Microsoft PowerPoint - 0930_0_Braunstein4/23/2021
Penny K. Sneed, MD, David R. Raleigh, MD PhD, Jean L. Nakamura, MD, Shannon E. Fogh, MD, Steve E. Braunstein, MD PhD
Dept. of Radiation Oncology University of California San Francisco
CNS Case-Based Learning: Brain Metastasis Postoperative Rx
CNS Case-Based Learning: Brain Metastasis Postoperative Rx
CT C/A/P negative
70 yo , 50 pk-yr tob hx, COPD, 1 wk of expressive aphasia; mild R-sided weakness
MRI: 7 x 5 x 5 hetero. enhancing L frontal mass (atyp meningioma vs PNET vs ependymoma vs metastasis)
Indications for SurgeryIndications for Surgery
Single (or dominant) lesion
Histologic diagnosis in question
Symptomatic
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Post-gad
Path: poorly differentiated carcinoma
B. Whole brain radiotherapy only
C. SRS or SBRT only
D. WBRT + SRS or SBRT
E. Wait for further testing, and consider immunotherapy or targeted therapy
What postoperative brain treatment would you recommend for this patient? What postoperative brain treatment would you recommend for this patient?
A. Observation 50-60% risk of local recurrence by 6-12 mo (Patchell RA, JAMA 1998; Kocher M [EORTC], J Clin Oncol 2011; Mahajan A, Lancet Oncol 2017)
B. Whole brain radiotherapy only Compared with SRS, yields better local and intracranial control, but more neurocognitive deterioration without improving survival time (Brown PD, Lancet Oncol 2017)
C. SRS or SBRT only Preferred choice according to NCCTG/N107C/ CEC3 randomized trial (Brown PD, Lancet Oncol 2017)
D. WBRT + SRS or SBRT Not studied in combination in postop setting; for definitive rx, SRS alone results in less neurocognitive decline without compromising survival time (Brown PD, JAMA 2016)
E. Wait for further testing, and consider immunotherapy or targeted therapy Immunotherapy or targeted therapy may be reasonable in the postop setting for melanoma or EGFR, ALK, or ROS1 NSCLC extrapolating from experience in patients with small, asymptomatic brain mets. Need data.
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Overall Survival Cognitive-decline-free Surv
SRS
WBRT
Brown PD, et al. Lancet Oncol, 2017; 18:1049-1060 Resection + postop WBRT vs. SRS 48 instit US & Canada; 194 pts randomized; 12-20 Gy
to cavity+2 mm; higher dose to any unresected mets
(>1 SD ↓ in at least 1/6 tests)
Median 6-mo 6-mo 6-mo survival intracranial surgical cognitive
n time control bed control deterioration
Brown PD, et al. Lancet Oncol, 2017; 18:1049-1060
NCCTG N107C/CEC3 TrialNCCTG N107C/CEC3 Trial
SRS 98 12.2 mo 55% 80% 52% WBRT 96 11.6 mo 81% 87% 85%
p=0.70 p<0.0001 p= 0.00031 p=0.00068
Among 54 long-term survivors with testing @ ≥ 1 yr, cognitive deterioration in 37% of SRS pts vs. 89% of WBRT patients
No difference in risk of LMD (7% vs 5% at 12 mo)
20% of SRS patients had salvage WBRT
Soliman H et al, Neurosurgery 2019
Resection Cavity Post-Op SBRT Resection Cavity Post-Op SBRT
137 resection cavities in 122 patients treated to median of 30 Gy in 5 fxs (range, 25-35 Gy)
CTV incl cavity edge and dura with 0.5-1 cm margin along meninges; PTV 2 mm
Median F/U 16 mo; MST 17 mo One-year results: 84% local control 45% distant brain failure 22% leptomeningeal disease (higher risk with
breast cancer and STR)
Further shrinkage of cavity on MRI @ 5 wks PET/CT neg.; unkn. 1º; no actionable mutations
Linac SBRT to 25 Gy / 5 fractions
30 Gy 25 Gy 20 Gy 15 Gy 10 Gy
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coronalaxial
SA-CME QuestionSA-CME Question
In the NCCTG N107C/CEC3 trial of post- operative SRS vs WBRT, which outcome was significantly improved in the SRS arm?
A. Overall survival time B. Risk of cognitive deterioration [lower]
C. Surgical bed control D. Intracranial control E. None of the above
SA-CME QuestionSA-CME Question In the NCCTG N107C/CEC3 trial of post- operative SRS vs WBRT, which outcome was significantly improved in the SRS arm?
X A. Overall survival time (12.2 vs 11.6 mo, NS)
B. Risk of cognitive deterioration (Neurocognitive deterioration at 6 months 52% for SRS vs 85% for WBRT, p=0.00031)
X C.Surgical bed control (80% vs 87% at 6 mo)
X D. Intracranial control (55% vs 81% at 6 mo)
Brown PD, et al. Lancet Oncol, 2017; 18:1049-1060
CNS Case-Based Learning: Recurrent Meningioma
CNS Case-Based Learning: Recurrent Meningioma
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Case presentation
• 33 year-old female with a history of right frontal meningioma, WHO grade I, status post gross total resection 10 years ago
• Now presenting with an symptomatic radiographic multifocal recurrence in the resection cavity
• Gross total resection of atypical meningioma, WHO grade II, with MIB1 labeling index of 10%
Case presentation
A. Close imaging surveillance
B. DNA methylation profile to establish molecular risk
C. Adjuvant radiotherapy to a total dose of 54Gy with a 1.5-2 cm isotropic CTV expansion around the resection cavity
D. Adjuvant radiotherapy to a total dose of 59.4-60Gy with a 1.5-2 cm anisotropic expansion around the resection cavity
CME question
• Which of the following statements are not applicable to the design of the NRG BN-003 and EORTC 1308 (ROAM) trials?
A. Atypical meningioma
Brastianos et al. Advances in multidisciplinary therapy for meningiomas. Neuro Oncol 2019
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CME question
• Which of the following statements are not applicable to the design of the NRG BN-003 and EORTC 1308 (ROAM) trials?
A. Atypical meningioma
Brastianos et al. Advances in multidisciplinary therapy for meningiomas. Neuro Oncol 2019
CNS Case-Based Learning: Spine Metastasis
CNS Case-Based Learning: Spine Metastasis
Case Presentation
• 2 years prior:  neck pain, C4 involvement > radiotherapy at OSH
• Present:  c/o L neck pain, L arm weakness
• PET/CT – multiple FDG avid and lytic lesions
• Exam: Complete  flaccid  weakness of L arm, sparing of L hand 0/5 L deltoid, 0/5 L biceps
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Challenge:  Bulky epidural disease, contact with the spinal cord
OSH  SBRT to C4      4 Gy x 5 Audience survey: What approach would you favor in this case?
A.  No further radiotherapy
C. Intensity modulated radiotherapy 
D.  SBRT single fraction
E.  SBRT multiple fractions
Audience survey: If reirradiation, what approach/fractionation would you  use?
A.   AP/PA 8 Gy x 1
B. 3DCRT 3 Gy x 10
C. IMRT 3 Gy x 10
D.   SBRT single fraction
E.   SBRT multiple fractions
CME Question:  which of below statements are in the HyTec Guidelines regarding reirradiation SBRT?
A.  Keep Spinal cord Dmax 20 Gy in 1 fraction
B.  Keep Spinal cord Dmax 20 Gy in 2 fractions
C. PRV margins of 13 mm on the spinal cord are typical
D.  Minimum time interval to reirradiation should be at least 56 months        E.  C and D
HyTec Organspecific Paper:  Spinal cord dose tolerance to Stereotactic Body Radiation Therapy   A. Sahgal, JH Chang, et.  al. IJROBP ePub October 2019
CME Question:  which of below statements are true regarding  reirradiation SBRT?
A.  Keep Spinal cord Dmax 20 Gy in 1 fraction
B.  Keep Spinal cord Dmax 20 Gy in 2 fractions
C.  PRV margins of 13 mm on the spinal cord are typical
D.  Minimum time interval to reirradiation should be at least 5 months           E.  C and D
HyTec Organspecific Paper:  Spinal cord dose tolerance to Stereotactic Body Radiation Therapy   A. Sahgal, JH Chang, et.  al. IJROBP ePub October 2019
SBRT ARCS, 5 Gy x 5 to 72% IDL C35
max      mean    Ccord      22.95 Gy 6.16 Gy
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Case Presentation
• Pt is a 41 yo M dx w/metastatic FIGO IVB endometrial ca
• Therapy: Peritoneal, renal, lung metastases, on  lenvatinib/pembrolizumab
• Presentation: complex seizure
• Imaging: CT/MRI brain: 3.5 cm enhancing R frontal lobe mass
• Exam: ECOG 0, AOx3, motor/sensory intact
Audience survey: Postresection, what approach would you favor in this case?
A. Whole brain radiotherapy
C. Single session radiosurgery
E. Observation
>20 total  additional  lesions
CME Question:  Which of the following statements regarding adjuvant  whole brain radiotherapy dose (30 Gy in 10 fractions vs 37.5 Gy in 15  fractions) were concluded from the posthoc analysis of N107C trial?
A. WBRT 30 Gy/10 fractions had worse intracranial tumor control
B. WBRT 30 Gy/10 fractions had more highgrade toxicity
C. WBRT 37.5 Gy/15 fractions yielded better surgical bed control
D. WBRT 37.5 Gy/15 fractions improved overall survival
E. WBRT 30 Gy vs 37.5 Gy had equivalent time to cognitive impairment
CME Question:  Which of the following statements regarding adjuvant  whole brain radiotherapy dose (30 Gy in 10 fractions vs 37.5 Gy in 15  fractions) were concluded from the posthoc analysis of N107C trial?
A. WBRT 30 Gy/10 fractions had worse intracranial tumor control
B. WBRT 30 Gy/10 fractions had more highgrade toxicity
C. WBRT 37.5 Gy/15 fractions yielded better surgical bed control
D. WBRT 37.5 Gy/15 fractions improved overall survival
E. WBRT 30 Gy vs 37.5 Gy had equivalent time to cognitive impairment
Trifiletti et al. Optimizing Whole Brain Radiation Therapy Dose and Fractionation: Results From a Prospective Phase 3 Trial  (NCCTG N107C [Alliance]/CEC.3).  IJROBP 2020.
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Hippocampal Avoidance WBRT
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Parotid Avoidance WBRT
Lacrimal Avoidance WBRT
30 Gy in 10 fractions with 9 Gy in 3 fractions boost to surgical bed
CNS Case-Based Learning: High Grade Glioma
CNS Case-Based Learning: High Grade Glioma
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Case Presentation
• Pt is a 44 yo F p/w R sided weakness, L cingulate lesion s/p  biopsy f/b STR. Path c/w GBM, IDH wt
• Therapy:  60 Gy EBRT with concurrent/adj Temozolomide
Case continued
• 1 yr later evidence of progression on interval imaging
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Audience survey: What approach would you favor in this case of recurrent  glioblastoma?
A. Optimal supportive care
E. Hypofractionated external beam radiotherapy
CME Question:  Which of the following statements regarding re irradiation of high grade glioma is correct?
A. OS following reirradiation is independent of performance status
B. Smaller retreatment volumes are associated with poorer outcome
C. Shorter time between radiation courses yields improved OS
D. Median OS >20 months from reirradiation in favorable patients
E. Older patient age at reirradiation is associated with improved OS
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CME Question:  Which of the following statements regarding re irradiation of high grade glioma is correct?
A. OS following reirradiation is independent of performance status
B. Smaller retreatment volumes are associated with poorer outcome
C. Shorter time between radiation courses yields improved OS
D. Median OS >20 months from reirradiation in favorable patients
E. Older patient age at reirradiation is associated with improved OS
Kessel et al. PLOS ONE. 2017; Chapman et al. Neuro Oncol Pract 2019 Chapman et al. 
Neuro Onc Pract 2019