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• AUC of dose–response models is sensitive to the observational dose-range of the fitted data • AUC value of NTCP models is driven by intrinsic characteristics of the model and by the clinical setting of the data used to develop them. • AUC is problematic when used to compare the discriminative performance of NTCP models. Normal tissue complication probability (NTCP) models are probabilistic models that describe the risk of radio-induced toxicity in tissues or organs. In the field of radiotherapy, the area under the ROC curve (AUC) is widely used to estimate the performance in risk prediction of NTCP models. In this work, we derived an analytical expression of the AUC for the logistic NTCP model in the case of both symmetrical and asymmetrical dose (to the normal tissue) windows around D 50. Using numerical simulations, we studied the behavior of the AUC in general clinical settings, enforcing non-logistic NTCP models (Lyman-Kutcher-Burman and LogEUD) and including risk factors beyond the dose. We validated our findings using real-world radiotherapy data sets of prostate cancer patients. Our analytical expression of the AUC made explicit the dependence on both the steepness of the logistic curve (β) and the dose window width (w), showing that an increase of w pushes AUC towards higher values. Increasing values of the AUC with increasing values of w were consistently observed across simulated data sets with diverse clinical settings from published studies and real clinical data sets. Our results reveal that the AUC of NTCP models inherits intrinsic characteristics from the clinical setting of the data set on which the models are developed, and warn against the use of the AUC to compare the performance of models constructed upon data from trials in which substantially different dose ranges were administered or accounting for different risk factors beyond the dose. [ABSTRACT FROM AUTHOR]

[Display omitted] • We designed a national survey to quantify interest in scientific activities of MPEs. • 34.7% of the respondents dedicated <10% of their working time to research activities. • Time spent on scientific activities was not enough for 67.5% of the respondents. • The lack of time was the most frequent (77%) barrier to scientific activities. The "FutuRuS" working group of the Italian Association of Medical Physics and Health Physics (AIFM) designed a survey (SicAS) to get feedback from its members regarding their interests and their experience in taking part in scientific activities and events, with the objective of focusing future efforts of the AIFM towards increasing the scientific activity of the medical physics expert (MPE). SicAS was sent out in March 2022 to all AIFM members by newsletter and official communication. SicAS was structured into three sections: personal information and institution of affiliation information, involvement in scientific activities, interest in and commitment to scientific activities. Responses were collected in a fully anonymised mode from the Google Forms platform and analysed with descriptive statistics. Out of 1289 members (active at the end of 2021), 467 responded to the Survey (response rate of 36%). The Survey results highlighted that AIFM members ranked the involvement of the MPE in scientific activities as highly relevant to the profession. However, 34.7% indicated devoting less than 10% of their working time to scientific activities. 67.5% of the respondents were dissatisfied with the time spent on scientific activities. The primary barrier was the lack of time (77%), followed by a lack of mentoring (32%). SicAS highlighted the need for AIFM initiatives to support members' scientific activities. National societies should help develop and support networks between members, create links among universities, hospitals, research institutions and industries, and provide guidelines and learning platforms for enhancing the MPEs' involvement in scientific activities. [ABSTRACT FROM AUTHOR]

Aim To investigate late gastrointestinal toxicity in a large pooled population of prostate cancer patients treated with radical radiotherapy. Normal tissue complication probability models were developed for late stool frequency and late rectal pain. Methods and materials Population included 1336 patients, 3-year minimum follow-up, treated with 66–80 Gy. Toxicity was scored with LENT-SOMA-scale. Two toxicity endpoints were considered: grade ⩾2 rectal pain and mean grade (average score during follow-up) in stool frequency >1. DVHs of anorectum were reduced to equivalent uniform dose (EUD). The best-value of the volume parameter n was determined through numerical optimization. Association between EUD/clinical factors and the endpoints was investigated by logistic analyses. Likelihood, Brier-score and calibration were used to evaluate models. External calibration was also carried out. Results 4% of patients (45/1122) reported mean stool frequency grade >1; grade ⩾2 rectal pain was present in the TROG 03.04 RADAR population only (21/677, 3.1%): for this endpoint, the analysis was limited to this population. Analysis of DVHs highlighted the importance of mid-range doses (30–50 Gy) for both endpoints. EUDs calculated with n = 1 (OR = 1.04) and n = 0.35 (OR = 1.06) were the most suitable dosimetric descriptors for stool frequency and rectal pain respectively. The final models included EUD and cardiovascular diseases (OR = 1.78) for stool frequency and EUD and presence of acute gastrointestinal toxicity (OR = 4.2) for rectal pain. Conclusion Best predictors of stool frequency and rectal pain are consistent with findings previously reported for late faecal incontinence, indicating an important role in optimization of mid-range dose region to minimize these symptoms highly impacting the quality-of-life of long surviving patients. [ABSTRACT FROM AUTHOR]

Purpose To assess bladder spatial-dose parameters predicting acute urinary toxicity after radiotherapy for prostate cancer (PCa) through a pixel-wise method for analysis of bladder dose-surface maps (DSMs). Materials & methods The final cohort of a multi-institutional study, consisting of 539 patients with PCa treated with conventionally (CONV:1.8–2 Gy/fr) or moderately hypo-fractionated radiotherapy (HYPO:2.2–2.7 Gy/fr) was considered. Urinary toxicity was evaluated through the International Prostate Symptoms Score (IPSS) administered before and after radiotherapy. IPSS increases ⩾10 and 15 points at the end of radiotherapy (ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15) were chosen as endpoints. Average DSMs (corrected into 2 Gy-equivalent doses) of patients with/without toxicity were compared through a pixel-wise method. This allowed the extraction of selected spatial descriptors discriminating between patients with/without toxicity. Previously logistic models based on dose-surface histograms (DSH) were considered and replaced with DSM descriptors. Discrimination power, calibration and log-likelihood were considered to evaluate the impact of the inclusion of spatial descriptors. Results Data of 375/539 patients were available. ΔIPSS ⩾ 10 was recorded in 76/375 (20%) patients, while 30/375 (8%) experienced ΔIPSS ⩾ 15. The posterior dose at 12 mm from the bladder base (roughly corresponding to the trigone region) resulted significantly associated to toxicity in the whole/HYPO populations. The cranial extension of the 75 Gy isodose along the bladder central axis was the best DSM-based predictor in CONV patients. Multi-variable models including DSM descriptors showed better discrimination (AUC = 0.66–0.77) when compared to DSH-based models (AUC = 0.58–0.71) and higher log-likelihoods. Conclusion DSMs are correlated with the risk of acute GU toxicity. The incorporation of spatial descriptors improves discrimination and log-likelihood of multi-variable models including dosimetric and clinical parameters. [ABSTRACT FROM AUTHOR]

The purpose of this study was to quantify the impact of inter-fraction modifications of bladder during RT of prostate cancer on bladder dose surface maps (DSM). Eighteen patients treated with daily image-guided Tomotherapy and moderate hypofractionation (70–72.8 Gy at 2.5–2.6 Gy/fr in 28 fractions and full bladder) were considered. Bladder contours were delineated on co-registered daily Megavoltage CT (MVCT) by a single observer and copied on the planning CT to generate dose–volume/surface histograms (DVH/DSH) and bladder DSMs. Discrepancies between planned and daily absorbed doses were analyzed through the average of individual systematic errors, the population systematic errors and the population random errors for the DVH/DSHs and DSMs. In total, 477 DVH/DSH and 472 DSM were available. DSH and DVH showed small population systematic errors of absolute surfaces (<3.4 cm 2 ) and volumes (<8.4 cm 3 ) at the highest doses. The dose to the posterior bladder base assessed on DSMs showed a mean systematic error below 1 Gy, with population systematic and random errors within 4 and 3 Gy, respectively. The region surrounding this area shows higher mean systematic errors (1–3 Gy), population systematic (8–11 Gy) and random (5–7 Gy) errors. In conclusion, DVH/DSH and DSMs are quite stable with respect to inter-fraction variations in the high-dose region, within about 2 cm from bladder base. Larger systematic variations occur in the anterior portion and cranially 2.5–3.5 cm from the base. Results suggest that dose predictors related to the high dose area (including the trigone dose) are likely to be sufficiently reliable with respect to the expected variations due to variable bladder filling. [ABSTRACT FROM AUTHOR]

Purpose Development of NTCP models of late severe urinary symptoms after radical RT for prostate cancer (PCa). Methods Patients were enrolled in a prospective, multicentre, observational trial in 2010–2014 and treated with conventional (74–80 Gy at 1.8–2 Gy/fr) or moderately hypofractionated IMRT (65–75.2 Gy at 2.2–2.7 Gy/fr). Bladder dose-surface histograms were corrected to 2 Gy/fr equivalent doses (EQD2) and reduced to Equivalent Uniform Doses at varying α / β and n. Urethral stricture requiring urethrotomy and bleeding (assessed by the physicians) and late obstructive symptoms and incontinence (through ICIQ and IPSS questionnaires) were evaluated before RT, at its completion and every 6 months until 5 years of follow-up. Incidence of late obstructive symptoms was defined as an increase of ⩾10 points with respect to baseline in the IPSS, at least once between 6–36 months after RT; incidence of incontinence as the sum ICIQ3 + ICIQ4 > 5, with the same timing, in continent patients before RT (ICIQ3 + ICIQ4 = 0). Maximum likelihood estimation (MLE) was employed for calculating the best-fit NTCP parameters (EUD50 and k) of all symptoms. Results 319 patients were followed for ⩾36 months with at least 3 follow-up evaluations. 27/319 (23%) patients exhibited at least one severe late urinary symptom (details in Table). Bleeding, obstructive symptoms and incontinence showed greater incidence for hypofractionation and EQD2 > 78 Gy. The highest likelihood was obtained for very low n in all cases; low α / β was found for all the endpoints except stricture. Figure shows the best-fit NTCP parameters: incontinence and bleeding curves were steeper with rising EUD. Conclusions Incidence of late severe urinary symptoms in patients treated with IMRT for PCa was about 20%. Bladder seems to act as a serial organ and all the symptoms significantly depend on the prescribed dose. In addition, all the symptoms, except for stenosis, show a surprisingly important effect of hypofractionation. [ABSTRACT FROM AUTHOR]

Purpose To develop a modelling procedure for late rectal bleeding (LRB) that goes beyond maximum likelihood model fitting of data. Thus, to create a metamodel for grade 2–3 (G23) and grade 3 (G3) LRB starting from literature evidence and validate it on a large population. Methods Metamodelling allows to highlight specific features of the model itself. Characteristics that predictive models for LRB have in common are: the global harmony of radiobiological parameters (volume effect parameter, n, steepness of the curve, k, and dose parameter associated to 50% of complication probability, D50) and specific clinical factors that frequently occur. Models including rectal Equivalent Uniform Dose (EUD) with/without patient-related dose-modifying factors (DMF) were retrieved by literature search. Dosimetric coefficients were resolved by weighted mean of published values, using their standard deviation as weight. Identified clinical features, expressed by DMF, were differently weighted taking into account the prevalence of the features and the size of the study. Finally, both factors were inserted in a modified logit-EUD model. Metamodel was validated on a pooled population (3DCRT/IMRT) of three international cohorts. Performance was assessed through calibration. Results Literature search identified rectal EUD, previous abdominal surgery, hormone therapy and use of cardiovascular drugs as relevant features: associated coefficients are presented in Table 1. Validation cohort included 1591 pts with 240 (15%) LRBG23 and 98 (6.2%) LRBG3 pts. The calibration (Fig. 1) showed the following results: concerning LRBG23 the slope was equal to 0.22 (R2 = 0.38); the corresponding values for LRBG3 were 1.12 and 0.97. Conclusions A metamodel for prediction of LRB was derived from literature. LRBG3 model was successfully validated on a large population proving to be a valuable tool for predicting toxicity before RT. The model for LRBG23 predicted very well toxicity rate below 25% (which involved 87% of the population) while partially failing at higher probabilities. [ABSTRACT FROM AUTHOR]

A system (Calypso, Varian Medical Systems) based on the localization of electromagnetic transponders (ELM-TRNs) permanently implanted in the prostate allows real-time tracking during radiotherapy treatments. Development and validation of a dedicated software for ELM-TRNs signal analysis to quantify the amplitude of the intra-fraction prostate motion induced by patient's breathing, both in supine and prone position. For each treatment session, the software automatically identifies the breathing frequency on the power density spectrum of the recorded signal and creates a bandpass filter around this frequency. The obtained filter is then applied to selectively compute the breathing-induced harmonic excursion of the prostate around its nominal position. The software was validated with a moving phantom (QUASAR, Modus Medical Devices), provided with home-made inserts containing three ELM-TRNs. Harmonic motions along the three main directions were tracked at several known frequencies and amplitudes. The calculated frequencies and amplitudes were compared to the expected ones. The software was then applied to signals of patients who underwent radiotherapy treatments in supine or prone position. The software automatically computed the correct frequencies and amplitudes within a 0.6% and a 110 μm uncertainty, respectively, without any significant difference among the three main directions. The software was demonstrated to properly work on signals acquired both with supine and prone patients. A software to quantify prostate motion due to patient's breathing was successfully developed, in-phantom validated and applied to supine and prone patients, highlighting significant motion differences between the two setups. None. Work partially funded by AIRC-(IG-14300). [ABSTRACT FROM AUTHOR]