Lecture 17-18 Hyperthermia treatment for tumors
Lecture 17-18 Hyperthermia treatment for tumors
Hyperthermia treatment for tumors Tumor Microenvironment Microvasculature Stage of tumor: 1.Dormant(no vasculature) 2.Vascularization (inducer:vascular growth factors) 3.Growth and Metastasis(new tumors) 4.Suppression of new tumors(inhibitors from main tumor), Necrotic(less perfusion in tumor center (in animal at least) ->average perfusion decrease)
Hyperthermia treatment for tumors • Tumor Microenvironment & Microvasculature – Stage of tumor: 1. Dormant (no vasculature) 2. Vascularization (inducer: vascular growth factors) 3. Growth and Metastasis (new tumors) 4. Suppression of new tumors (inhibitors from main tumor), Necrotic (less perfusion in tumor center (in animal at least) ->average perfusion decrease)
I.E, w256 Carcinosarcoma in rats (R.K.Jain,1977) Wo=WoN i in necrotic zone =10 WoN i in viable zone Canine lymphosarcoma (Tuttle etal.1964;Straw etal, 1974 Wb=1.2+15.1(r/R)2ml/min/g
I.E. w256 Carcinosarcoma in rats (R.K. Jain, 1977) Wb= WbN in necrotic zone =10 WbN in viable zone Canine lymphosarcoma (Tuttle etal. 1964; Straw etal, 1974) Wb=1.2+15.1(r/R)2 ml/min/g
Therapeutic approaches: Anti-angiogenic drug (Dr.Moses.J.Folkman Boston Children's Hospital May,1998. Newa week Blood supply↓ Hyperthermia
Therapeutic approaches: Blood supply ↓ Anti-angiogenic drug (Dr. Moses.J.Folkman Boston Children’s Hospital May, 1998. Newa week Hyperthermia
Hyperthermia effect 1866(Busch):erysipelas (insect)attack >high fever->cure for a facial sarcoma 189i(coley小：bacterial toxins→high fever (cancer patients)>reduced cancer size 1900:experiments done in lab animals> thermal dose (elevated temp.,duration)> effective treatment
Hyperthermia effect 1866(Busch): erysipelas (insect) a Ʃack →high fever → cure for a facial sarcoma 1891(coley): bacterial toxins → high fever (cancer pa Ɵents) → reduced cancer size 1900: experiments done in lab animals → thermal dose (elevated temp., dura Ɵon) → effective treatment
1970s&1980s: Exp.studies at the cellular level> tumor cells are more sensitive to heat than normal cells due to abnormal molar ratios of cholesterol phospholipid Elevated temperature at 43C for a period of time is more lethal to tumor cells. cholesterol phospholipid↑→heat resistance of cells↑
1970s&1980s: Exp. studies at the cellular level → • tumor cells are more sensitive to heat than normal cells due to abnormal molar ratios of cholesterol phospholipid – Elevated temperature at 43℃ for a period of time is more lethal to tumor cells. cholesterol phospholipid↑ → heat resistance of cells ↑
1980s-present Numerous Exp Clinical trials Hyperthermia alone->partial reduction of tumor size Hyperthermia w/ionized(reduced hypoxia)radiation therapy -better results Hyperthermia (increased circulation,increased vascular wall permeability to drugs)->better results
1980s-present – Numerous Exp & Clinical trials – Hyperthermia alone->partial reduction of tumor size – Hyperthermia w/ ionized (reduced hypoxia) radiation therapy -> better results – Hyperthermia (increased circulation, increased vascular wall permeability to drugs) -> better results
Effective Hyperthermia treatment a.Heating source selection: Surface Heating (local or whole body)-"Boundary condition" Hot water bath or moist air incubator Space suit and blanket techniques ● Infrared radiation Hot wax bath(molten paraffin wax having melting point of46℃) Regional systemic perfusion with heated blood Implantation of a heat source and electrocoagulation
Effective Hyperthermia treatment a. Heating source selection: Surface Heating (local or whole body)-”Boundary condition” • Hot water bath or moist air incubator • Space suit and blanket techniques • Infrared radiation • Hot wax bath (molten paraffin wax having melting point of 46 ℃ ) • Regional & systemic perfusion with heated blood • Implantation of a heat source and electrocoagulation
Volumetric heating (deep-seated tumors)-"q" Utrasonic:Sound wave particle oscillation mechanical energy converted to thermal energy by frictional losses 人f=C 0.2Mhz"hot spot" (2)air doesn't allow transmission->not for tissue containing air:like chest cavity
Volumetric heating (deep-seated tumors) –”q” • Utrasonic: Sound wave → particle oscillation → mechanical energy converted to thermal energy by frictional losses 0 0.2Mhz<f<3MHz C 1500m/s sound speed in water for a plane-paralled beam: exp( ) attenuation coefficient ( , ) (1) rapid absorption in bone "hot spot" n f C II x f tissue f λ α α = ≈ = − → (2) air doesn't allow transmission not for tissue containing air: like chest cavity →
Microwave:electromagnetic energy converted to thermal energy by dielectric and resistive losses λf=C10Mhz<f<100GHz C=3.0*10%m/s speed of light at r distrance from the MW source a general expresion: (r)wm]54R().pecific absorption ratep a~absorption coefficient ~f(s,o) g-dielective constant ~f (tissue,f) o-electrical conductivity -f(tissue,A
• Microwave: electromagnetic energy converted to thermal energy by dielectric and resistive losses 8 - 3 10 100 C=3.0 10 m/s speed of light at r distrance from the MW source a general expresion: ( )[w.m ] ( ),specific absorption rate absorption coefficient r n f C Mhz f GHz e q r SAR r P r α λ α = << ∗ = ⋅ (, ) dielective constant ( , ) electrical conductivity ( , ) n n n f f tissue f f tissue f ε σ ε σ − − ∼