Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma

서영범,김승현,김지영,김자은,도윤식,김진욱,김용휘,우현구,김세혁,강신혁,김학재,김태민,이순태,최승홍,박성혜,김일한,김동규,박철기 대한암학회 2017 Cancer Research and Treatment Vol.49 No.2

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 those with low HOXA11 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.

A National Consensus Survey for Current Practice in Brain Tumor Management I: Antiepileptic Drug and Steroid Usage

Sung Kwon Kim,Jangsup Moon,Jin Mo Cho,Kyung Hwan Kim,김세훈,김영일,김영준,Ho Sung Kim,도윤식,박재성,Ji Eun Park,서영범,Kyoung-Su Sung,송진호,Chan Woo Wee,Wan-Soo Yoon,윤홍인,Se-Hoon Lee,임도훈,임정호,장종희,한명훈,홍제범,Kihwan Hwang,박철기,이 대한뇌종양학회 2020 Brain Tumor Research and Treatment Vol.8 No.1

Background: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors. As part I of the survey, the aim of this study is to evaluate national patterns of clinical practice about antiepileptic drug (AED) and steroid usage for management of brain tumors. Methods: A web-based survey was sent to all members of the KSNO by email. The survey included 9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questions were developed by consensus of the Guideline Working Group. Results: The overall response rate was 12.8% (54/423). Regarding AED usage, the majority of respondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperative period. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naive patients, and others prescribed AED as the case may be. The duration of AED prophylaxis showed wide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) was the most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents use steroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoral edema (90.9%) was considered as the most important factor determining steroid usage followed by degree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue the steroids within a week after surgery if there are no specific medical conditions, while 7.3% preferred slow tapering up to a month after surgery. Conclusion: The survey demonstrated the prevailing practice patterns on AED and steroid usage in neuro-oncologic field among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain tumor patients.

A National Consensus Survey for Current Practice in Brain Tumor Management II: Diffuse Midline Glioma and Meningioma

Sung Kwon Kim,윤홍인,Wan-Soo Yoon,Jin Mo Cho,Jangsup Moon,Kyung Hwan Kim,김세훈,김영일,김영준,Ho Sung Kim,도윤식,박재성,Ji Eun Park,서영범,Kyoung-Su Sung,송진호,Chan Woo Wee,Se-Hoon Lee,임도훈,Jung Ho Im,장종희,한명훈,홍제범,Kihwan Hwan 대한뇌종양학회 2020 Brain Tumor Research and Treatment Vol.8 No.1

Background The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors. As part II of the survey, the aim of this study is to evaluate the national patterns of clinical practice for patients with diffuse midline glioma and meningioma. Methods A web-based survey was sent to all members of the KSNO by email. The survey included 4 questions of diffuse midline glioma and 6 questions of meningioma (including 2 case scenarios). All questions were developed by consensus of the Guideline Working Group. Results In the survey about diffuse midline glioma, 76% respondents performed histologic confirmation to identify H3K27M mutation on immunohistochemical staining or sequencing methods. For treatment of diffuse midline glioma, respondents preferred concurrent chemoradiotherapy with temozolomide (TMZ) and adjuvant TMZ (63.8%) than radiotherapy alone (34.0%). In the survey about meningioma, respondents prefer wait-and-see policy for the asymptomatic small meningioma without peritumoral edema. However, a greater number of respondents had chosen surgical resection as the first choice for all large size meningiomas without exception, and small size meningiomas with either peritumoral edema or eloquent location. There was no single opinion with major consensus on long-term follow-up plans for asymptomatic meningioma with observation policy. As many as 68.1% of respondents answered that they would not add any adjuvant therapies for World Health Organization grade II meningiomas if the tumor was totally resected including dura. Conclusion The survey demonstrates the prevailing clinical practice patterns for patients with diffuse midline glioma and meningioma among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of diffuse midline glioma and meningioma.

A National Consensus Survey for Current Practice in Brain Tumor Management III: Brain Metastasis and Primary Central Nervous System Lymphoma

Sung Kwon Kim,Ji Eun Park,Kyung Hwan Kim,Jin Mo Cho,문장섭,Wan-Soo Yoon,김세훈,김영일,김영준,Ho Sung Kim,도윤식,박재성,윤홍인,서영범,Kyoung-Su Sung,송진호,Chan Woo Wee,Se-Hoon Lee,임도훈,임정호,장종희,한명훈,홍제범,Kihwan Hwang,Chul-Kee Park 대한뇌종양학회 2020 Brain Tumor Research and Treatment Vol.8 No.1

Background: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted the nationwide questionnaire survey for diverse queries facing to treat patients with brain tumor. As part III of the survey, the aim of this study is to evaluate the national patterns of clinical practice for patients with brain metastasis and primary central nervous system lymphoma (PCNSL). Methods: A web-based survey was sent to all members of the KSNO by email. The survey included 7 questions of brain metastasis and 5 questions of PCNSL, focused on the management strategies in specific situations. All questions were developed by consensus of the Guideline Working Group. Results: In the survey about brain metastasis, respondents preferred surgical resection with adjuvant treatment for patients with a surgically accessible single brain metastatic lesion less than 3 cm in size without extracranial systemic lesions. However, most respondents considered radiosurgery for surgically inaccessible lesions. As the preferred treatment of multiple brain metastases according to the number of brain lesions, respondents tended to choose radiotherapy with increasing number of lesions Radiosurgery was mostly chosen for the brain metastases of less than or equal to 4. In the survey about PCNSL, a half of respondents choose high-dose methotrexate-based polychemotherapy as the first-line induction therapy for PCNSL. The consolidation and salvage therapy showed a little variation among respondents. For PCNSL patients with cerebrospinal fluid dissemination, intrathecal chemotherapy was most preferred. Conclusion: The survey demonstrates the prevailing clinical practice patterns for patients with brain metastasis and PCNSL among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain metastasis and PCNSL.