1.Fate of Brain Metastasis With Cerebrospinal Fluid Space Invasion Based on MRI Findings: Clinical Features and Factors Affecting Progression to Overt Leptomeningeal Metastasis
Yoontae HONG ; Haechan SONG ; Ho-Shin GWAK ; Yun-Sik DHO ; Sang Hoon SHIN ; Heon YOO ; Kyu-Chang WANG
Brain Tumor Research and Treatment 2026;14(1):35-46
Background:
Parenchymal brain metastasis (BM) and its extended growth into cerebrospinal fluid(CSF) pathways or surgical spillage could result in leptomeningeal metastasis (LM). We defined BM with epipial spread or dural attachment on MRI as BM with CSF space invasion (BM-CSFi), regardless of CSF cytology results, and evaluated its clinical course after BM resection.
Methods:
We retrospectively reviewed 297 patients who underwent craniotomy for BM exclud-ing patients followed for <6 months or without follow-up MRI. Primary outcomes were proportion of patients progressing to overt LM and time to progression. We also evaluated clinical and radiologic variables to identify risk factors for LM progression.
Results:
A total of 91 patients (30.6%) developed overt LM, with median time to progressionof 7.9 months during 18.3 months follow-up after the craniotomy. On multivariable analysis, preoperative MRI evidence of dural attachment with enhancement (hazard ratio [HR], 5.59; p=0.002), primary small cell lung cancer (HR, 4.92; p=0.026), infratentorial BM location (HR, 2.14; p=0.019), and postoperative cumulative CSF cytology positive rate ≥50% (HR, 7.13; p=0.012) were independent risk factors for LM progression. The mode of resection and postoperative radiotherapy or systemic chemotherapy were not significantly associated with LM progression.
Conclusion
BM-CSFi, defined by preoperative MRI findings, may represent a clinically importantprecursor of LM. Our findings highlight the need for close monitoring of patients with BM-CSFi and the development of management protocols to minimize the risk of LM progression.
2.Long-Term Remission of Recurrent Anaplastic Oligodendroglioma With WT-1-Specific CD8+ T-Cell Therapy:A Case Report
Ho-Shin GWAK ; Beom Kyu CHOI ; Young Joo LEE ; Na Young HAN ; Kook Hee YANG
Brain Tumor Research and Treatment 2025;13(2):65-72
We report a case of complete remission in anaplastic oligodendroglioma following adoptive cell therapy (ACT) with autologous Wilms tumor 1 (WT-1)-specific CD8+ T cells. A 40-year-old woman referred to our hospital for adjuvant chemotherapy after recurrent anaplastic oligodendroglioma initially presented with a left frontal tumor, diagnosed through seizure onset, and subtotal resection confirmed oligodendroglioma (WHO grade 2). Radiation therapy treated the residual tumor, achieving partial remission until recurrence 2.5 years later when malignant transformation to anaplastic oligodendroglioma (WHO grade 3) occurred following a second craniotomy. After three cycles of procarbazine, lomustine, and vincristine chemotherapy, the residual tumor stabilized for 3 years. However, follow-up MRI identified a new enhancing lesion, prompting a third craniotomy. Recurrent anaplastic oligodendroglioma was confirmed, and adjuvant proton beam therapy and temozolomide chemotherapy were initiated. Two years later, another enhancing lesion appeared on the adjacent medial frontal lobe. Following multidisciplinary review, we introduced WT-1-specific ACT. Although transient swelling was observed 1 month post-therapy, the tumor demonstrated a response within 3–9 months. Continued regression led to complete remission—confirmed via MRI at the 15-month follow-up and sustained for 4.7 years. The patient’s peripheral blood monocyte profiles and immune-associated cytokine analysis indicated T-cell activation following WT-1 sensitization.
3.Differential Diagnosis of a Well-Enhancing Intracisternal Lesion in a Breast Cancer Patient
Brain Tumor Research and Treatment 2025;13(1):34-38
This case introduces the differential diagnosis of a well-enhancing lesion in the prepontine cistern of a 55-year-old female patient who was diagnosed with recurrent metastatic breast cancer. The patient was diagnosed with breast cancer 11 years ago and underwent a mastectomy and subsequent adjuvant therapy. Tamoxifen had been given for 5 years, and the treatment was completed. Five years after, she found a lung nodule on her routine chest X-ray examination. Based on her past medical history, systemic cancer work-up was done and it revealed multiple lesions in T10 vertebra, lungs, and mediastinal lymph nodes. Trans-bronchial needle aspiration was performed and the biopsy was a metastatic breast cancer. Brain MRI was taken as she was complaining of headache and it showed a welldefined, ovoid enhancing 0.9-cm nodule in the right prepontine cistern. Neuro-oncology tumor board evaluated the lesion as more likely to be an asymptomatic neurogenic tumor rather than metastasis based on radiological features including brainstem surfaced location, slightly high signal intensity on T2-weighted image and no diffusion restriction. To rule out leptomeningeal metastasis, a serial cerebrospinal fluid cytology examination (×3) was done and negative for malignant cells. Follow-up brain MRIs of 2 and 9 months showed no significant changes in the pre-pontine enhancing lesion.
4.Long-Term Remission of Recurrent Anaplastic Oligodendroglioma With WT-1-Specific CD8+ T-Cell Therapy:A Case Report
Ho-Shin GWAK ; Beom Kyu CHOI ; Young Joo LEE ; Na Young HAN ; Kook Hee YANG
Brain Tumor Research and Treatment 2025;13(2):65-72
We report a case of complete remission in anaplastic oligodendroglioma following adoptive cell therapy (ACT) with autologous Wilms tumor 1 (WT-1)-specific CD8+ T cells. A 40-year-old woman referred to our hospital for adjuvant chemotherapy after recurrent anaplastic oligodendroglioma initially presented with a left frontal tumor, diagnosed through seizure onset, and subtotal resection confirmed oligodendroglioma (WHO grade 2). Radiation therapy treated the residual tumor, achieving partial remission until recurrence 2.5 years later when malignant transformation to anaplastic oligodendroglioma (WHO grade 3) occurred following a second craniotomy. After three cycles of procarbazine, lomustine, and vincristine chemotherapy, the residual tumor stabilized for 3 years. However, follow-up MRI identified a new enhancing lesion, prompting a third craniotomy. Recurrent anaplastic oligodendroglioma was confirmed, and adjuvant proton beam therapy and temozolomide chemotherapy were initiated. Two years later, another enhancing lesion appeared on the adjacent medial frontal lobe. Following multidisciplinary review, we introduced WT-1-specific ACT. Although transient swelling was observed 1 month post-therapy, the tumor demonstrated a response within 3–9 months. Continued regression led to complete remission—confirmed via MRI at the 15-month follow-up and sustained for 4.7 years. The patient’s peripheral blood monocyte profiles and immune-associated cytokine analysis indicated T-cell activation following WT-1 sensitization.
5.Differential Diagnosis of a Well-Enhancing Intracisternal Lesion in a Breast Cancer Patient
Brain Tumor Research and Treatment 2025;13(1):34-38
This case introduces the differential diagnosis of a well-enhancing lesion in the prepontine cistern of a 55-year-old female patient who was diagnosed with recurrent metastatic breast cancer. The patient was diagnosed with breast cancer 11 years ago and underwent a mastectomy and subsequent adjuvant therapy. Tamoxifen had been given for 5 years, and the treatment was completed. Five years after, she found a lung nodule on her routine chest X-ray examination. Based on her past medical history, systemic cancer work-up was done and it revealed multiple lesions in T10 vertebra, lungs, and mediastinal lymph nodes. Trans-bronchial needle aspiration was performed and the biopsy was a metastatic breast cancer. Brain MRI was taken as she was complaining of headache and it showed a welldefined, ovoid enhancing 0.9-cm nodule in the right prepontine cistern. Neuro-oncology tumor board evaluated the lesion as more likely to be an asymptomatic neurogenic tumor rather than metastasis based on radiological features including brainstem surfaced location, slightly high signal intensity on T2-weighted image and no diffusion restriction. To rule out leptomeningeal metastasis, a serial cerebrospinal fluid cytology examination (×3) was done and negative for malignant cells. Follow-up brain MRIs of 2 and 9 months showed no significant changes in the pre-pontine enhancing lesion.
6.Long-Term Remission of Recurrent Anaplastic Oligodendroglioma With WT-1-Specific CD8+ T-Cell Therapy:A Case Report
Ho-Shin GWAK ; Beom Kyu CHOI ; Young Joo LEE ; Na Young HAN ; Kook Hee YANG
Brain Tumor Research and Treatment 2025;13(2):65-72
We report a case of complete remission in anaplastic oligodendroglioma following adoptive cell therapy (ACT) with autologous Wilms tumor 1 (WT-1)-specific CD8+ T cells. A 40-year-old woman referred to our hospital for adjuvant chemotherapy after recurrent anaplastic oligodendroglioma initially presented with a left frontal tumor, diagnosed through seizure onset, and subtotal resection confirmed oligodendroglioma (WHO grade 2). Radiation therapy treated the residual tumor, achieving partial remission until recurrence 2.5 years later when malignant transformation to anaplastic oligodendroglioma (WHO grade 3) occurred following a second craniotomy. After three cycles of procarbazine, lomustine, and vincristine chemotherapy, the residual tumor stabilized for 3 years. However, follow-up MRI identified a new enhancing lesion, prompting a third craniotomy. Recurrent anaplastic oligodendroglioma was confirmed, and adjuvant proton beam therapy and temozolomide chemotherapy were initiated. Two years later, another enhancing lesion appeared on the adjacent medial frontal lobe. Following multidisciplinary review, we introduced WT-1-specific ACT. Although transient swelling was observed 1 month post-therapy, the tumor demonstrated a response within 3–9 months. Continued regression led to complete remission—confirmed via MRI at the 15-month follow-up and sustained for 4.7 years. The patient’s peripheral blood monocyte profiles and immune-associated cytokine analysis indicated T-cell activation following WT-1 sensitization.
7.Differential Diagnosis of a Well-Enhancing Intracisternal Lesion in a Breast Cancer Patient
Brain Tumor Research and Treatment 2025;13(1):34-38
This case introduces the differential diagnosis of a well-enhancing lesion in the prepontine cistern of a 55-year-old female patient who was diagnosed with recurrent metastatic breast cancer. The patient was diagnosed with breast cancer 11 years ago and underwent a mastectomy and subsequent adjuvant therapy. Tamoxifen had been given for 5 years, and the treatment was completed. Five years after, she found a lung nodule on her routine chest X-ray examination. Based on her past medical history, systemic cancer work-up was done and it revealed multiple lesions in T10 vertebra, lungs, and mediastinal lymph nodes. Trans-bronchial needle aspiration was performed and the biopsy was a metastatic breast cancer. Brain MRI was taken as she was complaining of headache and it showed a welldefined, ovoid enhancing 0.9-cm nodule in the right prepontine cistern. Neuro-oncology tumor board evaluated the lesion as more likely to be an asymptomatic neurogenic tumor rather than metastasis based on radiological features including brainstem surfaced location, slightly high signal intensity on T2-weighted image and no diffusion restriction. To rule out leptomeningeal metastasis, a serial cerebrospinal fluid cytology examination (×3) was done and negative for malignant cells. Follow-up brain MRIs of 2 and 9 months showed no significant changes in the pre-pontine enhancing lesion.
8.Complete Remission of Dural-Based Leptomeningeal Metastasis in Patient With Non-Small Cell Lung Cancer by Osimertinib
Jemin HWANG ; Beung Chul AHN ; So Hyeon JI ; Ho-Shin GWAK
Brain Tumor Research and Treatment 2024;12(4):245-249
We report complete remission of dural-based leptomeningeal metastasis (LM) in an 80-year-old female patient with non-small cell lung cancer (NSCLC) by osimertinib. She was diagnosed with NSCLC (adenocarcinoma, T4N3M1a) 8 years ago. Mutation analysis of biopsied tissue revealed exon 19 deletion positive, and gefitinib was prescribed. Follow-up chest CT showed a radiological response, and wholebody positron emission tomography 3 years later revealed the disappearance of the previous high-uptake lesions. The medication was continued for maintenance but stopped 4 years later due to intolerable dermatitis. Two years after discontinuing chemotherapy, the patient had a gait disturbance, and brain MRI revealed a right cerebellar mass (diameter [d]=3 cm) with peritumoral edema, compatible with solitary brain metastasis. Retromastoid suboccipital craniotomy and gross total removal of the dura-attached lesion were performed. As the systemic cancer status evaluation revealed no radiological cancer lesion, only tumor bed radiation therapy was given (4,000 cGy/10 fractions) without re-introducing gefitinib. She was followed with a brain MRI at 6-month intervals, and a brain MRI 2 years postoperatively revealed a dural-based extra-axial mass in the left prepontine cistern (d=2.2 cm). Serial cerebrospinal fluid (CSF) cytology was positive for cancer cells. Upon LM diagnosis, the third-generation receptor tyrosine kinase inhibitor osimertinib was given. Two-month follow-up CSF cytology and five consecutive tests over 14 months demonstrated negative conversion. Five-month follow-up brain MRI revealed near complete remission of dural-based LM, and the response was maintained until the 13-month follow-up brain MRI.
9.Complete Remission of Dural-Based Leptomeningeal Metastasis in Patient With Non-Small Cell Lung Cancer by Osimertinib
Jemin HWANG ; Beung Chul AHN ; So Hyeon JI ; Ho-Shin GWAK
Brain Tumor Research and Treatment 2024;12(4):245-249
We report complete remission of dural-based leptomeningeal metastasis (LM) in an 80-year-old female patient with non-small cell lung cancer (NSCLC) by osimertinib. She was diagnosed with NSCLC (adenocarcinoma, T4N3M1a) 8 years ago. Mutation analysis of biopsied tissue revealed exon 19 deletion positive, and gefitinib was prescribed. Follow-up chest CT showed a radiological response, and wholebody positron emission tomography 3 years later revealed the disappearance of the previous high-uptake lesions. The medication was continued for maintenance but stopped 4 years later due to intolerable dermatitis. Two years after discontinuing chemotherapy, the patient had a gait disturbance, and brain MRI revealed a right cerebellar mass (diameter [d]=3 cm) with peritumoral edema, compatible with solitary brain metastasis. Retromastoid suboccipital craniotomy and gross total removal of the dura-attached lesion were performed. As the systemic cancer status evaluation revealed no radiological cancer lesion, only tumor bed radiation therapy was given (4,000 cGy/10 fractions) without re-introducing gefitinib. She was followed with a brain MRI at 6-month intervals, and a brain MRI 2 years postoperatively revealed a dural-based extra-axial mass in the left prepontine cistern (d=2.2 cm). Serial cerebrospinal fluid (CSF) cytology was positive for cancer cells. Upon LM diagnosis, the third-generation receptor tyrosine kinase inhibitor osimertinib was given. Two-month follow-up CSF cytology and five consecutive tests over 14 months demonstrated negative conversion. Five-month follow-up brain MRI revealed near complete remission of dural-based LM, and the response was maintained until the 13-month follow-up brain MRI.
10.Complete Remission of Dural-Based Leptomeningeal Metastasis in Patient With Non-Small Cell Lung Cancer by Osimertinib
Jemin HWANG ; Beung Chul AHN ; So Hyeon JI ; Ho-Shin GWAK
Brain Tumor Research and Treatment 2024;12(4):245-249
We report complete remission of dural-based leptomeningeal metastasis (LM) in an 80-year-old female patient with non-small cell lung cancer (NSCLC) by osimertinib. She was diagnosed with NSCLC (adenocarcinoma, T4N3M1a) 8 years ago. Mutation analysis of biopsied tissue revealed exon 19 deletion positive, and gefitinib was prescribed. Follow-up chest CT showed a radiological response, and wholebody positron emission tomography 3 years later revealed the disappearance of the previous high-uptake lesions. The medication was continued for maintenance but stopped 4 years later due to intolerable dermatitis. Two years after discontinuing chemotherapy, the patient had a gait disturbance, and brain MRI revealed a right cerebellar mass (diameter [d]=3 cm) with peritumoral edema, compatible with solitary brain metastasis. Retromastoid suboccipital craniotomy and gross total removal of the dura-attached lesion were performed. As the systemic cancer status evaluation revealed no radiological cancer lesion, only tumor bed radiation therapy was given (4,000 cGy/10 fractions) without re-introducing gefitinib. She was followed with a brain MRI at 6-month intervals, and a brain MRI 2 years postoperatively revealed a dural-based extra-axial mass in the left prepontine cistern (d=2.2 cm). Serial cerebrospinal fluid (CSF) cytology was positive for cancer cells. Upon LM diagnosis, the third-generation receptor tyrosine kinase inhibitor osimertinib was given. Two-month follow-up CSF cytology and five consecutive tests over 14 months demonstrated negative conversion. Five-month follow-up brain MRI revealed near complete remission of dural-based LM, and the response was maintained until the 13-month follow-up brain MRI.

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