Impact of androgen deprivation therapy on apparent diffusion coefficient and T2w MRI for histogram and texture analysis with respect to focal radiotherapy of prostate cancer.

PURPOSE: Accurate prostate cancer (PCa) detection is essential for planning focal external beam radiotherapy (EBRT). While biparametric MRI (bpMRI) including T2-weighted (T2w) and diffusion-weighted images (DWI) is an accurate tool to localize PCa, its value is less clear in the case of additional androgen deprivation therapy (ADT). The aim of this study was to investigate the value of a textural feature (TF) approach on bpMRI analysis in prostate cancer patients with and without neoadjuvant ADT with respect to future dose-painting applications. METHODS: 28 PCa patients (54-80 years) with (n = 14) and without (n = 14) ADT who underwent bpMRI with T2w and DWI were analyzed retrospectively. Lesions, central gland (CG), and peripheral zone (PZ) were delineated by an experienced urogenital radiologist based on localized pre-therapeutic histopathology. Histogram parameters and 20 Haralick TF were calculated. Regional differences (i. e., tumor vs. PZ, tumor vs. CG) were analyzed for all imaging parameters. Receiver-operating characteristic (ROC) analysis was performed to measure diagnostic performance to distinguish PCa from benign prostate tissue and to identify the features with best discriminative power in both patient groups. RESULTS: The obtained sensitivities were equivalent or superior when utilizing the TF in the no-ADT group, while specificity was higher for the histogram parameters. However, in the ADT group, TF outperformed the conventional histogram parameters in both specificity and sensitivity. Rule-in and rule-out criteria for ADT patients could exclusively be defined with the aid of TF. CONCLUSIONS: The TF approach has the potential for quantitative image-assisted boost volume delineation in PCa patients even if they are undergoing neoadjuvant ADT.

68Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy - diagnostic performance and impact on therapeutic decision-making.

OBJECTIVE: To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS: We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS: The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS: We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.

Time course of late rectal- and urinary bladder side effects after MRI-guided adaptive brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To analyze the time course of late rectal- and urinary bladder complications after brachytherapy for cervical cancer and to compare the incidence- and prevalence rates thereof. PATIENTS AND METHODS: A total of 225 patients were treated with external-beam radiotherapy (EBRT) and magnetic resonance imaging (MRI)-guided brachytherapy with or without chemotherapy. Late side effects were assessed prospectively using the Late Effects in Normal Tissue--Subjective, Objective, Management and Analytic (LENT/SOMA) scale. The parameters analyzed were time to onset, duration, actuarial incidence- (occurrence of new side effects during a defined time period) and prevalence rates (side effects existing at a defined time point). RESULTS: Median follow-up was 44 months. Side effects (grade 1-4) in rectum and bladder were present in 31 and 49 patients, 14 and 27 months (mean time to onset) after treatment, respectively. All rectal and 76 % of bladder side effects occurred within 3 years after radiotherapy. Mean duration of rectal events was 19 months; 81 % resolved within 3 years of their initial diagnosis. Mean duration of bladder side effects was 20 months; 61 % resolved within 3 years. The 3- and 5-year actuarial complication rates were 16 and 19 % in rectum and 18 and 28 % in bladder, respectively. The corresponding prevalence rates were 9 and 2 % (rectum) and 18 and 21 % (bladder), respectively. CONCLUSION: Late side effects after cervical cancer radiotherapy are partially reversible, but their time course is organ-dependent. The combined presentation of incidence- and prevalence rates provides the most comprehensive information.

Feasibility of transrectal ultrasonography for assessment of cervical cancer.

PURPOSE: To retrospectively compare the maximum target width and target thickness in patients with locally advanced cervical cancer between magnetic resonance imaging (MRI) and transrectal ultrasonography (TRUS) in the course of primary radiochemotherapy. PATIENTS AND METHODS: T2-weighted MRI and TRUS were performed on patients with locally advanced cervical cancer at the same timepoint-either at the time of diagnosis, or at the time of brachytherapy before or after insertion of the applicator. Patients treated from 2009 to 2011 were selected for this study based on the availability of MRI and TRUS at the defined time points. The target was defined as the complete macroscopic tumor mass and the remaining cervix and was measured on transversal planes. Descriptive statistics and a linear regression analysis were performed for the groups. RESULTS: Images from 17 patients were available for analysis. Mean maximum target width was 4.2 ± 0.83 cm and 4.2 ± 0.79 cm for MRI and TRUS, respectively. Mean maximum target thickness was 3.3 ± 1.03 cm and 3.1 ± 1.15 cm for MRI and TRUS, respectively. Linear regression analysis for target width and thickness between TRUS and MRI demonstrated a correlation with R(2) = 0.842 and R(2) = 0.943, respectively. CONCLUSION: The feasibility of TRUS for the assessment of local target extension could be demonstrated. Comparison of the target width and thickness showed a high correlation between TRUS and MRI, indicating the potential of TRUS for target definition in image-guided adaptive brachytherapy.

Assessment of accuracy and efficiency of atlas-based autosegmentation for prostate radiotherapy in a variety of clinical conditions.

BACKGROUND AND PURPOSE: The goal of the current study was to evaluate the commercially available atlas-based autosegmentation software for clinical use in prostate radiotherapy. The accuracy was benchmarked against interobserver variability. MATERIAL AND METHODS: A total of 20 planning computed tomographs (CTs) and 10 cone-beam CTs (CBCTs) were selected for prostate, rectum, and bladder delineation. The images varied regarding to individual (age, body mass index) and setup parameters (contrast agent, rectal balloon, implanted markers). Automatically created contours with ABAS(®) and iPlan(®) were compared to an expert's delineation by calculating the Dice similarity coefficient (DSC) and conformity index. RESULTS: Demo-atlases of both systems showed different results for bladder (DSC(ABAS) 0.86 ± 0.17, DSC(iPlan) 0.51 ± 0.30) and prostate (DSC(ABAS) 0.71 ± 0.14, DSC(iPlan) 0.57 ± 0.19). Rectum delineation (DSC(ABAS) 0.78 ± 0.11, DSC(iPlan) 0.84 ± 0.08) demonstrated differences between the systems but better correlation of the automatically drawn volumes. ABAS(®) was closest to the interobserver benchmark. Autosegmentation with iPlan(®), ABAS(®) and manual segmentation took 0.5, 4 and 15-20 min, respectively. Automatic contouring on CBCT showed high dependence on image quality (DSC bladder 0.54, rectum 0.42, prostate 0.34). CONCLUSION: For clinical routine, efforts are still necessary to either redesign algorithms implemented in autosegmentation or to optimize image quality for CBCT to guarantee required accuracy and time savings for adaptive radiotherapy.

Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients.

PURPOSE: The aim of this analysis was to compare the biochemical no evidence of disease (bNED) rates in low-risk prostate cancer patients treated at two centers of excellence using different approaches: seed brachytherapy (BT) and external beam radiotherapy (EBRT). MATERIALS AND METHODS: A total of 919 low-risk prostate cancer patients, treated from 1998-2008, were identified in the two databases. In Utrecht, 667 patients received I-125 BT applying a dose of 144 Gy. In Vienna, 252 patients were treated with EBRT, applying a local dose of 70 Gy in 82 patients and 74 Gy in 170 patients. bNED rates (Phoenix definition) were assessed. RESULTS: The median follow-up was 46 months (range 1-148 months). The 5-year actuarial bNED rates were 94% for BT patients and 88% for EBRT patients (p = 0.002)-84% for patients receiving 70 Gy and 91% for patients receiving 74 Gy, respectively. In the univariate analysis, patients receiving 70 Gy showed significantly worse outcome compared to BT (p = 0.001) and a difference close to significance compared to 74 Gy (p = 0.06). In the multivariate analysis including tumor stage, Gleason score, initial PSA, hormonal therapy, and dose, patients receiving 70 Gy EBRT showed significantly worse bNED rates compared to BT patients. CONCLUSION: Low-risk prostate cancer patients receiving 74 Gy by EBRT show comparable biochemical control rates to patients receiving seed brachytherapy, whereas patients receiving 70 Gy show significantly worse outcome.

A randomised controlled trial evaluating the effects of two workstation interventions on upper body pain and incident musculoskeletal disorders among computer operators.

BACKGROUND: Call centre work with computers is associated with increased rates of upper body pain and musculoskeletal disorders. METHODS: This one year, randomised controlled intervention trial evaluated the effects of a wide forearm support surface and a trackball on upper body pain severity and incident musculoskeletal disorders among 182 call centre operators at a large healthcare company. Participants were randomised to receive (1) ergonomics training only, (2) training plus a trackball, (3) training plus a forearm support, or (4) training plus a trackball and forearm support. Outcome measures were weekly pain severity scores and diagnosis of incident musculoskeletal disorder in the upper extremities or the neck/shoulder region based on physical examination performed by a physician blinded to intervention. Analyses using Cox proportional hazard models and linear regression models adjusted for demographic factors, baseline pain levels, and psychosocial job factors. RESULTS: Post-intervention, 63 participants were diagnosed with one or more incident musculoskeletal disorders. Hazard rate ratios showed a protective effect of the armboard for neck/shoulder disorders (HR = 0.49, 95% CI 0.24 to 0.97) after adjusting for baseline pain levels and demographic and psychosocial factors. The armboard also significantly reduced neck/shoulder pain (p = 0.01) and right upper extremity pain (p = 0.002) in comparison to the control group. A return-on-investment model predicted a full return of armboard and installation costs within 10.6 months. CONCLUSION: Providing a large forearm support combined with ergonomic training is an effective intervention to prevent upper body musculoskeletal disorders and reduce upper body pain associated with computer work among call centre employees.

Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors.

PURPOSE: To identify clinically relevant parameters predictive of late rectal bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum after conformal radiotherapy of prostate cancer. MATERIALS AND METHODS: One hundred and nine patients treated with 3D conformal radiotherapy between 1/1994 and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction (specified at the International Commission on Radiation Units and Measurements ICRU reference point). DVHs of the contoured rectum were analyzed by defining the absolute (aV) and relative (rV) rectum volume that received more than 30% (V30), 50% (V50), 70% (V70), 80% (V80), 90% (V90) and 100% (V100) of the prescribed dose. Additionally, a new aspect of DVH analysis was investigated by calculation of the area under the DVH-curve between several dose levels (area under the curve (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated in 3-6 months intervals and graded according to the EORTC/RTOG score. The median follow-up was 30 months (12-60 months). RESULTS: Univariate and multivariate stepwise Cox-Regression analysis including age, PTV, rectum size, rV100, rV90, rV80, rV70, rV50 rV30 and aV30 to aV100 were calculated. Late rectal bleeding (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum volume receiving > or = 90% of the prescribed dose (rV90) (P = 0.007) and inversely correlated in a significant way with the size of contoured rectum (P = 0.006) in multivariate analysis. In our series, a proportion of the rectum volume > or = 57% were included in the 90%-isodose (rV90 > or = 57%) in one half of the patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years. In the other half of the patients, when rV90 < 57%, the 3-year actuarial incidence was 11% (P < 0.03). CONCLUSION: Our data demonstrate a dose-volume relationship at the reference dose of 60 Gy ( approximately 90% of the prescribed dose) with respect to late rectal toxicity. The rV90 seems to be the most useful and easily obtained parameter when comparing treatment plans to evaluate the risk of rectal morbidity.

Endoscopic scoring of late rectal mucosal damage after conformal radiotherapy for prostatic carcinoma.

PURPOSE: To describe rectal mucosal damage in an endoscopic study after conformal radiotherapy of prostate cancer and to correlate this with clinical outcome. MATERIALS AND METHODS: Flexible rectosigmoidoscopy was performed on 44 patients who voluntarily accepted the examination. The median follow-up was 29 months (20-41 months) after 3-D-planned conformal radiotherapy of prostate cancer (66 Gy at the ICRU Reference point, 2 Gy per fraction). To enable a systematic topographic description of endoscopic findings the rectum was divided into four sections. Additionally we differentiated between anterior, posterior, right and left lateral rectal wall. Due to the lack of an existing valid graduation system for radiation induced proctitis, we introduced a six-scaled rectoscopy score for describing and reporting endoscopic findings based on the standardization of the endoscopic terminology published by the ESGE (European Society for Gastrointestinal Endoscopy). Endoscopic findings were compared to the EORTC/RTOG morbidity score. In addition, since 3-D dose distribution of organs at risks was available, a correlation could be made between the location of the rectal lesions and the absorbed dose at that level. RESULTS: In general, endoscopic findings increased from the proximal rectum to the anorectal transition, as well as from the posterior to the anterior rectum wall. Telangiectasia grade 1 and 2 were observed at the whole circumference, only telangiectasia grade 3 were limited to the high dose region at the anterior rectum wall. Similar results were found for congested mucosa (reddening and edematous mucosa). Correlation with symptoms, 7/9 patients who suffered from intermittent rectal bleeding (EORTC/RTOG grade 2) had multiple telangiectasia grade 2-3 and/or congested mucosa grade 3 and microulcerations. However, the same extent of mucosal damage (rectoscopy score 2-3) was found in seven out of 35 patients who have never developed a period of macroscopic rectal bleeding. CONCLUSION: Rectoscopy offers the possibility of detecting signs of tissue dysfunction below the level of subjective symptoms. Systematic analytic examinations such as rectoscopy, in addition to clinical examinations, as already foreseen in the LENT-SOMA-score, will be necessary due to the fact that even telangiectatic lesions have been observed for asymptomatic patients. For the opportunity of sharing and comparing data collected from endoscopy after radiotherapy a graduation system as proposed based on a standardisation of the endoscopic terminology will be necessary.

Three dimensional conformal photon radiotherapy at a moderate dose level of 66 Gy for prostate carcinoma: early results.

BACKGROUND: The therapeutic outcome and toxicity of 3-D conformal photon external beam therapy of prostate cancer is well documented in the literature. Progress is still in work for optimization of treatment strategies by risk-adapted dose escalation studies to improve local tumor control without increase of radiation side effects. PATIENTS AND METHODS: We present our experience of 291 patients treated between January 1994 and August 1997 with a 3-D planned four-field box technique and a central dose of 66 Gy. Biochemical response of patients with radiotherapy alone (group 1, n = 72 pts.) has been analyzed in detail. Acute radiation side effects are given for all patients (n = 291), late radiation side effects are given for patients treated between Jan 1994 and Jan 1996 with a median follow-up of 22 months (n = 115 pts.). RESULTS: We have observed a biochemical response (nadir PSA < 1 after 12 months, < 2 after 6 months) for patients treated with radiotherapy alone without hormone manipulation in 67%. Incidence of late rectal and bladder morbidity (grade 2 and 3) was 9.4% and 4%, respectively. CONCLUSION: Compared to other reports our results indicate a high rate of local tumor control (early biochemical response) and a low rate of late morbidity. Nevertheless, we will start a risk-adapted dose escalation study up to 74 Gy for unfavorable subgroups (G2-3, Gleason Score > 7, PSA > 10) to improve treatment outcome.

[Significance of a rectal balloon as internal immobilization device in conformal radiotherapy of prostatic carcinoma]. / Die Bedeutung eines Rektumballons als interne Immobilisation bei der konformalen Strahlentherapie des Prostatakarzinoms.

BACKGROUND: As known from the literature, prostate motion depends on different bladder and/or rectum fillings. The aim of this study was to analyze the influence of a rectum balloon catheter, used as an internal immobilization device, on prostate and rectum motion during the treatment course. Moreover we have analyzed if the balloon enables an increase of the distance between the prostate and the posterior rectum wall. PATIENTS AND METHODS: Ten patients with localized prostate cancer (T1 to T3) underwent computed tomographic examinations with and without rectal balloon (filled with 40 ml air) at 3 times during treatment course (at the start, middle and end of treatment). Edges of prostate, rectum and bladder were measured in relation to bony reference structures and compared for both examination series (with and without balloon). RESULTS: An increase of the distance between the prostate and the posterior rectal wall of 8 mm was observed at the base of the prostate when using the rectum balloon (Figures 1a,b and 2). Moreover prostate motion in the ventrodorsal direction > or = 4 mm (1 SD) was reduced from 6/10 patients (60%) to 1/10 patients (10%) using the rectal balloon (Table 3, Figure 3). In general, deviations in the latero-lateral and cranio-caudal directions were less (mean < or = 2 mm, 1 SD), no difference between both examination series (with and without balloon) was observed. CONCLUSION: Rectal balloon catheter offers a possibility to reduce prostate motion and rectum filling variations during treatment course. In addition it enables an increase in the distance between prostate and posterior rectal wall, which could enable an improved protection of the posterior rectal wall.