- CNS cancer
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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
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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
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Cancer Res Treat. 2021;53(4):983-990. Published online January 13, 2021
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DOI: https://doi.org/10.4143/crt.2020.1052
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Abstract
PDFPubReaderePub
- 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.
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Citations
Citations to this article as recorded by
- 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, Neuro-Oncology.2022; 24(8): 1389. CrossRef - 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
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ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor
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Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
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Cancer Res Treat. 2018;50(2):495-505. Published online May 22, 2017
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DOI: https://doi.org/10.4143/crt.2016.577
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Abstract
PDFPubReaderePub
- Purpose
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
Materials and Methods
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
Results
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK+ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
Conclusion
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.
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Citations
Citations to this article as recorded by
- Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features
Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo Journal of Pathology and Translational Medicine.2024; 58(1): 29. CrossRef - Multi-omics revealed that ELAVL3 regulates MYCN in neuroblastoma via immunogenic cell death: Risk stratification and experimental research
Peng Hong, Zaihong Hu, Jie Lin, Kongkong Cui, Zhiqiang Gao, Xiaomao Tian, Qinlin Shi, Tao Lin, Guanghui Wei International Journal of Biological Macromolecules.2024; 282: 137045. CrossRef - Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma
Manli Zhao, Weizhong Gu, Fei Liu, Lihua Yu, Yan Shu, Lei Liu, Jiahui Hu, Yang Liu, Hongfeng Tang, Jianhua Mao Pediatric and Developmental Pathology.2023; 26(2): 124. CrossRef - ALKGene Mutation and ALK Protein Expression in Advanced Neuroblastoma and the Potential Value in Risk Stratification in Fine-Needle Aspiration Biopsy Samples
Neha Bhardwaj, Manish Rohilla, Upasana Gautam, Amita Trehan, Deepak Bansal, Nandita Kakkar, Radhika Srinivasan American Journal of Clinical Pathology.2023;[Epub] CrossRef - Rapid detection of telomerase expression of neuroblastoma in paraffin-embedded tissue: combination of in situ hybridisation and quantitative PCR
Manli Zhao, Zhonghai Guan, Liang Gong, Fei Liu, Weizhong Gu, Lei Liu, Kewen Jiang, Jiabin Cai, Chunyue Feng, Chik Hong Kuick, Kenneth Tou En Chang, Jinhu Wang, Hongfeng Tang, Minzhi Yin, Jianhua Mao Pathology.2023; 55(7): 958. CrossRef - Interactions of Butyrylcholinesterase with Neuroblastoma-associated
Oncoproteins
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter Current Enzyme Inhibition.2023; 19(2): 109. CrossRef - Combined Detection of Copy Number Variations of MYCN and ALK using Droplet Digital Polymerase Chain Reaction to Identify High-Risk Patients with Neuroblastoma
Trupti Trivedi, Kinjal Panchal, Neha Bhalala, Priti Trivedi, Harsha Panchal World Neurosurgery.2022; 159: e48. CrossRef - ALK expression, prognostic significance, and its association with MYCN expression in MYCN non-amplified neuroblastoma
Dinesh Babu Somasundaram, Sheeja Aravindan, Nandita Gupta, Zhongxin Yu, Ashley Baker, Natarajan Aravindan World Journal of Pediatrics.2022; 18(4): 285. CrossRef - Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter Journal of Pediatric Hematology/Oncology.2022; 44(6): 293. CrossRef - Differential Impact of ALK Mutations in Neuroblastoma
Tara O'Donohue, Nitya Gulati, Audrey Mauguen, Brian H. Kushner, Neerav Shukla, M. I. Rodriguez-Sanchez, Nancy Bouvier, Stephen Roberts, Ellen Basu, Nai-Kong Cheung, Shakeel Modak JCO Precision Oncology.2021; (5): 492. CrossRef - The challenge of defining “ultra‐high‐risk” neuroblastoma
Daniel A. Morgenstern, Rochelle Bagatell, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Lucas Moreno, Julie R. Park, Andrew D. Pearson, Gudrun Schleiermacher, Dominique Valteau‐Couanet, Wendy B. London, Meredith S. Irwin Pediatric Blood & Cancer.2019;[Epub] CrossRef - ALK in Neuroblastoma: Biological and Therapeutic Implications
Ricky Trigg, Suzanne Turner Cancers.2018; 10(4): 113. CrossRef
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