Outcome and prognostic factors following palliative craniospinal irradiation for leptomeningeal carcinomatosis.

TomoTherapy carcinomatous meningitis leptomeningeal metastases neuroaxis neurologic function radiotherapy

Journal

Cancer management and research
ISSN: 1179-1322
Titre abrégé: Cancer Manag Res
Pays: New Zealand
ID NLM: 101512700

Informations de publication

Date de publication:
2019
Historique:
entrez: 31 1 2019
pubmed: 31 1 2019
medline: 31 1 2019
Statut: epublish

Résumé

Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10-15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45-59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0-2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival. Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3-34.0, 95% CI: 11.0-32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% ( CSI for the treatment of LC is feasible and may have therapeutic value in carefully selected patients, alleviating symptoms or delaying neurologic deterioration. OS after CSI was comparable to the rates described in current literature for patients with LC. The use of modern irradiation techniques such as helical IMRT is warranted to limit toxicity. Patient selection should take into account prognostic factors such as age, clinical performance, neurologic function and the availability of systemic treatment options.

Sections du résumé

BACKGROUND BACKGROUND
Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10-15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC.
PATIENTS AND METHODS METHODS
Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45-59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0-2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival.
RESULTS RESULTS
Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3-34.0, 95% CI: 11.0-32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (
CONCLUSION CONCLUSIONS
CSI for the treatment of LC is feasible and may have therapeutic value in carefully selected patients, alleviating symptoms or delaying neurologic deterioration. OS after CSI was comparable to the rates described in current literature for patients with LC. The use of modern irradiation techniques such as helical IMRT is warranted to limit toxicity. Patient selection should take into account prognostic factors such as age, clinical performance, neurologic function and the availability of systemic treatment options.

Identifiants

pubmed: 30697071
doi: 10.2147/CMAR.S182154
pii: cmar-11-789
pmc: PMC6340499
doi:

Types de publication

Journal Article

Langues

eng

Pagination

789-801

Déclaration de conflit d'intérêts

Disclosure The authors report no conflicts of interest in this work.

Références

Cancer Treat Rev. 1999 Apr;25(2):103-19
pubmed: 10395835
Clin Cancer Res. 1999 Nov;5(11):3394-402
pubmed: 10589750
Neurosurgery. 2000 Jul;47(1):49-54; discussion 54-5
pubmed: 10917346
Strahlenther Onkol. 2001 Apr;177(4):195-9
pubmed: 11370554
Eur J Cancer. 2002 Mar;38(4):487-96
pubmed: 11872340
Neurol Clin. 2003 Feb;21(1):25-66
pubmed: 12690644
Pediatr Blood Cancer. 2004 May;42(5):447-51
pubmed: 15049018
Br J Radiol. 2005 Jun;78(930):548-52
pubmed: 15900062
Cancer. 2006 May 1;106(9):2021-7
pubmed: 16583432
J Neurooncol. 2007 Aug;84(1):57-62
pubmed: 17310266
Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):510-4
pubmed: 17931798
Strahlenther Onkol. 2008 Jan;184(1):8-14
pubmed: 18188517
Neuro Oncol. 2008 Apr;10(2):208-15
pubmed: 18316473
Technol Cancer Res Treat. 2008 Jun;7(3):227-33
pubmed: 18473494
Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1155-61
pubmed: 19467796
Br J Radiol. 2009 Dec;82(984):1000-9
pubmed: 19581313
BMJ. 2009 Aug 17;339:b3016
pubmed: 19687093
Cancer. 1991 Mar 15;67(6):1685-95
pubmed: 2001559
Ann Oncol. 2010 Nov;21(11):2183-7
pubmed: 20430906
Neurology. 2010 May 4;74(18):1449-54
pubmed: 20439847
J Neurooncol. 1990 Dec;9(3):225-9
pubmed: 2086737
J Neurooncol. 2011 Sep;104(2):565-72
pubmed: 21234642
Technol Cancer Res Treat. 2011 Apr;10(2):187-95
pubmed: 21381797
Radiat Prot Dosimetry. 2011 Jul;146(1-3):364-6
pubmed: 21515620
Neuro Oncol. 2011 Dec;13(12):1364-9
pubmed: 21865399
J Thorac Oncol. 2012 Feb;7(2):382-5
pubmed: 22089116
J Clin Oncol. 2012 Feb 1;30(4):419-25
pubmed: 22203767
Strahlenther Onkol. 2012 Feb;188(2):148-53
pubmed: 22231633
Breast J. 2012 May-Jun;18(3):233-41
pubmed: 22487060
Lung Cancer. 2012 Jul;77(1):134-9
pubmed: 22487432
Cancer. 1979 Nov;44(5):1885-93
pubmed: 227582
J Thorac Oncol. 2013 Feb;8(2):185-91
pubmed: 23328548
J Thorac Oncol. 2013 May;8(5):599-605
pubmed: 23422833
J Neurooncol. 2013 May;113(1):83-92
pubmed: 23456656
Breast Cancer Res Treat. 2013 May;139(1):13-22
pubmed: 23588955
Radiat Oncol. 2013 Aug 13;8(1):200
pubmed: 23937907
Cancers (Basel). 2011 Oct 25;3(4):3972-90
pubmed: 24213120
Radiat Oncol. 2014 Jan 03;9:4
pubmed: 24387239
Radiother Oncol. 2014 Apr;111(1):47-51
pubmed: 24680378
J Korean Med Sci. 2014 Aug;29(8):1094-101
pubmed: 25120319
J Appl Clin Med Phys. 2014 Sep 08;15(5):4724
pubmed: 25207562
Acta Oncol. 2015 Jul;54(7):1075-8
pubmed: 25350525
J Clin Neurosci. 2015 Apr;22(4):632-7
pubmed: 25677875
Med Dosim. 2015 Winter;40(4):296-303
pubmed: 26002123
J Clin Neurosci. 2016 May;27:130-7
pubmed: 26778048
Lancet Oncol. 2016 Mar;17(3):287-98
pubmed: 26830377
J Neurooncol. 2016 Sep;129(2):329-35
pubmed: 27306442
Lung Cancer. 2016 Nov;101:76-81
pubmed: 27794411
J Radiat Res. 2017 Mar 1;58(2):238-246
pubmed: 28096196
Radiother Oncol. 2017 Apr;123(1):112-118
pubmed: 28283192
J Neurooncol. 2017 Sep;134(2):309-315
pubmed: 28577033
Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):37-46
pubmed: 28587051
J Neurooncol. 2017 Sep;134(2):317-324
pubmed: 28623604
Adv Radiat Oncol. 2017 Mar 10;2(2):220-227
pubmed: 28740935
Ann Oncol. 2017 Jul 1;28(suppl_4):iv84-iv99
pubmed: 28881917
Cancer Radiother. 2018 Feb;22(1):62-72
pubmed: 29195796
Ann Oncol. 2018 Mar 1;29(3):687-693
pubmed: 29293889
Acta Oncol. 2018 Sep;57(9):1240-1249
pubmed: 29698060
Phys Med. 2018 Apr;48:21-26
pubmed: 29728225
Biomed Res Int. 2018 Mar 21;2018:9153496
pubmed: 29750173
J Clin Oncol. 1987 Oct;5(10):1655-62
pubmed: 3309199
Cancer. 1978 Jul;42(1):283-6
pubmed: 667799
Cancer. 1982 Feb 15;49(4):759-72
pubmed: 6895713
J Clin Oncol. 1993 Mar;11(3):561-9
pubmed: 8445432
Control Clin Trials. 1996 Aug;17(4):343-6
pubmed: 8889347
Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51
pubmed: 9128946

Auteurs

Rami A El Shafie (RA)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Karina Böhm (K)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Dorothea Weber (D)

Institute of Medical Biometry and Informatics (IMBI), Heidelberg University Hospital, Heidelberg 69120, Germany.

Kristin Lang (K)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Fabian Schlaich (F)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Sebastian Adeberg (S)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Angela Paul (A)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany.

Matthias F Haefner (MF)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Sonja Katayama (S)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Florian Sterzing (F)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
Department of Radiation Oncology, Klinikum Kempten, Kempten 87439, Germany.

Juliane Hörner-Rieber (J)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Sarah Löw (S)

Department of Neurology, University Hospital of Heidelberg, Heidelberg 69120, Germany.

Klaus Herfarth (K)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany.

Jürgen Debus (J)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany.
German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.

Stefan Rieken (S)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany.

Denise Bernhardt (D)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.
National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany, rami.elshafie@med.uni-heidelberg.de.

Classifications MeSH