DOI QR코드

DOI QR Code

Cerebrospinal Fluid Profiles and Their Changes after Intraventricular Chemotherapy as Prognostic or Predictive Markers for Patients with Leptomeningeal Carcinomatosis

  • Kwon, Ji-Woong (Neuro-oncology Clinic, National Cancer Center) ;
  • Shim, Youngbo (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Gwak, Ho-Shin (Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy) ;
  • Park, Eun Young (Biostatistics Collaboration Team, National Cancer Center) ;
  • Joo, Jungnam (Biostatistics Collaboration Team, National Cancer Center) ;
  • Yoo, Heon (Neuro-oncology Clinic, National Cancer Center) ;
  • Shin, Sang-Hoon (Neuro-oncology Clinic, National Cancer Center)
  • Received : 2020.10.21
  • Accepted : 2020.12.30
  • Published : 2021.07.01

Abstract

Objective : Here, we evaluated whether cerebrospinal fluid (CSF) profiles and their changes after intraventricular chemotherapy for leptomeningeal carcinomatosis (LMC) could predict the treatment response or be prognostic for patient overall survival (OS) along with clinical factors. Methods : Paired 1) pretreatment lumbar, 2) pretreatment ventricular, and 3) posttreatment ventricular samples and their CSF profiles were collected retrospectively from 148 LMC patients who received Ommaya reservoir installation and intraventricular chemotherapy. CSF profile changes were assessed by calculating the differences between posttreatment and pretreatment samples from the same ventricular compartment. CSF cell counts were further differentiated into total and other based on clinical laboratory reports. Results : For the treatment response, a decreased CSF 'total' cell count tended to be associated with a 'controlled' increase in intracranial pressure (ICP) (p=0.059), but other profile changes were not associated with either the control of increased ICP or the cytology response. Among the pretreatment CSF profiles, lumbar protein level and ventricular cell count were significantly correlated with OS in univariable analysis, but they were not significant in multi-variable analysis. Among CSF profile changes, a decrease in 'other' cell count showed worse OS than 'no change' or increased groups (p=0.001). The cytological response was significant for OS, but the hazard ratio of partial remission was paradoxically higher than that of 'no response'. Conclusion : A decrease in other cell count of CSF after intraventricular chemotherapy was associated with poor OS in LMC patients. We suggest that more specific CSF biomarkers of cancer cell origin are needed.

Keywords

Acknowledgement

This work was supported by a grant (1910090-2) from the National Cancer Center, Korea. The sponsor had no role in the design or conduct of this research.

References

  1. Ahn JH, Lee SH, Kim S, Joo J, Yoo H, Lee SH, et al. : Risk for leptomeningeal seeding after resection for brain metastases: implication of tumor location with mode of resection. J Neurosurg 116 : 984-993, 2012 https://doi.org/10.3171/2012.1.JNS111560
  2. An YJ, Cho HR, Kim TM, Keam B, Kim JW, Wen H, et al. : An NMR metabolomics approach for the diagnosis of leptomeningeal carcinomatosis in lung adenocarcinoma cancer patients. Int J Cancer 136 : 162-171, 2015 https://doi.org/10.1002/ijc.28949
  3. Balm M, Hammack J : Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol 53 : 626-632, 1996 https://doi.org/10.1001/archneur.1996.00550070064013
  4. Boogerd W, Hart AA, van der Sande JJ, Engelsman E : Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. Cancer 67 : 1685-1695, 1991 https://doi.org/10.1002/1097-0142(19910315)67:6<1685::AID-CNCR2820670635>3.0.CO;2-M
  5. Boogerd W, van den Bent MJ, Koehler PJ, Heimans JJ, van der Sande JJ, Aaronson NK, et al. : The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer 40 : 2726-2733, 2004 https://doi.org/10.1016/j.ejca.2004.08.012
  6. Bruna J, Gonzalez L, Miro J, Velasco R, Gil M, Tortosa A, et al. : Leptomeningeal carcinomatosis: prognostic implications of clinical and cerebrospinal fluid features. Cancer 115 : 381-389, 2009 https://doi.org/10.1002/cncr.24041
  7. Chamberlain MC : Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol 38 : 135-140, 1998 https://doi.org/10.1023/A:1005982826121
  8. Chamberlain MC : Leptomeningeal metastasis. Curr Opin Oncol 22 : 627-635, 2010 https://doi.org/10.1097/CCO.0b013e32833de986
  9. Chamberlain MC, Glantz M, Groves MD, Wilson WH : Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk, and determining benefit of treatment. Semin Oncol 36(4 Suppl 2) : S35-S45, 2009 https://doi.org/10.1053/j.seminoncol.2009.05.005
  10. Chamberlain MC, Kormanik P : Carcinoma meningitis secondary to nonsmall cell lung cancer: combined modality therapy. Arch Neurol 55 : 506-512, 1998 https://doi.org/10.1001/archneur.55.4.506
  11. Chamberlain MC, Kormanik PA, Glantz MJ : A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases. Neuro Oncol 3 : 42-45, 2001 https://doi.org/10.1215/S1522851700000338
  12. Clamon G, Doebbeling B : Meningeal carcinomatosis from breast cancer: spinal cord vs. brain involvement. Breast Cancer Res Treat 9 : 213-217, 1987 https://doi.org/10.1007/BF01806382
  13. de Azevedo CR, Cruz MR, Chinen LT, Peres SV, Peterlevitz MA, de Azevedo Pereira AE, et al. : Meningeal carcinomatosis in breast cancer: prognostic factors and outcome. J Neurooncol 104 : 565-572, 2011 https://doi.org/10.1007/s11060-010-0524-y
  14. Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, et al. : Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer 77 : 1315-1323, 1996 https://doi.org/10.1002/(SICI)1097-0142(19960401)77:7<1315::AID-CNCR14>3.0.CO;2-4
  15. Freilich RJ, Krol G, DeAngelis LM : Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 38 : 51-57, 1995 https://doi.org/10.1002/ana.410380111
  16. Gauthier H, Guilhaume MN, Bidard FC, Pierga JY, Girre V, Cottu PH, et al. : Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol 21 : 2183-2187, 2010 https://doi.org/10.1093/annonc/mdq232
  17. Glantz MJ, Hall WA, Cole BF, Chozick BS, Shannon CM, Wahlberg L, et al. : Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer 75 : 2919-2931, 1995 https://doi.org/10.1002/1097-0142(19950615)75:12<2919::AID-CNCR2820751220>3.0.CO;2-9
  18. Glass JP, Melamed M, Chernik NL, Posner JB : Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology 29 : 1369-1375, 1979 https://doi.org/10.1212/WNL.29.10.1369
  19. Gleissner B, Chamberlain MC : Neoplastic meningitis. Lancet Neurol 5 : 443-452, 2006 https://doi.org/10.1016/S1474-4422(06)70443-4
  20. Grossman SA, Krabak MJ : Leptomeningeal carcinomatosis. Cancer Treat Rev 25 : 103-119, 1999 https://doi.org/10.1053/ctrv.1999.0119
  21. Groves MD, Glantz MJ, Chamberlain MC, Baumgartner KE, Conrad CA, Hsu S, et al. : A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies. Neuro Oncol 10 : 208-215, 2008 https://doi.org/10.1215/15228517-2007-059
  22. Gwak HS, Joo J, Kim S, Yoo H, Shin SH, Han JY, et al. : Analysis of treatment outcomes of intraventricular chemotherapy in 105 patients for leptomeningeal carcinomatosis from non-small-cell lung cancer. J Thorac Oncol 8 : 599-605, 2013 https://doi.org/10.1097/JTO.0b013e318287c943
  23. Gwak HS, Joo J, Shin SH, Yoo H, Han JY, Kim HT, et al. : Ventriculolumbar perfusion chemotherapy with methotrexate for treating leptomeningeal carcinomatosis: a phase II study. Oncologist 19 : 1044-1045, 2014 https://doi.org/10.1634/theoncologist.2014-0199
  24. Harstad L, Hess KR, Groves MD : Prognostic factors and outcomes in patients with leptomeningeal melanomatosis. Neuro Oncol 10 : 1010-1018, 2008 https://doi.org/10.1215/15228517-2008-062
  25. Herrlinger U, Forschler H, Kuker W, Meyermann R, Bamberg M, Dichgans J, et al. : Leptomeningeal metastasis: survival and prognostic factors in 155 patients. J Neurol Sci 223 : 167-178, 2004 https://doi.org/10.1016/j.jns.2004.05.008
  26. Hitchins RN, Bell DR, Woods RL, Levi JA : A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5 : 1655-1662, 1987 https://doi.org/10.1200/JCO.1987.5.10.1655
  27. Hyun JW, Shin HS, Kim SH, Kong SY, Yoo H, Gwak HS, et al. : CYFRA 21-1 levels in cerebrospinal fluid as a putative therapeutic monitoring biomarker for patients with leptomeningeal carcinomatosis: a pilot study. Cancer Biomark 28 : 81-89, 2020 https://doi.org/10.3233/CBM-190187
  28. Jayson GC, Howell A : Carcinomatous meningitis in solid tumours. Ann Oncol 7 : 773-786, 1996 https://doi.org/10.1093/oxfordjournals.annonc.a010755
  29. Lee JS, Melisko ME, Magbanua MJ, Kablanian AT, Scott JH, Rugo HS, et al. : Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer. Breast Cancer Res Treat 154 : 339-349, 2015 https://doi.org/10.1007/s10549-015-3610-1
  30. Lin NU, Lee EQ, Aoyama H, Barani IJ, Barboriak DP, Baumert BG, et al. : Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16 : e270-e278, 2015 https://doi.org/10.1016/S1470-2045(15)70057-4
  31. Morris PG, Reiner AS, Szenberg OR, Clarke JL, Panageas KS, Perez HR, et al. : Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol 7 : 382-385, 2012 https://doi.org/10.1097/JTO.0b013e3182398e4f
  32. Nakagawa H, Kubo S, Murasawa A, Nakajima S, Nakajima Y, Izumoto S, et al. : Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis and brain tumors. J Neurooncol 12 : 111-120, 1992
  33. Shim Y, Gwak HS, Kim S, Joo J, Shin SH, Yoo H : Retrospective analysis of cerebrospinal fluid profiles in 228 patients with leptomeningeal carcinomatosis : differences according to the sampling site, symptoms, and systemic factors. J Korean Neurosurg Soc 59 : 570-576, 2016 https://doi.org/10.3340/jkns.2016.59.6.570
  34. Singh SK, Agris JM, Leeds NE, Ginsberg LE : Intracranial leptomeningeal metastases: comparison of depiction at FLAIR and contrast-enhanced MR imaging. Radiology 217 : 50-53, 2000 https://doi.org/10.1148/radiology.217.1.r00oc3550
  35. Singh SK, Leeds NE, Ginsberg LE : MR imaging of leptomeningeal metastases: comparison of three sequences. AJNR Am J Neuroradiol 23 : 817-821, 2002
  36. Taillibert S, Laigle-Donadey F, Chodkiewicz C, Sanson M, Hoang-Xuan K, Delattre JY : Leptomeningeal metastases from solid malignancy: a review. J Neurooncol 75 : 85-99, 2005 https://doi.org/10.1007/s11060-004-8101-x
  37. Teplyuk NM, Mollenhauer B, Gabriely G, Giese A, Kim E, Smolsky M, et al. : MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol 14 : 689-700, 2012 https://doi.org/10.1093/neuonc/nos074
  38. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. : New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92 : 205-216, 2000 https://doi.org/10.1093/jnci/92.3.205
  39. Tu Q, Wu X, Le Rhun E, Blonski M, Wittwer B, Taillandier L, et al. : Cell-Search technology applied to the detection and quantification of tumor cells in CSF of patients with lung cancer leptomeningeal metastasis. Lung Cancer 90 : 352-357, 2015 https://doi.org/10.1016/j.lungcan.2015.09.008
  40. Twijnstra A, van Zanten AP, Hart AA, Ongerboer de Visser BW : Serial lumbar and ventricle cerebrospinal fluid lactate dehydrogenase activities in patients with leptomeningeal metastases from solid and haematological tumours. J Neurol Neurosurg Psychiatry 50 : 313-320, 1987 https://doi.org/10.1136/jnnp.50.3.313
  41. Waki F, Ando M, Takashima A, Yonemori K, Nokihara H, Miyake M, et al. : Prognostic factors and clinical outcomes in patients with leptomeningeal metastasis from solid tumors. J Neurooncol 93 : 205-212, 2009 https://doi.org/10.1007/s11060-008-9758-3
  42. Wasserstrom WR, Glass JP, Posner JB : Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 49 : 759-772, 1982 https://doi.org/10.1002/1097-0142(19820215)49:4<759::AID-CNCR2820490427>3.0.CO;2-7
  43. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. : Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28 : 1963-1972, 2010 https://doi.org/10.1200/JCO.2009.26.3541
  44. Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR : Treatment for meningeal carcinomatosis in breast cancer. Cancer 50 : 219-222, 1982 https://doi.org/10.1002/1097-0142(19820715)50:2<219::AID-CNCR2820500209>3.0.CO;2-7
  45. Yousem DM, Patrone PM, Grossman RI : Leptomeningeal metastases: MR evaluation. J Comput Assist Tomogr 14 : 255-261, 1990 https://doi.org/10.1097/00004728-199003000-00018