Principles of RadiationPrinciples of Radiation
OncologyOncology
Michael Underbrink, MDMichael Underbrink, MD
Anna Pou, MDA...
IntroductionIntroduction
• Increasing use for head and neck cancerIncreasing use for head and neck cancer
• Combined or as...
Radiation PhysicsRadiation Physics
• Basis – ionizing particles interact with cellularBasis – ionizing particles interact ...
External Beam IrradiationExternal Beam Irradiation
• Dual-energy linear accelerators generate:Dual-energy linear accelerat...
External Beam IrradiationExternal Beam Irradiation
BrachytherapyBrachytherapy
• Radioactive source in direct contact with tumorRadioactive source in direct contact with tumo...
BrachytherapyBrachytherapy
• LimitationsLimitations
– Tumor must be accessibleTumor must be accessible
– Well-demarcatedWe...
BrachytherapyBrachytherapy
RadiobiologyRadiobiology
• Ionizing radiation ejects an electron from aIonizing radiation ejects an electron from a
target...
RadiobiologyRadiobiology
RadiobiologyRadiobiology
• Random cell deathRandom cell death
– Deposition of energy & injury is random eventDeposition of...
4 R’s of radiation biology4 R’s of radiation biology
• RRepair of cellular damageepair of cellular damage
• RReoxygenation...
Repair of sublethal injuryRepair of sublethal injury
• Sublethal injury – cells exposed to sparseSublethal injury – cells ...
ReoxygenationReoxygenation
• Oxygen stabilizes free radicalsOxygen stabilizes free radicals
• Hypoxic cells require more r...
ReoxygenationReoxygenation
RedistributionRedistribution
• Cell cycle position sensitive cellsCell cycle position sensitive cells
• S phase – radiores...
RedistributionRedistribution
RepopulationRepopulation
• Increased regeneration of surviving fractionIncreased regeneration of surviving fraction
• Rapi...
RepopulationRepopulation
Dose-Response RelationsDose-Response Relations
• Control probability variablesControl probability variables
– Tumor sizeTu...
Dose-Response RelationsDose-Response Relations
FractionationFractionation
Fractionation SchedulesFractionation Schedules
• ConventionalConventional
– 1.8 to 2.0 Gy given 5 times/week1.8 to 2.0 Gy ...
Fractionation SchedulesFractionation Schedules
• HyperfractionationHyperfractionation
– 1.0 to 1.2 Gy bid/tid, 5 times/wee...
Treatment PrinciplesTreatment Principles
• Size and location of primarySize and location of primary
• Presence/absence and...
Treatment PrinciplesTreatment Principles
• Surgical salvage of primary radiation failures isSurgical salvage of primary ra...
Shrinking field techniqueShrinking field technique
• Initial dose = 45 to 50 Gy (4.5 to 5.0 weeks)Initial dose = 45 to 50 ...
Shrinking field techniqueShrinking field technique
Combined ModalitiesCombined Modalities
• Surgery and XRT complement each otherSurgery and XRT complement each other
• Surg...
Preoperative XRTPreoperative XRT
• AdvantagesAdvantages
– Unresectable lesions may become resectableUnresectable lesions m...
Postoperative XRTPostoperative XRT
• AdvantagesAdvantages
– Better surgical stagingBetter surgical staging
– Greater dose ...
ComplicationsComplications
• Acute Tissue ReactionsAcute Tissue Reactions
• Late Tissue ReactionsLate Tissue Reactions
Acute ToxicityAcute Toxicity
• Time onset depends on cell cycling timeTime onset depends on cell cycling time
• Mucosal re...
Acute ToxicityAcute Toxicity
• Mucositis – intensity-limiting side effect forMucositis – intensity-limiting side effect fo...
Acute ToxicityAcute Toxicity
Late ToxicityLate Toxicity
• Injury tends to be permanentInjury tends to be permanent
• Cells with low turnover (fibroblas...
Late ToxicityLate Toxicity
Late ToxicityLate Toxicity
• XerostomiaXerostomia
– Injury to serous acinar cellsInjury to serous acinar cells
– May have ...
Late ToxicityLate Toxicity
Late ToxicityLate Toxicity
• FibrosisFibrosis
– Serious problem, total dose limiting factorSerious problem, total dose lim...
Late ToxicityLate Toxicity
Late ToxicityLate Toxicity
• Central Nervous SystemCentral Nervous System
– Devastating to patientsDevastating to patients...
ConclusionsConclusions
• XRT key role in treatment of H&N cancerXRT key role in treatment of H&N cancer
• Fundamentals of ...
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Principles of Radiation Oncology

  1. 1. Principles of RadiationPrinciples of Radiation OncologyOncology Michael Underbrink, MDMichael Underbrink, MD Anna Pou, MDAnna Pou, MD
  2. 2. IntroductionIntroduction • Increasing use for head and neck cancerIncreasing use for head and neck cancer • Combined or as single modalityCombined or as single modality • Outline basic principles, radiobiologyOutline basic principles, radiobiology • General treatment approachGeneral treatment approach • Common complicationsCommon complications
  3. 3. Radiation PhysicsRadiation Physics • Basis – ionizing particles interact with cellularBasis – ionizing particles interact with cellular moleculesmolecules • Relies on transfer of energy created byRelies on transfer of energy created by secondary charged particles (usually electrons)secondary charged particles (usually electrons) • Break chemical bondsBreak chemical bonds • External beam vs. BrachytherapyExternal beam vs. Brachytherapy • Radiant energy is discrete yet randomRadiant energy is discrete yet random
  4. 4. External Beam IrradiationExternal Beam Irradiation • Dual-energy linear accelerators generate:Dual-energy linear accelerators generate: – Low energy megavoltage x-rays (4-6 MeV)Low energy megavoltage x-rays (4-6 MeV) – High energy x-rays (15-20 MeV)High energy x-rays (15-20 MeV) – Photon energyPhoton energy • Particle Radiation (electrons, protons, neutrons)Particle Radiation (electrons, protons, neutrons) • Photon therapy advantagesPhoton therapy advantages – Skin sparing, penetration, beam uniformitySkin sparing, penetration, beam uniformity • Head and Neck sites – 4-6 MeV x-ray or Co60Head and Neck sites – 4-6 MeV x-ray or Co60 gamma ray radiationgamma ray radiation
  5. 5. External Beam IrradiationExternal Beam Irradiation
  6. 6. BrachytherapyBrachytherapy • Radioactive source in direct contact with tumorRadioactive source in direct contact with tumor – Interstitial implants, intracavitary implants or surfaceInterstitial implants, intracavitary implants or surface moldsmolds • Greater deliverable doseGreater deliverable dose • Continuous low dose rateContinuous low dose rate • Advantage for hypoxic or slow proliferatorsAdvantage for hypoxic or slow proliferators • Shorter treatment timesShorter treatment times
  7. 7. BrachytherapyBrachytherapy • LimitationsLimitations – Tumor must be accessibleTumor must be accessible – Well-demarcatedWell-demarcated – Cannot be only modality for tumors with high riskCannot be only modality for tumors with high risk of regional lymph node metastasisof regional lymph node metastasis
  8. 8. BrachytherapyBrachytherapy
  9. 9. RadiobiologyRadiobiology • Ionizing radiation ejects an electron from aIonizing radiation ejects an electron from a target moleculetarget molecule • Distributed randomly within cellDistributed randomly within cell • Double-strand DNA breaks – lethalDouble-strand DNA breaks – lethal • Cell death: no longer able to undergo unlimitedCell death: no longer able to undergo unlimited cell divisioncell division • Direct vs. Indirect injury (free radicals – ODirect vs. Indirect injury (free radicals – O22)) • Inadequate cellular repair mechanisms impliedInadequate cellular repair mechanisms implied
  10. 10. RadiobiologyRadiobiology
  11. 11. RadiobiologyRadiobiology • Random cell deathRandom cell death – Deposition of energy & injury is random eventDeposition of energy & injury is random event – Same proportion of cells is damaged per doseSame proportion of cells is damaged per dose – 100 to 10 cell reduction = 10100 to 10 cell reduction = 1066 to 10to 1055 cell reductioncell reduction – Larger tumors require more radiationLarger tumors require more radiation – 101055 cells = nonpalpablecells = nonpalpable – Applies to normal tissue alsoApplies to normal tissue also • Therapeutic advantage – 4 R’s of radiobiologyTherapeutic advantage – 4 R’s of radiobiology
  12. 12. 4 R’s of radiation biology4 R’s of radiation biology • RRepair of cellular damageepair of cellular damage • RReoxygenation of theeoxygenation of the tumortumor • RRedistribution within theedistribution within the cell cyclecell cycle • RRepopulation of cellsepopulation of cells
  13. 13. Repair of sublethal injuryRepair of sublethal injury • Sublethal injury – cells exposed to sparseSublethal injury – cells exposed to sparse ionization fields, can be repairedionization fields, can be repaired • Killing requires greater total dose when given inKilling requires greater total dose when given in several fractionsseveral fractions • Most tissue repair in 3 hours, up to 24 hoursMost tissue repair in 3 hours, up to 24 hours • Allows repair of injured normal tissue, potentialAllows repair of injured normal tissue, potential therapeutic advantage over tumor cellstherapeutic advantage over tumor cells • Radioresistance – melanoma?Radioresistance – melanoma?
  14. 14. ReoxygenationReoxygenation • Oxygen stabilizes free radicalsOxygen stabilizes free radicals • Hypoxic cells require more radiation to killHypoxic cells require more radiation to kill • Hypoxic tumor areasHypoxic tumor areas – Temporary vessel constriction from massTemporary vessel constriction from mass – Outgrow blood supply, capillary collapseOutgrow blood supply, capillary collapse • Tumor shrinkage decreases hypoxic areasTumor shrinkage decreases hypoxic areas • Reinforces fractionated dosingReinforces fractionated dosing • Hypoxic cell radiosensitizers, selective chemoHypoxic cell radiosensitizers, selective chemo
  15. 15. ReoxygenationReoxygenation
  16. 16. RedistributionRedistribution • Cell cycle position sensitive cellsCell cycle position sensitive cells • S phase – radioresistantS phase – radioresistant • GG22 phase delay = increased radioresistancephase delay = increased radioresistance • RAD9 gene mutation – radiosensitive yeastRAD9 gene mutation – radiosensitive yeast • H-ras and c-myc oncogenes - GH-ras and c-myc oncogenes - G22 delaydelay • Fractionated XRT redistributes cellsFractionated XRT redistributes cells • Rapid cycling cells more sensitive (mucosa, skin)Rapid cycling cells more sensitive (mucosa, skin) • Slow cyclers (connective tissue, brain) sparedSlow cyclers (connective tissue, brain) spared
  17. 17. RedistributionRedistribution
  18. 18. RepopulationRepopulation • Increased regeneration of surviving fractionIncreased regeneration of surviving fraction • Rapidly proliferating tumors regenerate fasterRapidly proliferating tumors regenerate faster • Determines length and timing of therapy courseDetermines length and timing of therapy course • Regeneration (tumor) vs. Recuperation (normal)Regeneration (tumor) vs. Recuperation (normal) • Reason for accelerated treatment schedulesReason for accelerated treatment schedules • Reason against:Reason against: – Treatment delayTreatment delay – Protracted XRT, split course XRT (designed delay)Protracted XRT, split course XRT (designed delay)
  19. 19. RepopulationRepopulation
  20. 20. Dose-Response RelationsDose-Response Relations • Control probability variablesControl probability variables – Tumor sizeTumor size – XRT doseXRT dose • Favorable response curvesFavorable response curves – Small, well-vascularized tumorsSmall, well-vascularized tumors – Homogeneous tumorsHomogeneous tumors • Unfavorable response curvesUnfavorable response curves – Large, bulky tumors (hypoxia)Large, bulky tumors (hypoxia) – Heterogeneous, variable cell numbersHeterogeneous, variable cell numbers • Normal tissue injury risk increases with XRTNormal tissue injury risk increases with XRT dose (size of tumor)dose (size of tumor)
  21. 21. Dose-Response RelationsDose-Response Relations
  22. 22. FractionationFractionation
  23. 23. Fractionation SchedulesFractionation Schedules • ConventionalConventional – 1.8 to 2.0 Gy given 5 times/week1.8 to 2.0 Gy given 5 times/week – Total of 6 to 8 weeksTotal of 6 to 8 weeks – Effort to minimize late complicationsEffort to minimize late complications • Accelerated fractionationAccelerated fractionation – 1.8 to 2.0 Gy given bid/tid1.8 to 2.0 Gy given bid/tid – Similar total dose (less treatment time)Similar total dose (less treatment time) – Minimize tumor repopulation (increase local control)Minimize tumor repopulation (increase local control) – Tolerable acute complications (increased)Tolerable acute complications (increased)
  24. 24. Fractionation SchedulesFractionation Schedules • HyperfractionationHyperfractionation – 1.0 to 1.2 Gy bid/tid, 5 times/week1.0 to 1.2 Gy bid/tid, 5 times/week – Similar total treatment time (increased total dose)Similar total treatment time (increased total dose) – Increases total doseIncreases total dose – Potentially increases local controlPotentially increases local control – Same rates of late complicationsSame rates of late complications – Increased acute reactionsIncreased acute reactions
  25. 25. Treatment PrinciplesTreatment Principles • Size and location of primarySize and location of primary • Presence/absence and extent/incidence ofPresence/absence and extent/incidence of regional or distant metastasisregional or distant metastasis • General condition of patientGeneral condition of patient • Early stage cancersEarly stage cancers – Surgery alone = XRT aloneSurgery alone = XRT alone – Treatment choice depends on functional deficitsTreatment choice depends on functional deficits • Late stage – usually combination of treatmentsLate stage – usually combination of treatments
  26. 26. Treatment PrinciplesTreatment Principles • Surgical salvage of primary radiation failures isSurgical salvage of primary radiation failures is better than radiation salvage of surgical failurebetter than radiation salvage of surgical failure • Explains rationale behind organ preservationExplains rationale behind organ preservation strategiesstrategies • XRT tumor cell killing is exponential functionXRT tumor cell killing is exponential function – Dose required for tumor control is proportional toDose required for tumor control is proportional to the logarithm of the number of viable cells in thethe logarithm of the number of viable cells in the tumortumor
  27. 27. Shrinking field techniqueShrinking field technique • Initial dose = 45 to 50 Gy (4.5 to 5.0 weeks)Initial dose = 45 to 50 Gy (4.5 to 5.0 weeks) – Given through large portalsGiven through large portals – Covers areas of possible regional metastasis andCovers areas of possible regional metastasis and primaryprimary • Second dose = 15 to 25 Gy (1.5 to 2.5 weeks)Second dose = 15 to 25 Gy (1.5 to 2.5 weeks) – Boost field (gross tumor and small margin)Boost field (gross tumor and small margin) – Total dose of 60 to 75 Gy in 6 to 7.5 weeksTotal dose of 60 to 75 Gy in 6 to 7.5 weeks • Boost dose = 10 to 15 GyBoost dose = 10 to 15 Gy – Massive tumorsMassive tumors – Second field reduction at 60 to 65 GySecond field reduction at 60 to 65 Gy – Total of 7 to 8 weeksTotal of 7 to 8 weeks
  28. 28. Shrinking field techniqueShrinking field technique
  29. 29. Combined ModalitiesCombined Modalities • Surgery and XRT complement each otherSurgery and XRT complement each other • Surgery – removes gross tumor (bulky tumorsSurgery – removes gross tumor (bulky tumors are more difficult to control with XRT)are more difficult to control with XRT) • XRT – effective for microscopic disease, betterXRT – effective for microscopic disease, better with exophytic tumors than ulcerative oneswith exophytic tumors than ulcerative ones (Surgical failures may leave subclinical disease)(Surgical failures may leave subclinical disease) • Combining treatments counteracts limitationsCombining treatments counteracts limitations • Pre or Post-operative XRTPre or Post-operative XRT
  30. 30. Preoperative XRTPreoperative XRT • AdvantagesAdvantages – Unresectable lesions may become resectableUnresectable lesions may become resectable – Extent of surgical resection diminishedExtent of surgical resection diminished – Smaller treatment portalsSmaller treatment portals – Microscopic disease more radiosensitive (blood supply)Microscopic disease more radiosensitive (blood supply) – Decreased risk of distant metastasis from surgicalDecreased risk of distant metastasis from surgical manipulation?manipulation? • DisadvantagesDisadvantages – Decreased wound healingDecreased wound healing – Decreased safe dose (45 Gy in 4.5 weeks eradicatesDecreased safe dose (45 Gy in 4.5 weeks eradicates subclinical disease in 85% to 90% of patients)subclinical disease in 85% to 90% of patients)
  31. 31. Postoperative XRTPostoperative XRT • AdvantagesAdvantages – Better surgical stagingBetter surgical staging – Greater dose can be given safely (60 to 65 Gy in 6 toGreater dose can be given safely (60 to 65 Gy in 6 to 7 weeks)7 weeks) – Total dose can be based on residual tumor burdenTotal dose can be based on residual tumor burden – Surgical resection is easierSurgical resection is easier – Tissue heals betterTissue heals better • DisadvantagesDisadvantages – Distant metastasis by manipulation?Distant metastasis by manipulation? – Delay in postoperative treatment if healing problemsDelay in postoperative treatment if healing problems (poorer results if delayed more than 6 weeks)(poorer results if delayed more than 6 weeks)
  32. 32. ComplicationsComplications • Acute Tissue ReactionsAcute Tissue Reactions • Late Tissue ReactionsLate Tissue Reactions
  33. 33. Acute ToxicityAcute Toxicity • Time onset depends on cell cycling timeTime onset depends on cell cycling time • Mucosal reactions – 2Mucosal reactions – 2ndnd week of XRTweek of XRT • Skin reactions – 5Skin reactions – 5thth weekweek • Generally subside several weeks after completionGenerally subside several weeks after completion of treatmentof treatment • RTOG – acute toxicity <90 days from start ofRTOG – acute toxicity <90 days from start of treatment (epithelial surfaces generally heal withintreatment (epithelial surfaces generally heal within 20 to 40 days from stoppage of treatment)20 to 40 days from stoppage of treatment)
  34. 34. Acute ToxicityAcute Toxicity • Mucositis – intensity-limiting side effect forMucositis – intensity-limiting side effect for aggressive schedulesaggressive schedules • Accelerated fractionation – increase acuteAccelerated fractionation – increase acute toxicitiestoxicities • Conventional fractionation conservativelyConventional fractionation conservatively emphasized maximum tolerated dose is limited byemphasized maximum tolerated dose is limited by late not acute tissue injurylate not acute tissue injury
  35. 35. Acute ToxicityAcute Toxicity
  36. 36. Late ToxicityLate Toxicity • Injury tends to be permanentInjury tends to be permanent • Cells with low turnover (fibroblasts, neurons)Cells with low turnover (fibroblasts, neurons) • Develop within months to yearsDevelop within months to years • Xerostomia, dental caries, fibrosis, soft-tissueXerostomia, dental caries, fibrosis, soft-tissue necrosis, nerve tissue damagenecrosis, nerve tissue damage • Most common - xerostomiaMost common - xerostomia
  37. 37. Late ToxicityLate Toxicity
  38. 38. Late ToxicityLate Toxicity • XerostomiaXerostomia – Injury to serous acinar cellsInjury to serous acinar cells – May have partial recoveryMay have partial recovery – Results in dental caries (in or outside of fields)Results in dental caries (in or outside of fields) • Soft tissue necrosisSoft tissue necrosis – Mucosal ulceration, damage to vascular connectiveMucosal ulceration, damage to vascular connective tissuetissue – Can result in osteo-/chondroradionecrosisCan result in osteo-/chondroradionecrosis
  39. 39. Late ToxicityLate Toxicity
  40. 40. Late ToxicityLate Toxicity • FibrosisFibrosis – Serious problem, total dose limiting factorSerious problem, total dose limiting factor – Woody skin texture – most severeWoody skin texture – most severe – Large daily fractions increase riskLarge daily fractions increase risk • Ocular – cataracts, optic neuropathy, retinopathyOcular – cataracts, optic neuropathy, retinopathy • Otologic – serous otitis media (nasopharynx,Otologic – serous otitis media (nasopharynx, SNHL (ear treatments)SNHL (ear treatments)
  41. 41. Late ToxicityLate Toxicity
  42. 42. Late ToxicityLate Toxicity • Central Nervous SystemCentral Nervous System – Devastating to patientsDevastating to patients – Myelopathy (30 Gy in 25 fractions)Myelopathy (30 Gy in 25 fractions) • Electric shock from cervical spine flexion (Lhermitte sign)Electric shock from cervical spine flexion (Lhermitte sign) – Transverse myelitis (50 to 60 Gy)Transverse myelitis (50 to 60 Gy) – Somnolence syndrome (months after therapy)Somnolence syndrome (months after therapy) • Lethargy, nausea, headache, CN palsies, ataxiaLethargy, nausea, headache, CN palsies, ataxia • Self-limiting, transientSelf-limiting, transient – Brain necrosis (65 to 70 Gy) – permanentBrain necrosis (65 to 70 Gy) – permanent
  43. 43. ConclusionsConclusions • XRT key role in treatment of H&N cancerXRT key role in treatment of H&N cancer • Fundamentals of radiation physics andFundamentals of radiation physics and radiobiology explain rationale behind treatmentradiobiology explain rationale behind treatment schedules and complicationsschedules and complications • Basic knowledge important with regard toBasic knowledge important with regard to patient counselingpatient counseling

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