Thermal Therapy of Cancer - American Association of ... Therapy of CancerThermal Therapy of Cancer ... Thermal Therapy Treatment OptionsThermal Therapy Treatment Options Cryotherapy

Thermal Therapy of CancerThermal Therapy of CancerThermal Therapy of Cancer

Paul StaufferChris Diederich

Jean Pouliot

Radiation Oncology Dept.University of California, San Francisco

[email protected]

Paul StaufferChris Diederich

Jean Pouliot

Radiation Oncology Dept.University of California, San Francisco

[email protected] 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