Malnutrition is associated with poor survival in women receiving radiotherapy for cervical cancer.

OBJECTIVE: Cancer patients are at risk of malnutrition, which is associated with poor oncological outcomes. The aim of this study was to assess the incidence of malnutrition before, during, and after radiotherapy in locally advanced cervical cancer patients. In addition, we evaluated the impact of malnutrition on survival, and whether and when malnourished patients were referred to a dietitian. METHODS: This retrospective cohort study included cervical cancer patients who received primary or adjuvant radiotherapy with curative intent between January 2013 and January 2021. Patient and treatment characteristics, including longitudinal data on weight and dietary care, were retrieved from the electronic patient files. Malnutrition was defined by body mass index and weight loss according to the Global Leadership Initiative on Malnutrition (GLIM). Overall survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression analysis was used to estimate hazard ratios for key prognostic factors. RESULTS: A total of 294 patients were included. Median follow-up was 40 months (range 7-101 months). Malnutrition occurred in 44 patients (15%) at baseline, in 132 (45%) during radiotherapy, and in 63 (21%) during follow-up. Referral to a dietician occurred in 45% of the 138 patients who were malnourished before or during radiotherapy. Malnutrition was significantly associated with worse survival after adjusting for age, performance score, diabetes, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and nodal stage. The 3 year overall survival in patients with malnutrition was 77% (95% confidence interval (CI) 70% to 85%) and without malnutrition 89% (95% CI 83% to 95%); p=0.001). Independent significant risk factors for worse overall survival were: malnutrition, age ˃52 years, adenocarcinoma, FIGO stage III/IV, and N1 disease. CONCLUSION: Malnutrition was common in cervical cancer patients treated with radiotherapy and was associated with a shorter overall survival. Further studies are needed to evaluate the effectiveness of better monitoring of malnutrition and faster and better dietary intervention on survival and quality of life.

Comparison of the clinical performance of a hybrid Alba 4D and the AMC-4 locoregional hyperthermia systems.

OBJECTIVE: The in-house developed 70 MHz AMC-4 locoregional hyperthermia system has been in clinical use since 1984. This device was recently commercialized as the Alba 4D (Medlogix®, Rome, Italy), with a similar geometrical 4-waveguide design. At the time of this study a hybrid Alba 4D was installed at our center, which incorporated elements of the AMC-4. This study aims to compare clinical performance of both devices. METHODS: During one year after clinical acceptance of the hybrid Alba 4D, both devices were used for treatment delivery in patients scheduled for locoregional hyperthermia. Each patient started with the AMC-4, next sessions were allocated to either device. Possible differences between Alba 4D and AMC-4 sessions in power, achieved temperature T0, T10, T50, T90, T100, treatment time and complaints per session, were evaluated using linear mixed models (LMMs) for repeated measures with patient as random effect. RESULTS: From March 2018 to April 2019, eleven patients with cervical, pancreatic, vaginal carcinoma and uterine leiomyosarcoma received 27 locoregional hyperthermia sessions with the Alba 4D and 34 sessions with the AMC-4. Median number of sessions per patient was 5 (range 3-13). Treatment results for both devices were not significantly different: T50 was 40.5 ± 1.0 °C vs. 40.8 ± 0.7 °C, applied power was 500 ± 79 W vs. 526 ± 108 W, for the Alba 4D vs. AMC-4, respectively. CONCLUSION: Results of the first patients treated with the hybrid Alba 4D demonstrated comparable clinical performance of the Alba 4D and AMC-4 locoregional hyperthermia systems, and both devices are expected to yield similar favorable clinical results.

18F-FDG-PET/CT guided external beam radiotherapy volumes in inoperable uterine cervical cancer.

BACKGROUND: In patients with advanced stage cancer of the uterine cervix who undergo irradiation with curative intent, there is the necessity to treat all suspicious nodes on imaging. Our hypothesis was that adding fluorodeoxyglucose positron emission computer tomography/computer tomography (FDG-PET/CT) to the imaging workup would alter the external beam radiotherapy (EBRT) treatment plan, either resulting in an extended external beam radiotherapy (EBRT) field to the para-aortal region or an additional boost to suspicious nodes. Since extended field radiotherapy or additional boost can cause toxicity, our secondary aim was to assess the incidence of severe late bowel toxicity in patients treated with extended para-aortal EBRT-field and boost compared to elective pelvic radiotherapy. METHODS: Eighty-eight patients were enrolled. First, the optimal radiation treatment plan (EBRT and boost) was retrospectively determined based on magnetic resonance imaging (MRI) or FDG-PET/CT. Second, the severe bowel toxicity caused by the extended para-aortal field was assessed, based on the executed radiotherapy. RESULTS: Based on MRI 8/88 patients would receive EBRT with para-aortic extension, this was 21/88 for FDG-PET/CT. Based on MRI 47/704 lymph node regions would receive additional boost, while based on PET/CT 91/704. Late severe bowel toxicity was seen in 12/84 patients, 6/65 in the group who received elective pelvic irradiation and 6/19 with para-aortal EBRT and boost at common iliac and/or para-aortal lymph nodes. Significant worse overall survival was seen of patients who needed para-aortal irradiation. CONCLUSIONS: Addition of FDG-PET/CT leads to an extension of the elective EBRT volume and more suspicious lymph nodes receive a boost. However, when deciding to intensify radiation therapy, late severe bowel toxicity has to be taken into account.

Virtual unenhanced dual-energy computed tomography for photon radiotherapy: The effect on dose distribution and cone-beam computed tomography based position verification.

Background and Purpose: Virtual Unenhanced images (VUE) from contrast-enhanced dual-energy computed tomography (DECT) eliminate manual suppression of contrast-enhanced structures (CES) or pre-contrast scans. CT intensity decreases in high-density structures outside the CES following VUE algorithm application. This study assesses VUE's impact on the radiotherapy workflow of gynecological tumors, comparing dose distribution and cone-beam CT-based (CBCT) position verification to contrast-enhanced CT (CECT) images. Materials and Methods: A total of 14 gynecological patients with contrast-enhanced CT simulation were included. Two CT images were reconstructed: CECT and VUE. Volumetric Modulated Arc Therapy (VMAT) plans generated on CECT were recalculated on VUE using both the CECT lookup table (LUT) and a dedicated VUE LUT. Gamma analysis assessed 3D dose distributions. CECT and VUE images were retrospectively registered to daily CBCT using Chamfer matching algorithm.. Results: Planning target volume (PTV) dose agreement with CECT was within 0.35% for D2%, Dmean, and D98%. Organs at risk (OARs) D2% agreed within 0.36%. A dedicated VUE LUT lead to smaller dose differences, achieving a 100% gamma pass rate for all subjects. VUE imaging showed similar translations and rotations to CECT, with significant but minor translation differences (<0.02 cm). VUE-based registration outperformed CECT. In 24% of CBCT-CECT registrations, inadequate registration was observed due to contrast-related issues, while corresponding VUE images achieved clinically acceptable registrations. Conclusions: VUE imaging in the radiotherapy workflow is feasible, showing comparable dose distributions and improved CBCT registration results compared to CECT. VUE enables automated bone registration, limiting inter-observer variation in the Image-Guided Radiation Therapy (IGRT) process.

Towards artificial intelligence-based automated treatment planning in clinical practice: A prospective study of the first clinical experiences in high-dose-rate prostate brachytherapy.

PURPOSE: This prospective study evaluates our first clinical experiences with the novel ``BRachytherapy via artificial Intelligent GOMEA-Heuristic based Treatment planning'' (BRIGHT) applied to high-dose-rate prostate brachytherapy. METHODS AND MATERIALS: Between March 2020 and October 2021, 14 prostate cancer patients were treated in our center with a 15Gy HDR-brachytherapy boost. BRIGHT was used for bi-objective treatment plan optimization and selection of the most desirable plans from a coverage-sparing trade-off curve. Selected BRIGHT plans were imported into the commercial treatment planning system Oncentra Brachy . In Oncentra Brachy a dose distribution comparison was performed for clinical plan choice, followed by manual fine-tuning of the preferred BRIGHT plan when deemed necessary. The reasons for plan selection, clinical plan choice, and fine-tuning, as well as process speed were monitored. For each patient, the dose-volume parameters of the (fine-tuned) clinical plan were evaluated. RESULTS: In all patients, BRIGHT provided solutions satisfying all protocol values for coverage and sparing. In four patients not all dose-volume criteria of the clinical plan were satisfied after manual fine-tuning. Detailed information on tumour coverage, dose-distribution, dwell time pattern, and insight provided by the patient-specific trade-off curve, were used for clinical plan choice. Median time spent on treatment planning was 42 min, consisting of 16 min plan optimization and selection, and 26 min undesirable process steps. CONCLUSIONS: BRIGHT is implemented in our clinic and provides automated prostate high-dose-rate brachytherapy planning with trade-off based plan selection. Based on our experience, additional optimization aims need to be implemented to further improve direct clinical applicability of treatment plans and process efficiency.

ESTRO-ACROP recommendations for evidence-based use of androgen deprivation therapy in combination with external-beam radiotherapy in prostate cancer.

BACKGROUND AND PURPOSE: There is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. MATERIAL AND METHODS: A literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D'Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. RESULTS: Key issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. CONCLUSION: These ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.

The Effect of Contemporary Brachytherapy Practices on Prognosis in Women with Locally Advanced Cervical Cancer.

(1) Background: Over the past two decades use of new imaging modalities and the adaptation of applicators have allowed for advances in volumetric (3D) imaging-based brachytherapy practices for patients with locally advanced cervical cancer. The aim of this study was to compare the oncological outcome and toxicity for three consecutively introduced brachytherapy practices in a large single-center cohort; (2) Methods: Patients treated for cervical cancer with primary radiotherapy and curative intent were consecutively included in this retrospective, single-center cohort study from 2006 to 2019. This cohort was divided into three groups (CT, MRI, and MRI+needles) based on the timing of the introduction of a novel brachytherapy practice; 3D brachytherapy planning using CT- and MRI-guided adaptive brachytherapy and the use of parametrial interstitial needles, respectively. Actuarial estimates were compared between groups. Multivariable Cox regression analyses were performed to correct for other risk factors. Crude rates of severe (≥grade 3) late toxicity were reported; (3) Results: A total of 397 patients were included in this cohort. At a median follow-up of 40 months (interquartile range (IQR) 22-62), actuarial 3-year local control, pelvic control, disease-free survival, and overall survival for the entire cohort were 91% (95% (Confidence Interval (CI)) 88-94), 88% (95% CI 84-91), 69% (95% CI 64-74), and 75% (95% CI 70-79), respectively). Local control, disease-free survival, and overall survival were significantly improved in the MRI+needles group compared to the CT group (p = 0.040, p = 0.004, and p < 0.001, respectively). Independent risk factors for overall survival were treatment in either the CT or MRI group (vs. MRI+needles), older age at diagnosis, adeno (squamous) carcinoma, FIGO stage III/IV, and lymph node metastases. The crude rate of severe late toxicity was 27% in the CT, 26% in the MRI, and 20% in the MRI+needles group; (4) Conclusions: Prognosis in women with locally advanced cervical cancer treated with state-of-the-art MRI-guided adaptive brachytherapy combined with parametrial interstitial needles compares favorably to patients treated with more traditional CT only based brachytherapy.

Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients.

STUDY TYPE: Prognostic (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper. OBJECTIVE: To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT. PATIENTS AND METHODS: In 932 patients, who were treated with external radiotherapy (N=311) or brachytherapy (N=621) for their T1-3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT. Associations between the different fat measurements and risk of having high-risk (according to Ash et al., PSA>20 or Gleason score≥8 or T3) disease was measured. RESULTS: The median age (IQR) was 67.0 years (62.0-71.0) and median BMI (IQR) was 25.8 (24.2-28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04-1.08], P<0.001) CONCLUSION: Patients with a higher PFD had more often aggressive prostate cancer.

Survival after prostate brachytherapy in patients aged 60 years and younger.

OBJECTIVE: • To compare survival after prostate brachytherapy in patients aged ≤60 years with patients aged >60 years. PATIENTS AND METHODS: • We analysed 419 locally confined prostate cancer patients, treated between 1989 and 2001 with I-125 implantation monotherapy. • Endpoints were biochemical failure (BF) according to the +2 ng/mL definition, disease-specific and overall survival. • Patients were subdivided into age ≤60 years and age >60 years. • Cox proportional-hazards regression analyses were performed to study the independent effect of age on BF and disease-specific survival. RESULTS: • The younger cohort consisted of 87 patients (21%), with smaller prostate volumes and a lower average prostate cancer risk class than the older cohort, consisting of 332 patients (79%). Mean follow-up was 9.1 years (±sd 2.8) for the younger cohort and 8.3 years (±sd 2.9) for the older cohort. • The 10-year (95% CI) freedom from BF, disease-specific survival and overall survival rates were 63% (51-75), 87% (78-96) and 81% (69-89), respectively, for the younger cohort and 46% (39-54), 83% (78-89) and 60% (54-66), respectively, for the older patient cohort. • Although a trend for better freedom from BF and disease-specific survival was observed in younger patients, the difference proved not clinically significant. CONCLUSION: • Prostate cancer risk group and the year of treatment relate to outcome, but not age. With respect to prostate cancer curability, there seems no objection to offer brachytherapy to patients aged 60 years and younger.

Body mass index is not a prognostic marker for prostate-specific antigen failure and survival in Dutch men treated with brachytherapy.

OBJECTIVE: To examine the relationship between body mass index (BMI) and biochemical recurrence (BCR), cancer-specific (CSS) and overall survival (OS) in men treated with permanent prostate brachytherapy (PPB), as there is limited information on the affect of obesity on treatment outcomes for prostate cancer. PATIENTS AND METHODS: In all, 1530 patients with clinically localized prostate cancer who underwent PPB were studied. Clinical and pathological data were retrospectively obtained from medical records. The BMI was classified as normal (< 25 kg/m(2)), overweight (25-30 kg/m(2)) and obese (> or = 30 kg/m(2)). BCR was defined as a rise in PSA levels of > or = 2 ng/mL after the nadir had been reached. The cause of death was determined for each deceased patient. Patients with metastatic prostate cancer who died of any cause were classified as prostate cancer deaths. RESULTS In all, 617 (40%) patients were classified as having a normal weight, 754 (49%) overweight and 159 (10%) were obese. The Kaplan-Meier 8-year risk of BCR (95% confidence interval) was 33.3% (27.2-39.4), 29.2% (23.5-34.9) and 29.3% (12.4-46.2) for patients with a BMI of < 25 kg/m(2), 25-30 kg/m(2) and > or = 30 kg/m(2), respectively. The 8-year CSS was 88.2% (83.1-93.3), 88.6% (83.7-93.5) and 90.6% (79.9-101.4) and the 8-year OS was 70.1% (63.6-76.6), 72.9% (66.6-79.2) and 81.8% (69.3-94.3) for these three groups, respectively. Multivariate proportional hazard regression analyses of BMI and established prognostic factors for BCR confirmed the absence of any prognostic value of BMI on BCR, CSS and OS. CONCLUSIONS: BMI did not appear to have any prognostic value for BCR, CCS or OS in patients with clinically localized prostate cancer treated with PPB.

BioXmark® liquid fiducial markers for image-guided radiotherapy in muscle invasive bladder cancer: a safety and performance trial.

OBJECTIVE: This study evaluated the performance of the novel liquid fiducial marker (BioXmark®) in IGRT for bladder cancer. METHODS: 20 patients with muscle invasive bladder cancer were entered in this prospective, single center, Phase I-II study. The novel BioXmark® liquid markers were injected around the tumor using a flexible cystoscopy. Visibility and stability of the markers were evaluated on planning-CT and CBCT. Prospectively defined threshold for success was set at a visibility of 75%. RESULTS: In total, 76 markers were implanted in 20 patients. Of those, 60 (79% 95% CI ± 9%) were visible on CT scan. Due to the learning curve of the technique, the visibility improved in the last 75% of patients (86% visibility) compared to the first 25% of patients with 58% visibility. Concerning stability of the BioXmark® marker, all visible markers after CT acquisition were still detectable at the last CBCT without displacement. In 15/20 (75%) of the patients, three or more markers were visible on CT. No BioXmark® related adverse events were reported. CONCLUSION: The success rate of this novel fiducial marker was 79%, which is above the prospectively defined threshold rate. A distinct learning curve of the injection of the liquid marker was seen over the study period. The marker showed sustained visibility and positional stability during treatment phases and also appears to be safe and easy to inject. ADVANCES IN KNOWLEDGE: This novel liquid BioXmark® marker seems to be a very promising tool in daily-adaptive IGRT for bladder preserving chemoradiotherapy in muscle invasive bladder cancer.

Evaluation of bi-objective treatment planning for high-dose-rate prostate brachytherapy-A retrospective observer study.

PURPOSE: Bi-objective treatment planning for high-dose-rate prostate brachytherapy is a novel treatment planning method with two separate objectives that represent target coverage and organ-at-risk sparing. In this study, we investigated the feasibility and plan quality of this method by means of a retrospective observer study. METHODS AND MATERIALS: Current planning sessions were recorded to configure a bi-objective optimization model and to assess its applicability to our clinical practice. Optimization software, GOMEA, was then used to automatically generate a large set of plans with different trade-offs in the two objectives for each of 18 patients treated with high-dose-rate prostate brachytherapy. From this set, five plans per patient were selected for comparison to the clinical plan in terms of satisfaction of planning criteria and in a retrospective observer study. Three brachytherapists were asked to evaluate the blinded plans and select the preferred one. RESULTS: Recordings demonstrated applicability of the bi-objective optimization model to our clinical practice. For 14/18 patients, GOMEA plans satisfied all planning criteria, compared with 4/18 clinical plans. In the observer study, in 53/54 cases, a GOMEA plan was preferred over the clinical plan. When asked for consensus among observers, this ratio was 17/18 patients. Observers highly appreciated the insight gained from comparing multiple plans with different trade-offs simultaneously. CONCLUSIONS: The bi-objective optimization model adapted well to our clinical practice. GOMEA plans were considered equal or superior to the clinical plans. In addition, presenting multiple high-quality plans provided novel insight into patient-specific trade-offs.

Seminal vesicle invasion on multi-parametric magnetic resonance imaging: Correlation with histopathology.

OBJECTIVES: The pre-treatment risk of seminal vesicle (SV) invasion (SVI) from prostate cancer is currently based on nomograms which include clinical stage (cT), Gleason score (GS) and prostate-specific antigen (PSA). The aim of our study was to evaluate the staging accuracy of 3T (3T) multi-parametric (mp) Magnetic Resonance Imaging (MRI) by comparing the imaging report of SVI with the tissue histopathology. The additional value in the existing prediction models and the role of radiologists' experience were also examined. METHODS: After obtaining institutional review board approval, we retrospectively reviewed clinico-pathological data from 527 patients who underwent a robot-assisted radical prostatectomy (RARP) between January 2012 and March 2015. Preoperative prostate imaging with an endorectal 3T-mp-MRI was performed in all patients. Sequences consisted of an axial pre-contrast T1 sequence, three orthogonally-oriented T2 sequences, axial diffusion weighted and dynamic contrast-enhanced sequences. We considered SVI in case of low-signal intensity in the SV on T2-weighted sequences or apparent mass while diffusion-weighted and DCE sequences were used to confirm findings on T2. Whole-mount section pathology was performed in all patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI (index test) for the prediction of histological SVI (reference standard) were calculated. We developed logistic multivariable regression models including: clinical variables (PSA, cT, percentage of involved cores/total cores, primary GS 4-5) and Partin table estimates. MRI results (negative/positive exam) were then added in the models and the multivariate modeling was reassessed. In order to assess the extent of SVI and the reason for mismatch with pathology an MRI-review from an expert genitourinary radiologist was performed in a subgroup of 379 patients. RESULTS: A total of 54 patients (10%) were found to have SVI on RARP-histopathology. In the overall cohort sensitivity, specificity, PPV and NPV for SVI detection on MRI were 75.9%, 94.7%, 62% and 97% respectively. Based on our sub-analysis, the radiologist's expertise improved the accuracy demonstrating a sensitivity, specificity, PPV and NPV of 85.4%, 95.6%, 70.0% and 98.2%, respectively. In the multivariate analysis PSA (odds ratio [OR] 1.07, p=0.008), primary GS 4 or 5 (OR 3.671, p=0.007) and Partin estimates (OR 1.07, p=0.023) were significant predictors of SVI. When MRI results were added to the analysis, a highly significant prediction of SVI was observed (OR 45.9, p<0.0001). Comparing Partin, MRI and Partin with MRI predictive models, the areas under the curve were 0.837, 0.884 and 0.929, respectively. CONCLUSIONS: MRI had high diagnostic accuracy for SVI on histopathology. It provided added diagnostic value to clinical/Partin based SVI-prediction models alone. A key factor is radiologist's experience, though no inter-observer variability could be examined due to the availability of a single expert radiologist.

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

PURPOSE: To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. METHODS AND MATERIALS: We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. RESULTS: Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). CONCLUSIONS: A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival.

Predictors in the outcome of 125I brachytherapy as monotherapy for prostate cancer.

A number of different prostate cancer treatment modalities exist. Nomograms are used to assist clinicians and patients in choosing the most appropriate treatment. However, the predicted outcome for (125)I brachytherapy is much worse than what would be expected considering the actual survival rates. This underestimation may result in suboptimal treatment decisions. Therefore, better predictors for outcome after (125)I brachytherapy are necessary. The following factors, which may either influence outcome or predict outcome after brachytherapy, are discussed: tumor characteristics and risk stratification, patient age at treatment, obesity, adjuvant androgen-deprivation therapy, prostate-specific antigen bounce, implantation technique and dosimetry. For the prediction of outcome after (125)I brachytherapy, as long as the quality of the implant is optimal, only high-risk prostate cancer was found to have a negative impact on outcome.

Prostate brachytherapy and second primary cancer risk: a competitive risk analysis.

PURPOSE: To assess the risk of second primary cancer (SPC) after [(125)I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population. PATIENTS AND METHODS: In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison. RESULTS: A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18). CONCLUSION: Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.

Loose seeds versus stranded seeds in I-125 prostate brachytherapy: differences in clinical outcome.

PURPOSE: To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy. METHODS: From December 2000 until October 2006, we treated 896 T< or =2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n=538) or loose seed (n=358) I-125 implants. A total of 211 patients received a 6 months course of anti-androgen therapy, before treatment, for prostate volume reduction to <50 cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary. RESULTS: The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82-90) and 90% (85-95), the total 5-year bNED rate was 87% (85-90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34-0.97) for loose seeds versus stranded seeds. CONCLUSIONS: These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants.

Long-term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy.

PURPOSE: To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT). METHODS AND MATERIALS: Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for or=50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4-186 months); mean age was 67 years. RESULTS: Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival. CONCLUSIONS: These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.

The impact of acute urinary retention after iodine-125 prostate brachytherapy on health-related quality of life.

PURPOSE: To evaluate the impact of acute urinary retention (AUR) in patients treated with (125)I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR. METHODS AND MATERIALS: For 127 patients treated with (125)I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index. RESULTS: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patients who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value. CONCLUSION: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR.

Exploiting the spatiotemporal correlation in adaptive optics using data-driven H2-optimal control.

A recently proposed data-driven H2-optimal control approach is demonstrated on a laboratory setup. Most adaptive optics (AO) systems are based on a control law that neglects the temporal evolution of the wavefront. The proposed control approach is able to exploit the spatiotemporal correlation in the wavefront without assuming any form of decoupling. By analyzing the dynamic behavior of the wavefront sensor (WFS), it is shown that if the wavefront correction device can be considered static, the transfer function from control input to WFS output reduces to a two-tap impulse response and an integer number of samples delay. Considering this model structure, a data-driven identification procedure is developed to estimate the relevant parameters from measurement data. The specific structure allows for an analytical expression of the optimal controller in terms of the system matrices of the minimum-phase spectral factor of the atmospheric disturbance model. The performance of the optimal controller is compared with that of the standard AO control law. An analysis of the dominant error sources shows that optimal control may reduce the temporal error.