Cancer Research and Treatment

Original Article

Pediatric cancer

The Role of Early and Delayed Surgery for Infants with Congenital Brain Tumors: Jong Seok Lee, Ji Yeoun Lee, Kyung Hyun Kim, Sung-Hye Park, Eun Jung Koh, Seung-Ki Kim, Ji Hoon Phi; Cancer Res Treat. 2024;56(3):909-919. Published online December 28, 2023; DOI: https://doi.org/10.4143/crt.2023.1174

Abstract PDF Supplementary Material PubReader ePub: Purpose
The present study aimed to evaluate the role of early and delayed surgery in congenital brain tumors and analyze the clinical outcomes of infantile brain tumors.
Materials and Methods
We performed a retrospective cohort study on 69 infantile brain tumors at a single institution from January 2008 to June 2023. Outcomes were assessed as early mortality (within 30 days following surgery) to evaluate the risk of early surgery in congenital brain tumors. Outcomes of recurrence and overall survival were analyzed in infantile brain tumors.
Results
Surgery-related early mortality appeared to occur in young and low-body-weight patients. Cut-off values of age and body weight were found to be 1.3 months and 5.2 kg to avoid early mortality. Three patients (3/10, 30%) showed early mortality in the early surgery group, and early mortality occurred in one patient (1/14, 7.14%) in the delayed surgery group, whose tumor was excessively enlarged. Younger age at diagnosis (< 3 months of age; hazard ratios [HR], 7.1; 95% confidence intervals [CI], 1.4 to 35.6; p=0.018) and leptomeningeal seeding (LMS; HR, 30.6; 95% CI, 3.7 to 253.1; p=0.002) were significant independent risk factors for high mortality in infantile brain tumors.
Conclusion
We suggest delaying surgery until the patient reaches 1.3 months of age and weighs over 5.2 kg with short-term imaging follow-up unless tumors grow rapidly in congenital brain tumors. Younger ages and the presence of LMS are independent risk factors for high mortality in infantile brain tumors.

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Case Report

Osimertinib Combined with Systemic Chemotherapy for EGFR Mutant, T790M-Negative, Non–Small Cell Lung Cancer Patients Who Develop Leptomeningeal Metastases with Extracranial Progression to Prior EGFR TKI: Hye Ryeon Kim, Hyunji Jo, Hongsik Kim, Joohyun Hong, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin-Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2023;55(1):344-349. Published online March 26, 2022; DOI: https://doi.org/10.4143/crt.2021.1603

Abstract PDF PubReader ePub

Leptomeningeal metastasis (LM) is a rare but fatal clinical condition with a short survival time. The incidence of LM from epidermal growth factor receptor mutant (EGFRm) non–small cell lung cancer (NSCLC) has increased due to the limited efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the central nervous system (CNS). Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean overall survival from LM diagnosis was 14.7 months (95% confidence interval, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.

Citations

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Yi Yue, Yuqing Ren, Chunya Lu, Nan Jiang, Sihui Wang, Junkai Fu, Mengrui Kong, Guojun Zhang
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An overview of the therapeutic strategies for neoplastic meningitis due to breast cancer: when and why?
Mainak Bardhan, Debankur Dey, Vinay Suresh, Binish Javed, Vyshak Alva Venur, Neha Joe, Ritvika Kalidindi, Ahmad Ozair, Marium Khan, Reshma Mahtani, Simon Lo, Yazmin Odia, Manmeet S. Ahluwalia
Expert Review of Neurotherapeutics.2024; 24(1): 77. CrossRef
Osimertinib is associated with improved outcomes in pre-treated non-small cell lung cancer leptomeningeal metastases: A systematic review and meta-analysis
David J.H. Bian, Anna-Maria Lazaratos, Sarah M. Maritan, Andrea Quaiattini, Zhimin Zeng, Zhengfei Zhu, Ugur Sener, Rachna Malani, Yu Jung Kim, Eiki Ichihara, Victor Cohen, April A.N. Rose, Nathaniel Bouganim, Matthew Dankner
Heliyon.2024; 10(9): e29668. CrossRef
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Original Article

Effects of Postoperative Radiotherapy on Leptomeningeal Carcinomatosis or Dural Metastasis after Resection of Brain Metastases in Breast Cancer Patients: Boram Ha, Seung Yeun Chung, Yeon-Joo Kim, Ho-Shin Gwak, Jong Hee Chang, Sang Hyun Lee, In Hae Park, Keun Seok Lee, Seeyoun Lee, Tae Hyun Kim, Dae Yong Kim, Seok-Gu Kang, Chang-Ok Suh; Cancer Res Treat. 2017;49(3):748-758. Published online October 31, 2016; DOI: https://doi.org/10.4143/crt.2016.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer.
Materials and Methods
Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not.
Results
With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM.
Conclusion
WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

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Stroke associated with microvascular tumoral infiltration in a patient with metastatic breast cancer
Joshua Mangerel, Andres Rodriguez-Sein, Daniel Masri
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Revisiting the Role of Surgical Resection for Brain Metastasis
Joonho Byun, Jong Hyun Kim
Brain Tumor Research and Treatment.2023; 11(1): 1. CrossRef
Literature Review: Role of Neurosurgery in Leptomeningeal Carcinomatosis
Thaís Mitie Ogasawara, Thaís Yumi Kobayashi Batista, Rafael Rodrigues Pinheiro dos Santos, Ana Carla Mondek Rampazzo, Caroline Amane Pessoa Badaoui, Igor Ruan de Araújo Caetano, Jonathan Vinícius Martins, Maria Letícia Nogueira, José Ângelo Guarnieri, Car
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Iatrogenic Leptomeningeal Carcinomatosis Following Craniotomy for Resection of Metastatic Serous Ovarian Carcinoma: A Systematic Literature Review and Case Report
Brittany M. Stopa, Joshua A. Cuoco, Srijan Adhikari, Douglas J. Grider, Cara M. Rogers, Eric A. Marvin
Frontiers in Surgery.2022;[Epub] CrossRef
Autocrine GMCSF Signaling Contributes to Growth of HER2+ Breast Leptomeningeal Carcinomatosis
Khairul I. Ansari, Arunoday Bhan, Mika Saotome, Antariksh Tyagi, Bony De Kumar, Clara Chen, Motoki Takaku, Rahul Jandial
Cancer Research.2021; 81(18): 4723. CrossRef
Leptomeningeal carcinomatosis in patients with breast cancer
Maria Alice Franzoi, Gabriel N. Hortobagyi
Critical Reviews in Oncology/Hematology.2019; 135: 85. CrossRef
Leptomeningeal Metastases
Jerome J. Graber, Santosh Kesari
Current Treatment Options in Oncology.2018;[Epub] CrossRef
Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study
Seung Yeun Chung, Jong Hee Chang, Hye Ryun Kim, Byoung Chul Cho, Chang Geol Lee, Chang-Ok Suh
Radiation Oncology Journal.2017; 35(2): 153. CrossRef

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Case Report

Intrathecal Trastuzumab Treatment in Patients with Breast Cancer and Leptomeningeal Carcinomatosis: Won-Young Park, Han-Jo Kim, Kyoungha Kim, Sang-Byung Bae, Namsu Lee, Kyu-Taek Lee, Jong-Ho Won, Hee-Sook Park, Sang-Cheol Lee; Cancer Res Treat. 2016;48(2):843-847. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.234

Abstract PDF PubReader ePub

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.

Citations

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The research progress on meningeal metastasis in solid tumors
Yi Yue, Yuqing Ren, Chunya Lu, Nan Jiang, Sihui Wang, Junkai Fu, Mengrui Kong, Guojun Zhang
Discover Oncology.2025;[Epub] CrossRef
An overview of the therapeutic strategies for neoplastic meningitis due to breast cancer: when and why?
Mainak Bardhan, Debankur Dey, Vinay Suresh, Binish Javed, Vyshak Alva Venur, Neha Joe, Ritvika Kalidindi, Ahmad Ozair, Marium Khan, Reshma Mahtani, Simon Lo, Yazmin Odia, Manmeet S. Ahluwalia
Expert Review of Neurotherapeutics.2024; 24(1): 77. CrossRef
Intrathecal Trastuzumab for HER2-Positive Cancer of Unknown Primary Leptomeningeal Metastasis: A Case Report
Kohei Oka, Shun Futamura, Taishi Harada
Cureus.2024;[Epub] CrossRef
A Review on the Efficacy and Safety of Intrathecal Administration of Novel Medications for Leptomeningeal Metastases in Solid Cancers
Fatemeh Jafari, Mohammad Moeini Nodeh, Hesamoddin Hosseinjani, Hamed Baharara, Sajad Azad, Omid Arasteh, Thomas P. Johnston, Amirhossein Sahebkar
Current Medicinal Chemistry.2024; 31(19): 2732. CrossRef
Leptomeningeal Carcinomatosis from Solid Tumor Malignancies: Treatment Strategies and Biomarkers
Rachna Malani, Ankush Bhatia, Allison Betof Warner, Jonathan T. Yang
Seminars in Neurology.2023; 43(06): 859. CrossRef
Leptomeningeal metastases: the future is now
Rimas V. Lukas, Jigisha P. Thakkar, Massimo Cristofanilli, Sunandana Chandra, Jeffrey A. Sosman, Jyoti D. Patel, Priya Kumthekar, Roger Stupp, Maciej S. Lesniak
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Durable Effect of Pyrotinib and Metronomic Vinorelbine in HER2-Positive Breast Cancer With Leptomeningeal Disease: A Case Report and Literature Review
Yajing Chi, Mao Shang, Liang Xu, Heyi Gong, Rongjie Tao, Lihua Song, Baoxuan Zhang, Sha Yin, Binbin Cong, Huihui Li
Frontiers in Oncology.2022;[Epub] CrossRef
Intrathecal administration of anti-HER2 treatment for the treatment of meningeal carcinomatosis in breast cancer: A metanalysis with meta-regression
Flora Zagouri, Panagiotis Zoumpourlis, Emilie Le Rhun, Rupert Bartsch, Eleni Zografos, Kleoniki Apostolidou, Meletios-Athanasios Dimopoulos, Matthias Preusser
Cancer Treatment Reviews.2020; 88: 102046. CrossRef
Leptomeningeal carcinomatosis in patients with breast cancer
Maria Alice Franzoi, Gabriel N. Hortobagyi
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Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy
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Nicholas B. Figura, Victoria T. Rizk, Avan J. Armaghani, John A. Arrington, Arnold B. Etame, Hyo S. Han, Brian J. Czerniecki, Peter A. Forsyth, Kamran A. Ahmed
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Kelsey M Bowman, Priya Kumthekar
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Intrathecal trastuzumab in the management of HER2+ breast leptomeningeal disease: a single institution experience
Nicholas B. Figura, Wendy Long, Michael Yu, Timothy J. Robinson, Sepideh Mokhtari, Arnold B. Etame, Nam D. Tran, Roberto Diaz, Hatem Soliman, Heather S. Han, Solmaz Sahebjam, Peter A. Forsyth, Kamran A. Ahmed
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Niyanta N. Kumar, Michelle E. Pizzo, Geetika Nehra, Brynna Wilken-Resman, Sam Boroumand, Robert G. Thorne
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J. Remon, E. Le Rhun, B. Besse
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Ciara C. O’Sullivan, Nicole N. Davarpanah, Jame Abraham, Susan E. Bates
Seminars in Oncology.2017; 44(2): 85. CrossRef
Leptomeningeal disease: current diagnostic and therapeutic strategies
Gautam Nayar, Tiffany Ejikeme, Pakawat Chongsathidkiet, Aladine A. Elsamadicy, Kimberly L. Blackwell, Jeffrey M. Clarke, Shivanand P. Lad, Peter E. Fecci
Oncotarget.2017; 8(42): 73312. CrossRef
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Original Articles

Treatment Results of Postoperative Radiation Therapy for Malignant and Atypical Meningioma: Sang Min Yoon, Seung Do Ahn, Hyesook Chang, Eun Kyung Choi, Jong Hun Kim, Sang wook Lee, Chang Jin Kim, Jung Hun Kim, Byung Deuk Kwon; Cancer Res Treat. 2002;34(2):139-144. Published online April 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.2.139

Abstract PDF

PURPOSE
We evaluated the survival rate, prognostic factors and patterns of failure in malignant and atypical meningiomas, and investigated the role of radiation therapy in the treatment of these tumors.
MATERIALS AND METHODS
We retrospectively reviewed nineteen patients treated at Asan Medical Center between Mar. 1994 and Jun. 2000 with histologically confirmed malignant or atypical meningiomas. The median patient age was 52 years. The extent of surgery prior to radiation was gross total resection in 13 and subtotal resection in 6. Eleven patients were referred for radiation immediately after diagnosis and the remainder after at least one recurrence. All patients received megavoltage radiation to a median dose of 55.8 Gy. The median follow-up period was 41 months.
RESULTS
Eleven patients (57.9%) showed no evidence of disease, five patients died of meningioma and three were alive with disease. The 5-year overall and relapse-free survivals were 75.9 and 50.6%, respectively. There were no statistically significant prognostic factors found to be associated with relapse-free survival by univariate or multivariate analysis. During the follow-up period, no significant treatment-related complications were detected.
CONCLUSION
The major patterns of failure were in-field recurrence. In order to reduce local failure, a higher radiation dose may be needed and a high precision therapy should be considered.

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Revisiting Adjuvant Radiotherapy After Gross Total Resection of World Health Organization Grade II Meningioma
Christopher S. Graffeo, Heather E. Leeper, Avital Perry, Joon H. Uhm, Daniel J. Lachance, Paul D. Brown, Daniel J. Ma, Jamie J. Van Gompel, Caterina Giannini, Derek R. Johnson, Aditya Raghunathan
World Neurosurgery.2017; 103: 655. CrossRef

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Leptomeningeal Carcinomatosis in Solid Tumors; Clinical Manifestation and Treatment: Joon Oh Park, Hyun Joon Shin, Hyung Jong Kim, Sang Wook Lee, Hei Cheul Jeung, Seung Min Kim, Nae Choon Yoo, Hyun Cheol Chung, Joo Hang Kim, Byung Soo Kim, Jin Sik Min, Jae Kyung Roh; J Korean Cancer Assoc. 2001;33(1):34-40.

Abstract PDF: PURPOSE
Leptomeningeal carcinomatosis occurs in about 5% of patients with solid tumor and is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. In general, the most commom cancers that involved the leptomeninges are breast cancer, lung cancer, and malignant melanoma.
MATERIALS AND METHODS
We investigated 25 patients presented with multiple neurologic symptoms and signs who were diagnosed with leptomeningeal carcinomatosis at the Yonsei Cancer Center from January 1990 to December 1999.
RESULTS
The primary disease of leptomeningeal carcinomatosis were stomach cancer (10 cases), breast cancer (7 cases), lung cancer (5 cases), unknown primary cancer (2 cases) and common bile duct cancer (1 case). All patients were presented with multiple neurologic symptoms and signs involving the central nervous system (CNS), cranial nerve or spinal nerves. Twenty-one of twenty- five patients were treated with intrathecal chemotherapy, radiotherapy, or combination therapy. Fourteen of them (66.7%) experienced improvement or stabilization of neurologic symptom and sign. The median survival was 122 days (10-2190).
CONCLUSION
In conclusion, although early diagnosis and active treatment of leptomeningeal carcinomatosis may improve the quality of life in selected patients, the median survival was relatively short. Therefore, new diagnostic and therapeutic strategy for leptomeningeal carcinomatosis were needed.

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Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer: Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):464-474.

Abstract PDF: PURPOSE
Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer.
MATERIALS AND METHODS
The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years.
RESULTS
The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good.
CONCLUSION
Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.

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A Case of Cryptococcal Meningitis in a Brest Cancer Patient with Liver Metastasis, Suffering from Herpes Zoster: Chul Woo Ahn, Wook Jin Chung, Beom Seok Kim, Se Hang Cho, Sun Young Rha, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Hee Jung Kim, Kwang Gil Lee; J Korean Cancer Assoc. 1997;29(3):540-540.

Abstract PDF: Cryptococcosis is a relatively common mycosis of human caused by a worldwide Cryptococcus neoformans. Cryptococcosis occurs more frequently in immuno-compromised hosts such as patients with lymphoma, AIDS, leukemia and other debilitating diseases which manifest a condition of altered cell mediated immunity. Also cancer patients with anticancer chemotherapy are at high risk. Cryptococcosis is primarily a pulmonary disease that remains asymptomatic and unrecognised in most cases. Meningitic and meningoencephalitc forms are more frequently diagnosed because of their striking clinical symptoms.Meningoencephalitis is an uncommon form of cryptoccocosis that often leads to coma and death within a short time, if it is not quickly diagnosed and treated properly. The treatment of choice for the cryptococcosis consists of intravenous amphotericin B and 5-fluorocytocine. We report a case of cryptococcal meningitis in 47-year-old female breast cancer patient with liver metastasis after systemic chemotherapy. She complained headach, fever and diagnosed as cryptococcal meningitis after the India ink smear and culture of CSF. After treated with amphotericin B, her conditions were improved.

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Malignant Histiocytosis Invoving Meninges - A case report -: Cheol Seung Youn, Hyeon Kim, Dong Myeong Lim, Dae Cheol Wee, Yeun Keun Lim, Hyang Soon Yeo, Hong Bae Park, Young Hyu Kim, Sang Woo Juhng, Sang Woo Juhng; J Korean Cancer Assoc. 1994;26(2):337-345.

Abstract PDF: A l7-year-old girl presented with fever and headache. A brain CT found tentorial thickening that mimicked tuberculous meningitis. She had received antituberculous medication, which failed to respond, and subsequently developed anemia, hepato-plenomegaly and lymph- adenopathy. A bone marrow aspiration revealed erythrophagocytic histiocytes and a lymph node biopsy disclosed lysozyme positive malignant histiocytes. She died 7 months after the onset of the illness. We report a case of malignant histiocytosis involving meninges at initial presentation.

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