Prostatic displacement during extreme hypofractionated radiotherapy using volumetric modulated arc therapy (VMAT)

Abstract Background To determine prostate displacement during extreme hypofractionated volume modulated arc radiotherapy (VMAT) using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers. Methods A total of 150 image pairs were obtained from 30 patients who underwent extreme hypofractionated radiotherapy to a dose of 40 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal x-rays before and after treatment and were used to determine intra-fraction prostate displacement. Results The mean prostate displacements were 0.03 ± 1.23 mm (1SD), 0.18 ± 1.55 mm, and 0.37 ± 1.95 mm in the left-right, superior-inferior, and anterior-posterior directions, respectively. The mean 3D displacement was 2.32 ± 1.55 mm. Only 6 (4%) fractions had a 3D displacement of >5 mm. The average time of treatment delivery for a given fraction was 195 ± 59 seconds. Conclusions The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy delivered via VMAT, continues to be small. Clinical margins typically used in a similar fixed-angle IMRT treatment are adequate. The use of VMAT in further extreme hypofractionation may limit prostatic motion uncertainties that would be otherwise be associated with longer treatment times

Biochemical, pathologic, toxicity, and quality-of-life outcomes in a five-fraction hypofractionated accelerated radiotherapy treatment using standard linear accelerators and gold seed fiducials

186 Background: Biological dose escalation through hypofractionated image-guided radiotherapy (H-IGRT) holds the promise of improved patient outcomes, system capacity but decreased cost. In 2006 we initiated a prospective trial of H-IGRT of patients with low risk localized prostate cancer. In this report, we report the toxicities, quality of life (QOL), biochemical and pathologic outcomes of this cohort with more mature follow-up. Methods: A phase I/II study in which patients with T1-2b, Gleason≤6, and PSA≤10 ng/ml prostate cancer received 35 Gy in 5 fractions, once a week over 29 days. No patients received hormone therapy. Treatment was delivered with intensity modulated radiotherapy (IMRT) on standard linear accelerators, with daily image guidance using gold seed fiducials, and a 4 mm CTV-PTV margin. CTCAE v3.0 and RTOG late morbidity scores were used to assess acute and late toxicities, respectively. QOL was assessed by the Expanded Prostate Cancer Index Composite (EPIC). Biochemical control (BC) was defined by the Phoenix definition, adjusted for benign bounce. Results: As of September 2011, 83 patients have completed treatment with a median follow-up of 42 months (range 12–60 months). Median age was 67y (42 – 82y). 78 patients (92%) were T1a-c; all had Gleason 6 cancers; median PSA was 5.3 (0.8 – 9.9 ng/ml). 82 (99%) had BC; the remaining patient had a negative biopsy and a history of chronic prostatitis. The median PSA on last visit was 0.69 ng/ml (.02 – 2.6 ng/ml). Of 59 patients who have had a biopsy to date, 2 (3%) were positive but both are under BC. The following toxicities were observed: acute grade 3+: 0% GI, 1% GU, 0% fatigue; late grade 3+: 1% GI, 1% GU. Median transformed QOL scores at baseline (0.5 SD) and 36mo follow-up are: urinary – 95% (4.1), 93%; bowel – 96% (4.8), 96%; sexual – 65% (13.7), 51%; and hormonal – 95% (5.3), 95%. Conclusions: This novel technique employing standard linear accelerators to deliver an extreme hypofractionated schedule of radiotherapy is feasible, well tolerated and shows excellent pathologic and biochemical control. A randomized study versus standard fractionation should be performed. </jats:p

Comparison of acute toxicity in patients treated with a 4-field box or IMRT to deliver elective pelvic nodal irradiation for localized high-risk prostate cancer

69 Background: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. Even though studies show a clear dosimetric benefit to bowel and bladder, there is a lack of good data demonstrating decreased toxicity with the use of IMRT in this setting. Methods: From 2004-2010, 230 patients with localized high risk prostate cancer were enrolled into 3 sequential prospective phase I/II trials of delivering EPNI (45 Gy) along with a concomitant hypofractionated IMRT boost to the prostate (67.5 Gy total) in 25 fractions over 5 weeks time. All patients were to receive 3 years of adjuvant androgen deprivation. During the accrual period, the method used to deliver the EPNI portion of the treatment changed as new literature emerged about target volumes for EPNI. The 3 methods used to deliver EPNI in this large cohort were 1) 4FB, 2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al (IMRT-Shih), and 3) IMRT with nodal volumes as suggested by RTOG (IMRT-RTOG). Common Terminology Criteria for Adverse Events v3.0 was used to assess acute toxicity prospectively during treatment and then at 3 months. Results: For EPNI, 94 patients were treated with a 4FB, 53 were treated with IMRT-Shih, and 83 were treated with IMRT-RTOG. There were no acute grade 3 GI toxicities. Patients in the 4FB group had higher rates of acute grade ≥ 2 proctitis compared to the IMRT-Shih and IMRT-RTOG groups (16.0% vs 2.0% vs 2.4%, p=0.0009). The 4FB group also had higher rates of grade ≥ 2 flatulence compared to the 2 other IMRT groups (17.0% vs 7.6% vs 0%, p&lt;0.0001). With regards to acute GU toxicities, patients in the 4FB group had higher rates of grade ≥ 3 urinary frequency compared to the 2 other IMRT groups (5.3% vs 0% vs 0%, p=0.027). Conclusions: In this non-randomized comparison, IMRT resulted in statistically significant decreases in acute proctitis, flatulence, and urinary frequency when compared to a 4FB technique to deliver EPNI in localized high risk prostate cancer. Analysis for possible confounding factors will be performed. </jats:p