cyberknife publications currently cover… · cyberknife radiosurgery for arteriovenous...
TRANSCRIPT
CYBERKNIFE® PUBLICATIONS CURRENTLY COVER…
Head and neck tumors(Primary and metastatic tumors of buccal space,
pharynx and larynx, nasopharynx cancer,schwannoma, recurrences)
Cancerous or non-cancerous intracranial tumors(Brain metastases, meningiomas, neurinomas, gliomas, astrocytomas,
pituitary adenomas, vestibular schwannomas, trigeminal neuralgia, arteriovenous malformations)
Lung cancer(Early stage lung cancer, pulmonary
metastases, recurrences)
Pancreas cancer(Inoperable patients, recurrences)
Spine cancer(Benign tumors, spinal metastases,
primary malignant tumors, spinal AVMs)
Prostate cancer(low and intermediaite risk prostatecancer, high risk prostate cancer,
recurrences)
Liver cancer(Inoperable primary liver cancer,
metastases)
Breast cancer
Osseous metastases
100% OF THE BODY COVERED
3
GENERAL INFORMATIONTechnical paper
5
Kilby et al., The CyberKnife® Robotic Radiosurgery System in 2010. Tech in Cancer Research & Therapy, 2010 (Accuray)
l Lead article in new special issue of TCRT
l A complete technical description of the CyberKnife® VSI™ System
l First complete technical review of system since the late 1990s
l Updates technical advancements of the CyberKnife System
l Includes detailed review of studies of geometric accuracy
l Relation of technical developments to expansion of clinical applications is reviewed
l Open access makes it freely available to anyone with internet access:http://www.tcrt.org//mc_images/category/4309/02-kilby_ tcrt_9_5.pdf
GENERAL INFORMATIONTechnical papers 5
INTRACRANIAL 6Clinical papersPrimary / Metastatic CancersFunctional DiseaseVersus Gamma Knife
Technical papers 8AccuracyTreatment plansIntrafraction motionCyberKnife® System Accuracy: Intracranial
HEAD AND NECK 9Clinical papers
SPINE 10Clinical and technical papersMetastasesPrimary lesions / AVMsXsight® Spine accuracyXsight® Spine Tracking Clinical Data
LUNG 12Clinical papersPrimary, metastases, recurrencesPrimary Lung Cancer - Disease ControlQuality of Life
Technical papers 14Monte Carlo dose calculation Tracking model error minimal in clinical use4D planning does not encompass all movementSynchrony® tracking in phantoms
BREAST 15Posters Astro 2010
LIVER 16Clinical papers
PANCREAS 17Clinical papers
PROSTATE 18Clinical papersTechnical papers
INTRACRANIALClinical papers
6 7
Primary / Metastatic Cancers
Adler JR, Jr., Gibbs IC, Puataweepong P, et al. Visual field preservation after multisession cyberknife radiosurgeryfor perioptic lesions. Neurosurgery 2006;59:244-254; discussion 244-254.
Colombo F, Casentini L, Cavedon C, et al. Cyberknife radio-surgery for benign meningiomas: short-term results in199 patients. Neurosurgery 2009;64:A7-13.
The introduction of the CyberKnife extended the indicationto 63 patients (30%) who could not have been treated by single-session radiosurgical techniques.
l All patients were either symptomatic or harbored growingtumors
l In 150 patients with lesions larger than 8 mL or with tumorssituated close to critical structures, the dose was deliveredin 2 to 5 daily fractions
l The tumor volume was unchanged in 148 patients, decreasedin 36 patients and increased in 7 patients)
l 93.4% control rate at 5 year follow up
Muacevic A, Kufeld M, Wowra B, et al. Feasibility, safety,and outcome of frameless image-guided robotic radio-surgery for brain metastases. J Neurooncol 2009.
Sakamoto GT, Blevins N, Gibbs IC. Cyberknife radiotherapyfor vestibular schwannoma. Otolaryngol Clin North Am 2009;42:665-675.
Soltys SG, Adler JR, Lipani JD, et al. Stereotactic radio-surgery of the postoperative resection cavity for brainmetastases.Int J Radiat Oncol Biol Phys 2008;70:187-193.
Tuniz F, Soltys SG, Choi CY, et al. Multisession cyberknife stereotactic radiosurgery of large, benign cranial base tumors: preliminary study. Neurosurgery 2009;65:898-907; discussion 907.
Functional Disease
Adler JR, Jr., Bower R, Gupta G, et al. Nonisocentric radio-surgical rhizotomy for trigeminal neuralgia. Neurosurgery 2009;64: A84-90.
Examined clinical outcomes in TN patients who underwentlesioning with “optimized” nonisocentric radiosurgical parameters
l 6-mm segment of nerve was treated with a marginal prescription dose of 58.3 Gy and a maximal dose of 73.5 Gy
l At a mean follow-up of 14.7 months, patient-rated outcomeswere:
- excellent in 33 patients (72%)- good in 11 patients (24%)- poor/no improvement in 2 patients (4%)
Facial numbness was reported in 7 patients (15%)
l Target: Elongated segment of the retrogasserian cisternalportion of the trigeminal sensory root
Fariselli L, Marras C, De Santis M, et al. CyberKnife radiosurgery as a first treatment for idiopathic trigeminalneuralgia.Neurosurgery 2009;64:A96-101.
Colombo F, Cavedon C, Casentini L, et al. Early results ofCyberKnife radiosurgery for arteriovenous malformations.J Neurosurg 2009;111:807-819
CyberKnife treatment planning allowed use of functionalMRI and angiograms to help accurately delineate the AVMsand critical structures
l 279 AVM patients treated with CyberKnife® System l AVM volumes ranged from 0.1 to 42 ccl Delivered dose 22.5-30 Gy, mostly single fractionl Follow-up (median): 31 months; 80 patients with 36+ monthsl Excellent Toxicity Outcomes:
- No permanent complications, even though 20 patientshad AVMs next to critical structures
l Efficacy Outcomes:- High rate AVM obliteration: complete AVM obliterationin 81.2% patients at 36 months
- 91% complete obliteration in small AVMs- Low interim bleeding rate observed
l Obliteration rates were significantly better than their previousLINAC-based results
l Use of functional MRI and angiograms to accurately delineateAVMs and critical structures
Versus Gamma Knife
Wowra B, Muacevic A, Tonn JC. Quality of radiosurgeryfor single brain metastases with respect to treatment technology: a matched-pair analysis. J Neurooncol 2009;94:69-77.
The radiosurgical dose can be better tailored to the targetwith the CK than with the GK. This result, a more homogeneousdose distribution, and a lower peripheral dose represent an advantage of the CyberKnife in regard of the radiationprotection.
l Retrospective matched-pair analysis of 2 groups of 63 patients:All treated in a single fraction either with Gamma Knife®
(GK) or CyberKnife® System (CK)l Minimum marginal dose was significantly different
- 19.4 ± 2.5 Gy for GK and 18.4 ± 1.5 Gy for CK- Central tumor dose was also lower for CK
l Conformality, homogeneity, and volume of non-tumor tissue receiving 10 Gy or more were significantly better forCyberKnife treatment plans
l Clinical outcomes were nearly identical between groups- Local control at 12-18 months was 94.6% for GK and93.8% for CK
INTRACRANIAL Technical papers
8
Accuracy
Antypas C, Pantelis E. Performance evaluation of a CyberK-nife G4 image-guided robotic stereotactic radiosurgery system. Phys Med Biol 2008;53:4697-4718.
Fu D, Kuduvalli G. A fast, accurate, and automatic 2D-3Dimage registration for image-guided cranial radiosurgery.Med Phys 2008;35:2180-2194.
Muacevic A, Kufeld M, Wowra B, et al. Feasibility, safety,and outcome of frameless image-guided robotic radiosur-gery for brain metastases. J Neurooncol 2009.
Treatment plans
Collins SP, Coppa ND, Zhang Y, et al. CyberKnife(R) radio-surgery in the treatment of complex skull base tumors:analysis of treatment planning parameters. Radiat Oncol 2006;1:46.
Yu C, Jozsef G, Apuzzo ML, et al. Dosimetric comparisonof CyberKnife with other radiosurgical modalities for anellipsoidal target. Neurosurgery 2003;53:1155-1162; discussion 1162-1153.
Intrafraction motion
Hoogeman MS, Nuyttens JJ, Levendag PC, et al. Timedependence of intrafraction patient motion assessed byrepeat stereoscopic imaging. Int J Radiat Oncol Biol Phys 2008;70:609-618.
Murphy MJ. Intrafraction geometric uncertainties in frameless image-guided radiosurgery. Int J Radiat Oncol Biol Phys 2009;73:1364-1368.
Murphy MJ, Chang SD, Gibbs IC, et al. Patterns of patientmovement during frameless image-guided radiosurgery. Int J Radiat Oncol Biol Phys 2003;55:1400-1408.
CyberKnife® System Accuracy: Intracranial
Total system error
l Scan, plan, irradiate, compare computed and measureddose distributions
l Includes all sources of delivery error: imaging, image transfer,planning, tracking, robot, linac
6D Skull tracking
l Relies on intrafraction imaging to continually assess targetmovement
l Total clinical accuracy of about 0.50 mm- 0.44 +/- 0.12 mm, Antypas et al. 2008- 0.34 +/- 0.16 mm for a target 2 cm from the rotationcenter, Fu et al. 2008
- 0.48 +/- 0.22 mm, Muacevic et al. 2009
9
HEAD AND NECKClinical papers
Hara W, Loo BW, Jr., Goffinet DR, et al. Excellent localcontrol with stereotactic radiotherapy boost after externalbeam radiotherapy in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2008;71:393-400.
Heron DE, Ferris RL, Karamouzis M, et al. Stereotactic body radiotherapy for recurrent squamous cell carcinoma of thehead and neck: results of a phase I dose-escalation trial. Int J Radiat Oncol Biol Phys 2009;75:1493-1500.
Roh KW, Jang JS, Kim MS, et al. Fractionated stereotacticradiotherapy as reirradiation for locally recurrent head andneck cancer. Int J Radiat Oncol Biol Phys 2009;74:1348-1355.
Teguh DN, Levendag PC, Noever I, et al. Treatment Techniques and Site Considerations Regarding Dysphagia-Related Quality of Life in Cancer of the Oropharynx andNasopharynx. Int J Radiat Oncol Biol Phys 2008.
10 11
SPINEClinical and technical papers
Metastases
Gagnon GJ, Nasr NM, Liao JJ, et al. Treatment of spinaltumors using cyberknife fractionated stereotactic radiosurgery: pain and quality-of-life assessment aftertreatment in 200 patients. Neurosurgery 2009;64:297-306; discussion 306-297.
l 200 patients with 274 primary and metastatic spinal tumors - 76% of patients reported pain at the tumor site before treatment
l CyberKnife® treatment mean dose 26.4 Gy in 3 fractions
l 1 month after treatment- Pain scores had decreased significantly after treatmentand decreased over the entire 4-year follow-up period
- 38% of the patients reported that they were completelypain-free
l Significant continued improvement over 48 months follow-upl Physical Quality of Life (QOL) were not reduced by SRS;Mental QOL improved
l Side effects were mild and self-limited, and no late radiationtoxicity was observed
l Patients with the worst initial pain showed the most impro-vement
SRS of metastatic and primary spinal tumors with the CyberKniferesults in robust and durable improvement in pain and maintenance of the physical and mental quality of life
Gerszten PC, Burton SA, Ozhasoglu C, et al. Radiosurgeryfor spinal metastases: clinical experience in 500 cases froma single institution. Spine 2007;32:193-199.
A prospective non-randomized longitudinal cohort study
l Maximum single-fraction doses of 12.5 to 25 Gy (mean 20 Gy)l Long-term pain improvement occurred in 290 of 336 cases(86%) treated for pain indication
l Radiographic control:- 90% long term tumor control for cases treated with radiosurgery as primary modality
- 88% tumor control for previously treated lesions
l Clinical improvement in 84% of the cases with pre-treatment neurological deficits
l No case of radiation-induced myelitis
Conclusions
Single-fraction spinal CyberKnife® stereotactic radiosurgeryfor metastases is both safe and clinically effective.
Furweger et al. Patient motion and targeting accuracy in robotic spinal radiosurgery: 260 single-fraction fiducial-free cases. Int J Radiat Oncol Biol Phys 2010;78:937-945.
l Clinical patient data were used to evaluate the tracking performance of the algorithm and quality assurance
l 77 spine patients treated with the CyberKnife® System - 51 patients treated using Xsight® Spine Tracking (no fiducials)
- 26 patients treated using fiducial tracking- 10,522 X-ray image pairs
l Collected under many technical and clinical conditions- Using G3 (short stands) or G4 (in-floor and on-floor detectors)
- All spine regions- Wide range of patient sizes- Clinical conditions included osteoporosis and implanted surgical hardware (cages, rods & screws)
l Overall median targeting error 0.48 mm
Gibbs IC, Kamnerdsupaphon P, Ryu MR, et al. Image-guidedrobotic radiosurgery for spinal metastases. Radiother Oncol 2007;82:185-190.
Sahgal A, Ames C, Chou D, et al. Stereotactic body radio-therapy is effective salvage therapy for patients with priorradiation of spinal metastases. Int J Radiat Oncol Biol Phys 2009;74:723-731.
Primary lesions / AVMs
Dodd RL, Ryu MR, Kamnerdsupaphon P, et al. CyberK-nife radiosurgery for benign intradural extramedullary spinal tumors.Neurosurgery 2006;58:674-685; discussion 674-685.
Sinclair J, Chang SD, Gibbs IC, et al. Multisession CyberKnife radiosurgery for intramedullary spinal cordarteriovenous malformations. Neurosurgery 2006;58:1081-1089; discussion 1081-1089.
Xsight® Spine accuracy
Antypas C, Pantelis E. Performance evaluation of a CyberKnife G4 image-guided robotic stereotactic radio-surgery system. Phys Med Biol 2008;53:4697-4718.
Ho AK, Fu D, Cotrutz C, et al. A study of the accuracyof Cyberknife spinal radiosurgery using skeletal struc-ture tracking. Neurosurgery 2007;60:147-156.
Muacevic A, Staehler M, Drexler C, et al. Technical des-cription, phantom accuracy, and clinical feasibility for fi-ducial-free frameless real-time image-guided spinalradiosurgery. J Neurosurg Spine 2006;5:303-312.
Xsight® Spine Tracking Clinical Data
Evaluation Clinical patient data used to evaluate thetracking performance of the algorithm and quality assurance.Int J Radiat Oncol Biol Phys 2009;78.
l 77 spine patients previously treated with the CyberKnife®
- 51 patients treated using Xsight Spine Tracking (no fiducials)
- 26 patients treated using fiducial tracking
l 10,522 X-ray image pairs- Collected under many technical and clinical conditions- Using G3 (short stands) or G4 (in-floor and on-floor detectors)
- All spine regions- Wide range of patient sizes- Clinical conditions included osteoporosis and implanted surgical hardware (cages, rods & screws)
l Overall median targeting error 0.48 mm
LUNGClinical papers
12 13
Primary, metastases, recurrences
Coon D, Gokhale AS, Burton SA, et al. Fractionated stereotactic body radiation therapy in the treatment ofprimary, recurrent, and metastatic lung tumors: the roleof positron emission tomography/computed tomography-based treatment planning. Clin Lung Cancer 2008;9:217-221.
Kim MS, Yoo SY, Cho CK, et al. Stereotactic body radiationtherapy using three fractions for isolated lung recurrencefrom colorectal cancer. Oncology 2009;76:212-219.
Primary and metastaticcentral lung tumorsNuyttens JJ, van der Voort van Zyp NC, Praag J, et al. Outcome of Four-dimensional Stereotactic Radiotherapyfor Centrally Located Lung Tumors.Radiother Oncol 2012;102:383-387.
This study is important for the CyberKnife differentiation strategy. It shows that the Synchrony Respiratory TrackingSystem allows narrow PTV margins, so that high SBRT dosescan be delivered with relatively low toxicity to the centralchest region, where SBRT has been shown to carry a high riskof serious complications, including death, within 2 cm of theprimary central airways of the lung.
l 56 patients (39 with primary NSCLC, 17 with solitary metastases) with 58 tumors in the central chest
l Median tumor diameter was 4.1 cm (range 1.2–10.5 cm)l Synchrony motion tracking & automatic correction allowednarrow margins (5 mm GTV to PTV)
l Near-esophagus tumors treated with 6 fractions of 8 Gyl Dose for other tumors escalated from 45 Gy (in 5 fractions)to 60 Gy (in 5 fractions)
l At median follow-up of 23 months- 2-year local tumor control was 76% for all tumors
- 85% for BED >100 Gy- 60% for BED <100 Gy
- Overall 2-year survival 60%l Three-year cancer-specific survival 80% for patients withearly stage l NSCLC and 58% for patients with metastases
l Toxicity- No acute or late grade 4 or 5 toxicity- Low grade esophagitis in 11% of patients- “Toxicity amongst lowest reported to date” for centrallesions
Key Points
l “Two-year tumor control and overall survival have beencomparable to that generally reported for SBRT of peripheral NSCLC lesions for patients treated to BED =100 Gy, and toxicity has been among the lowest reportedfor central lesions”
Primary Lung Cancer - Disease Control
Brown WT, Wu X, Fayad F, et al. Application of robotic stereotactic radiotherapy to peripheral stage I non-smallcell lung cancer with curative intent. Clin Oncol (R Coll Radiol) 2009;21:623-631.
Collins BT, Vahdat S, Erickson K, et al. Radical cyberknife radiosurgery with tumor tracking: an effective treatmentfor inoperable small peripheral stage I non-small celllung cancer. J Hematol Oncol 2009;2:1.
Vahdat S, Oermann E, Collins SP, et al. CyberKnife radio-surgery for inoperable stage IA non-small cell lung cancer:18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment.J Hematol Oncol 2010;3:6
l N/dose: 20 pts with inoperable NSCLC / 42-60 Gy in 3 fx l Follow-up: 43 months medianl Disease control: 2-year local control 95%; overall survival 90%
Key Points
l This is the third published update on these Georgetownpatients
l Two-year local control was 95% and overall survival was90% (Kaplan-Meier estimates)
l Single recurrence identified initially on FDG-PETl “Local control and survival following CyberKnife radiosurgeryfor stage IA NSCLC is exceptional”
Quality of Life
Van der Voort van Zyp NC, van der Holt B, van Klaveren RJ,et al. Stereotactic body radiotherapy using real-time tumortracking in octogenarians with non-small cell lung cancer. Lung Cancer 2010 Sep; 69(3):296-301
l Aggressive treatment for octogenarians?- With palliative treatment only, most patients die of the disease
- 5-year survival post-surgery is 34%-57%, but surgeryis hard on patients
- SBRT may be a less invasive approach to curativetreatment
l 38 patients 80+ years of age were treated with 45-60 Gyin 3-6 fractions (more fractions for central and large tumors
l Toxicity- 5% acute, 16% late Grade 3 tox (temporary chestpain, shortness of breath)
l Outcomes at 23 months’ median follow-up- 2-year local control 100%- Overall survival 65% at 1 year, 44% at 2 years (90%for T1 tumors)
Van der Voort van Zyp NC, Prevost JB, van der Holt B,et al. Quality of life after stereotactic radiotherapy forstage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2010 May;77(1):31-37.
l N/dose: 39 pts with inoperable T1/2 NSCLC / 48-60 Gy in3-5 fx
l Follow-up: 17 months median l Disease control: 2-year local control 97%; overall survival62%; QOL maintained or improved
l Late toxicity: Low-grade fatigue and dyspnea in some /chest wall pain in 2 pts
Key Points
l Goal of study was to asses quality of life (QOL) after CyberKnife® treatment of inoperable NSCLC
l No severe toxicity in 6 patients with central lung tumorsl COPD symptoms not worsened by SBRTl High rate of 2-year local controll Preservation of physical QOL; improved emotional QOL
Collins et al., CyberKnife Radiosurgery with TumorTracking: An Effective Treatment for Inoperable SmallPeripheral Stage I Non-Small Cell Lung Cancer.Journal of Hematology & Oncology, 2009 (Georgetown)
The use of hundreds of lightly weighted beams… rather thana few heavily weighted ones has prevented the infrequent but potentially severe skin injuries reported… using other radiosurgical instruments
l 20 medically inoperable Stage I NSCLC patients treatedwith 42-60 Gy in 3 fractions
l All tumors were peripherally located and small (mean diameter 2.2 cm)
l Excellent toxicity profile- 8/12 patients with lesions close to the chest wall developed mild chest wall discomfort that resolved
- One patient developed Grade III pneumonitis butwas on concurrent chemotherapy (Gefitnib)
l Pulmonary functions tests were stable throughout follow-upof 24 months
l Excellent local control and survival- 100% local control at 2 years- 87% overall survival at 2 years
LUNGTechnical papers
14 15
Synchrony® tracking in phantoms
Muacevic A, Drexler C, Wowra B, et al. Technical Description, Phantom Accuracy, and Clinical Feasibilityfor Single-session Lung Radiosurgery Using RoboticImage-guided Real-time Respiratory Tumor Tracking.Technol Cancer Res Treat 2007;6:321-328.
Nioutsikou E, Seppenwoolde Y, Symonds-Tayler JR, et al. Dosimetric investigation of lung tumor motion compen-sation with a robotic respiratory tracking system: an experimental study. Med Phys 2008;35:1232-1240.
Wong KH, Dieterich S, Tang J, et al. Quantitative Measurement of CyberKnife Robotic Arm Steering. Technol Cancer Res Treat 2007;6:589-594.
Tracking model error minimal in clinical use
Hoogeman M, Prevost JB, Nuyttens J, et al. Clinical accuracy of the respiratory tumor tracking system of thecyberknife: assessment by analysis of log files. Int J Radiat Oncol Biol Phys 2009;74:297-303.
4D planning does not encompass all movement
Minn AY, Schellenberg D, Maxim P, et al. Pancreatic TumorMotion on a Single Planning 4D-CT Does Not CorrelateWith Intrafraction Tumor Motion During Treatment. Am J Clin Oncol 2009.
Image-guided RT needs to involve real-time verification of tumor position during treatment delivery for optimal RTtreatment outcomes
l Assessed 4D-CT use for accurately predicting intra-fractionmotion of pancreatic tumors
- Pancreatic tumor motion likely similar to tumors inthe lower lobes of the lungs
l Motion as indicated in pre-treatment 4D-CT was comparedto tumor motion shown in Synchrony® tracking logs for 20patients treated with the CyberKnife® System
l 4D-CT predicted motion in SI and AP directions (with error);not in LR direction
- A single 4D-CT may not be sufficient to predictorgan movement caused by patient respiratory mo-tion during an actual course of treatment.
l In 16/20 patients, if 4D-CT was only used to model motion,>10% of tumor motion would be missed during treatment
- Clinical implications of this error may be decreasedtumor control rates and increased normal tissuetoxicity
Monte Carlo dose calculation
Wilcox EE, Daskalov GM, Lincoln H, et al. Comparison ofplanned dose distributions calculated by Monte Carlo andRay-Trace algorithms for the treatment of lung tumorswith cyberknife: a preliminary study in 33 patients. Int J Radiat Oncol Biol Phys 2010;77:277-284.
Key Points
l Compared of lung dose distributions calculated by Ray-Tracing (EPL) and Monte Carlo (MC) algorithms
l 33 patients were treated to 35-60 Gy prescribed to an isodose line to obtain 95% target coverage
l EPL consistently overestimated doses; median ratio of EPLto MC max dose was 1.16 (range, 1-1.63)
l Discrepancy was greatest in cases where beams crossedlong low-density tissue
l Doses to critical structures such as spinal cord, heart, and esophagus were overestimated by 1-2 Gy
l Authors recommend using MC to calculate all lung SBRTdose distributions
BREAST
Chen PY, Vicini FA. Partial breast irradiation. Patient selection, guidelines for treatment, and current results.
Front Radiat Ther Oncol. 2007;40:253-71. Review.l Review of partial breast irradiation, a hypofractionated radiotherapy technique for treatment of breast tumor resection cavities. Similar CyberKnife treatment approachesare under consideration.
Posters Astro 2010
Compared CyberKnife® to photon mini-tangents, IMRT, and electrons as a boostto whole-breast RT
Fan et al. #3306 (Charlie Ma, Senior Author) Fox ChaseCancer Center. Planning the Breast Boost: DosimetricComparison of CyberKnife, Photon Mini Tangents, IMRT,and Electron Techniques.
l Plan dose/ fx : 10 Gy in 2 fx for CK / 10 Gy in 5 fx for RTl OAR doses : Max lung dose, lung V40, heart, and skin dosesall lower with CK
Outcomes
l Conformality superior for CyberKnife : CK=1.22 Mini-tangents=4.8 IMRT=2.1 Electrons=2.4
l Maximum lung dose and V40 superior for CyberKnifel Skin and heart doses lower for deep targets with CyberKnife
Conclusions
l “The CyberKnife delivers a significantly more conformaldose… and also allows for real time tracking using the surgical clips as fiducial markers.”
l “These advantages could result in reduced toxicity by reducing the dose to the surrounding breast tissue outsideof the boost, skin, chest wall, lung or heart.”
Evaluated CyberKnife® dose plans forpartial breast irradiation (PBI) of earlystage breast cancer
Heinzerling et al. #3390 (Bob Timmerman, Senior Author) U Texas Southwest - Comparative Dose-Volume Analysisfor CyberKnife and 3D Conformal Partial Breast IrradiationTreatment of Early Stage Breast Cancer
l Plan dose/ fx : 34 Gy in 10 fx for CK and 3DCRT (15 mm margin, less near skin & chest)
l OAR doses : Dose to lung, heart, normal breast lower withCK; skin doses not sig. different
l 10 patients with clearly delineated lumpectomy cavitieswere re-planned
l 3DCRT treatment plans used 4-5 non-coplanar beams
Outcomes
l CTV coverage was superior for CyberKnife (Median 98% forck, 95% for SDCRT)
l Doses outside the PTV were significantly lower with CyberKnife
Conclusions
l “When the advantages of CK to account for target motionand setup error are considered, CK would even further reduce dose to OARs.”
l “Reduction in dose to the normal breast seen with the CKsystem may translate into better cosmetic outcomes and iscurrently being evaluated in a phase I trial at our institution.”
16 17
LIVER Clinical papers
Vautravers et Dewas. Image-guided robotic stereotacticbody radiation therapy liver metastases: is there a dose response relationship?Int J. Radiation Oncology Biol. Phys. 2011 Mar 4.
l 42 patients: 62 metastases, were treated with two dose levelsof 40 Gy in four Dose per Fraction (23) and 45 Gy in threeDose per Fraction (13)
l Disease control: 1-year local control 90%; 2-year local control86%; overall survival 90%
l Toxicity : Grade 1 or 2 nausea, one patient Grade 3 epi-dermitis
l Follow up (median): 14,3 months
Key Points:
l No significant difference between 40 and 45 Gyl B better local control with the higher dosel Combined a local treatment with chemotherapyl Cases of toxicity milder than those reported in the literaturefor SBRT treatments
l Treatment with 45 Gy seemed to increase local control without additional toxicity.
Ambrosino G, Polistina F, Costantin G, et al. Image-guidedrobotic stereotactic radiosurgery for unresectable liver metastases: preliminary results. Anticancer Res 2009;29:3381-3384.
l 27 patients with unresectable liver metastases were includedin these series
l Patients were treated with a median dose of 36 Gy (range25-60 Gy) in 3 fractions
l Median follow up was 13 months (range, 6-16 months)l Overall tumor control was 74.1% (inhibition of growth or reduction in size)
l Mild or moderate transient hepatic dysfunction was evidentin 9 patients and minor complications in 5
Louis et al. Stereotactic radiotherapy of hepatocellular carcinoma: preliminary results. Technol Cancer Res Treat 2010; 9:479-487.
l N/Dose: 25 pts / 45 Gy in 3 fx,10-12 days l Follow up (median): 12,7 monthsl Disease control (actuarial): 2-year LC: 95%, 1-yr OS 79%; 2-yrOS 59%
l Toxicity: 2 acute Grade 3; Late Grade 3 in 2 pts (10%), duodenalulcer in 3
Key Points:
l Patients ineligible for any other treatment mode (ChildA5—B9); all inoperable, poor-prognosis patients
l Short-lived mild hepatic pain, nausea, fatigue in 48% at 3 months
l Grade 2 (2 pts) and 3 (1 pt) duodenal ulcer in early patientswho exceeded dose constraints
l Local control superior to other studies; survival comparablel A multicenter Phase II study funded by French NCI is planned
Choi BO, Choi IB, Jang HS, et al. Stereotactic body radiation therapy with or without transarterial chemoembolizationfor patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer 2008;8:351.
Goodman KA, Wiegner EA, Maturen KE, et al. Dose-Escalation Study of Single-Fraction Stereotactic Body Radiotherapy for Liver Malignancies. Int J Radiat Oncol Biol Phys in press.
l 26 patients: 19 metastases, 5 IHCC, 2 recurrent HCCl Dose-escalated from 18 to 30 Gy in a single fractionl Median follow-up: 17.3 months (range, 2-55 months)
- At 12 months, risk of local failure 23%- Median survival: 28.6 months - Overall 2-year actuarial survival 50.4%- Mets: 49.4%, Primary: 53.6%
l Toxicity - No Grade 3 or higher toxicity- Acute: 3.8% Grade 2- Late: 7.7% Grade 2- No dose-limiting toxicity
l Good local control and survival, minimal acute and long-termtoxicity
Stintzing S, Hoffmann RT, Heinemann V, et al. Framelesssingle-session robotic radiosurgery of liver metastases incolorectal cancer patients. Eur J Cancer in press.
PANCREASClinical papers
Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of thepancreas. Cancer 2009;115:665-672.
Koong AC, Le QT, Ho A, et al. Phase I study of stereotacticradiosurgery in patients with locally advanced pancreaticcancer.Int J Radiat Oncol Biol Phys 2004;58:1017-1021.
Mahadevan A, Jain S, Goldstein M, et al. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys in press.
18
PROSTATE Clinical papers
Freeman & King. Stereotactic body radiotherapy forlow-risk prostate cancer: five-year outcomes.Radiation Oncology 2011
Key Points:
l First of CyberKnife® treatment of prostate that includes 5-year year follow-up
l Combined data from Naples (35 Gy) and Stanford (36.25 Gy)l 5-year disease-free survival 93% (within range of othertreatments)
l Generally low rates of mild GU and GI toxicity (within rangeof other treatments)
l “SBRT may benefit patients by reducing travel costs andlost work time, allowing a more immediate return to normal,daily routines, and potentially reducing health care costs”
King CR, Brooks JD, Gill H, et al. Stereotactic body radiotherapy for localized prostate cancer: interim results of a prospective phase II clinical trial. Int J Radiat Oncol Biol Phys 2009;73:1043-1048.
Efficacy of CyberKnife® Prostate RadiosurgeryCyberKnife® hypofractionation has “early and late toxicityprofile no worse than with dose-escalated radiotherapy delivered at conventional fractionation”
l 41 patients treated in 5 fractions of 7.25 Gyl 100% PSA response rate at median of 33 monthsl Urethral/rectal toxicity profile comparable to EBRT
Bolzicco et al. Image-guided stereotactic body radiationtherapy for clinically localized prostate cancer: preliminaryclinical results.Technol Cancer Res Treat 2010; 9:473-477
Key Points:
l 22 low-risk, 23 intermediate-risk (17 received ADT)l Patients were of an “advanced age” and were deemed“ineligible for surgery”
l Grade 3 urinary toxicity occurred in a former TURP patientl Neither prostate volume nor ADT status affected toxicityl Second European addition to the prostate SBRT evidencebase
Friedland et al. Image-guided stereotactic body radio-therapy: an emerging treatment approach for localizedprostate cancer. Technol Cancer Res Treat 2009;8:387-392.
Key Points:
l 97% biochemical control at median 24 monthsl Urethral/rectal toxicity profile comparable to EBRTl Erectile function preserved in 81% of patients at 2 years
- EF preservation for open surgery and conventionalradiation therapy ranges from 50-70 percent
Technical papersFuller DB, Naitoh J, Lee C, et al. Virtual HDR(SM) CyberKnife Treatment for Localized Prostatic Carcinoma:Dosimetry Comparison With HDR Brachytherapy andPreliminary Clinical Observations. Int J Radiat Oncol Biol Phys 2008;70:1588-1597.
Hossain S, Xia P, Chuang C, et al. Simulated real timeimage guided intrafraction tracking-delivery for hypo-fractionated prostate IMRT. Med Phys 2008;35:4041-4048.
Hossain S, Xia P, Huang K, et al. Dose gradient gear target-normal structure interface for nonisocentric CyberKnife andisocentric intensity-modulated body radiotherapy forprostate cancer. Int J Radiat Oncol Biol Phys in press.Xie Y, Djajaputra D, King CR, et al. Intrafractional motion of the prostate during hypofractionated radiotherapy.Int J Radiat Oncol Biol Phys 2008;72:236-246.
Zhu et al., Tradeoffs of integrating real-time tracking intoIGRT for prostate cancer treatment.Phys Med Biol, 2009; Duke University
The advantage of using the Calypso system for real-time prostate tracking, to improve accuracy by a few millimeters,is diminished in comparison to the loss of MRI/MRS optionsfor more accurate post-treatment follow-up and monitoring
l Studied Calypso system with phantom and patients at eachstage of treatment
l Assessed whether transponders were displaced or heatedby MRI, and whether they caused image artifacts on MRI
l Large artifacts were visible on MRIl “Calypso transponders will hinder the use of pelvic MRI/MRSfor follow-up studies, limiting assessment options for thephysician and the patients.”