Dosimetric Parameters Predictive of Treatment-Related Toxicity in High Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer.

Abstract

High dose-rate (HDR) brachytherapy as monotherapy is an effective treatment for patients with low- and intermediate-risk prostate cancer and is increasingly being offered as a 2-fraction protocol. There is a lack of consensus on the optimal dosimetric planning parameters to use, or whether there is any benefit summating dosimetric parameters from more than one implant. Our goal is to determine planning parameters associated with disease control, toxicity and health-related quality of life (HRQOL). Data were collected on 83 patients with low- and intermediate-risk prostate cancer who received 2 fractions of 13.5 Gy HDR brachytherapy without androgen-deprivation therapy as part of a randomized phase II clinical trial. An in-house deformable, registration algorithm was used to co-register and dose-summate the plans from both implants for each patient. Acute and late GU and GI toxicities were measured using CTCAE 4.0 and HRQOL was measured in urinary, bowel, sexual and hormonal domains using the EPIC scores. Treatment efficacy was assessed through PSA measurement and imaging with or without biopsy where indicated. Covariates included baseline clinical factors, disease characteristics and treatment dosimetric parameters. Cox proportional hazards was performed to evaluate covariates impact on treatment toxicity and efficacy, and logistic regression analysis evaluated covariates impact on HRQOL. Among the 83 patients, median prostate volume was 46.7cm3. Median summated planning target volume receiving 100% prescription dose (PTV V100%) was 97.4%, median PTV V150% 42.4% and median PTV V200% 15.5%. Median highest dose to the 1cm3 rectum (D1cc) was 66.9% of the prescription dose and median rectum V80% was 0.008cm3. Median urethral D1cc was 99.0% of the prescription dose, median urethral Dmax 121.7% and median urethral D10% 116.2%. Grade ≥2 GI toxicity was uncommon (3.7% acute and 8.5% late), but grade ≥2 GU toxicity was reported in 73.2% (acute) and 46.3% (late) patients. Rectum D1cc and V80% were found to be significantly associated with grade 2 or higher acute GI toxicity, while use of a-blocker at baseline was associated with grade ≥2 acute GU toxicity. Similarly, use of a-blocker was associated with late grade ≥2 GU toxicity, but with no dosimetric associations. No other variables were associated with treatment-related toxicities. Only rectum D1cc was significantly associated with changes in bowel EPIC scores. Estimated 5-year biochemical disease-free survival was 93.9% and 5-year cumulative incidence of local failure was 3.8%. HDR monotherapy with 27 Gy delivered in 2 fractions in treatment of prostate cancer is well tolerated with high rates of disease control and minimal toxicity. Dose summation between 2 fractions of HDR brachytherapy is feasible, with rectal dose predicting acute GI toxicity. The lack of association between dose metrics and urinary toxicity raises the potential for further dose escalation.