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PurposeTo assess the reproducibility of the dose–volume distribution of the initial simulation CT, generated using volumetric modulated arc therapy (VMAT) planning, during the radiotherapy of the prostatic bed based on weekly cone beam CTs (CBCT).MethodsTwenty-three patients, after radical prostatectomy were treated with adjuvant or salvage radiotherapy between July and December 2016 and considered for this evaluation. Weekly CBCT scans (n = 138) were imported into the treatment planning system, and the clinical tumor volume (CTV), the rectum and the bladder were contoured. The initially calculated dose distribution and the dose–volume histograms generated from weekly CBCTs were compared. The prostatic fossa dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 50, 60 and 65 Gy during the treatment were compared to the initial plan, with statistical significance determined using the one-sample t‑test.ResultsMarked variations in the total organ volume of the rectum and the bladder were observed. The correlation between rectum volume and V50 was not significant (p = 0.487), while the bladder volume and V50 demonstrated a significant correlation. There was no correlation between urinary bladder volume and CTV. The change in rectal volume correlated significantly with CTV. The dose coverage (D98% and D95%) to the prostatic bed could be achieved for all patients due to the ventral shift in the volume differences of the rectum.ConclusionWeekly CBCTs can be considered as adequate verification tools to assess the interfractional variability of the CTV and organs at risk. The proven volume changes in the urinary bladder and the rectum do not compromise the final delivered dose in the CTV.

Background Prospective trials have demonstrated the advantage of dose-escalated radiotherapy for the biochemical and clinical control of intermediate risk prostate cancer. Dose escalation improves outcomes but increases risks of urinary and bowel toxicity. Recently the contribution of “spacers” positioned in the septum between the rectum and the prostate could improve the functional results of intensity modulated radiation therapy (IMRT). To date most of the evaluated devices were polyethylen glycol (PEG) and hyaluronic acid (HA). Men on the Spacer arm had decreased bowel toxicity and less decline in both urinary and bowel quality of life as compared to Control men in a randomized trial. Methods This is an interventional, multi-center study to evaluate the use of biodegradable inflatable balloon for patients with intermediate risk prostate cancer treated by IMRT (74 to 80 Gy, 2 Gy/fraction) with daily image guided radiotherapy. Discussion This multicenter prospective study will yield new data regarding dosimetric gain and implantation stages of Bioprotect balloon. Acute and late toxicities and quality of life will be registered too. Trial registration NCT02478112 , date of registration: 15/06/2015.

To analyze the efficacy of Green Light photoselective vaporization of the prostate (PVP) in elderly high-risk benign prostatic hyperplasia (BPH) patients with glands over 80 ml. From December 2013 to February 2016, we allocated 84 elderly (age 71–97) high-risk patients who underwent preoperative transrectal ultrasound (TRUS) examination with glands over 80 ml and divided them into two groups to receive 120 W (n = 40) and 180 W (n = 44) PVP. All the patients have been observed at least one intraoperative comorbidity: hypertension, diabetes mellitus, NYHA II, or combined. They were followed up for 12 months. All the conventional parameters were compared in this study. All the patients received successful operations without severe complications, and no patient needed blood transfusion. The operation time and catheterization time of the 180 W patients were significantly shorter than that of the 120 W patients (p < 0.05). The International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, maximum flow rate (Qmax), and residual urine volume (RUV) in both groups have been significantly improved. PVP is safe and effective for high-risk aging patients with gland over 80 ml. In addition, 180 W XPS system has a short operation time and catheterization time and less inflammatory response.

Background Due to physical characteristics, ions like protons or carbon ions can administer the dose to the target volume more efficiently than photons since the dose can be lowered at the surrounding normal tissue. Radiation biological considerations are based on the assumption that the α/β value for prostate cancer cells is 1.5 Gy, so that a biologically more effective dose could be administered due to hypofractionation without increasing risks of late effects of bladder (α/β = 4.0) and rectum (α/β = 3.9). Methods/Design The IPI study is a prospective randomized phase II study exploring the safety and feasibility of primary hypofractionated irradiation of the prostate with protons and carbon ions in a raster scan technique. The study is designed to enroll 92 patients with localized prostate cancer. Primary aim is the assessment of the safety and feasibility of the study treatment on the basis of incidence grade III and IV NCI-CTC-AE (v. 4.02) toxicity and/or the dropout of the patient from the planned therapy due to any reason. Secondary endpoints are PSA-progression free survival (PSA-PFS), overall survival (OS) and quality-of-life (QoL). Discussion This pilot study aims at the evaluation of the safety and feasibility of hypofractionated irradiation of the prostate with protons and carbon ions in prostate cancer patients in an active beam technique. Additionally, the safety results will be compared with Japanese results recently published for carbon ion irradiation. Due to the missing data of protons in this hypofractionated scheme, an in depth evaluation of the toxicity will be created to gain basic data for a following comparison study with carbon ion irradiation. Trial registration Clinical Trial Identifier: NCT01641185 (clinicaltrials.gov)

Background Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 × 6.1 Gy) by using sequential MRIs. Methods Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.

Background Derivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment. Methods One hundred and eighteen patients received EBRT in 23 fractions of 2 Gy and HDR (TG43 algorithm) in 3 fractions of 6.5 Gy. Results for the Late Effects of Normal Tissues — Subjective, Objective, Management and Analytic toxicity assessments were available with a median follow-up of 72 months. The HDR CT was deformably-registered to the EBRT CT. Doses were corrected for dose fractionation. Rectum dose-volume histogram (DVH) parameters were calculated in two ways. (1) Distribution-adding: parameters were calculated after the EBRT dose distribution was 3D-summed with the registered HDR dose distribution. (2) Parameter-adding: the EBRT DVH parameters were added to HDR DVH parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate parameters with late peak toxicity (dichotomised at grade 1 or 2). Results The 48–80, 40–63 and 49–55 Gy dose regions from distribution-adding were significantly correlated with rectal bleeding, urgency/tenesmus and stool frequency respectively. Additionally, urgency/tenesmus and anorectal pain were associated with the 25–26 Gy and 44–48 Gy dose regions from distribution-adding respectively. Parameter-adding also indicated the low-mid dose region was significantly correlated with stool frequency and proctitis. Conclusions This study confirms significant dose-histogram effects for gastrointestinal toxicities after including deformable registration to combine phases of EBRT/HDR prostate cancer treatment. The findings from distribution-adding were in most cases consistent with those from parameter-adding. The mid-high dose range and near maximum doses were important for rectal bleeding. The distribution-adding mid-high dose range was also important for stool frequency and urgency/tenesmus. We encourage additional studies in a variety of institutions using a variety of dose accumulation methods with appropriate inter-fraction motion management. Trial registration NCT NCT00193856 . Retrospectively registered 12 September 2005.

Purpose: To compare acute gastrointestinal (GI) and genitourinary (GU) toxicity between patient groups with localized prostate adenocarcinoma, treated with conventionally fractionated (CFRT) and hypofractionated (HFRT) three-dimensional conformal external-beam radiotherapy (3D-CRT). Patients and Methods: 91 patients were enrolled into a randomized study with a minimum follow-up of 3 months. 44 men in the CFRT arm were irradiated with 74 Gy in 37 fractions at 2 Gy per fraction for 7.5 weeks. 47 men in the HFRT arm were treated with 57 Gy in 17 fractions for 3.5 weeks, given as 13 fractions of 3 Gy plus four fractions of 4.5 Gy. The clinical target volume (CTV) included the prostate and the base of seminal vesicles. The CTV-to-PTV (planning target volume) margin was 8–10 mm. Study patients had portal imaging and/or simulation performed on the first fractions and repeated at least weekly. Results: No acute grade 3 or 4 toxicities were observed. The grade 2 GU acute toxicity proportion was significantly lower in the HFRT arm: 19.1% versus 47.7% (χ 2 -test, p = 0.003). The grade 2 GU acute toxicity-free survival was significantly better in the HFRT arm (log-rank test, p = 0.008). The median duration of overall GI acute toxicity was shorter with HFRT: 3 compared to 6 weeks with CFRT (median test, p = 0.017). Conclusion: In this first evaluation, the HFRT schedule is feasible and induces acceptable or even lower acute toxicity compared with the toxicities in the CFRT schedule. Extended follow-up is needed to justify this fractionation schedule’s safety in the long term.

A deep-neural-network (DNN) was successfully used to predict clinically-acceptable dose distributions from organ contours for intensity-modulated radiotherapy (IMRT). To provide the next step in the DNN-based plan automation, we propose a DNN that directly generates beam fluence maps from the organ contours and volumetric dose distributions, without inverse planning. We collected 240 prostate IMRT plans and used to train a DNN using organ contours and dose distributions. After training was done, we made 45 synthetic plans (SPs) using the generated fluence-maps and compared them with clinical plans (CP) using various plan quality metrics including homogeneity and conformity indices for the target and dose constraints for organs at risk, including rectum, bladder, and bowel. The network was able to generate fluence maps with small errors. The qualities of the SPs were comparable to the corresponding CPs. The homogeneity index of the target was slightly worse in the SPs, but there was no difference in conformity index of the target, V 60Gy of rectum, the V 60Gy of bladder and the V 45Gy of bowel. The time taken for generating fluence maps and qualities of SPs demonstrated the proposed method will improve efficiency of the treatment planning and help maintain the quality of plans.

Intensity-modulated radiation therapy (IMRT) has recently become popular in Japan. Prostate cancer is indisputably one of the main targets of IMRT. However, the current status and interfacility differences in dose-prescription policies for prostate IMRT are unknown. Therefore, a nationwide survey of 43 institutions that had implemented prostate IMRT was conducted by sending a questionnaire regarding the above-mentioned issues. Thirty-three institutions (77%) had responded to the questionnaire by the end of October 2010. A total of 5245 patients with localized prostate cancer had been treated with IMRT by the end of 2009. Regular multileaf collimator-based techniques were the most common beam delivery method. Dose-prescription policies were divided into four major categories: isocenter-based (@isocenter), dose delivered to 95% of the planning target volume (PTV) (D95)-based (D95@PTV), mean dose to the PTV-based (Mean@PTV), and mean dose to the clinical target volume (CTV)-based (@CTV). The mean doses of the CTV and PTV, and the volume of the PTV receiving 95% of the dose (V95) were significantly higher with the D95@PTV policy than with the other prescription policies. Low-dose areas and hot spots were observed within the PTV in plans with @isocenter and @CTV policies. In conclusion, there are currently considerable differences among institutions in Japan regarding target doses for prostate IMRT. The D95@PTV prescription policy resulted in significant dose escalation compared with the other policies. These differences should be taken into consideration when interpreting treatment outcomes and creating multi-institutional protocols in the future.

Treatment selection for men undergoing curative treatment for prostate cancer is often a challenging decision in view of the goal of maximising cure while maintaining quality of life. Previous quality-of-life comparisons suggest that specific outcomes are associated with type of treatment (surgery vs radiation); however, the functional anatomy approach, starting with nerve-sparing prostatectomy, assumes that quality-of-life outcomes are established by anatomic preservation. Emerging applications of the functional anatomy approach for prostate radiation will ultimately allow for individualised treatments that address the normal tissue variants visible on MRI. Such approaches will encompass all essential functions affected by treatment including genitourinary, rectal, and sexual functions. In this Review, we outline the current techniques in functional anatomy-based preservation related to sexual outcomes, and outline the capacity of vessel-sparing radiotherapy to preserve sexual function in 90% of patients at the 5 year follow-up while maintaining excellent cure rates.