ki Chung, Myung-Ju Ahn
Cancer Res Treat. 2022;54(3):719-727.   Published online November 1, 2021
DOI: https://doi.org/10.4143/crt.2021.1019
AbstractAbstract PDFPubReaderePub
Purpose
Salivary gland cancers (SGCs) are relatively rare but comprise various histologic subtypes, which complicates design of prospective trials. Systemic chemotherapy plays a limited role in treatment of SGCs, but cisplatin and docetaxel showed efficacy in a previous preclinical study. Here, we conduct a prospective, phase II study to evaluate the efficacy and toxicities of cisplatin plus weekly docetaxel in patients with metastatic or recurrent SGC.
Materials and Methods
We included patients with histologically confirmed SGCs of the following subtypes: mucoepidermoid carcinoma, adenocarcinoma, ductal carcinoma, or adenoid cystic carcinoma. Patients had no prior systemic chemotherapy for metastatic or recurrent tumors and at least one measurable lesion. Patients were treated with docetaxel 35 mg/m2 (D1, 8) and cisplatin 70 mg/m2 (D1) every 21 days.
Results
Forty-one patients were enrolled between April 2014 and October 2020. The median age was 58 years (range, 32 to 73 years). The most common histologic subtype was adenoid cystic carcinoma (63.4%), followed by ductal carcinoma (24.4%). The most common metastatic site was the lung (75.6%). The median treatment cycle was 5.5 (range, 3 to 8), and the objective response rate was 46.3%, with three complete responses. The median duration of response was 6.8 months (interquartile range, 4.0 to 10.2). The progression-free survival and overall survival were 9.4 months (95% confidence interval [CI], 8.4 to 10.5) and 28.2 months (95% CI, 22.7 to 33.6), respectively. There were no treatment-related deaths. The most common grade 3/4 adverse events were neutropenia (4.9%) and fatigue (4.9%).
Conclusion
Cisplatin plus weekly docetaxel is effective and tolerable with manageable toxicity as first-line therapy in patients with metastatic or recurrent SGC.

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    Alec J. Kacew, Glenn J. Hanna
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Lung and Thoracic cancer
Long-term Survival in Non–Small Cell Lung Cancer Patients with Metachronous Brain-Only Oligorecurrence Who Underwent Definitive Treatment
Hongsik Kim, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2022;54(1):150-156.   Published online May 6, 2021
DOI: https://doi.org/10.4143/crt.2021.306
AbstractAbstract PDFPubReaderePub
Purpose
Metachronous brain-only oligorecurrence in patients with non–small cell lung cancer (NSCLC) is a rare event with favorable prognosis, but the clinical outcome has not been fully determined. We retrospectively analyzed clinical outcomes and prognostic factors in metachronous brain-only oligorecurrence in patients with NSCLC who underwent definitive treatment.
Materials and Methods
We reviewed 4,437 NSCLC patients without oncogenic driver mutations who underwent definitive treatment between 2008 and 2018. Among them, we identified 327 patients who developed 1 to 5 brain metastases with or without systemic metastasis. Of the 327 patients, 71 had metachronous brain-only oligorecurrence without extracranial progression and were treated with local therapy to the brain. Overall survival (OS), progression-free survival (PFS), and prognostic factors affecting OS were analyzed.
Results
The median OS was 38.9 months (95% confidence interval [CI], 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient had a survival period of 115 months. Through multivariate analysis, Eastern Cooperative Oncology Group ≥ 1 (hazard ratio, 5.33; p=0.005) was associated with poor survival. There was no significant difference in OS between patients with local therapy and those with local plus systemic therapy (18.5 months vs. 34.7 months, p=0.815).
Conclusion
Metachronous brain-only oligorecurrence NSCLC patients who underwent definitive treatment experienced long-term survival with local therapy, highlighting the unique patient population. The role of systemic chemotherapy in this patient population requires further investigation.

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    Takahiro Suzuki, Shoichi Deguchi, Keigo Matsushima, Shinya Katsumata, Hideaki Kojima, Maeda Koki, Hayato Konno, Mitsuhiro Isaka, Takuma Oishi, Yasuhisa Ohde, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi
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Case Report
EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation
Sehhoon Park, Bo Mi Ku, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Se-Hoon Lee, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2020;52(4):1288-1290.   Published online June 22, 2020
DOI: https://doi.org/10.4143/crt.2020.278
AbstractAbstract PDFPubReaderePub
The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

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Original Articles
Clinical Characteristics and Outcomes of Non-small Cell Lung Cancer Patients with HER2 Alterations in Korea
Kangkook Lee, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2020;52(1):292-300.   Published online July 26, 2019
DOI: https://doi.org/10.4143/crt.2019.186
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Human epidermal growth factor receptor 2 (HER2) alterations are found in approximately 1%-3% of non-small cell lung cancers (NSCLCs). We evaluated the clinical features and outcomes of NSCLC harboring HER2 alteration detected by next-generation sequencing (NGS) in Korea.
Materials and Methods
A total of 1,108 patients who were diagnosed with NSCLC between December 2015 and December 2017 were screened and analyzed by NGS. Medical records were reviewed retrospectively to analyze the clinical characteristics and outcomes from various treatments.
Results
HER2 alterations were identified in 36 NSCLC patients. Of the patients, 22 (61.1%) had an exon 20 in-frame insertion mutation, 15 (41.7%) had HER2 amplification, and one had both. The median patient age was 58 years, 55.6% were male, and 50.0% were never-smokers. Adenocarcinoma was predominant (88.9%). The most common metastatic site was bone (58.3%), and 66.7% of patients were stage IV at initial diagnosis. Six patients (16.7%) had a coexistent sensitizing epidermal growth factor receptor (EGFR) mutation, and two patients (5.6%) had anaplastic lymphoma kinase (ALK) rearrangement. With a median 14 months of follow-up, the median progression-free survival of first-line treatment was 6 months (95% confidence interval, 4.172 to 7.828), and median overall survival was not reached. The proportions of adenocarcinoma, never-smokers, and metastasis to the liver were higher in the exon 20 in-frame insertion mutation group, whereas coexistence of EGFR mutation was more frequently found in the HER2 amplification group.
Conclusion
HER2-altered NSCLC showed distinct clinical features. Moreover, different characteristics were identified between the HER2 in-frame insertion mutation group and the HER2 amplification group.

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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 EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13
Kwai Han Yoo, Su Jin Lee, Jinhyun Cho, Ki Hyeong Lee, Keon Uk Park, Ki Hwan Kim, Eun Kyung Cho, Yoon Hee Choi, Hye Ryun Kim, Hoon-Gu Kim, Heui June Ahn, Ha Yeon Lee, Hwan Jung Yun, Jin-Hyoung Kang, Jaeheon Jeong, Moon Young Choi, Sin-Ho Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):718-726.   Published online September 3, 2018
DOI: https://doi.org/10.4143/crt.2018.324
AbstractAbstract PDFPubReaderePub
Purpose
The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Materials and Methods
We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles.
Results
A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms.
Conclusion
The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

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Clinical Outcomes of EGFR Exon 20 Insertion Mutations in Advanced Non-small Cell Lung Cancer in Korea
Seonggyu Byeon, Youjin Kim, Sung Won Lim, Jang Ho Cho, Sehoon Park, Jiyun Lee, Jong-Mu Sun, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(2):623-631.   Published online July 23, 2018
DOI: https://doi.org/10.4143/crt.2018.151
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for approximately 4% of all EGFR mutations. Given the rarity of this mutation, its clinical outcomes are not fully established.
Materials and Methods
Between 2009 and 2017, non-small cell lung cancer (NSCLC) patients who showed an exon 20 insertion were retrospectively reviewed for clinical characteristics and outcomes, including responses to chemotherapy (CTx) or targeted therapy.
Results
Of 3,539 NSCLC patients who harbored an activating EGFR mutation, 56 (1.6%) had an exon 20 insertion. Of the advanced NSCLC patients, 27 of 1,479 (1.8%) had an exon 20 insertion. The median overall survival was 29.4 months (95% confidence interval 9.3 to 49.6) for 27 advancedNSCLC patients. The 22 patientswho received systemic CTx achieved a 50.0% response rate and a 77.2% disease control rate, with 4.2 months of progressionfree survival. Six patients received EGFR tyrosine kinase inhibitors (TKIs). Three of the four patients that had only an exon 20 insertion showed progressive disease, while one showed stable disease. The othertwo patients had an exon 20 insertion and another EGFR mutation and achieved a partial response.
Conclusion
The incidence of an exon 20 insertion mutation is rare in Korea and occasionally accompanied by other common EGFR mutations. Although the response to systemic CTx. in these patients is comparable to that of patients with other mutations, the response rate to firstor second-generation EGFR TKIs is quite low. Therefore, the development of a more efficient agent is urgently needed.

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Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib
Youjin Kim, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Jong-Mu Sun
Cancer Res Treat. 2019;51(2):502-509.   Published online June 13, 2018
DOI: https://doi.org/10.4143/crt.2018.117
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib.
Materials and Methods
We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016.
Results
In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months).
Conclusion
First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

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Case Report
Rare Mechanism of Acquired Resistance to Osimertinib in Korean Patients with EGFR-mutated Non-small Cell Lung Cancer
Jiyun Lee, Joon Ho Shim, Woong-Yang Park, Hee Kyung Kim, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Cancer Res Treat. 2019;51(1):408-412.   Published online May 23, 2018
DOI: https://doi.org/10.4143/crt.2018.138
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Epidermal growth factor receptor (EGFR)‒tyrosine kinase inhibitors (TKIs) are effective clinical therapeutics for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib, a thirdgeneration EGFR TKI, has proven effective against T790M mutations. However, the vast majority of patients acquire resistance following successful treatment. A 59-year-old female patient with metastatic NSCLC developed resistance after 43 weeks of osimertinib. CancerSCAN of the metastatic liver lesion revealed a EGFR C797G mutation at an allele frequency of 72%, a preexisting T790M mutation (73%) in cis and an exon 19 deletion (87%). Another 53-year-old female patient developed systemic progression after 10 months of osimertinib. CancerSCAN of the lung biopsy identified an EGFR L718Q mutation at an allele frequency of 7%, concomitant PIK3CA E545K (12.90%) and preexisting EGFR L858R (38%), but loss of the T790M mutation. The heterogeneity of osimertinib resistance mechanisms warrants further investigation into novel or combination agents to overcome the rare acquired resistances.

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Original Articles
Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients
Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park
Cancer Res Treat. 2019;51(1):211-222.   Published online April 23, 2018
DOI: https://doi.org/10.4143/crt.2018.132
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study
Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim
Cancer Res Treat. 2018;50(2):488-494.   Published online May 22, 2017
DOI: https://doi.org/10.4143/crt.2016.584
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

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Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer
Min-Young Lee, Bo Mi Ku, Hae Su Kim, Ji Yun Lee, Sung Hee Lim, Jong-Mu Sun, Se-Hoon Lee, Keunchil Park, Young Lyun Oh, Mineui Hong, Han-Sin Jeong, Young-Ik Son, Chung-Hwan Baek, Myung-Ju Ahn
Cancer Res Treat. 2017;49(4):906-914.   Published online December 26, 2016
DOI: https://doi.org/10.4143/crt.2016.424
AbstractAbstract PDFPubReaderePub
Purpose
Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group.
Materials and Methods
Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString’s nCountertechnology and mutational analysiswas performed by directDNA sequencing.Data describing the clinicopathological characteristics and clinical courses were retrospectively collected.
Results
Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations.
Conclusion
In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

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Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea
Byung Sup Kim, Ho Jun Seol, Do-Hyun Nam, Chul-Kee Park, Il Han Kim, Tae Min Kim, Jeong Hoon Kim, Young Hyun Cho, Sang Min Yoon, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Chang-Ok Suh, Tae-Young Jung, Kyung-Hwa Lee, Chae-Yong Kim, In Ah Kim, Chang-Ki Hong, Heon Yoo, Jin Hee Kim, Shin-Hyuk Kang, Min Kyu Kang, Eun-Young Kim, Sun-Hwan Kim, Dong-Sup Chung, Sun-Chul Hwang, Joon-Ho Song, Sung Jin Cho, Sun-Il Lee, Youn-Soo Lee, Kook-Jin Ahn, Se Hoon Kim, Do Hun Lim, Ho-Shin Gwak, Se-Hoon Lee, Yong-Kil Hong
Cancer Res Treat. 2017;49(1):193-203.   Published online June 27, 2016
DOI: https://doi.org/10.4143/crt.2015.473
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample.
Materials and Methods
A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively.
Results
After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients,respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period.
Conclusion
Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

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    Haihui Jiang, Yong Cui, Junmei Wang, Song Lin
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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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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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    Rashmi R. Shah
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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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    Yamei Hu, Zigang Dong, Kangdong Liu
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    International Journal of Molecular Sciences.2024; 25(11): 6220.     CrossRef
  • Interleukin-6 serves as a critical factor in various cancer progression and therapy
    Asma’a H. Mohamed, Abdulrahman T. Ahmed, Waleed Al Abdulmonem, Dmitry Olegovich Bokov, Alaa Shafie, Hussein Riyadh Abdul Kareem Al-Hetty, Chou-Yi Hsu, Mohammed Alissa, Shahid Nazir, Mohammad Chand Jamali, Mustafa Mudhafar
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  • A strategic review of STAT3 signaling inhibition by phytochemicals for cancer prevention and treatment: Advances and insights
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  • Expression of STAT3, IL27p28 and IL12p35 is deregulated and linked to autoimmune markers in chronic spontaneous urticaria
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    Clinical and Experimental Dermatology.2024;[Epub]     CrossRef
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  • Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer
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  • JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens
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  • Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay
    Xueying Fan, Mingjing Meng, Baoting Li, Hui Chen, Jincheng Tan, Keyang Xu, Shilin Xiao, Hiu-Yee Kwan, Zhongqiu Liu, Tao Su
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  • C188-9, a specific inhibitor of STAT3 signaling, prevents thermal burn-induced skeletal muscle wasting in mice
    Yuko Ono, Masafumi Saito, Kazuho Sakamoto, Yuko Maejima, Shingen Misaka, Kenju Shimomura, Nobuto Nakanishi, Shigeaki Inoue, Joji Kotani
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  • Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review)
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  • Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer
    Shumin Ouyang, Huaxuan Li, Linlin Lou, Qiuyao Huang, Zhenhua Zhang, Jianshan Mo, Min Li, Jiaye Lu, Kai Zhu, Yunjie Chu, Wen Ding, Jianzheng Zhu, Ziyou Lin, Lin Zhong, Junjian Wang, Peibin Yue, James Turkson, Peiqing Liu, Yuanxiang Wang, Xiaolei Zhang
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  • Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers
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  • A Broad-Based Characterization of a Cell-Penetrating, Single Domain Camelid Bi-Specific Antibody Monomer That Targets STAT3 and KRAS Dependent Cancers
    Sunanda Singh, Genoveva Murillo, Justin Richner, Samara P. Singh, Erica Berleth, Vijay Kumar, Rajendra Mehta, Vijay Ramiya, Ashutosh S. Parihar
    International Journal of Molecular Sciences.2022; 23(14): 7565.     CrossRef
  • Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy
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    Cellular Oncology.2022; 45(6): 1073.     CrossRef
  • STAT3 and Its Targeting Inhibitors in Oral Squamous Cell Carcinoma
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    Cells.2022; 11(19): 3131.     CrossRef
  • The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities
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  • An update on investigational therapies that target STAT3 for the treatment of cancer
    Matteo Santoni, Francesca Miccini, Alessia Cimadamore, Francesco Piva, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Rodolfo Montironi, Nicola Battelli
    Expert Opinion on Investigational Drugs.2021; 30(3): 245.     CrossRef
  • RETRACTED: GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression
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  • Phytochemicals Targeting JAK–STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models
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  • Development and Validation of an IL6/JAK/STAT3-Related Gene Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma
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  • Emerging role of signal transducer and activator of transcription 3 (STAT3) in pituitary adenomas
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  • Interleukin-6 and colorectal cancer development
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  • Ailanthone suppresses the activity of human colorectal cancer cells through the STAT3 signaling pathway
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  • Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells
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    International Journal of Radiation Biology.2020; 96(4): 434.     CrossRef
  • Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization
    Jan Jamroskovic, Mara Doimo, Karam Chand, Ikenna Obi, Rajendra Kumar, Kristoffer Brännström, Mattias Hedenström, Rabindra Nath Das, Almaz Akhunzianov, Marco Deiana, Kazutoshi Kasho, Sebastian Sulis Sato, Parham L. Pourbozorgi, James E. Mason, Paolo Medini
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  • Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1
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    Cell Death & Disease.2020;[Epub]     CrossRef
  • JAK/STAT signaling in hepatocellular carcinoma
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  • JAK–STAT pathway targeting for the treatment of inflammatory bowel disease
    Azucena Salas, Cristian Hernandez-Rocha, Marjolijn Duijvestein, William Faubion, Dermot McGovern, Severine Vermeire, Stefania Vetrano, Niels Vande Casteele
    Nature Reviews Gastroenterology & Hepatology.2020; 17(6): 323.     CrossRef
  • Targeting STAT3 in cancer and autoimmune diseases
    Tohid Gharibi, Zohreh Babaloo, Arezoo Hosseini, Meghdad Abdollahpour-alitappeh, Vida Hashemi, Faroogh Marofi, Kazem Nejati, Behzad Baradaran
    European Journal of Pharmacology.2020; 878: 173107.     CrossRef
  • Betacellulin drives therapy resistance in glioblastoma
    Qiwen Fan, Zhenyi An, Robyn A Wong, Xujun Luo, Edbert D Lu, Albert Baldwin, Manasi K Mayekar, Franziska Haderk, Kevan M Shokat, Trever G Bivona, William A Weiss
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  • A novel small molecule STAT3 inhibitor SLSI-1216 suppresses proliferation and tumor growth of triple-negative breast cancer cells through apoptotic induction
    Soo Kyung Park, Woong Sub Byun, Seungbeom Lee, Young Taek Han, Yoo-Seong Jeong, Kyungkuk Jang, Suk-Jae Chung, Jeeyeon Lee, Young-Ger Suh, Sang Kook Lee
    Biochemical Pharmacology.2020; 178: 114053.     CrossRef
  • STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects
    Milad Ashrafizadeh, Ali Zarrabi, Sima Orouei, Vahideh Zarrin, Ebrahim Rahmani Moghadam, Amirhossein Zabolian, Shima Mohammadi, Kiavash Hushmandi, Yashar Gharehaghajlou, Pooyan Makvandi, Masoud Najafi, Reza Mohammadinejad
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  • Towards the Inhibition of Protein–Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives
    Matteo Mori, Ettore Gilardoni, Luca Regazzoni, Alessandro Pedretti, Diego Colombo, Gary Parkinson, Akira Asai, Fiorella Meneghetti, Stefania Villa, Arianna Gelain
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  • Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer


    Yan Lin, Ziqin He, Jiazhou Ye, Ziyu Liu, Xiaomin She, Xing Gao, Rong Liang
    OncoTargets and Therapy.2020; Volume 13: 13023.     CrossRef
  • Systemic Therapy for Hepatocellular Carcinoma: Advances and Hopes
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  • Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma
    Yung-Hsing Huang, Mohammad Reza Vakili, Ommoleila Molavi, Yuen Morrissey, Chengsheng Wu, Igor Paiva, Amir Hasan Soleimani, Forugh Sanaee, Afsaneh Lavasanifar, Raymond Lai
    Cancers.2019; 11(2): 248.     CrossRef
  • Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma
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    Cancer Research and Treatment.2019; 51(2): 510.     CrossRef
  • IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2
    Xiaodong Chen, Feng Chen, Yu Ren, Guobin Weng, Lijun Xu, Xiang Xue, Peter C. Keng, Soo Ok Lee, Yuhchyau Chen
    Journal of Cancer Research and Clinical Oncology.2019; 145(6): 1471.     CrossRef
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    World Journal of Gastroenterology.2019; 25(17): 2058.     CrossRef
  • Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells
    Gianluca Civenni, Domenico Albino, Dheeraj Shinde, Ramiro Vázquez, Jessica Merulla, Aleksandra Kokanovic, Sarah N. Mapelli, Giuseppina M. Carbone, Carlo V. Catapano
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review
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    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors
    Emily A. Irey, Chelsea M. Lassiter, Nicholas J. Brady, Pavlina Chuntova, Ying Wang, Todd P. Knutson, Christine Henzler, Thomas S. Chaffee, Rachel I. Vogel, Andrew C. Nelson, Michael A. Farrar, Kathryn L. Schwertfeger
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  • Elevated HOX gene expression in acute myeloid leukemia is associated with NPM1 mutations and poor survival
    Ádám Nagy, Ágnes Ősz, Jan Budczies, Szilvia Krizsán, Gergely Szombath, Judit Demeter, Csaba Bödör, Balázs Győrffy
    Journal of Advanced Research.2019; 20: 105.     CrossRef
  • Antitumor activity of novel pyrazole-based small molecular inhibitors of the STAT3 pathway in patient derived high grade glioma cells
    Liang Zhang, Timothy E. Peterson, Victor M. Lu, Ian F. Parney, David J. Daniels, Ilya Ulasov
    PLOS ONE.2019; 14(7): e0220569.     CrossRef
  • Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis
    Yali Li, Cailing Gan, Yange Zhang, Yan Yu, Chen Fan, Yuanle Deng, Qianyu Zhang, Xi Yu, Yiwen Zhang, Liqun Wang, Fang He, Yongmei Xie, Tinghong Ye, Wenya Yin
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  • Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status
    Tadashi Ashizawa, Akira Iizuka, Chie Maeda, Emiko Tanaka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Takuya Kawata, Shoichi Deguchi, Koichi Mitsuya, Nakamasa Hayashi, Akira Asai, Mamoru Ito, Ken Yamaguchi, Yasuto Akiyama
    Immunology Letters.2019; 216: 43.     CrossRef
  • Signal Transducer and Activator of Transcription Protein 3 (STAT3): An Update on its Direct Inhibitors as Promising Anticancer Agents
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  • The effects of signal transducer and activator of transcription three mutations on human platelets
    Floor E. Aleva, Frank L. van de Veerdonk, Yang Li, Rahajeng N. Tunjungputri, Sami Simons, Philip G. De Groot, Mihai M. Netea, Yvonne F. Heijdra, Quirijn de Mast, André J.A.M. van der Ven
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  • Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells
    Sung Ho Kim, Hyo Soon Yoo, Moon Kyung Joo, Taehyun Kim, Jong-Jae Park, Beom Jae Lee, Hoon Jai Chun, Sang Woo Lee, Young-Tae Bak
    BMC Cancer.2018;[Epub]     CrossRef
  • Linker Variation and Structure–Activity Relationship Analyses of Carboxylic Acid-based Small Molecule STAT3 Inhibitors
    Francisco Lopez-Tapia, Christine Brotherton-Pleiss, Peibin Yue, Heide Murakami, Ana Carolina Costa Araujo, Bruna Reis dos Santos, Erin Ichinotsubo, Anna Rabkin, Raj Shah, Megan Lantz, Suzie Chen, Marcus A. Tius, James Turkson
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  • Decoy-Based, Targeted Inhibition of STAT3: A New Step forward for B Cell Lymphoma Immunotherapy
    Mario M. Soldevilla, Fernando Pastor
    Molecular Therapy.2018; 26(3): 675.     CrossRef
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  • Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs
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    Journal of Leukocyte Biology.2018; 104(3): 499.     CrossRef
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    Pharmacology & Therapeutics.2018; 192: 100.     CrossRef
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  • Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance
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  • STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
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  • Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors
    Masaki Miura, Takeshi Miyatsuka, Takehiro Katahira, Shugo Sasaki, Luka Suzuki, Miwa Himuro, Yuya Nishida, Yoshio Fujitani, Taka-aki Matsuoka, Hirotaka Watada
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  • A First-in-Human Phase I Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers
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  • Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome
    Konstantin Masliantsev, Baptiste Pinel, Anaïs Balbous, Pierre-Olivier Guichet, Gaëlle Tachon, Serge Milin, Julie Godet, Mathilde Duchesne, Antoine Berger, Christos Petropoulos, Michel Wager, Lucie Karayan-Tapon
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  • Discovery of an Orally Selective Inhibitor of Signal Transducer and Activator of Transcription 3 Using Advanced Multiple Ligand Simultaneous Docking
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  • Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
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  • Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells
    Davide Genini, Lara Brambilla, Erik Laurini, Jessica Merulla, Gianluca Civenni, Shusil Pandit, Rocco D'Antuono, Laurent Perez, David E. Levy, Sabrina Pricl, Giuseppina M. Carbone, Carlo V. Catapano
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  • Identification of novel small molecules that inhibit STAT3-dependent transcription and function
    Iryna Kolosenko, Yasmin Yu, Sander Busker, Matheus Dyczynski, Jianping Liu, Martin Haraldsson, Caroline Palm Apergi, Thomas Helleday, Katja Pokrovskaja Tamm, Brent D. G. Page, Dan Grander, Aamir Ahmad
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  • Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid leukemia
    Hui-Er Gao, Yue Sun, Ya-Hui Ding, Jing Long, Xiao-Lei Liu, Ming Yang, Qing Ji, Ying-Hui Li, Yue Chen, Quan Zhang, Ying-Dai Gao
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  • Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation
    Verena Leidgens, Judith Proske, Lisa Rauer, Sylvia Moeckel, Kathrin Renner, Ulrich Bogdahn, Markus J. Riemenschneider, Martin Proescholdt, Arabel Vollmann-Zwerenz, Peter Hau, Corinna Seliger
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    Yu Dong, Takuya Furuta, Hemragul Sabit, Tomohiro Kitabayashi, Shabierjiang Jiapaer, Masahiko Kobayashi, Yasushi Ino, Tomoki Todo, Lei Teng, Atsushi Hirao, Shi-Guang Zhao, Mitsutoshi Nakada
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  • Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma
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  • Preclinical Characterization of 3β-(N-Acetyl l-cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer
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  • A Positive TGF-β/c-KIT Feedback Loop Drives Tumor Progression in Advanced Primary Liver Cancer
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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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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.

Citations

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  • Treatment decisions, clinical outcomes, and pharmacoeconomics in the treatment of patients with EGFR mutated stage III/IV NSCLC in Germany: an observational study
    Wolfgang Schuette, Peter Schirmacher, Wilfried E. E. Eberhardt, Manfred Dietel, Ute Zirrgiebel, Lars Muehlenhoff, Michael Thomas
    BMC Cancer.2018;[Epub]     CrossRef
  • Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study
    Dae Ho Lee, Hiroshi Isobe, Hubert Wirtz, Sabina Bandeira Aleixo, Phillip Parente, Filippo de Marinis, Min Huang, Ashwini Arunachalam, Smita Kothari, Xiting Cao, Nello Donnini, Ann-Marie Woodgate, Javier de Castro
    BMC Health Services Research.2018;[Epub]     CrossRef
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