Phase I Dose-Escalation Study of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer

University of Texas Southwestern, Dallas, TX 75390, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 04/2011; 29(15):2020-6. DOI: 10.1200/JCO.2010.31.4377
Source: PubMed

ABSTRACT To evaluate the tolerability of escalating doses of stereotactic body radiation therapy in the treatment of localized prostate cancer.
Eligible patients included those with Gleason score 2 to 6 with prostate-specific antigen (PSA) ≤ 20, Gleason score 7 with PSA ≤ 15, ≤ T2b, prostate size ≤ 60 cm(3), and American Urological Association (AUA) score ≤ 15. Pretreatment preparation required an enema and placement of a rectal balloon. Dose-limiting toxicity (DLT) was defined as grade 3 or worse GI/genitourinary (GU) toxicity by Common Terminology Criteria of Adverse Events (version 3). Patients completed quality-of-life questionnaires at defined intervals.
Groups of 15 patients received 45 Gy, 47.5 Gy, and 50 Gy in five fractions (45 total patients). The median follow-up is 30 months (range, 3 to 36 months), 18 months (range, 0 to 30 months), and 12 months (range, 3 to 18 months) for the 45 Gy, 47.5 Gy, and 50 Gy groups, respectively. For all patients, GI grade ≥ 2 and grade ≥ 3 toxicity occurred in 18% and 2%, respectively, and GU grade ≥ 2 and grade ≥ 3 toxicity occurred in 31% and 4%, respectively. Mean AUA scores increased significantly from baseline in the 47.5-Gy dose level (P = .002) as compared with the other dose levels, where mean values returned to baseline. Rectal quality-of-life scores (Expanded Prostate Cancer Index Composite) fell from baseline up to 12 months but trended back at 18 months. In all patients, PSA control is 100% by the nadir + 2 ng/mL failure definition.
Dose escalation to 50 Gy has been completed without DLT. A multicenter phase II trial is underway treating patients to 50 Gy in five fractions to further evaluate this experimental therapy.

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    • "The current evidence for SABR as primary treatment for localized PCa is mainly in the form of small trials or series, 13 using Cyberknife™ and 6 using linacs [18] [19] [20] [21] [22] [23] [24]. There is variation in dose-fractionation schedules, organ-at-risk constraints, use of androgen deprivation, CTV–PTV margins, IGRT techniques and inclusion of SV within the CTV (most often the SV are not treated, even in non-low risk patients). "
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    ABSTRACT: To develop a class solution for prostate Stereotactic Ablative Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT). Seven datasets were used to compare plans using one 360° arc (1FA), one 210° arc (1PA), two full arcs and two partial arcs. Subsequently using 1PA, fifteen datasets were compared using (i) 6mm CTV-PTV margins, (ii) 8mm CTV-PTV margins and (iii) including the proximal SV within the CTV. Monaco™ 3.2 (Elekta™) was used for planning with the Agility™ MLC system (Elekta™). Highly conformal plans were produced using all four arc arrangements. Compared to 1FA, 1PA resulted in significantly reduced rectal doses, and monitor units and estimated delivery times were reduced in six of seven cases. Using 6mm CTV-PTV margins, planning constraints were met for all fifteen datasets. Using 8mm margins required relaxation of the uppermost bladder constraint in three cases to achieve adequate coverage, and, compared to 6mm margins, rectal and bladder doses significantly increased. Including the proximal SV required relaxation of the uppermost bladder and rectal constraints in two cases, and rectal and bladder doses significantly increased. Prostate SABR VMAT is optimal using 1PA. 6mm CTV-PTV margins, compatible with daily fiducial-based IGRT, are consistently feasible in terms of target objectives and OAR constraints.
    Radiotherapy and Oncology 12/2013; 110(2). DOI:10.1016/j.radonc.2013.10.036 · 4.86 Impact Factor
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    • "These high doses are considered to lie near the plateau of the known sigmoidal dose–response for prostate cancer where the 5-year bRFS rates lie above the 90% level. Given this observation, we feel further escalation of SBRT doses above 40 Gy is not warranted at this time and would not be prudent given the potential for higher rates of grade 3 GI and GU toxicities shown for SBRT to 50 Gy [18]. Higher doses could hypothetically be necessary for SBRT among patients with high-risk localized Table 1 Patient and treatment characteristics (n = 1100 ). "
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    ABSTRACT: The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested. A total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003-11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25Gy in 4-5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2ng/ml above nadir was analyzed with the Kaplan Meier method. With a median follow-up of 36months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ⩽6, 7 and ⩾8, respectively (p=0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p<0.001). No differences were observed with ADT (p=0.71) or as a function of total dose (p=0.17). A PSA bounce of >0.2ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively. PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients.
    Radiotherapy and Oncology 09/2013; 109(2). DOI:10.1016/j.radonc.2013.08.030 · 4.86 Impact Factor
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    • "33.5 Gy in 5 fx 40 L 41 - - 90% at 4 years Boike et al. 2011 [12] "
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    ABSTRACT: To evaluate the feasibility and early side effects of a short course hypo-fractionated SBRT programme with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams. A prospective phase I-II study, started on February 2012. Inclusion criteria were: age <= 80 years, WHO-PS <= 2, PSA <= 20 ng/ml, histologically proven prostate adenocarcinoma, T1-T2 stage, no distant metastases, no previous surgery other than TURP, no malignant tumours in the previous 5 years, IPSS 0--7. The schedule was 35Gy in 5 alternative days. SBRT was delivered with RapidArc VMAT, with 10MV FFF photons. Toxicity assessment was performed according to CTCAE v4.0 scale. EPIC questionnaires assessed Quality-of-Life.. Neo-adjuvant/concomitant hormonal-therapy was prescribed according to risk classification. SpaceOARTM gel was optionally implanted to increase the separation space between the prostate and the rectal wall. Median follow-up was 11 months (range: 5--16); 40 patients were recruited in the protocol and treated.. According to NCCN criteria, 26/40 patients were low-risk and 14/40 were intermediate risk. Median age was 70 years (56--80), median initial PSA was 6.25 ng/ml (0.50-13.43 ng/ml). Median Gleason score was 6 (6--7). All patients completed the treatment as programmed (median 11.8 days (9--22). Acute Toxicities were as follow: Rectum G0: 30/40 cases (75%); G1: 6/40 (15%); G2: 4/40 (10%). Genito-urinary: G0: 16/40 (40%); G1: 8/40 (20%); G2: 16/34 (40%). In two G2 urinary retention cases, intermittent catheter was needed. No acute G3 or greater toxicity was found. Median treatment time was 126 sec (120--136). SpaceOARTM was implanted in 8 patients. PSA reduction from the pre-treatment value of the marker was documented in all patients. Early findings suggest that SBRT with RapidArc and FFF beams for prostate cancer in 5 fractions is feasible and tolerated in acute setting. Longer follow-up is needed for assessment of late toxicity and outcome.
    Radiation Oncology 07/2013; 8(1):171. DOI:10.1186/1748-717X-8-171 · 2.36 Impact Factor
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