Dose Escalation By Imrt And Organ Trackingin Prostate Cancer

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

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

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

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)

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

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

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

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

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

Urinary toxicity CTC vs. 2.0

Rectal toxicity CTC vs. 2.0

Results: Conformity

95% isodose

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

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

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

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

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

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

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

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

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.

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