Cancer Research and Treatment

Original Articles

Clinical Relevance of Starting Alectinib at a Reduced Dose in Patients with ALK-Positive Non-Small Cell Lung Cancer: Junkyu Kim, Min-Ji Kim, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Received December 14, 2024 Accepted April 22, 2025 Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1209 [Accepted]

Abstract PDF: Purpose
Alectinib has been approved for Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) at 300mg twice daily in Japan, lower than global standard of 600mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses.
Materials and Methods
This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared.
Results
Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (HR 0.82, 95% CI, 0.44-1.51; p=0.51) and overall survival (HR 0.51, 95% CI, 0.20-1.21; p=0.13). Superior outcome with 300mg was remarkable in patients with lower body weight (≤60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300mg group exhibited a slight increase in incidence of CNS failure (HR 1.76, 95% CI, 0.53-5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600mg group, 50% of which requiring dose reduction.
Conclusion
Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

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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

Abstract PDF PubReader ePub

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

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Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials
D. Ross Camidge, Shunichi Sugawara, Masashi Kondo, Hye Ryun Kim, Myung-Ju Ahn, James C.H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Kentarou Kudou, Takayuki Asato, Bradley Hupf, Florin Vranceanu, Robert J. Fram, Yuichiro O
Lung Cancer.2025; 201: 108424. CrossRef
Effectiveness of First-Line Treatment with Anaplastic Lymphoma Kinase and ROS1 Protoncogene Inhibitors in Non-Small Cell Lung Cancer Patients—Real-World Evidence of Two Polish Cancer Centers
Michał Gil, Kinga Winiarczyk, Paweł Krawczyk, Kamila Wojas-Krawczyk, Aleksandra Łomża-Łaba, Adrian Obara, Łukasz Gajek, Katarzyna Reszka, Andrzej Tysarowski, Jarosław Buczkowski, Izabela Chmielewska, Tomasz Jankowski, Magdalena Szuba-Gil, Maciej Strzemski
Cancers.2025; 17(7): 1253. CrossRef
Oncogenic Fusions in NSCLC: From Mechanisms to Clinical Applications
Nyein Wint Yee Theik, Suset Almuinas De Armas, Daniel Rosas, Amy Kiamos, Nyein Nyein Thaw Dar, Ahmed Shoreibah, Atif Hussein, Luis E. Raez
International Journal of Molecular Sciences.2025; 26(8): 3802. CrossRef
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

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Sarcoma

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single-Center Study: Xin Liu, Chengcheng Gong, Jieyun Zhang, Wanjing Feng, Yanjing Guo, Youzhou Sang, Chunmeng Wang, Yong Chen, Jian Wang, Lin Yu, Xiaowei Zhang, Zhiguo Luo; Cancer Res Treat. 2023;55(3):1001-1010. Published online March 3, 2023; DOI: https://doi.org/10.4143/crt.2022.894

Abstract PDF Supplementary Material PubReader ePub

Purpose
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood.
Materials and Methods
We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed.
Results
Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients.
Conclusion
Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

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Clinicopathological Characteristics of Inflammatory Myofibroblastic Tumor: A Single Center Retrospective Cohort Study
Xiaoyan Si, Shafei Wu, Ruie Feng, Mengzhao Wang, Hanping Wang, Xiaotong Zhang, Li Zhang, Kaifeng Xu
Thoracic Cancer.2025;[Epub] CrossRef
Case report: Intra-abdominal inflammatory myofibroblastic tumor with mucinous features: a case of rapid recurrence and dissemination post-surgery
Xingchen Li, Jie Li, Chunxiao Liang, Qing Zou
Frontiers in Oncology.2025;[Epub] CrossRef
Clinical diagnosis and treatment of abdominal inflammatory myofibroblastic tumors
Qiang Zhang, Zhi-wei Zhang, Jing Fan, Zhuo-Ma Ji, Chun-Yan Wang, Feng Liu
Discover Oncology.2025;[Epub] CrossRef
Therapeutic strategy and prognostic analysis of inflammatory myofibroblastic tumor in the head and neck: a retrospective study
Feng Liu, Yanchao Qin, Zhiwei Zhang, Mengru Li, Bowei Feng, Wei Ding, Shubin Dong
PeerJ.2025; 13: e19315. CrossRef
Inflammatory myofibroblastic tumor of the adrenal gland: A case report
Jiyao Yang, Hongjin Shi, Haifeng Wang, Yidao Liu
Urology Case Reports.2024; 55: 102763. CrossRef
Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations
Francisco Cristóbal Muñoz-Casares, Javier Martín-Broto, Pedro Cascales-Campos, Juan Torres-Melero, Irene López-Rojo, José Gómez-Barbadillo, Luis González-Bayón, Ana Sebio, César Serrano, Sara Carvalhal, Joaquim Abreu de Souza, Alexandre Souza, Guillermo F
Cancers.2024; 16(15): 2646. CrossRef
Thoracic epithelioid inflammatory myofibroblastic sarcoma: a rare and aggressive disease with case report and literature review
Linke Yang, Pei Li, Runze Liu, Baomin Feng, Huiqing Mao, Xiaoyong Tang, Guangjian Yang
Discover Oncology.2024;[Epub] CrossRef
Metastasized inflammatory myofibroblastic tumor of uterine origin
Thomas Bartl, Michael Deavers, Ryan Blair Kieser, Pedro T Ramirez
International Journal of Gynecological Cancer.2024; 34(10): 1643. CrossRef
Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib—a case report
Rafał Becht, Kajetan Kiełbowski, Justyna Żychowska, Wojciech Poncyljusz, Aleksandra Łanocha, Katarzyna Kozak, Ewa Gabrysz-Trybek, Paweł Domagała
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Rare giant epithelioid inflammatory myofibroblastic sarcoma of the abdominal cavity in a child: a case report and review of the literature
Jinzhou Li, Haixing Su, Sheng Zhang, Xianyun Chen, Chongzhi Hou, Tao Cheng
Frontiers in Oncology.2024;[Epub] CrossRef
Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment
PAULINA CHMIEL, ALEKSANDRA SłOWIKOWSKA, ŁUKASZ BANASZEK, ANNA SZUMERA-CIEćKIEWICZ, BARTłOMIEJ SZOSTAKOWSKI, MATEUSZ J. SPAłEK, TOMASZ ŚWITAJ, PIOTR RUTKOWSKI, ANNA M. CZARNECKA
Oncology Research.2024; 32(7): 1141. CrossRef

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Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing: Eunhyang Park, Hyo Sup Shim; Cancer Res Treat. 2020;52(2):543-551. Published online November 8, 2019; DOI: https://doi.org/10.4143/crt.2019.305

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use.
Materials and Methods
Patients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared.
Results
A total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31).
Conclusion
Even though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.

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Prognostic value of preoperative circulating tumor DNA in non-small cell lung cancer: a systematic review and meta-analysis
Jiamin Lu, Yuqian Feng, Kaibo Guo, Leitao Sun, Shanming Ruan, Kai Zhang
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Dong-Won Kang, Sun-Kyeong Park, Sokbom Kang, Eui-Kyung Lee
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European Journal of Cancer.2023; 193: 113310. CrossRef
Clinicopathological Characteristics of NRG1 Fusion–Positive Solid Tumors in Korean Patients
Yoon Jin Cha, Chung Lee, Bio Joo, Kyung A Kim, Choong-kun Lee, Hyo Sup Shim
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Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer: Su-Jung Kim, Soyeon Kim, Dong-Wan Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yusoo Lee, Jaemoon Koh, Yoon Kyung Jeon, Dae Seog Heo; Cancer Res Treat. 2019;51(3):1231-1240. Published online December 31, 2018; DOI: https://doi.org/10.4143/crt.2018.486

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer.
Materials and Methods
We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed.
Results
PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163).
Conclusion
PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.

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Immunomodulatory role of oncogenic alterations in non-small cell lung cancer: a review of implications for immunotherapy
Maritza Ramos-Ramírez, Enrique Caballe-Pérez, José Lucio-Lozada, Eunice Romero-Nuñez, Cesar Castillo-Ruiz, Lorena Dorantes-Sánchez, Diana Flores-Estrada, Gonzalo Recondo, Pedro Barrios-Bernal, Luis Cabrera-Miranda, Heyman Bravo-Dominguez, Norma Hernández-
Cancer and Metastasis Reviews.2025;[Epub] CrossRef
Association of PD-L1 expression and clinical outcomes in ROS1 - rearranged advanced non-small cell lung cancer treated with crizotinib
Huixian Zhang, Ziheng Zhang, Ningning Yan, Xingya Li
Frontiers in Oncology.2024;[Epub] CrossRef
Co-Occurrence of ALK rearrangement and KRAS G12C mutation in NSCLC: Report of two cases
M Siringo, F Larocca, A Spagnuolo, G Gentile, M Anile, D Diso, D Santini, A Gelibter
Current Problems in Cancer: Case Reports.2024; 14: 100291. CrossRef
Characterizing the immune tumor microenvironment in ALK fusion-positive lung cancer: state-of-the-art and therapeutical implications
Marco Sposito, Serena Eccher, Luca Pasqualin, Ilaria Mariangela Scaglione, Alice Avancini, Daniela Tregnago, Ilaria Trestini, Jessica Insolda, Adele Bonato, Stefano Ugel, Lisa Derosa, Michele Milella, Sara Pilotto, Lorenzo Belluomini
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Crizotinib in Combination with Everolimus Synergistically Inhibits Proliferation of Anaplastic Lymphoma Kinase‒Positive Anaplastic Large Cell Lymphoma: Wendan Xu, Ji-Won Kim, Woo June Jung, Youngil Koh, Sung-Soo Yoon; Cancer Res Treat. 2018;50(2):599-613. Published online June 19, 2017; DOI: https://doi.org/10.4143/crt.2016.357

Abstract PDF Supplementary Material PubReader ePub

Purpose
Anaplastic large cell lymphoma (ALCL) is a rare aggresive non-Hodgkin lymphoma, of which over 50% of cases have an aberrant nucleophosmin (NPM)‒anaplastic lymphoma kinase (ALK) fusion protein. Both mechanistic target of rapamycin (mTOR) inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated.
Materials and Methods
We evaluated the anti-proliferative effects of everolimus and/or crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1, and lung adenocarcinoma cell line, NCI-H2228.
Results
We found that individually, both everolimus and crizotinib potently inhibited cell growth in a dose-dependent manner in both Karpas 299 and SU-DHL-1 cells. A combination of these agents synergistically inhibited proliferation in the two cell lines. Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus. Combination treatment also significantly increased G0/G1 cell-cycle arrest, DNA damage, and apoptosis compared with everolimus or crizotinib alone in ALK-positive ALCL cells. In the Karpas 299 xenograft model, the combination treatment exerted a stronger antitumor effect than monotherapies, without significant change in body weight. The synergistic effect of everolimus and crizotinib was also reproduced in the ALK-positive lung adenocarcinoma cell line NCI-H2228. The combination treatment abrogated phosphoinositide 3-kinase/AKT and mTOR signaling pathways with little effect on the Ras/ERK pathway in NCI-H2228 cells.
Conclusion
Crizotinib combinedwith everolimus synergistically inhibits proliferation of ALK-positive ALCL cells. Our results suggest that this novel combination is worthy of further clinical development in patients with ALK-positive ALCL.

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The PI3K signaling pathway; from normal lymphopoiesis to lymphoid malignancies
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ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor: Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn; Cancer Res Treat. 2018;50(2):495-505. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.577

Abstract PDF PubReader ePub

Purpose
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
Materials and Methods
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
Results
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK⁺ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
Conclusion
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.

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Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features
Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo
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Multi-omics revealed that ELAVL3 regulates MYCN in neuroblastoma via immunogenic cell death: Risk stratification and experimental research
Peng Hong, Zaihong Hu, Jie Lin, Kongkong Cui, Zhiqiang Gao, Xiaomao Tian, Qinlin Shi, Tao Lin, Guanghui Wei
International Journal of Biological Macromolecules.2024; 282: 137045. CrossRef
Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma
Manli Zhao, Weizhong Gu, Fei Liu, Lihua Yu, Yan Shu, Lei Liu, Jiahui Hu, Yang Liu, Hongfeng Tang, Jianhua Mao
Pediatric and Developmental Pathology.2023; 26(2): 124. CrossRef
ALKGene Mutation and ALK Protein Expression in Advanced Neuroblastoma and the Potential Value in Risk Stratification in Fine-Needle Aspiration Biopsy Samples
Neha Bhardwaj, Manish Rohilla, Upasana Gautam, Amita Trehan, Deepak Bansal, Nandita Kakkar, Radhika Srinivasan
American Journal of Clinical Pathology.2023;[Epub] CrossRef
Rapid detection of telomerase expression of neuroblastoma in paraffin-embedded tissue: combination of in situ hybridisation and quantitative PCR
Manli Zhao, Zhonghai Guan, Liang Gong, Fei Liu, Weizhong Gu, Lei Liu, Kewen Jiang, Jiabin Cai, Chunyue Feng, Chik Hong Kuick, Kenneth Tou En Chang, Jinhu Wang, Hongfeng Tang, Minzhi Yin, Jianhua Mao
Pathology.2023; 55(7): 958. CrossRef
Interactions of Butyrylcholinesterase with Neuroblastoma-associated Oncoproteins
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
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Combined Detection of Copy Number Variations of MYCN and ALK using Droplet Digital Polymerase Chain Reaction to Identify High-Risk Patients with Neuroblastoma
Trupti Trivedi, Kinjal Panchal, Neha Bhalala, Priti Trivedi, Harsha Panchal
World Neurosurgery.2022; 159: e48. CrossRef
ALK expression, prognostic significance, and its association with MYCN expression in MYCN non-amplified neuroblastoma
Dinesh Babu Somasundaram, Sheeja Aravindan, Nandita Gupta, Zhongxin Yu, Ashley Baker, Natarajan Aravindan
World Journal of Pediatrics.2022; 18(4): 285. CrossRef
Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Journal of Pediatric Hematology/Oncology.2022; 44(6): 293. CrossRef
Differential Impact of ALK Mutations in Neuroblastoma
Tara O'Donohue, Nitya Gulati, Audrey Mauguen, Brian H. Kushner, Neerav Shukla, M. I. Rodriguez-Sanchez, Nancy Bouvier, Stephen Roberts, Ellen Basu, Nai-Kong Cheung, Shakeel Modak
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The challenge of defining “ultra‐high‐risk” neuroblastoma
Daniel A. Morgenstern, Rochelle Bagatell, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Lucas Moreno, Julie R. Park, Andrew D. Pearson, Gudrun Schleiermacher, Dominique Valteau‐Couanet, Wendy B. London, Meredith S. Irwin
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ALK in Neuroblastoma: Biological and Therapeutic Implications
Ricky Trigg, Suzanne Turner
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Case Report

SEC31A-ALK Fusion Gene in Lung Adenocarcinoma: Ryong Nam Kim, Yoon-La Choi, Mi-Sook Lee, Maruja E. Lira, Mao Mao, Derrick Mann, Joshua Stahl, Abel Licon, So Jung Choi, Michael Van Vrancken, Joungho Han, Iwona Wlodarska, Jhingook Kim; Cancer Res Treat. 2016;48(1):398-402. Published online February 17, 2015; DOI: https://doi.org/10.4143/crt.2014.254

Abstract PDF Supplementary Material PubReader ePub

Anaplastic lymphoma kinase (ALK) fusion is a common mechanism underlying pathogenesis of non-small cell lung carcinoma (NSCLC) where these rearrangements represent important diagnostic and therapeutic targets. In this study, we found a new ALK fusion gene, SEC31A-ALK, in lung carcinoma from a 53-year-old Korean man. The conjoined region in the fusion transcript was generated by the fusion of SEC31A exon 21 and ALK exon 20 by genomic rearrangement, which contributed to generation of an intact, in-frame open reading frame. SEC31A-ALK encodes a predicted fusion protein of 1,438 amino acids comprising the WD40 domain of SEC31A at the N-terminus and ALK kinase domain at the C-terminus. Fluorescence in situ hybridization studies suggested that SEC31A-ALK was generated by an unbalanced genomic rearrangement associated with loss of the 3′-end of SEC31A. This is the first report of SEC31A-ALK fusion transcript in clinical NSCLC, which could be a novel diagnostic and therapeutic target for patients with NSCLC.

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Ka‐Won Noh, Mi‐Sook Lee, Seung Eun Lee, Ji‐Young Song, Hyun‐Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong‐Yang Park, Se‐Hoon Lee, Yoon‐La Choi
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Original Article

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

Abstract PDF PubReader ePub

Purpose
To investigate the impact of targeted treatment on direct medical costs of patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Medical records of 108 stage IIIB/IV NSCLC patients treated in Seoul National University Hospital between 2003 and 2009, were reviewed to collect medical resources utilization data from the diagnosis of stage IIIB/IV NSCLC to the end of active anti-cancer treatment. The direct medical costs were calculated by multiplying the number of medical resources used by the unit price. All costs were expressed in US dollars for each patient. Results The mean total direct medical costs were $34,732 (standard deviation, 21,168) in the study cohort. The mean total direct medical costs were higher in epidermal growth factor receptor (EGFR) mutation (EGFR MT)–positive patients than EGFR wild-type (EGFR WT) patients ($41,403 vs. $30,146, p=0.005). However, the mean monthly direct medical costs did not differ significantly between EGFR MT–positive patients and EGFR WT patients ($2,120 vs. $2,702, p=0.119) because of the longer duration of active anti-cancer treatment in EGFR MT–positive patients. This discrepancy was mainly attributable to EGFR MT–positive patients’ lower non-chemotherapy costs ($948 vs. $1,522, p=0.007). The total and monthly direct medical costs of ALK fusion–positive patients who did not receive ALK inhibitors did not differ from WT/WT patients. Conclusion This study suggests that the availability of targeted agents for EGFR MT–positive patients lowers the mean monthly medical costs by prolonging survival and diminishing the use of other medical resources, despite the considerable drug costs.

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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
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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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