Hippocampal sparing whole brain radiation therapy- Making a case!
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Transcript of Hippocampal sparing whole brain radiation therapy- Making a case!
• Physicist and chemist• Winnipeg, Manitoba, Canada• 2nd person to die of criticality
accident (Manhattan Project)• Proposed dollar unit of reactivity• Louis Slotin
May 21st 1946
“Everything I do is slow. I walk, talk, and think slowly… I still have no short-term memory…
Much of the time I can't even remember the names of relatives and close friends… I am always confused…
Because I look normal and often sound normal, people assume I am normal. But I'm not…
I get depressed a lot knowing that I will never have my competence back.”
-Sontag Foundation Distinguished Scientists Awards ceremony speech at the Society for Neuro-Oncology Meeting, Toronto,
Canada, November 20, 2004
- Susan Sontag (full time homemaker and mother / Cancer & brain radiation survivor )
• Whole-brain radiotherapy (WBRT) is the most widely used treatment option for patients with multiple brain metastases
• Benefits• rapid palliation of neurologic symptoms • improved local control as an adjuvant to
resection or radiosurgery. • prolongs time to neurocognitive function (NCF)
decline.( deterioration in NCF preceded self-reported quality of life decline by up to 153 days)
WBRT
• Before 1970, the human brain was
thought to be radioresistant;
• the acute central nervous system
(CNS) syndrome occurs after single
doses of ≥30 Gy, and white matter
necrosis can occur at fractionated
doses of ≥60 Gy
CNS Toxicity
• Radiation necrosis of the brain typically occurs 3 months to several years after radiotherapy (median 1–2 years)
• Emami et al • 5% risk of radionecrosis at 5 years
with a dose of 60 Gy to one-third of the brain with standard fractionation
• Quantec : For standard fractionation, the incidence of radionecrosis appears to be • <3% for a dose of <60 Gy. • 5% with a dose of 72 Gy • 10% with a dose of 90 Gy. However
But that’s not what we are talking about!!
• Early neurocognitive decline, within the first 1-4 months, which primarily reflects memory.
• Long-term serious and permanent adverse effects, including cognitive deterioration in other domains and cerebellar dysfunction
• As many as11% of long-term brain metastases survivors (>12 months) treated with WBRT develop severe dementia, especially with the use of larger dose-per-fraction schedules
Neuro-cognitive toxicity in WBRT
• According to the principle of double effect, • “sometimes it is permissible to
cause a harm as a side effect (or “double effect”) of bringing about a good result even though it would not be permissible to cause such a harm as a means to bringing about the same good end.”
Doctrine of Double Effect
St. Thomas Aquinas; Summa Theologica (II-II, Qu.
64, Art.7)
• radiation-induced injury to
proliferating neuronal progenitor cells
in the subgranular zone of the
hippocampi
PATHOGENESIS
• Approximately 100 000 patients
per year in the United States with
primary and metastatic brain tumor
survive long enough (>6 months) to
develop radiation-induced brain
injury
Is this a big deal in these stage IV patients?
• At 4 months• HA-WBRT versus WBRT
• 7% vs 30% memory score decline
• measured by the Hopkins Verbal Learning Test (HVLT).
• By 6 months post-treatment, decline was 2 percent, on average
RTOG 0933
American Society for Radiation Oncology (ASTRO) 55th Annual Meeting; 2013
• MRI:• 3D-SPGR axial MRI scan of the head with standard axial and coronal
FLAIR, axial T2-weighted and gadolinium contrast-enhanced T1-weighted sequence acquisitions .
• 1.25mm slice thickness is preferred to contour the hippocampus accurately. Slice thickness of 1.5mm or less is permitted.
• Obtain in supine position; immobilization devices used for CT simulation and daily radiation treatments not necessary.
• CT Simulation:• Non-contrast treatment-planning CT scan of the entire head region.
• 1.25-1.5mm slice thickness is preferred for accurate hippocampal sparing planning. Slice thickness of 2.5mm or less is permitted.
• Immobilize patient in supine position using an immobilization device such as an Aquaplast mask over the head. Treat patients in the immobilization device.
• MRI-CT Fusion:• Fuse the 3D-SPGR MRI and the treatment-planning CT.
SIM INFO (0933)
HA-WBRT IMRTPlanning
PTV D2% ≤ 37.5 GyD98% ≥ 25 Gy
Hippocampus D100% ≤ 9 GyMaximum dose ≤ 16 Gy
Optic Nervesand Chiasm
Maximum dose ≤ 37.5 Gy
0933 dose constraints
Recursive Partitioning Analysis (RPA)
RPA Stages For Brain Metastases
Stage Characteristics Median Survival (mo)
IKPS >=70, age <65, primary
controlled, no other extracranial mets
7.1
II all others 4.2
III KPS <70 2.3
GPA Criteria For Brain Metastases
Variable 0 Points0.5
Points1 Point 2 Points 3 Points 4 Points
NSCLC/SCLC
Age >60 50-59 <50 - - -
KPS <70 70-80 90-100 - - -
No. Cranial Mets
>3 2-3 1 - - -
Extra-cranial Mets
Present - Absent - - -
Renal/Melanoma
KPS <70 - 70-80 90-100 - -
No. Cranial Mets
>3 - 2-3 1 - -
Breast/GIKPS <70 - 70 80 90 100
Median OS Survival (months)
GPA Score
NSCLC
SCLC Melanoma
Renal cell
Breast GI
0-1 3.0 2.8 3.4 3.3 6.1 3.1
1.5-2.5 6.5 5.3 4.7 7.3 9.4 4.4
3.0 11.3 9.6 8.8 11.3 16.9 6.9
3.5-4.0 14.8 17.0 13.2 14.8 18.7 13.5
Overall 7.0 4.9 6.7 9.6 11.9 5.4
• 58 y/o nurse & smoker• c/o headache, nausea, mental status
changes• CT showed 3 metastasis : radiologic
diagnosis• No other site of primary on CT T/A/P• no other etiology suspected
CASE SUMMARY
RPA Stages For Brain Metastases
Stage Characteristics Median Survival (mo)
IKPS >=70, age <65, primary
controlled, no other extracranial mets
7.1
II all others 4.2
III KPS <70 2.3
GPA Criteria For Brain Metastases
Variable 0 Points0.5
Points1 Point 2 Points 3 Points 4 Points
NSCLC/SCLC
Age >60 50-59 <50 - - -
KPS <70 70-80 90-100 - - -
No. Cranial Mets
>3 2-3 1 - - -
Extra-cranial Mets
Present - Absent - - -
Renal/Melanoma
KPS <70 - 70-80 90-100 - -
No. Cranial Mets
>3 - 2-3 1 - -
Breast/GIKPS <70 - 70 80 90 100
Median OS Survival (months)
GPA Score
NSCLC
SCLC Melanoma
Renal cell
Breast GI
0-1 3.0 2.8 3.4 3.3 6.1 3.1
1.5-2.5 6.5 5.3 4.7 7.3 9.4 4.4
3.0 11.3 9.6 8.8 11.3 16.9 6.9
3.5-4.0 14.8 17.0 13.2 14.8 18.7 13.5
Overall 7.0 4.9 6.7 9.6 11.9 5.4
• Patients ≤50 years old • SRS alone
• median survival of 13.6 months• SRS plus WBRT
• 8.2 months for patients ≤50 who were treated.
• Patients >50 years old had a median survival of 10.1 months when treated with SRS alone, and 8.6 months for those who received SRS plus WBRT.