Avezaat, CJJ

Dippel, Diederik

Ree, TC

Sillevis Smitt, Peter

van den Bent, Martin

Vecht, CJ

Undetermined

EUR Research Repository

EUR Research Information PortalLeptomeningeal metastasis after surgical resection of brain metastasesPublished in:Journal of Neurology Neurosurgery and PsychiatryPublication status and date:Published: 01/01/1998Document VersionPublisher's PDF, also known as Version of recordCitation for the published version (APA):Ree, TC., Dippel, D., Avezaat, CJJ., Sillevis Smitt, P., Vecht, CJ., & van den Bent, M. (1998). Leptomeningeal metastasisafter surgical resection of brain metastases. Journal of Neurology Neurosurgery and Psychiatry, 66, 225-227.http://hdl.handle.net/1765/9057Link to publication on the EUR Research Information PortalTerms and Conditions of UseExcept as permitted by the applicable copyright law, you may not reproduce or make this material available to any third partywithout the prior written permission from the copyright holder(s). Copyright law allows the following uses of this materialwithout prior permission:            • you may download, save and print a copy of this material for your personal use only;            • you may share the EUR portal link to this material.In case the material is published with an open access license (e.g. a Creative Commons (CC) license), other uses may beallowed. Please check the terms and conditions of the specific license.Take-down policyIf you believe that this material infringes your copyright and/or any other intellectual property rights, you may request itsremoval by contacting us at the following email address: openaccess.library@eur.nl. Please provide us with all the relevantinformation, including the reasons why you believe any of your rights have been infringed. In case of a legitimate complaint,we will make the material inaccessible and/or remove it from the website. 1999;66;225-227 J. Neurol. Neurosurg. Psychiatry  Charles J Vecht and Martin J van den Bent Taco C van der Ree, Diederik W J Dippel, C J J Avezaat, P A E Sillevis Smitt,   of brain metastasesLeptomeningeal metastasis after surgical resection http://jnnp.bmj.com/cgi/content/full/66/2/225Updated information and services can be found at:  These include: References http://jnnp.bmj.com/cgi/content/full/66/2/225#otherarticles3 online articles that cite this article can be accessed at:   Rapid responses http://jnnp.bmj.com/cgi/eletter-submit/66/2/225You can respond to this article at:  serviceEmail alertingtop right corner of the article Receive free email alerts when new articles cite this article - sign up in the box at theTopic collections (856 articles) Other Oncology  (3647 articles) Other Neurology  (157 articles) Neuropathology   Articles on similar topics can be found in the following collections  Notes    http://www.bmjjournals.com/cgi/reprintformTo order reprints of this article go to:  http://www.bmjjournals.com/subscriptions/ go to: Journal of Neurology, Neurosurgery, and PsychiatryTo subscribe to  on 6 December 2006 jnnp.bmj.comDownloaded from SHORT REPORTLeptomeningeal metastasis after surgical resectionof brain metastasesTaco C van der Ree, Diederik W J Dippel, C J J Avezaat, P A E Sillevis Smitt,Charles J Vecht, Martin J van den BentAbstractObjective—To determine the incidenceand risk factors for leptomeningeal me-tastasis after surgery for brain metastasisof solid tumors.Methods—Review of the records of allpatients operated on for brain metastasisbetween January 1990 and August 1995.Results—In this period 28 patients under-went surgery for brain metastasis, ofwhom 27 were available for evaluation inthis study. Median survival after crani-otomy was 11 months. Nine patients (33%)developed leptomeningeal metastasis 2–13months after surgery, which included sixof the nine patients operated on for poste-rior fossa metastasis (p=0.05). In fivepatients, leptomeningeal metastasis wasthe only site of recurrence. Three patientsdeveloped the leptomeningeal metastasisas bulky tumour along the spinal cord,which is a rare presentation. No other riskfactors for the development of leptome-ningeal metastasis other than surgery forposterior fossa metastasis were identified.Conclusions—There is an increased riskof leptomeningeal metastasis after sur-gery for posterior fossa metastasis. Futuretrials should consider the value of anactive approach to this complication inthese patients.(J Neurol Neurosurg Psychiatry 1999;66:225–227)Keywords: brain metastasis; leptomeningeal metastasis;surgeryRandomised studies on patients with singlebrain metastasis with absent or controlledextracranial tumour activity have shown alonger survival after resection followed byradiation therapy compared with radiationtherapy alone.1 In his monograph, Posnermentions the development of leptomeningealmetastasis as one of the unresolved questions insurgical therapy for brain metastasis.2 In onestudy 38% of patients developed leptomenin-geal metastasis after surgery for a cerebellarmetastasis, but only 4.7% of patients treatedfor a supratentorial metastasis.3 An increasedincidence of spinal intradural metastasis aftersurgery for posterior fossa metastasis was alsobriefly mentioned in an older publication.4 Bycontrast, another series with a larger pro-portion of patients treated for infratentorialmetastasis reported only 5.5% leptomeningealrecurrences.5 However, most series on surgeryfor brain metastasis did not consider suchrecurrences. To determine the incidence ofleptomeningeal metastasis after surgery forbrain metastasis, we reviewed the records of allpatients who had undergone brain metastasisresection in a 5.5 year period at the Daniel denHoed Cancer Center (DHCC) in Rotterdam.Patients and methodsMETHODSThe records of all patients with brain metasta-sis from solid tumours treated at the DHCC inthe period January 1990 to August 1995 werereviewed. Evaluable for this study were patientstreated at the DHCC at the time of resection orradiation therapy of brain metastasis. Patientsreferred to the DHCC at a later stage of theirdisease (for example, for leptomeningeal dis-ease) were excluded. We recorded the primarytumour histology, location of brain metastasis(supratentorial v infratentorial), depth of me-tastasis (superficial<1cm; deep>cm), extent ofresection, postoperative therapy, diagnosis ofleptomeningeal metastasis, and interval be-tween resection and diagnosis of leptomenin-geal metastasis. The extent of resection wasbased on the peroperative judgement of theneurosurgeon, not on postoperative imaging.The diagnosis of leptomeningeal metastasiswas made if malignant cells were present in theCSF, or in the presence of typical neuroimag-ing findings, such as leptomeningeal enhance-ment extending in cerebral sulci or spinalintradural extramedullary tumour deposits.6The survival and leptomeningeal metastasisfree survival were calculated from the date ofsurgery to the time of study (October 1996) orto the date of death, using Kaplan-Meiersurvival analysis. The eVect of clinical variableson survival and leptomeningeal metastasis freesurvival was assessed by the log rank test. Thelevel of statistical significance was taken asp<05 (two sided).PATIENTSTwenty eight patients were treated with surgeryfor brain metastasis between January 1990 andAugust 1995. One patient, who died from car-J Neurol Neurosurg Psychiatry 1999;66:225–227 225Department ofNeuro-Oncology, DrDaniel den HoedCancer Center,Rotterdam, TheNetherlandsT C van der ReeP A E Sillevis SmittC J VechtM J van den BentDepartment ofNeurologyT C van der ReeD W J DippelDepartment ofNeurosurgery,University Hospital,Rotterdam, TheNetherlandsC J J AvezaatCorrespondence to:Dr Martin J van den Bent,Dr Daniel den Hoed CancerCenter, PO Box 5201, 3008AE Rotterdam, TheNetherlands. Telephone0031 10 4391415; fax 003110 4845743; email:bent@neuh.azr.nlReceived 30 December 1997and in revised form15 June 1998Accepted 13 July 1998 on 6 December 2006 jnnp.bmj.comDownloaded from diopulmonary failure 10 days after surgery, wasexcluded from further analysis. The clinicalcharacteristics of the remaining 27 patients areshown in the table. Four patients had someevidence of progressive systemic disease at thetime of surgery, which was considered of minorclinical importance. No patient was suspectedof having leptomeningeal metastasis at physicalexamination or neuroimaging at the time ofsurgery. Brain metastasis was located supraten-torially in 18 patients, nine patients were oper-ated on for infratentorial lesions. Twenty fivepatients received adjuvant whole brain radio-therapy. Several radiation fraction scheduleswere used, 19 patients received an additionalboost to the tumour. Two patients were notirradiated. One patient with small cell lungcancer received systemic chemotherapy. Theother patient was operated on for a local recur-rence of a solitary brain metastasis 6 monthsafter radiation therapy.ResultsFollow up was complete in all patients. Mediansurvival after resection of brain metastasis was11 months (range 2 to 73 months), six patientswere still alive at the time of final analysis. Nineof the 27 patients (33.3%) developed leptome-ningeal metastasis. The 2 year leptomeningealmetastasis free survival was 54% (95% CI27%–75%, fig 1). In five patients, the leptome-ningeal metastasis was cytologically confirmed.In the other four patients the MRI showedtypical abnormalities of leptomeningeal metas-tasis. In three of the nine patients withleptomeningeal metastasis MRI showed bulkyintradural extramedullary tumour at the levelof the cervical or thoracic spinal cord (fig 2).Nine patients had an infratentorial locationof metastasis, six of these developed leptome-ningeal metastasis. Three of the 18 patients(16,7%) with a supratentorial metastasis werediagnosed with leptomeningeal metastasis. Theleptomeningeal metastasis free survival wassignificantly shorter in patients with an in-fratentorial lesion (fig 1, p=0.05, log rank). Theextent of resection of brain metastasis, theextent of systemic disease, or treatment with anadditional radiation boost were not related todevelopment of leptomeningeal metastasis.In five patients the leptomeningeal metasta-sis was the only site of recurrence of metastaticcancer after surgical removal of the brainmetastasis. The other four patients had concur-rent systemic or cerebral tumour recurrence(local or distant), either before or at the sametime as the diagnosis of leptomeningeal metas-tasis. Median survival after diagnosis of lep-tomeningeal metastasis was 5 months (range 1Clinical characteristics of 27 patients with resection of brainmetastasisSexMale 16Female 11Age at resection:Median (range) 49 (29-70)Primary tumour:Lung 8Genitourinary 6Melanoma 6Breast 5Gastrointestinal 2Location of brain metastasis:Supratentorial 18Infratentorial 9Depth of BM:Superficial (<1 cm) 14Deep (>1 cm) 9Unknown 4Extent of resectionTotal 23Subtotal 4Figure 1 Survival, leptomeningeal metastasis freesurvival in the whole group, and leptomeningeal metastasisfree survival after surgery for infratentorial andsupratentorial brain metastasis.0.810.60.400.272Time (months)BLM-free survival480 24InfratentorialSupratentorial0.810.60.400.272Time (months)ASurvival480 24SurvivalLM-free survivalFigure 2 Gadolinium enhanced MRI of the spine,showing bulky intradural, extramedulary metastasis at thelevel of the 5th and 6th thoracic vertebral bodies (arrow).226 van der Ree, Dippel, Avezaat, et al on 6 December 2006 jnnp.bmj.comDownloaded from to 58 months). At the time of this study twopatients with leptomeningeal metastasis werestill alive, 5 and 58 months after diagnosis.DiscussionLeptomeningeal metastasis is a relatively infre-quent complication of solid tumours. The mostcommon solid tumours associated with it arebreast cancer, melanoma, and small cell lungcancer.7 8 Most patients with leptomeningealmetastasis have advanced disease, only rarely isit the initial or sole presentation of cancer. Inthis group of 27 patients treated with surgeryfor brain metastasis nine patients (33%) devel-oped leptomeningeal metastasis, in five of themthis was the only site of relapse. The risk ofleptomeningeal metastasis was significantlyhigher in patients operated on for an infraten-torial metastasis. Although in four patients theleptomeningeal metastasis was not cytologi-cally proved, we do not doubt the diagnosis asthe MRI showed typical abnormalities usingthe criteria proposed by Freilich et al.6 Despitethe high frequency of leptomeningeal metasta-sis, the median survival of 11 months after sur-gery in this group is comparable with otherseries on surgery for a single brainmetastasis.1 3 5The incidence of leptomeningeal metastasisin this study population exceeds that reportedin studies on leptomeningeal metastasis in acancer population. The crucial question iswhether our findings should be regarded as aconsequence of surgery or that they can beexplained otherwise. With longer survival aftersurgery for solitary brain metastasis, patientsare longer at risk of developing a leptomenin-geal recurrence, but our data exceed the 3 yearactuarial risk of 25% for leptomeningealmetastasis as found in small cell lung cancer.9Tumours that metastasise to the brain also pre-dispose for leptomeningeal metastasis, and thefrequency is increased in posterior fossa metas-tasis. However, the incidence of leptomenin-geal metastasis after surgery for posterior fossabrain metastasis which we found exceeds thereported 25% 1 year actuarial risk for spinalintradural seeding in fossa posteriormetastasis.10 Another explanation for our find-ings is that leptomeningeal metastasis alreadyexisted at the time of surgery, or alternatively,that the fossa posterior tumours were in factleptomeningeal metastasis. However, none ofthe patients had clinical signs or symptoms ofleptomeningeal metastasis at the time ofsurgery.On the other hand, intraoperative tumourspill is a well recognised complication of surgi-cal oncology, and this may of course also hap-pen during surgery for brain metastasis.11 Ourseries oVers two more arguments for a relationwith the surgical intervention. Firstly, leptome-ningeal metastasis was a solitary recurrence infive of nine patients, whereas most patientswith leptomeningeal metastasis develop thiswhile having widely metastasised cancer. Sec-ondly, in three of our patients MRI of the spineshowed bulky intradural extramedullarytumour at the level of cervical or thoracic spinalcord (fig 2). In our experience, this is anuncommon presentation of leptomeningealmetastasis. A similar presentation of leptome-ningeal metastasis after brain metastasis sur-gery was described by Norris et al.12 We thinkthat these intradural metastases were due todrop metastasis, arrested along the spinal cord.Our results are in agreement with two otherstudies, in which a 33%–38% incidence of lep-tomeningeal metastasis after removal of poste-rior fossa brain metastasis was reported.3 4Recently, another series reported leptomenin-geal metastasis in four out of 10 patients oper-ated on for infratentorial metastasis, by con-trast with only one of 55 patients operated onfor supratentorial metastasis.12 The increasedrisk of leptomeningeal metastasis after surgeryfor posterior fossa metastasis may be due to themore intimate contact with the subarachnoidspace and the cisterna magna, which may oVera nidus for tumour cells not present over thecerebral hemisphere.3These data support a postoperative screen-ing for leptomeningeal metastasis after surgeryfor fossa posterior metastasis. If tumour cellsare present, further treatment may be consid-ered (either intrathecal chemotherapy inchemotherapy sensitive tumours, or neuraxisradiation in tumours resistant to chemo-therapy). Future trials are needed to showwhether this would be useful and to define therole of these measures.1 Vecht ChJ, Haaxma-Reiche H, Noordijk EM, et al.Treatment of single brain metastasis: radiotherapy alone orcombined with neurosurgery? Ann Neurol 1993;33:583–90.2 Posner JB. Neurologic complications of cancer. Philadelphia:FA Davis, 1995:102.3 DeAngelis leptomeningeal metastasis, Mandell LR, ThalerHT, et al. The role of postoperative radiotherapy afterresection of single brain metastases. Neurosurgery 1989;24:798–805.4 Dosoretz DE, Blitzer PH, Rusell AH, et al. Management ofsolitary metastasis to the brain: the role of elective brainirradiation following complete surgical resection. Int JRadiation Oncology Biol Phys 1980;6:1727–30.5 Smalley SR, Schray MF, Laws ER, et al. Adjuvant radiationtherapy after surgical resection of solitary brain metastasis:association with pattern of failure and survival. Int J RadiatOncol Biol Phys 1987;13:1611–6.6 Freilich RJ, Krol G, DeAngelis LM. Neuroimaging and cer-ebrospinal fluid cytology in the diagnosis of leptomeningealmetastasis. Ann Neurol 1995;38:51–7.7 Olson ME, Chernik NL, Posner JB. Infiltration of theleptomeninges by systemic cancer. A clinical and patho-logic study. Arch Neurol 1974;30:122–37.8 Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treat-ment of leptomeningeal metastases from solid tumors:experience with 90 patients. Cancer 1982;49:759–72.9 Rosen ST, Aisner J, Makuch RW, et al. Carcinomatous men-ingitis in small cell lung cancer: a clinicopathologicalreview of the National Cancer Institute experience.Medicine 1982;61:45–53.10 MirimanoV RO, Choi NC. Intradural spinal metastases inpatients with posterior fossa brain metastases from variousprimary cancers. Oncology 1987;44:232–6.11 Fortner JG. Inadvertent spread of cancer at surgery. J SurgOncol 1993;53:191–6.12 Norris LK, Grossman SA, Olivi A. Neoplastic meningitisfollowing surgical resection of isolated cerebellarmetastasis: a potentially preventable complication. JNeurooncol 1997;32:215–23.Leptomeningeal metastasis after surgical resection of brain metastases 227 on 6 December 2006 jnnp.bmj.comDownloaded from 

Leptomeningeal metastasis after surgical resection of brain metastases

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Leptomeningeal metastasis after surgical resection of brain metastases

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