Stereotactic Body RadiationTherapy (SBRT) I: Radiobiology ... · 1 Stanley H. Benedict, Ph.D....
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Transcript of Stereotactic Body RadiationTherapy (SBRT) I: Radiobiology ... · 1 Stanley H. Benedict, Ph.D....
1
Stanley H. Benedict, Ph.D.University of Virginia
Kamil Yenice, Ph.D.University of Chicago
AAPM 2008 50th Annual Meetin g, Hous ton, TexasTherapy Contin uing Educat ion Course: SBRT: I & IIMonday, Jul y 28, 2008: 7:30 – 9:25AM
Stereotactic Body Radiation Therapy (SBRT) II:Physics and Dosimetry Consideratio ns
Stereotactic Body Radiation Therapy (SBRT) I:Radio biology and Clinical Expe rien ce
Brian Kavanagh, M.D., MPHUniversity of Colorado
Eric Chang, M.D.UT MD Anderson
Conflict of interestdisclosure
I haveno conflict of interest to disclose.
OutlineEvolution from conventionalRT to SRSto SBRT
Epidemiology, Rationale, Indicationsusing SBRTfor spinal metastases
Radiobiologyof SBRT
MD Anderson clinical pathwayfor spinal metastases
Summaryof Results from Li terature
Casepresentations
Summaryandconclusion
•Historical ly fractionated RT required large safetymargins~2cm around tumor for treatment uncertainties
•Associated with unacceptable toxicity at singledoselevelsneededfor tumor response
•CT-treatment planning, and hi-precision targeting withstereotaxy has permitted safedelivery of single-doseRT to intracra nial lesions(SRS)with very small tono margins
IG-IMSRT Evolution
2
•SRSfor brain metastasisyields:1-, 2-yr FFP 50% for 15--18Gy
and>80% for 22-24Gy
(Vogelbaum, J Neurosurg 104:907-12,2006)
•Current SBRT technology includesIG robotic techniques,MLC,inverseplanning software to generate IMRT plansconforming to tumor with steepdosegradientsneedednear OARs suchas spinal cord
IG-IM SRT Evolution Evolution of intracranial SRSto SBRT…
IntracranialSRS Extracranial SBRTdelivery systems
3
93 pts18-24 Gy x 1Spinal cord <12-14 GyCauda max 15.6GyLC 90%F/U 15mosOS 15mos
IJROBP 71:484-90,2008
Background on Spinal MetastasesA common sequelae of cancer, present in 30 – 70% patients at
post mortem examination, of which 14% will be symptomatic (pain, neurologic sx’s) at sometime during their illness1
40% of skeletal metastases occur in the spine which is themost common osseous site of tumor spread
Conventional radiation therapy widely used but is inherently limited by spinal cord tolerance
1Perrin RG. Metastatic tumors of theaxial spine.Curr Opin Oncol 1992:4:545-532
Epidemiologyof SpinalMetastases
Klimo , P. et al. Oncol ogi st2004;9:188 -196
SBRT
SBRT?
4
RATIONALE
• Manyptsdevelop recurrentor progressivepain,tumorprogressionor neurologic deteriorationdespiteconventional externalbeamirradiation,radiopharmaceuticals,surgery,or systemic therapy
• Patientsare very interestedin noninvasivetreatmentoptionsfor spinal metastaseswhich arenot amenableto orare refractory to conventionalirradiation
GENERAL INDICATIONS
LIMITED DISEASE - Newly diagnosed solitary or oligo- spinal metastases
PRIMARY - “Radioresistant” subtypes
POST-OP – adjuvant or elective treatment
SALVAGE - surgical or RT recurrences
Spinal instability is a contraindi cation
“Therapeutic Window” for conventionalRT
Radiosensitive lymphomas, germcell tumorsetc.
5
Previously irradiatedspinalcord,melanomasRenal cell cancer, sarcomasetc.
Little or notherapeuticwindow existsforconventionalirradiation
SBRT dosimetrically widensthe therapeuticwindowbylowering doseto theOAR
OAR
Astrahan M, IJROBP 71:3:963,2008
DT is transition dose at which final porti on of curve becomelinear
L imitations in the linear-quadratic model for high doses
Astrahan M, IJROBP 71:3:963,2008
6
Park C, Timmerman RD, IJROBP 71:3:963-4,2008.
Single Fraction Equivalent Dose(SFED) vs BED
For high doseablative RT
Defined -asdosein a singlefx that would havesamebiological effect asany largedaily dose
fractionation regimen
Park C, Timmerman RD, IJROBP 71:3:963-4,2008.
Park C, Timmerman RD, IJROBP 71:3:963-4,2008
80%
10%20%
50%
90%
(a)
90%
80%
50%
20%B
C
(b)
A
Spinal Cord Radiation Exposure
Ryu S et al. Cancer109: 628-36, 2007
Henry Ford group proposes 10 Gy to 10% spinal cord astolerance
7
White Matter Necrosisof Rat spinal cord
•Major causeof paralysis•Occurs within 120 - 210 daysafter irradiation 20 Gy x 1•Pathogenesisfocusedon either primary glial or vascular
ori ginCharacterizedby demyelination, lossof axons,focal
necrosis,liquefactive necrosis after > 20 Gy x 1Vascular edema is usually associatedwith development
of white matter necrosis
Bijl HP et al. Van Der Kogel AJ, IJROBP 52:205-11,2002
20mm 8mm 4mm 2mm
Single
Bijl HP et al. Van Der Kogel AJ, IJROBP 52:205-11,2002
IsoeffectDose(ED50) according to irradiated length of rat cord
Bijl HP et al. Van Der Kogel AJ, IJROBP 52:205-11,2002
CentralBeam
GrazingLateralBeams(constantdepth doseprof ile)
High precision proton irrad iation of rat spinal cord
Bijl HP et al, IJROBP 61:543-551,2005
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White matternecrosisin left latcolumn aftergrazing irradi ation
Extensive whiteMatter necrosisinDorsal column
No lesionsin grayMatter or lateralcolumnsBijl HP et al, IJROBP 61:543-551,2005
Regional Differencesin Radiosensitivity in Rat Spinal Cord
Full widthAndLateralbeam
CentralBeam
Dose-responseCurvesfor Paralysis
Bijl HP et al, IJROBP 61:543-551, 2005
Bath/ShowerDose-responseof Paralysisof Limbs toUnmodulatedProtons in Rat Cervical Spinal Cord
Spinal cord toleranceof relatively small volumes(shower)stronglyaffectedby low doseirra diation (bath)
Bijl HP et al. IJROBP 64:1204-10,2006
Referral fromneurosurgerymedicaloncologyradiationoncologyself referral
Multi -disciplinaryTumor board• Patient selection•Discussionof complex cases•Triaging candidates
Jointconsultationpain,QOL assessment,Neurological exam,
informedconsent,video,Protocol registration
SBRTsimulation1. immobilization2. intrathecalcontrast3. CT acquisition
IMRT treatmentplanningQ/A dosimetry-film-ion chamber
Treatment setupCT acquisitionimagefusion, DRR,port film, delivery
Protocol follow-up q3 monthspain,QOL,neuroexam,MRI
SpinerecurrenceOr newdisease
Clinical Pathway for Stereotactic Body Radiotherapy program
9
013/15
Pain relief
12mo39.6Mets18M il ker-zabel
2003
3 severe
mypthy
84%
Symptomatic
improvement
9mo16-25/
1-5
Mets74Gibbs
2007
4/222cases
(1.8%)
>80%9-23mo222Total
1 (3%)3 increased
symptoms
23mo16-30
/1-5fx
Benign32Dodd
2006
0
M81%LC
11mo70/33
20/5
Primary and
metastases
35Yamada
2005
02 progression12mo59.4-70.2/33-38fxs
20 (20-55.8)/4-31fxs
Primary and
metastases
16Bilsky
2004
085%
control
9mo30/5 or
27/3
Mets63Chang
2007
cxsOutcomeF/UDosePathologyNSeries
Selectedstereotactic spineradiation therapyseries(FRACTIONATED)Selectedstereotactic spineradationseries(SINGLE SESSION)
2radiculit
1 radnecrosis
Painrelief
32/34tumors
NA25/10+6-8x1
26mets
9prim
31Benzil
2004
4/656
(0.6%)~90%2-45mos8-25656Total
03worse2316-30/1-5fxsBenign19Dodd
2006
0LTC
90%
21(3-53)20(12-25)Mets336Gerszten
2007
090%15 (2-45)18-24Mets93Yamada
2008
1 radiation
injury
85% painrelief
6.4 (0.5-49)8-18Mets177Ryu
2007
cxsOutcomeF/u
(mos)
Dose
(Gy)
PathNSeries
M.D. ANDERSON PHASEI AND II DATA Patient Positioning Accuracy and Safety Data
Int J Radiat Oncol Biol Phys 59:1288-1294, 2004
10
Dates enrolled Nov 2002 – Mar 2005Patientsn 63Male 38 (60%)Female 25 (40%)
Age (yrs)Median 59Range 21-82
HistologyRenal cell 25 (39.7%)Breast 9 (14.3%)Sarcoma 8 (12.7%)Lung 7 (11.1%)Melanoma 2 (3.2%)Colon 1 (1.6%)Unk Primary 2 (3.2%)Other 9 (14.3%)
KPS score60 4 (6.3%)70 17 (27%)80 17 (27%)90 25 (39.7%)
RESULTS - Patient Characteristics RESULTS - Tumor CharacteristicsTumor volume (cc)median 37.4range 1.6 –357.9
Spinal Metastases (n)One 51Two 12
Lesion LocationSpinal 61Paraspinal 13
Levelcervical 5 (6.7%)thoracic 43 (57%)lumbar 26 (34.7%)sacral 1 (1.3%)
RESULTS - Follow-up of Tumor and Vital Status
Vital Statusalive 26 (41%)dead 37 (59%)
Tumor statusStable 57 (77%)Progressed 17 (23%)
Follow-upMedian 21.3mosRange 0.5– 49.6 mos
11
PAIN AND SYMPTOM CONTROL
Narcotic use decreased from 60% (baseline), 44% (3mos), 36% (6mos)
MDASI showed reduction in pain (p<0.001), sleep disturbance(p<0.01),with no added impairment of daily function, while fatigue severityunchanged.
Pain incidence Pain severity
25%
6.7%
12
Neurotoxicity evaluation
Grade 1headache(1)
numbness(1)*
tingling (4)*
numbnessand tingling (1)*
(all reversible)
Grade 2 -4none
Grade 3-4 toxicity
Grade3
Nausea(1)
Fatigue(1)
Non-cardiacchestpain (1)
Pain,severetongueedema,trismus(1)
Grade4
None
ReportedToxicity in Literature CLINICAL CASES
FractionatedSBRT
13
Case1: 46 M previouslyirradiated(40 Gy in 16 fxs)Lung cancerT12 metastasis progressed (biopsy proven)
July2004
July2005
Case2: 52 M solitary renal cell carcinoma metastasis centered on cervical vertebrae 2
14
Case3: 20 F plasmacytomacausingbackpain, failedconventionalRT andsurgery
-Extradural extension causing cord compression at T10
-Needle bx revealed plasmacytoma-45 Gy in 25 fractions to T9-11
-3 mos later, recurred below: Epidural dz T11-12. RT was not an option at the time
-Laminectomy, facetectomy, resection tumor-4 mo later recurred above: Rt T7-8 neuroforamen-Received SBRT to epidural disease-Attending college and remains disease-free 4
years later
Neuroforaminal and Epidural Disease
Patternsof Failure
15
Summaryandconclusions
• LiteratureandphaseI/II datasupport thesafetyand effectivenessof stereotacticbodyradiosurgeryfor thespine
• POFdatasuggestroutinelytreatingthepediclesand posterior elementsusing a wide bonymarginposterior to thediseasedvertebrae.
• Prospectivetrials areneededto determinethetruespinal cord toleranceandto compareefficacy ofSBRS againstconventionalRT
All thefollowing are indicationsforperformingstereotacticbody
radiosurgeryfor spinal metastasesEXCEPT?:
10
25%
25%
25%
25% 1. Solitaryor oligometastatic disease
2. Failure of prior XRT or surgery
3. Spinalinstability
4. Grossresidualdiseaseafter surgery
Basedon pooledpublisheddataon spinal metastases,SBRTis associatedwith a crude local control rate of:
25%
25%
25%
25%
10
1. 65-70%
2. 70-75%
3. 75-80%
4. 80%or higher
Thefollowing statements regarding spinal cordtoleranceto singlesessionsteretoactic body
radiosurgery(SBRS)are trueEXCEPT:
25%
25%
25%
25%
10
1. Humanspinal cordtoleranceunknown
2. <12Gy hasbeenreported assafe
3. 10 Gy to 10%of thespinal cord volume4. Ratspinal cord tolerance canbedirectly
appliedto humans