Purpose: The purpose of this study is to study the evolution of quality of life (QoL) in the first 5 years following Intensity-modulated radiation therapy (IMRT) for prostate cancer (PCa) and to determine possible associations with clinical/treatment data. Material and methods: Patients were enrolled in a prospective multicentre observational trial in 2010-2014 and treated with conventional (74–80 Gy, 1.8–2 Gy/fr) or moderately hypofractionated IMRT (65–75.2 Gy, 2.2–2.7 Gy/fr). QoL was evaluated by means of EORTC QLQ-C30 at baseline, at radiation therapy (RT) end, and every 6 months up to 5 years after IMRT end. Fourteen QoL dimensions were investigated separately. The longitudinal evaluation of QoL was analysed by means of Analysis of variances (ANOVA) for multiple measures. Results: A total of 391 patients with complete sets of questionnaires across 5 years were available. The longitudinal analysis showed a trend toward the significant worsening of QoL at RT end for global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. QoL worsening was recovered within 6 months from RT end, with the only exception being physical functioning. Based on ANOVA, the most impaired time point was RT end. QoL dimension analysis at this time indicated that acute Grade ≥ 2 gastrointestinal (GI) toxicity significantly impacted global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. Acute Grade ≥ 2 genitourinary (GU) toxicity resulted in lower role functioning and higher pain. Prophylactic lymph-nodal irradiation (WPRT) resulted in significantly lower QoL for global health, fatigue, appetite loss, and diarrhoea; lower pain with the use of neoadjuvant/concomitant hormonal therapy; and lower fatigue with the use of an anti-androgen. Conclusions: In this prospective, longitudinal, observational study, high radiation IMRT doses delivered for PCa led to a temporary worsening of QoL, which tended to be completely resolved at six months. Such transient worsening was mostly associated with acute GI/GU toxicity, WPRT, and higher prescription doses.

Background and purpose: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study. Materials and methods: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade >= 2 (G2+) lymphopenia (ALC < 800/mu L). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap. Results: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V >= 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/ 0.88) and confirmed by validation. Conclusions: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.

Background and purpose: To assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. Materials and methods: Complete data of 415 patients enrolled in a multi institute, prospective trial (#NCT02803086) treated with radical (31%), adjuvant (33%) and salvage (36%) intent at a median dose to pelvic nodes/lymph-nodal area of 53 Gy were available. The most severe changes between baseline and radiotherapy mid-point/end toxicity assessed by Inflammatory Bowel Disease Questionnaire (only Bowel Domain) were considered (DIBDQ). The 25th percentile values of these score variations were set as endpoints. DVHs of bowel loops for patients with/without toxicity were compared for each end-point, having excluded patients with baseline scores <5 (rate ranging between 2% and 7% according to the endpoint): the resulting best dosimetric predictors were combined with selected clinical parameters through multivariate logistic regression (MVA) to derive predictive models. Results: Delta IBDQ ranged between 0.2-1.5 points considering separately each IBDQ symptom. Only four symptoms (IBDQ1 = frequency, IBDQ5 = diarrhea, IBDQ17 = gas passage, IBDQ24 = urgency) showed a median worsening >= 1; DVH predicted the risk of worse symptoms for IBDQ5, IBDQ24 and overall Bowel Domain. At multivariable analysisDVHs (best cut-off: V46Gy >= 80 cc) and baseline scores (Odd-Ratio:0.35-0.65) were independently associated to the three end-points. The resulting models were reliable (H&L test: 0.453-0.956), well calibrated (calibration plot: slope = 0.922-1.069, R-2 = 0.725-0.875) andmoderately discriminative (Area Under the Curve:0.628-0.669). A bootstrap-based validation confirmed their robustness. Conclusion: Constraining the bowel loops (V46 < 80 cc) may reduce the risk of several moderate intestinal symptoms, with a much greater impact for patients with lower IBDQ baseline scores. (C) 2021 Elsevier B.V. All rights reserved.

AIM:Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field.MATERIAL AND METHODS:At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches.RESULTS:Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed.CONCLUSION:The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

BACKGROUND To evaluate the outcome of patients treated with salvage radiotherapy after radical prostatectomy and to investigate the effects of independent predictors on survival. METHODS From January 2000 to December 2015, 234 patients with biochemical/clinical recurrences after radical prostatectomy were submitted to salvage radiotherapy (SRT). One hundred and fifty-seven patients (67%) received three-dimensional (3D) conformal radiotherapy while 77 patients (33%) were treated with intensity-modulated radiotherapy (IMRT) or IMRT/image-guided radiotherapy by tomotherapy. The median RT dose to prostate bed was 70.2 Gy (range: 66-79 Gy). The investigated endpoints were biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS). Different covariates were considered to investigate predictors of survival. RESULTS With a median follow-up of 117 months the BRFS, CRFS, DMFS and PCSS at 10 years were 54%, 84%, 90%, and 94%, respectively. In multivariate analysis (MVA), the pathological Gleason Score (pGS) was the most important factor affecting BRFS, CRFS, DMFS and PCSS (P<0.007, HR>1.55); pathological stage (pT) was predictor of BRFS (P=0.007, HR=1.7) and PCSS (P=0.02, HR=4.2), and the last prostate-specific antigen during follow-up was an important survival predictor of CRFS (P=0.004, HR=1.26) and PCSS (P<0.0001, HR=1.04). The time between surgery and the start of SRT was correlated with BRFS (P<0.0001, HR=0.987) and CRFS (P=0.047, HR=0.989). In univariate analysis (UVA), positive surgical margins at the prostatectomy specimen improved BRFS (P=0.01, HR=0.54), CRFS (P=0.05, HR=0.46) and DMFS (P=0.005, HR=0.13) after SRT. CONCLUSIONS At long-term follow-up, excellent outcome results of SRT on BRFS, CRFS, DMFS, and PCSS were obtained. Several prognostic factors such as pGS, pT and surgical margin status were found to be predictors of survival.

OBJECTIVE:This study was undertaken to model the biochemical free survival at 5 years and to evaluate the parameters defining dose-response curve, dose-fractionation radiosensitivity and repopulation.METHODS:It was carried out a literature search on Pubmed to retrieve data sets of patients treated with external beam radiation therapy of 1.8-4.0 Gy per fraction and overall treatment time of 3 to 10 weeks. 10 groups were identified, based on risk class and androgen deprivation therapy (ADT). Dose-response curve D50 (dose at 50% probability of control) and g50 (steepness), α/β (dose-fractionation radiosensitivity), and repopulation parameters, dprolif and Tprolif , were calculated. Bootstrap-based cross-validation was performed and median and 95% CI (confidence interval) were evaluated.RESULTS:25 data sets, including 20,310 patients, were considered. The median (95% CI) D50 and g50 values were 62 (CI 53 - 66) Gy and 1.6 (0.8 - 2.4). ADT patients showed lower values of D50 and g50 (57 ± 5 Gy and 1.1 ± 0.4) compared to no-ADT patients (65 ± 2 Gy and 2.3 ± 0.6), with p < 0.0001 and p = 0.002. If we did not consider any dependence on overall treatment time, the median (95% CI) value of α/β was 1.4 (1.0 - 1.9) Gy with p < 0.0001 for all patients. The median values of dproli f and Tprolif were 0.0 to 0.3 Gy/d and 18-40 days.CONCLUSION:Dose-response curve resulted dependent on risk class and ADT, with higher steepness for no-ADT patients. Low values of dose-fractionation radiosensitivity were found, supporting the use of moderate hypofractionated radiotherapy in each risk class. A limited dependence on repopulation was observed.ADVANCES IN KNOWLEDGE:Prostate cancer response to moderate hypofractionated radiotherapy was reliably quantified considering risk class and androgen deprivation therapy.

S845ESTRO 38 the first search were charity/NGO sites (46%), followed by sponsored medical news sites (28%), hospital/university sites (20%) and governmental sites (6%).Websites operated by charity organizations had significantly higher DISCERN Plus scores (mean score: 55.5 ± 9.3) compared to hospital sites (mean score: 47.3 ± 9.6, p<0.042) and medical news sites (mean score: 46.1 ± 6.1, p<0.009), respectively.The JAMA benchmark criteria were fulfilled for all four sections in 13%, for three, two and one in 13%, 31% and 40%, respectively.Only 13% of all websites were HON code certified.All analyzed websites had a focus on curative teletherapy, 76%, 51% and 22% of all websites mentioned brachytherapy, active surveillance and palliative radiotherapy, respectively.In 57% the procedure of radiotherapy was described in detail.Special radiation techniques like "hypo-fractionation", "Intensity modulated Radiotherapy (IMRT)", "Image guided Radiotherapy (IGRT)" and "proton therapy" were mentioned in 37%, 72%, 27% and 31% of all analyzed websites, respectively. ConclusionThe quality of websites on radiotherapy and prostate cancer directed at laypersons is promising.The fact that we were unable to find a simple strategy for the identification of high quality websites (i.e.HON code certification, JAMA benchmark criteria, ALEXA ranking or different search engines) emphasizes the responsibility of the treating physicians to interpret and rank the vast quantity of information and value of personal contact with the treating radio-oncologist in order to integrate and interpret the information found online.

Purpose To improve quality and reduce variability of plans by developing a statistical ideal dose volume histogram (SI-DVH). From SI-DVH, a custom-built metric based on 21 functions was created to evaluate radiotherapic plans quantitatively. Methods CT images and ROIs of 37 VMAT prostate patients were analysed using the software PlanIQ (SNC). PlanIQ defines regions of DVH that are difficult to reach, based on an ideal dose gradient. According to this dose distribution, the minimal dose to OARs is predominantly dictated by the geometric relationship between OARs and PTV and by the prescribed dose. An average SI-DVH for each OAR was created with feasibility equal to 0.1% (impossible) and 10% (difficult) (i.e. Fig. 1). Then we created a custom-built metric by applying a linearly dependent scoring system based on QUANTEC constraints and on the SI-DVH; we defined PQM (Plan Quality Metric), sum of all the scores on target and OARs. We evaluated the quality of retrospective plans by calculating PQM. Then we replanned ten prostate cases, applying the new SI-DVH in the optimizer as objective to achieve. We calculated ΔPQM, defined as the percentage difference between replanned PQM and PQM obtained previously. Results Setting the maximum PQM to 200, ideally achievable, we obtained a median PQM equal to 133 (82 ÷ 177). After replanning we increased the value obtained a median replanned PQM equal to 161 and an average Δ PQM equal to 10% (5% ÷ 16%) and in terms of dose distribution we observed a decrease up to 10% of the dose to the OARs. Conclusions SI-DVH is a promising method which allows for quantification and optimization of plans against historical experiences based on contouring, protocol preparation and dose scheduling. The hard score and an ideal DVH to reach could aid planners in generating plans that push the limits defined by QUANTEC that can easily achievable. To improve quality and reduce variability of plans by developing a statistical ideal dose volume histogram (SI-DVH). From SI-DVH, a custom-built metric based on 21 functions was created to evaluate radiotherapic plans quantitatively. CT images and ROIs of 37 VMAT prostate patients were analysed using the software PlanIQ (SNC). PlanIQ defines regions of DVH that are difficult to reach, based on an ideal dose gradient. According to this dose distribution, the minimal dose to OARs is predominantly dictated by the geometric relationship between OARs and PTV and by the prescribed dose. An average SI-DVH for each OAR was created with feasibility equal to 0.1% (impossible) and 10% (difficult) (i.e. Fig. 1). Then we created a custom-built metric by applying a linearly dependent scoring system based on QUANTEC constraints and on the SI-DVH; we defined PQM (Plan Quality Metric), sum of all the scores on target and OARs. We evaluated the quality of retrospective plans by calculating PQM. Then we replanned ten prostate cases, applying the new SI-DVH in the optimizer as objective to achieve. We calculated ΔPQM, defined as the percentage difference between replanned PQM and PQM obtained previously. Setting the maximum PQM to 200, ideally achievable, we obtained a median PQM equal to 133 (82 ÷ 177). After replanning we increased the value obtained a median replanned PQM equal to 161 and an average Δ PQM equal to 10% (5% ÷ 16%) and in terms of dose distribution we observed a decrease up to 10% of the dose to the OARs. SI-DVH is a promising method which allows for quantification and optimization of plans against historical experiences based on contouring, protocol preparation and dose scheduling. The hard score and an ideal DVH to reach could aid planners in generating plans that push the limits defined by QUANTEC that can easily achievable.

Purpose Radiotherapy, alone or combined with chemotherapy, is a treatment modality used frequently in head and neck cancer. It is important to delineate organs in the head and neck at risk for radiation-induced swallowing dysfunction (RISD). Irradiation of the Pharyngeal Constrictor Muscle (PSCM) seems to play a crucial role in swallowing dysfunctions and in particular in the voice and speech quality changes. Purpose of our retrospective study was to identify which dose volume histogram parameters are most important to predict patient radiation-induced swallowing dysfunction, voice and speech quality. Methods Patients with head and neck cancer who previously underwent Tomotherapy treatment are selected. The prescribed radiotherapy is based on SIB technique for all PTVs irradiated simultaneously over 30 daily. Doses of 67.5, 60 and 54–57 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Upper PSCM, middle PSCM and lower PSCM were outlined separately and DVHs are stored for each patient using basal planning CT and weekly MVCT. Univariate and multivariate analysis will be used to identify novel dosimetric predictors of toxicity and predictors of quality of life assessed using appropriate questionnaires taking into consideration the actual delivered dose. Results The study started in July 2017 and the up to now 8 patients have been included in the study. Preliminary results suggest the importance of taking into consideration the dosimetric information based on basal planning CT and MVCT in order to improve the evaluation of toxicity rate and occurrence, which are still ongoing. Conclusions Dosimetric factors based on planning CT and MVCT seem to improve the identification of appropriate predictors of toxicity. More patients are to be included in the study to fully confirm these preliminary results.

Purpose: The aim of this paper is to characterize two different EPID-based solutions for pre-treatment VMAT quality assurance, the 2D portal dosimetry and the 3D projection technique. Their ability to catch the main critical delivery errors was studied. Methods: Measurements were performed with a linac accelerator equipped with EPID aSi1000, Portal Dose Image Prediction (PDIP), and PerFRACTION softwares. Their performances were studied simulating perturbations of a reference plan through systematic variations in dose values and micromultileaf collimator position. The performance of PDIP, based on 2D forward method, was evaluated calculating gamma passing rate (% GP) between no-error and error-simulated measurements. The impact of errors with PerFRACTION, based on 3D projection technique, was analyzed by calculating the difference between reference and perturbed DVH (%Delta D). Subsequently pre-treatment verification with PerFRACTION was done for 27 patients of different pathologies. Results: The sensitivity of PerFRACTION was slightly higher than sensitivity of PDIP, reaching a maximum of 0.9. Specificity was 1 for PerFRACTION and 0.6 for PDIP. The analysis of patients' DVHs indicated that the mean %Delta D was (1.2 +/- 1.9)% for D2%, (0.6 +/- 1.7)% for D95% and (- 0.0 +/- 1.2)% for Dmean of PTV. Regarding OARs, we observed important discrepancies on DVH but that the higher dose variations were in low dose area (< 10 Gy). Conclusions: This study supports the introduction of the new 3D forward projection method for pretreatment QA raising the claim that the visualization of the delivered dose distribution on patient anatomy has major advantages over traditional portal dosimetry QA systems.