Cancer Research and Treatment

Original Articles

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; Received September 27, 2024 Accepted November 8, 2024 Published online November 11, 2024; DOI: https://doi.org/10.4143/crt.2024.945 [Epub ahead of print]

Abstract PDF PubReader ePub: 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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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

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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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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The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-institutional Retrospective Study (KROG 18-11): Joo Ho Lee, Seung Hyuck Jeon, Chul-Kee Park, Sung-Hye Park, Hong In Yoon, Jong Hee Chang, Chang-Ok Suh, Su Jeong Kang, Do Hoon Lim, In Ah Kim, Jin Hee Kim, Jung Ho Im, Sung-Hwan Kim, Chan Woo Wee, Il Han Kim; Cancer Res Treat. 2022;54(1):65-74. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2021.142

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).
Materials and Methods
A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.
Results
The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).
Conclusion
This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

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Application and effect evaluation of microsurgical resection combined with intensity-modulated radiation therapy in the treatment of intracranial solitary fibrous tumor/hemangiopericytoma
Jingcheng Jiang, Xiaoqin Qu, Han Wang, Chao Zhang, Qingshan Deng, Xiaoping Xu, Jun Qiu, Lihua Qu, Yong Yi
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Development of an MRI‐Based Comprehensive Model Fusing Clinical, Radiomics and Deep Learning Models for Preoperative Histological Stratification in Intracranial Solitary Fibrous Tumor
Xiaohong Liang, Kaiqiang Tang, Xiaoai Ke, Jian Jiang, Shenglin Li, Caiqiang Xue, Juan Deng, Xianwang Liu, Cheng Yan, Mingzi Gao, Junlin Zhou, Liqin Zhao
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Intradural Extramedullary Solitary Fibrous Tumor of the Thoracic Spinal Cord
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Cureus.2021;[Epub] CrossRef

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Central nervous system

Survival, Prognostic Factors, and Volumetric Analysis of Extent of Resection for Anaplastic Gliomas: Je Beom Hong, Tae Hoon Roh, Seok-Gu Kang, Se Hoon Kim, Ju Hyung Moon, Eui Hyun Kim, Sung Soo Ahn, Hye Jin Choi, Jaeho Cho, Chang-Ok Suh, Jong Hee Chang; Cancer Res Treat. 2020;52(4):1041-1049. Published online April 23, 2020; DOI: https://doi.org/10.4143/crt.2020.057

Abstract PDF PubReader ePub

Purpose
The aim of this study is to evaluate the survival rate and prognostic factors of anaplastic gliomas according to the 2016 World Health Organization classification, including extent of resection (EOR) as measured by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) and the T2-weighted MRI.
Materials and Methods
The records of 113 patients with anaplastic glioma who were newly diagnosed at our institute between 2000 and 2013 were retrospectively reviewed. There were 62 cases (54.9%) of anaplastic astrocytoma, isocitrate dehydrogenase (IDH) wild-type (AAw), 18 cases (16.0%) of anaplastic astrocytoma, IDH-mutant, and 33 cases (29.2%) of anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted.
Results
The median overall survival (OS) was 48.4 months in the whole anaplastic glioma group and 21.5 months in AAw group. In multivariate analysis, age, preoperative Karnofsky Performance Scale score, O⁶-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative tumor volume, and EOR measured from the T2 MRI sequence were significant prognostic factors. The EOR cut-off point for OS measured in contrast-enhanced T1-weighted MRI and T2-weighted MRI were 99.96% and 85.64%, respectively.
Conclusions
We found that complete resection of the contrast-enhanced portion (99.96%) and more than 85.64% resection of the non-enhanced portion of the tumor have prognostic impacts on patient survival from anaplastic glioma.

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SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas
Peng Wang, Jingjing Zhang, Shuai He, Boan Xiao, Xiaobin Peng
Cancer Cell International.2020;[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,
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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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Jan Stepka, Mariusz Dotka, Maciej Kosiński, Piotr Suchecki, Maciej Hobot, Igor Piotrowski
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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
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Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline
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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
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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, Jeo
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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
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Effects of Postoperative Radiotherapy on Leptomeningeal Carcinomatosis or Dural Metastasis after Resection of Brain Metastases in Breast Cancer Patients: Boram Ha, Seung Yeun Chung, Yeon-Joo Kim, Ho-Shin Gwak, Jong Hee Chang, Sang Hyun Lee, In Hae Park, Keun Seok Lee, Seeyoun Lee, Tae Hyun Kim, Dae Yong Kim, Seok-Gu Kang, Chang-Ok Suh; Cancer Res Treat. 2017;49(3):748-758. Published online October 31, 2016; DOI: https://doi.org/10.4143/crt.2016.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer.
Materials and Methods
Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not.
Results
With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM.
Conclusion
WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

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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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