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Pachymeningeal disease: a systematic review and metanalysis

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Abstract

Background

Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors.

Methods

A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023.

Results

We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9–38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status.

Conclusion

While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.

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Data Availability

Research data are stored in an institutional repository and will be shared upon reasonable request to the corresponding author.

References

  1. Johnson JDYB (1996) Demographics of brain metastasis. Neurosurg Clin N Am 7(3):337–344

    Article  CAS  PubMed  Google Scholar 

  2. Enrique GV, Irving SR, Ricardo BI, Jesus FL, Alan RM, Inigo VAA et al (2019) Diagnosis and management of brain metastases: an updated review from a radiation oncology perspective. J Cancer Metastasis Treat. ;2019

  3. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ et al (1998) Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. J Am Med Assoc 280(17):1485–1489

    Article  CAS  Google Scholar 

  4. O’Halloran PJ, Gutierrez E, Kalyvas A, Mohan N, Atallah S, Kalia S et al (2021) Brain metastases: a modern Multidisciplinary Approach. Can J Neurol Sci / J Canadien des Sci Neurologiques 48(2):189–197

    Article  Google Scholar 

  5. Roy A, Patchell (2003) The management of brain metastases. Cancer Treat Rev 29(6):533–540

    Article  Google Scholar 

  6. Wang JL, Elder JB (2020) Techniques for Open Surgical Resection of Brain Metastases. Neurosurg Clin N Am [Internet]. ;31(4):527–36. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1042368020300553

  7. Ashok Modha SRS& PHG (2005) Surgery of brain metastases – is there still a place for it? J Neurooncol 75:21–29

    Article  Google Scholar 

  8. Roy A, Patchell, Phillip A, Tibbs JWW et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500

    Article  Google Scholar 

  9. Brown PD, Ballman KV, Cerhan JH, Anderson SK, Carrero XW, Whitton AC et al (2017) Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 18(8):1049–1060

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cagney DN, Lamba N, Sinha S, Catalano PJ, Bi WL, Alexander BM et al (2019) Association of Neurosurgical Resection with Development of Pachymeningeal Seeding in Patients with Brain Metastases. JAMA Oncol. ;5(5):703–9. https://doi.org/10.1001/jamaoncol.2018.7204

  11. Gutiérrez-Valencia E, Kalyvas A, Villafuerte CJ, Millar BA, Laperriere N, Conrad T et al (2022) Factors correlating with survival following adjuvant or definitive radiosurgery for large brain metastases. Neuro Oncol [Internet]. ; Available from: https://academic.oup.com/neuro-oncology/advance-article/doi/https://doi.org/10.1093/neuonc/noac106/6574580

  12. Turner BE, Prabhu RS, Burri SH, Brown PD, Pollom EL, Milano MT et al (2020) Nodular Leptomeningeal Disease—A Distinct Pattern of Recurrence After Postresection Stereotactic Radiosurgery for Brain Metastases: A Multi-institutional Study of Interobserver Reliability. Int J Radiat Oncol Biol Phys [Internet]. ;106(3):579–86. https://doi.org/10.1016/j.ijrobp.2019.10.002

  13. Prabhu RS, Turner BE, Asher AL, Marcrom SR, Fiveash JB, Foreman PM et al (2021) Leptomeningeal disease and neurologic death after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis. Adv Radiat Oncol [Internet]. ;6(2):100644. https://doi.org/10.1016/j.adro.2021.100644

  14. Kalyvas A, Gutierrez-Valencia E, Lau R, Ye XY, O’Halloran PJ, Mohan N et al (2023) Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery. J Neurooncol [Internet]. ;163(1):269–79. Available from: https://link.springer.com/https://doi.org/10.1007/s11060-023-04325-3

  15. Le Rhun E, Weller M, Brandsma D, Van den Bent M, de Azambuja E, Henriksson R, Boulanger T, Peters S, Watts C, Wick W, Wesseling P, Rudà R, Preusser M, EANO Executive Board and ESMO Guidelines Committee (2017) ;. EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours. Ann Oncol. ;28(suppl_4):iv84-iv99. https://doi.org/10.1093/annonc/mdx221

  16. R Core Team. R: A Language and Environment for Statistical Computing [Internet]. Vienna, Austria (2016) ; Available from: https://www.R-project.org/

  17. Hothorn T, Hornik K, van de Wiel MA, Zeileis A Implementing a Class of Permutation Tests: The coin Package. J. Stat. Soft. [Internet]. 2008 Nov. 13;28(8):1–23. Available from: https://www.jstatsoft.org/index.php/jss/article/view/v028i08

  18. Balduzzi S, Rücker G, Schwarzer G (2019) 22(4) How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health [Internet]. 153–160. https://doi.org/10.1136/ebmental-2019-300117

  19. Prabhu RS, Akinyelu T, Vaslow ZK, Matsui JK, Haghighi N, Dan T et al (2023) Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases. JAMA Oncol [Internet]. ;1;9(8):1066–1073. https://doi.org/10.1001/jamaoncol.2023.1629

  20. Evin C, Eude Y, Jacob J, Jenny C, Bourdais R, Mathon B et al (2023) Hypofractionated postoperative stereotactic radiotherapy for large resected brain metastases. Cancer Radiother [Internet]. ;27(2):87–95. https://doi.org/10.1016/j.canrad.2022.07.006

  21. Morshed RA, Saggi S, Cummins DD, Molinaro AM, Young JS, Viner JA et al (2023) Identification of risk factors associated with leptomeningeal disease after resection of brain metastases. J Neurosurg [Internet]. ;1–12. https://doi.org/10.3171/2022.12.jns221490

  22. Abdulhaleem M, Ruiz J, O’Neill S, Hughes RT, Qasem S, Strowd RE et al (2023) Collagen deposition within brain metastases is associated with leptomeningeal failure after cavity-directed radiosurgery. Neurooncol Adv [Internet]. ;5(1). https://doi.org/10.1093/noajnl/vdac186

  23. Teyateeti A, Brown PD, Mahajan A, Laack NN, Pollock BE (2021) Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery. Neurooncol Adv [Internet]. ;3(1):vdab036–vdab036. https://doi.org/10.1093/noajnl/vdab036

  24. Prabhu RS, Dhakal R, Vaslow ZK, Dan T, Mishra MV, Murphy ES et al (2021) Preoperative Radiosurgery for Resected Brain Metastases: The PROPS-BM Multicenter Cohort Study. Int J Radiat Oncol Biol Phys [Internet]. ;111(3):764–72. https://doi.org/10.1016/j.ijrobp.2021.05.124

  25. Shi S, Sandhu N, Jin MC, Wang E, Jaoude JA, Schofield K et al (2020) Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of Over 500 Cavities. Int J Radiat Oncol Biol Phys [Internet]. ;106(4):764–71. https://doi.org/10.1016/j.ijrobp.2019.11.022

  26. Nguyen TK, Sahgal A, Detsky J, Atenafu EG, Myrehaug S, Tseng CL et al (2020) Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases. Neuro Oncol [Internet]. ;22(1):84–93. https://doi.org/10.1093/neuonc/noz144

  27. Prabhu RS, Turner BE, Asher AL, Marcrom SR, Fiveash JB, Foreman PM et al (2019) A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases. Neuro Oncol [Internet]. ;21(8):1049–59. https://doi.org/10.1093/neuonc/noz049

  28. Johnson MD, Avkshtol V, Baschnagel AM, Meyer K, Ye H, Grills IS et al (2016) Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated with Stereotactic Radiosurgery. Int J Radiat Oncol Biol Phys [Internet]. ;94(3):537–43. https://doi.org/10.1016/j.ijrobp.2015.11.022

  29. Burri SH, Ward MC, Prabhu RS, Hobgoblins (2020) Iron Lungs, and Surgical Perturbation Failure? Int J Radiat Oncol Biol Phys [Internet]. ;108(4):996–8. https://doi.org/10.1016/j.ijrobp.2020.06.032

  30. Soliman H, Ruschin M, Angelov L, Brown PD, Chiang VLS, Kirkpatrick JP et al (2018) Consensus Contouring Guidelines for Postoperative Completely Resected Cavity Stereotactic Radiosurgery for Brain Metastases. Int J Radiat Oncol Biol Phys [Internet]. ;100(2):436–42. https://doi.org/10.1016/j.ijrobp.2017.09.047

  31. Byrne JD, Botticello T, Niemierko A, Shih HA, Loeffler JS, Oh KS (2020) Post-operative radiation therapy to the surgical cavity with standard fractionation in patients with brain metastases. Sci Rep [Internet]. ;10(1). https://doi.org/10.1038/s41598-020-63158-6

  32. ClinicalTrials.gov. Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease [Internet]. (n.d.) [cited 2023 Sep 2]. Available from: https://clinicaltrials.gov/study/NCT04114981

  33. Boyle R, Thomas M, Adams JH (1980) Diffuse involvement of the leptomeninges by tumour–a clinical and pathological study of 63 cases. Postgrad Med J [Internet]. ;56(653):149–58. https://doi.org/10.1136/pgmj.56.653.149 therapeutic targets. Cancer Discov [Internet]. 2015;5(11):1164–77. Available from: https://doi.org/10.1158/2159-8290.cd-15-0369

  34. Marcrom SR, Foreman PM, Colvin TB et al (2019) Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease. Adv Radiat Oncol. ;5(1):34–42. Published 2019 Aug 5. https://doi.org/10.1016/j.adro.2019.07.016

  35. Dohm A, McTyre ER, Okoukoni C et al (2018) Staged Stereotactic Radiosurgery for Large Brain Metastases: Local Control and Clinical Outcomes of a One-Two Punch Technique. Neurosurgery. ;83(1):114–121. https://doi.org/10.1093/neuros/nyx355

  36. Asher AL, Burri SH, Wiggins WF, Kelly RP, Boltes MO, Mehrlich M et al (2014) A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys [Internet]. ;88(4):899–906. https://doi.org/10.1016/j.ijrobp.2013.12.013

  37. Davies MA, Saiag P, Robert C et al (2017). Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. ;18(7):863–873. https://doi.org/10.1016/S1470-2045(17)30429-1

  38. McArthur GA, Maio M, Arance A et al (2017). Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study. Ann Oncol. ;28(3):634–641. https://doi.org/10.1093/annonc/mdw641

  39. Reungwetwattana T, Nakagawa K, Cho BC et al (2018). CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non–small-cell lung cancer. J Clin Oncol. ;36(33):3290–3297. https://doi.org/10.1200/jco.2018.78.3118

  40. Peters S, Camidge DR, Shaw AT et al (2017) Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer. N Engl J Med. ;377(9):829–838. https://doi.org/10.1056/nejmoa1704795

  41. Camidge DR, Kim DW, Tiseo M et al (2018). Exploratory analysis of brigatinib activity in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer and brain metastases in two clinical trials. J Clin Oncol. ;36(26):2693–2701. https://doi.org/10.1200/jco.2017.77.5841

  42. Sutherland S, Ashley S, Miles D et al (2010). Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases—the UK experience. Br J Cancer. ;102(6):995–1002. https://doi.org/10.1038/sj.bjc.6605586

  43. Lin NU, Murthy RK, Abramson V et al (2023) Tucatinib vs Placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: updated exploratory analysis of the HER2CLIMB randomized clinical trial [published correction appears in JAMA Oncol 9(2):284]. JAMA Oncol 9(2):197–205. https://doi.org/10.1001/jamaoncol.2022.5610

  44. Tawbi HA, Forsyth PA, Hodi FS et al (2021) Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol 22(12):1692–1704. https://doi.org/10.1016/S1470-2045(21)00545-3

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Funding

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Authors and Affiliations

  1. MHA Radiation Medicine Program, Princess Margaret Cancer Center, University of Toronto, 7th Floor, OPG Building, 700 University Ave., Toronto, ON, M5G2M9, Canada

    Enrique Gutiérrez-Valencia, Kurl Jamora, Barbara-Ann Millar & David B. Shultz

  2. Department of Radiation Oncology, Western National Medical Center, University of Guadalajara, Jalisco, Mexico

    Irving Sánchez, Adrián Valles, Omar Díaz, Ricardo Balderrama, Jesús Fuentes, Victor Ruiz, José Rodríguez, Carlos Saavedra, Lorena Velázquez-Pulido, Eduard Cadavid, Luis E. Ayala-Hernández, Alejandro Villalvazo & Luis H. Bayardo

  3. Department of Radiation Oncology, Cancer Center ABC, The American British Cowdray Medical Center, Mexico City, Las Americas, 01120, Mexico

    Tomás F. González

  4. Division of Neurosurgery, Toronto Western Hospital - University of Toronto, Toronto, ON, Canada

    Aristotelis Kalyvas & Kaiyun Yang

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  1. Enrique Gutiérrez-Valencia
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Contributions

Author contributions Conceptualization: EGV, IS, AV, JR, CS, BAM and DBS. Methodology: EGV, IS, JR, CS, LEAH, LHB, KJ, AK, KY, BAM, and DBS. Data collection: EGV, IS, AV, OD, TFG, RB, JF, VR, JR, CS, LVP, EC, AV, LHB, KJ, AK, KY. BAM and DBS. Data analysis: EGV, IS, LEAH, LHB, KJ, AK, KY, BAM, and DBS. Data interpretation: EGV, IS, AV, OD, TFG, RB, JF, VR, JR, CS, LVP, EC, AV, LHB, KJ, AK, KY. BAM, and DBS. Writing—original draft preparation: EGV, IS and DBS. Editing/approving final manuscript: all authors.

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Correspondence to Enrique Gutiérrez-Valencia.

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Enrique Gutiérrez-Valencia, Irving Sánchez Denotes share first authorship.

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Gutiérrez-Valencia, E., Sánchez, I., Valles, A. et al. Pachymeningeal disease: a systematic review and metanalysis. J Neurooncol 165, 29–39 (2023). https://doi.org/10.1007/s11060-023-04476-3

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