Intensity Modulated Radiation Therapy IMRT for Prostate Cancer

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Intensity Modulated Radiation Therapy (IMRT) for
Prostate Cancer

• Brian P. Quaranta, MD
• 21st Century Oncology
• Asheville, NC, USA

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Outline

• 1. Technical aspects of radiation delivery
  including IMRT
• 2. Why IMRT is better than 3D
• 3. Goals and results of IMRT
• 4. Potential disadvantages
• 5. Summary

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Part 1

• Technical Aspects

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The Progression of Technology

• In order to understand what were doing now, and
  where were going, its necessary to be
  acquainted with the past

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1970s 1980s

• Treatment plans designed using x-rays and lead
  blocks
• Ability to localize the prostate limited b/c soft
  tissue structures not well visualized with x-rays
• Prostate cancer treatment doses were generally in
  the range of 60 Gy

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1980s-1990s 3D Conformal Radiation

• Patient has CT scan in treatment position
• Radiation oncologist outlines the prostate,
  seminal vesicles, bladder, rectum, femoral heads
• Computer then generates a 3D representation of
  all of the structures and their spatial
  relationships
• Radiation oncologist can use this information to
  design beams that more accurately target tumor
  and avoid normal tissues
• Increased confidence in location resulted in
  smaller fields, which led to higher doses,
  generally around 70 Gy

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21st Century IMRT

• Stands for Intensity-Modulated Radiation
  Therapy
• Often touted as a new treatment in fact it is
  a new way of delivering good old photons
• Means that the dose delivered through the beam
  aperture is different in different locations the
  intensity of the beam is modulated intentionally
• Has allowed increase of dose into the 76-81 Gy
  range

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How to modulate the beam

• Method 1 Dynamic multi-leaf collimator
• Method 2 Individually computer designed brass
  modulators
• Two different approaches that achieve the same
  goal

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MLC in action
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Modulator-Based IMRT

• Multiple beams are designed
• Computer and planning team design each beam
  including how much dose should be delivered
  through each portion of the beam
• For each beam, a brass modulator is designed by
  computer to allow a certain percentage of the
  beam energy to pass through

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• A complete set of modulators for a prostate
  treatment

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IMRT Notes

• Patients usually receive 5-7 beams per day
• Treatment is given 5 days per week for about 8
  weeks
• Patient lies on a table and receives high-energy
  x-rays
• It does not hurt
• Side effects accumulate slowly over time
• Acutely they generally they include mild fatigue,
  urinary irritation, and bowel irritation

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Machine delivering treatment at 21st Century
Oncology
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Part 2. Why IMRT Is Superior to 3D

• Modulating the beam allows for superior control
  of the dose

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3D Dosimetry
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IMRT Dosimetry
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IMRT Dosimetry Prostate Cancer
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Prostate IMRT Post-Prostatectomy
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Part 3. Goal of IMRT

• To deliver higher doses than with 3D technique
  while maintaining or improving the side effect
  profile.

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Side effects

• Definitions
• Late gastrointestinal toxicity
• Grade 2 moderate diarrhea and colic bowel
  movement gt 5x/day intermittent bleeding
• Grade 3 obstruction or bleeding requiring
  surgery
• Late genitourinary toxicity
• Grade 2 moderate frequency intermittent
  hematuria
• Grade 3 severe frequency and dysuria frequent
  hematuria reduction in bladder capacity lt150 cc

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IMRT side effects 1

• Vora et al, Mayo Clinic, 2007
• 416 patients treated with 3D or IMRT
• 3D dose 68.4 Gy
• IMRT dose 75.6 Gy
• Late toxicity
• 3D 68.4 Gy IMRT 75.6 Gy
• Gr 2 GU 17 23
• Gr 3 GU 5 6
• Gr 2 GI 14 23
• Gr 3 GI 2 1
• No significant differences

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IMRT side effects 2

• Su et al (U Chicago) 2006
• Compared 355 pts treated with 3D to 70 Gy with
  106 patients treated with IMRT to 76 Gy
• 3D 70 Gy IMRT 76 Gy
• GI Gr 2 8 3
• GI Gr 3 3 3
• GU Gr 2 21 19
• GU Gr 3 2 4
• Despite higher dose, IMRT patients had the same
  chronic GU toxicity and significantly less GI
  toxicity

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More on Safety Compared to 3D treatment, IMRT
allows us to

• Decrease bowel toxicity and sexual dysfunction
  (Namiki et al 2006)
• Decrease bowel toxicity (Sanguineti et al 2006,
  Jani et al 2006)
• Reduce bowel treated to high dose in whole-pelvic
  RT (Ashman et al 2005, Nutting et al 2000 )
• Spare penile structures and potentially reduce
  sexual dysfunction (Kao 2004)

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ConclusionIMRT allows increased dose with the
same or lower rates of toxicity
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Critical Point for Understanding Radiation Therapy

• Almost any localized tumor can be cured by
  radiation therapy
• All you have to do is administer enough dose

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The Trick

• is to be able to give enough dose without
  excessively damaging the patient
• With some tumors (lung, brain, pancreas) we have
  not been very successful at this
• With prostate cancer, we have made significant
  strides

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Benefits of Dose Escalation 1

• Zeitman et al, 2005, Massachusetts General
  Hospital, Randomized trial
• 393 Patients with localized disease
• Randomized to 70.2 vs. 79.2 Gy
• Boost was delivered via proton beam
• 5 yr PSA control was 80.4 vs. 61.4

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Benefits of Dose Escalation 2

• Peeters et al 2006
• 669 Patients with T1-4 prostate cancer
• Randomized to 68 vs 78 Gy
• FFS improved with higher dose
• 64 vs 54

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What have we learned?

• Answer
• 1. IMRT enables us to deliver higher doses
  safely
• 2. Three randomized trials demonstrate that
  Higher doses are more effective at controlling
  prostate cancer

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Results of IMRT

• Patients should be stratified by risk group
• Low risk PSA lt10, GS lt6, T1 or T2a
• Intermediate Risk PSA 10-20 or GS 7 or T2c
• High Risk PSA gt20 or GS gt8 or T3
• Prognostic value of these groups has been
  validated in numerous studies

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Sloan-Kettering 3D (n743) and IMRT (n772)

• PSA Control Rates
• (Risk group)
• Dose Low Intermediate High
• (Gy) () () ()
• 3D 64-70 59 42 21
• 3D 76 81 60 42
• 3D 81 98 87 70
• IMRT 81-86 92 86 81

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Sloan-Kettering 3D and IMRT

• Toxicity
• Late Grade 2-3 GI toxicity
• MSKCC 3D gt75 Gy 17
• MSKCC IMRT 81-86 Gy 2

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IMRT Results 2 Mayo Clinic Scottsdale

• 271 pts treated with 3D to 68.4 Gy
• 145 pts treated with IMRT to 75.6 Gy
• 5 yr PSA Relapse-Free survival
• 3D 68.4 Gy IMRT 75.6 Gy
• Low 76 87.5
• Int 50.1 72.6
• High 35 60.2

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IMRT Results 3 Ghent, Belgium

• 133 pts treated with IMRT
• Dose 74-76 Gy
• Intermediate and high-risk patients had
  concurrent androgen deprivation
• 5 year PSA relapse-free survival
• Low 100
• Int 94
• High 74

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Results Conclusions

• Dose escalation results in superior control of
  prostate cancers
• IMRT allows delivery of higher doses than 3D
  treatment with equal or reduced side effects
• Published data support excellent results for IMRT

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Sloan-Kettering Recommendations

• Despite the added labor intensity necessary
  for quality assurance and treatment verification
  for the implementation of IMRT, the superior dose
  distributions, resulting in enhanced conformality
  achieved with this technique, make IMRT the
  approach of choice for high-dose radiotherapy
  delivery.
• Zelefsky et al 2002

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Part IV Things to consider about IMRT

• Time Effort
• Longer treatment planning
• Ties up computers
• Physicists need to
• Provide QA, often
• After hours
• Cost

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Treatment Comparisons
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• Low-Risk Patients
• Treatment Study 5 yr PSA control
• Surgery Sharkey 2002 92
• Duke 2002 89
• U Penn 1998 83
• Johns Hopkins 2001 95
• Seeds Seattle 2000 94
• MSKCC 2000 88
• IMRT MSKCC 2006 92
• Mayo 2007 87.5
• Ghent 2007 100

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• Intermediate-Risk Patients
• Treatment Study 5 yr PSA control
• Surgery Sharkey 2002 72
• Duke 2002 69
• U Penn 1998 65
• Johns Hopkins 2001 73
• Seeds Seattle 2000 82
• MSKCC 2000 77
• IMRT MSKCC 2006 86
• Mayo 2007 72.6
• Ghent 2007 94

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• High-Risk Patients
• Treatment Study 5 yr PSA control
• Surgery Sharkey 2002 52
• Duke 2002 40
• U Penn 1998 30
• Johns Hopkins 2001 44
• Seeds Seattle 2000 65
• MSKCC 2000 38
• IMRT MSKCC 2006 81
• Mayo 2007 60.2
• Ghent 2007 74

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Why does IMRT look so good for high-risk patients?

• Chance for extracapsular extension is 60 or
  higher in this group of patients
• IMRT allows us to treat tissue around the
  prostate in addition to the prostate itself
• Surgery and seed implants are more localized
  treatments

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Conclusions

• IMRT allows for safe delivery of higher doses
  compared to prior external radiation treatments
• This has allowed for improved PSA control rates
  and decreased side effects
• These results appear to compare favorably to
  other treatment methods
• IMRT is the preferred method for radiation
  treatment