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 9, 2024 Published online November 11, 2024; DOI: https://doi.org/10.4143/crt.2024.945 [Accepted]

Abstract PDF: Purpose
To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).
Materials and Methods
Newly diagnosed patients with IDH 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

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.

Citations

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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
Journal of Magnetic Resonance Imaging.2024; 60(2): 523. CrossRef
Meningeal Solitary Fibrous Tumor: A Single-Center Retrospective Cohort Study
Siyer Roohani, Yasemin Alberti, Maximilian Mirwald, Felix Ehret, Carmen Stromberger, Soleiman Fabris Roohani, Katja Bender, Anne Flörcken, Sven Märdian, Daniel Zips, David Kaul, Manish Charan
Sarcoma.2024; 2024: 1. CrossRef
Repeated Radiation Therapy of Recurrent Solitary Fibrous Tumors of the Brain: A Medical Case History Over 20 Years
Anna Carla Piccardo, Sabrina Gurdschinski, Sybille Spieker, Christof Renner, Piotr Czapiewski, Markus Wösle, I. Frank Ciernik
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Intracranial solitary fibrous tumors: Clinical, radiological, and histopathological insights along with review of literature
Adil Aziz Khan, Sana Ahuja, Dipanker Singh Mankotia, Sufian Zaheer
Pathology - Research and Practice.2024; 260: 155456. CrossRef
Central nervous system solitary fibrous tumors: Case series in accordance with the WHO 2021 reclassification. Framework for patient surveillance
V. Matthijs, R. Beckers, C. Vanden Broecke, F. Dedeurwaerdere, J. Van Dorpe, D. Vanhauwaert, G. Hallaert
Acta Neurochirurgica.2024;[Epub] CrossRef
Recurrence of Solitary Fibrous Tumor in the Spinal Cord Following Gross Total and Subtotal Resection: A Case Report of Recurrence 19 Years of Post-total Resection and Systematic Literature Review
Satoka SHIDOH, Kazutoshi HIDA, Yoshitaka ODA, Toru SASAMORI, Prabin SHRESTHA, Jangbo LEE, Satoshi YAMAGUCHI
NMC Case Report Journal.2024; 11: 297. CrossRef
The Role of Radical Radiotherapy in Sinonasal Myopericytoma: A Case Report and Literature Overview
Anna Merlotti, Stefania Martini, Riccardo Vigna Taglianti, Alessia Reali, Giuseppe Signorini, Silvana Parisi, Francesca De Felice
EMJ Oncology.2023;[Epub] CrossRef
Intracranial Solitary Fibrous Tumour Management: A French Multicentre Retrospective Study
Marine Lottin, Alexandre Escande, Luc Bauchet, Marie Albert-Thananayagam, Maël Barthoulot, Matthieu Peyre, Mathieu Boone, Sonia Zouaoui, Jacques Guyotat, Guillaume Penchet, Johan Pallud, Henry Dufour, Evelyne Emery, Michel Lefranc, Sébastien Freppel, Houm
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Solitary fibrous tumor of the central nervous system invading and penetrating the skull: A case report
Qiyan Lin, Jiabin Zhu, Xiaofeng Zhang
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Impact of extent of resection and postoperative radiotherapy on survival outcomes in intracranial solitary fibrous tumors: a systematic review and meta-analysis
Sae Min Kwon, Min Kyun Na, Kyu-Sun Choi, Tae Ho Lim, Hyungoo Shin, Juncheol Lee, Heekyung Lee, Wonhee Kim, Youngsuk Cho, Jae Guk Kim, Chiwon Ahn, Bo-Hyoung Jang
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Radiotherapy for rare primary brain tumors
E. Mesny, P. Lesueur
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Salah-Edine Safi, Julie Godfrain, Herbert Rooijakkers, Frederic Collignon, Mario Ganau
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Surgical Management of Craniospinal Axis Solitary Fibrous Tumors: A Single-Institution Case Series and Comprehensive Review of the Literature
Anthony J. Piscopo, A. J. Chowdhury, Nahom Teferi, Sarah Lee, Meron Challa, Michael Petronek, Kathryn Eschbacher, Girish Bathla, John M. Buatti, Patrick Hitchon
Neurosurgery.2023;[Epub] CrossRef
Clinical Features, Management, and Prognostic Factors of Intracranial Solitary Fibrous Tumor
Jingdian Liu, Sisi Wu, Kai Zhao, Junwen Wang, Kai Shu, Ting Lei
Frontiers in Oncology.2022;[Epub] CrossRef
Toward Better Understanding and Management of Solitary Fibrous Tumor
Karineh Kazazian, Elizabeth G. Demicco, Marc de Perrot, Dirk Strauss, Carol J. Swallow
Surgical Oncology Clinics of North America.2022; 31(3): 459. CrossRef
Effect of Different Treatments for Intracranial Solitary Fibrous Tumors: Retrospective Analysis of 31 Patients
Qinghua Li, Wenshuai Deng, Peng Sun
World Neurosurgery.2022; 166: e60. CrossRef
Sixteen-Year Follow-Up in a Cavernous Sinus Hemangiopericytoma: Improved Outcomes over Radiotherapy Advances
Beatrice Detti, Lilia Bardoscia, Antonio Rosario Pisani, Salvatore Cozzi, Manuele Roghi, Paolo Mammucci, Angela Sardaro
Brain Sciences.2022; 12(9): 1209. CrossRef
Solitary Fibrous Tumor of the Jugular Foramen: A Case Report and Review of the Histopathologic Classification
Mallory Raymond, Philip Ryan Elvis, Tiffany Baker, William Alexander Vandergrift, Theodore McRackan
Otology & Neurotology.2022; 43(10): e1208. CrossRef
A Comprehensive Review on Solitary Fibrous Tumor: New Insights for New Horizons
Javier Martin-Broto, Jose L. Mondaza-Hernandez, David S. Moura, Nadia Hindi
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Intradural Extramedullary Solitary Fibrous Tumor of the Thoracic Spinal Cord
Zachary T Olmsted, Joanna Tabor, Omer Doron, Hossein Hosseini, Daniel Schneider, Ross Green, Samuel J Wahl, Daniel M Scuibba, Randy S D'Amico
Cureus.2021;[Epub] CrossRef

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Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae: Joo Ho Lee, Keun-Yong Eom, Ji Hoon Phi, Chul-Kee Park, Seung Ki Kim, Byung-Kyu Cho, Tae Min Kim, Dae Seog Heo, Kyung Taek Hong, Jung Yoon Choi, Hyoung Jin Kang, Hee Young Shin, Seung Hong Choi, Soon Tae Lee, Sung Hye Park, Kyu-Chang Wang, Il Han Kim; Cancer Res Treat. 2021;53(4):983-990. Published online January 13, 2021; DOI: https://doi.org/10.4143/crt.2020.1052

Abstract PDF PubReader ePub

Purpose
We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.
Materials and Methods
Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.
Results
The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.
Conclusion
De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Citations

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NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors
Eric Eunshik Kim, Chul-Kee Park, Seung-Ki Kim, Ji Hoon Phi, Sun Ha Paek, Jung Yoon Choi, Hyoung Jin Kang, Joo Ho Lee, Jae Kyung Won, Hongseok Yun, Sung-Hye Park
Acta Neuropathologica Communications.2024;[Epub] CrossRef
Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up
Masayuki Kanamori, Shunji Mugikura, Osamu Iizuka, Naoko Mori, Yoshiteru Shimoda, Ichiyo Shibahara, Rei Umezawa, Keiichi Jingu, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Kyoko Suzuki, Hidenori Endo
Journal of Neuro-Oncology.2024; 170(1): 173. CrossRef
Excluding prepontine cistern from whole ventricle radiotherapy target volume in localized germinoma
Hyejo Ryu, Joo Ho Lee
Radiation Oncology Journal.2023; 41(1): 48. CrossRef
Intracranial Germinomas: Diagnosis, Pathogenesis, Clinical Presentation, and Management
Natalia Kremenevski, Michael Buchfelder, Nirjhar Hore
Current Oncology Reports.2023; 25(7): 765. CrossRef
Proton therapy for pediatric diencephalic tumors
Adam J. Grippin, Susan L. McGovern
Frontiers in Oncology.2023;[Epub] CrossRef
Intracranial Germinoma—Association between Delayed Diagnosis, Altered Clinical Manifestations, and Prognosis
Iwona Jabłońska, Marcin Goławski, Elżbieta Nowicka, Katarzyna Drosik-Rutowicz, Anna Trybus, Rafał Tarnawski, Marcin Miszczyk
Cancers.2023; 15(10): 2789. CrossRef
Outcomes of intracranial germinoma—A retrospective multinational Asian study on effect of clinical presentation and differential treatment strategies
Kyung-Nam Koh, Ru Xin Wong, Dong-Eun Lee, Jung Woo Han, Hwa Kyung Byun, Hong In Yoon, Dong-Seok Kim, Chuhl Joo Lyu, Hyoung Jin Kang, Kyung Taek Hong, Joo Ho Lee, Il Han Kim, Ji Hoon Phi, Seung-Ki Kim, Tai-Tong Wong, Hsin-Lun Lee, I-Chun Lai, Yu-Mei Kang,
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Photon versus proton whole ventricular radiotherapy for non‐germinomatous germ cell tumors: A report from the Children's Oncology Group
David Y. Mak, Zain Siddiqui, Zhihui Amy Liu, Hitesh Dama, Shannon M. MacDonald, Shengjie Wu, Erin S. Murphy, Matthew D. Hall, Victor Malkov, Arzu Onar‐Thomas, Sameera Ahmed, Girish Dhall, Derek S. Tsang
Pediatric Blood & Cancer.2022;[Epub] CrossRef
Factors Influencing Craniospinal Relapse of Intracranial Germinoma After Complete Remission
Takao Tsurubuchi, Kei Hara, Shingo Takano, Ai Muroi, Hiroko Fukushima, Masashi Mizumoto, Noriaki Sakamoto, Masahide Matsuda, Hiroyoshi Akutsu, Hideyuki Sakurai, Eiichi Ishikawa
World Neurosurgery.2022; 166: e325. CrossRef
Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma
Cristina Ilcus, Horatiu Silaghi, Carmen Emanuela Georgescu, Carmen Georgiu, Anca Ileana Ciurea, Simona Delia Nicoara, Cristina Alina Silaghi
Journal of Personalized Medicine.2021; 11(7): 661. CrossRef

10,813 View
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10 Web of Science
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Central nervous system

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma: Changhee Park, Tae Min Kim, Jeong Mo Bae, Hongseok Yun, Jin Wook Kim, Seung Hong Choi, Soon-Tae Lee, Joo Ho Lee, Sung-Hye Park, Chul-Kee Park; Cancer Res Treat. 2021;53(2):389-398. Published online November 9, 2020; DOI: https://doi.org/10.4143/crt.2020.694

Abstract PDF Supplementary Material PubReader ePub

Purpose
The treatment outcomes and genomic profiles of diffuse midline glioma (DMG) in adult patients are rarely characterized. We performed a retrospective study to evaluate the clinicogenomic profiles of adult patients with brain DMG.
Materials and Methods
Patients aged ≥ 18 years diagnosed with brain DMG at Seoul National University Hospital were included. The clinicopathological parameters, treatment outcomes, survival, and genomic profiles using 82-gene targeted next-generation sequencing (NGS) were analyzed. The 6-month progression-free survival (PFS6) after radiotherapy and overall survival (OS) were evaluated.
Results
Thirty-three patients with H3-mutant brain DMG were identified. The median OS from diagnosis was 21.8 months (95% confidence interval [CI], 13.2 to not available [NA]) and involvement of the ponto-medullary area tended to have poor OS (median OS, 20.4 months [95% CI, 9.3 to NA] vs. 43.6 months [95% CI, 18.2 to NA]; p=0.07). Twenty-four patients (72.7%) received radiotherapy with or without temozolomide. The PFS6 rate was 83.3% (n=20). Patients without progression at 6 months showed significantly prolonged OS compared with those with progression at 6 months (median OS, 24.9 months [95% CI, 20.4 to NA] vs. 10.8 months [95% CI, 4.0 to NA]; p=0.02, respectively). Targeted NGS was performed in 13 patients with DMG, among whom nine (69.2%) harbored concurrent TP53 mutation. Two patients (DMG14 and DMG23) with PIK3CA^R38S+E545K and KRAS^G12A mutations received matched therapies. Patient DMG14 received sirolimus with a PFS of 8.4 months.
Conclusion
PFS6 after radiotherapy was associated with prolonged survival in adult patients with DMG. Genome-based matched therapy may be an encouraging approach for progressive adult patients with DMG.

Citations

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The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study
Vincenzo Di Nunno, Giuseppe Lombardi, Matteo Simonelli, Giuseppe Minniti, Angela Mastronuzzi, Valentina Di Ruscio, Martina Corrà, Marta Padovan, Marta Maccari, Mario Caccese, Giorgia Simonetti, Arianna Berlendis, Mariangela Farinotti, Bianca Pollo, Manila
Journal of Neuro-Oncology.2024; 167(1): 145. CrossRef
Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort
Nobuhide Hayashi, Junya Fukai, Hirokazu Nakatogawa, Hiroshi Kawaji, Ema Yoshioka, Yoshinori Kodama, Kosuke Nakajo, Takehiro Uda, Kentaro Naito, Noriyuki Kijima, Yoshiko Okita, Naoki Kagawa, Yoshinobu Takahashi, Naoya Hashimoto, Hideyuki Arita, Koji Takano
Acta Neuropathologica Communications.2024;[Epub] CrossRef
How to treat histone 3 altered gliomas: molecular landscape and therapeutic developments
Vincenzo Di Nunno, Enrico Franceschi, Lidia Gatto, Alicia Tosoni, Stefania Bartolini, Alba Ariela Brandes
Expert Review of Clinical Pharmacology.2023; 16(1): 17. CrossRef
Genomic profiles of IDH-mutant gliomas: MYCN-amplified IDH-mutant astrocytoma had the worst prognosis
Kwanghoon Lee, Seong-Ik Kim, Eric Eunshik Kim, Yu-Mi Shim, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Hongseok Yun, Hyunju Lee, Sung-Hye Park
Scientific Reports.2023;[Epub] CrossRef
Radiotherapy and radio‐sensitization in H3K27M‐mutated diffuse midline gliomas
Chao Liu, Shuwen Kuang, Lei Wu, Quan Cheng, Xuan Gong, Jun Wu, Longbo Zhang
CNS Neuroscience & Therapeutics.2023; 29(7): 1721. CrossRef
Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy
A. Knight, P. Horsley, A. Yuile, J. Yim, M. Suh, V. Venketesha, M. Kastelan, H. Wheeler, M. Back
Journal of Neuro-Oncology.2023; 163(1): 281. CrossRef
Differences in survival prognosticators between children and adults with H3K27M‐mutant diffuse midline glioma
Xuan Gong, Shuwen Kuang, Dongfeng Deng, Jun Wu, Longbo Zhang, Chao Liu
CNS Neuroscience & Therapeutics.2023; 29(12): 3863. CrossRef
Adult spinal cord diffuse midline glioma, H3 K27-altered mimics symptoms of central nervous system infection: a case report
Xue Chen, Yi Li, Hui Bu, YueLi Zou, JunYing He, Hu Liu
Frontiers in Neurology.2023;[Epub] CrossRef
Clinicogenetic characteristics and the effect of radiation on the neural stem cell niche in subventricular zone-contacting glioblastoma
Jee Ye Kahng, Byung-Hee Kang, Soon-Tae Lee, Seung Hong Choi, Tae Min Kim, Chul-Kee Park, Jae-Kyung Won, Sung-Hye Park, Jaeman Son, Joo Ho Lee
Radiotherapy and Oncology.2023; 186: 109800. CrossRef
H3 K27M-Altered Diffuse Midline Gliomas: A Review
Karol Wiśniewski, Andrew Ghaly, Kate Drummond, Andreas Fahlstrӧm
Indian Journal of Neurosurgery.2023; 12(02): 104. CrossRef
Adult diffuse midline gliomas H3 K27-altered: review of a redefined entity
Carlos Axel López-Pérez, Xochitl Franco-Mojica, Ricardo Villanueva-Gaona, Alexandra Díaz-Alba, Marco Antonio Rodríguez-Florido, Victor Garcia Navarro
Journal of Neuro-Oncology.2022; 158(3): 369. CrossRef
H3K27M-Altered Diffuse Midline Gliomas Among Adult Patients: A Systematic Review of Clinical Features and Survival Analysis
Othman Bin-Alamer, Adrian E. Jimenez, Tej D. Azad, Chetan Bettegowda, Debraj Mukherjee
World Neurosurgery.2022; 165: e251. CrossRef
Molecular profile and clinical features of patients with gliomas using a broad targeted next generation‑sequencing panel
Ourania Romanidou, Paraskevi Apostolou, Kyriakos Kouvelakis, Kyriakos Tsangaras, Alexia Eliades, Achilleas Achilleos, Charalambos Loizides, Christos Lemesios, Marios Ioannides, Elena Kypri, George Koumbaris, Kyriaki Papadopoulou, Athanasios Papathanasiou,
Oncology Letters.2022;[Epub] CrossRef

8,433 View
229 Download
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A Nationwide, Population-Based Epidemiology Study of Primary Central Nervous System Tumors in Korea, 2007-2016: A Comparison with United States Data: Ho Kang, Sang Woo Song, Johyun Ha, Young-Joo Won, Chul-Kee Park, Heon Yoo, Kyu-Won Jung; Cancer Res Treat. 2021;53(2):355-366. Published online October 7, 2020; DOI: https://doi.org/10.4143/crt.2020.847

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to determine the epidemiologic characteristics and survival of patients with primary brain and other central nervous system (CNS) tumors in Korea and to compare our findings with those from the United States.
Materials and Methods
We collected data on primary brain and CNS tumors diagnosed between 2007 and 2016 from the Korea Central Cancer Registry. The age-standardized incidence rates (ASRs) and 5-year relative survival rates (RSRs) were evaluated. We applied the classification and definitions of the Central Brain Tumor Registry of the United States to our analysis for direct comparison with United States data.
Results
A total of 115,050 primary brain and CNS tumors were identified, and the ASR of all tumors was 22.01 per 100,000 individuals, which was lower than the 23.41 in the United States. However, the ASR of malignant tumors was significantly lower herein (4.27) than in the United States (7.08). Meningeal tumors were the most common histologic group among all tumors (ASR, 8.32). The 5-year RSR of all primary brain and other CNS tumors was 86.4%, and that of all malignant tumors was 44.1%, which was higher than the 35.8% observed in the United States. Among malignant tumors, glioblastomas had the lowest 5-year RSR (12.1%).
Conclusion
In Korea, malignant brain and other CNS tumors have a lower incidence and better survival outcome.

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Peter Y M Woo, Stephen Yau, Tai-Chung Lam, Jenny K S Pu, Lai-Fung Li, Louisa C Y Lui, Danny T M Chan, Herbert H F Loong, Michael W Y Lee, Rebecca Yeung, Carol C H Kwok, Siu-Kie Au, Tze-Ching Tan, Amanda N C Kan, Tony K T Chan, Calvin H K Mak, Henry K F Ma
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Intracranial Germinomas: Diagnosis, Pathogenesis, Clinical Presentation, and Management
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Interim Tumor Progression and Volumetric Changes of Surgical Cavities during the Surgery-to-Radiotherapy Interval in Anaplastic Gliomas: Implications for Additional Pre-radiotherapy Magnetic Resonance Imaging: Chan Woo Wee, Il Han Kim, Chul-Kee Park, Jin Wook Kim; Cancer Res Treat. 2020;52(2):524-529. Published online October 31, 2019; DOI: https://doi.org/10.4143/crt.2019.520

Abstract PDF PubReader ePub

Purpose
This study was designed to investigate the incidence of interim disease progression (IPD) and volumetric changes of the surgical cavity (SC) during the surgery-to-radiotherapy interval (SRI), and eventually assess the value of magnetic resonance imaging (MRI) at the time of radiotherapy (RT) planning in newly diagnosed anaplastic gliomas.
Materials and Methods
Among 195 anaplastic glioma patients who underwent RT, 121 were evaluable with two separate MRIs during SRI. The presence of IPD was determined using the updated Response Assessment in Neuro-Oncology size criteria. In 84 patients who underwent surgical resection, each SC was contoured by a radiation oncologist and the volumetric changes of the SCs were calculated between the two separate MRIs. Daily rate of change in the SC volume was calculated assuming an exponential and linear change.
Results
Five of 121 patients (4.13%) demonstrated IPD during SRI, and the incidence was significantly higher in patients undergoing biopsy (vs. surgical resection, 12.9% vs. 1.1%, p=0.015) and in patients with remnant contrast-enhancing tumor after surgery (15.8 vs. 2.0%, p=0.027). The mean daily rate of absolute change in SC was 1.06% (95% confidence interval [CI], 0.89 to 1.23) and 0.89% (95% CI, 0.77 to 1.02) according to the exponential and linear model, respectively. The expected mean volumetric change at 2 weeks were 16.64% (95% CI, 13.77 to 19.52) and 12.51% (95% CI, 10.77 to 14.26), respectively.
Conclusion
IPD during the SRI is rare in surgically resected anaplastic gliomas. However, pre-RT MRI is essential for accurate RT-target delineation and disease evaluation for patients initiating RT beyond postoperative 2 weeks and undergoing biopsy, respectively.

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Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma—an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial
Stefan Dietzsch, Annett Braesigk, Clemens Seidel, Julia Remmele, Ralf Kitzing, Tina Schlender, Martin Mynarek, Dirk Geismar, Karolina Jablonska, Rudolf Schwarz, Montserrat Pazos, Damien C. Weber, Silke Frick, Kristin Gurtner, Christiane Matuschek, Semi Be
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Jun Liu, Xiaodong Li, Xueping Leng, Bo Zhong, Yanhong Liu, Liang Liu, Mohammad Farukh Hashmi
Contrast Media & Molecular Imaging.2022;[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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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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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
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Impact of upfront adjuvant chemoradiation on survival in patients with molecularly defined oligodendroglioma: the benefits of PCV over TMZ
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Executive summary of American Radium Society’s appropriate use criteria for the postoperative management of lower grade gliomas
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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
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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.

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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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Dihydropyrimidinase‐like 2 can serve as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia
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Zong-Qing Zheng, Gui-Qiang Yuan, Guo-Guo Zhang, Qian-Qian Nie, Zhong Wang
Discover Oncology.2023;[Epub] CrossRef
HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury
Xiang-Long Li, Bin Wang, Fu-Bing Yang, Li-Gang Chen, Jian You
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U Sangeetha Shenoy, Divya Adiga, Shama Prasada Kabekkodu, Keith D Hunter, Raghu Radhakrishnan
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High expression ofHOXA4in patients with glioma indicates unfavorable clinical outcomes
Zhenghong Yu, Zhendong Liu, Xiaoyu Lian, Xingbo Cheng, Binfeng Liu, Bo Zhang, Hongbo Wang, Jialin Wang, Ang Li, Zhishuai Ren, Bo Pang, Rongjun Qian, Yanzheng Gao
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C. Kong, Z. Zhu, Y. Li, P. Xue, L. Chen
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Srikumar Chakravarthi, Barani Karikalan
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Céline S. Gonçalves, Elisa Le Boiteux, Philippe Arnaud, Bruno M. Costa
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Expression Profile and Prognostic Values of HOXA Family Members in Laryngeal Squamous Cell Cancer
Jinyun Li, Meng Ye, Chongchang Zhou
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Methylation in HOX Clusters and Its Applications in Cancer Therapy
Ana Paço, Simone Aparecida de Bessa Garcia, Renata Freitas
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Zewei Tu, Lei Wu, Peng Wang, Qing Hu, Chuming Tao, Kuangxun Li, Kai Huang, Xingen Zhu
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Lu‐Yan Shen, Ting Zhou, Ya‐Bing Du, Qi Shi, Ke‐Neng Chen
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Youwei Zhang, Yuan Yuan, Yang Li, Peiying Zhang, Pingsheng Chen, Sanyuan Sun
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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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Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma: Yongjun Cha, Yu Jung Kim, Se-Hoon Lee, Tae-Min Kim, Seung Hong Choi, Dong-Wan Kim, Chul-Kee Park, Il Han Kim, Jee Hyun Kim, Eunhee Kim, Byungse Choi, Chae-Yong Kim, In Ah Kim, Dae Seog Heo; Cancer Res Treat. 2017;49(1):129-140. Published online May 18, 2016; DOI: https://doi.org/10.4143/crt.2015.466

Abstract PDF PubReader ePub

Purpose
Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established.
Materials and Methods
Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups.
Results
Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups.
Conclusion
In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.

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