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Management of CNS Oligometastases Liam A. Mulroy Radiation Oncology October 2011.

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Presentation on theme: "Management of CNS Oligometastases Liam A. Mulroy Radiation Oncology October 2011."— Presentation transcript:

1 Management of CNS Oligometastases Liam A. Mulroy Radiation Oncology October 2011

2 LAM 2011 Disclosures No financial disclosures! But... 2

3 LAM 2011 Disclosures I have given an awful lot of whole brain radiation therapy in my career I am bald (Rogaine did not help) I am a Toronto Maple Leafs fan 3

4 LAM 2011 Presentation Outline I What is Oligometastatic Disease? Prognostic Factors: From RPA to GPA WBRT and SRS: Current Perspectives Neurocognitive Impairment from RT Hippocampal Avoidance(HA) IMRT for WBRT and SIB of Metastases Example Case Conclusions 4

5 LAM 2011 What is Oligometastatic Disease? Im not sure... Oligo means a few RTOG and EORTC enrolled patients with 1-3 mets JROSG-99-1 enrolled 1-4 mets PMH oligo brain mets clinic accepts patients with up to 6 mets 5

6 LAM 2011 What is Oligometastatic Disease? Should we think about total volume of intracranial mets as well as the # of mets? SRS alone for oligomets and delay WBRT? 6

7 LAM 2011 What is Oligometastatic Disease? 7

8 LAM 2011 What is Oligometastatic Disease? Should we think about the total volume of intracranial metastases? M.Follwell/PMH presentation at CARO 2011: Baseline Cumulative Volume >6.0 cc predictive for decreased O.S. I am still confused about oligometastatic disease…. RCT have included 1-4 mets 8

9 LAM 2011 RTOG RPA Classification Gaspar et al,IJROBP 1997 Vol. 37:

10 LAM 2011 RTOG RPA Survival Gaspar et al, IJROBP 1997 Vol. 37: RPA CLASS RPA CLASS MEDIAN SURVIVAL (months) (months) I II II III III

11 LAM 2011 Brain Mets DS GPA Sperduto et al IJROBP Vol.77,No.3 pp ,2010 Disease specific and includes patients treated with S, SRS and WBRT Far more complicated than traditional RTOG RPA GPA score out of 4 makes sense in USA

12 LAM 2011 Brain Mets GPA Sperduto et al IJROBP Vol.77,No.3 pp ,2010 Prognostic index based on 4,259 patients Retrospective S,SRS,WBRT Disease specific

13 LAM 2011 Brain Mets GPA Sperduto et al IJROBP Vol.77,No.3 pp ,2010

14 LAM 2011 Brain Mets GPA Sperduto et al IJROBP Vol.77,No.3 pp ,2010

15 LAM 2011 Brain Metastases: Current Perspectives WBRT improves CNS disease control i.e. micrometastases in the rest of the brain WBRT results in significant neurocognitive impairment WBRT does not improve overall survival 15

16 LAM 2011 Brain Metastases: Current Perspectives What are some of the endpoints to be considered when assessing RT (WBRT or SRS) for brain metastases? Local Control of existing mets CNS Control (mets and micro-mets) Overall Survival 16

17 LAM 2011 Brain Metastases: Current Perspectives What are some of the endpoints to be considered when assessing RT (WBRT or SRS) for brain metastases? Quality of Life Functional Independence Neurocognitive Function Steroid Requirements 17

18 LAM 2011 Brain Metastases: Current Perspectives What other aspects should be considered when assessing RT (WBRT or SRS) for brain metastases? $$$$ Availability and timely access to RT How much RT, how often to deliver RT in patients with limited life expectancy? 18

19 LAM 2011 Brain Metastases: Current Perspectives Which are the most important endpoints when assessing whole brain radiation therapy? Remember that the treatment intent is palliative

20 LAM 2011 Early Season Overachievers 20

21 LAM 2011 EORTC Kocher et al, JCO 29: , 2011 Adjuvant WBRT vs. Observation after SRS or S in Patients with 1-3 Cerebral Metastases 359 patients accrued

22 LAM 2011 EORTC SRS in 199, S in % NSCLC S arm: 95% had single mets; larger lesions vs. SRS and more often in post. fossa WBRT 30 Gy/10 fr. SRS 20 Gy peripheral dose, maximum lesion diameter 35 mm Patient groups well balanced 22

23 LAM 2011 CEREBELLAR MET Primary NSCLC

24 LAM 2011 EORTC : SRS or S +/- WBRT 24

25 LAM 2011 EORTC

26 LAM 2011 EORTC

27 LAM 2011 EORTC WBRT in patients with 1-3 mets does not prolong overall survival or survival with functional independence after S or SRS WBRT reduces local progression, intracranial progression and improves PFS After S alone local progression rate is 59% at 2 years 27

28 LAM 2011 EORTC Greater incidence of serious adverse events in WBRT arm(13 vs. 3 SAE) Results very similar to Patchell (S) and JROSG-99-1 (SRS) trials Reasonable to delay WBRT in patients with limited # mets Local therapy (e.g SRS) to surgical bed after resection? 28

29 LAM 2011 Neurocognition and WBRT Neurocognition in Patients Treated with SRS or SRS plus WBRT: A Randomized Controlled Trial Chang et al Lancet Oncol : patients randomized Primary endpoint: HVLT-R at 4 months WBRT 30 Gy/12 fractions 29

30 LAM 2011 Neurocognition and WBRT Trial closed early (58 patients) Significant difference in total recall at 4 months, SRS and WBRT inferior to SRS Chang et al Lancet Oncol :

31 LAM 2011 Inferior survival in SRS+WBRT arm Patients in SRS arm received more chemo and started earlier Salvage surgery more common in SRS arm 31 Does WBRT Adversely Effect Overall Survival? Chang et al Lancet Oncol :

32 LAM 2011 No adverse effect in JROSG-99-1) 132 patients, accrual , 1-4 mets median survival 7.5 months WBRT + SRS vs. 8.0 months SRS 32 Does WBRT Adversely Effect Overall Survival? Aoyama et al, JAMA 2006; 295:

33 LAM 2011 Does WBRT Adversely Effect Overall Survival? Negative effect in Chang trial not seen in JROSG-99-1, EORTC (reviewed earlier) and a surgical trial published by Patchell No survival benefit as an adjuvant therapy 33

34 LAM 2011 Hippocampal Avoidance Section HIPPOCAMPUSHIPPOPOTAMUS 34

35 LAM 2011 Hippocampal Avoidance Emerging evidence suggests that a neural stem cell compartment in the hippocampus is key to the pathogenesis of neurocognitive deficits observed after cranial RT Neural progenitor cells are anatomically clustered within the dentate gyrus of the hippocampus 35

36 LAM 2011 Hippocampal Avoidance 36

37 LAM 2011 Hippocampal Avoidance Following RT neural progenitor cells become less proliferative, more apoptotic, more likely to adopt a gliogenic fate Inflammation in the area surrounding the neural stem cells is a major contributing factor to RT effect 37

38 LAM 2011 Hippocampal Avoidance Hippocampus + 5 mm= Hippocampal Avoidance Region Planning study by Gondi et al (5 patients) showed mean HAR of 3.3 cubic cm HAR represents approx. 2% of whole brain volume 38

39 LAM 2011 Hippocampal Avoidance Gondi et al, Radiother. Oncol. 95: % mets occur outside HAR 39

40 LAM 2011 Hippocampal Avoidance HA-WBRT technique (Gondi et al) 40

41 LAM 2011 Hippocampal Avoidance HA-WBRT may prevent/reduce neurocognitive impairment RTOG 0933 is evaluating HA-WBRT and NCF HA-WBRT should only be done within clinical trials at this time Save the hippos! 41

42 LAM 2011 WBRT and SIB SIB=simultaneous integrated boost of metastases Tomotherapy or VMAT are efficient ways of delivering SIB with WBRT UWO (Rodrigues et al) performed an elegant Phase I clinical to assess safety of this approach using helical tomotherapy 42

43 LAM 2011 WBRT and SIB Rodrigues et al, IJROBP Vol.80, No.4, pp , 2011 Phase I Trial 48 patients, 70 mets WBRT 30 Gy/10 fr. with SIB 5-30 Gy in 5 Gy increments Well tolerated, no dose limiting toxicities even at 60 Gy/10 fr. Median O.S months 43

44 LAM 2011 WBRT and SIB Rodrigues et al, IJROBP Vol.80, No.4, pp ,

45 LAM 2011 WBRT and SIB Rodrigues et al, IJROBP Vol.80, No.4, pp ,

46 LAM 2011 WBRT with SIB and HA Hsu et al, IJROBP 2009 It can be done if you let Fred do it! Planning study at BCCA 10 patients,18 mets SIB mets Gy WBRT Gy/15 fr Mean hippocampal dose 5.23 Gy-2 46

47 LAM 2011 WBRT with SIB and HA Hsu et al, IJROBP

48 LAM 2011 WBRT with SIB and HA Hsu et al, IJROBP

49 LAM 2011

50 Example Case Various options year old female,metastatic breast cancer,excellent condition RTOG RPA class 2 GPA 3 or 4, median survival months 6 mets, largest/symptomatic met excised 50

51 LAM 2011

52 Conclusions Various management options should be considered and treatment should be individualized WBRT should not be abandoned but must evolve/improve HA-WBRT and SIB should be studied- in clinical trials that Atlantic Canadians can participate in 52


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