Radiation Therapy in Prostate CancerCurrent Status and New Advances

Arno J. Mundt MDProfessor and ChairmanDept Radiation OncologyMoores Cancer CenterUCSD

PresentationWelcome

Overview of UCSD, Moores Cancer Center and Radiation Oncology

Radiation Therapy and Prostate Cancer

Questions and Answers

University of California San DiegoYoungest UC School (Founded in 1960)Medical School (1968)

UCSDTrue Gem of the UC system16 Nobel Prize Winners 3 Nobel Prize Winners in MedicineAnnual Government Research grants exceed 700 MillionRanked in the top 15 Medical Schools in the USA (alongside Harvard, Stanford, etc.)

Rebecca and John MooresCancer Center

Opened in May 2005270,000 square foot state-of-the-art facilityOne of only 39 National Cancer Institute Designated Comprehensive Cancer Centers in the USA

UCSD Cancer Center

UCSD Radiation OncologyNew DepartmentNew Faculty

Recruiting experts from around the countryNew Equipment

Focus on bringing the San Diego region the latest in treatment technologies

Radiation OncologyUniversity of California San Diego

CurrentDepartment

ExpansionResearch Center

Proton Treatmentand Research

Radiation TherapyUse of high energy x-rays to

treat cancerLong history in the treatment

of cancer1st patient in 1896 within 2

months of the discovery of X-rays

Wilhelm Roentgen (1845-1923)Discovers X-rays in 1895

Radiation TherapyRT is used today in the treatment of nearly all cancers in the bodyTwo-thirds of all cancer patients in the USA receive RTBoth adults and childrenMany non-cancers as well

Radiation Modalities

External Beam →Involves the use of

photons and electrons

←Brachytherapy“Close therapy”Radioactive sources (Cs137, Ir192, I125) placed either in a cavity (intracavitary) or within (interstitial) a tumor

Radiation Therapy and Prostate CancerFirst used to

treat prostate cancer in 1909

Radioactive Radium inserted into the urethra (brachytherapy)

Machines of the day could not produce sufficiently

penetrating beams London (1920)

•Recognized that asuperior approach wouldbe to insert radium needlesdirectly into the prostate(interstitial brachytherapy)

•More of the prostate couldbe treated with lessdamage to the urethra

Radiation Therapy and Prostate Cancer

Prostate Brachytherapy Urology Textbook (1926)

Early Prostate Brachytherapy

Prostate Implant (1917)

Radiation Therapy in Prostate Cancer

Enthusiasm for brachytherapy and RT in general in prostate cancer decreased after WWIIMany patients treated were not curedMainstay of treatment became radical surgeryExcitement also surrounding discovery of the ability to treat with hormones

Radiation Therapy in Prostate Cancer

Interest in RT returned in the 1960sDevelopment of megavoltage (high energy) machinesHighly penetrating beams which treat the prostate without excessive skin toxicity

Malcolm BagshawStanford University

Demonstrated that prostate cancer is curable with external beam (megavoltage) RT

Stanford University (1962)

Radiation Therapy in Prostate Cancer

Brachytherapy revived in the late 1960’sRadioactive seeds were implanted directly at the time of the surgery Long-term results were not goodDifficult to obtain good distribution of the radioactive seeds in the prostateParts of the tumor were not treated adequately

Prostate Brachytherapy

Brachytherapy later improved by performing procedure under ultrasound guidanceBetter distribution of seeds in prostate

Interest decreased today due to urinary side effects and advances in external beam RT

Free Hand Technique Ultrasound Guided

External Beam AdvancesBetter, more powerful machines

Intensity Modulated RT (IMRT)

Image-Guided RT (IGRT)

Proton Therapy

External Beam Treatment Machines1920’sLow energyPoor penetrationUnable to treat the prostate without skin toxicity

1950sModerate EnergyImproved penetrationLess skin toxicity

TodayComputer controlled Linear accelerators

Multiple high energy beamsIMRT and IGRT

Conventional Prostate RTMultiple beams focused on the prostateAttempts made to shield surrounding normal rectum and bladderConsiderable volumes of normal tissues treated exposing patients to toxicity

Intensity Modulated RT (IMRT)Novel RT approachFirst developed in the early 1990sIncreasingly popular todayUse of computers to conform the radiation dose in 3 dimensions to the shape of the prostate (“shrink wrap”)Reduces dose to bladder and rectumReduces toxicity risk

Conventional RT field withshaped edgesThe beam has equal intensityacross its surface

IMRT field divided intodifferent “beamlets”

IMRT in Prostate Cancer

Conventional RT

IMRT Plan

IMRT in Prostate CancerBetter focusing allows us to reduce risk of toxicity to rectum and bladderAlso allows us to safely use higher doses to improve cure ratesAlso being used to potentially reduce risk of impotence by reducing irradiation of the penile bulb

RT in Prostate CancerResults of RT in prostate cancer now rival best results of surgery

Long-term comparisons show equal cure rates for early stage patients

Early Stage Prostate Cancern Endpoint 10-year Result

External Beam RTMass General 1396 PSA Control* 42%MD Anderson 643 PSA Control* 61%***Fox Chase 408 PSA Control** 59%***

Radical ProstatectomyMayo Clinic 3170 PSA <2 µg/L 52%Washington University 925 PSA <6 µg/L 61%Johns Hopkins 2404 PSA <2 µg/L 74%

*Defined as PSA <10 µg/L and absence of 2 rises after a nadir**Absence of 3 consecutive rises after a nadir***8-year results

Prostate IMRTHigher doses possible with IMRT may even result in better PSA control rates

Memorial Sloan Kettering Data

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Intermediaten=322

Unfavorablen=175

RT and Prostate CancerExcellent results also achieved treating patients with a rising PSA after prostatectomyIf initiated prior to significant rise in PSA, high cure rates are possibleAlso commonly used to improve the outcome of patients who undergo surgery but have a positive margin

Image Guided RT (IGRT)Current interest focused on image guided RT (IGRT)Method to use imaging in the treatment room to improve the delivery of IMRTNot a replacement for IMRTIMRT focuses the radiation on the prostate while IGRT ensures that it is aimed correctly everyday

IGRTNew Radiation Machines image patients and deliver radiationAllows one to see where the tumor is everyday immediately before treatmentVery important since many tumors including prostate cancer may move from day to dayIf you do not account for movement, you will miss the prostate

ProstateProstate

Bladder Bladder

Rectum Rectum

Varian On-Board Imaging System

Varian Trilogy Machine (UCSD)

Radiation

Imaging

IGRT and Prostate CancerTwo ApproachesTrack implanted (non-radioactive) seeds in the prostatePerform daily CT scans of the prostateBoth methods allow the treatment beams to be re-adjusted based on prostate location

On-Board Imaging IGRT

• Small gold seeds implanted in prostate• IGRT system used to match position everyday• <1-2 minutes

DRR Planning Film OBI

On-Board Imaging IGRT

• Alternatively, a daily CT can be performed• Used to ensure proper alignment of prostate

DRR Planning Film OBI

IGRT in Prostate CancerCurrently studying the benefit of IGRT in these patients

Studying which method (seeds or CT) is the optimal approach

IGRTIncreasing interest focusing on using sophisticated imaging to improve targeting of IMRT treatmentTraditional approaches simply treat the entire prostateNew approaches help focus treatment on the tumor itselfAllow higher more effective doses to be concentrated on the cancer

Color Doppler

Proton TherapyRevolution in the treatment of cancerProtons unlike conventional x-rays enter the body and stop!Allows treatment to be highly focused

Proton TreatmentProstate Cancer

Proton Therapy Prostate CancerThe future of prostate cancer treatmentCurrent approaches not idealUnable to do IMRT or IGRTProstate immobilized by placing a balloon in the rectum everydayNew proton machines will be substantially better with ability to do IMRT and localize the prostate with imaging

ConclusionsRadiation therapy has a long history in the treatment of prostate cancerCurrently RT occupies a major role in the treatment of prostate cancerNew approaches (IMRT and IGRT) improve the delivery and efficacy of treatmentProton therapy with IMRT and IGRT is clearly the future

Questions and AnswersA.J. Mundt MDProfessor and Chair858-822-6046amundt@ucsd.edu

Ajay Sandhu MDChief, Prostate Cancer Service858-822-6046

Kevin Murphy MDMedical Director858-822-6046