Outcome and Prognostic Factors Following Palliative Craniospinal Irradiation for Leptomeningeal Carcinomatosis

Median OS at 19.3 weeks in our current analysis compares favorably to that in previously published analyses in patients with LC: for LC from non-small-cell lung cancer, two relatively large analyses, including 125 and 149 patients, have been published by Morris et al⁶ and Lee et al,¹³ respectively. Median OS estimates were 12.9 and 15.0 weeks in those cohorts that received heterogeneous treatment regimens, including WBRT and RT to the involved regions and differing combinations with ITC and/or systemic chemotherapy. A small subgroup of patients, for whom the administration of EGFR-TKIs was indicated, showed a favorable median OS of up to 14 months.⁶ Similar analyses for breast cancer patients have been recently reviewed by Kak et al.⁵⁶ In several mid-sized cohorts of between 60 and 100 patients, median OS estimates of 10–16 weeks could be achieved.^7,57–59Therapeutic modalities comprised mostly ITC with methotrexate and second-line thiotepa, although Le Rhun et al described a reasonably sized cohort of 103 patients treated with liposomal cytarabine as a first-line therapy, achieving a median OS of 16.3 weeks.¹² Overall results for breast cancer are thus comparable to those previously discussed for lung cancer.

A recent publication by Brower et al assessed the outcome of 124 patients with LC from heterogeneous solid tumors, including unfavorable histologies such as small-cell lung-cancer.¹⁴ In this unselected patient collective, median OS at 9.2 weeks was slightly inferior to the works mentioned before.¹⁴ In our analysis, no statistical significance could be found for the impact of primary histology and in view of the recently discussed works, this is possibly due to the limited number of patients.

In the published literature, as well as our current analysis, survival seems to be highly dependent on patient selection. This is demonstrated most clearly in clinical performance manifesting itself as a central and consistent prognostic factor throughout the great majority of publications available on the subject of LC.^{13–16,60–62} Our analysis is in agreement with that body of literature in confirming the prognostic value of the KPI. For a more comprehensive assessment of the patients’ neurologic function, the NFS scale has proven a useful tool with independent prognostic significance. Its key value lies in providing functional quantification to a reasonable extent and summarizing the neurologic symptoms for better comparability. Several recent publications have confirmed the role and applicability of the NFS for the clinical assessment of baseline status and treatment outcome in patients with CNS metastases.^30,63 Age at LC diagnosis was identified as another prognostic factor in our analysis and in this, consistency can be found with the widely established recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) indices for the prognostic evaluation of CNS metastases.^64–66 The statistically significant identification of these factors despite the limited number of patients in the current analysis emphasizes their decisiveness and suggests that it is, in fact, a very select subgroup of patients that may benefit from CSI as a palliative measure. Furthermore, this implies that rigorous patient selection, based on thorough clinical assessment, and interdisciplinary decision making are necessary to choose the best treatment approach after LC diagnosis.

Limitations of the current study include its retrospective nature and the small number of patients, as well as a possible selection bias, owing to the fact that CSI for the palliative treatment of LC is not an approach generally recommended by the current guidelines. Consequently, it was decided upon on an individual basis for each patient in this group and for differing reasons, including mostly young age, good performance and clinically estimated benefit. Furthermore, the very small number of patients receiving ITC in our cohort permits no assessment of the effect ITC may have had on survival. Analogously, in the era of targeted therapies with proven efficacy inside the CNS,^67,68 comparative data with this form of treatment would be warranted.

CONCLUSION

To the best of our knowledge, this is the larger of only two cohorts in the current literature, for which the specific effect of CSI in the palliative treatment of LC has been evaluated. We could demonstrate treatment feasibility and potential therapeutic value in carefully selected patients, alleviating preexisting symptoms or delaying neurologic deterioration. OS after CSI was comparable to rates described in the current literature for patients with LC. To achieve a reasonable toxicity profile, the use of modern irradiation techniques, such as helical IMRT, is warranted. Patient selection should be done on an individual basis, taking into account prognostic factors such as age, clinical performance, neurologic function and the availability of systemic treatment options.

Ethics approval

Ethics approval for the study and a waiver of written informed consent, as applicable to the retrospective in-house research, were granted by the Heidelberg University ethics committee on April 12, 2018 (#S-172/2018). Patient confidentiality was maintained by anonymizing patient data to remove any identifying information.

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Rami A El Shafie,^1,2 Karina Böhm,^1,2 Dorothea Weber,³ Kristin Lang,^1,2 Fabian Schlaich,^1,2 Sebastian Adeberg,^1,2 Angela Paul,^1,2,4 Matthias F Haefner,^1,2 Sonja Katayama,^1,2 Florian Sterzing,^1,2,5 Juliane Hörner-Rieber,^1,2 Sarah Löw,⁶ Klaus Herfarth,^1,2,4 Jürgen Debus,^1,2,4,7 Stefan Rieken,^1,2,4 Denise Bernhardt^1,2

¹Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany; ²National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany; ³Institute of Medical Biometry and Informatics (IMBI), Heidelberg University Hospital, Heidelberg 69120, Germany; ⁴Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany; ⁵Department of Radiation Oncology, Klinikum Kempten, Kempten 87439, Germany; ⁶Department of Neurology, University Hospital of Heidelberg, Heidelberg 69120, Germany; ⁷German Cancer Research Center (DKFZ), Heidelberg 69120, Germany

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Acknowledgment

This work received indirect financial support by Heidelberg University young investigator grants to RAES, DB and JHR.

Disclosure

The authors report no conflicts of interest in this work.

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Source: Cancer Management and Research

Originally published January 17, 2019.