MRI assessment of seminal vesicle involvement by prostate cancer using T2 signal intensity and volume.

BACKGROUND: Seminal vesicle involvement (SVI) in patients with newly diagnosed prostate cancer is associated with high rates of treatment failure and tumor recurrence; correct identification of SVI allows for effective management decisions and surgical planning. METHODS: This single-center retrospective study analyzed MR images of the seminal vesicles from patients undergoing radical prostatectomy with confirmed T3b disease, comparing them to a control group without SVI matched for age and Gleason grade with a final stage of T2 or T3a. Seminal vesicles were segmented by an experienced uroradiologist, "raw" and bladder-normalized T2 signal intensity, as well as SV volume, were obtained. RESULTS: Among the 82 patients with SVI, 34 (41.6%) had unilateral invasion, and 48 (58.4%) had bilateral disease. There was no statistically significant difference in the degree of distension between normal and involved seminal vesicles (P = 0.08). Similarly, no statistically significant difference was identified in the raw SV T2 signal intensity (P = 0.09) between the groups. In the 159 patients analyzed, SVI was prospectively suspected in 10 of 82 patients (specificity, 100%; sensitivity, 12.2%). In all these cases, lesions macroscopically invaded the seminal vesicle, and the raw T2 signal intensity was significantly lower than that in the SVI and control groups (P = 0.02 and 0.01). CONCLUSION: While signal intensity measurements in T2-weighted images may provide insight into T3b disease, our findings suggest that this data alone is insufficient to reliably predict SVI, indicating the need for further investigation and complementary diagnostic approaches.

Associations of PTEN and ERG with Magnetic Resonance Imaging Visibility and Assessment of Non-organ-confined Pathology and Biochemical Recurrence After Radical Prostatectomy.

BACKGROUND: Diagnosing clinically significant prostate cancer (PCa) is challenging, but may be facilitated by biomarkers and multiparametric magnetic resonance imaging (MRI). OBJECTIVE: To determine the association between biomarkers phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) with visible and invisible PCa lesions in MRI, and to predict biochemical recurrence (BCR) and non-organ-confined (non-OC) PCa by integrating clinical, MRI, and biomarker-related data. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a population-based cohort of men with PCa, who underwent preoperative MRI followed by radical prostatectomy (RP) during 2014-2015 in Helsinki University Hospital (n = 346), was conducted. A tissue microarray corresponding to the MRI-visible and MRI-invisible lesions in RP specimens was constructed and stained for PTEN and ERG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of PTEN and ERG with MRI-visible and MRI-invisible lesions were examined (Pearson's χ2 test), and predictions of non-OC disease together with clinical and MRI parameters were determined (area under the receiver operating characteristic curve and logistic regression analyses). BCR prediction was analyzed by Kaplan-Meier and Cox proportional hazard analyses. RESULTS AND LIMITATIONS: Patients with MRI-invisible lesions (n = 35) had less PTEN loss and ERG-positive expression compared with patients (n = 90) with MRI-visible lesions (17.2% vs 43.3% [p = 0.006]; 8.6% vs 20.0% [p = 0.125]). Patients with invisible lesions had better, but not statistically significantly improved, BCR-free survival probability in Kaplan-Meier analyses (p = 0.055). Rates of BCR (5.7% vs 21.1%; p = 0.039), extraprostatic extension (11.4% vs 44.6%; p < 0.001), seminal vesicle invasion (0% vs 21.1%; p = 0.003), and lymph node metastasis (0% vs 12.2%; p = 0.033) differed between the groups in favor of patients with MRI-invisible lesions. Biomarkers had no independent role in predicting non-OC disease or BCR. The short follow-up period was a limitation. CONCLUSIONS: PTEN loss, BCR, and non-OC RP findings were more often encountered with MRI-visible lesions. PATIENT SUMMARY: Magnetic resonance imaging (MRI) of the prostate misses some cancer lesions. MRI-invisible lesions seem to be less aggressive than MRI-visible lesions.

Knowledge-Based Assessment of Focal Dose Escalation Treatment Plans in Prostate Cancer.

PURPOSE: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model. METHODS AND MATERIALS: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans. RESULTS: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86). CONCLUSIONS: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans.

Effect of observation size and apparent diffusion coefficient (ADC) value in PI-RADS v2.1 assessment category 4 and 5 observations compared to adverse pathological outcomes.

OBJECTIVE: To compare observation size and apparent diffusion coefficient (ADC) values in Prostate Imaging Reporting and Data System (PI-RADS) v2.1 category 4 and 5 observations to adverse pathological features. MATERIALS AND METHODS: With institutional review board approval, 267 consecutive men with 3-T MRI before radical prostatectomy (RP) between 2012 and 2018 were evaluated by two blinded radiologists who assigned PI-RADS v2.1 scores. Discrepancies were resolved by consensus. A third blinded radiologist measured observation size and ADC (ADC.mean, ADC.min [lowest ADC within an observation], ADC.ratio [ADC.mean/ADC.peripheral zone {PZ}]). Size and ADC were compared to pathological stage and Gleason score (GS) using t tests, ANOVA, Pearson correlation, and receiver operating characteristic (ROC) analysis. RESULTS: Consensus review identified 267 true positive category 4 and 5 observations representing 83.1% (222/267) PZ and 16.9% (45/267) transition zone (TZ) tumors. Inter-observer agreement for PI-RADS v2.1 scoring was moderate (K = 0.45). Size was associated with extra-prostatic extension (EPE) (19 ± 8 versus 14 ± 6 mm, p < 0.001) and seminal vesicle invasion (SVI) (24 ± 9 versus 16 ± 7 mm, p < 0.001). Size ≥ 15 mm optimized the accuracy for EPE with area under the ROC curve (AUC) and sensitivity/specificity of 0.68 (CI 0.62-0.75) and 63.2%/65.6%. Size ≥ 19 mm optimized the accuracy for SVI with AUC/sensitivity/specificity of 0.75 (CI 0.66-0.83)/69.4%/70.6%. ADC metrics were not associated with pathological stage. Larger observation size (p = 0.032), lower ADC.min (p = 0.010), and lower ADC.ratio (p = 0.010) were associated with higher GS. Size correlated better to higher Gleason scores (p = 0.002) compared to ADC metrics (p = 0.09-0.11). CONCLUSION: Among PI-RADS v2.1 category 4 and 5 observations, size was associated with higher pathological stage whereas ADC metrics were not. Size, ADC.minimum, and ADC.ratio differed in tumors stratified by Gleason score. KEY POINTS: • Among PI-RADS category 4 and 5 observations, size but not ADC can differentiate between tumors by pathological stage. • An observation size threshold of 15 mm and 19 mm optimized the accuracy for diagnosis of extra-prostatic extension and seminal vesicle invasion. • Among PI-RADS category 4 and 5 observations, size, ADC.minimum, and ADC.ratio differed comparing tumors by Gleason score.

Characterization and PI-RADS version 2 assessment of prostate cancers missed by prebiopsy 3-T multiparametric MRI: Correlation with whole-mount thin-section histopathology.

OBJECTIVES: To determine the clinical and histopathologic characteristics of missed prostate cancers and their Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score on a pre-biopsy MRI and subsequent MR-ultrasound (US) fusion biopsy. METHODS: We analysed 59 prostate cancer patients who underwent a 3-T MRI prior to an MR-US fusion biopsy and subsequent radical prostatectomy. A radiologist initially reviewed these cases to correlate target lesions and pathology-proven lesions. The patients were categorized as detected or missed prostate cancer cases. Three radiologists independently assigned the PI-RADS v2 score for each case. The missed lesions were further categorized as suspicious or invisible by consensus. The clinical characteristics, PI-RADS v2 scores, and histopathologic features were thereby obtained. RESULTS: Thirty seven (62.7%) of the 59 study cases had a detected prostate cancer and 22 (37.3%) as having missed cancer. Seventeen (77.3%) of the 22 missed patients had a clinically significant lesion. The missed cancer cases had a smaller tumour volume, and higher ADC ratio than the detected cancer cases. Fourteen (63.6%) of the missed lesions were not visible on MRI, even though 71.4% of these cancers were clinically significant. Invisible but clinically significant cancers had a tumour volume below 1 cm3 in 70% of cases. CONCLUSIONS: A negative MRI result does not rule out the current PI-RADS v2 definition of a clinically significant prostate cancer as these tumours can be missed if their volume is below 1 cm3.

The applied research of simultaneous image acquisition of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) in the assessment of patients with prostate cancer.

We aimed to evaluate the feasibility of simultaneous image acquisition of multiple instantaneous switchable scan (MISS) for prostate magnetic resonance imaging (MRI) on 3T. Fifty-three patients were scanned with MRI due to suspected prostate cancer. Twenty-eight of them got histological results. First, two readers assessed the structure delineation and image quality based on images of conventional T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) (CTD). Second, two readers identified the index lesion together, and then, reader one evaluated the contrast of index lesion on T2WI and signal ratio on apparent diffusion coefficient map. Third, they assigned Prostate Imaging Reporting and Data System (PI-RADS) score in consensus for the index lesion. After 4 weeks, the images of MISS were reviewed by the same readers following the same process. Finally, two readers gave preference for image interpretation, respectively. Kappa coefficient, Wilcoxon signed-rank test, paired-sample t-test, Bland-Altman analysis, and receiver operating characteristic (ROC) analysis were used for statistical analysis. The acquisition time of CTD was 6 min and 10 s, while the acquisition time of MISS was 4 min and 30 s. Interobserver agreements for image evaluation were κ = 0.65 and κ = 0.80 for CTD and MISS, respectively. MISS-T2WI showed better delineation for seminal vesicles than CTD-T2WI (reader 1: P < 0.001, reader 2: P = 0.001). The index lesion demonstrated higher contrast in MISS-T2WI (P < 0.001). The PI-RADS scores based on CTD and MISS exhibited high ability in predicting clinically significant cancer (area under curve [AUC] = 0.828 vs 0.854). Readers preferred to use MISS in 41.5%-47.2% of cases. MISS showed comparable performance to conventional technique with less acquisition time.

Per-organ assessment of subject-induced susceptibility distortion for MR-only male pelvis treatment planning.

BACKGROUND: Patient-specific distortions, particularly near tissue/air interfaces, require assessment for magnetic resonance (MR) only radiation treatment planning (RTP). However, patients are dynamic due to changes in physiological status during imaging sessions. This work investigated changes in subject-induced susceptibility distortions to pelvic organs at different bladder states to support pelvis MR-only RTP. METHODS: Pelvises of 9 healthy male volunteers were imaged at 1.0 Tesla (T), 1.5 T, and 3.0 T. Subject-induced susceptibility distortion field maps were generated using a dual-echo gradient-recalled echo (GRE) sequence with B0 field maps obtained from the phase difference between the two echoes acquired at several bladder volume states (3-4/subject, 32 overall). T2 turbo spin echo images were also acquired at each bladder state for organ delineation. Magnet central frequency was tracked over time. Distortion map differences and boxplots were computed to characterize changes within the clinical target volume (CTV), bladder, seminal vesicles, and prostate volumes. RESULTS: The time between the initial and final B0 maps was 42.6 ± 13.9 (range: 13.2-62.1) minutes with minimal change in magnet central frequency (0.02 ± 0.05 mm (range: - 0.06 - 0.12 mm)). Subject-induced susceptibility distortion across all bladder states, field strengths, and subjects was relatively small (1.4-1.9% of all voxels in the prostate and seminal vesicles were distorted > 0.5 mm). In the bladder, no voxels exhibited distortions > 1 mm. An extreme case acquired at 3.0 T with a large volume of rectal air yielded 27.4-34.6% of voxels within the CTVs had susceptibility-induced distortions > 0.5 mm across all time points. CONCLUSIONS: Our work suggests that subject-induced susceptibility distortions caused by bladder/rectal conditions are generally small and subject-dependent. Local changes may be non-negligible within the CTV, thus proper management of filling status is warranted. Future work evaluating the impact of multiple models to accommodate for extreme status changes may be advantageous.

The Australian laparoscopic non robotic radical prostatectomy experience - analysis of 2943 cases (USANZ supplement).

OBJECTIVES: To analyse the Australian experience of high-volume Fellowship-trained Laparoscopic Radical Prostatectomy (LRP) surgeons. MATERIALS AND METHODS: 2943 LRP cases were performed by nine Australian surgeons. The inclusion criteria were a prospectively collected database with a minimum of 100 consecutive LRP cases. The surgeons' LRP experience commenced at various times from July 2003 to September 2009. Data were analysed for demographic, peri-operative, oncological and functional outcomes. RESULTS: The mean age of patients were 61.5 years and mean preoperative PSA 7.4 ng/ml. Mean operating time was 168 minutes with conversion to open surgery in 0.5% and a blood transfusion rate of 1.1%. Overall mean length of stay was 2.5 days. 73.6% of pathological specimens were pT2 and 86.3% had Gleason Score >7. Overall positive surgical margins (PSM) occurred in 15.9% with pT2 PSM 9.8%, pT3a PSM 30.8% and pT3b PSM 39.2%. Mean urinary continence at 12 months was 91.4% (data available from five surgeons). Mean 12 months potency after bilateral nerve spare was 47.2% (data available from four surgeons). Biochemical recurrence occurred in 10.6% (mean follow up 17 months). CONCLUSION: The Australian experience of Fellowship trained surgeons performing LRP demonstrates favourable peri-operative, oncological and functional outcomes in comparison to published data for open, laparoscopic and robotic assisted radical prostatectomy. In our Australian centres, LRP remains an acceptable minimally invasive surgical treatment for prostate cancer despite the increasing use of robotic assisted surgery.

[Transurethral seminal vesiculoscopy for the treatment of vesiculitis with hemospermia:A report of 64 cases].

Objective: To explore the treatment of vesiculitis with hemospermia by transurethral seminal vesiculoscopy. Methods: We treated 64 cases of vesiculitis with hemospermia by transurethral seminal vesiculoscopy. During the operation,we removed the stones and inflammatory substances and collected seminal vesicle fluid to be cultured for bacteria,ureaplasma urealyticum(UU),chlamydia trachomatis(CT),and mycoplasma hominis(MH),followed by infusion of levofloxacin at 0. 3 g/100 ml into the seminal vesicle. Regular follow-up was conducted post-operatively. Results: All the operations were successfully accomplished, the operation time averaging(40 ± 15) min(25- 50 min). The ejaculatory duct opening was observed on the verumontanum surface in the posterior urethra in 2 cases, abnormal passages found in the prostatic utricle in 8 cases, and seminal vesicle fenestration from the prostatic utricle conducted in the other 54 cases(32 by seminal vesiculoscopy and 22 with holmium laser). Stones were seen in the prostatic utricle in 5 cases, in the seminal vesicle in 6 cases, and in both the prostatic utricle and seminal vesicle in 2 cases. Culture of the seminal vesicle fluid showed the acinetobacter to be positive in 1 case and UU, CT, and MH to be negative. At 3 months after surgery, hemospermia was cured in 52 cases, relieved in 8,and unimproved in 4. Conclusion: Seminal vesicle fenestration drainage by transurethral seminal vesiculoscopy for the treatment of vesiculitis with hemospermia has the advantages of short operation time, high effectiveness and no obvious complications and can also be employed for the examination of the seminal vesicle as well as removal of stones and inflammatory substances.

Upfront androgen deprivation therapy with salvage radiation may improve biochemical outcomes in prostate cancer patients with post-prostatectomy rising PSA.

PURPOSE: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. METHODS AND MATERIALS: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at the University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. RESULTS: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores ≤7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). CONCLUSIONS: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in which ADT could provide the most benefit remain open questions.

Diagnostic utility of P504S/p63 cocktail, prostate-specific antigen, and prostatic acid phosphatase in verifying prostatic carcinoma involvement in seminal vesicles: a study of 57 cases of radical prostatectomy specimens of pathologic stage pT3b.

CONTEXT: Seminal vesicle invasion by prostatic carcinoma is directly associated with tumor staging; verification is challenging when the tumor demonstrates cribriform or papillary growth patterns or there are back-to-back small-gland proliferations. P504S is overexpressed in prostatic carcinoma and high-grade prostatic intraepithelial neoplasia with cytoplasmic immunoreactivity. p63 has positive immunoreactivity in basal cell nuclei of benign prostatic glands. Many researchers use a combination of these antibodies and their different colors. OBJECTIVE: To evaluate the usefulness of a single-color P504S/p63 cocktail immunostain in verifying prostatic carcinoma within the seminal vesicle. DESIGN: Sections from 57 radical prostatectomy specimens of pathologic stage pT3b that contain seminal vesicle with prostatic carcinoma involvement were immunostained with primary antibodies against prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) and a cocktail of antibodies against P504S and p63. RESULTS: Prostatic carcinoma cells from all 57 cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and no p63 nuclear staining. Seminal vesicle epithelium from all 57 cases was negative for all 3 markers with distinct p63 nuclear staining of the basal cells. Benign prostatic tissue was positive for PSA and PAP, as well as for p63, but negative for P504S. CONCLUSIONS: The P504S/p63 one-color cocktail is a practical and cost-effective stain to differentiate prostatic carcinoma that involves the seminal vesicle from seminal vesicle epithelium. It is superior to PSA or PAP when sections contain both seminal vesicle and benign glands because PSA and PAP cannot distinguish benign from malignant glands.

Prostate localization on daily cone-beam computed tomography images: accuracy assessment of similarity metrics.

PURPOSE: To evaluate different similarity metrics (SM) using natural calcifications and observation-based measures to determine the most accurate prostate and seminal vesicle localization on daily cone-beam CT (CBCT) images. METHODS AND MATERIALS: CBCT images of 29 patients were retrospectively analyzed; 14 patients with prostate calcifications (calcification data set) and 15 patients without calcifications (no-calcification data set). Three groups of test registrations were performed. Test 1: 70 CT/CBCT pairs from calcification dataset were registered using 17 SMs (6,580 registrations) and compared using the calcification mismatch error as an endpoint. Test 2: Using the four best SMs from Test 1, 75 CT/CBCT pairs in the no-calcification data set were registered (300 registrations). Accuracy of contour overlays was ranked visually. Test 3: For the best SM from Tests 1 and 2, accuracy was estimated using 356 CT/CBCT registrations. Additionally, target expansion margins were investigated for generating registration regions of interest. RESULTS: Test 1-Incremental sign correlation (ISC), gradient correlation (GC), gradient difference (GD), and normalized cross correlation (NCC) showed the smallest errors (mu +/- sigma: 1.6 +/- 0.9 approximately 2.9 +/- 2.1 mm). Test 2-Two of the three reviewers ranked GC higher. Test 3-Using GC, 96% of registrations showed <3-mm error when calcifications were filtered. Errors were left/right: 0.1 +/- 0.5mm, anterior/posterior: 0.8 +/- 1.0mm, and superior/inferior: 0.5 +/- 1.1 mm. The existence of calcifications increased the success rate to 97%. Expansion margins of 4-10 mm were equally successful. CONCLUSION: Gradient-based SMs were most accurate. Estimated error was found to be <3 mm (1.1 mm SD) in 96% of the registrations. Results suggest that the contour expansion margin should be no less than 4 mm.

Assessment of the contraceptive efficacy of the aqueous extract of Aegle marmelos Corr. leaves in male albino rats.

The present study was conducted to evaluate the contraceptive effect of an aqueous extract from the leaves of Aegle marmelos (AMLAq) on the reproductive organs of male rats with an emphasis on reversibility. Adult male rats were treated daily with different doses of AMLAq, i.e., 150, 300 and 600 mg/kg bw/day for 60 days. The data presented in this study demonstrate that the weight of the reproductive organs was reduced significantly in all the treatment groups. AMLAq induced a significant decrease in the sperm motility and sperm density of the Cauda epididymis and testes. The reduction in fertility was 50%, 85% and 100%, respectively, in the treatment groups. The testosterone level also significantly declined. Biochemical analysis of the reproductive tissues for sialic acid, protein, glycogen, fructose, ascorbic acid, acid and alkaline phosphatase indicated a significant decrease whereas testicular cholesterol level significantly increased indicating alterations in the biochemical milieu of the genital organs. Fertility and other effects gradually returned to control levels 120 days after cessation of treatment. No clinical signs of side effects on general metabolism were detected throughout the treatment, and after withdrawal, body weight gain was similar in all groups together with no alterations in the weight of vital organs', hematological and serological parameters.

Probabilistic cumulative risk assessment of anti-androgenic pesticides in food.

In this paper, we present a cumulative risk assessment of three anti-androgenic pesticides (vinclozolin, procymidone and prochloraz) using the relative potency factor (RPF) approach and an integrated probabilistic risk assessment (IPRA) model. RPFs for each substance were estimated for three reproductive endpoints (ano-genital distance, and weights of the seminal vesicles and the musculus levator ani/bulbocavernosus) in male rat foetuses exposed in utero. The cumulative dietary intake was estimated based on consumption data and residue data from the Netherlands. The IPRA model combines variability in both exposure and sensitivity between individuals into a distribution of individual margins of exposures (IMoEs) and IMoEs of 1 or less indicate a possible concern. The assessment did not result in IMoEs < or = 1. The endpoint 'weight of seminal vesicles' resulted in the lowest IMoEs (0.1th percentile: 198) and the fraction of individuals with IMoEs<1000 was 1.43%. For the two other endpoints, the fractions were slightly lower. Thus, cumulative dietary exposure of Dutch women to vinclozolin, procymidone and prochloraz is not likely to be of concern for the reproductive development of their male foetuses. However, other anti-androgenic substances and exposure routes should also be included in the cumulative assessment to make it more comprehensive.

The role of seminal vesicle motion in target margin assessment for online image-guided radiotherapy for prostate cancer.

PURPOSE: For patients with intermediate- and high-risk prostate cancer, the seminal vesicles (SVs) are included in the clinical target volume (CTV). The purposes of this study are to investigate interfraction motion characteristics of the SVs and determine proper margins for online computed tomography image guidance. METHODS AND MATERIALS: Twenty-four patients, each with 16 daily helical computed tomography scans, were included in this study. A binary image mask was used for image registration to determine daily organ motion. Two online image-guided radiotherapy strategies (prostate only and prostate + SVs) were simulated in a hypofractionated scheme. Three margin designs were studied for both three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT). In prostate-only guidance, Margin A was uniformly applied to the whole CTV, and Margin B was applied to the SVs with a fixed 3-mm prostate margin. In prostate plus SV guidance, Margin C was uniformly applied to the CTV. The minimum margins were sought to satisfy the criterion that minimum cumulative CTV dose be more than those of the planning target volume in the plan for greater than 95% of patients. RESULTS: The prostate and SVs move significantly more in the anterior-posterior and superior-inferior than right-left directions. The anterior-posterior motion of the prostate and SVs correlated (R(2) = 0.7). The SVs move significantly more than the prostate. The minimum margins found were 2.5 mm for three-dimensional conformal radiotherapy and 4.5, 4.5, and 3.0 mm for Margins A, B, and C for IMRT, respectively. Margins for IMRT were larger, but the irradiated volume and doses to critical structures were smaller. Minimum margins of 4.5 mm to the SVs and 3 mm to the prostate are recommended for IMRT with prostate-only guidance. CONCLUSIONS: The SVs move independently from the prostate gland, and additional margins are necessary for image-guided radiotherapy.

Mathematical model for evaluating incidence of acute rectal toxicity during conventional or hypofractionated radiotherapy courses for prostate cancer.

PURPOSE: To describe the radiation-induced acute rectal toxicity (ART) using a modified Lyman-Kutcher-Burman normal tissue complication probability model and parameters set, taking into account the overall treatment time. METHODS AND MATERIALS: A total of 160 patients underwent three-dimensional conformal radiotherapy to the prostate and seminal vesicles and were randomized to receive 80 Gy in 40 fractions within 8 weeks (Group A) or 62 Gy in 20 fractions within 5 weeks, 4 d/wk (Group B). An additional 52 patients (Group C) underwent intensity-modulated radiotherapy with a hypofractionation schedule consisting of 56 Gy, delivered in 16 fractions (4/wk) of 3.5 Gy. Patients were followed for ART weekly during treatment. The overall treatment time, rectal dose-volume histograms, and ART status, defined as Radiation Therapy Oncology Group Grade 2 or greater gastrointestinal toxicity, were used to determine the modified Lyman-Kutcher-Burman model parameters. The m and n values were obtained from the cohort, and the tolerance doses for 50% complication probability for uniform irradiation [TD(50)(1)(k)] were obtained for each fractionation schedule indicated with k. RESULTS: Of 212 patients treated with localized prostate radiotherapy, 65 developed Grade for > or = 1 week during treatment. The m and n value was 0.17 and 0.08, respectively. The TD(50)(1)(k) parameter was 79, 62.5, and 53 Gy, respectively for Group A, B, and C. CONCLUSION: The optimized modified Lyman-Kutcher-Burman normal tissue complication probability model allowed us to describe the ART data from conventional and hypofractionated regimens, using the dose-volume histograms and overall treatment time. This model could prove useful in designing hypofractionation schedules to reduce the incidence of ART.

What CTV-to-PTV margins should be applied for prostate irradiation? Four-dimensional quantitative assessment using model-based deformable image registration techniques.

PURPOSE: To quantify adequate anisotropic clinical target volume (CTV)-to-planning target volume (PTV) margins for three different setup strategies used during prostate irradiation: (1) no setup corrections, (2) on-line corrections determined from bony anatomy, and (3) on-line corrections determined from gold markers. METHOD AND MATERIALS: Three radiation oncologists independently delineated the CTV on computed tomography images of 30 prostate cancer patients. Eight repeat scans were acquired to allow simulation of the delivered dose distributions in changing geometry. Different registration approaches were taken to mimic the different setup strategies. A surface model-based deformable image registration system was used to warp the delivered dose distributions back to the dose in the planning computed tomography scan. On the basis of the geometric extent of the underdosed areas, a set of anisotropic margins was derived to ensure a minimal dose to the CTV of 95% for 90% of the patients. RESULTS: Without setup correction, margins of approximately 11 mm for the corpus of the prostate and 15 mm for the seminal vesicles were required. These margins could be reduced to 8 and 13 mm when aligning the patient to the bony anatomy and to 3 and 8 mm aligning the patient to implanted gold markers. A larger margin at the apex was required to account for the significant observer variability and steep dose gradients at this location (11 mm using skin marker registration, 9 mm using bony anatomy registration, and 6 mm using gold marker registration). CONCLUSIONS: Novel voxel tracking techniques have enabled us to calculate accumulated dose distributions and design accurate three-dimensional CTV-to-PTV margins for prostate irradiation.