Igrt for cervical cancer feb 8 2013 920 a cancer ci 2013

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  • estimated dose that resulted in a 10% risk of grade 2-4 rectal toxicity was 61.8 Gy
  • Igrt for cervical cancer feb 8 2013 920 a cancer ci 2013

    1. 1. IGRT for Gyn Cancer? Akila N. Viswanathan, MD MPHBrigham and Women’s/Dana-Farber Cancer Center Harvard Medical School
    2. 2. Why use IGRT in Gyne?• Decrease toxicity• Dose escalation• Most important area for IGRT is in image guided brachytherapy
    3. 3. Major Issues with IMRT/IGRT• Need for continual replanning given rapid regression of tumor• High margin for error with tight margins• Increase in integral dose• Longer treatment times
    4. 4. Indications for IMRT/IGRT Cervix• Nodal involvement (pelvic or PAN) – Maximize boost dose• Para-aortic node treatment – Reduce small bowel dose• Boost sidewall in region inaccessible to brachytherapy• Recurrence in radiated area (re-irradiation)• NOT for routine treatment• NOT a replacement for brachytherapy
    5. 5. Mobile uterus, Cervix, NormalTissues
    6. 6. Decrease tumor size @1cm/week
    7. 7. Uterus Contouring• ? Include whole uterus −Account for motion? −Varies with bladder filling −Hard to know where cervix ends and uterus begins
    8. 8. Movement of cervix on CT Beadle et al IJROBP 2009;73:235-41• Center of the cervix: – 2.1 cm superior-inferior – 1.6 cm anterior-posterior – 0.82 right-left lateral Mean maximum changes in the perimeter of the cervix: 2.3 cm and 1.3 cm in the superior and inferior 1.7 cm in the anterior, 1.8 cm in the posterior 0.76 and 0.94 cm in the right and left lateral
    9. 9. Movement on CT• Haripotepornkul NH, Nath SK, Scanderbeg D, Saenz C, Yashar CM. Evaluation of intra- and inter-fraction movement of the cervix during intensity modulated radiation therapy. Radiother Oncol 2011;98:347-51• Tyagi N, Lewis JH, Yashar CM, et al. Daily online cone beam computed tomography to assess interfractional motion in patients with intact cervical cancer. Int J Radiat Oncol Biol Phys 2011;80:273-80• Within and between radiation treatments, cervical motion averaged approximately 3mm in any given direction with maximal movement of the cervix up to 18 mm from baseline
    10. 10. In addition to movement, must account for errors in contouring
    11. 11. RTOG consensus on contouring theCTV for intact cervix patients
    12. 12. Background & Aim• More conformal radiotherapy  accurate target definition important – Cervix Cancer Clinical Target Volume (CTV) definitions variable• Aim: Evaluate the variability in CTV delineation in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group (RTOG). 4F pelvis RT IMRT (12/10)
    13. 13. Methods & Materials• Clinical Case: – 35yo G4P3 – clinical stage 1B poorly differentiated adenocarcinoma of cervix. – No adenopathy or metastatic disease seen on staging investigations. – MRI report confirms no parametrial, uterosacral ligament or myometrial invasion.• MR & CT data sets made available• Participants asked to contour: – GTV – Cervix (if seen) – Uterus – Upper vagina (3cm) – Parametria• Online (ITC RRT; Washington U) or on participant’s treatment planning software.Fig 1. Sample images (sagittal & axial) from clinical case. Figure 1 (13/10)
    14. 14. Results • 19 participants contoured on axial MR images •Sagittal MR & axial CT images available for reference Sensitivity Specificity Kappa Structure (Avg±SD) (Avg±SD) measure* GTV 0.84±0.14 0.96±0.04 0.68§ Cervix 0.55±0.24 0.98±0.03 0.42§ Uterus 0.68±0.22 0.97±0.03 0.57§ Vagina 0.58±0.13 0.99±0.01 0.53§ Parametria 0.48±0.27 0.99±0.02 0.42§*corrected for chance §p-value <0.0001 (14/10)
    15. 15. Results Parametria Vagina Uterus Cervix GTV Kappa ==0.53 Kappa = 0.42 Kappa 0.68 0.57 0.42 Kappa Level of Agreement measure0.81 - 1.00 Almost perfect0.61 - 0.80 Substantial0.41 - 0.60 Moderate0.21 - 0.40 Fair0.01 - 0.20 Slight No agreement 0.00 above chance Complete -1.00 disagreement(Landis JR, Koch GG. 1977) (15/10)
    16. 16. Results – 95% agreement GTV Cervix Vagina UterusParametria CTV CTV consensus consensus (16/10)
    17. 17. • Specificity was high – Greater certainty about what should NOT be included in CTV• Sensitivity was moderate – Greater difficulty determining the interface between various CTV components• Challenging case: – Extreme ante-version of uterus – Ability to view sagittal images• Substantial organ motion, deformation and tumor regression for this site is not addressed in this work.
    18. 18. Parametria &change dependingon volume ofbladder Courtesy of Karen Lim, Princess Margaret Hospital
    19. 19. Assessment of location• Ultrasound: imprecise• kV imaging: rough estimate• Cone beam CT: Intensive resource utilization
    20. 20. IMRT/IGRT• No clear outcome benefit in cervix ca or postop endometrial cancer• Greatest potential benefit in nodal recurrence
    21. 21. Rectal Sparing• May be dangerous due to need to include presacral nodes (mesorectal), uterosacral ligaments, and internal iliac nodes• Rectal filling may vary• NOT recommended
    22. 22. Definitive Contouring• Consider a CTV that includes the uterus/cervix, parametrial tissues, vagina, and pelvic nodes, (common, internal & external, obturator, and iliacs, presacral nodes) with exclusion only of small bowel and some bladder and sigmoid• Need @3cm margin on CTV for uterine PTV; 1.5 cm on CTV cervix for PTV• No sparing of rectum or posterior bladder; potential sparing of small bowel with para- aortic nodal field
    23. 23. Is IMRT/IGRT Ready for Prime Time in the Therapy of Cervical Cancer?• For post-operative therapy – maybe – Still need prospective verification of targets (RTOG 0418) – Rectal movement remains a concern• For definitive therapy in cervical cancer – No • Organ motion and volume changes during therapy remain a significant issue• For para-aortic nodes, spare small bowel• Re-irradiation – unknown sequelae
    24. 24. PET/CT Fusion Nodal ContourIMRT for Nodal boost 54-65 Gy
    25. 25. Post-operative PAN positive no residual LN (45 Gy)
    26. 26. Vaginal recurrence• Pelvic LN+• 45 Gy region• 65 Gy pelvic mass and LN+
    27. 27. SBRT as a boost• Node recurrence, sidewall recurrence• Higher normal tissue dose• Long term complication rate HDR SBRT
    28. 28. SBRT for Recurrent Cervix Ca Dose FailureDeodato et al. 30 Gy/6 fractions 7/11 FAILOncol Repo 22:415-419 2 Grade 4 fistulae1 pt w vaginal recurrence 1 Grade 4 ileusGuckenberger et al. 50 Gy + 5 Gy x 3 Fx 7/10 FAILRad onc 94:53-597 central recurrences
    29. 29. HDR SBRT HDR SBRTImages courtesy of A. Damato
    30. 30. Post-operative IMRT: RTOG Atlas www.rtog.org
    31. 31. Image-Based Brachytherapy for Gynecologic Cancers
    32. 32. Can IMRT replace brachytherapy? NO After 45 Gy EBRT• Complex internal organ motion – Brachy fixed to target• Tumor response• The proximity of critical structures leaves little room for error in EBRT planning
    33. 33. Volume Based TreatmentBrachytherapy IMRTMoves with patient Does not move with patient Difficult to adjust with response
    34. 34. Brachytherapy is Necessary• Tumor control probability correlated with RT dose and cervix ca volume Fletcher, Shukovsky J Radiol Electrol 56:383-400, 1975 External beam only External Beam + brachytherapy4 y PC 45% 67%4 y Survival 19% 46%Lanciano JROBP 20:95, 1991Local Control 40% 52%Montana Cancer 57:148, 1986
    35. 35. Ultrasound• Suspected uterine preforation• Retroverted uterus• Absence of endocervical canal• Extreme anteversion of uterus
    36. 36. What might appear acceptable on Xray, may not be acceptable in 3D Posterior placement Proper placement Viswanathan ASTRO 9/25/08
    37. 37. CT-Based Brachytherapy• CT-simulators available in most radiation oncology departments• Easy transition from film-based dosimetry to CT- based dosimetry
    38. 38. MRI/CT Compatible Applicators•MRI/CT compatible applicators inserted brachytherapy suite Secure fixation of applicator within pt (vaginal packing and perineal bar)
    39. 39. CT-Based Brachytherapy• Rule out uterine perforation
    40. 40. CT-Based Brachytherapy• Assess location and position of applicator relative to the uterus
    41. 41. Use of ContrastDrain bladder bladderClamp foley60 cc of 10%hypaque contrastinto bladder50 cc barium rectumrectum
    42. 42. Organs at Risk:Bladder, Rectum, Sigmoid, Small Bowel Rectum Bladder
    43. 43. CT based targets vs. MR- imaging • GTV – T2 bright areas • HR-CTV – cervix + visible/palpable disease at brachy IR CTV • IR-CTV – 1 cm margin around HR-CTV + initial sites of involvement GTV HR CTV • CT definitions: • CT-CTV – 3cm above applicator • CE (Clinical exam)-CTV – includes vaginal extensionGYN GEC ESTRO Recommendations (I) Radioth.Oncol. 2005, 74:235-245
    44. 44. CT Gyne Brachy Improves Outcomes: Prospective French STIC trial Median Overall Imaging Local Disease Survival (%) Mode of Follow Grade 3-4 # St During control specific treatment up Toxicity BT (%) Survival (%) (years) IB-705 2 IIIB76 BT and Sx Xray 92 87 95 14.689 BT and Sx CT 100 90 96 8.9 ChRT/BT142 Xray 85 73 85 12.5 and SX ChRT/BT163 CT 93 77 86 8.8 and SX118 ChRT/BT Xray 74 55 65 22.7117 ChRT/BT CT 78.5* 60 74 2.6
    45. 45. External beam response DiagnosisMRI 1st fraction Viswanathan ASTRO 9/25/08
    46. 46. Similar OAR contours no significant differences Viswanathan et al. Int J Radiat Oncol Biol, 2005• Width larger on CT – Good for covering parametrium Bladder – No issues with toxicity• Height not determined on MR CT unless referring to an CT HR-CTV MRI – Estimate 3 cm on average – Always treat entire length Rectum of tandem
    47. 47. Brachytherapy exemplifies…• Point versus volume Viswanathan ASTRO 11/3/09
    48. 48. 3D Brachytherapy Outcomes• 145 patients• Historical comparison• Significant ↑ – OS 53 to 64% – CSS 62 to 74% – Tumors > 5cm • OS 28 to 58% Viswanathan ASTRO 11/3/09 Pötter et al. Rad Oncol 2007
    49. 49. Physical-Biological Documentation of Gynecologic HDR BT EQD2: BED/1.2 BED= nd(1+d/alpha-beta ratio) BED: 5.5Gy x 5 (1 + 5.5/10)=42.625 Gy EQD2: 42.625/1.2 = 35.5 Gy
    50. 50. Plan for each HDR fraction required Radioth Oncol 81:269, 2006 Viswanathan ASTRO 9/25/08
    51. 51. HDR/PDR Treatment Planning: Dose OptimizationStandard plan Optimized plan Viswanathan ASTRO 11/3/09
    52. 52. Practical implementation• Standard plan mimics LDR loadings• Optimization superiorly – sigmoid/small bowel – Treat entire tandem length +/- 1cm• Optimization posteriorly - rectum – Watch dwell weight changes carefully • Set to local rather than global • Change individual positions rather than regions• Optimization anteriorly – bladder – Very high doses; no risk to tumor coverage• “Over-coverage” versus “underdosage” Viswanathan ASTRO 11/3/09
    53. 53. Summary• IMRT – CAUTION – OK for nodal boost, PAN treatment, recurrence – Not standard for primary cervical ca – NOT a substitute for brachytherapy – Use image guidance with brachytherapy to reduce toxicity and maximize tumor coverage

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