Dose Escalation By Imrt And Organ Trackingin Prostate Cancer
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Transcript of Dose Escalation By Imrt And Organ Trackingin Prostate Cancer
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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
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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
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Objectives
To assess toxicity of dose escalation to 80 Gyby 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
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Background – Effect of dose escalation on outcome
Study Dose Effect
Proton boost Shipley, IJROBP 1995 (rand.)
75.6 vs 67.2 CGE
Poorly diff. tumoursLocal control
Zietman, JAMA 2005 (rand.)
79.2 vs 70.2 Gy
Biochemical control in low and higher risk group
3D CRT boost Pollack, IJROBP 2002(rand.)
78 Gy vs70 Gy
Intermediate to high riskFFF
3D CRT Dearneley, BJC 2005 (rand.)
74 vs 64 Gy Biochemical control (ns)
Hanks, IJROBP 2002 (prospective non rand.)
Dose (67 –81 Gy)
Biochemical control and freedom from distant metastasis
IMRT Leibel, Semin Oncol 2003 (retrospective)
81-86.4 Gy vs75.6 Gy vs64.8-70.2 Gy
In all risk categories benefit of dose escalation (PSA relapse free survival)
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Background – Toxicity and dose escalation
Study Toxicity score Method/constraint Effect
3D CRT Boersma, IJROBP 1998
RTOG/EORTC, LENT/SOMA (adapted)
Rectal wallV 65 40%V 70 30%V 75 5%
Cutoff levels for severe rectal bleeding
IMRT Leibel, Semin Oncol 2003
RTOG 81 Gy IMRT vs81 Gy 3D CRT
75.6-81 vs 64.8-70.2 3D CRT86.4 vs 81 Gy IMRT
Rectal wall V 47 <53%Bladder wall V 47 <53%
Grade 2-3 late rectal bleeding
Grade 2(-3) late rectal bleeding
Constraints
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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 lowNCCN guidelines, www.nccn.com
• 24/34 pts concomitant androgen deprivation
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Patients and Methods
• Implantation of 3 fiducialgold 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 10Roach, J Urol 1993
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Patients and Methods
• PTV = CTV and 3/5 mm marginsVetterli, 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 modeRadMode Vetterli, Med Phys 31 (4), April 2004
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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
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Urinary toxicity CTC vs. 2.0
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Rectal toxicity CTC vs. 2.0
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Results: Conformity
95% isodose
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DVH Rectal mucosaMedian and range of 42 patients
15.19.4 7.3 3.80
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80Dose [Gy]
Volume [%]
= Constraints for grade ≥ 2 toxicity
< 53 % ¹< 40 % ²
< 30 % ²
< 5 % ²
¹ Leibel et al, Semin Oncol, 2003; ² Boersma et al, IJROBP, 1998
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DVH Bladder wallMedian and range of 42 patients
27,9
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70 80Dose [Gy]
Volume %
= Constraints for grade ≥ 2 toxicity
< 53 %
Leibel et al, Semin Oncol, 2003
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Rectal toxicity
Rectal symptoms during treatment(34 patients)
0102030405060708090
100
Diarrhea Rectal pain Rectalbleeding
Perc
ent o
f pat
ient
s
Grade 1Grade 2Grade 3
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Rectal toxicity
Rectal symptoms at follow-up(34 patients)
0102030405060708090
100
Diarrhea Rectal pain Rectalbleeding
Perc
ent o
f pat
ient
s
Grade 1Grade 2Grade 3
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Rectal toxicity
Grade 1 or more rectal symptoms before treatment, during treatment and at follow-up (34 patients)
0102030405060708090
100
Diarrhea Rectal pain Rectalbleeding
Perc
ent o
f pat
ient
s
pretreatmentacutefollow-up
Hemorrhoids = risk factor for late rectal bleedingCheung, IJROBP 2004
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Urinary toxicity
Urinary symptoms during treatment(34 patients)
0102030405060708090
100
Frequen
cy/urg
eUrin
ary re
tentio
n
AlguriaHem
aturia
Incontin
ence
Perc
ent o
f pat
ient
s
Grade 1Grade 2Grade 3
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Urinary toxicity
Urinary symptoms at follow-up(34 patients)
0102030405060708090
100
Frequen
cy/urg
eUrin
ary re
tentio
n
AlguriaHem
aturia
Incontin
ence
Perc
ent o
f pat
ient
s
Grade 1Grade 2Grade 3
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Urinary toxicity
Grade 2 or more urinary symptomsbefore treatment, during treatment and at follow-up
(34 patients)
0102030405060708090
100
Frequen
cy/urg
eUrin
ary re
tentio
n
AlguriaHem
aturia
Incontin
ence
Perc
ent o
f pat
ient
s
pretreatmentacutefollow-up
Impact of pretreatment symptoms on late toxicityPeeters, IJROBP 2005
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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.
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Moderation is a fatal thing. . . Nothing succeeds like excess.(Oscar Wilde)