Cancer Research and Treatment

Original Articles

CNS cancer

Association between Levetiracetam Use and Survival in Patients with Glioblastoma: A Nationwide Population-Based Study: Yeonhu Lee, Eunyoung Lee, Tae Hoon Roh, Se-Hyuk Kim; Cancer Res Treat. 2025;57(2):369-377. Published online September 6, 2024; DOI: https://doi.org/10.4143/crt.2024.355

Abstract PDF PubReader ePub: Purpose
This study aimed to investigate whether levetiracetam (LEV), the most used antiepileptic drug, influences survival in patients with glioblastoma (GBM), using a national database.
Materials and Methods
This study used data from the Korea Health Insurance Review and Assessment database. Patients diagnosed with GBM between 2007-2018 treated with standard therapy were included. The study population was divided into long-term (≥ 60 days) and short-term (< 30 days) LEV groups. A separate long-term valproic acid (VPA) group (≥ 60 days) was identified for comparison. Demographics, disease characteristics, and treatment parameters were collected. Kaplan-Meier method and Cox regression were used to compare survival outcomes between the groups.
Results
Overall, 2,971 patients were included, with 1,319 and 1,652 in the short-term and long-term LEV groups, respectively. The median overall survival (OS) for the entire population was 19.15 months post-surgery. Kaplan-Meier analysis revealed a significantly longer median OS in the long-term LEV group versus the short-term LEV group. After adjusting for confounders, Cox proportional hazard analysis revealed an association of long-term LEV use with improved survival, which was also observed in a subgroup analysis of patients without preoperative seizure history. The long-term LEV group demonstrated longer median OS, compared with the long-term VPA group.
Conclusion
Our nationwide population-based study found an association between long-term LEV use and improved survival in patients with GBM, regardless of preoperative seizure history. Prospective studies are needed to validate these findings and investigate the potential impact of LEV on the survival outcomes of patients with GBM.

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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.

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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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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
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
Journal of Clinical Oncology.2024; 42(21): 2588. CrossRef
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
Neuro-Oncology.2024; 26(10): 1839. CrossRef
The Role of Systemic Therapies in the Treatment of Grades 1-4 Gliomas
Jan Stepka, Mariusz Dotka, Maciej Kosiński, Piotr Suchecki, Maciej Hobot, Igor Piotrowski
Cureus.2024;[Epub] CrossRef
Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline
Nimish A. Mohile, Hans Messersmith, Na Tosha Gatson, Andreas F. Hottinger, Andrew Lassman, Jordan Morton, Douglas Ney, Phioanh Leia Nghiemphu, Adriana Olar, Jeffery Olson, James Perry, Jana Portnow, David Schiff, Anne Shannon, Helen A. Shih, Roy Strowd, M
Journal of Clinical Oncology.2022; 40(4): 403. CrossRef
Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline
Nimish A Mohile, Hans Messersmith, Na Tosha N Gatson, Andreas F Hottinger, Andrew B Lassman, Jordan Morton, Douglas Ney, Phioanh Leia Nghiemphu, Adriana Olar, Jeffery Olson, James Perry, Jana Portnow, David Schiff, Anne Shannon, Helen A Shih, Roy Strowd,
Neuro-Oncology.2022; 24(3): 358. CrossRef
Executive summary of American Radium Society’s appropriate use criteria for the postoperative management of lower grade gliomas
Martin C. Tom, Michael T. Milano, Samuel T. Chao, Scott G. Soltys, Jonathan P.S. Knisely, Arjun Sahgal, Seema Nagpal, Simon S. Lo, Siavash Jabbari, Tony J.C. Wang, Manmeet S. Ahluwalia, Marian Simonson, Joshua D. Palmer, Melanie Hayden Gephart, Lia M. Hal
Radiotherapy and Oncology.2022; 170: 79. CrossRef
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, Jeo
Cancer Research and Treatment.2022; 54(2): 396. CrossRef
The Risk of Heart Disease-Related Death Among Anaplastic Astrocytoma Patients After Chemotherapy: A SEER Population-Based Analysis
Qi Lin, Jia-Hao Bao, Fei Xue, Jia-Jun Qin, Zhen Chen, Zhong-Rong Chen, Chao Li, Yi-Xuan Yan, Jin Fu, Zhao-Li Shen, Xian-Zhen Chen
Frontiers in Oncology.2022;[Epub] CrossRef
Association between a prior cancer history and prognosis in adult patients with high‑grade glioma
Dongjie He, Peiwen Wu, Gaiyan Li, Siying Zhu, Qiming Wang, Qiuju Shao, Hao Chang
Journal of Clinical Neuroscience.2022; 106: 20. CrossRef

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Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma: Young-Bem Se, Seung Hyun Kim, Ji Young Kim, Ja Eun Kim, Yun-Sik Dho, Jin Wook Kim, Yong Hwy Kim, Hyun Goo Woo, Se-Hyuk Kim, Shin-Hyuk Kang, Hak Jae Kim, Tae Min Kim, Soon-Tae Lee, Seung Hong Choi, Sung-Hye Park, Il Han Kim, Dong Gyu Kim, Chul-Kee Park; Cancer Res Treat. 2017;49(2):387-398. Published online July 19, 2016; DOI: https://doi.org/10.4143/crt.2016.106

Abstract PDF Supplementary Material PubReader ePub

Purpose
Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance.
Materials and Methods
The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis.
Results
The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith lowHOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified.
Conclusion
The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

Citations

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Intratumoral IL-12 delivery via mesenchymal stem cells combined with PD-1 blockade leads to long-term antitumor immunity in a mouse glioblastoma model
Junseong Park, Soon A. Park, Yoon-Seob Kim, Dokyeong Kim, Sun Shin, Sug Hyung Lee, Sin-Soo Jeun, Yeun-Jun Chung, Stephen Ahn
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