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Malignant Brain Tumors______________________________________________ Cerebral Metastases ______________________________________________ Glioma ______________________________________________ Ependymoma ______________________________________________ Pineoblastoma ______________________________________________

What are the problems we need to solve ? ________________________________in fractionated radiotherapynegative prognosislocal tumor controlprevention of new brain metastasesmultiple metastasesside effectsradioresistant metastaseselderly patients

A meta-analysis of the literature (2005) showed only onetrial that compared WBRT versus supportive care alone Median survival in the prednisone alone arm was 10 weeks in the combined WBRT arm 14 weeksHorton J, Baxter DH, Olson KB, et al. The management of metastases to the brain byirradiation and corticosteroids. Am J Roent Rad Ther Nucl Med 1971;3:334.

Criteria for survival root (all patients) n=1200 patRPA Classes(recursive tree)________________ KPS >70 KPS <70 n=1011 n=175 primary cancer controlled n=588 Class III primary cancer not controlled 14.6% : n=413 2.3 months age <65 y n=424 age >65 ymetastasisBrain only metastasis n=236 Brain and other sites Class II 65.7% : Class I 4.2 months 19.7% : 7.1 months Gaspar et al.: Int J Biol Phys 37, No 4, 1997

Survival afterFractionated Whole Brain Radiotherapy SUMMARY3 retrospective studies with 2682 patients median survival of 3.4 - 4.1 months 2 prospective randomized studieswith a median survival of 2.8-3.9 months

Response Rates (CR or PR) after Fractionated Whole Brain Radiotherapy Prospective Randomized Studies response rate (CR or PR): 24 % in WBRT only treatment armEyre HJ, Ohlsen JD, Frank J, et al. Randomized trial of radiotherapy versus radiotherapy plusmetronidazole for the treatment of metastatic cancer to brain. J Neurooncol 1984;2:325–30.

Response Rates (CR or PR) after Fractionated Whole Brain Radiotherapy prospective trial of fractionated radiotherapy of various brain metastases complete or partial response in 38%Suh JH, Stea B, Nabid A, Kresl JJ, Fortin A, Mercier JP, Senzer N, Chang EL, Boyd AP, Cagnoni PJ, Shaw E. Phase III studyof efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol. 2006 Jan 1;24(1):106-14

Response Rates (CR or PR) after Fractionated Whole Brain Radiotherapy In patients with brain metastases from colorectal cancer the local control rates at 6 months were 17% after 10 x 3 Gy local control rates at 6 months were 50% after higher dosesHeisterkamp C, Haatanen T, Schild SE, Rades D. Dose escalation in patients receiving whole-brain radiotherapy for brainmetastases from colorectal cancer. Strahlenther Onkol. 2010 Feb;186(2):70-5. Epub 2010 Jan 26.

Response Rates (CR or PR) after Fractionated Whole Brain Radiotherapy SUMMARY Response Rate of 17%-50%one prospective study shows a response rate of 38%

tumor control and survivalafter Radiosurgery___________

Gamma Knife Radiosurgery for Metastases___________________ Karolinska Series 2007 n=301 713 evaluable metastases documented Tumor control 94.3% (n=673/713) no control (recurrence or 5.6 % (n=40/713) uncontrolled ARE)

Karolinska Series 2007 n=301 Survival after Gamma Knife in selected indications median survival breast ca: ! ! 15 mo ca pulm : !! ! 7.7 mo melanoma: ! 7.5 mo renal ca:! ! ! 6.1 mo ca recti/colon:! 3.4 mo combined : ! 7.5 mosurvival (mo)

Brain Metastases Survival after Gamma KnifeKarnofsky <70 median survival 2.2 mo (n=74)Karnofsky >70 median survival 9.6 mo (n=225) Log-Rank p<0.0001 Karolinska Series 2007 n=301

Metastases local control after Gamma Knife treatment (in series > 100 pat) number of ______________ 5 series : 1169 patients single / multiple patients tumor control patientsGaudy-Marqueste, Regis, Grob.Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):809-16. various both 106 83.7 %Simonová G, Roman L.Expert Rev Anticancer Ther. 2003 Dec;3(6879-90. various both 400 90Hasegawa T, Germanwala, Lunsford..Neurosurgery. 2003 Jun;52(6):1318-26 various both 172 87 %Chen JC, Apuzzo MLStereotact Funct Neurosurg. 1999;73(1-4):60-3. various both 190 89 %Lippitz et al. current study various both 301 95 %

Treatment Number of patients median survival local tumour control lung cancer metastases modality Months NSCLCFlannery TW, Patchell RA, Kwok Y. Gamma Knife 42 18Int J Radiat Oncol Biol Phys. 2008 +Sep 1;72(1):19-23. Epub 2008 Feb 14 WBRT (synchronous, solitary brain metastasis)Kong DS, Park K. J Korean Med Sci. Gamma Knife 35 122006 Jun;21(3):527-32Li B, Wang L. Int J Cancer. 2000 Feb LINAC 151 5.7 100 %20;90(1):37-45 + (WBRT alone) 9.3 WBRT (SRS alone) (single brain metastasis) 10.6 (SRS+WBRT)Sheehan J,Lunsford LD Gamma Knife 27 18 81%J Neurosurg. 2005 Jan;102 Suppl: Small cell lung247-54 cancerPan HC, Steiner L. J Neurosurg. Gamma Knife 191 15 84.4% (< 0.5 cm3) 94% (0.5-2 cm3) 89.1% (2-42005 Jan;102 Suppl:128-33 + cm3) WBRTGerosa M. Bricolo A. J Neurosurg. Gamma Knife 504 14.5 94%2005 Jan;102 Suppl:75-80Jawahar A, Nanda A. J Neurosurg. Gamma Knife 44 7 73 %2004 May;100(5):842-7 mean prescription dose 15.35 Gy (11-22Gy)Flannery TW, Regine WF. Lung Gamma Knife 72 15.7Cancer. 2003 Dec;42(3):327-33 + WBRT solitary brain metastasisSheehan JP, Lunsford LD. J Gamma Knife 273 10 84 % from GKS treatmentNeurosurg. 2002 Dec;97(6):1276-81 15 from the diagnosis of brain metastases

Treatment Number of patients median survival local tumour control lung cancer metastases modality Months NSCLCSerizawa T Yamaura A. J Neurosurg. Gamma Knife 211 8.6 98% (1-year2002 Dec;97(5 Suppl):484-8 NSCLC tumour control rate)Serizawa T Yamaura A. J Neurosurg. Gamma Knife 34 9.1 94.5% (1-year2002 Dec;97(5 Suppl):484-8 SCLC tumour control rate)Zabel A, Debus J. Lung Cancer. 2002 LINAC 86 4.5 76 %Jul;37(1):87-94 NSCLC (median overall actuarial survival) (overall local control rate) 8.3 (median actuarial survival time with 96 % metachronous onset of brain metastases) (actuarial local control rate after 3 3.3 months) patients with synchronous onsetHoffman R, Larson DA. Cancer J. Gamma Knife (?) 113 12 81 % (1-year local freedom from progression)2001 Mar-Apr;7(2):121-31 NSCLCKim YS, Lunsford LD. Cancer. 1997 Gamma Knife 77 10 85 %Dec 1;80(11):2075-83 NSCLC

Treatment Number of patients median survival local tumour control breast cancer modality Months metastasesAkyurek S, Woo SY. Am J Clin Linac or 34 19 79%Oncol. 2007 Jun;30(3):310-4. (1) WBRT+LinacGoyal S, , Steiner L. J Neurosurg. Gamma Knife 43 132005 Aug;103(2):218-23. (35)Muacevic A, Wowra B. Cancer. Gamma Knife 151 10 94%2004 Apr 15;100(8):1705-11. (78) 34.9 (RPA class I) 9.1 (RPA class II) 7.9 (RPA class III)Levin KJ, Zamorano L. J Gamma Knife 12 11.5Neurosurg. 2002 Dec;97(5 Suppl):663-5. (60)Amendola BE, Bloch L. Cancer J. Gamma Knife 68 7.8 94%2000 Mar-Apr;6(2):88-92. (2)Firlik KS, Lunsford LD. Ann Surg Gamma Knife 30 13 93%Oncol. 2000 Jun;7(5):333-8. (27)

Treatment Number of patients median survival local tumour control colo-rectal carcinoma modality Months metastasesHasegawa T, Lunsford LD. Gamma Knife 39 5 84%Surg Neurol. 2003 Dec;60(6):506-14 (40)Schoeggl A, Zauner C . Int J Gamma Knife 35 6 96%Colorectal Dis. 2002 May;17(3):150-5. (116)

CONCLUSION Local tumor control after stereotactic radiosurgery:in 25/28 published Gamma Knife studies with a total of 2620 patients the local control was 81-98%

Karolinska Series 2009 n=301 Limitation : Tumor Volume ! 100,0 90,0 80,0 70,0 60,0 50,0 40,0 30,0 20,0 10,0 0,0 <12 mm 12-24 mm >24 mmControl rates :diameter <12 mm: 99 % , 12-24 mm: 89%, and >24mm 83 %

CONCLUSION Local tumor control after Gamma Knife radiosurgery: in 25/28 published Gamma Knife studies with a total of 2620 patients the local control was 81-98% after Fractionated Whole Brain Radiotherapyrandomised studies with a response rate of 24%-38% at higher doses (>30 Gy) 50%

Documented Outcome after Conventional fractionated Radiotherapy of multiple cerebral metastases ________________ University Medical Centre Charite, Humboldt University, Berlin-Buch, Germany. retrospective study, breast cancer patients ( 1969- 1995) 145 patients were treated with megavoltage irradiation (60 cobalt or 6MV) of the whole brain using opposed fields (30 Gy ) Median survival multiple cerebral metastases: 5.75 monthsEur J Cancer. 1999 Apr;35(4):580-5. Radiologische Universitatsklinik Freiburg, Germany. 916 patients with resection and whole brain radiotherapy (WBRT, n = 257) or WBRT alone (n = 659) ( 1985 – 2000) Median survival of the whole group was 3.4 monthsRadiother Oncol. 2002 Jun;63(3):339-45 Department of Neurosurgery, University of Minnesota Hospital and Clinic, Minneapolis 55455, USA.729 patients ( 1973 to 1993) Multiple metastases were present in 345 patients (47%). Median survival : 3 months Cancer 1996 Oct 15; 78 (8):1781-8

Myths about fractionated radiotherapy________________________________fractionated radiotherapyis necessary in multiple brain metastases ?WBRT treats microscopic disease andprevents new metastases ?

Distant Metastases after Fractionated Whole Brain Radiotherapy Prospective Randomized Study Distant metastases in 41.5 % 12-month actuarial rate after (WBRT +SRS)Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K,Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brainmetastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. Distant metastases in 34% 12 months after WBRT Rades D, Pluemer A, Veninga T, Hanssens P, Dunst J, Schild SE. Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases. Cancer. 2007 Nov 15;110(10):2285-92.

CONCLUSIONDistant Metastases appear in 34-41 % after Fractionated Whole Brain Radiotherapy. WBRT does not protect from new metastases

distant metastases afterGamma Knife___________

Karolinska Series 2009 n=301new remote metastases 43 % (n=124/288) FU information available in 288/301 (95.6%)

Radiosurgically treated patients experienced new metastases outside the initial target area in 39%- 52%Shirato H, Takamura A, Tomita M, Suzuki K, Nishioka T, Isu T, Kato T, Sawamura Y, Miyamachi K, Abe H, Miyasaka K.Stereotactic irradiation without whole-brain irradiation for single brain metastasis. Int J Radiat Oncol Biol Phys. 1997 Jan15;37(2):385-91Chidel MA, Suh JH, Reddy CA, Chao ST, Lundbeck MF, Barnett GH : Application of recursive partitioning analysis andevaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosedbrain metastases. Int J Radiat Oncol Biol Phys 2000 Jul 1;47(4):993-9).Chougule PB, Burton-Williams M, Saris S, Zheng Z, Ponte B, Noren G, Alderson L, Friehs G, Wazer D, Epstein MRandomized treatment of brain metastasis with gamma knife radiosurgery, whole brain radiotherapy or Both Int. J. RadiationOncology Biology Physics Volume 48, Number 3. Supplement, p 114, 2000

CONCLUSION Distant Metastases outside the initial target areaappear in 39%- 64% of radiosurgically treated patients Distant Metastases appear in 34-41 % after Fractionated Whole Brain Radiotherapy. WBRT does not protect from new metastases

In case of distant recurrences after initial treatment Gamma Knife radiosurgery can be used again

Side Effects after Fractionated Whole Brain Radiotherapy Learning and Memory Functions Adult patients were evaluated prospectively with serial cognitive testing, before, during and after fractionated radiotherapy Fractionated radiotherapy caused cognitive dysfunction immediately after the beginning of radiotherapy in patients with brain metastases. “These effects were more pronounced in patients with above-average performance at baseline.”Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, Wenz F.Memory function before and after whole brain radiotherapy in patients with and without brainmetastases. Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1311-8. Epub 2008 Apr 28.

Prospective Randomized Study RTOG protocol 95-08: Whole Brain Radiotherapy with and without Stereotactic Neurosurgery Boost for unresected brain metastases Patients in the WBRT + SRS group had more stable and improved performance statusAndrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J,Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Lancet. 2004 May 22;363(9422):1665-72.Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases:phase III results of the RTOG 9508 randomised trial.

learning and memory functions inWBRT + radiosurgery vs. radiosurgery alone___________

Side Effects after Fractionated Whole Brain Radiotherapy Learning and Memory Functions Prospective Randomized Study Patients with1-3 brain metastases were randomly assigned and stratified byrecursive partitioning analysis class, number of brain metastases, and radioresistant histology. The primary endpoint was neurocognitive functionthe trial was stopped by the data monitoring committee because... patients randomly assigned to receive SRS plus WBRT weresignificantly more likely to show a decline in learning andmemory function (mean posterior probability of decline 52%)at 4 months than patients assigned to receive SRS alone(mean posterior probability of decline 24%)Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS, MaorMH, Meyers CA. Neurocognition in patients with brain metastases treated with radiosurgery orradiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009 Oct 2.

CONCLUSION Side EffectsImpairment of Learning and Memory Functions significantly more frequentafter Fractionated Whole Brain Radiotherapy than after stereotactic Radiosurgery

Fractionated Whole Brain Radiotherapy in Radioresistant Metastases: Renal Cell Cancer Cleveland Clinic: WBRT in brain metastases of renal cell carcinoma median survival of 3 months after WBRTCannady SB, Cavanaugh KA, Lee SY, Bukowski RM, Olencki TE, Stevens GH, Barnett GH, Suh JH. Results of whole brainradiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study.Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):253-8 MD Anderson: WBRT in 70 patients with multiple brain metastases of renal cell cancer treated overall median survival time of 3 months from diagnosis of the brain metastases. In 76 % the causes of death were neurologic.Wrónski M, Maor MH, Davis BJ, Sawaya R, Levin VA.External radiation of brain metastases from renal carcinoma: aretrospective study of 119 patients from the M. D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):753-9

Fractionated Whole Brain Radiotherapy in Radioresistant Metastases: Melanoma University Hospital Luebeck, Germany: WBRT in brain metastases of melanoma control rates rates at 6 months after 10x3 Gy : 23 % after higher doses : 50 % control rates rates at 12 months after 10x3 Gy : 0% after higher doses : 13 %Rades D, Heisterkamp C, Huttenlocher S, Bohlen G, Dunst J, Haatanen T, Schild SE. Dose Escalation of Whole-BrainRadiotherapy for Brain Metastases from Melanoma. Int J Radiat Oncol Biol Phys. 2009 Sep 2.

CONCLUSIONNo tumor control after WBRT of radioresistant metastases

tumor control and survival afterGamma Knife for radioresistant metastases___________

Stereotactic Radiosurgery in “Radioresistant” Brain MetastasesMayo Clinic:stereotactic radiosurgery for 83 "radioresistant" brain metastases (41 pat)56% had multiple metastases.(renal cell carcinoma (n=16), melanoma (n=23), and sarcoma (n=2). median overall survival : 14.2 months after SRS. median survival RPA Class I: 23.5 months median survival RPA Class II or III: 10.5 months 12% recurred locally (of 73 tumors) Patients who received adjuvant WBRT in addition to SRS had 6- month actuarial local control of 100% as compared with 85% among those who did not receive WBRT (P = 0.018). Brown PD, Brown CA, Pollock BE, Gorman DA, Foote RL.Stereotactic radiosurgery for patients with "radioresistant" brain metastases. Neurosurgery. 2008 Feb;62 Suppl 2:790-801.

Treatment Number median survival Local malignant melanoma modality of patients Months tumour control metastasesPowell JW,, Hahn SS. et al. J Gamma Knife 50 5.1 63%Neurosurg. 2008 Dec;109 Suppl:122-8 12-month rate for freedom from local progressionBrown PD, Foote RL. et al Gamma Knife 23 14.2Neurosurgery. 2008 Feb;62 Suppl 23.5 (RPA class I) 10.5 (RPA class II+III)2:790-801Mathieu D, Lunsford LD. et al.: Gamma Knife 244 5.3 86.2Neurosurgery. 2007 Mar;60(3):471-81Gaudy-Marqueste C, Grob JJ. et al. Int Gamma Knife 106 5.09 83.7J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):809-16. Epub 2006 May 6Radbill AE, Markert JM. et al. Cancer. Gamma Knife 51 6.5 812004 Aug 15;101(4):825-33 14.25 (RPA class I) 5 (RPA class II+III)Yu C, Apuzzo ML, Petrovich Z.. Int J Gamma Knife 122 7Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1277-87Mingione V, Steiner L. J Neurosurg. Gamma Knife 45 10.4 822002 Mar;96(3):544-51Lavine SD, Apuzzo ML. Neurosurgery. Gamma Knife 45 8 971999 Jan;44(1):59-64; discussion 64-6Grob JJ, Bonerandi JJ. Eur J Cancer. Gamma Knife 35 22 (for solitary brain metastasis) 98.21998 Jul;34(8):1187-92 7.5 (for single brain metastasis and (at 3 months) metastases elsewhere) 4 (for multiple brain metastases)Mori Y, Lunsford LD. Int J Radiat Oncol Gamma Knife 60 7 90Biol Phys. 1998 Oct 1;42(3):581-9.(75)Seung SK, Larson DA. Cancer J Sci Gamma Knife 55 8.75 77Am. 1998 Mar-Apr;4(2):103-9. (119)

Treatment Number of patients median survival local tumour control renal cell cancer modality Months metastasesPowell JW, Hahn SS.J Neurosurg. Gamma Knife 23 5.1 93.6%2008 Dec;109 Suppl:122-8 (104) 12-month rate for freedom from local progressionShuto T, Nagano H. J Neurosurg. Gamma Knife 69 9.5 82.62006 Oct;105(4):555-60. (130)Muacevic A, Wowra B. Minim Gamma Knife 85 11.1 94Invasive Neurosurg. 2004 Aug;47(4): 24.2 (RPA class I) 9.2 (RPA class II)203-8. (77) 7.5 (RPA class III)Noel G, Mazeron JJ. Urol Oncol. LINAC 28 11 93%2004 Jan-Feb;22(1):25-31. (92) 12-month local control ratesSheehan JP, Lunsford LD.. J Gamma Knife 69 13 96%Neurosurg. 2003 Feb;98(2):342-9.(125)Hoshi S, Yoshimoto T. Int J Urol. Gamma Knife 42 12.52002 Nov;9(11):618-25; (46)Hernandez L, Diaz F. J Neurosurg. Gamma Knife + 29 72002 Dec;97(5 Suppl):489-93. (43) WBRT 18 (RPA class I) 8.5 (RPA class II) 5.3 (RPA class III)Mori Y, Lunsford LD. Cancer. 1998 Gamma Knife 35 11 90Jul 15;83(2):344-53. (74)

CONCLUSIONGamma Knife treatment of radioresistant metastases High local control (81-98%) in 12/14 published series in 867/972 patients

multiple brain metastases___________

patients with 3-6 radiosurgically treated brain metastases showed arrest in the growth of irradiated tumors achieved in 82% patients. Mean survival after diagnosis of brain disease was 12 monthsJawahar A, Shaya M, Campbell P, Ampil F, Willis BK, Smith D, Nanda A. Role of stereotactic radiosurgery as a primarytreatment option in the management of newly diagnosed multiple (3-6) intracranial metastases. Surg Neurol. 2005 Sep;64(3):207-12

Brain Metastases Survival after Gamma KnifeSingle Metastasis : median survival 11.1 mo (n=113)Multiple Metastases: median survival 5.7 mo (n=188) Log-Rank :p<0.0001 Karolinska Series 2009 n=301

Multiple Cerebral Metastases of Malignant Melanomabefore Gamma Knife treatmentbefore Gamma Knife treatment follow-up 3 years after radiosurgery follow-up 3 years after radiosurgery

multiple brain metastases of lung cancer3D dose plan for Gamma Knife radiosurgery of the frontal and parietalmetastasis (prescription dose 18Gy).b. Follow-up 2 months after radiosurgery. Significant response

Brain Metastases Survival after Gamma KnifeSurvival vs. Number of Metastases at Initial Treatment for patients with Karnofsky >70 median survival 2 mets ! (n=71): 5.6 mo 3 mets ! (n=37): 8.9 mo 4 mets ! (n=26) : 6 mo 5 mets ! (n=26): 5.9 mo 6 mets ! (n=11): 5.4 mo Wilcoxon ! p=0.5977 Log-Rank ! p=0.2949 Karolinska Series 2009 n=301

Brain Metastases Survival after Gamma KnifeSurvival vs. Number of Metastases at Initial Treatment median survival single mets ! (n=113): 11.1 mo 2-6 mets ! (n=171): 6 mo 7-10 mets ! (n=17) :! 2.8 mo Wilcoxon ! p=0.0001 Log-Rank ! p=0.0001 Karolinska Series 2009 n=301

“In patients with one to three brain metastases ... radiosurgery may be considered ...”This recommendation is based primarily on three prospective randomised trialsKondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC: Stereotactic radiosurgery plus whole brain radiotherapy versusradiotherapy alone for patients multiple brain metastases. Int J Radiat Oncol Biol Phys 1999, 45:427-34.Chougule PB, Burton-Williams M, Saris S, Zheng Z, Ponte B, Noren G, Alderson L, Friehs G, Wazer D, Epstein M:Randomized treatment of brain metastases with gamma knife radiosurgery, whole brain radiotherapy or both [abstract]. Int JRadiat Oncol Biol Phys 2000, 48:114.Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP,Souhami L, Rotman M, Mehta MP, Curran WJ Jr: Whole brain radiation therapy with or without sterotactic readiosurgery boostfor patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 2004,363:1665-72 the number of metastases was defined by the inclusion criteria

hypothesis:In patients with multiple brain metastases the survival may not be related to the number of cerebral tumors

BUTStereotactic Radiosurgery for brain metastases :survival was significantly better in patients who had 1 to 3 metastases(median, 8.5 months)compared with patients who had ≥ 4 metastases (median, 6.3 months)DiLuna ML, King JT Jr, Knisely JP, Chiang VL. Prognostic factors for survival after stereotactic radiosurgery vary with thenumber of cerebral metastases. Cancer. 2007 Jan 1;109(1):135-45.

521 patients treated with Gamma Knife radiosurgery :For both overall survival and neurological survival, the differencesbetween a few (</=3) and many (4-10) brain lesions were not significantPatients with more than 10 metastases had a significantly poorerprognosis than those with less than 10 tumours.Serizawa T, Saeki N, Higuchi Y, Ono J, Iuchi T, Nagano O, Yamaura A. Gamma knife surgery for brain metastases:indications for and limitations of a local treatment protocol. Acta Neurochir (Wien). 2005 Jul;147(7):721-6; discussion 726.Epub 2005 May

CONCLUSIONMany studies do not show an impact of the number of brain metastases on survivalThere may be a subgroup of patients with a very high number of metastases (>7) with a worse outcome

so far no report of side effects related to treatednumber of metastases (only related to volume)___________________

BUTLarge Volumes Metastasesshould not be treated with Radiosurgery___________________

Gamma Knife treatment (10 cc, 18 Gy) 6 weeks after treatment 7 months after Gamma Knife treatment recurrence after 12 months

Tumors withindividual follow-up of > 9 months and diameter > 10mm (n=153)___________________ARE and Volume of 10Gy Isodose p=0.00271= uncomplicated mean=14.4cc 2= ARE mean 24.8 cc

Conventional fractionated radiotherapyhas not shown to be more effective in patients with multiple brain metastases with regard to survival or local control

In particular in patients with a limited prognosis it is important that Gamma Knife radiosurgery is•less invasive•less time consuming for the patient•has lower side effects•provides higher local control•has sufficient efficacy against all brain metastases•including “radioresistant” metastases•is applicable in the elderly patient

Consequences _____________________________________Larger tumors with direct mass effect have to be resected Increase of radiosurgically treated volume is so far impossible

Conclusions ___________________ Karolinska Policy _____________________________Microsurgery Fractionated WBRT Gamma Knife more than all other metastasesin larger (>2.5-3cm) 6 metastases (?)andsymptomatic leptomeningealtumors seeding

Anaplastic Astrocytoma__________________________________________

Alternatives _____________Radiosurgical boost after WBRT or surgeryRadiosurgical treatment at glioma recurrence

189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4 ____________________________ Multivariate analysis showed that survival was associated with : lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery.Larson DA, Gutin PH, McDermott M, Lamborn K, Sneed PK, Wara WM, Flickinger JC, Kondziolka D, Lunsford LD, Hudgins WR,Friehs GM, Haselsberger K, Leber K, Pendl G, Chung SS, Coffey RJ, Dinapoli R, Shaw EG, Vermeulen S, Young RF, Hirato M,Inoue HK, Ohye C, Shibazaki T. Gamma knife for glioma: selection factors and survival. Int J Radiat Oncol Biol Phys. 1996 Dec1;36(5):1045-53.

a recursive partitioning technique was used to analyze survival in 1578patients entered in three Radiation Therapy Oncology Group malignantglioma trials from 1974 to 1989 that used several radiation therapy (RT)regimens with and without chemotherapy or a radiation sensitizer. Thisapproach creates a regression tree according to prognostic variables thatclassifies patients into homogeneous subsets by survival. Twenty-sixpretreatment characteristics and six treatment-related variables wereanalyzed. Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst. 1993 May 5;85(9):704-10.

Goals and expectations __________________________________________ RTOG recursive partitioning classes Class II: AA > 50y Karnowsky 70-100 Class III: AA or GBM, <50y, Karnowsky >90 Class IV: GBM, <50y, Karnowsky < 90 or AA, > 50y, Karnowsky > 70 Class V: GBM postop., >50y, Karnowsky > 70 Class VI: GBM postop >50y, Karnowsky < 70Curran Wj et al.: ,, J.Natl.Cancer Inst. 85:704-710; 1993Curran Wj et al.: J.Natl.Cancer Inst. 85:704-710; 1993

Goals and expectations __________________________________________ RTOG recursive partitioning classes : Median Survival Class II: 37 months Class III: 18 months Class IV: 11 months Class V: 9 months Class VI: 5 monthsCurran Wj et al.: ,, J.Natl.Cancer Inst. 85:704-710; 1993Curran Wj et al.: J.Natl.Cancer Inst. 85:704-710; 1993

Standard postoperative radiotherapy and radiosurgical boost Median RTOG Median 2-year RTOG 2-year Survival Class Survival survival Class survival (months) III IIIAA or GBM AA or GBM < 50y, 19.5 35 < 50y, 29.5 58 KPS>90 KPS> 90 IV IVAA or GBM AA or GBM < 50y, 11.1 15 < 50y, 19.2 23 KPS> 70 KPS> 70 V VAA or GBM AA or GBM > 50y, 8.9 6 > 50y, 18.2 23 KPS< 70 KPS< 70 RTOG protocols Linac - Based radiosurgery Sarkaria et al: Shrieve et al: J.Neurosurg 90, 1999 Int J Radiat Oncol Biol Phys Vol.32, No 4,931-941, 1995 78 Pat, 1988-95, median volume: 9.4 cc 1578 pat fro 3 RTOG prot

Standard postoperative radiotherapy and radiosurgical boost Median RTOG Median 2-year RTOG 2-year Survival Class Survival survival Class survival (months) III IIIAA or GBM AA or GBM < 50y, 19.5 35 < 50y, 39 73 KPS>90 KPS> 90 IV IVAA or GBM AA or GBM < 50y, 11.1 15 < 50y, 16 24 KPS> 70 KPS> 70 V VAA or GBM AA or GBM > 50y, 8.9 6 > 50y, 19 26 KPS< 70 KPS< 70 RTOG protocols Gamma Knife radiosurgery Sarkaria et al: Kondziolka et al: Neurosurg 41, 4, 1997 Int J Radiat Oncol Biol Phys Vol.32, No 4,931-941, 1995 107 Pat, 0.6-20cc, median volume: 9.4 cc 1578 pat fro 3 RTOG prot

Median Median RTOG 2-year RTOG 2-year Survival Survival Class survival Class survival (months) (months) III III AA or GBM AA or GBM < 50y, 29.5 58 < 50y, 39 73 KPS> 90 KPS> 90 IV IV AA or GBM AA or GBM < 50y, 19.2 23 < 50y, 16 24 KPS> 70 KPS> 70 V V AA or GBM AA or GBM > 50y, 18.2 23 > 50y, 19 26 KPS< 70 KPS< 70 Gamma KnifeLinac - Based radiosurgery Shrieve et al: J.Neurosurg 90, 1999 radiosurgery Kondziolka et al: Neurosurg 41, 4, 1997 78 Pat, 1988-95, median volume: 9.4 cc 107 Pat, 0.6-20cc, median volume: 9.4 cc

GBM Radiosurgical Boost within 6 weeks of the completion of EBRT _________________ EBRT plus GK-SRS boost : median survival of 25 months (n=31) EBRT alone : median survival of 13 months (n=33)The addition of a GK-SRS boost in conjunction with surgery and EBRTsignificantly improved the overall survival time in this retrospectiveseries of patients with GBM.Nwokedi EC, DiBiase SJ, Jabbour S, Herman J, Amin P, Chin LS. Gamma knife stereotactic radiosurgery for patients withglioblastoma multiforme. Neurosurgery. 2002 Jan;50(1):41-6; discussion 46-7.

Radiosurgical boost after WBRT or surgery unresectable GBMs located in eloquent areas _________________________ Gamma Knife surgery (GKS) followed by radiotherapy 10 patients underwent GKS followed by fractionated radiotherapy. 9 patients : radiotherapy alone after biopsy-proven diagnosis served as the control group. median patient survival time was 52 weeks and the median overall survival time was 28 weeks in the control group. The difference was not statistically significant (p = 0.0758).Kong DS, Nam DH, Lee JI, Park K, Kim JH. Preservation of quality of life by preradiotherapy stereotactic radiosurgery forunresectable glioblastoma multiforme. J Neurosurg. 2006 Dec;105 Suppl:139-43.

Radiosurgical boost after WBRT or surgery RTOG 93-05 _________________________ Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol.203 patients with supratentorial GBM (tumor < or =40 mm) were randomly assigned either topostoperative SRS followed by EBRT (60 Gy) plus BCNU Days 1-3 every 8 weeks for six cycles)or to EBRT with BCNU alone.Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):853-60. Randomized comparison of stereotactic radiosurgery followed byconventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastomamultiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Souhami L, Seiferheld W, Brachman D, PodgorsakEB, Werner-Wasik M, Lustig R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran WJ Jr.

Radiosurgical boost after WBRT or surgery RTOG 93-05 _________________________The American Society for Therapeutic Radiology and Oncology (ASTRO)evidence-based review of the role of radiosurgery for malignant glioma. median survival in the radiosurgery group was 13.5 months median survival for the standard treatment group was 13.6 months Conclusion: Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning.Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):853-60. Randomized comparison of stereotactic radiosurgery followed byconventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastomamultiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Souhami L, Seiferheld W, Brachman D, PodgorsakEB, Werner-Wasik M, Lustig R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran WJ Jr.

Radiosurgical boost after WBRT or surgery _________________________The American Society for Therapeutic Radiology and Oncology (ASTRO)evidence-based review of the role of radiosurgery for malignant glioma. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), Cochrane library (2004 issue 2) In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (1997-2004), ASTRO (1997-2004), European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched.Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):47-55. The American Society for Therapeutic Radiology and Oncology (ASTRO)evidence-based review of the role of radiosurgery for malignant glioma. Tsao MN, Mehta MP, Whelan TJ, Morris DE, HaymanJA, Flickinger JC, Mills M, Rogers CL, Souhami L.

Radiosurgical boost after WBRT or surgery _________________________ The (ASTRO) evidence-based review There is Level I evidence that the use of radiosurgery boost followed by external beam radiotherapy and carmustine (BCNU) does not confer benefit with respect to overall survival, quality of life, or patterns of failure as compared with external beam radiotherapy and BCNU. There is Level I-III evidence of toxicity associated with radiosurgery boost as compared with external beam radiotherapy alone.Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):47-55. The American Society for Therapeutic Radiology and Oncology (ASTRO)evidence-based review of the role of radiosurgery for malignant glioma. Tsao MN, Mehta MP, Whelan TJ, Morris DE, HaymanJA, Flickinger JC, Mills M, Rogers CL, Souhami L.

Radiosurgical treatment at glioma recurrence _________________________

Radiosurgical treatment at glioma recurrence SRS as a salvage treatment for recurrent malignant gliomas _________________________prospective cohort study, 114 consecutive patientsCompared with a historic control group,SRS significantly prolonged survival as a salvage treatment in patientswith recurrent glioblastomas (23 months vs 12 months; P < .0001) Cancer. 2008 May 1;112(9):2046-51. Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Kong DS, Lee JI, Park K, Kim JH, Lim DH, Nam DH.

Radiosurgical treatment at glioma recurrence Gamma Knife as an "upfront" adjuvant therapy after surgery or at the time of tumor progression _________________________ 51 consecutive patients Adjuvant GK-SRS performed at tumor progression seems to increase median survival to 16.7 months compared with 10 months when performed after the time of initial tumor resection.Hsieh PC, Chandler JP, Bhangoo S, Panagiotopoulos K, Kalapurakal JA, Marymont MH, Cozzens JW, Levy RM, Salehi S.Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients withglioblastoma multiforme. Neurosurgery. 2005 Oct;57(4):684-92; discussion 684-92.

Glioma WHO III-IVpostoperative Remnant/Recurrence ____________________ Karolinska Hospital Ernest Dodoo 55 consecutive Patients 20 pat WHO III / 35 pat WHO IV treated 1/2001 - 7/2007 for tumor recurrences after conventional resection and WBRT Median Min dose : 20 Gy (14-22 Gy) Median Max dose: 45 Gy (30-77Gy) median Tumor volume : 5.2 cc median radiol. follow-up: 16.5 months 110427

Survival after Initial diagnosis Astrocytoma WHO III:median survival after initial diagnosis 49.6 months (19.2-122.5) Astrocytoma WHO IV:median survival after initial diagnosis 24.5 months (5.4-84.4) 110427

Survival after Gamma Knife Treatment Astrocytoma WHO III: median survival after Gamma Knife 24.2 months (5-68.1)Astrocytoma WHO IV: median survival after initial treatment 11.3 months (2.5-62.8) 110427

Standard postoperative radiotherapy and radiosurgical boost Median Median 2-yearRPA Class RPA Class Survival Survival survival (months) II AA 61.2 III IIIAA or GBM AA or GBM < 50y, 19.5 35 < 50y, 28.9 KPS>90 KPS> 90 IV IVAA or GBM AA or GBM < 50y, 11.1 15 < 50y, 28 KPS> 70 KPS> 70 V VIAA or GBM AA or GBM > 50y, 8.9 6 > 50y, 22.1 KPS< 70 KPS< 70 RTOG protocols Karolinska Gamma Knife Sarkaria et al: Int J Radiat Oncol Biol Phys Study survival after diagnosis Vol.32, No 4,931-941, 1995 1578 pat fro 3 RTOG prot 55 Pat, median volume: 5.2 cc 110427

Treatment GBM recurrence after failure of conventional treatment (resection, WBRT,chemotherapy) median survival after number of study histology method survival after radiosurgery for patients diagnosis recurrenceNeurosurg Rev. 2009 Oct;32(4):417-24. Epub 2009 Jul glioblastoma25. Villavicencio AT, 26 and glioma Cyber Knife 21 7Burneikiene S, Romanelli P, WHO IIIFariselli L, McNeely L, LipaniJD, Chang SD, Nelson EL,J Neurooncol. 2009 Sep;94McIntyre M,Epub 2009Adler29.(3):409-18. Broggi G, MarJR Jr.Pouratian N, Crowley RW, 26 glioblastoma Gamma Knife 17.4Sherman JH, Jagannathan J,Sheehan JP.Cancer. 2008 May 1;112(9):2046-51. Kong DS, Lee JI,Park K, Kim JH, Lim DH, Nam 114 glioblastoma ? 23DH.Strahlenther Onkol. 2009Apr;185(4):235-40. Epub 2009 HypofractionatedApr 16. Fokas E, Wacker U, 53 glioblastoma stereotactic 27Gross MW, Henzel M, radiotherapyEncheva E, Engenhart-CabillicCancer. 2005 Nov 15;104R.(10):2168-73. Combs SE,Widmer V, Thilmann C, Hof H, 32 glioblastoma stereotactic Linac 22 10Debus J, Schulz-Ertner D.Dodoo, Lippitz, Karolinskaseries 35 glioblastoma Gamma Knife 24.5 11.3

Treatment GBM recurrence after failure of conventional treatment (resection, WBRT,chemotherapy) median survival after number of study histology method survival after radiosurgery for patients diagnosis recurrenceNeurosurg Rev. 2009 Oct;32(4):417-24. Epub 2009 Jul25. Villavicencio AT, Cyber Knife 21 7Burneikiene S, Romanelli P,Fariselli L, McNeely L, LipaniJD, Chang SD, Nelson EL,J Neurooncol. 2009 Sep;94McIntyre M,Epub 2009Adler29.(3):409-18. Broggi G, MarJR Jr.Pouratian N, Crowley RW, Gamma Knife 17.4Sherman JH, Jagannathan J,Sheehan JP.Cancer. 2008 May 1;112(9):2046-51. Kong DS, Lee JI,Park K, Kim JH, Lim DH, Nam ? 23DH.Strahlenther Onkol. 2009Apr;185(4):235-40. Epub 2009 HypofractionatedApr 16. Fokas E, Wacker U, stereotactic 27Gross MW, Henzel M, radiotherapyEncheva E, Engenhart-CabillicCancer. 2005 Nov 15;104R.(10):2168-73. Combs SE,Widmer V, Thilmann C, Hof H, stereotactic Linac 22 10Debus J, Schulz-Ertner D.Dodoo, Lippitz, Karolinskaseries Gamma Knife 24.5 11.3

Treatment Glioma WHO III recurrence after failure of conventional treatment (resection, WBRT,chemotherapy) median survival after number of study histology method survival after radiosurgery for patients diagnosis recurrenceCancer. 2008 May 1;112(9):2046-51. Kong DS, Lee JI, glioma 114 ? 37.5Park K, Kim JH, Lim DH, Nam WHO IIIDH.Strahlenther Onkol. 2005 fractionatedDec;181(12):768-73. Combs glioma 40 stereotactic 48 16SE, Gutwein S, Thilmann C, WHO IIIDebus J, Schulz-Ertner D. radiotherapyDodoo, Lippitz, Karolinska glioma 20 Gamma Knife 49.6 24.2series WHO III

Glioblastoma(postoperative recurrence) 1. Gamma Knife treatment 7/03 (13 Gy) follow-up after 5 months FDG-PET after 5 months with metabolic activity 2.treatment according to PET (18 Gy) follow-up after 8 months

GLIOBLASTOMA 3 YEAR FOLLOW-UP 73 year old female pat. S.I.at treatment 031223 3.5 months 040407 RECURRENCE and RETREATMENT 33 months 060809 36 months 061214

Gamma Knife Radiosurgery of Glioblastoma at treatmentperipheral dose 10 Gy 9 months 16 months 19 months

Adverse Radiation Effects after Gamma KnifeSecondary increasing volume 3-6 months after GK ________________________ WHO III 38 % (8/21) 2nofu WHO IV 65 % (17/26) 2nofu Increasing Volume after 3-6 months not dependent of WHO class

Conclusion __________ Gamma Knife or Linac radiosurgery : no proven beneﬁt for radiosurgical boostafter initial treatment (resection and EBRT)

Conclusion __________Radiosurgical Retreatment: Risk for development of adverse radiation effects with edema and even subsequent need for resection

Conclusion __________ Gamma Knife or Linac radiosurgeryallow treatment of tumor recurrence in anaplastic glioma and glioblastoma potentially increase the survival

ependymoma____________ WHO classiﬁcation • myxopapillary ependymoma WHO I • subependymoma WHO I • ependymoma WHO II • anaplastic ependymoma WHO III

ependymoma____________ependymoma are considered to be radiosensitivechemotherapy not very effectivebenign ependymoma: 5-year survival 55-87 %malignant ependymoma :5-year survival 10-47%problem: leptomeningeal seeding

Case study๏ ependymoma initially WHO II operation -94๏ Gamma Knife 990506 (15 Gy 4.vent)๏ GK 001130 new tumor๏ local recurrence operated 010308๏ 3 local recurrences GK 011129๏ 2 new tumors GK 021017๏ operation 031124 ARE/local recurrence(after GK 011129)๏ GK new tumor 040603๏ operation 060210 lat vent (after GK 040603)๏ now anaplastic ependymoma III๏ operation 071019๏ Gamma Knife new tumors (#2-#7) 080208๏ operation of a frontal tumor too large for GK (#8) 080222๏ Gamma Knife new tumors (#8-#11) 21 Gy 080513๏ Gamma Knife new tumors (#11-#21) 21 Gy 090120๏ operation of frontal postoperative recurrence (#8) 090110๏ Gamma Knife 3 new tumors (#21-24) 22 Gy 090506๏ general progress 100108๏ Patient died 100417

ependymoma who III011129 031107 090304

ependymoma who III021017 040603 080221

ependymoma who III 100108

Anaplastic Ependymoma Long-Term Follow-up_______________________ Karolinska Hospital 7 consecutive patients 1990-2004 median age: 11.2 years (2.5-39.6) Median Min Dose: 18 Gy (12-22) median vol: 0.5 cc (0.01-7) all operated before previous conv fractionated Rx: 71 % (5/7)median survival : 14.4 months spinal metastases 50 %

Ependymoma and Radiosurgery _____________ number of follow- progressive doses control rate patients up diseaseLo SS, Abdulrahman R, Desrosiers PM, 14 Gy 30.3 moFakiris AJ, Witt TC, Worth RM, Dittmer PH, 7 77 %Desrosiers CM, Frost S, Timmerman RD. J (12-20) (8-65)Neurooncol. 2006 Aug;79(1):51-6Mansur DB, Drzymala RE, Rich KM, Klein EE, 9 56% 4/9Simpson JR. J Neurooncol. 2004 Jan;66(1-2): 14-20 Gy 28 mo187-90. (2 anapl) 3 year progress.free progress.diseaseJawahar A, Kondziolka D, Flickinger JC,Lunsford LD. Stereotact Funct Neurosurg. 16 Gy 22 21 mo 62.3% 41 %1999;73(1-4):23-30. (10-20) anaplastic ! (4-84) (5y actuarial control) distant new tumorsStafford SL, Pollock BE, Foote RL, Gorman DA, 12Nelson DF, Schomberg PJ. Cancer. 2000 Feb 18 Gy 22.5 mo 68 % 17 %15;88(4):870-5. recurrent (12-24) (2.5-60) (3y infield control) distant new tumors ependymo current Karolinska Series 16.4 Gy 15 78 mo 50% spinal median benign median 84.6% 1989-2004 11/13 FU tumors (5-22) ependymoma (2.4-165) 18 Gy 7 14.4 mo current Karolinska Series median anaplastic median 1990-2001 (12-22) ependymoma survival

conclusion ependymoma _______________ high grade : limited local control 62% distant metastases in 41% median survival 14 months

pineal parenchymal tumors__________________ pineoblastoma pineocytoma mixed pineocytoma/pineoblastoma In Europe and US: 0.4-1% % of all adult intracranial tumors

pineal parenchymal tumors__________________ pineoblastoma pineocytoma problem: spinal seeding in ca 45 % treatment: operation/biopsy craniospinal radiation

Pineoblastoma _____________ beforeresection at Gamma Knife 3 year FU treatment 5 y after op and fract Rx L.F. 32 y.m

Pineoblastoma _____________ Seeding 41 months after radiosurgery 6 years after conv fractionated RadiotherapyL.F. 32 y.m

Pineoblastoma: after Radiosurgery _____________ number of tumor leptomening, doses patients control seedingReyns, Peragut, Blond, Regis 4/5 15 GyActa Neurochir (Wien) 2006 Jan; 148(1), 5-11 5 2/5 recurrence and 1/5 (11-20) retreatmentHasegawa T, Kondziolka D,Hadjipanayis CG, Flickinger JC, 15.3 Gy 4/4Lunsford LD. Neurosurgery. 2002 Oct;51 4 1/4 (12-20) mean FU 52mo(4):880-9. 1/2Kobayashi T, Kida Y, Mori Y. 15.7 Gy 2 FU 30mo 0/2J Neurooncol. 2001 Sep;54(3):301-9. 1recurrence 13mo initial tumorCurrent Series Karolinska 13.5 Gy median survival 7 regression1994-2005 (10-20) 14.6 months in majority

Pineoblastoma Long-Term Follow-up _______________________ Karolinska Hospital7 consecutive Patients 1994-2005 median age: 32.8 yearsMedian Min Dose: 13.5 Gy (10-20) median survival: 14.6 moInitially Pineoblastoma responded

conclusion pineoblastoma _______________ often good initial local control prescription doses 14-15 Gy Cave: risk for local recurrence

conclusion anaplastic ependymoma _______________ limited local control of ca 60% distant metastases in 41% median survival 14 months Cave: spinal tumors distant new tumors

conclusion radiosurgery for malignant glioma _______________currently no role as immediate boost after conventional treatment (surgery + fractionated Rx) possible role as treatment for recurrenceafter conventional treatment (surgery + fractionated Rx)

conclusion radiosurgery for brain metastases _______________•provides effective local control against all brainmetastases including “radioresistant” metastases•can be used for recurrences after surgery ofconventional fractionated radiotherapy•no direct correlation between number of brainmetastases (2-7?) and prognosis

bodo.lippitz@cromwellhospital.com

Isrs2011 course 05

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