Search

Purpose: To investigate the potential of texture analysis applied on T2‐w and postcontrast T1‐w images acquired before radiotherapy for prostate cancer (PCa) and 12 months after its completion in quantitatively characterizing local radiation effect on the muscular component of internal obturators, as organs potentially involved in urinary toxicity. Methods: T2‐w and postcontrast T1‐w MR images were acquired at 1.5 T before treatment (MRI1) and at 12 months of follow‐up (MRI2) in 13 patients treated with radiotherapy for PCa. Right and left internal obturator muscle contours were manually delineated upon MRI1 and then automatically propagated on MRI2 by an elastic registration method. Planning CT images were coregistered to both MRIs and dose maps were deformed accordingly. A high‐dose region receiving >55 Gy and a low‐dose region receiving <55 Gy were identified in each muscle volume. Eighteen textural features were extracted from each region of interest and differences between MRI1 and MRI2 were evaluated. Results: A signal increase was highlighted in both T2‐w and T1‐w images in the portion of the obturators near the prostate, i.e., in the region receiving medium‐high doses. A change in the spatial organization was identified, as an increase in homogeneity and a decrease in contrast and complexity, compatible with an inflammatory status. In particular, the region receiving medium‐high doses presented more significant or, at least, stronger differences. Conclusions: Texture analysis applied on T1‐w and T2‐w MR images has demonstrated its ability in quantitative evaluating radiation‐induced changes in obturator muscles after PCa radiotherapy. [ABSTRACT FROM AUTHOR]

Background and purpose Urinary incontinence following radiotherapy (RT) for prostate cancer (PCa) has a relevant impact on patient’s quality of life. The aim of the study was to assess the unknown dose–effect relationship for late patient-reported urinary incontinence (LPRUI). Methods and materials Patients were enrolled within the multi-centric study DUE01. Clinical and dosimetry data including the prescribed 2 Gy equivalent dose (EQD2) were prospectively collected. LPRUI was evaluated through the ICIQ-SF questionnaire filled in by the patients at RT start/end and therefore every 6 months. Patients were treated with conventional (74–80 Gy, 1.8–2 Gy/fr) or moderately hypo-fractionated RT (65–75.2 Gy, 2.2–2.7 Gy/fr) in 5 fractions/week with intensity-modulated radiotherapy. Six different end-points of 3-year LPRUI, including or not patient’s perception (respectively, subjective and objective end-points), were considered. Multivariable logistic models were developed for each end-point. Results Data of 298 patients were analyzed. The incidence of the most severe end-point (ICIQ-SF > 12) was 5.1%. EQD2 calculated with alpha–beta = 0.8 Gy showed the best performance in fitting data: the risk of LPRUI markedly increased for EQD2 > 80 Gy. Previous abdominal/pelvic surgery and previous TURP were the clinical factors more significantly predictive of LPRUI. Models showed excellent performances in terms of goodness-of-fit and calibration, confirmed by bootstrap-based internal validation. When included in the analyses, baseline symptoms were a major predictor for 5 out of six end-points. Conclusions LPRUI after RT for PCa dramatically depends on EQD2 and few clinical factors. Results are consistent with a larger than expected impact of moderate hypo-fractionation on the risk of LPRUI. As expected, baseline symptoms, as captured by ICIQ-SF, are associated to an increased risk of LPRUI. [ABSTRACT FROM AUTHOR]

Purpose/objective Prospectively assessing clinical/dosimetry factors affecting the acute worsening of urinary functionality after radiotherapy for prostate cancer. Material/methods DUE01 population was considered, including patients treated with conventional or moderate hypo-fractionation (2.2–2.7 Gy/fr). Relevant clinical factors were collected, urinary symptoms were self-reported through the International Prostate Symptom Score (IPSS) before and at the end of radiotherapy; while absolute weekly dose–surface histograms (DSH w ) were chosen as dosimetry descriptors. An IPSS increase of at least 10 and 15 points (ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15) were chosen as endpoints. Patients with baseline IPSS > 20 were excluded. Relevant factors were chosen through a bootstrap-based in silico methodology. Results Complete information was available for 380 patients: 77/380 (20%) and 28/380 (7%) with ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15, respectively. Neoadjuvant hormone was protective (OR = 0.49 and 0.69). DSH w at 8.5 Gy/week and 12 Gy/week were risk factors, with additional risk for patients who use cardiovascular drugs and anti-hypercholesterolemia drugs. In the hypo-fractionated subgroup ( n = 209) the role of cardiovascular drugs (OR = 2.16) for ΔIPSS ⩾ 10 and anti-hypercholesterolemia drugs (OR = 2.80) for ΔIPSS ⩾ 15, together with DSH w (10 Gy/week and 12.5 Gy/week, respectively), was confirmed. Conclusion Current study shows a dose–surface/volume effect for acute large worsening of urinary functionality; several clinical variables largely impact the risk and especially all the factors related with vascular diseases. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors. Materials and methods: Questionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up ⩾6years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3years after RT was also investigated. Results: Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2–G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p =0.016) ⩾G1 lrb was significantly associated with V75Gy (OR=1.07). In multivariate analysis, ⩾G1 linc was associated with V40Gy (OR=1.015), use of antihypertensive medication (OR=0.38), abdominal surgery before RT (OR=4.7), haemorrhoids (OR=2.6), and G2–G3 acute faecal incontinence (OR=4.4), a nomogram to predict the risk of long-term ⩾G1 linc was proposed. Importantly, the prevalence of ⩾G1 linc was significantly correlated with the mean incontinence score during the first 3years after RT (OR=16.3). Conclusions: Long-term (median: 7years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3years after RT. Linc was associated with several risk factors. [Copyright &y& Elsevier]

The aim of this study was to evaluate the correlation between the 'true' absolute and relative dose-volume histograms (DVHs) of the bladder wall, dose-wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose-surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose-volume/surface histogram. Correlation was quantified for selected dose-volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD < 5%): DVH5 showed the best agreement. The correlation was slightly better for absolute (R = 0.80-0.94) compared to relative (R = 0.66-0.92) histograms. The DSH was also found to be highly correlated with the DWH, although slightly higher deviations were generally found. The DVH was not a good surrogate of the DWH (R < 0.7 for most of parameters). When comparing the two treatment techniques, more pronounced differences between relative histograms were seen for IMRT with respect to 3DCRT (p < 0.0001). [ABSTRACT FROM AUTHOR]

Study Type - Therapy (decision analysis) Level of Evidence 2b What's known on the subject? and What does the study add? The benefits of the multidisciplinary approach in oncology are widely recognised. In particular, managing patients with prostate cancer within a multidisciplinarity and multiprofessional context is of paramount importance, to address the complexity of a disease where patients may be offered multiple therapeutic and observational options handled by different specialists and having severe therapy-induced side-effects. The present study describes the establishing of a multidisciplinary clinic at the Prostate Cancer Programme of Milan Istituto Nazionale dei Tumori, its effects on the quality of care provided, and strategies implemented to meet upcoming needs and improve quality standards. Having analysed the data of the 2260 multidisciplinary clinics held from March 2005 to March 2011, our dynamic and modifiable organisational model was evaluated for ways to optimise the human resources, offer high-quality standards, meet new needs and ultimately reduce costs. The study is focused on the organisational aspects and adds a perspective from one of the major oncological centres of reference in Italy and in Europe. OBJECTIVES To describe the establishing of a multidisciplinary clinic for men with prostate cancer at the Istituto Nazionale Tumori, Milan., To evaluate the quality of care provided and to describe the management changes implemented to improve standards and meet new needs., MATERIALS AND METHODS In March 2005, we established a multidisciplinary clinic comprising weekly clinics and case-discussion sessions., We have altered the organisational model periodically to meet new needs and improve quality., RESULTS We held 2260 multidisciplinary clinics up to March 2011., For stage distribution, patients with low-risk prostate cancer increased to a peak of 61% in 2009, probably because of the anticipation of diagnosis and the active surveillance expertise of the Prostate Cancer Programme at Istituto Nazionale Tumori, Milan. The slight decrease in 2010 might be due to the availability of robot-assisted prostatectomy in several hospitals in Milan, and the start of a multicentre active surveillance protocol in December 2009., In terms of the efficacy of our multidisciplinary strategy, 11% of drug therapies (mostly hormones) prescribed outside our institute were terminated in the multidisciplinary clinic, and 6% of indications formulated in the multidisciplinary clinics were altered during the case-discussion sessions., CONCLUSIONS The multidisciplinary approach needs to be adaptable to meet new needs and improve quality., Our experience has proved successful for both physicians and patients. The team agrees on strategies; complex cases are managed by a multidisciplinary team; dedicated psychologists contribute their knowledge and perspectives; and patients report the feeling of being cared for. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD50s: the ratio of TD50s with and without including the clinical variable was the dose-modifying factor (D mod). Results: Abdominal surgery (surg) was a risk factor for G2–G3 bleeding, reflecting in a TD50 =82.7Gy and 88.4Gy for patients with and without surg (D mod =0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2–G3 bleeding (D mod =0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod(surg) and D mod(colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score ⩾1. Best-fit n values were 0.03–0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties. [Copyright &y& Elsevier]

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose–volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2–3 RTOG/EORTC acute LGI toxicity (p = 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR = 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR = 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p = 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR = 1.029). Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy of sodium butyrate enemas (NABUREN) in prostate cancer radiation therapy (RT) in reducing the incidence, severity, and duration of acute RT-induced proctitis. Methods and Materials: 166 patients, randomly allocated to 1 of 4 groups (rectal sodium butyrate 1 g, 2 g, or 4 g daily or placebo), were treated with NABUREN during and 2 weeks after RT. The grade of proctitis was registered in a daily diary. The correlation between NABUREN and proctitis was investigated through χ2 statistics. The toxicity endpoints considered were as follows: total number of days with grade ≥1 proctitis (≥G1); total number of days with grade ≥2 proctitis (≥G2); ≥G1 and ≥G2 proctitis lasting at least 3 and 5 consecutive days starting from week 4 (≥G1+3d, ≥G2+3d); damaging effects of RT on rectal mucosa as measured by endoscopy. The relationship between endpoints and pretreatment morbidities, hormonal therapy, presence of diabetes or hypertension, abdominal surgery, or hemorrhoids was investigated by univariate analysis. Results: The patients were randomly allocated to the 4 arms. No difference in the distribution of comorbidities among the arms was observed (P>.09). The mean ≥G1 and ≥G2 proctitis were 7.8 and 4.9 for placebo and 8.9 and 4.7 for the NABUREN group, respectively. No favorable trend in reduction of incidence, severity, and duration of ≥G1 and ≥G2 proctitis was observed with NABUREN use. In univariate analysis, ≥G1+3d toxicity was found to be related to hemorrhoids (P=.008), and a slight correlation was found between ≥G2 proctitis and hormonal therapy (P=.06). The RT effects on rectal mucosa as based on endoscopic assessment were mainly related to diabetes (P<.01). Endoscopy data at 6 week showed no significant difference between the placebo and butyrate arms. The other investigated endpoints were not correlated with any of the clinical risk factors analyzed. Conclusion: There was no evidence of efficacy of NABUREN in reducing the incidence, severity, and duration of acute radiation proctitis. There was a correlation between some endpoints and clinical risk factors. [Copyright &y& Elsevier]

Abstract: Background and purpose: DUE01 is an observational study aimed at developing predictive models of genito-urinary toxicity of patients treated for prostate cancer with conventional (1.8–2Gy/fr, CONV) or moderate hypo-fractionation (2.35–2.7Gy/fr, HYPO). The current analysis focused on the relationship between bladder DVH/DSH and the risk of International Prostate Symptoms Score (IPSS)⩾15/20 at the end of radiotherapy. Materials and methods: Planning and relevant clinical parameters were prospectively collected, including DVH/DSH, LQ-corrected (DVHc/DSHc) and weekly (DVHw/DSHw) histograms. Best parameters were selected by the differences between patients with/without IPSS⩾15/20 at the end of radiotherapy. Logistic uni- and backward multi-variable (MVA) analyses were performed. Results: Data of 247 patients were available (CONV: 116, HYPO: 131). Absolute DVHw/DSHw and DVHc/DSHc predicted the risk of IPSS⩾15 at the end of radiotherapy (n =77/247); an MVA model including baseline IPSS, anti-hypertensive, T stage, the absolute surface receiving ⩾8.5Gy/week and ⩾12.5Gy/week was developed (AUC=0.78, 95% CI: 0.72–0.83). Similar AUC values were found if replacing DSHw with DVHw/DVHc/DSHc parameters. The impact of dose–volume/surface parameters remained when excluding patients with baseline IPSS⩾15 and in HYPO. IPSS⩾20 at the end of radiotherapy (n =27/247) was mainly correlated to baseline IPSS and T stage. Conclusions: Although the baseline IPSS was the main predictor, constraining v8.5w<56cc and v12.5w<5cc may significantly reduce acute GU toxicity. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate and discuss the role of specific types of abdominal surgery (SURG) before radical radiation therapy as a risk factor for late rectal toxicity in prostate cancer patients. Methods: Results concerning questionnaire-based scored late bleeding and faecal incontinence in 718 patients with a complete follow-up of 36months were analysed, focusing on the impact of specific pre-radiotherapy abdominal/pelvic surgery procedures. Patients were accrued in the prospective study AIROPROS 0102. Different types of surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) were considered as covariates together with a number of different parameters previously found to be predictive of late toxicity and including clinical as well as dosimetric parameters. Univariate (UVA) and multivariate (MVA) logistic analyses were carried out. Results: In total 69/718 patients were previously submitted to one or more surgical procedures, mostly cholecystectomy (n =21) and appendectomy (n =27). Actuarial incidences of G2–G3 and G3 bleeding were 52 (7.2%) and 24 (3.3%) respectively; 19 (2.6%) chronic incontinence events were registered. Cholecystectomy was found to be highly correlated with late rectal bleeding at UVA: OR=4.3 and p =0.006 for G2–G3 and OR=5.4 and p =0.01 for G3. Considering MVA (including dosimetric and clinical factors), G2–G3 bleeding was significantly correlated to cholecystectomy (OR=6.5, p =0.002), V75Gy (OR=1.074, p =0.003) and secondarily with appendectomy (OR=2.7, p =0.10), presence of acute radioinduced rectal bleeding (OR=1.70, p =0.21) and androgen deprivation (OR=0.67, p =0.25). Appendectomy (OR=5.9, p =0.004) and cholecystectomy (OR=5.5, p =0.016) were very strong predictors of G3 bleeding with V75Gy playing a less significant role (OR=1.037, p =0.26). Conversely, no specific surgery was correlated with actuarial or chronic incontinence. Conclusions: This analysis highlights previous SURG as the best predictor of late rectal bleeding. Among the different types of abdominal surgery, cholecystectomy and appendectomy play the major role, especially for severe late bleeding. [Copyright &y& Elsevier]

Abstract: Purpose: Assessing the predictors of late rectal toxicity after high-dose conformal radiotherapy for prostate cancer. Methods: One thousand one hundred thirty-two patients entered a prospective observational multicentric study; late rectal toxicity was evaluated by a self-reported questionnaire. Results concerning bleeding and faecal incontinence of 718/1132 patients with a complete follow-up at 36months were analysed. The correlation between a number of clinical–dosimetric parameters and moderate/severe toxicity was investigated by univariate and multivariate logistic analyses. Results: Fifty-two (7.2%) and 57/718 (7.9%) patients were scored as moderate/severe bleeders and faecal incontinents, respectively; 19/57 incontinent patients showed persistent incontinence at 36months. Bleeding was mainly correlated with V75Gy while severe bleeding was mainly correlated with the previous abdominal/pelvic surgery; a different rectal dose–volume relationship in the two groups of patients (with/without surgery) was found. Moderate/severe acute toxicity was weakly correlated to late bleeding. The best predictor of faecal incontinence was acute toxicity (OR=4 and 7 for chronic and actuarial incontinence, respectively). Conclusion: The application of rectal dose–volume constraints limited the incidence of rectal bleeding. The risk of bleeding may be further reduced by limiting V75Gy<5% and, in the case of patients previously submitted to abdominal/pelvic surgery, V70Gy<15–20%. Faecal incontinence seems to be mainly a consequential effect after acute toxicity. [Copyright &y& Elsevier]

Background and purpose Intestinal toxicity is commonly experienced during whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. The aim of the current study was to assess bowel dose–volume relationships for acute patient-reported intestinal symptoms of patients treated with WPRT for prostate cancer. Materials and methods Complete data of 206 patients were available; the median dose to pelvic nodes was 51.8 Gy (range 50.4–54.4, 1.7–2 Gy/fr). Intestinal symptoms were assessed as changes in the Inflammatory Bowel Disease Questionnaire scores relative to the Bowel Domain (IBDQ-B) between baseline and radiotherapy mid-point/end. The 25th percentiles of the most severe worsening from baseline (ΔIBDQ-B) were set as end-points. The impact of bowel loops and sigmoid colon dose–volume/surface parameters as well as selected clinical parameters were investigated using multivariate logistic regression. Results Analyses were focused on the four questions showing a median ΔIBDQ-B > 0. No dose volume/surface parameters were predictive, other than ΔIBDQ5 ≥ 3 (loose stools): when grouping patients according to bowel DVHs (high risk: V20 > 470 cc, V30 > 245 cc, V42 > 110 cc; low risk: all the remaining patients), a two-variable model including high-risk DVH-shape (OR: 9.3) and age (protective, OR: 0.94) was assessed. The model showed good calibration (slope: 1.003, R 2 = 0.92) and was found to be robust after bootstrap-based internal validation. Conclusions Constraining the bowel loops may reduce the risk of loose stools. The risk is higher for younger patients. [ABSTRACT FROM AUTHOR]

Radiotherapy is one of the main treatment choices for non-metastatic prostate cancer (PCa), although development of radioresistance limits its effectiveness. Mounting evidence supports the ability of microRNAs to interfere with different radioresistance-associated pathways, suggesting their potential as radiosensitizers. Here, we demonstrate that reconstitution of miR-875-5p, whose expression is down-regulated in PCa clinical samples and directly correlates with that of E-cadherin, was able to enhance radiation response in PCa cell lines and xenografts through EGFR direct targeting. Consistent with the established role of EGFR in sustaining epithelial-to-mesenchymal transition (EMT) and promoting DNA repair following radiation-induced nuclear translocation, we found that miR-875-5p reconstitution in PCa cells counteracted EMT and impaired DNA lesion clearance. Down-regulation of the EMT-inducing transcription factor ZEB1, which also plays a role in homologous recombination-mediated repair of DNA lesions by regulating CHK1 expression, was found to be a major determinant of miR-875-5p-induced radiosensitization, as confirmed by phenocopy experiments showing that siRNA-mediated ZEB1 knock-down was able to reproduce the microRNA radiosensitizing effect. Overall, our data support the clinical interest in developing a novel therapeutic approach based on miR-875-5p reconstitution to increase PCa response to radiotherapy. [ABSTRACT FROM AUTHOR]

Improving quality of life is a key issue for patients with prostate cancer (PCa). Lifestyle interventions could positively impact the quality of life of patients. However, there is no clear-cut understanding of the role of diet, exercise and risky behaviour reduction in improving the quality of life of men with PCa. The aim of this review was to systematically summarize randomized controlled trials on lifestyle in PCa patients with quality of life as main outcome. 17 trials were included. Most of them referred to exercise interventions (71%) and involved men undergoing androgen deprivation therapy (47%). Exercise studies yielded the greater amount of positive results on quality of life outcomes (67%), followed by dietary interventions (50%) and combined lifestyle interventions (33%). In particular, supervised exercise programs with resistance training sessions were the ones producing greater convincing evidence for benefits on quality of life. Further studies with high methodological quality providing adequate information to develop evidence-based, personalized lifestyle interventions that can effectively ameliorate PCa-related quality of life are needed. [ABSTRACT FROM AUTHOR]

Purpose To develop a method for investigating local dose effects on the bladder after prostate cancer radiotherapy based on dose–surface maps (DSMs). Background and purpose DSMs of patients included in a prospective study (DUE01) were generated by virtually cutting bladder contours at the points intersecting the sagittal plane passing through its center-of-mass: maps were laterally normalized and aligned at the posterior inferior point. The average DSMs of patients with/without toxicity, the DSMs of differences and t statistic were used to select regions better discriminating patients with toxicity. A total of 72 patients with no/mild urinary symptoms before radiotherapy and who were treated with moderate hypo-fractionation (2.5–2.65 Gy/fr, 70–74 Gy) were considered, and the endpoint was an International Prostate Symptoms Score (IPSS)⩾15 at the end of therapy (IPSSend ⩾ 15, n = 25/72). Results The DSMs of patients with/without toxicity were significantly different ( p < 0.05). The percentage of bladder circumference receiving >50–70 Gy at 5–7 mm from the base was associated with an IPSSend ⩾ 15 (odds ratios: 1.03–1.07). Different patterns were recognized for specific symptoms. With frequency/urgency, a quasi-threshold effect on the absolute posterior dose at 5–12 mm from the base (2 Gy equivalent doses = 80–82 Gy, α / β = 3–5 Gy) was observed. Conclusions Local-dose effects for acute symptoms were detected in a group of patients treated within a moderately hypo-fractionated protocol. The results for frequency/urgency were consistent with a threshold effect on the trigone. [ABSTRACT FROM AUTHOR]

Abstract: The correlation between bladder dose–wall-histogram (DWH) and dose–volume-histogram (DVH), dose–surface-histogram (DSH), and DVH-5/10 was investigated in a group of 28 patients; bladder walls were drawn on T2-MRI. DVH showed the poorest correlation with DWH; DSH or DVH-5/10 should be preferred in planning; absolute DVH may be used for radical patients, although less robust. [Copyright &y& Elsevier]

Purpose: Within a multicenter study (DUE-01) focused on the search of predictors of erectile dysfunction and urinary toxicity after radiotherapy for prostate cancer, a dummy run exercise on penile bulb (PB) contouring on computed tomography (CT) images was carried out. The aim of this study was to quantitatively assess interobserver contouring variability by the application of the generalized DICE index. Methods and Materials: Fifteen physicians from different Institutes drew the PB on CT images of 10 patients. The spread of DICE values was used to objectively select those observers who significantly disagreed with the others. The analyses were performed with a dedicated module in the VODCA software package. Results: DICE values were found to significantly change among observers and patients. The mean DICE value was 0.67, ranging between 0.43 and 0.80. The statistics of DICE coefficients identified 4 of 15 observers who systematically showed a value below the average (p value range, 0.013 — 0.059): Mean DICE values were 0.62 for the 4 “bad” observers compared to 0.69 of the 11 “good” observers. For all bad observers, the main cause of the disagreement was identified. Average DICE values were significantly worse from the average in 2 of 10 patients (0.60 vs. 0.70, p < 0.05) because of the limited visibility of the PB. Excluding the bad observers and the “bad” patients,” the mean DICE value increased from 0.67 to 0.70; interobserver variability, expressed in terms of standard deviation of DICE spread, was also reduced. Conclusions: The obtained values of DICE around 0.7 shows an acceptable agreement, considered the small dimension of the PB. Additional strategies to improve this agreement are under consideration and include an additional tutorial of the so-called bad observers with a recontouring procedure, or the recontouring by a single observer of the PB for all patients included in the DUE-01 study. [Copyright &y& Elsevier]

Abstract: Background and purpose: To report the long-term biochemical control of a non-randomized trial comparing standard (STD) and hyper-fractionated (HFX) radiation schedules for prostate cancer treatment. Materials and methods: Between 1993 and 2003, 370 patients entered the study; 330/370 (STD: 179; HFX: 151) were evaluable for current analysis. Median doses were 79.2Gy and 74Gy for HFX (1.2Gy/fr, two daily fractions) and STD (2Gy/fr), respectively; median follow-up was 7.5yr. The two regimens were compared in terms of biochemical relapse-free survival (according to ASTRO definition, bRFS) by univariate (log-rank test) and multivariate analyses (Cox regression hazard model). Based on published relationships between EQD2 and 5-yr biochemical control, α/β values for each subgroup could be estimated. Results: 7.5yr bRFS were 53.4% (±4.4%, 95% CI) and 65.4% (±4.0%) for HFX and STD, respectively (p =0.13); HFX was associated with a poorer outcome in NCCN low+intermediate patients (7.5yr bRFS: 56.6% vs 73.5%, p =0.048) while no differences were seen for high-risk patients (7.5yr bRFS: 44.1% vs 45.3%). Multivariate analysis revealed that NCCN risk grouping (high vs low+intermediate; OR: 0.59, p =0.009) and age (< vs ⩾70yr; OR: 0.67, p =0.03) were the main predictors of worse bRFS. In the subgroups of low+intermediate-risk patients <70yr, the poorer outcome of HFX was more evident (7.5yr bRFS: 47.1% vs 70.9%, p =0.078) while no difference was seen for older patients (7.5yr bRFS: 69.4% vs 72.0%, p =0.76). Our α/β estimates differ between low+intermediate-risk and high-risk patients. Conclusions: The bRFS long-term results of this non-randomized trial are consistent with different sensitivities to fractionation depending on NCCN risk grouping. The impact of age on the outcome of HFX for younger low+intermediate patients is consistent with an incomplete repair effect in older patients. [Copyright &y& Elsevier]