Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases

Clinical article

Restricted access

Object

This study evaluated the efficacy of postoperative Gamma Knife surgery (GKS) to the tumor cavity following gross-total resection of a brain metastasis.

Methods

A retrospective review was conducted of 700 patients who were treated for brain metastases using GKS. Forty-seven patients with pathologically confirmed metastatic disease underwent GKS to the postoperative resection cavity following gross-total resection of the tumor. Patients who underwent subtotal resection or who had visible tumor in the resection cavity on the postresection neuroimaging study (either CT or MR imaging with and without contrast administration) were excluded. Radiographic and clinical follow-up was assessed using clinic visits and MR imaging. The radiographic end point was defined as tumor growth control (no tumor growth regarding the resection cavity, and stable or decreasing tumor size for the other metastatic targets). Clinical end points were defined as functional status (assessed prospectively using the Karnofsky Performance Scale) and survival. Primary tumor pathology was consistent with lung cancer in 19 cases (40%), melanoma in 10 cases (21%), renal cell carcinoma in 7 cases (15%), breast cancer in 7 cases (15%), and gastrointestinal malignancies in 4 cases (9%). The mean duration between resection and radiosurgery was 15 days (range 2–115 days). The mean volume of the treated cavity was 10.5 cm3 (range 1.75–35.45 cm3), and the mean dose to the cavity margin was 19 Gy. In addition to the resection cavity, 34 patients (72%) underwent GKS for 116 synchronous metastases observed at the time of the initial radiosurgery.

Results

The mean radiographic follow-up duration was 14 months (median 10 months, range 4–37 months). Local tumor control at the site of the surgical cavity was achieved in 44 patients (94%), and tumor recurrence at the surgical site was statistically related to the volume of the surgical cavity (p = 0.04). During follow-up, 34 patients (72%) underwent additional radiosurgery for 140 new (metachronous) metastases. At the most recent follow-up evaluation, 11 patients (23%) were alive, whereas 36 patients had died (mean duration until death 12 months, median 10 months). Patients who showed good systemic control of their primary tumor tended to have longer survival durations than those who did not (p = 0.004). At the last clinical follow-up evaluation, the mean Karnofsky Performance Scale score for the overall group was 78 (median 80, range 40–100).

Conclusion:

Radiosurgery appears to be effective in terms of providing local tumor control at the resection cavity following resection of a brain metastasis, and in the treatment of synchronous and metachronous tumors. These data suggest that radiosurgery can be used to prevent recurrence following gross-total resection of a brain metastasis.

Abbreviations used in this paper: GKS = Gamma Knife surgery; KPS = Karnofsky Performance Scale; WBRT = whole brain radiation therapy.

Article Information

Address correspondence to: Jason P. Sheehan, M.D., Ph.D., Department of Neurological Surgery, University of Virginia Health Sciences Center, Box 800212, Charlottesville, Virginia 22908. email: jps2f@hscmail.mcc.virginia.edu.

Please include this information when citing this paper: published online April 10, 2009; DOI: 10.3171/2008.11.JNS08818.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Summary of patients and treatments. Forty-seven patients received GKS to the resection cavity. Three patients received WBRT prior to radiosurgery, whereas 34 patients had concomitant radiosurgery for a synchronous metastasis. Thirteen patients showed no radiographically visible tumor at treatment. Three of these patients underwent upfront WBRT. All 10 of the remaining patients required treatment for metachronous disease (5 underwent radiosurgery and 5 underwent WBRT).

  • View in gallery

    Graphs of the 116 synchronous tumors (left) and 140 metachronous tumors (right) grouped according to volume and primary pathology (tumor type). Left: Tumor size was stable or decreased in 94 cases (81%, black circles), with 16 tumors not visible on follow-up MR imaging (open circles). The 22 tumors that appeared to grow in size (triangles) occurred more commonly in melanoma and renal cell carcinoma. Right: Tumor size was stable or decreased in 105 cases (74%, black circles), with 43 tumors not visible on follow-up MR imaging (open circles). Thirty-five tumors appeared to grow in size (triangles). GI = gastrointestinal.

  • View in gallery

    Graph of Kaplan-Meier curves showing the time to treatment failure at the resection cavity (solid line) versus time to tumor growth for the 57 of 257 tumors (22 synchronous and 35 metachronous metastases) that did not respond to radiosurgery (dotted line).

  • View in gallery

    Graph showing the number of patients with systemic disease control and progressive disease control correlated with survival. In the 47 patients treated, those with systemic disease control had the highest correlation with survival (p = 0.03, Student t-test). Ten (83%) of 12 patients with systemic control were alive at the most recent follow-up evaluation, whereas 34 (97%) of 35 patients with progressive systemic disease were dead.

  • View in gallery

    Graph of Kaplan-Meier curves depicting survival in patients who received postoperative WBRT (solid line) compared with patients who did not (dotted line). No statistically significant difference in survival was observed.

  • View in gallery

    Graph depicting the relationship between KPS score and tumor burden. Although patients who received WBRT had lower KPS scores on follow-up, this result likely reflects the fact that these patients had a higher tumor load.

References

  • 1

    Andrews RJGluck DSKonchingeri RH: Surgical resection of brain metastases from lung cancer. Acta Neurochir (Wien) 138:3823891996

  • 2

    Batchelor TDeAngelis LM: Medical management of cerebral metastases. Neurosurg Clin N Am 7:4354461996

  • 3

    Bindal RKSawaya RLeavens MELee JJ: Surgical treatment of multiple brain metastases. J Neurosurg 79:2102161993

  • 4

    Chang ELWefel JSMaor MHHassenbusch SJ IIIMahajan ALang FF: A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery 60:2772842007

  • 5

    Coia LRAaronson NLinggood RLoeffler JPriestman TJ: A report of the consensus workshop panel on the treatment of brain metastases. Int J Radiat Oncol Biol Phys 23:2232271992

  • 6

    Cooper JSSteinfeld ADLerch IA: Cerebral metastases: value of reirradiation in selected patients. Radiology 174:8838851990

  • 7

    Dagnew EKanski JMcDermott MWSneed PKMcPherson CBreneman JC: Management of newly diagnosed single brain metastasis using resection and permanent iodine-125 seeds without initial whole-brain radiotherapy: a two institution experience. Neurosurg Focus 22:3E32007

  • 8

    Davis PCHudgins PAPeterman SBHoffman JC Jr: Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging. AJNR Am J Neuroradiol 12:2933001991

  • 9

    DeAngelis LMDelattre JYPosner JB: Radiation-induced dementia in patients cured of brain metastases. Neurology 39:7897961989

  • 10

    Eichler AFLoeffler JS: Multidisciplinary management of brain metastases. Oncologist 12:8848982007

  • 11

    Gaspar LScott CRotman MAsbell SPhillips TWasserman T: Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:7457511997

  • 12

    Gutierrez ANWesterly DCTome WAJaradat HAMackie TRBentzen SM: Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys 69:5895972007

  • 13

    Halpern JKishel SPPark JTsukada YJohnson RJAmbrus JL: Radiation induced brain edema in primates, studied with sequential brain cat scanning and histopathology. Protective effect of sodium meclofenamate A preliminary report. Res Commun Chem Pathol Pharmacol 45:4634701984

  • 14

    Jagannathan JPetit JHBalsara KHudes RChin LS: Long-term survival after gamma knife radiosurgery for primary and metastatic brain tumors. Am J Clin Oncol 27:4414442004

  • 15

    Jagannathan JSherman JHMehta GUChin LS: Radiobiology of brain metastasis: applications in stereotactic radiosurgery. Neurosurg Focus 22:3E42007

  • 16

    Kased NHuang KNakamura JLSahgal ALarson DAMcDermott MW: Gamma Knife radiosurgery for brainstem metastases: the UCSF experience. J Neurooncol 2007

  • 17

    Kresl JPueschel JPorter RYan EMcDermott MSneed P: Surgical resection and postoperative radiosurgery for single brain metastases. Neuro Oncol 5:3382003. (Abstract)

  • 18

    Lang FFSawaya R: Surgical management of cerebral metastases. Neurosurg Clin N Am 7:4594841996

  • 19

    Lang FFSawaya R: Surgical treatment of metastatic brain tumors. Semin Surg Oncol 14:53631998

  • 20

    Leksell L: The stereotaxic method and radiosurgery of the brain. Acta Chir Scand 102:3163191951

  • 21

    Loeffler JSKooy HMWen PYFine HACheng CWMannarino EG: The treatment of recurrent brain metastases with stereotactic radiosurgery. J Clin Oncol 8:5765821990

  • 22

    Lunsford LDFlickinger JC: Radiosurgery plus or minus whole brain radiation therapy for the treatment of brain metastases. An editorial comment. Surg Neurol 66:4614622006

  • 23

    Mathieu DKondziolka DFlickinger JCFortin DKenny BMichaud K: Tumor bed radiosurgery after resection of cerebral metastases. Neurosurgery [epub ahead of print]2008

  • 24

    Mehta MPRodrigus PTerhaard CHRao ASuh JRoa W: Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol 21:252925362003

  • 25

    Mehta MPShapiro WRGlantz MJPatchell RAWeitzner MAMeyers CA: Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. J Clin Oncol 20:344534532002

  • 26

    Meyers CASmith JABezjak AMehta MPLiebmann JIllidge T: Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol 22:1571652004

  • 27

    Mintz BJTuhrim SAlexander SYang WCShanzer S: Intracranial metastases in the initial staging of bronchogenic carcinoma. Chest 86:8508531984

  • 28

    Muacevic AKreth FWHorstmann GASchmid-Elsaesser RWowra BSteiger HJ: Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg 91:35431999

  • 29

    Nieder CSchwerdtfeger KSteudel WISchnabel K: Patterns of relapse and late toxicity after resection and whole-brain radiotherapy for solitary brain metastases. Strahlenther Onkol 174:2752781998

  • 30

    Packer RJ: Radiation-induced neurocognitive decline: the risks and benefits of reducing the amount of whole-brain irradiation. Curr Neurol Neurosci Rep 2:1311332002

  • 31

    Patchell RA: The management of brain metastases. Cancer Treat Rev 29:5335402003

  • 32

    Patchell RARegine WF: The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases. Technol Cancer Res Treat 2:1111152003

  • 33

    Patchell RATibbs PARegine WFDempsey RJMohiuddin MKryscio RJ: Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280:148514891998

  • 34

    Patchell RATibbs PAWalsh JWDempsey RJMaruyama YKryscio RJ: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:4945001990

  • 35

    Pollock BE: An evidence-based medicine review of stereotactic radiosurgery. Prog Neurol Surg 19:1521702006

  • 36

    Regine WFRogozinska AKryscio RJTibbs PAYoung ABPatchell RA: Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases. Am J Clin Oncol 27:5055092004

  • 37

    Rogers LRRock JPSills AKVogelbaum MASuh JHEllis TL: Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases. J Neurosurg 105:3753842006

  • 38

    Schackert GSteinmetz AMeier USobottka SB: Surgical management of single and multiple brain metastases: results of a retrospective study. Onkologie 24:2462552001

  • 39

    Sheehan JNiranjan AFlickinger JCKondziolka DLunsford LD: The expanding role of neurosurgeons in the management of brain metastases. Surg Neurol 62:32412004

  • 40

    Shehata MKYoung BReid BPatchell RASt Clair WSims J: Stereotatic radiosurgery of 468 brain metastases < or = 2 cm: implications for SRS dose and whole brain radiation therapy. Int J Radiat Oncol Biol Phys 59:87932004

  • 41

    Smith MLLee JY: Stereotactic radiosurgery in the management of brain metastasis. Neurosurg Focus 22:3E52007

  • 42

    Soltys SGAdler JRLipani JDJackson PSChoi CYPuataweepong P: Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys 70:1871932008

  • 43

    Sundaresan NGalicich JHBeattie EJ Jr: Surgical treatment of brain metastases from lung cancer. J Neurosurg 58:6666711983

  • 44

    Syk ETorkzad MRBlomqvist LLjungqvist OGlimelius B: Radiological findings do not support lateral residual tumour as a major cause of local recurrence of rectal cancer. Br J Surg 93:1131192006

  • 45

    Tasdemiroglu EPatchell RAKryscio R: Neurological complications of childhood malignancies. Acta Neurochir (Wien) 141:131313211999

  • 46

    Vecht CJHaaxma-Reiche HNoordijk EMPadberg GWVoormolen JHHoekstra FH: Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?. Ann Neurol 33:5835901993

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 203 203 87
Full Text Views 184 184 3
PDF Downloads 133 133 2
EPUB Downloads 0 0 0

PubMed

Google Scholar