Cancer Research and Treatment

Original Articles

CNS cancer

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

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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

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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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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.

Citations

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