Dose Escalation By Imrt And Organ Trackingin Prostate Cancer

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Dose Escalation By Imrt And Organ Trackingin Prostate Cancer

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 10. Urinary toxicity CTC vs. 2.0
  11. 11. Rectal toxicity CTC vs. 2.0
  12. 12. Results: Conformity 95% isodose
  13. 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. 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. 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. 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. 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. 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 ia n ce e io rg ur en u nt /u at lg in te cy em A nt re en H co y u ar In eq rin Fr U
  19. 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 io rg ur u nt /u e at lg in te cy em A nt re en H co y u ar In eq rin Fr U
  20. 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 A em nc nt re co ue H y ar In eq rin Fr U Impact of pretreatment symptoms on late toxicity Peeters, IJROBP 2005
  21. 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. 22. Moderation is a fatal thing. . . Nothing succeeds like excess. (Oscar Wilde)

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