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Front. Oncol. | doi: 10.3389/fonc.2018.00641

Palliative radiotherapy for leptomeningeal carcinomatosis – analysis of outcome, prognostic factors and symptom response

 Rami A. El Shafie1, 2*, Karina Böhm1, Dorothea Weber3, Kristin Lang1, Fabian Schlaich1, Sebastian Adeberg1, Angela Paul1, Matthias F. Haefner1, Sonja Katayama1, 4,  Juliane Hoerner-Rieber1, 5, Philipp Hoegen1, 5, Sarah Löw5, Jürgen Debus1, 5, 6, 7, 8,  Stefan Rieken1, 5, 8 and  Denise Bernhardt1, 5
  • 1National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Germany
  • 2Department of Radiation Oncology, Heidelberg University Hospital, Germany
  • 3Institut für Medizinische Biometrie und Informatik, UniversitätsKlinikum Heidelberg, Germany
  • 4Department of Radiation Oncology, Heidelberg University Hospital, Germany
  • 5Department of Radiation Oncology, Heidelberg University Hospital, Germany
  • 6Clinical Cooperation Unit Radiation Oncology (E050), German Cancer Research Center (DKFZ), Germany
  • 7Partner Site Heidelberg, German Cancer Research Center (DKFZ), German Cancer Consortium, German Cancer Research Center (DKFZ), Germany
  • 8Heidelberg University Hospital, Heidelberger Ionenstrahl-Therapiezentrum, Universitätsklinikum Heidelberg, Germany

Introduction:
The purpose of this article is to report our institution’s ten-year experience on palliative radiotherapy for the treatment of leptomeningeal carcinomatosis (LC), assessing survival, neurologic outcome and prognostic factors.

Patients and methods:
We retrospectively analyzed 110 patients who received palliative radiotherapy for LC between 2008 and 2018. The most common histologies were breast cancer (n=43, 39.1%) and non-small cell lung cancer (NSCLC) (n=31, 28.2%). Radiotherapy was administered as whole-brain radiotherapy (WBRT) (n=51, 46.4.0%), focal spinal RT (n=11, 10.0%) or both (n=47, 42.7%). 25 patients (22.7%) were selected for craniospinal irradiation. Clinical performance and neurologic function were quantified on the neurologic function scale (NFS) before and in response to therapy. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for survival.

Results:
98 patients (89.1%) died and 12 (10.9%) were alive at the time of analysis. Median OS from LC diagnosis and from the beginning of RT was 13.9 weeks (IQR: 7.1 – 34.0) and 9.9 weeks (IQR: 5.3 – 26.3), respectively. In univariate analysis, prognostic of longer OS were a Karnofsky performance scale index (KPI) of ≥70% (HR 0.20, 95%-CI: [0.13; 0.32], p<0.001), initially moderate neurological deficits (NFS ≤2) (HR 3.15, 95%-CI: [1.90; 5.20], p<0.001), symptom response to RT (HR 0.41, 95%-CI: [0.26; 0.66], p<0.001) and the administration of systemic therapy (HR 0.51, 95%-CI: [0.33; 0.78], p=0.002). Prognostic of inferior OS were high-grade myelosuppression (HR 3.62, 95%-CI: [1.8; 7.4], p<0.001) and serum LDH levels >500 U/l (HR 3.59, 95%-CI: [1.61; 8.01], p=0.002). Clinical performance, symptom response and serum LDH stayed independently prognostic for survival in multivariate analysis. RT was well tolerated and except for grade III myelosuppression in 19 cases (17.3%), no high-grade acute toxicities were observed. Neurologic symptom stabilization was achieved in 83 cases (75.5%) and a sizeable improvement in 39 cases (35.5%).

Conclusion:
Radiotherapy is a well-tolerated and efficacious means of providing symptom palliation for patients with LC, delaying neurologic deterioration while probably not directly influencing survival. Prognostic factors such as clinical performance, neurologic response and serum LDH can be used for patient stratification to facilitate treatment decisions.

Keywords: leptomeningeal metastases, Carcinomatous meningitis, neurologic function, Radiotherapy, palliative, Whole-brain radiotherapy, Craniospinal irradiation

Received: 12 Oct 2018; Accepted: 06 Dec 2018.

Edited by:

Sean P. Collins, School of Medicine, Georgetown University, United States

Reviewed by:

Shahed N. Badiyan, Washington University in St. Louis, United States
Ima Paydar, Hospital of the University of Pennsylvania, United States  

Copyright: © 2018 El Shafie, Böhm, Weber, Lang, Schlaich, Adeberg, Paul, Haefner, Katayama, Hoerner-Rieber, Hoegen, Löw, Debus, Rieken and Bernhardt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD. Rami A. El Shafie, Heidelberg Institute for Radiation Oncology (HIRO), National Center for Radiation Oncology (NCRO), Heidelberg, 69120, Baden-Württemberg, Germany, rami.elshafie@med.uni-heidelberg.de