Predictors of toxicity in single fraction prostate HDR with EBRT. Dr Gail Tsang

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1 Predictors of toxicity in single fraction prostate HDR with EBRT Dr Gail Tsang

2 Methods Fellowship, Sunnybrook Hospital, Toronto Single institutional, prospective study Intermediate risk prostate cancer <=T2b, Gls 7, PSA < 20ng/ml or Gls 6, PSA ng/ml Prostate vol <60cc CT and bone scan clear of metastases No TURP, previous pelvic radiation or androgen ablation therapy

3 Methods Single prostate HDR to 15Gy EBRT 37.5 Gy/ 15 fractions 2 weeks later 123 patients, median follow up 1.95 years Follow up month 1, 3, 6, 12, 18, 24, 36 PSA and exam per visit, TRUS biopsy at 2 yrs Acute toxicity defined as occurring in first 3 m

4 Assessment Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) was used IPSS (International Prostate Symptom Score) for urinary symptoms IIEF ( International Index of Erectile Function) for erectile function Expanded Prostate Cancer Index Composite (EPIC) for health related quality of life, 4 domains: urinary, gastrointestinal, sexual and hormonal

5 Patient characteristics Parameters Value Age 67 ( 51 83) years PSA 6.8 (2-18.6) ng/ml Gleason score 6 9 (7%) (93%) Clinical stage T1c 78 (63%) T2a 41 (33%) T2b 5 (4%) Prostate volume 31 (14 59 ) cc IPSS 5 (0 25)

6 Methods - HDR TRUS guided 14 to 18 transperineal HDR catheters CT compatible markers in catheters, positions relative to fiducial markers noted on PA radiographs PTV = prostate with no margin Fluoroscopic and cone beam imaging, correct catheter displacement prior to treatment delivery Single fraction of 15 Gy to PTV Aim V100 >95%, V150<40%, V200< 14%, Umax < 118%, R max < 80%, B max < 80%

7 HDR dosimetry data Variable CTV vol Median value 44 (17 86) cc V (89 100)% V (5.2 34) % Homogeneity index 0.68 ( ) Umax Rmax Rectal V80 Bmax 20.2 ( ) Gy 17.3 ( ) Gy 0.76 ( ) cc 21.8 ( ) Gy

8 EBRT Planning CT on day after HDR CTV = prostate and lower half of seminal vesicles PTV = CTV with 1 cm uniform margin 4 field, 3D conformal, 18 MV 37.5 Gy /15 fractions, 95% to cover PTV

9 Results All pts complete treatment without interruption Median PSA decrease from median of 6.8 ng/ml to 0.7 ng/ml at 18 months and 0.5 ng/ml at 24 months 16 out of 17 biopsies at 2 yrs showed no malignancy, 1 showed adenocarcinoma and radiation effect

10 Acute toxicity (n=123) Grade GU (1.6%) (35%) (61.8%) (1.6%) Gastro (35%) (58.5%) (6.5%)

11 Late toxicity (n=122) Grade GU (9%) (42.6%) (47.5%) (0.9%) Gastro (48.4%) (41%) (10.6%)

12 Erectile function Gd 1 erectile impotence in 24% of pts Gd 2 in 60%, Gd 3 in 10% of pts Significant difference between baseline and month 12 and 24 Median IIEF score 19 at baseline, 6 at 12 months and 10.5 at 24 months

13 Grade 2+ toxicity Acute Late GU 63.4 % 48.3 % Gastro 6.5 % 10.6 %

14 Acute GU toxicity - 1 Univariate logistic regression analysis Gd 2+ urinary toxicity related to: higher baseline IPSS (p=0.0213) higher V100 (p=0.0013) higher V200 (p=0.0226) lower urinary bother score on EPIC (p=0.0491) No sig. relation to CT vol, Umax, B max

15 Acute GU toxicity - 2 Multivariate logistic regression analysis: Baseline IPSS score (p=0.0056) V100 (p=0.0051) V200 (p=0.0367) Significantly related to acute gd2+ urinary toxicity

16 Acute GU toxicity - 3 Using Receiver Operating Characteristic (ROC) analysis, threshold value above which increases risk of gd 2+ toxicity V100 > V200 > Baseline IPSS >8

17 Acute Gastro. toxicity With univariate logistic regression analysis No variable is significantly related to gd 2+ gastro toxicity Urinary bother score has limited effect on outcome ( p=0.0528)

18 Late GU toxicity - 1 Univariate logistic regression analysis showed late gd 2+ urinary toxicity related to: Higher CTV volume (p=0.0291) Higher baseline IPSS (p=0.0405) lower urinary score (p=0.0063) lower sexual score (p=0.0444) lower urinary function (p=0.0226) lower urinary bother (p=0.0118) Lower sexual function (p=0.0126)

19 Late GU toxicity - 2 Using multivariate logistic regression analysis Gd 2+ toxicity significantly related to: Urinary score (p=0.0151) Sexual function score (p=0.0183) Excluding EPIC scores, CT volume remain significant (p=0.0291) No sig. relationship with Umax, B max

20 Late GU toxicity - 3 Using ROC analysis to find threshold that discriminate pts with late gd 2+ GU toxicity CTV volume > 42.8 Baseline IPSS >14

21 Late Gastro. Toxicity - 1 Using univariate logistic regression analysis, 6 EPIC scores are sig. related to the grade 2+ late gastro. toxicity Lower value of urinary score (p=0.0047) Lower value of hormonal score (p=0.0034) Urinary function (p=0.0307) Urinary bother (p=0.0025) Hormonal function (p=0.0106) Hormonal bother (p=0.0037)

22 Late Gastro. Toxicity - 2 Multivariate logistic regression analysis Only urinary score is sig. related to outcome Other variables not significantly related to the outcome, including CT vol, R max, Rectal V80

23 Conclusion Acute urinary toxicity is associated with baseline IPSS, V100 and V200 Late urinary toxicity is associated with CTV volume No dosimetric or volume variables were associated with acute or late GI toxicity The variables help to better select pts for this regime Longer follow up is required to establish late toxicity Larger sample size and randomised study required to compare with conventional fractionation regime

24 Thank You

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