1. DOSE ESCALATION BY IMRT AND
ORGAN TRACKING
IN PROSTATE CANCER – ACUTE AND
„EARLY LATE“ TOXICITY
Vock J, Kemmerling L, Vetterli D, Manser P, Bigler R, Tille J,
Behrensmeier F, Omlin A, Matzinger O, Gut P, Thalmann S, Mini R,
Greiner RH, Aebersold DM
Department of Radiation Oncology, University of Bern,
Inselspital

2. Background
SASRO 2005:
• 18 patients 80 Gy IMRT/organ tracking
• Assessment of acute toxicity
• Analysis of dose volume histograms
– organs at risk (bladder and rectum)
– planning target volume

3. Objectives
To assess toxicity of dose escalation to 80 Gy
by use of IMRT and organ tracking
• By describing toxicity to rectum and bladder during
treatment and at follow-up of ≥ 6 mo
• By comparing dose volume histograms (bladder wall
and rectal wall) of patients with known constraints
for late toxicity

4. Background – Effect of dose escalation on outcome
Study Dose Effect
Proton boost Shipley, IJROBP 1995 75.6 vs 67.2 Poorly diff. tumours
(rand.) CGE Local control
Zietman, JAMA 2005 79.2 vs 70.2 Biochemical control in low
(rand.) Gy and higher risk group
3D CRT boost Pollack, IJROBP 2002 78 Gy vs Intermediate to high risk
(rand.) 70 Gy FFF
3D CRT Dearneley, BJC 2005 74 vs 64 Gy Biochemical control (ns)
(rand.)
Hanks, IJROBP 2002 Dose (67 – Biochemical control and
(prospective non rand.) 81 Gy) freedom from distant
metastasis
IMRT Leibel, Semin Oncol 81-86.4 Gy vs In all risk categories benefit of
2003 (retrospective) dose escalation (PSA relapse
75.6 Gy vs
free survival)
64.8-70.2 Gy

5. Background – Toxicity and dose escalation
Study Toxicity score Method/constraint Effect
3D CRT Boersma, IJROBP RTOG/EORTC, Rectal wall Cutoff levels for
1998 LENT/SOMA V 65 40% severe rectal
(adapted) V 70 30% bleeding
V 75 5%
IMRT Leibel, Semin Oncol RTOG 81 Gy IMRT vs Grade 2-3 late
2003 81 Gy 3D CRT rectal bleeding
Grade 2(-3) late
75.6-81 vs 64.8-70.2
rectal bleeding
3D CRT
86.4 vs 81 Gy IMRT
Constraints
Rectal wall V 47 <53%
Bladder wall V 47 <53%

6. Patients and Methods
• 42 prostate cancer patients treated with 80 Gy
(IMRT and organ tracking) between 06/2004 and
12/2005
34 patients with follow-up of ≥ 6 months (median 9,
•
range 6–16) included in this presentation
• Median age 68 (54–82) years
• Risk of recurrence:
18 pts high, 8 intermediate, 8 low
NCCN guidelines, www.nccn.com
• 24/34 pts concomitant androgen deprivation

7. Patients and Methods
• Implantation of 3 fiducial
gold markers into
prostate guided by
endorectal ultrasound
before IMRT planning
• MRI/planning CT image fusion in 28/34 patients
CTV = prostate ± base of seminal vesicles
•
(included if risk of seminal vesicle involvement
> 15%, 19/34 pts)
Roach III: PSVinvolvement = PSA + (Gleason score – 6) x 10
Roach, J Urol 1993

8. Patients and Methods
• PTV = CTV and 3/5 mm margins
Vetterli, Radiother Oncol 2006 (accepted)
• Inverse planning and DVH analysis using Eclipse®
TPS
• IMRT delivered by dynamic MLC / sliding window
• Organ tracking: daily use of EPID with dose saving
acquisition mode
RadMode Vetterli, Med Phys 31 (4), April 2004

9. Patients and Methods
Urinary and rectal symptoms scored according
to the CTC scale (version 2.0)
• Before treatment onset
• During treatment
• At a median follow-up of 9 (6-16) months

10. Urinary toxicity CTC vs. 2.0

11. Rectal toxicity CTC vs. 2.0

12. Results: Conformity
95% isodose

13. DVH Rectal mucosa
Volume [%]
Median and range of 42 patients
100
90
80
70
60
< 53 % ¹
50
< 40 % ²
40
< 30 % ²
30
20
15.1
<5%²
10 9.4 7.3
3.8
0
0 10 20 30 40 50 60 70 80
Dose [Gy]
= Constraints for grade ≥ 2 toxicity
¹ Leibel et al, Semin Oncol, 2003; ² Boersma et al, IJROBP, 1998

14. DVH Bladder wall
Volume %
Median and range of 42 patients
100
90
80
70
60
< 53 %
50
40
27,9
30
20
10
0
0 10 20 30 40 50 60 70 80
Dose [Gy]
= Constraints for grade ≥ 2 toxicity
Leibel et al, Semin Oncol, 2003

15. Rectal toxicity
Rectal symptoms during treatment
(34 patients)
100
Percent of patients
90
80
70
Grade 1
60
50 Grade 2
40 Grade 3
30
20
10
0
Diarrhea Rectal pain Rectal
bleeding

16. Rectal toxicity
Rectal symptoms at follow-up
(34 patients)
100
Percent of patients
90
80
70
Grade 1
60
50 Grade 2
40 Grade 3
30
20
10
0
Diarrhea Rectal pain Rectal
bleeding

17. Rectal toxicity
Grade 1 or more rectal symptoms before treatment,
during treatment and at follow-up (34 patients)
100
Percent of patients
90
80
70
pretreatment
60
50 acute
40 follow-up
30
20
10
0
Diarrhea Rectal pain Rectal
bleeding
Hemorrhoids = risk factor for late rectal bleeding
Cheung, IJROBP 2004

18. Urinary toxicity
Urinary symptoms during treatment
(34 patients)
100
Percent of patients
90
80
70
Grade 1
60
50 Grade 2
40 Grade 3
30
20
10
0
ria
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19. Urinary toxicity
Urinary symptoms at follow-up
(34 patients)
100
Percent of patients
90
80
70
Grade 1
60
50 Grade 2
40 Grade 3
30
20
10
0
ia
ria
n
e
e
nc
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co
y
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ar
In
eq
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Fr
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20. Urinary toxicity
Grade 2 or more urinary symptoms
before treatment, during treatment and at follow-up
(34 patients)
100
Percent of patients
90
80
70
pretreatment
60
50 acute
40 follow-up
30
20
10
0
n
ia
ge
ce
ia
io
ur
ur
en
ur
nt
lg
at
y/
in
te
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em
nc
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re
co
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H
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ar
In
eq
rin
Fr
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Impact of pretreatment symptoms on late toxicity
Peeters, IJROBP 2005

21. Conclusion
• Dose-escalated IMRT with 80 Gy and organ tracking
is generally well tolerated.
It leads to limited acute and „early late“ urinary
toxicity and minimal rectal toxicity.
• Follow-up studies to assess long-term toxicity (and
efficacy) are necessary.

22. Moderation is a fatal thing. . .
Nothing succeeds like excess.
(Oscar Wilde)