Leptomeningeal Carcinomatosis from Solid Tumor Malignancies: Treatment Strategies and Biomarkers

Abstract

Leptomeningeal metastases/diseases (LMDs) are a late-stage complication of solid tumor or hematologic malignancies. LMD is spread of cancer cells to the layers of the leptomeninges (pia and arachnoid maters) and subarachnoid space seen in 3 to 5% of cancer patients. It is a disseminated disease which carries with it significant neurologic morbidity and mortality. Our understanding of disease pathophysiology is currently lacking; however, advances are being made. As our knowledge of disease pathogenesis has improved, treatment strategies have evolved. Mainstays of treatment such as radiotherapy have changed from involved-field radiotherapy strategies to proton craniospinal irradiation which has demonstrated promising results in recent clinical trials. Systemic treatment strategies have also improved from more traditional chemotherapeutics with limited central nervous system (CNS) penetration to more targeted therapies with better CNS tumor response. Many challenges remain from earlier clinical detection of disease through improvement of active treatment options, but we are getting closer to meaningful treatment.

Keywords

Leptomeningeal disease - Lepotomeningeal carcinomatosis - central nervous system - cerebrospinal fluid

Publikationsverlauf

Artikel online veröffentlicht:
21. November 2023

• References

• 1 O'Reilly MA, Chinnery T, Yee ML. et al. Preliminary investigation of focused ultrasound-facilitated drug delivery for the treatment of leptomeningeal metastases. Sci Rep 2018; 8 (01) 9013
• 2 Ricciardi GRR, Russo A, Franchina T. et al. Efficacy of T-DM1 for leptomeningeal and brain metastases in a HER2 positive metastatic breast cancer patient: new directions for systemic therapy - a case report and literature review. BMC Cancer 2018; 18 (01) 97
• 3 Soffietti R, Pellerino A, Rudà R. Neuro-oncology perspective of treatment options in metastatic breast cancer. Future Oncol 2018; 14 (17) 1765-1774
• 4 Wang N, Bertalan MS, Brastianos PK. Leptomeningeal metastasis from systemic cancer: review and update on management. Cancer 2018; 124 (01) 21-35
• 5 Scott BJ, Oberheim-Bush NA, Kesari S. Leptomeningeal metastasis in breast cancer - a systematic review. Oncotarget 2016; 7 (04) 3740-3747
• 6 Griguolo G, Pouderoux S, Dieci MV. et al. Clinicopathological and treatment-associated prognostic factors in patients with breast cancer leptomeningeal metastases in relation to tumor biology. Oncologist 2018; 23 (11) 1289-1299
• 7 Morikawa A, Jordan L, Rozner R. et al. Characteristics and outcomes of patients with breast cancer with leptomeningeal metastasis. Clin Breast Cancer 2017; 17 (01) 23-28
• 8 Figura NB, Rizk VT, Armaghani AJ. et al. Breast leptomeningeal disease: a review of current practices and updates on management. Breast Cancer Res Treat 2019; 177 (02) 277-294
• 9 Pellerino A, Internò V, Mo F, Franchino F, Soffietti R, Rudà R. Management of brain and leptomeningeal metastases from breast cancer. Int J Mol Sci 2020; 21 (22) 8534
• 10 Remsik J, Chi Y, Tong X. et al. Leptomeningeal metastatic cells adopt two phenotypic states. Cancer Rep (Hoboken) 2022; 5 (04) e1236
• 11 Er EE, Valiente M, Ganesh K. et al. Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization. Nat Cell Biol 2018; 20 (08) 966-978
• 12 Boire A, Zou Y, Shieh J, Macalinao DG, Pentsova E, Massagué J. Complement component 3 adapts the cerebrospinal fluid for leptomeningeal metastasis. Cell 2017; 168 (06) 1101-1113.e13
• 13 Chi Y, Remsik J, Kiseliovas V. et al. Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis. Science 2020; 369 (6501) 276-282
• 14 Le Rhun E, Devos P, Weller J. et al. Prognostic validation and clinical implications of the EANO ESMO classification of leptomeningeal metastasis from solid tumors. Neuro Oncol 2021; 23 (07) 1100-1112
• 15 Lin X, Fleisher M, Rosenblum M. et al. Cerebrospinal fluid circulating tumor cells: a novel tool to diagnose leptomeningeal metastases from epithelial tumors. Neuro-oncol 2017; 19 (09) 1248-1254
• 16 Pentsova EI, Shah RH, Tang J. et al. Evaluating cancer of the central nervous system through next-generation sequencing of cerebrospinal fluid. J Clin Oncol 2016; 34 (20) 2404-2415
• 17 Malani R, Fleisher M, Kumthekar P. et al. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer. J Neurooncol 2020; 148 (03) 599-606
• 18 Nayak L, Fleisher M, Gonzalez-Espinoza R. et al. Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors. Neurology 2013; 80 (17) 1598-1605 , discussion 1603
• 19 Lee JS, Melisko ME, Magbanua MJ. et al. Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer. Breast Cancer Res Treat 2015; 154 (02) 339-349
• 20 van Bussel MTJ, Pluim D, Milojkovic Kerklaan B. et al. Circulating epithelial tumor cell analysis in CSF in patients with leptomeningeal metastases. Neurology 2020; 94 (05) e521-e528
• 21 Diaz M, Singh P, Kotchetkov IS. et al. Quantitative assessment of circulating tumor cells in cerebrospinal fluid as a clinical tool to predict survival in leptomeningeal metastases. J Neurooncol 2022; 157 (01) 81-90
• 22 Wijetunga NA, Boire A, Young RJ. et al. Quantitative cerebrospinal fluid circulating tumor cells are a potential biomarker of response for proton craniospinal irradiation for leptomeningeal metastasis. Neurooncol Adv 2021; 3 (01) vdab181
• 23 Freret ME, Wijetunga NA, Shamseddine AA. et al. Early detection of leptomeningeal metastases among patients undergoing spinal stereotactic radiosurgery. Adv Radiat Oncol 2022; 8 (02) 101154
• 24 Hirano Y, Konishi K, Ejima Y. Utility of whole brain radiation therapy for leptomeningeal carcinomatosis. Int J Clin Oncol 2020; 25 (07) 1432-1439
• 25 Graber JJ, Kesari S. Leptomeningeal metastases. Curr Treat Options Oncol 2018; 19 (01) 3
• 26 Wolf A, Donahue B, Silverman JS, Chachoua A, Lee JK, Kondziolka D. Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases. J Neurooncol 2017; 134 (01) 139-143
• 27 Figura NB, Rizk VT, Mohammadi H. et al. Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy. Breast Cancer Res Treat 2019; 175 (03) 781-788
• 28 Buszek SM, Chung C. Radiotherapy in leptomeningeal disease: a systematic review of randomized and non-randomized trials. Front Oncol 2019; 9: 1224
• 29 Brown PD, Pugh S, Laack NN. et al; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-oncol 2013; 15 (10) 1429-1437
• 30 Devecka M, Duma MN, Wilkens JJ. et al. Craniospinal irradiation (CSI) in patients with leptomeningeal metastases: risk-benefit-profile and development of a prognostic score for decision making in the palliative setting. BMC Cancer 2020; 20 (01) 501
• 31 Harada H, Mitsuya K, Asakura H. et al. Cranio-spinal irradiation for leptomeningeal carcinomatosis: a pilot study. Int J Radiat Oncol Biol Phys 2014; 90: S310-S310
• 32 El Shafie RA, Böhm K, Weber D. et al. Palliative radiotherapy for leptomeningeal carcinomatosis-analysis of outcome, prognostic factors, and symptom response. Front Oncol 2019; 8: 641
• 33 El Shafie RA, Böhm K, Weber D. et al. Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis. Cancer Manag Res 2019; 11: 789-801
• 34 Brown AP, Barney CL, Grosshans DR. et al. Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 2013; 86 (02) 277-284
• 35 Yang TJ, Wijetunga NA, Yamada J. et al. Clinical trial of proton craniospinal irradiation for leptomeningeal metastases. Neuro-oncol 2021; 23 (01) 134-143
• 36 Yang JT, Wijetunga NA, Pentsova E. et al. Randomized Phase II trial of proton craniospinal irradiation versus photon involved-field radiotherapy for patients with solid tumor leptomeningeal metastasis. J Clin Oncol 2022; 40 (33) 3858-3867
• 37 Bowman KM, Kumthekar P. Medical management of brain metastases and leptomeningeal disease in patients with breast carcinoma. Future Oncol 2018; 14 (04) 391-407
• 38 Brastianos PK, Lee EQ, Cohen JV. et al. Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Nat Med 2020; 26 (08) 1280-1284
• 39 Glitza IC, Haymaker C, Bernatchez C. et al. Intrathecal administration of tumor-infiltrating lymphocytes is well tolerated in a patient with leptomeningeal disease from metastatic melanoma: a case report. Cancer Immunol Res 2015; 3 (11) 1201-1206
• 40 Yang JCH, Kim SW, Kim DW. et al. Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: the BLOOM study. J Clin Oncol 2020; 38 (06) 538-547
• 41 Nakagawa H, Yui Y, Sasagawa S, Itoh K. Evidence for intrathecal sodium butyrate as a novel option for leptomeningeal metastasis. J Neurooncol 2018; 139 (01) 43-50
• 42 Jaeckle KA, Dixon JG, Anderson SK. et al. Intra-CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases. Cancer Med 2020; 9 (21) 7935-7942
• 43 Glitza Oliva IC, Ferguson SD, Bassett Jr R, Foster AP, John I, Hennegan TD, Rohlfs M, Richard J, Iqbal M, Dett T, Lacey C, Jackson N, Rodgers T, Phillips S, Duncan S, Haydu L, Lin R, Amaria RN, Wong MK, Diab A, Davies MA. Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results. Nature medicine 2023; 29 (04) 898-905
• 44 Lavaud P, Rousseau B, Ajgal Z. et al. Bi-weekly very-high-dose lapatinib: an easy-to-use active option in HER-2-positive breast cancer patients with meningeal carcinomatosis. Breast Cancer Res Treat 2016; 157 (01) 191-192
• 45 Dudani S, Mazzarello S, Hilton J. et al. Optimal management of leptomeningeal carcinomatosis in breast cancer patients-a systematic review. Clin Breast Cancer 2016; 16 (06) 456-470
• 46 Niwińska A, Pogoda K, Michalski W, Kunkiel M, Jagiełło-Gruszfeld A. Determinants of prolonged survival for breast cancer patient groups with leptomeningeal metastasis (LM). J Neurooncol 2018; 138 (01) 191-198
• 47 Park WY, Kim HJ, Kim K. et al. Intrathecal trastuzumab treatment in patients with breast cancer and leptomeningeal carcinomatosis. Cancer Res Treat 2016; 48 (02) 843-847
• 48 Kapke JT, Schneidewend RJ, Jawa ZA, Huang CC, Connelly JM, Chitambar CR. High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: case series and review of the literature. Hematol Oncol Stem Cell Ther 2019; 12 (04) 189-193
• 49 Klement GL, Arkun K, Valik D. et al. Future paradigms for precision oncology. Oncotarget 2016; 7 (29) 46813-46831
• 50 Chen TW, Jan IS, Chang DY. et al. Systemic treatment of breast cancer with leptomeningeal metastases using bevacizumab, etoposide and cisplatin (BEEP regimen) significantly improves overall survival. J Neurooncol 2020; 148 (01) 165-172
• 51 Morikawa A, de Stanchina E, Pentsova E. et al. Phase I study of intermittent high-dose lapatinib alternating with capecitabine for HER2-positive breast cancer patients with central nervous system metastases. Clin Cancer Res 2019; 25 (13) 3784-3792
• 52 Keime-Guibert F, Napolitano M, Delattre JY. Neurological complications of radiotherapy and chemotherapy. J Neurol 1998; 245 (11) 695-708
• 53 Fernandes L, de Matos LV, Cardoso D. et al. Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review. CNS Oncol 2020; 9 (04) CNS65
• 54 Melisko ME, Assefa M, Hwang J, DeLuca A, Park JW, Rugo HS. Phase II study of irinotecan and temozolomide in breast cancer patients with progressing central nervous system disease. Breast Cancer Res Treat 2019; 177 (02) 401-408