Cancer Research and Treatment

Original Articles

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

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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.

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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
Genetic alteration analysis of non-pediatric diffuse midline glioma, H3 K27-altered
Hanbin Jang, Seyoung Moon, Hyun Jung Kwon, Sejoon Lee, Gheeyoung Choe, Kyu Sang Lee
Human Pathology.2024; 154: 105709. 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

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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
Strahlentherapie und Onkologie.2022; 198(3): 282. CrossRef
Effect of 3D Slicer Preoperative Planning and Intraoperative Guidance with Mobile Phone Virtual Reality Technology on Brain Glioma Surgery
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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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
Biomedicine & Pharmacotherapy.2024; 173: 115790. CrossRef
Dihydropyrimidinase‐like 2 can serve as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia
Fenglin Li, Qing Ling, Jiaying Lian, Ying Chen, Chao Hu, Min Yang, Xiang Zhang, Chenying Li, Shihui Mao, Wenle Ye, Xia Li, Xiangjie Lin, Wenwen Wei, Xin Huang, Jiajia Pan, Yu Qian, Jinghan Wang, Ying Lu, Jie Jin
Cancer Medicine.2023; 12(7): 8319. CrossRef
Development and validation of a predictive model in diagnosis and prognosis of primary glioblastoma patients based on Homeobox A family
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
Neural Regeneration Research.2022; 17(5): 1096. CrossRef
Molecular implications of HOX genes targeting multiple signaling pathways in cancer
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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Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review
Sara Momtazmanesh, Nima Rezaei
Frontiers in Oncology.2021;[Epub] CrossRef
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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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N6-Methylandenosine-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Lower-Grade Glioma Patients
Zewei Tu, Lei Wu, Peng Wang, Qing Hu, Chuming Tao, Kuangxun Li, Kai Huang, Xingen Zhu
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Oncologic and Functional Outcomes after Partial Nephrectomy Versus Radical Nephrectomy in T1b Renal Cell Carcinoma: A Multicenter, Matched Case-Control Study in Korean Patients: Hoon Ah Jang, Jin Wook Kim, Seok Soo Byun, Sung Hoo Hong, Young Jun Kim, Young Hyun Park, Kyung Suk Yang, Seok Cho, Jun Cheon, Seok Ho Kang; Cancer Res Treat. 2016;48(2):612-620. Published online June 5, 2015; DOI: https://doi.org/10.4143/crt.2014.122

Abstract PDF PubReader ePub

Purpose
The study was to compare the oncologic and functional outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for pathologically proven T1b renal cell carcinoma using pair-matched groups.
Materials and Methods
We reviewed our prospectively maintained database for RN and PN in T1b renal tumors surgically treated between 1999 and 2011 at five institutions in Korea. Of 611 patients treated with PN or RN for a solitary and NX/N0 M0 renal mass (4-7 cm), 577 (PN, 100; RN, 477) patients with pathologically confirmed pT1b remained for analysis. Study subjects were grouped by PN or RN, then matched by age, sex, comorbidities, body mass index, tumor size and depth, histologic type, and preoperative estimated glomerular filtration rate (eGFR) using propensities score. To evaluate oncologic outcomes, overall survival (OS), cancer- specific survival (CSS), and progression-free survival (PFS) rates were analyzed. The functional outcomes were evaluated by postoperative eGFR.
Results
The median follow-up in the RN group was 48.1 and 42.6 months in the PN group. The estimated 10-year CSS rate (PN 85.7% vs. RN 84.4%, p=0.52) and 5- and estimated 10-year PFS rates (PN: 86.4% and 79.2% vs. RN: 86.0% and 66.1%, p=0.66) did not differ significantly between groups. The estimated 10-year OS rate was significantly higher in the PN group (85.7%) compared to the RN group (73.3%) (p=0.003). PN was less likely to induce new-onset chronic kidney disease (CKD) and end-stage CKD compared with RN.
Conclusion
Our study suggests that patients treated with PN demonstrate a superior OS rate and postoperative renal function with analogous CSS and PFS rates compared with pair-matched patients treated with RN.

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