John Logue

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Radiotherapy

• John Logue

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Radiation Therapy in Locally AdvancedProstate
cancer

• John Logue
• Department of Clinical Oncology
• Christie Hospital
• Manchester

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Necessity of Radiotherapyin Prostate Cancer
Ideal
Benefit
Stage
4
Areas of Equipoise in Radiation Management of
Locally Advanced Prostate Cancer

• Radiation dose/ fractionation
• Radiation Technique
• Use Duration of Hormonal therapy
• Adjuvant systemic therapy

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Is More always better?

• Dose Escalation

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Dose Escalation affects the outcome in Prostate
CancerZelefsky et al IJROBP 413,491, 1998

• Is local control improved by increasing the dose?
  YES

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Phase III Dose Escalation studies

• Dutch 70 vs 76 Gy Completed
• MRC RT01 64 vs 74Gy NAHT completed
• PROG 95-09 70.2GyE vs 79.2GyE
• Pollack Study 70 vs 78 Gy
• Pollack et al J Clin Oncol 2000 18 3904-3911

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PSA lt 10
PSA gt10
Pollack et al J Clin Oncol 2000 18 3904-3911
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3D CRT Dose Escalation
Bladder
PTV
Rectum
CTV
Prostate seminal vesicles
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MDAH TrialToxicityGrade 2 , 3 Rectal Toxicity

• Rectal Volume-70Gy

Dose
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IMRT Widening the Therapeutic Ratio
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Rectal doses for 57Gy plans
.
4 Field CRT
IMRT
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Is More always better?

• Fractionation

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3DCRT Prostate ExperienceIJROBP 575, 1254-9,
2003

• 705 men with prostate cancer
• Treated between 1995-98
• Mean age 68 years (range 49-84)
• T1-4, N0, M0
• 4 field conformal radiotherapy
• PTV-prostate plus all/base of the seminal
  vesicles dependent on risk criteria with a 1cm
  margin
• No neo-adjuvant hormonal therapy
• 50Gy in 16 fractions over 22 days
• Median follow up 48 months (range 1- 82)
• Failure by ASTRO Consensus

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Disease Characteristics

• Number ()
• T1 125 (18)
• T2 365 (52)
• T3/4 215 (30)
• Gleason 2-6 463 (66)
• Gleason 7-10 242 (34)
• PSA lt 10 291 (41)
• 10 to lt 20 228 (32)
• gt20 186 (26)

Median pre treatment PSA 13ng/ml (0.6-270).
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Results

• Number bNED
• Good Prognosis 181 82
• (stage T1/2, PSA lt10ng/ml
• Gleason score lt7)
• Intermediate Prognosis 247 56
• (one raised value)
• Poor Prognosis 277 39
• (2 or more raised values)

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Comparison Of Results 5Year Actuarial PSA RFS
Liebel et al Sem Oncol 2003 305
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Equivalent Doses ?

• a/ß ratio 1.5  
• 50Gy/16 154
• 66Gy/33 154
• 70.2/ 39 154
•  
•  

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Dose Escalation Strategies
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Hypofractionated Dose escalation utilising IMRT
in Prostate cancer ( HIPRO)

• Phase II study
• May 2002 December 2003
• 57Gy
• 30 patients May-Dec 2002
• Median follow up 21 months (19-26)
• 9 Grade I Rectal toxicity
• 60Gy December 2003
• Median Follow up 11 months (8-15)

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HYPOFRACTIONATED DOSE ESCALATION FOR PROSTATE
CANCER (HIPRO)

• ELIGIBILITY
• T2b-T3 N0, M0 carcinoma of prostate
• Gleason score gt6
• PSAgt 10 ng/ml
• NEO-ADJUVANT HT
• DOSE FINDING
• 54Gy, 57Gy, 60Gy

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Class Solution
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Acute Toxicity Comparison
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Rectal Toxicity IMRT

• RTOG late toxicity ()
• Grade 1 2 3
• MSK 81-86.4 Gy 12.6 1.4 0.8
• Christie 57Gy 9 0 0

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Conventional or Hypofractionated High Dose
Intensity Modulated Radiotherapy for Prostate
Cancer CHHIP

• Conventional Fractionations
• 74Gy 37F 7.5 weeks
•  
• T1B - T3A N0 M0
• Risk of LN involvement 30 Hypofractionation
  Schedule 1
• PSA lt40ng/ml 57Gy 19F 3.8 weeks
•  
• Hypofractionation Schedule 2
• 60Gy 20F 4.0 weeks

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Phase III Fractionation Trials
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Optimising Radiation Delivery IGRT

• Elekta SL20 linac
• iView MV imager
• KV imager at 90 deg to gantry head
• Fluoroscopy bony structures and markers
• 3D Cone beam CT images soft tissue structures

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SERIAL XVI PROSTATE
Day 1
Day 2
RTP
Day 3
Day 4
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BAT ULTRASOUND
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Implanted Markers
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HDR Brachytherapy
Dose Escalation Intensity Modulated Brachytherapy
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Current HDR schedules
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Is More always better?
Whole Pelvic XRT
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Whole Pelvic Radiotherapy

• Confounding Retrospective series
• Old Randomised Studies( Stanford, RTOG 77-06)
• Changing Practise
• PCOS 1989 92
• 1994 52
• 1999 23
• Re visited following RTOG 94-13

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RTOG 94-13 RT

• 1323 patients Risk of LN gt 15
• WP RT
• Conventional 4-field technique ( gt16x16cm)
• 50.4 Gy for whole pelvis
• 19.8 Gy for prostate boost
• PO RT
• Limited to prostate and seminal vesicles
• 70.2 Gy
• 4 months HT (NCHT or AHT)

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No difference in 4 yr progression-free survival
for pt with NCHT compared with AHT
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Progression-free survival of WP RT (54.2)
compared with PO RT (47)
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4 yr progression-free advantage for all arm,60,
44, 49, 50
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Areas of Equipoise in Radiation Management of
Locally Advanced Prostate Cancer

• Radiation dose/ fractionation CHIPP
• Radiation Technique HDR
• Pelvic XRT ??
• Duration of Hormonal therapy
• Adjuvant systemic therapy