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Thermal Therapy of CancerThermal Therapy of CancerThermal Therapy of Cancer
Paul StaufferChris Diederich
Jean Pouliot
Radiation Oncology Dept.University of California, San Francisco
stauffer@radonc17.ucsf.edu
Paul StaufferChris Diederich
Jean Pouliot
Radiation Oncology Dept.University of California, San Francisco
stauffer@radonc17.ucsf.edu UCUCSFSF
HyperthermiaHyperthermia
Definition
Mechanisms
Rationale: Thermal Enhancing Ratio (TER)
Dosimetry
Overview of Technology for Thermal Therapy
Clinical Applications
Hyperthermia
T = 41-45°C for 30-60 minΔT = 4 - 8°C
Dose = Cumulative Equivalent Minutes at 43°C for the T90 temperature
(CEM43oCT)
Hyperthermia
T = 41-45°C for 30-60 minΔT = 4 - 8°C
Dose = Cumulative Equivalent Minutes at 43°C for the T90 temperature
(CEM43oCT)
Hyperthermia Mechanisms
• Increases perfusion, permeability, pH, pO2
• Increases metabolic activity, drug uptake
• Radiosensitization, Chemosensitization
• Some cell kill at higher temperatures/doses
Hyperthermia Mechanisms
• Increases perfusion, permeability, pH, pO2
• Increases metabolic activity, drug uptake
• Radiosensitization, Chemosensitization
• Some cell kill at higher temperatures/doses
Hyperthermia RationaleHyperthermia Rationale
C3H Mammary Carcinoma
(a) (b) (c) Fig. 2 – Rationale for combining heat and radiation for treatment of recurrent chestwall disease. Data from demonstrates: (a) increased TER for simultaneous heat and radiation in C3H mammary carcinoma, (b) clinical impact of TER=1.5 obtained from a compilation of human data in the literature, and (c) TER up to 5.0 for simultaneous heat and radiation in C3H mammary carcinoma compared to TER plateau of 2.0 for sequentially applied modalities.
The synergistic effect of heat and radiation is quantified by the Thermal Enhancement Ratio (TER) defined as:The synergistic effect of heat and radiation is quantified by the Thermal Enhancement Ratio (TER) defined as:
TER =RT dose without heat
RT dose for equivalent effect with heat
DosimetryDosimetry
Body is thermally auto-regulated
Heating an organ is like bringing a heater in an air conditioned room!
Feedback Control / Power Steering
Heating deviceHeating device Temperature elevationTemperature elevation
Heating MechanismsHeating Mechanisms
Thermal conductionThermal conduction
ElectromagneticRF, MW
ElectromagneticRF, MW
Mechanical frictionUS
Mechanical frictionUS
ExternalExternal
ExternalExternal
Interstitial / intracavitaryInterstitial / intracavitary
Interstitial / intracavitaryInterstitial / intracavitary
Interstitial / intracavitaryInterstitial / intracavitary
Clinical Applications of Thermal TherapyClinical Applications of Thermal Therapy
Hyperthermia (41 - 45oC or < 100 CEM)Cancer Therapy with Radiation or Chemotherapy
Heat-Activated Gene Therapy, Liposome Release
Accelerate Wound and Bone Healing
Organ Preservation (Stimulate Heat Shock Proteins / Rewarming)
Thermal Therapy Treatment OptionsThermal Therapy Treatment Options
CryotherapyT = < - 50°C for >10 min
ΔT = - 90°C
HyperthermiaT = 41-45°C for 30-60 min
ΔT = 4 - 8°C
Thermal AblationT > 50°C for >4-6 min
ΔT = > 13°C
MechanismsFreeze/Thaw transition disrupts cell membrane
Complete cellular destruction
MechanismsIncreases perfusion, permeability, pH, pO2Increases metabolic activity, drug uptakeRadiosensitization, ChemosensitizationSome cell kill at higher temperatures/doses
MechanismsProtein DenaturizationNecrosisCoagulationNot subtle effects
Potential HT TechniquesThermal Conduction
Potential HT TechniquesExternal
Scanned Focused USLarge Focused US Arrays
Interstitial - IntracavitaryRF, MW, US, LaserThermal Conduction
Potential HT TechniquesExternal
RF, MW, USInterstitial - Intracavitary
RF, MW, USThermal Conduction
Ferroseeds, ThermorodsDC Resistance WiresHot Water TubesLaser/Fiberoptic Diffuser Crystals
Equipment Availability100% Commercial
Equipment Availability40% Commercial60% University - Under Development
Equipment Availability75% Commercial
10% PMA50% IDE Trials40% Under Development
25% University - Under Development
Devices and Techniques
for
Heating Tissue
Devices and Techniques
for
Heating Tissue
Available Heating ModalitiesAvailable Heating Modalities
Thermal Conduction Equilibrium of Thermal Gradients
ElectromagneticRadiofrequency Current Electron Flow between Atoms
Joule Heating
Microwave Radiation Oscillations of Polar H2O Molecules Dielectric Heating
Laser Absorption of Light Energy
UltrasoundPressure Wave Compression – Expansion Forces
Mechanical Friction Losses
Superficial HeatingSuperficial Heating
Electromagnetic TechniquesWaveguide / Horn
Single or multiple aperture arraysPhased or non-phased arraysStationary or robotically scanned
Microstrip ApplicatorsSingle or multiple aperturePlanar or conformalSpirals - Stationary or scanningPatches, annular slots, etc
Dipole Surface ArrayStationary or scanning
RF Capacitive PlateHybrid
Inductive loop “current sheet”Multimode feed “HEMA”
Laser
Conventional10x10 Horn Waveguide
Lucite Cone Waveguide
Reitveld & VanRhoon IJH 1999
Superficial Hyperthermia434 MHz Microwave - Deeper Penetration
Superficial HyperthermiaSuperficial Hyperthermia434 MHz Microwave 434 MHz Microwave -- Deeper PenetrationDeeper Penetration
Lucite Cone Applicator Lucite Cone Applicator
Gerard VanRhoon
Current Sheet Applicators (CSA)Current Sheet Applicators (CSA)
Multiple Frequencies - 915, 433 Phased Array - Deeper Penetration
J Hand, M Gopal, T Cetas
Microstrip Applicators
Stanford Blanket
Microstrip Applicators
Stanford Blanket
Lee, Fessenden, KappLee, Fessenden, Kapp
Flexible Conformal Microwave Array Applicator 6 mm Water Bolus
24 Aperture CMA 16 Aperture CMA
Flexible Conformal Microwave Array Applicator 6 mm Water Bolus
24 Aperture CMA 16 Aperture CMA
Vest Bolus
40 Aperture CMA47 x 29 = 1363 cm2
40 Aperture CMA47 x 29 = 1363 cm2 Stauffer, Rossetto, NeumanStauffer, Rossetto, Neuman
Possible Treatment ConfigurationsPatient’s Preference
Standing - Pacing Lying Down Sitting
Thermometry Solutions for the Future
2D Thermal Monitoring Sheet
Thermometry Solutions for the Future
2D Thermal Monitoring Sheet
CMA Applicator
ThermalMonitoring
Array
MW Array Controller
Fiber ArrayReadout
Fiber Ribbon Cable
Ipitek Corp.
Combination ApplicatorSimultaneous Heat and Brachytherapy
Combination ApplicatorSimultaneous Heat and Brachytherapy
Rectangular 17 x 35 cm
Rectangular 17 x 35 cm
L-Shape 52 x 32 cmL-Shape
52 x 32 cm
Preparations for Simultaneous HT/RT Treatment Setup and Preplan
Preparations for Simultaneous HT/RT Treatment Setup and Preplan
15 x 15 cm
Target HDRHDR
3D Conformal Dose PlanIPSA -------> Plato
3D Conformal Dose PlanIPSA -------> Plato
Skin Surface Contour
PCB Array
13x13x1 cmTarget
Water Bolus
Deep HeatingDeep Heating
Ultrasound TechniquesUltrasound TechniquesPiston Transducer
UnfocusedFocused - Convex shape or Focusing lens
Lightly - no gain
Tightly - high gain
Stationary or Robotically scanned
Transducer ArraysPlanar or Geometric focus
Stationary lightly focused
Stationary lightly focused - scanning reflector
Mechanically or electrically scanned transducers
Lightly focused transducer array
Focused transducer array
Radiofrequency Plate Electrodes8 - 27 MHz
Radiofrequency Plate ElectrodesRadiofrequency Plate Electrodes8 8 -- 27 MHz27 MHz
Scanned Focused Ultrasound Scanned Focused Ultrasound Scanned Focused Ultrasound
Spherical Section ArrayFocused Ultrasound
Spherical Section ArrayFocused Ultrasound
19921992 20022002
Evolving Technologies – Deep HeatingEvolving Technologies – Deep Heating
19821982
4 Antenna Pairs1 Ring
Sigma 60
12 Ch, 24 Antennas3 Rings
Sigma-Eye
1 Power Channel
RF- 8
Magnetrode
APAS
InterstitialInterstitial
Multi-needle LCF hyperthermia systemdesigned for hyperthermia combined with brachytherapy. (Photos courtesy of Peter Corry, William Beaumont Hospital).
Multi-needle LCF hyperthermia systemdesigned for hyperthermia combined with brachytherapy. (Photos courtesy of Peter Corry, William Beaumont Hospital).
Interstitial microwave antennas suitable for hyperthermia in combination with interstitial brachytherapy (with permission from BSD Medical Corp.).
Interstitial microwave antennas suitable for hyperthermia in combination with interstitial brachytherapy (with permission from BSD Medical Corp.).
Directional Ultrasound Applicators
360 deg. USApplicators1
2
3
54
6
30
32
34
36
38
40
42
44
46
48
50
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5Position (cm)
Tem
pera
ture
(C)
Probe 1 - Catheter 1Probe 2 - Catheter 2Probe 3 - Catheter 6Probe 4 - Catheter 3Probe 5 - Catheter 5Probe 6 - Catheter 4
4 x 10 mm Applicator
3 x 10 mm2 x 10 mm Quick-Connects
RF Power
Water-FlowPorts
Ultrasound Applicator 13-g Catheter
(A) Interstitial ultrasound applicators suitable for heating in combination with HDR brachytherapy; (B) CT image of a brachytherapy implant pattern in the prostate, with directional ultrasound applicators placed posterior with energy directed anterior to protect the rectum. (C) Measured temperature profiles.
(A) Interstitial ultrasound applicators suitable for heating in combination with HDR brachytherapy; (B) CT image of a brachytherapy implant pattern in the prostate, with directional ultrasound applicators placed posterior with energy directed anterior to protect the rectum. (C) Measured temperature profiles.
Evolutionary Trends – Heating CapabilitiesEvolutionary Trends Evolutionary Trends –– Heating CapabilitiesHeating Capabilities
First Simple Structures (e.g. Single Waveguide, Piston)Centrally Peaked SAR - Power Up / Down ControlNo pre-Tx planning or real-time adjustment of SAR1-8 Stationary Temperature SensorsSmall Treatment Volumes (e.g. < 3-4 cm diameter)
Second Planar Arrays2-D Treatment Planning - Lateral Adjustment of SAR4 - 16 Controllable Sources8 - 16 Temperature Sensors, Thermal MappingModerate Size Treatment Volumes
Emerging Electrically or Physically Phase Focused ArraysStationary Conformal ArraysSite-Optimized ApplicatorsNon-Invasive Temperature & Physiologic Effect MonitoringPatient Specific Treatment Planning - 3-D Power Steering
Generation
1980’s1980’s
1990’s1990’s
20002000
So Why Isn’t Everyone Offering HT(Depends on Who You Talk To)
So Why Isn’t Everyone Offering HT(Depends on Who You Talk To)
Reimbursement rate too low AdministratorsSpace and personnel demands too high Administrators
Can not heat all patients/sites CliniciansCan not deliver precise Tdose as prescribed Clinicians
Equipment is terrible PhysicistsBetter equipment not available commercially Physicists
Difficult to setup and deliver in many sites OperatorsUncomfortable for some patients Operators
• Optimum combination of HT with RT
Long duration moderate vs. short duration high temp. HTPulsed vs. continuous RT with simultaneous HT
• Optimum administration of HT with CT
Identify best compromise of temperature/thermal dose forVessel permeability, extravasation, cell metabolism and uptake
• Are we investigating all appropriate clinical applications
Can we justify treating earlier stage disease/whichMore aggressive combinations of HT + RT + CT
Current Challenges - BiologyCurrent Challenges - Biology
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