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      11C Choline PET Guided Salvage Radiotherapy with Volumetric Modulation Arc Therapy and Hypofractionation for Recurrent Prostate Cancer after HIFU Failure : Preliminary Results of Tolerability and Acute Toxicity

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          Abstract

          The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer follow-up is needed to assess late toxicity and definitive outcomes.

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          Volumetric modulated arc therapy: IMRT in a single gantry arc.

          In this work a novel plan optimization platform is presented where treatment is delivered efficiently and accurately in a single dynamically modulated arc. Improvements in patient care achieved through image-guided positioning and plan adaptation have resulted in an increase in overall treatment times. Intensity-modulated radiation therapy (IMRT) has also increased treatment time by requiring a larger number of beam directions, increased monitor units (MU), and, in the case of tomotherapy, a slice-by-slice delivery. In order to maintain a similar level of patient throughput it will be necessary to increase the efficiency of treatment delivery. The solution proposed here is a novel aperture-based algorithm for treatment plan optimization where dose is delivered during a single gantry arc of up to 360 deg. The technique is similar to tomotherapy in that a full 360 deg of beam directions are available for optimization but is fundamentally different in that the entire dose volume is delivered in a single source rotation. The new technique is referred to as volumetric modulated arc therapy (VMAT). Multileaf collimator (MLC) leaf motion and number of MU per degree of gantry rotation is restricted during the optimization so that gantry rotation speed, leaf translation speed, and dose rate maxima do not excessively limit the delivery efficiency. During planning, investigators model continuous gantry motion by a coarse sampling of static gantry positions and fluence maps or MLC aperture shapes. The technique presented here is unique in that gantry and MLC position sampling is progressively increased throughout the optimization. Using the full gantry range will theoretically provide increased flexibility in generating highly conformal treatment plans. In practice, the additional flexibility is somewhat negated by the additional constraints placed on the amount of MLC leaf motion between gantry samples. A series of studies are performed that characterize the relationship between gantry and MLC sampling, dose modeling accuracy, and optimization time. Results show that gantry angle and MLC sample spacing as low as 1 deg and 0.5 cm, respectively, is desirable for accurate dose modeling. It is also shown that reducing the sample spacing dramatically reduces the ability of the optimization to arrive at a solution. The competing benefits of having small and large sample spacing are mutually realized using the progressive sampling technique described here. Preliminary results show that plans generated with VMAT optimization exhibit dose distributions equivalent or superior to static gantry IMRT. Timing studies have shown that the VMAT technique is well suited for on-line verification and adaptation with delivery times that are reduced to approximately 1.5-3 min for a 200 cGy fraction.
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            High-intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure.

            To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high-intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU. Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, 'PSA nadir plus', PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined. The data from 285 patients (stage
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              IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients treated with post-operative adjuvant or salvage radiotherapy after radical prostatectomy.

              To investigate the role of IMRT in reducing the risk of acute genito-urinary (GU), upper gastrointestinal (uGI) and lower gastrointestinal (lGI) toxicity following whole-pelvis irradiation (WPRT) after radical prostatectomy. 172 consecutive patients with prostate cancer were post-operatively irradiated to the prostatic bed (PB) and pelvic lymph-nodal area with adjuvant (n=100) or salvage (n=72) intent. Eighty-one patients underwent three-dimensional conformal (3DCRT) WPRT, while the remaining 91 underwent IMRT (54/91 with helical tomotherapy (HTT); 37/91 with Linac intensity-modulated RT (LinacIMRT)). Patients treated with IMRT experienced a decreased risk of acute toxicity. The crude incidence of grade > or =2 toxicity was GU 12.3% vs. 6.6% (p=0.19); lGI 8.6% vs. 3.2% (p=0.14); uGI 22.2% vs. 6.6% (p=0.004), for 3DCRT and IMRT, respectively. With respect to uGI and lGI, the acute toxicity profile of the HTT patients was even better when compared to that of 3DCRT patients (crude incidence:1.8% and 0.0%, respectively). Treatment interruptions due to uGI toxicity were 11/81 in the 3DCRT group vs. 2/91 in the IMRT group (p=0.006). The risk of acute toxicity following post-operative WPRT delivered by means of IMRT was reduced compared to that of 3DCRT. The most significant reduction concerned uGI, mainly owing to better bowel sparing with IMRT.
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                Author and article information

                Journal
                Technol Cancer Res Treat
                Technol. Cancer Res. Treat
                TCT
                sptct
                Technology in Cancer Research & Treatment
                SAGE Publications (Sage CA: Los Angeles, CA )
                1533-0346
                1533-0338
                October 2014
                October 2014
                : 13
                : 5
                : 395-401
                Affiliations
                [1 ]Department of Radiotherapy, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano-Milan, Italy
                [2 ]Department of Nuclear Medicine, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano-Milan, Italy
                [3 ]Department of Urology, Clinica Columbus, Milan, Italy
                Author notes
                [*] [* ]Filippo Alongi, M.D. Phone: +39/0282246244; +39/0282247454 Fax: 139/02248509 E-mail: filippo.alongi@ 123456humanitas.it
                Article
                10.7785_tcrtexpress.2013.600268
                10.7785/tcrtexpress.2013.600268
                4527415
                24000995
                6d885ada-4432-46ed-b8a2-e8384e3e4a53
                © Adenine Press (2014)

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License ( http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 29 March 2013
                : 24 May 2013
                : 17 June 2013
                Categories
                Articles

                pet,hifu,salvage radiotherapy,prostate
                pet, hifu, salvage radiotherapy, prostate

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