Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer.

Purpose: High-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. Methods: Patients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. Results: We recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. Conclusion: SIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study.

BACKGROUND: Intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation. MATERIAL AND METHODS: We used data from the "RCMI pelvis" prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting. RESULTS: The mean total cost for HT, €2019 3,069 (95% CI, 2,885-3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443-2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment. CONCLUSION: Use of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.

Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial.

PURPOSE: The optimal frequency of prostate cancer image guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. MATERIALS AND METHODS: This phase 3 randomized trial recruited patients with N0 localized prostate cancer. The total IGRT doses in the prostate ranged from 70 Gy to 80 Gy, sparing the lymph nodes. Patients were randomly assigned (1:1) to 2 prostate IGRT frequency groups: daily and weekly (ie, on days 1, 2, and 3 and then weekly). The primary outcome was 5-year recurrence-free survival. Secondary outcomes included overall survival and toxicity. Post hoc analyses included biochemical progression-free interval, clinical progression-free interval, and other cancer-free interval. RESULTS: Between June 2007 and November 2012, 470 men from 21 centers were randomized into the 2 groups. Median follow-up was 4.1 years. There was no statistically significant difference in recurrence-free survival between the groups (hazard ratio [HR] = 0.81; P = .330). Overall survival was worse in the daily group than in the weekly group (HR = 2.12 [95% confidence interval (CI), 1.03-4.37]; P = .042). Acute rectal bleeding (grade ≥1) was significantly lower in the daily group (6%) (n = 14) than in the weekly group (11%) (n = 26) (P = .014). Late rectal toxicity (grade ≥1) was significantly lower in the daily group (HR = 0.71 [95% CI, 0.53-0.96]; P = .027). Biochemical progression-free interval (HR = 0.45 [95% CI, 0.25 - 0.80]; P = .007) and clinical progression-free interval (HR = 0.50 [95% CI, 0.24-1.02]; P = .057) were better in the daily group, whereas other cancer-free interval was worse in the daily group (HR = 2.21 [95% CI, 1.10-4.44]; P = .026). CONCLUSIONS: Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.

2D EPID dose calibration for pretreatment quality control of conformal and IMRT fields: A simple and fast convolution approach.

PURPOSE: This work presents an original algorithm that converts the signal of an electronic portal imaging device (EPID) into absorbed dose in water at the depth of maximum. METHODS: The model includes a first image pre-processing step that accounts for the non-uniformity of the detector response but also for the perturbation of the signal due to backscatter radiation. Secondly, the image is converted into absorbed dose to water through a linear conversion function associated with a dose redistribution kernel. These two computation parameters were modelled by correlating the on-axis EPID signal with absorbed dose measurements obtained on square fields by using an ionization chamber placed in water at the depth of maximum dose. The accuracy of the algorithm was assessed by comparing the dose determined from the EPID signal with the dose derived by the treatment planning system (TPS) using the ϒ-index. These comparisons were performed on 8 conformal radiotherapy treatment fields (3DCRT) and 18 modulated fields (IMRT). RESULTS: For a dose difference and a distance-to-agreement set to 3% of the maximum dose and 2 mm respectively, the mean percentage of points with a ϒ-value less than or equal to 1 was 99.8% ± 0.1% for 3DCRT fields and 96.8% ± 2.7% for IMRT fields. Moreover, the mean gamma values were always less than 0.5 whatever the treatment technique. CONCLUSION: These results confirm that our algorithm is an accurate and suitable tool for clinical use in a context of IMRT quality assurance programmes.

Cost of prostate image-guided radiation therapy: results of a randomized trial.

PURPOSE: This cost analysis aimed to quantify the cost of IGRT in relation to IGRT frequency and modality with Cone Beam Computed Tomography (CBCT) or orthogonal electronic portal imaging with fiducial markers (EPI-FM). MATERIAL AND METHODS: Patients undergoing IGRT for localized prostate cancer were randomized into two prostate control frequencies (daily or weekly). Costs were calculated based on the micro-costing results according to hospitals' perspectives (in Euros, 2009) and the time horizon was radiation therapy. RESULTS: A total of 208 patients were enrolled in seven French cancer centers. A total of 6865 fractions were individually analyzed. The mean total treatment fraction duration was 21.0 min for daily CBCT and 18.3 min for daily EPI-FM. Increasing the control frequency from weekly to daily increased the mean treatment fraction duration by 7.3 min (+53%) for CBCT and 1.7 min (+10%) for EPI-FM (p ≤ 0.01). The mean additional cost per patient of daily controls compared with weekly controls was €679 and €187 for CBCT and EPI-FM, respectively (p<0.0001). CONCLUSIONS: The incremental costs due to different prostate IGRT strategies are relatively moderate, suggesting that daily IGRT combined with intensity-modulated RT (IMRT) could be administered in cases of high-dose radiation delivery to the prostate.