Stereotactic body radiotherapy (SIB-VMAT technique) to dominant intraprostatic lesion (DIL) for localized prostate cancer: a dose-escalation trial (DESTROY-4).

PURPOSE: DESTROY-4 (DOSE-ESCALATION STUDY OF STEREOTACTIC BODY RADIATION THERAPY) was a Phase I trial aimed to evaluate the safety and the feasibility of escalating doses of stereotactic body radiation therapy (SBRT) on MRI-defined Dominant Intraprostatic Lesion (DIL) in low- and intermediate-risk pCa patients using a simultaneous integrated boost-volumetric arc therapy (SIB-VMAT) technique. METHODS: Eligible patients included those with low- and intermediate-risk prostate carcinoma (NCCN risk classes) and an International Prostatic Symptoms Score (IPSS) ≤ 15. No restriction about DIL and prostate volumes was set. Pretreatment preparation required an enema and the placement of intraprostatic gold fiducials. SBRT was delivered in five consecutive daily fractions. For the first three patients, the DIL radiation dose was set at 8 Gy per fraction up to a total dose of 40 Gy (PTV1) and was gradually increased in succeeding cohorts to total doses of 42.5 Gy, 45.0 Gy, 47.5 Gy, and finally, 50.0 Gy, while keeping the prescription of 35 Gy/7 Gy per fraction for the entire prostate gland. Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal (GI) or genitourinary (GU) toxicity occurring within 90 days of follow-up (Common Terminology Criteria of Adverse Events scale 4.0). Patients completed quality-of-life questionnaires at defined intervals. RESULTS: Twenty-four patients with a median age of 75 (range, 58-89) years were enrolled. The median follow-up was 26.3 months (8.9-84 months). 66.7% of patients were classified as intermediate-risk groups, while the others were low-risk groups, according to the NCCN guidelines. Enrolled patients were treated as follows: 8 patients (40 Gy), 5 patients (42.5 Gy), 4 patients (45 Gy), 4 patients (47.5 Gy), and 3 patients (50 Gy). No severe acute toxicities were observed. G1 and G2 acute GU toxicities occurred in 4 (16%) and 3 patients (12.5%), respectively. Two patients (8.3%) and 3 patients (12.5%) experienced G1 and G2 GI toxicities, respectively. Since no DLTs were observed, 50 Gy in five fractions was considered the MTD. The median nadir PSA was 0.20 ng/mL. A slight improvement in QoL values was registered after the treatment. CONCLUSION: This trial confirms the feasibility and safety of a total SIB-VMAT dose of 35 Gy on the whole gland and 50 Gy on DIL in 5 fractions daily administered in a well-selected low- and intermediate-risk prostate carcinoma population. A phase II study is ongoing to confirm the tolerability of the schedule and assess the efficacy.

Radiotherapy of Prostate Carcinoma: A Comparison of the Predictive Role of EAU Versus NCCN Risk Stratification Systems.

BACKGROUND/AIM: To compare the predictive efficacy of National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) risk stratification systems in radiotherapy of prostate cancer. PATIENTS AND METHODS: One-thousand-nine-hundred-nine patients treated with definitive (1,074), adjuvant (381), and salvage radiotherapy (454) were analysed. RESULTS: Both systems significantly predicted biochemical-relapse-free-survival, metastasis-free-survival, and disease-free-survival, while only the NCCN system correlated with local-control in the definitive radiotherapy group. In the adjuvant setting, both systems failed to predict all outcomes. In the salvage setting, only the NCCN system significantly predicted biochemical-relapse-free-survival, metastasis-free-survival and disease-free-survival. CONCLUSION: This analysis confirms the efficacy of both systems in definitive radiotherapy and suggests the utility of the NCCN also in salvage radiotherapy.

Optimized stereotactic volumetric modulated arc therapy as an alternative to brachytherapy for vaginal cuff boost. A dosimetric study.

We evaluate the role of stereotactic body radiotherapy using volumetric modulated arc therapy (VMAT) technique as an alternative to high-dose rate brachytherapy (HDR-BT) in the treatment of vaginal cuff in postoperative endometrial cancer. CT scans of 8 patients were used in this study. The clinical target volume (CTV) was defined as the 0.5 cm tissue around the applicator (then subtracting the applicator). Total dose was 30Gy delivered in 5 fractions. In HDR-BT, dose was prescribed at a distance of 0.5 cm from the surface applicator. For VMAT irradiation, a planning target volume (PTV) was obtained from CTV by an expansion of 3 mm. Two VMAT plans were generated using a full arc rotation. The first plan was optimized with an anatomy-based optimization module (PO-VMAT) using a 1mm multileaf collimator beam margin to enhance dose heterogeneity and dose fallout outside the target. The second plan was generated with a full-inverse planning module (FI-VMAT). Conformity (CI100, CI50, CI25), gradient (GI) indexes, and integral doses were calculated. To account for various dose heterogeneity distributions we calculated the equivalent uniform dose (EUD) using the Niemerko model. A Kruskal-Wallis analysis of variance followed by Dunn's-type multiple comparisons was performed. Dose distributions were more heterogeneous with HDR-BT: Dmean was 144.2% of prescription dose for CTV in HDR-BT and 118.5 and 108.6% for PTV in PO-VMAT and FI-VMAT, respectively. The mean values of EUD for CTV were 136.9%, 130.0 %, and 111.0% of prescription dose in HDR-BT, PO-VMAT, and FI-VMAT plans, respectively. GI indexes were 2.81, 3.41, and 4.14 for HDR-BT, PO-VMAT, and FI-VMAT, respectively. Near-maximal doses (D0.1cc) for rectum and bladder were significantly higher in HDR-BT plans compared to PO-VMAT and FI-VMAT plans (rectum: 131.2% vs112.8% vs 112.0%, respectively; bladder: 129.2% vs 108.7%, and 109.8%, respectively). PO-VMAT plans were able to mimic the HDR-BT dose distribution, showing a successful capability of highly conformal dose distribution, EUD values similar to HDR-BT, and steep dose-gradient outside PTV, then providing a reasonable alternative to brachytherapy.

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study.

AIM: To report the outcome of hypofractionated radiotherapy after radical prostatectomy (RP) for prostate cancer (PCa) using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT). PATIENTS AND METHODS: A total of 124 patients with PCa at high risk of relapse after RP or diagnosis of biochemical relapse were included. Patients received 62.5 Gy to the prostate bed and 45 Gy to pelvic nodes in 25 fractions. Androgen-suppressive therapy was prescribed based on National Comprehensive Cancer Network risk categories. RESULTS: Median follow-up was 30 months. Only two patients (1.6%) developed grade 3 or more acute toxicity: one grade 3 skin toxicity (0.8%) and one grade 4 genitourinary toxicity (0.8%). Grade 2 acute gastrointestinal and genitourinary toxicity was recorded in 24.2% and 17.7% of patients, respectively. Five-year grade 2 or more gastrointestinal and genitourinary toxicity was 1.1% and 7.3%, respectively. Five-year biochemical relapse-free survival was 86.5%. CONCLUSION: After RP, hypofractionated IMRT-SIB demonstrated a favorable toxicity profile and encouraging results in terms of relapse-free survival.