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Spatial Transcriptomic Landscape of Brain Metastases from Triple-Negative Breast Cancer: Comparison of Primary Tumor and Brain Metastases Using Spatial Analysis
Jihwan Yoo, Inho Park, Hyun Jung Kim, Hun Ho Park, Sora Lee, Jee Hung Kim, Yoon Jin Cha
Received January 8, 2025  Accepted April 13, 2025  Published online April 15, 2025  
DOI: https://doi.org/10.4143/crt.2025.033    [Accepted]
AbstractAbstract PDF
Purpose
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, with approximately 30% of patients eventually developing brain metastases (BM), which result in poor outcomes. An understanding of the tumor microenvironment (TME) at both primary and metastatic sites offers insights into the mechanisms underlying BM and potential therapeutic targets.
Materials and Method
Spatial RNA sequencing (spRNA-seq) was performed on primary TNBC and paired BM tissues from three patients, one of whom had previously received immune checkpoint inhibitors before BM diagnosis. Specimen regions were categorized into tumor, proximal, and distal TME based on their spatial locations. Gene expression differences across these zones were analyzed, and immune cell infiltration was estimated using TIMER. A gene module analysis was conducted to identify key gene clusters associated with BM.
Results
Distinct gene expression profiles were noted in the proximal and distal TMEs. In BM, the proximal TME exhibited neuronal gene expression, suggesting neuron-tumor interactions compared to tumor, and upregulation of epithelial genes compared to the distal TME. Immune cell analysis revealed dynamic changes in CD8+ T cells and macrophages across the tumor and TME zones. Gene module analysis identified five key modules, including one related to glycolysis, which correlated with patient survival. Drug repurposing analysis identified potential therapeutic targets, including VEGFA, RAC1, EGLN3, and CAMK1D.
Conclusion
This study provides novel insights into the transcriptional landscapes in TNBC BM using spRNA-seq, emphasizing the role of neuron-tumor interactions and immune dynamics. These findings suggest new therapeutic strategies and underscore the importance of further research.
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Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy
Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, In Gyu Hwang, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, In Sook Woo, Soojung Hong, Tae-Yong Kim, Ji Yeon Baek, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Hun-Mo Ryoo, Kyung Hee Lee, Jee Hyun Kim
Cancer Res Treat. 2019;51(3):1249-1256.   Published online January 2, 2019
DOI: https://doi.org/10.4143/crt.2018.451
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy.
Materials and Methods
Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC).
Results
The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006).
Conclusion
KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

Citations

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  • Comparison of two frailty screening tools in older patients with colorectal cancer
    Han Zhao, Xinlin Lu, Senshuang Zheng, Danmei Wei, Lizhong Zhao, Yuan Wang, Geertruida H. de Bock, Wenli Lu
    BMC Geriatrics.2023;[Epub]     CrossRef
  • Prevalence and Predictive Factors for Upfront Dose Reduction of the First Cycle of First-Line Chemotherapy in Older Adults with Metastatic Solid Cancer: Korean Cancer Study Group (KCSG) Multicenter Study
    In Gyu Hwang, Minsuk Kwon, Jin Won Kim, Se Hyun Kim, Yun-Gyoo Lee, Jin Young Kim, Su-Jin Koh, Yoon Ho Ko, Seong Hoon Shin, Soojung Hong, Tae-Yong Kim, Sun Young Kim, Hyun Jung Kim, Hyo Jung Kim, Myung Ah Lee, Jung Hye Kwon, Yong Sang Hong, Kyung Hee Lee,
    Cancers.2021; 13(2): 331.     CrossRef
  • A single-arm feasibility study of gradual dose de-escalation of antiemetic dexamethasone for older patients receiving chemotherapy
    Koung Jin Suh, Seonghae Yoon, Jin Won Kim, Seo Hyun Yoon, Ji-Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jee Hyun Kim
    Journal of Geriatric Oncology.2021; 12(6): 922.     CrossRef
  • Predictive Value of Geriatric Oncology Screening and Geriatric Assessment in Older Patients with Solid Cancers: Protocol for a Danish prospective cohort study (PROGNOSIS-G8)
    Helena Møgelbjerg Ditzel, Ann-Kristine Weber Giger, Cecilia Margareta Lund, Henrik Jørn Ditzel, Afsaneh Mohammadnejad, Per Pfeiffer, Jesper Ryg, Trine Lembrecht Jørgensen, Marianne Ewertz
    Journal of Geriatric Oncology.2021; 12(8): 1270.     CrossRef
  • The Globalization of Geriatric Oncology: From Data to Practice
    Ravindran Kanesvaran, Supriya Mohile, Enrique Soto-Perez-de-Celis, Harpreet Singh
    American Society of Clinical Oncology Educational Book.2020; (40): e107.     CrossRef
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18F-FDG/PET May Help to Identify a Subgroup of Patients with T1-T2 Breast Cancer and 1-3 Positive Lymph Nodes Who Are at a High Risk of Recurrence after Mastectomy
Jee Suk Chang, Jeongshim Lee, Hyun Jung Kim, Kyung Hwan Kim, Mijin Yun, Seung Il Kim, Ki Chang Keum, Chang-Ok Suh, Yong Bae Kim
Cancer Res Treat. 2016;48(2):508-517.   Published online September 9, 2015
DOI: https://doi.org/10.4143/crt.2015.172
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to assess the utility of positron emission tomography (PET) for predicting recurrence among patients with T1-T2/N1 breast cancer who were treated with mastectomy. Materials and Methods Of 712 consecutive patients with T1-T2/N1 breast cancer treated during 2003-2012, 109 had undergone preoperative 18F-fluorodeoxyglucose/PET and were included. Metabolic (maximum standardized uptake value [SUVmax]), volumetric (metabolic tumor volume [MTV]), and combined (total lesion glycolysis [TLG]) indices were measured. The resulting values were analyzed and compared with clinical outcome.
Results
At the median follow-up of 46.7 months, the 3-year relapse-free survival (RFS) rate was 95.2%. SUVmax (area under curve, 0.824) was more useful than MTV or TLG as a means of identifying patients at high risk for any recurrence. In multivariate analysis, SUVmax remained an independent risk factor for RFS (p=0.006). Using the method of Contal and O’Quigley, a SUVmax threshold of 5.36 showed the best predictive performance. The PET-based highrisk group (≥ 5.36 in either breast or nodes) had more T1c-T2, high-grade, hormone-receptor negative, and invasive ductal carcinoma tumors than the low-risk group (< 5.36 in both breast and nodes). The prognosis was much worse when high SUVmax (≥ 5.36) was detected in nodes (p < 0.001). In the no-radiotherapy cohort, the PET-based high-risk group had increased risk of locoregional recurrence when compared to the low-risk group (p=0.037). Conclusion High SUVmax on preoperative PET showed association with elevated risk of locoregional recurrence and any recurrence. Pre-treatment PET may improve assessments of recurrence risk and clarify indications for post-mastectomy radiotherapy in this subset of patients.

Citations

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    Soong June Bae, Sung Gwe Ahn, Jung Hwan Ji, Chih Hao Chu, Dooreh Kim, Janghee Lee, Soeun Park, Chihwan Cha, Joon Jeong
    Journal of Breast Cancer.2022; 25(6): 485.     CrossRef
  • Significance of Metabolic Tumor Volume at Baseline and Reduction of Mean Standardized Uptake Value in 18F-FDG-PET/CT Imaging for Predicting Pathological Complete Response in Breast Cancers Treated with Preoperative Chemotherapy
    Tomoko Higuchi, Yukie Fujimoto, Hiromi Ozawa, Ayako Bun, Reiko Fukui, Yoshimasa Miyagawa, Michiko Imamura, Kazuhiro Kitajima, Koichiro Yamakado, Yasuo Miyoshi
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    Nuclear Medicine Communications.2019; 40(11): 1112.     CrossRef
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    The Breast.2019; 48: 73.     CrossRef
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    Wei Diao, Fangfang Tian, Zhiyun Jia
    European Journal of Radiology.2018; 105: 1.     CrossRef
  • Differential Prognostic Impact of Strong PD-L1 Expression and 18F-FDG Uptake in Triple-negative Breast Cancer
    Seo Hee Choi, Jee Suk Chang, Ja Seung Koo, Jong Won Park, Joo Hyuk Sohn, Ki Chang Keum, Chang-Ok Suh, Yong Bae Kim
    American Journal of Clinical Oncology.2018; 41(11): 1049.     CrossRef
  • Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from 18F-FDG PET/CT in operable triple-negative breast cancer
    Yong-il Kim, Yong Joong Kim, Jin Chul Paeng, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, Keon Wook Kang
    European Journal of Nuclear Medicine and Molecular Imaging.2017; 44(11): 1787.     CrossRef
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    Ryusuke Murakami, Yoshimitsu Fukushima, Hitomi Tani, Kotomi Iwata, Shinichiro Kumita, Maki Nakai, Tomoko Kurita, Keiko Yanagihara, Hiroyuki Takei, Miyuki Matsubara
    Open Journal of Medical Imaging.2017; 07(03): 112.     CrossRef
  • Volume-based metabolic parameter of breast cancer on preoperative 18F-FDG PET/CT could predict axillary lymph node metastasis
    Young-Sil An, Doo Kyoung Kang, Yongsik Jung, Tae Hee Kim
    Medicine.2017; 96(45): e8557.     CrossRef
  • Trends in the Application of Postmastectomy Radiotherapy for Breast Cancer With 1 to 3 Positive Axillary Nodes and Tumors ≤5 cm in the Modern Treatment Era
    Jee Suk Chang, Jung Eun Choi, Min Ho Park, Sung Hoo Jung, Byung Ock Choi, Hyung Seok Park, Seho Park, Yong Bae Kim
    Medicine.2016; 95(19): e3592.     CrossRef
  • Prognostic significance of preoperative 18F-FDG PET/CT for breast cancer subtypes
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Clinical Outcome of Gastric Cancer Patients with Bone Marrow Metastases
Ji Yeon Kwon, Jina Yun, Han Jo Kim, Kyoung-Ha Kim, Se-Hyung Kim, Sang-Cheol Lee, Hyun Jung Kim, Sang Byung Bae, Chan Kyu Kim, Nam Su Lee, Kyu Taek Lee, Seong Kyu Park, Jong-Ho Won, Dae Sik Hong, Hee Sook Park
Cancer Res Treat. 2011;43(4):244-249.   Published online December 27, 2011
DOI: https://doi.org/10.4143/crt.2011.43.4.244
AbstractAbstract PDFPubReaderePub
PURPOSE
The prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases.
MATERIALS AND METHODS
We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009.
RESULTS
The median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas. The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p<0.001). The causes of death were tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and disseminated intravascular coagulation (1 patient, 4%). There were no chemotherapy-related deaths.
CONCLUSION
Palliative chemotherapy could be considered in advanced gastric cancer patients with bone marrow metastases as a treatment option.

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Efficacy and Safety of Oxaliplatin, 5-Fluorouracil, and Folinic Acid Combination Chemotherapy as First-Line Treatment in Metastatic or Recurrent Gastric Cancer
Han Jo Kim, Jun Young Eun, Young Woo Jeon, Jina Yun, Kyoung Ha Kim, Se Hyung Kim, Hyun Jung Kim, Sang-Cheol Lee, Sang Byung Bae, Chan Kyu Kim, Nam Su Lee, Kyu Taek Lee, Seong-Kyu Park, Jong-Ho Won, Dae Sik Hong, Hee Sook Park
Cancer Res Treat. 2011;43(3):154-159.   Published online September 30, 2011
DOI: https://doi.org/10.4143/crt.2011.43.3.154
AbstractAbstract PDFPubReaderePub
PURPOSE
We retrospectively determined the efficacy and safety of the combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer.
MATERIALS AND METHODS
Between January 2006 and August 2009, 39 patients with histologically-confirmed, metastatic or recurrent gastric cancer underwent chemotherapy, and the results were retrospectively investigated. The chemotherapy regimen consisted of oxaliplatin (100 mg/m2) and FA (200 mg/m2; 2-hour infusion), then 5-FU (2,400 mg/m2; 46-hour continuous infusion) every 2 weeks.
RESULTS
Thirty-nine patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1 to 16). Of the 32 evaluable patients, zero patients achieved a complete response and 11 patients achieved a partial response (response rate, 28.2%). The median time-to-progression and overall survival were 4.3 months (95% confidence interval [CI], 2.0 to 6.5 months) and 9.8 months (95% CI, 3.5 to 16.0 months), respectively. The main hematologic toxicity was anemia, which was observed in 119 cycles (56.7%). Grade 3/4 neutropenia was observed in 32 cycles (15.2%). The main non-hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. No treatment-related deaths were reported.
CONCLUSION
This study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.

Citations

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    Journal of Proteomics.2022; 266: 104682.     CrossRef
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Phase II Clinical Trial of Genexol(R) (Paclitaxel) and Carboplatin for Patients with Advanced Non-small Cell Lung Cancer
Han Jo Kim, Kyoung Ha Kim, Jina Yun, Se Hyung Kim, Hyun Jung Kim, Sang-Cheol Lee, Sang Byung Bae, Chan Kyu Kim, Nam Su Lee, Kyu Taek Lee, Do-Jin Kim, Seong-Kyu Park, Jong-Ho Won, Dae Sik Hong, Hee Sook Park
Cancer Res Treat. 2011;43(1):19-23.   Published online March 31, 2011
DOI: https://doi.org/10.4143/crt.2011.43.1.19
AbstractAbstract PDFPubReaderePub
PURPOSE
This phase II clinical trial was conducted to evaluate the activity and safety of a combination treatment of paclitaxel (Genexol(R)) plus carboplatin in patients with advanced non-small cell lung cancer.
MATERIALS AND METHODS
Chemotherapy-naive patients having histologically confirmed advanced or metastatic non-small cell lung cancer were enrolled. Genexol(R) was administered at 225 mg/m2 intravenous (IV) infusion over 3 hours, followed by carboplatin (area under the concentration-time curve=6) IV on day 1 every 3 weeks.
RESULTS
Twenty-eight patients were enrolled between January 2003 and January 2005. A total of 110 cycles of chemotherapy were given. The median number of chemotherapy cycles was 4. A total of 25 study patients were evaluable. On an intent-to-treat basis, there were ten partial responses (response rate 35.7%). The median time-to-progression was 3.2 months (95% confidence interval [CI], 1.5 to 4.9) and the median overall survival was 8.2 months (95% CI, 4.1 to 12.3). The main hematologic grade 3/4 toxicity was neutropenia, which was observed in 14 (50.0%) patients. The main non-hematologic toxicity was peripheral neuropathy, which was observed in 12 patients (42.9%). Grade 3/4 neuropathy occurred in 8 patients (28.6%) and three patients discontinued treatment because of neuropathy.
CONCLUSION
In this trial, the combination of Genexol(R) and carboplatin showed significant activity as first line treatment for patients with advanced or metastatic non-small cell lung cancer. However, a modest dose reduction of Genexol(R) is needed due to sensory neuropathy.

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