Cancer Research and Treatment

Original Articles

CNS cancer

To Use or Not to Use: Temozolomide in Elderly Patients with IDH Wild-Type MGMT Promoter Unmethylated Glioblastoma Treated with Radiotherapy: Chan Woo Wee, Joo Ho Lee, Hye In Lee, Jina Kim, Jong Hee Chang, Seok-Gu Kang, Eui Hyun Kim, Ju Hyung Moon, Jaeho Cho, Chul-Kee Park, Chae-Yong Kim, Kihwan Hwang, Hong In Yoon, In Ah Kim; Cancer Res Treat. 2025;57(3):693-700. Published online November 11, 2024; DOI: https://doi.org/10.4143/crt.2024.945

Purpose
This study aimed to identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated O6-methylguanine-DNA methyltransferase promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).
Materials and Methods
Newly diagnosed patients with Isocitrate dehydrogenase wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.3%), 60 Gy in 30 fractions, or 61.2 Gy in 34 fractions. For patients treated with RT plus TMZ (60.4%), TMZ was administered concurrently with RT, followed by six adjuvant cycles. The primary endpoint was overall survival.
Results
During a median follow-up of 11.3 months for survivors, the median survival was 12.2 months. The median survival duration significantly improved with the addition of TMZ to RT compared with that with RT alone (13.6 months vs. 10.5 months, p=0.028). In the multivariable analysis adjusted for clinical, radiological, and genetic biomarkers, the addition of TMZ significantly improved overall survival (hazard ratio, 0.459; p=0.006). In subgroup analysis, median survival was especially improved by 4-5 months in patients with residual disease (p < 0.001), Karnofsky performance status ≥ 60 (p=0.033), and age ≤ 75 years (p=0.090). A significant benefit of TMZ was noted only in patients with two or three of the above factors (median survival, 14.1 months vs. 10.5 months; p=0.014).
Conclusion
The addition of TMZ significantly improved the survival of patients with eGBM-unmethylated treated with RT. The suggested criteria for the specific subgroup in these patients warrant external validation for clinical application.

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Age is not enough: Clinical and therapeutic predictors of survival in elderly patients with de novo glioblastoma
Raquel Gutiérrez-González, Zulema Herrero, Ana Royuela, Victor Bello, Paula Moreno, Alvaro Zamarron
Neuro-Oncology Advances.2026;[Epub] CrossRef
Multi-Omics and Machine Learning Analyses Reveal PIK3CG, PRKCD, and TRIM22 as Potential Markers of Poor Prognosis and Immune Activation in Glioblastoma
Myung-Hoon Han, Yung-Kyun Noh, Hyunkee Kim, Kyu Shik Kim, Dong-Hoon Kim, Un Suk Jung, Kyung Suk Lee, Mi Jung Kwon, Seoung Wan Chae, Kyueng-Whan Min
Journal of Korean Medical Science.2026;[Epub] CrossRef

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Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment for Elderly Glioblastoma Patients: Hye In Lee, Jina Kim, In Ah Kim, Joo Ho Lee, Jaeho Cho, Rifaquat Rahman, Geoffrey Fell, Chan Woo Wee, Hong In Yoon; Cancer Res Treat. 2025;57(2):378-386. Published online September 11, 2024; DOI: https://doi.org/10.4143/crt.2024.680

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics for elderly patients with glioblastoma (eGBM), and to compare the efficacy of different radiotherapy schedules.
Materials and Methods
This multi-institutional retrospective study included patients aged ≥ 65 years who underwent surgical resection followed by radiotherapy with or without temozolomide (TMZ) for newly diagnosed eGBM. Based on the significant factors identified in the multivariate analysis for overall survival (OS), the molecular GPA for eGBM (eGBM-molGPA) was established.
Results
A total of 334 and 239 patients who underwent conventionally fractionated radiotherapy (CFRT) and hypofractionated radiotherapy (HFRT) were included, respectively, with 86% of patients receiving TMZ-based chemoradiation. With a median follow-up of 17.4 months (range, 3.3 to 149.9 months), the median OS was 18.7 months for CFRT+TMZ group, 15.1 months for HFRT+TMZ group, and 10.4 months for radiotherapy alone group (CFRT+TMZ vs. HFRT+TMZ: hazard ratio [HR], 1.52; p < 0.001 and CFRT+TMZ vs. radiotherapy alone: HR, 2.52; p < 0.001). In a combined analysis with the NOA-08 and Nordic trials, CFRT+TMZ group exhibited the highest survival rates among all treatment groups. The eGBM-molGPA, which integrated four clinical and three molecular parameters, stratified patients into low-, intermediate-, and high-risk groups. CFRT+TMZ significantly improved OS compared to HFRT+TMZ or radiotherapy alone in the low-risk (p=0.023) and intermediate-risk groups (p < 0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p=0.770).
Conclusion
CFRT+TMZ may be more effective than HFRT+TMZ or radiotherapy alone for selected eGBM patients. The novel eGBM-molGPA model can guide treatment selection for this patient population.

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Hypofractionated vs. conventional fractionated radiotherapy in the temozolomide era for elderly patients with glioblastoma: a systematic review and meta-analysis by the Korean Society for Neuro-Oncology
Eunji Kim, Hye In Lee, Tae Hoon Roh, Young Zoon Kim, Do Hoon Lim, Se Jin Cho, Kihwan Hwang, Chan Woo Wee
Journal of Neuro-Oncology.2026;[Epub] CrossRef
Comparative analysis of outcome, recurrence patterns, and dosimetry in glioblastoma patients treated according to RTOG versus EORTC contouring guidelines
Gero Wieger, Patricia Meixner, Alicia Bicu, Frederik M Glatting, Frank A Giordano, Arne Mathias Ruder
Neuro-Oncology Practice.2026; 13(2): 301. CrossRef
Efficacy and safety of hypofractionated radiotherapy for melanoma brain metastases: a retrospective study
Yacheng Wang, Heng Zhang, Zibo Tang, Dehua Kang, Weihao Xie, Xiaoshi Zhang, Lixia Lu
Frontiers in Oncology.2026;[Epub] CrossRef
Hypofractionated MR-guided radiotherapy for glioblastoma: Institutional online adaptive workflow using MR-linac
Alonso La Rosa, Giorgia Yang, Beatriz Moreno, Laura Zaragoza, Inmaculada Navarro, Concepción Huertas, Carlos Ferrer, Raúl Matute, Ana Castaño, Patricia Arroyo, Beatriz Sánchez, Daniel Camacho, Silvia Lago, Juan Camilo Urrea, Moisés Sáez, Rosa Morera
Medical Dosimetry.2026;[Epub] CrossRef

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Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study): Grace S. Ahn, Kihwan Hwang, Tae Min Kim, Chul Kee Park, Jong Hee Chang, Tae-Young Jung, Jin Hee Kim, Do-Hyun Nam, Se-Hyuk Kim, Heon Yoo, Yong-Kil Hong, Eun-Young Kim, Dong-Eun Lee, Jungnam Joo, Yu Jung Kim, Gheeyoung Choe, Byung Se Choi, Seok-Gu Kang, Jeong Hoon Kim, Chae-Yong Kim; Cancer Res Treat. 2022;54(2):396-405. Published online July 6, 2021; DOI: https://doi.org/10.4143/crt.2021.393

Abstract PDF Supplementary Material PubReader ePub

Purpose
The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).
Materials and Methods
In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B).
Results
Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33).
Conclusion
The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Citations

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Sleep disturbances in brain tumors: a narrative review
Qiang Liang, Tianyi Hu, Tong Yang, Yawen Pan, Karen Spruyt, Xinyan Zhang, Qiang Li
Frontiers in Oncology.2025;[Epub] CrossRef
Achievements of international rare cancers networks and consortia in the neuro-oncology field
Vincenzo Di Nunno, Enrico Franceschi, Ahmed Idbaih
Current Opinion in Oncology.2024; 36(6): 554. CrossRef
Prevalence and management of sleep disturbance in adults with primary brain tumours and their caregivers: a systematic review
Jason A. Martin, Nicolas H. Hart, Natalie Bradford, Fiona Naumann, Mark B. Pinkham, Elizabeth P. Pinkham, Justin J. Holland
Journal of Neuro-Oncology.2023; 162(1): 25. CrossRef
Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats
Anastasia Strokotova, Dmitry Sokolov, Olga Molodykh, Elena Koldysheva, Evgenii Kliver, Victor Ushakov, Maxim Politko, Nadezhda Mikhnevich, Galina Kazanskaya, Svetlana Aidagulova, Elvira Grigorieva
Biomedical Reports.2023;[Epub] CrossRef

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Pediatric cancer

Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults: Hee Young Ju, Meerim Park, Jun Ah Lee, Hyeon Jin Park, Seog Yun Park, June Hyuk Kim, Hyun Guy Kang, Hee Chul Yang, Byung-Kiu Park; Cancer Res Treat. 2022;54(2):563-571. Published online June 14, 2021; DOI: https://doi.org/10.4143/crt.2021.178

Abstract PDF PubReader ePub

Purpose
No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults.
Materials and Methods
We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m² intravenously on day 1, irinotecan, 50 mg/m²/day intravenously on days 1-5, and temozolomide, 100 mg/m²/day orally on days 1-5.
Results
A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality.
Conclusion
The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Citations

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A Randomized, open-label, phase 2 study evaluating abemaciclib in combination with irinotecan and temozolomide in patients with relapsed or refractory Ewing sarcoma
Alba Rubio-San-Simon, Marilena Cesari, Melissa Bear, Cristina Mata, Ayumu Arakama, Holly Knoderer, Amanda Sykes, Jonathan Boss, Gertjan van Hal, Antoine Italiano
EJC Paediatric Oncology.2026; 7: 100525. CrossRef
ZC3H7B-BCOR Primary Breast Sarcoma: Diagnostic and Therapeutic Challenges of an Ultra-rare Sarcoma in an Uncommon Location
Miguel Esperança-Martins, António Syder Queiroz, Ana Gradil, Lia Bruno, Cátia Felício, Rui Bernardino, João Timóteo, Rita Rosado Santos, Ana Paula Marques Sousa, Cecília Melo-Alvim, Maria Inês Leite, Dolores López-Presa, Natália Alves, Brian A. Van Tine
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Scientific Reports.2025;[Epub] CrossRef
MGMT protein expression is a reliable predictive biomarker for temozolomide‐containing chemotherapy in osteosarcoma
Yoshinori Uchihara, Katsutsugu Umeda, Yosuke Yamada, Hiroaki Ito, Keiji Tasaka, Kiyotaka Isobe, Ryo Akazawa, Naoko Kawabata, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Takashi Noguchi, Akio Sakamoto, Yoshiki Arakawa, Ayumu Arakawa, Nobuyuki Yamamoto,
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Qian Chen, Kai Zheng, Ming Xu, Ning Yan, Gong Hai, Xiuchun Yu
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Irinotecan/temozolomide/vincristine

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Acetylenic Synthetic Betulin Derivatives Inhibit Akt and Erk Kinases Activity, Trigger Apoptosis and Suppress Proliferation of Neuroblastoma and Rhabdomyosarcoma Cell Lines
Sylwia K. Król, Ewa Bębenek, Magdalena Dmoszyńska-Graniczka, Adrianna Sławińska-Brych, Stanisław Boryczka, Andrzej Stepulak
International Journal of Molecular Sciences.2021; 22(22): 12299. CrossRef

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Review Article

Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors in Korea: Literature Review and Expert Opinion: Changhoon Yoo, Chung Ryul Oh, Seung-Tae Kim, Woo Kyun Bae, Hye-Jin Choi, Do-Youn Oh, Myung-Ah Lee, Baek-Yeol Ryoo; Cancer Res Treat. 2021;53(2):291-300. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.1233

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Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

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Cancers.2025; 17(18): 2992. CrossRef
Lanreotide acetate subcutaneous injection-induced granulomatous inflammation after surgery for neuroendocrine tumor of unknown primary origin
Susumu Saigusa, Hiroyuki Sakurai, Hiroyuki Fujikawa, Shuyo Watanabe, Kosuke Fukumochi, Yo Uchiyama, Tomomi Mohri, Yoshifumi Hirokawa, Koji Tanaka
International Cancer Conference Journal.2025; 15(1): 80. CrossRef
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H. Jeong, J. Shin, J.H. Jeong, K.-p. Kim, S.-M. Hong, Y.-i. Kim, J.-S. Ryu, B.-Y. Ryoo, C. Yoo
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Original Articles

Central nervous system

Mutant IDH1 Enhances Temozolomide Sensitivity via Regulation of the ATM/CHK2 Pathway in Glioma: Lin Lin, Jinquan Cai, Zixiao Tan, Xiangqi Meng, Ruiyan Li, Yang Li, Chuanlu Jiang; Cancer Res Treat. 2021;53(2):367-377. Published online October 13, 2020; DOI: https://doi.org/10.4143/crt.2020.506

Abstract PDF PubReader ePub

Purpose
Isocitrate dehydrogenase 1 (IDH1) mutations are the most common genetic abnormalities in low-grade gliomas and secondary glioblastomas. Glioma patients with these mutations had better clinical outcomes. However, the effect of IDH1 mutation on drug sensitivity is still under debate.
Materials and Methods
IDH1-R132H mutant cells were established by lentivirus. IDH1-R132H protein expression was confirmed by western blot. The expression of ataxia telangiectasia mutated (ATM) signaling pathway and apoptosis-related proteins were detected by immunofluorescence and western blot. Temozolomide (TMZ) induced cell apoptosis was detected by flow cytometry. Tumor cell proliferation was detected by Cell Counting Kit-8. In vivo nude mice were used to confirm the in vitro roles of IDH1 mutation.
Results
We established glioma cell lines that expressed IDH1-R132H mutation stably. We found that TMZ inhibited glioma cells proliferation more significantly in IDH1 mutant cells compared to wild type. The IC₅₀ of TMZ in IDH1-R132H mutant group was less than half that of wild-type group (p < 0.01). TMZ significantly induced more DNA damage (quantification of γH2AX expression in IDH1 mutation vs. wild type, p < 0.05) and apoptosis (quantification of AnnexinV+propidium iodide–cells in IDH1 mutation versus wild type, p < 0.01) in IDH1 mutant gliomas compared to wild-type gliomas. The ATM-associated DNA repair signal was impaired in IDH1 mutant cells. Inhibiting the ATM/checkpoint kinase 2DNA repair pathway further sensitized IDH1 mutant glioma cells to chemotherapy. We found that IDH1 mutation significantly inhibited tumor growth in vivo (the tumor size was analyzed statistically, p < 0.05). Moreover, we confirmed that gliomas with IDH1 mutation were more sensitive to TMZ in vivo compared to wild type significantly and the results were consistent with the in vitro experiment.
Conclusion
These results provide evidence that combination of TMZ and ATM inhibitor enhances the antitumor effect in IDH1 mutant gliomas.

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Hong-Chieh Tsai, Kuo-Chen Wei, Pin-Yuan Chen, Chiung-Yin Huang, Ko-Ting Chen, Ya-Jui Lin, Hsiao-Wei Cheng, Yi-Rou Chen, Hsiang-Tsui Wang
Frontiers in Oncology.2021;[Epub] CrossRef

13,036 View
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Concurrent and Adjuvant Temozolomide for Newly Diagnosed Grade III Gliomas without 1p/19q Co-deletion: A Randomized, Open-Label, Phase 2 Study (KNOG-1101 Study): Kihwan Hwang, Tae Min Kim, Chul-Kee Park, Jong Hee Chang, Tae-Young Jung, Jin Hee Kim, Do-Hyun Nam, Se-Hyuk Kim, Heon Yoo, Yong-Kil Hong, Eun-Young Kim, Dong-Eun Lee, Jungnam Joo, Yu Jung Kim, Gheeyoung Choe, Byung Se Choi, Seok-Gu Kang, Jeong Hoon Kim, Chae-Yong Kim; Cancer Res Treat. 2020;52(2):505-515. Published online October 28, 2019; DOI: https://doi.org/10.4143/crt.2019.421

Abstract PDF PubReader ePub

Purpose
We investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.
Materials and Methods
This was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m²/day) followed by adjuvant temozolomide (150-200 mg/m²/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.
Results
The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.
Conclusion
Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

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Impact of upfront adjuvant chemoradiation on survival in patients with molecularly defined oligodendroglioma: the benefits of PCV over TMZ
Jordina Rincon-Torroella, Maureen Rakovec, Anita L. Kalluri, Kelly Jiang, Carly Weber-Levine, Megan Parker, Divyaansh Raj, Josh Materi, Sadra Sepehri, Abel Ferres, Karisa C. Schreck, Iban Aldecoa, Calixto-Hope G. Lucas, Haris I. Sair, Kristin J. Redmond,
Journal of Neuro-Oncology.2025; 171(1): 35. CrossRef
IDH mutant high-grade gliomas
Santosh Valvi, Maryam Fouladi, Michael J. Fisher, Nicholas G. Gottardo
Frontiers in Molecular Neuroscience.2025;[Epub] CrossRef
Multidisciplinary Management of Isocitrate Dehydrogenase–Mutated Gliomas in a Contemporary Molecularly Defined Era
Rupesh Kotecha, David Schiff, Arnab Chakravarti, Jessica L. Fleming, Paul D. Brown, Vinay K. Puduvalli, Michael A. Vogelbaum, Vinai Gondi, Marco Gallus, Hideho Okada, Minesh P. Mehta
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The IDH paradox: Meta-analysis of alkylating chemotherapy in IDH-wild type and -mutant lower grade gliomas
Connor J Kinslow, Soumyajit Roy, Fabio M Iwamoto, Paul D Brown, David M DeStephano, Peter D Canoll, Summer S Qureshi, Matthew Gallito, Michael B Sisti, Jeffrey N Bruce, David P Horowitz, Lisa A Kachnic, Alfred I Neugut, James B Yu, Minesh P Mehta, Simon K
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Cureus.2024;[Epub] CrossRef
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Grace S. Ahn, Kihwan Hwang, Tae Min Kim, Chul Kee Park, Jong Hee Chang, Tae-Young Jung, Jin Hee Kim, Do-Hyun Nam, Se-Hyuk Kim, Heon Yoo, Yong-Kil Hong, Eun-Young Kim, Dong-Eun Lee, Jungnam Joo, Yu Jung Kim, Gheeyoung Choe, Byung Se Choi, Seok-Gu Kang, Jeo
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High-Dose Metformin Plus Temozolomide Shows Increased Anti-tumor Effects in Glioblastoma In Vitro and In Vivo Compared with Monotherapy: Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang; Cancer Res Treat. 2018;50(4):1331-1342. Published online January 10, 2018; DOI: https://doi.org/10.4143/crt.2017.466

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo.
Materials and Methods
We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5×105 U87 cells and treatedwith metformin, TMZ, and the combination for 4weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway.
Results
The combination of TMZ and metformin showed higher cytotoxicity than single agents in U87, U251, and A172 cell lines. A combination of high-dose metformin and TMZ showed the highest apoptotic activity. The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression. The median survival of each group was 43.6, 55.2, 53.2, 65.2, and 71.3 days for control, metformin treatment (2 mg/25 g/day or 10 mg/25 g/day), TMZ treatment (15 mg/kg/day), combination treatment with low-dose metformin and TMZ, and combination treatment with high-dose metformin and TMZ, respectively. Expression of fatty acid synthase (FASN) was significantly decreased in tumor specimens treated with metformin and TMZ.
Conclusion
The combination of metformin and TMZ was superior to monotherapy using metformin or TMZ in terms of cell viability in vitro and survival in vivo. The combination of high-dose metformin and TMZ inhibited FASN expression in an orthotopic model. Inhibition of FASN might be a potential therapeutic target of GBM.

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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

Abstract PDF PubReader ePub

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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Frontiers in Neurology.2022;[Epub] CrossRef
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Journal of Clinical Medicine.2022; 11(20): 6052. CrossRef
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PLOS ONE.2021; 16(1): e0244275. CrossRef
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Alexandra McAleenan, Claire Kelly, Francesca Spiga, Ashleigh Kernohan, Hung-Yuan Cheng, Sarah Dawson, Lena Schmidt, Tomos Robinson, Sebastian Brandner, Claire L Faulkner, Christopher Wragg, Sarah Jefferies, Amy Howell, Luke Vale, Julian P T Higgins, Kathr
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Journal of Cancer Research and Clinical Oncology.2020; 146(11): 2817. CrossRef
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Oncotarget.2017; 8(12): 20354. CrossRef

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