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The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Background and Purpose: MR-guided radiotherapy (MRgRT) online plan adaptation accounts for tumor volume changes, interfraction motion and thus allows daily sparing of relevant organs at risk. Due to the high interfraction variability of bladder and rectum, patients with tumors in the pelvic region may strongly benefit from adaptive MRgRT. Currently, fast automatic annotation of anatomical structures is not available within the online MRgRT workflow. Therefore, the aim of this study was to train and validate a fast, accurate deep learning model for automatic MRI segmentation at the MR-Linac for future implementation in a clinical MRgRT workflow., Materials and Methods: For a total of 47 patients, T2w MRI data were acquired on a 1.5 T MR-Linac (Unity, Elekta) on five different days. Prostate, seminal vesicles, rectum, anal canal, bladder, penile bulb, body and bony structures were manually annotated. These training data consisting of 232 data sets in total was used for the generation of a deep learning based autocontouring model and validated on 20 unseen T2w-MRIs. For quantitative evaluation the validation set was contoured by a radiation oncologist as gold standard contours (GSC) and compared in MATLAB to the automatic contours (AIC). For the evaluation, dice similarity coefficients (DSC), and 95% Hausdorff distances (95% HD), added path length (APL) and surface DSC (sDSC) were calculated in a caudal-cranial window of ± 4 cm with respect to the prostate ends. For qualitative evaluation, five radiation oncologists scored the AIC on the possible usage within an online adaptive workflow as follows: (1) no modifications needed, (2) minor adjustments needed, (3) major adjustments/ multiple minor adjustments needed, (4) not usable., Results: The quantitative evaluation revealed a maximum median 95% HD of 6.9 mm for the rectum and minimum median 95% HD of 2.7 mm for the bladder. Maximal and minimal median DSC were detected for bladder with 0.97 and for penile bulb with 0.73, respectively. Using a tolerance level of 3 mm, the highest and lowest sDSC were determined for rectum (0.94) and anal canal (0.68), respectively. Qualitative evaluation resulted in a mean score of 1.2 for AICs over all organs and patients across all expert ratings. For the different autocontoured structures, the highest mean score of 1.0 was observed for anal canal, sacrum, femur left and right, and pelvis left, whereas for prostate the lowest mean score of 2.0 was detected. In total, 80% of the contours were rated be clinically acceptable, 16% to require minor and 4% major adjustments for online adaptive MRgRT., Conclusion: In this study, an AI-based autocontouring was successfully trained for online adaptive MR-guided radiotherapy on the 1.5 T MR-Linac system. The developed model can automatically generate contours accepted by physicians (80%) or only with the need of minor corrections (16%) for the irradiation of primary prostate on the clinically employed sequences., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors report institutional collaborations with TheraPanacea, Elekta, Philips, Kaiku and PTW Freiburg which provided technical and/or financial support. TheraPanacea developed the proposed model, but were not involved in the analysis and scoring of the testing dataset.], (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Purpose: In pediatric bladder/prostate-rhabdomyosarcoma, the rate of bladder preservation after neoadjuvant chemotherapy is high, with an excellent oncological outcome. Information about functional urological long-term outcomes is rare., Methods: Data of all patients who had undergone bladder-preserving surgery with or without brachytherapy at our institution between 2009 and 2020 were analyzed retrospectively. Detailed urological function was assessed focusing on age-related continence, bladder capacity and urodynamic findings., Results: We identified 40 patients, median age at surgery of 27 months (range 9-191), and 32 patients additionally received postoperative high-dose-rate brachytherapy. The median follow-up was 32.5 months (range 6-125). The bladder capacity increased from median 66.7% (21.1-180) of expected bladder capacity related to age 3 months after surgery to 87.4% (58.1-181.8) 9 months after surgery. In the group of aged > 6-year-old, continence was 94% (83% with brachytherapy, 100% without brachytherapy). Erectile function was normal in 92% (90% with brachytherapy, 100% without brachytherapy). Bladder capacity was more than 65% expected bladder capacity related to age in 70% (60% with brachytherapy, 86% without brachytherapy). 65% of all patients need neither anticholinergic drugs nor low-dose antibiotics (63% with brachytherapy, 71% without brachytherapy)., Conclusions: Bladder preservation with good functional outcome can be achieved in localized bladder/prostate-rhabdomyosarcoma. In selected cases, supportive brachytherapy additionally contributes to an improvement in the oncological outcome with calculable risks for bladder and erectile function. Careful urological aftercare should be a fixed priority after oncological follow-ups., (© 2022. The Author(s).)

Background: Stereotactic body radiotherapy (SBRT) concepts for dose escalation are increasingly used for bone metastases in patients with oligometastatic or oligoprogressive disease. For metastases that are not suitable for SBRT-regimens, a treatment with 30/40 Gy with simultaneous integrated boost (SIB) in 10 fractions represents a possible regimen. The aim of this study was to investigate the feasibility of this concept and the acute and subacute toxicities., Patients and Methods: Clinical records for dose-escalated radiotherapy of all consecutive patients treated with this regimen were evaluated retrospectively (24 patients with 28 target volumes for oncologic outcomes and 25 patients with 29 target volumes for treatment feasibility and dose parameters analysis). Analysis of radiotherapy plans included size of target volumes and dosimetric parameter for target volumes and organs at risk (OAR). Acute and subacute toxicities were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) V4.0., Results: The most common localization was the spine (71.4%). The most common histology was prostate cancer (45.8%). Oligometastatic or oligoprogressive disease was the indication for dose-escalated radiotherapy in 19/24 patients (79.2%). Treatment was feasible with all patients completing radiotherapy. Acute toxicity grade 1 was documented in 36.0% of the patients. During follow up, one patient underwent surgery due to bone instability. The 1-year local control and patient-related progression-free survival (PFS) were 90.0 ± 6.7% and 33.3 ± 11.6%, respectively., Conclusions: Dose-escalated hypofractionated radiotherapy with simultaneous integrated boost for bone metastases resulted in good local control with limited acute toxicities. Only one patient required surgical intervention. The regimen represents an alternative to SBRT in selected patients., (© 2022 Vlatko Potkrajcic, Arndt-Christian Mueller, Bettina Frey, Cihan Gani, Daniel Zips, Ruediger Hoffmann, Sandra Frantz, Verena Warm, Frank Paulsen, Franziska Eckert, published by Sciendo.)

Purpose: The extent of lymphadenectomy and clinical features influence the risk of occult nodes in node-negative prostate cancer. We derived a simple estimation model for the negative predictive value (npv) of histopathologically node-negative prostate cancer patients (pN0) to guide adjuvant treatment., Methods: Approximations of sensitivities in detecting lymph node metastasis from current publications depending on the number of removed lymph nodes were used for a theoretical deduction of a simplified formulation of npv assuming a false node positivity of 0., Results: A theoretical formula of npv = p(N0IpN0) = (100 - prevalence) / (100 - sensitivity × prevalence) was calculated (sensitivity and preoperative prevalence in %). Depending on the number of removed lymph nodes (nLN), the sensitivity of pN0-staged prostate cancer was derived for three sensitivity levels accordingly: sensitivity = f(nLN) = 9 × nLN /100 for 0 ≤ nLN ≤ 8 and f(nLN) = (nLN + 70) /100 for 9 ≤ nLN ≤ 29 and f(nLN) = 1 for nLN ≥ 30., Conclusion: We developed a theoretical formula for estimation of the npv in pN0-staged prostate cancer patients. It is a sine qua non to use the formula in a clinically experienced context before deciding to electively irradiate pelvic lymph nodes or to intensify adjuvant systemic treatment., (© 2021. The Author(s).)

This retrospective study aimed at clinical evaluation of autonomous radiotherapy planning for ten prostate cancer cases, including organ-at-risk/target contouring and treatment planning. Five experts scored the clinical acceptability of each step using a 4-level Likert-scale resulting in 78%, 66% and 90% acceptance. For 6/10 patients the entire workflow was considered acceptable., Competing Interests: Conflicts of interest The Department of Radiation Oncology Tübingen receives within the frame of research agreements financial and technical support as well as sponsoring for travels and scientific symposia from Elekta AB (Stockholm, Sweden), TheraPanacea (Paris, France), Philips GmbH (Best, The Netherlands); Dr. Sennewald Medizintechnik GmbH (München, Germany), PTW Freiburg (Germany)., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The influence of radiotherapy on patient immune cell subsets has been established by several groups. Following a previously published analysis of immune changes during and after curative radiotherapy for prostate cancer, this analysis focused on describing correlations of changes of immune cell subsets with radiation treatment parameters., Patients and Methods: For 13 patients treated in a prospective trial with radiotherapy to the prostate region (primary analysis) and five patients treated with radiotherapy to prostate and pelvic nodal regions (exploratory analysis), already published immune monitoring data were correlated with clinical data as well as radiation planning parameters such as clinical target volume (CTV) and volumes receiving 20 Gy (V20) for newly contoured volumes of pelvic blood vessels and bone marrow., Results: Most significant changes among immune cell subsets were observed at the end of radiotherapy. In contrast, correlations of age and CD8 + subsets (effector and memory cells) were observed early during and 3 months after radiotherapy. Ratios of T cells and T cell proliferation compared to baseline correlated with CTV. Early changes in regulatory T cells (Treg cells) and CD8 + effector T cells correlated with V20 of blood vessels and bone volumes., Conclusions: Patient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects., Trial Registration Number: NCT01376674, 20.06.2011., (© 2021. The Author(s).)

Background: Local ablative radiotherapy (aRT) of oligometastatic prostate cancer (PCa) is very promising and has become a focus of current clinical research., Objective: We hypothesize that aRT is safe and effective in gallium-68 prostate-specific membrane antigen targeted positron emission tomography (PSMA-PET)-staged oligometastatic PCa patients., Design, Setting, and Participants: A nonrandomized, prospective, investigator-initiated phase 2 trial recruited patients with oligometastatic PCa (five or fewer lymph node or osseous metastases) after local curative therapy, without significant comorbidity and androgen deprivation therapy (ADT), at two German centers from 2014 to 2018., Intervention: All PSMA-PET-positive metastases were treated with aRT. No systemic therapy was initiated., Outcome Measurements and Statistical Analysis: The primary endpoint was treatment-related toxicity (grade ≥2) 24 mo after aRT. A one-sided single-sample test of proportions was planned to test whether the endpoint occurs in <15% of the patients. Key secondary endpoints were time to progression of prostate-specific antigen (PSA) and time to ADT, which were associated with potential prognostic factors by Cox regression., Results and Limitations: Of 72 patients, 63 received aRT (13% dropout rate). The median follow-up was 37.2 mo. No treatment-related grade ≥2 toxicity was observed 2 yr after treatment. The median time to PSA progression and time to ADT were 13.2 and 20.6 mo, respectively. Of the patients, 21.4% were free of PSA progression after 3 yr., Conclusions: It was observed that aRT is safe, and midterm PSA progression and ADT-free time were achieved in one of five patients. Randomized clinical trials are indicated to further evaluate the option of delaying ADT in selected patients., Patient Summary: In this clinical trial, 63 patients with up to five metastases of prostate cancer without androgen deprivation therapy were included. We showed that local ablative radiotherapy is safe and that one in five patients had no recurrent prostate-specific antigen value after 3 yr. Local ablative radiotherapy might be an option to avoid systemic therapy in selected patients., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hybrid devices of MR-scanners and linear accelerators (MR-Linacs) represent a new and promising extension of radiotherapeutic options for prostate cancer. The potential advantage of magnetic resonance imaging (MRI) over computed tomography (CT) for soft tissue contrast is well-known and leads to more consistent and smaller target volumes and improved normal tissue sparing., Objectives: This article presents an overview of clinical experience, indications, advantages and challenges of utilizing a 1.5 T MR-Linac in the setting of radiotherapy of prostate cancer., Results: All current indications for radiotherapy of prostate cancer can be treated with an MR-Linac. The advantages include daily MR-based imaging in treatment position and daily adaption of the treatment plan on current anatomy (adaptive radiotherapy). Additionally, functional MRI sequences might be exploited to enhance treatment individualization and response assessment. Ultimately treatment on an MR-Linac might further increase the therapeutic window. The limitations of using MR-Linac include treatment complexity and the duration of each session., Conclusions: MR-Linacs expand the spectrum of radiotherapeutic options for prostate cancer. Increased precision can be reached with daily MRI-based target volume definition and plan adaption. Clinical studies are necessary to identify patient groups who would benefit most from radiotherapy on a MR-Linac., (© 2021. The Author(s).)

Background: Cure- and toxicity rates after intensity-modulated radiotherapy (IMRT) of prostate cancer are dose-and volume dependent. We prospectively studied the potential for organ at risk (OAR) sparing and compensation of tumor movement with the coverage probability (CovP) concept., Patients and Methods: Twenty-eight prostate cancer patients (median age 70) with localized disease (cT1c-2c, N0, M0) and intermediate risk features (prostate-specific antigen [PSA] < 20, Gleason score ≤ 7b) were treated in a prospective study with the CovP concept. Planning-CTs were performed on three subsequent days to capture form changes and movement of prostate and OARs. The clinical target volume (CTV) prostate and the OARs (bladder and rectum) were contoured in each CT. The union of CTV1-3 was encompassed by an isotropic margin of 7 mm to define the internal target volume (ITV). Dose prescription/escalation depended on coverage of all CTVs within the ITV. IMRT was given in 39 fractions to 78 Gy using the Monte-Carlo algorithm. Short-term androgen deprivation was recommended and given in 78.6% of patients., Results: Long-term toxicity was evaluated in 26/28 patients after a median follow-up of 7.1 years. At last follow-up, late bladder toxicity (Radiation Therapy Oncology Group, RTOG) G1 was observed in 14.3% of patients and late rectal toxicities (RTOG) of G1 (7.1%) and of G2 (3.6%) were observed. No higher graded toxicity occurred. After 7.1 years, biochemical control (biochemically no evidence of disease, bNED) was 95.5%, prostate cancer-specific survival and the distant metastasis-free survival after 7.1 years were 100% each., Conclusions: CovP-based IMRT was feasible in a clinical study. Dose escalation with the CovP concept was associated by a low rate of toxicity and a high efficacy regarding local and distant control., (© 2021 Daniel Wegener, Bernhard Berger, Zhoulika Outtagarts, Daniel Zips, Frank Paulsen, Martin Bleif, Daniela Thorwarth, Markus Alber, Oliver Dohm, Arndt-Christian Müller, published by Sciendo.)

Purpose: The surgical approach to localized bladder/prostate rhabdomyosarcoma in children may change due to a new radiotherapeutic modality. We assessed the impact of brachytherapy following surgery for local tumor control, and report surgical techniques and outcomes., Materials and Methods: We retrospectively analyzed the records of all children who underwent surgery for bladder/prostate rhabdomyosarcoma, including tumor relapse, at our institution from 2009 onward., Results: A total of 38 patients with a median age of 29 months (range 10 to 134) met inclusion criteria. Five-year overall survival was 92.8% (95% CI 72.9 to 98.1), and event-free survival at a median followup of 12 months (range 3 to 111) was 73.7% (95% CI 53.4 to 86.2). Three treatment groups were defined, ie bladder preserving surgery combined with brachytherapy, bladder preserving surgery alone and cystectomy. Five-year event-free survival rates for the 3 groups were 85.6% (95% CI 61.2 to 95.2), 66.7% (95% CI 27.2 to 88.2) and 50% (95% CI 5.8 to 84.5), respectively. Bladder preserving surgery was performed in 33 patients (87%), of whom 23 (70%) also underwent brachytherapy, while cystectomy was performed in 5 (13%). Reconstructive procedures varied depending on tumor location and spread., Conclusions: Combining brachytherapy with surgery results in a high bladder preservation rate and improves event-free survival compared to surgery alone in children with bladder/prostate rhabdomyosarcoma. The combination is also effective in treating local tumor relapse, and is associated with less extensive reconstructive procedures due to exclusion of tumors of unfavorable size and location for brachytherapy.

Purpose: Cure- and toxicity rates of prostate IGRT can both be affected by ill-chosen planning target volume (PTV) margins. For dose-escalated prostate radiotherapy, we studied the potential for organ at risk (OAR) sparing and compensation of prostate motion with robust plan optimization using the coverage probability (CovP) concept compared to conventional PTV-based IMRT. Material and methods: We evaluated plan quality of CovP-plans for 27 intermediate risk prostate cancer patients treated in a prospective study (78 Gy/39 fractions). Clinical target volume (CTV) and OARs were contoured on three separate CTs to capture movement and deformation. To define the internal target volume (ITV), the union of CTV1-3 was encompassed by an isotropic margin of 7 mm for the planning process. CovP-dose distribution is optimized considering weight factors for IMRT constraints derived from probabilities of systematic organ displacement in the three CTs. CovP-dose volume histograms (DVHs) were compared with additionally calculated conventional PTV-based IMRT plans. PTV-based IMRT was planned on one-single CT with an isotropically expanded CTV to generate the PTV (i.e., CTV1 + 7mm) and was evaluated on the two other CTs. Results: The CovP-concept showed higher robustness in target volume coverage. Target miss was frequently observed with PTV-based IMRT, resulting in cold spots until 70 Gy with the CovP-concept. The target dose at 74 Gy was comparable, while further the dose-escalation (75-78 Gy) was improved with PTV-based IMRT. However, dose-escalation with PTV-based IMRT was associated with increased OAR-doses, especially in high-dose areas. Conclusions: Probabilistic dose-escalated IMRT was feasible in this prospective study. Comparison of the CovP-concept with PTV-based IMRT revealed superiority with regard to target-coverage and sparing of OARs. The CovP-concept implements a robust plan optimization strategy for organ deformation and motions and could, therefore, serve as a less demanding compromise on the way to adaptive IGRT avoiding daily time-consuming re-planning. SUMMARYWe evaluated the robustness of coverage probability (CovP)-based IMRT plans within a prospective study for prostate cancer radiotherapy. The treatment plans were compared with newly calculated conventional PTV-based IMRT plans. We were able to show that CovP led to a clearly more robust target coverage by avoiding hot spots at OARs compared to conventional PTV-based IMRT. In addition, negative consequences of an inflated PTV can be ameliorated by a more relaxed CovP-based dose prescription.

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement - n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients., Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN-pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample., Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation., Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy., Methods: Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions., Results: From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks., Conclusions: This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach., Trial Registration: German Clinical Trials Register DRKS00003273.

Purpose: Irradiation of adjuvant lymph nodes in high-risk prostate cancer was shown to be associated with improved rates of biochemical nonevidence of disease in the Radiation Therapy Oncology Group trial (RTOG 94-13). To account for the highly individual lymphatic drainage pattern we tested an intensity-modulated radiation therapy (IMRT) approach based on the determination of pelvic sentinel lymph nodes (SN)., Methods and Materials: Patients with a risk of more than 15% lymph node involvement were included. For treatment planning, SN localizations were included into the pelvic clinical target volume. Dose prescriptions were 50.4 Gy to the adjuvant area and 70.0 Gy to the prostate. All treatment plans were generated using equivalent uniform dose (EUD)-based optimization algorithms and Monte Carlo dose calculations and compared with 3D conventional plans., Results: A total of 25 patients were treated and 142 SN were detectable (mean: n = 5.7; range, 0-13). Most SN were found in the external iliac (35%), the internal iliac (18.3%), and the iliac commune (11.3%) regions. Using a standard CT-based planning target volume, relevant SN would have been missed in 19 of 25 patients, mostly in the presacral/perirectal area (22 SN in 12 patients). The comparison of conventional 3D plans with the respective IMRT plans revealed a clear superiority of the IMRT plans. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG criteria) occurred., Conclusions: Distributions of SN are highly variable. Data for SN derived from single photon emission computed tomography are easily integrated into an IMRT-based treatment strategy. By using SN data the probability of a geographic miss is reduced. The use of IMRT allows sparing of normal tissue irradiation.

Background: The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging., Methods: Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5-3 hours after injection of 250 MBq 99mTc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 x 1.8 Gy / week) to the pelvis and 70.0 Gy (5 x 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed., Results: Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred., Conclusion: IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients.

Purpose: To evaluate the consequences of a planning volume definition based on multiple CTs and the application of off-line setup error correction for the treatment of prostate cancer with intensity-modulated radiotherapy (IMRT). Further, to compare various setup correction protocols (SCP) by their influence on the average dose distributions., Materials and Methods: A planning target volume (PTV) consisting of the bounding volume of prostate contours of five CTs (CTV&#95;hull) plus an additional margin of 5mm and a virtual Rectum&#95;hull volume (the solid bounding volume of the five corresponding rectum contours) are used for treatment planning. Simulations of treatment courses with the non-parametric bootstrap method allow to estimate the distribution of the expected equivalent uniform dose (EUD). The impact of off-line setup error correction protocols is evaluated based on estimated EUD distributions., Results: Off-line SCP allow to achieve the intended prostate and rectum EUD and a reliable coverage of the CTV despite the reduced margins. The EUD of the virtual hull volumes is a good estimate for the EUD of prostate and rectal wall., Conclusion: Treatment planning based on Rectum&#95;hull and CTV&#95;hull plus setup margin as PTV in combination with SCP results in a robust and safe IMRT planning concept.

Background: Early stage prostate cancer can be treated successfully by interstitial brachytherapy with 125-iodine seeds. A quality-assurance programme is presented that was designed for this purpose for internal clinical use. Furthermore the requirements of the new German Ordinance Governing Radiation Protection (StrlSchV) that came into force on August 1, 2001, are taken into account., Material and Methods: For the 125-iodine monotherapy of the prostate we used RAPID STRANDS (Amersham Health, Braunschweig, Germany). According to the guidelines of the new Ordinance Governing Radiation Protection, the determination of the body dose of the staff is made to rely on the new measurement quantities H(p) (10) and H(p) (0.07). The nominal air kerma rate of the seeds is measured with a calibrated well-chamber of the type HDR 1000 Plus and an electrometer of the type MAX 4000 (Standard Imaging Inc., USA). The ultrasound images of the prostate are produced by an ultrasound device of the type Falcon 2101 (B-K Medical, Denmark). For treatment planning the programme VariSeed (Varian, Darmstadt, Germany) was employed. Correct loading of the needles is controlled by autoradiography before implantation. After the implantation radiation-protection measurements in the operating room are carried out., Results: As regards the personnel, for the depth personal dose equivalent Hp(10) and relating to two applications each, measurement values between 0 microSv and 14 microSv resulted. The control of the radiation exposure of the hands revealed superficial personal dose values H(p) (0.07) of up to 1 mSv. The nominal air kerma rates of the RAPID STRANDS were all lying within the 95% confidence interval guaranteed by the producer. The autoradiographs documented -- except for one case -- the correct loading of the needles. The interstitial transperineal prostate implantation of the 125-iodine seeds succeeded as planned with all patients. Until now no contamination of the operating room was detected by the radiation-protection measurements., Conclusion: The physical-technical quality assurance programme presented here covers the whole physical-technical range of the internal clinical quality assurance and could be integrated into the course of the treatment without any problems. It has th following advantages: The autoradiographic documentation of the correctly loaded needles serves as proof that the prerequisite for the production of the prescribed physical dose distribution is fulfilled. The internal clinical determination of the nominal air kerma rate is the basis for a correct dose application.

Background: Interstitial brachytherapy with I-125 seeds can be used for successful treatment of early stage prostate cancer. There is presented the technique of permanent transperineal implantation of I-125 seeds with intraoperative treatment planning which is suited for the treatment of prostate cancer up to the clinical stage of T2a., Material and Methods: Some weeks before the implantation of the seeds the prostate volume is determined using transrectal ultrasound (TRUS) so as to estimate the required number of I-125 seeds. At the outset of the treatment the prostate is stabilized by two perineally inserted needles. Subsequently there is carried out an ultrasound guided treatment planning that allows to optimize the distribution of the seeds within the prostate. In interstitial brachytherapy we use RAPID STRANDS((R)), i. e. the I-125 seeds are embedded in vicryl suture at distances of 1 cm. During implantation of the I-125 seeds the transversal placement of the applicator needles is controlled by TRUS and the cranio-caudal placement of the applicator needles is controlled using the fluoroscopic unit as well as TRUS. About 4 weeks after the implantation of the seeds there is carried out a postoperative computation of the dose distribution of the implant using CT imaging., Results: The procedure possesses the advantage that ultrasound imaging, treatment planning and seed implantation are carried out with the prostate remaining in an unaltered position. During implantation the combined imaging of TRUS and fluoroscopy allows a safe placement of the seeds with in the prostate., Conclusion: The methods for the calculation of the actually attained dose distribution must still be optimized, because the postoperative examination of the individual results has so far been possible only with difficulties resulting from methodological inconveniences.

Background: Conformal radiotherapy techniques as used in prostate treatment allow to spare normal tissue by conforming the radiation fields to the shape of the planning target volume (PTV). To be able to fully utilize the advantages of these techniques correct patient positioning is an important prerequisite. This study employing an electronic portal imaging device (EPID) investigated the positioning uncertainties that occur in the pelvic region for different patient positioning devices., Patients and Methods: 15 patients with prostate cancer were irradiated with or without rectal balloon/pelvic mask at a linear accelerator with multileaf collimator (MLC). For each patient multiple portal images were taken from different directions and compared to the digitally reconstructed radiographs (DRRs) of the treatment planning system and to simulation films (Table 1, Figure 1)., Results: In spite of different positioning devices, all patients showed comparable total positioning uncertainties of 4.0 mm (lateral), 4.5 mm (cranio-caudal) and 1.7 mm (dorso-ventral). The lateral positioning error was reduced for the pelvic mask patients while the cranio-caudal error increased (Table 2, Figure 2). A systematic and a random component sum up to the total positioning error, and a good estimate of the magnitudes of the two is possible from six to eight portal images (Figure 3)., Conclusions: With a small number of portal images it is possible to find out the systematic and random positioning error of a patient. Knowledge of the random error can be used to resize the treatment margin which is clinically relevant since this error differs greatly for different patients (Figure 4). Image analysis with EPID is convenient, yet has some problems. For example, one only gets indirect information on the movement of the ventral rectum wall (Figure 5). The successful operation of positioning devices, although, needs further improvement--especially if one focuses on IMRT.

Simple Summary: In this clinical trial, 63 patients with a total of 89 prostate cancer metastases identified on PSMA-PET were included, none of them undergoing androgen deprivation therapy. We showed that local ablative radiotherapy controls >90% of the metastases, but progression at other sites is common after two years. Local ablative radiotherapy may be an option to at least temporarily avoid systemic therapy in selected patients. Progression of prostate-specific antigen (PSA) values after curative treatment of prostate cancer patients is common. Prostate-specific membrane antigen (PSMA-) PET imaging can identify patients with metachronous oligometastatic disease even at low PSA levels. Metastases-directed local ablative radiotherapy (aRT) has been shown to be a safe treatment option. In this prospective clinical trial, we evaluated local control and the pattern of tumor progression. Between 2014 and 2018, 63 patients received aRT of 89 metastases (MET) (68 lymph node (LN-)MET and 21 bony (OSS-)MET) with one of two radiation treatment schedules: 50 Gy in 2 Gy fractions in 34 MET or 30 Gy in 10 Gy fractions in 55 MET. The mean gross tumor volume and planning target volume were 2.2 and 14.9 mL, respectively. The median follow-up time was 40.7 months. Local progression occurred in seven MET, resulting in a local control rate of 93.5% after three years. Neither treatment schedule, target volume, nor type of lesion was associated with local progression. Regional progression in the proximity to the LN-MET was observed in 19 of 47 patients with at least one LN-MET (actuarial 59.3% free of regional progression after 3 years). In 33 patients (52%), a distant progression was reported. The median time to first tumor-related clinical event was 16.6 months, and 22.2% of patients had no tumor-related clinical event after three years. A total of 14 patients (22%) had another aRT. In conclusion, local ablative radiotherapy in patients with PSMA-PET staged oligometastatic prostate cancer may achieve local control, but regional or distant progression is common. Further studies are warranted, e.g., to define the optimal target volume coverage in LN-MET and OSS-MET. [ABSTRACT FROM AUTHOR]