External Beam RT IN CArcinoma PROSTATE.pptx

external beam radiotherapy planning in case of carcinoma prostate.

1. EBRT IN PROSTATE CANCER BY- Dr. Pallavi Jain

2. CONTENTS Indication of EBRT Ebrt planning and delivery techniques- 2D 3D CRT IMRT Rt dose Dose escalation in ca prostate Hypofractionation in ca prostate Emerging modalities in prostate ca treatment IGRT Proton

3. Treatment algorithm for very low risk group ( NCCN guideline) 3

4. ACTIVE SURVEILLANCE1 • Active surveillance involves actively monitoring the course of disease with the expectation to intervene with curative intent if the cancer progresses. PSA = 6 monthly DRE = 12 monthly Biopsy = 12 monthly MRI = 12 monthly Observation involves monitoring the course of prostate cancer with the expectation to deliver palliative therapy for development of symptoms Goal of observation is to maintain QOL by avoiding non curative treatment when prostate cancer is unlikely to cause mortality or significant morbidity

5. How to calculate life expectancy Social Security Administration tables WHOs life tables by country 5

6. Treatment algorithm for low risk group ( NCCN guideline) 6

7. Treatment Options for Intermediate Favorable Risk Group 7

8. Treatment Options for Intermediate Unfavorable Risk Group 8

9. Treatment Options for High and Very High Risk Group 9

10. Indications for RT T N0 N1 M1 PSA GS SURVELLIANCE SURGERY Radical RT Radical Brachytherapy HT T1a + <10 <6 YES RP+ PLND RT BRACY T1b + <10 <6 YES RP+ PLND (<2% +ve nodes) RT BRACY T1c + <10 <6 YES RP+ PLND (>2% +ve nodes) RT BRACY T2a + RT + ADT T2b + RT + ADT T2c + 10 to 20 7 YES RP+ PLND RT + ADT + BRACHY BOOST BRACY Y T3a + >20 8to 10 RP+ PLND RT + ADT BRACHY BOOST Y T3b + RT + ADT BRACHY BOOST Y T4 + RT + ADT BRACHY BOOST ADT Any T + RT + ADT Y Any T / N + RT ADT

11. Indications for radical RT in Ca Prostate T1b, T2, T3 LN involvement detected by nodal sampling Risk of LN involvement ≥ 15% Documented SVI Gleason score ≥6 high intermediate risk (>50% + biopsies)

12. Roach formula: Percentage risk of seminal vesicle involvement = PSA + [(GS - 6) × 10] Percentage risk of LN involvement = 2/3 PSA + [(GS - 6) × 10]

13. Rationale: Increased local control eradicating microscopic periprostatic disease/ decresed distant mets / improved survival Local failure as a function of site and post op RT Site Without RT (%) With RT(%) SVI + 45 14 Capsule + 31 12 Margins + 25 1 Adjuvant RT: after Radical Prostatectomy Roach et al 2003 IJROBP

14. Indicat ions: pT3/4 Close & + ve margin Extra Capsular extension  Invasion to Seminal vesicle Extraprostatic extensions Multiple nodes Poorly diff Ca R 1 resection Pre OP PSA > 10ng/ml Pre OP PSA velocity > 2ng/ml/year  Post RP – Recurrent disease  Post RP - early PSA failures

15. Advantages of pelvic EBRT: Primary lesion along with periprotatic tissue and pelvic LNs are homogenously irradiated Surgical complication avoided Good local control

16. ebRT TECHNIQUES 2 D 3 D Conformal IMRT Rapid arc IGRT Tomotherapy CK SRS / SRT SBRT Proton

17. Mostly patients are treated supine with knee rest or vac lock to consistently align thighs. Alternatively, patients may be treated prone with thermoplastic shell immobilization. However, a randomized trial by Bayley et al. (2004) noted that there was significantly less prostate motion in the supine position and that the prone position resulted in increased dose to critical structures. For simulation, patients are instructed to have a full bladder and an empty rectum (following an enema). IV contrast help in better LN delineation. Rectal marker may be placed. CT Simulation

18. Four Field – AP/PA portals Treatment Volume- Prostate, SV, prostatic urethra and margin of 1-1.5cm for T 1- T 2 lesion and pelvic LNs to be included if the lesion is T 3 Field size : 15X15 cm (approx.) Superior border- L 5 -S 1 Inferior border- 1.5-2 cm distal to junction of prostatic and membranous urethra (lower border of ischial tuberosity) Lateral border- 1.5-2 cm lateral to bony pelvis CONVENTIONAL EBRT PORTALS

19. Anterior margin-0.5 to 1 cm posterior to projected cortex of Symphysis pubis. Posterior margin-S 2-3 interspace to include the upper presacral LNs

20. Boost Field Prostate+ SV- 12X14 cm(approx.) Superior border extend to the top of the acetabulum 3-5 cm above pubis Inferior border – caudal to ischial tuberosity Laterally to include 2/3 of the obturator foramen Anterior border 1.5 cm posterior to ant . margin of pubic symphysis Posterior border 2 cm behind the rectal marker

21. Dose- 66-72.4 Gy/7wk@ 1.8-2 Gy/# 45-50 Gy/5wk to whole pelvis followed by a boost of 20 Gy to the prostate

22. 3D- CRT Target Low Risk Disease Intermediate Risk High Risk Primary CTV Prostate +/ - Proximal SV Prostate + Proximal SV Prostate + Gross extracapsular disease + Entire SV Nodal CTV -- optional B/l Internal + External Iliac + obturator + presacral LN Practical Essential of IMRT – Chao et al GTV – Includes the primary tumor in prostate CT simulation alone may result in 30-40% overestimation of prostatic volume MRI may help to identify apex , base and neurovascular bundle more precisely Use of MR spectroscopy for this has been investigational Krempien et al IJROBP 2002;53(5) 1350-60 Roach et al Oncology 2001

23. 24 Penile bulb Apex of prostate contoured on CT Apex of prostate contoured on MRI

24. 25 Contouring of mid prostate on CT and MRI Mid prostate on CT scan Rectum Mid prostate on MRI

25. Contouring of base of prostate on CT and MRI No inclusion or inclusion of proximal 1.4 cm of the SV (in the axial plane) according to institutional policy 26

26. RTOG GU Consensus on pelvic LN CTV volumes Commence contouring the pelvic CTV LN volumes at the L5/S1 interspace (the level of the distal common iliac and proximal presacral LN). Place a 7-mm margin around the iliac vessels connecting the ext. and internal iliac contours on each slice, carving out bowel, bladder, and bone. (Lawton et al. 2008; Lawton et al. 2012)

27. Contour presacral lymph nodes (subaortic only) S1 through S3, posterior border being the ant. sacrum, and ant. border approximately 10 mm ant. to the ant. sacral bone carving out bowel, bladder, and bone.

28. Stop external iliac CTV LN contours at the top of the femoral heads (bony landmark for the inguinal ligament). Stop contours of the obturator CTV LN at the top of the pubic.

29. PTV = CTV + 1-cm margin in all directions except posteriorly at the interface with the rectum, where the margin is reduced to 0.6 cm. Rationale: Expected movement with respiration : Craniocaudal – 1-1.2 cm A-P - 0.5 cm Lateral- 0.7cm

30. 3D- CRT Standard 3D conformal beam arrangement- six coplanar fields, including two lateral, two anterior and two posterior oblique beams 6-field plan, the two lateral beams typically deliver ~1/2 of the dose to the isocenter with the four oblique beams contributing the rest. The beam weights of the anterior oblique and posterior oblique beams adjusted to obtain a uniform dose within the PTV and to place the hot spots away from the rectum

31. Axial (left) and Coronal (right) Isodose Distribution by 3DCRT

32. CTV – Adjuvant RT In the p/o setting, the CTV is based on preop imaging, histopathologic size of the prostate, tumor extent, surgical margins, and input from the Urologist. CTV Extension – EORTC 22911 Superior : just above pubic symphysis anteriorly and including surgical clips or 5 mm above inferior border of vas deferens. Inferior : top of penile bulb or 8 mm below vesicourethral anastamosis . Anterior : posterior edge of pubic symphysis including entire bladder neck until above symphysis. Posterior : anterior aspect of rectum and mesorectal fascia. Lateral : medial edge of obturator internus muscles. PTV expansion: 0.6–1.5 cm

33. IMRT IMRT may be used for both whole pelvic and boost portions of treatment. With whole pelvic IMRT, careful review of lymph node mapping is recommended. IMRT provides more conformality with tight dose constraints for bladder, rectum and head of femur with a scope for dose escalation with out compromising acute and late toxicity. Shih et al.2005; Taylor et al. 2005; Chao and Lin 2002.

34. IMRT dose constraints Bladder V75 <25%, V70 <35%, V65 <25–50%, V55 <50%, V40 <50%. Rectum V75 <15%, V70 <20–25%, V65 <17%, V60 <40%, V50 <50%, V40 <35–40%. Femoral heads: V50 <10%, Dmax = 66 Gy Penile bulb: Mean dose <52.5 Gy In addition to DVH analyses, a slice by slice (axial and sagittal) analysis of the isodose lines was done to ensure that the 90% isodose line falls within the half width margin of the rectum and 50% isodose line falls within the full width of the rectum on all axial slices Practical Essential of IMRT – Chao et al

35. WHY IMRT

36. DOSE OF RADIOTHERAPY

37. Best results with high dose external Cure Rate (PSA cure) in 2991 : Zelefsky et al

38. Years Prostate Cancer Relapse Rate by Radiation Dose < 72Gy 72 - 82Gy 82Gy Kupelian . IJROBP 2008:71:16

39. Dose Escalation

40. DOSE OF RADIOTHERAPY Conventional Fractionation :

41. Hypofractionation In Prostate Ca Two major approaches • Moderate hypofractionation 2.5 – 3.5 Gy/# • Extreme hypofractionation/ Ultrahypofractionation > 5 Gy/#

42. Inclusion Criteria : PS 0-1 T1b–T3aN0M0 GS <8 PSA < 30 ng / mL Risk of SV invol < 30% All received 6 months of androgen deprivation therapy before and during RT Treatment Arms- 74Gy/37# 60Gy/20# 57Gy/19# Result :  60 Gy was non-inferior to 74 Gy No significant differences in OS  Evaluation of the lower 57 Gy was inconclusive: it cannot be stated to be non-inferior to the 74 Gy but it was inferior to the 60 Gy group 44

43. Moderate hypofractionation trials Trial Risk group Arms EQD2 (1.8) Primary outcome Result CHHiP (n - 3216) LR – 15% IR – 73% HR – 12% 74Gy/37# (1065) 60Gy/20# (1074) 57Gy/19# (1077) 74 75.8 72 Biochem – clinical failure 1.Standard arm 2.Non inferior 3.Not non-inf PROFIT (n- 1204) IR 78Gy/39# (598) 60Gy/20# (407) 78 75.8 Biochem – clinical failure 1.Standard arm 2.Non inferior RTOG 0415 (n – 1067) LR 73.8Gy/41# (542) 70Gy/28# (550) 69.9 79.2 DFS 1.Standard arm 2.Non inferior HYPRO (n – 800) IR – 26% HR – 74% 78Gy/39# (397) 64.5Gy/19# (407) 78 88.2 RFS 1.Standard arm 2.Not superior

44. Acute Toxicity Trial Arms EQD2 (10) Peak acute toxicity (Grade II or more) GU (%) p value GI (%) p value CHHiP (n - 3216) 74Gy/37# (1065) 60Gy/20# (1074) 57Gy/19# (1077) 74 65 61.8 46 49 46 - NS NS 25 38 38 - S S PROFIT (n- 1204) 78Gy/39# (598) 60Gy/20# (407) 78 65 27 27 - NS 10 16 - S RTOG 0415 (n – 1067) 73.8Gy/41# (542) 70Gy/28# (550) 72.6 72.9 24.7 23.7 - NS 9.7 9.9 - NS HYPRO (n – 800) 78Gy/39# (397) 64.5Gy/19# (407) 78 72 58 61 - NS 31 42 - S S – Significant; NS – Non significant Acute Toxicity

45. Irrespective of the peak acute toxicity, the rates of toxicity at the end of 3 months were similar in all studies

46. comments • In men with LR and IR prostate cancer with or without radiation to the seminal vesicles, • In men with HR prostate cancer, moderate hypofractionation should be offered if pelvic nodes are planned to be excluded. Acute and Late toxicities are comparable to conventional RT. Discuss the limited follow-up beyond five years for most of existing RCTs.

47. • Regimens suggested: • 60Gy delivered in 20 fractions of 3Gy • 70Gy delivered in 28 fractions of 2.5Gy One optimal regimen cannot be determined since fractionation schemes have not been compared head to head • Efficacy of moderately hypofractionated EBRT regimens does not appear to be impacted by • patient age, -- comorbidity, • anatomy, -- urinary function

48. Extreme hypofractionation ( Ultrahypofractionation )

49. Extreme hypofractionation trials Trial Risk group Arms EQD2 (1.8) Primary outcome Result HYPO–RT–PC (n - 1200) IR – 89% HR – 11% 78Gy/39# (591) 42.7Gy/7# (589) 78 88.8 Biochem – clinical failure 1.Standard arm 2.Non inferior Munsuru et al (n- 582) LR 76Gy/38# (66) 35Gy/5# (84) 76 81.1 6yr Bioch – clinical failure Not reported Katz et al. (n – 515) LR – 63% IR – 30% HR – 7% 35 – 36.25 Gy/5# (515) 81.1 – 86.3 8yr DFS 1.93.6% 2.84.3% 3.65.0% Loblaw et al. (n – 602) LR 74 – 79.8Gy/37 – 42# (40) 35Gy/5# (40) 74 – 78 81.1 6yr bFFS 1.Standard arm 2.Better sig

50. Late Toxicity Trial Arms EQD2 (3) Cumulative late toxicity (Gr. II or more) GU (%) p value GI (%) p value HYPO–RT–PC (n - 1200) 78Gy/39# (591) 42.7Gy/7# (589) 78 77.7 18 17 - NS 10 10 - NS Munsuru et al. (n- 582) 76Gy/38# (66) 35Gy/5# (84) 76 70 19.7 12 - S 7.6 4.8 - S Katz et al. (n – 515) 35 – 36.25 Gy/5# (515) 70 74.3 - 1.7 - Loblaw et al. (n – 602) 74 – 79.8Gy/37 – 42# (40) 35Gy/5# (40) 74 – 78 70 - 1 - - 1 - - Only RCT; data is for 5 year followup S – Significant; NS – Non significant

51. In men with LR and IR prostate cancer ultrahypofractionation may be offered In men with HR prostate cancer, ultrahypofractionation should not be offered due to insufficient data The recommendations apply to – prostate volume < 100 cc – Mild to moderate urinary symptoms at baseline (IPSS < 20)

52. Regimens suggested: – 3500 to 3625 cGy in 5 fractions of 700 to 725 cGy may be offered to low- and intermediate-risk patients with prostate sizes less than 100 cm3. Five-fraction doses above 3625 cGy to the planning target volume is not suggested due to risk of late toxicity Five-fraction prostate ultrahypofractionation using consecutive daily treatments is not suggested due to potential increased risk of late urinary and rectal toxicity

53. NCCN recommended dose fractionation

54. Image Guided Radiotherapy(IGRT)

55. Image guidance Given susceptibilities for organ deformation, and intra- and interfraction organ motion, EBRT is typically combined with: Ultrasound KV or MV cone-beam CT Feducials implants Transponders (calypso system)

56. B-Mode Acquisition and Targeting system Rationale: emission of high frequency sound waves to produce images of internal anatomy. transducer is encased in a probe applied to the skin surface, reflecting sound waves back as echoes when a change in impedance is encountered due to density differences between tissues. The time an echo takes to return is used to calculate the depth of tissue interface. USG (BAT system)

57. 60 CBCT or MVCT Techniques integrates imaging with LINAC. Visualization of exact tumor localization. Acquiring multiple planar images produced by KV or MV cone beam rotating 360 degree .around the patients. Filtered back projection algorithm is used to reconstruct the volumetric images of target volume. Disadv : cannot be used to obtain intrafractional motion information

58. Used to monitor motion during radiotherapy treatment •Detector's position is tracked by optical cameras •Allows near real-time continuous tracking without using ionizing radiation •Requires invasive procedure for implantation Fiducial implantation

59. Conventional ct scanner housed in the treatment room and shares the couch with the accelerator. Images can be taken before each treatment. Couch moved in axial direction to take ct images. Couch is rotated back into alignment with the accelerator gantry for treatment. Neither the couch nor the patient is moved realtive to the treatment isocenter. Adv: High resolution 3-D volumetric data of patient anatomy in the treatment Coordinates- 1) useful in target localization prior to treatment 2) reconstructing dose distribution (ADAPTIVE RADIOTHERAPY) CT on rails

60. Transponders •Based on real time localization of electromagnetic transponders implanted into the tumor. * Transponders: tiny oscillating circuits (1.8 x 8.6 mm2) When excited by an electromagnetic field, emit a unique resonant frequency signal - DETECTED BY MAGNETIC ARRAY POSITIONED CLOSE TO THE PATIENT. - Magnetic array: Source coils - generate signals to excite the transponders Sensor coils-receive unique frequency signal returned by the responders. •Fast enough to track tumour motion during treatment. ELECTROMAGNETIC FIELD TRACKING:

61. Lower Risk of Side Effects with Image Guided IMRT compared to IMRT

62. Better Cure Rates with Image Guided IMRT compared to IMRT for Prostate Intermediate Risk High Risk

63. SBRT in prostate cancer 68

64. S tereotactic radiotherapy (SRT) are techniques to administer precisely directed, high-dose irradiation that tightly conforms to target to create a desired radiobiologic response while minimizing radiation dose to surrounding normal tissue . (Perez and brady 7 th edition) Delivered in 1-5 fractions/stages Based on the use of image-guided approaches 69

65. Potential to improve Therapeutic window Higher local control Better QOL Shorter treatment course

66. Most studies includes low and intermediate risk patients Doses are variable. Most common dose 36.25 Gy in 5 fractions Some prospective trials uses higher doses >40Gy in 5 Fr. bRFS are comparable to conventional in most studies IGRT is advisable (ASTRO) Studies have used different techniques and machines -  (Outcome is not different among 3D / CYBERKNIFE/ IGRT)

67. Thank you