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Background: Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not known., Methods: EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m 2 every 6 weeks) or lomustine (110 mg/m 2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene (IDH) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0-2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union's Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028., Discussion: EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma., Trial Registration: ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023., (© 2024. The Author(s).)

Purpose: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams., Materials and Methods: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments., Results: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively., Conclusions: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic radiosurgery is efficacious and safe in the treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity., Objective: Demonstrating adaptive staged-dose Gamma Knife radiosurgery (ASD-GKRS) being a safe and effective treatment for large brain metastases., Materials and Methods: We retrospectively analyzed our series of patients treated with two-stage Gamma Knife radiosurgery for large brain metastases in [BLINDED], between February 2018 and May 2020., Results: Forty patients with large brain metastases underwent adaptive staged-dose Gamma Knife radiosurgery, with median prescription dose of 12 Gy and a median interval between stages of 30 days. At three-month follow-up, the survival rate was 75.0% with a local control rate of 100%. At six-month follow-up, the survival rate was 75.0% with a local control rate of 96.7%. The mean volume reduction was 21.81 cm 3 (16.76-26.86; 95% CI). The difference between baseline volume and six-month follow-up volume was statistically significant., Conclusions: Adaptive staged-dose Gamma Knife radiosurgery is a safe, non-invasive and effective treatment for brain metastases, with a low rate of side effects. Large prospective trials are needed to strengthen data obtained about the effectiveness and safety of this technique in managing large brain metastases., Competing Interests: None

Objective: To outline a practical method of performing prostate cancer radiotherapy in patients with bilateral metal hip prostheses with the standard resources available in a modern general hospital. The proposed workflow is based exclusively on magnetic resonance imaging (MRI) to avoid computed tomography (CT) artifacts., Case Description: This study concerns a 73-year-old man with bilateral hip prostheses with an elevated risk prostate cancer. Magnetic resonance images with assigned electron densities were used for planning purposes, generating a synthetic CT (sCT). Imaging acquisition was performed with an optimized Dixon sequence on a 1.5T MRI scanner. The images were contoured by autosegmentation software, based on an MRI database of 20 patients. The sCT was generated assigning averaged electron densities to each contour. Two volumetric modulated arc therapy plans, a complete arc and a partial one, where the beam entrances through the prostheses were avoided for about 50° on both sides, were compared. The feasibility of matching daily cone beam CT (CBCT) with MRI reference images was also tested by visual evaluations of different radiation oncologists., Conclusions: The use of magnetic resonance images improved accuracy in targets and organs at risk (OARs) contouring. The complete arc plan was chosen because of 10% lower mean and maximum doses to prostheses with the same planning target volume coverage and OAR sparing. The image quality of the match between performed CBCTs and MRI was considered acceptable. The proposed method seems promising to improve radiotherapy treatments for this complex category of patients.

Purpose: The EORTC Radiation Oncology Group uses a Facility Questionnaire (FQ) to collect information from its member radiation oncology departments. We analysed the FQ database for patient-related workload, staffing levels and infrastructure to determine developments in radiation oncology departments in the clinical trials community., Materials & Methods: We exported the FQ database in August 2019. Departments were included if their FQ was created or updated within the two preceding years. Observations were compared with previous evaluations of the FQ database., Results: In total, 161 departments from 24 mostly European countries were analysed. The average number of patients per department increased by 3.0% to 2,453 (2013: 2,381). The annual number of patients decreased by 7.4% to 225 per radiation oncologist (2013: 243) and by 7.9% to 326 per medical physicist (2013: 354). In contrast, the number of patients increased by 23.3% to 106 per radiation therapist (RTT) (2013: 86) and per treatment unit by 3.9 % to 485 (2013: 467). In a pairwise comparison of departments that were available in 2013 and 2019, the number of patients per radiation oncologist (p = 0.02) and per physicist (p = 0.0003) decreased significantly. The number of departments that own a dedicated PET-CT scanner more than doubled (2013: 4%; 2019: 9%) and the availability of stereotactic body radiation therapy (SBRT) increased by 31.8% to 85.7% of the departments (2013: 65%)., Conclusion: The case-related workload per radiation oncologist and per physicist continues to decrease but increases per RTT and treatment unit. This is likely driven by an increased use of complex techniques, multimodality imaging and the implementation of automation in radiation oncology departments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group (GHG) is a collaborative group of Radiation Therapy Quality Assurance (RTQA) Groups harmonizing and improving RTQA for multi-institutional clinical trials. The objective of the GHG OAR Working Group was to unify OAR contouring guidance across RTQA groups by compiling a single reference list of OARs in line with AAPM TG 263 and ASTRO, together with peer-reviewed, anatomically defined contouring guidance for integration into clinical trial protocols independent of the radiation therapy delivery technique., Materials and Methods: The GHG OAR Working Group comprised of 22 multi-professional members from 6 international RTQA Groups and affiliated organizations conducted the work in 3 stages: (1) Clinical trial documentation review and identification of structures of interest (2) Review of existing contouring guidance and survey of proposed OAR contouring guidance (3) Review of survey feedback with recommendations for contouring guidance with standardized OAR nomenclature., Results: 157 clinical trials were examined; 222 OAR structures were identified. Duplicates, non-anatomical, non-specific, structures with more specific alternative nomenclature, and structures identified by one RTQA group were excluded leaving 58 structures of interest. 6 OAR descriptions were accepted with no amendments, 41 required minor amendments, 6 major amendments, 20 developed as a result of feedback, and 5 structures excluded in response to feedback. The final GHG consensus guidance includes 73 OARs with peer-reviewed descriptions (Appendix A)., Conclusion: We provide OAR descriptions with standardized nomenclature for use in clinical trials. A more uniform dataset supports the delivery of clinically relevant and valid conclusions from clinical trials., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The WHO declared 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a public health emergency of international concern. The National and Regional Health System has been reorganized, and many oncological patients died during this period or had to interrupt their therapies. This study summarizes a single-centre experience, during the COVID-19 period in Italy, in the treatment of brain metastases with Gamma Knife stereotactic radiosurgery (GKRS)., Methods: We retrospectively analysed our series of patients with brain metastases who underwent GKRS at the Niguarda Hospital from February 24 to April 24, 2020., Results: We treated 30 patients with 66 brain metastases. A total of 22 patients came from home and 8 patients were admitted to the emergency room for urgent neurological symptoms. Duration of stay was limited to 0-1 day in 17 patients. We chose to treat a cluster of 9 patients, whose greater lesion exceeded 10 cm3, with 2-stage modality GKRS to minimize tumour recurrence and radiation necrosis., Conclusion: Due to the COVID-19 pandemic, the whole world is at a critical crossroads about the use of health care resources. During the COVID-19 outbreak, the deferral of diagnostic and therapeutic procedures and a work backlog in every medical specialty are the natural consequences of reservation of resources for COVID-19 patients. GKRS improved symptoms and reduced the need for open surgeries, allowing many patients to continue their therapeutic path and sparing beds in ICUs. Neurosurgeons have to take into account the availability of stereotactic radiosurgery to reduce hospital stay, conciliating safety for patients and operators with the request for health care coming from the oncological patients and their families., (© 2020 S. Karger AG, Basel.)

Purpose: Quality assurance (QA) for clinical trials is important. Lack of compliance can affect trial outcome. Clinical trial QA groups have different methods of dose distribution verification and analysis, all with the ultimate aim of ensuring trial compliance. The aim of this study was to gain a better understanding of different processes to inform future dosimetry audit reciprocity., Materials: Six clinical trial QA groups participated. Intensity modulated treatment plans were generated for three different cases. A range of 17 virtual 'measurements' were generated by introducing a variety of simulated perturbations (such as MLC position deviations, dose differences, gantry rotation errors, Gaussian noise) to three different treatment plan cases. Participants were blinded to the 'measured' data details. Each group analysed the datasets using their own gamma index (γ) technique and using standardised parameters for passing criteria, lower dose threshold, γ normalisation and global γ., Results: For the same virtual 'measured' datasets, different results were observed using local techniques. For the standardised γ, differences in the percentage of points passing with γ < 1 were also found, however these differences were less pronounced than for each clinical trial QA group's analysis. These variations may be due to different software implementations of γ., Conclusions: This virtual dosimetry audit has been an informative step in understanding differences in the verification of measured dose distributions between different clinical trial QA groups. This work lays the foundations for audit reciprocity between groups, particularly with more clinical trials being open to international recruitment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: The phase III EORTC 1219-DAHANCA 29 intergroup trial evaluates the influence of nimorazole in patients with locally advanced head and neck cancer when treated with accelerated radiotherapy (RT) in combination with chemotherapy. This article describes the results of the RT Benchmark Case (BC) performed before patient inclusion., Materials and Methods: The participating centers were asked to perform a 2-step BC, consisting of (1) a delineation and (2) a planning exercise according to the protocol guidelines. Submissions were prospectively centrally reviewed and feedback was given to the submitting centers. Sørensen-Dice similarity index (DSI) and the 95th percentile Hausdorff distance (HD) were retrospectively used to evaluate the agreement between the centers and the expert contours., Results: Fifty-four submissions (34 delineation and 20 planning exercises) from 19 centers were reviewed. Nine (47%) centers needed to perform the delineation step twice and three (16%) centers 3 times before receiving an approval. An increase in DSI-value and a decrease in HD, in particular for the prophylactic Clinical Target Volume (pCTV), could be found for the resubmitted cases. No unacceptable variations could be found for the planning exercise., Conclusions: These BC-results highlight the need for effective and prospective RTQA in clinical trials. Even with clearly defined protocol guidelines, delineation and not planning remain the main reason for unacceptable protocol variations. The introduction of more objective quantitative analysis methods, such as the HD and DSI, in future trials might strengthen the evaluation by experts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The goal of modern radiotherapy is to deliver a lethal amount of dose to tissue volumes that contain a significant amount of tumour cells while sparing surrounding unaffected or healthy tissue. Online image guided radiotherapy with stereotactic ultrasound, fiducial-based planar X-ray imaging or helical/conebeam CT has dramatically improved the precision of radiotherapy, with moving targets still posing some methodical problems regarding positioning. Therefore, requirements for precise target delineation and identification of functional body structures to be spared by high doses become more evident. The identification of areas of relatively radioresistant cells or areas of high tumor cell density is currently under development. This review outlines the state of the art of MRI integration into treatment planning and its importance in follow up and the quantification of biological effects. Finally the current state of the art of online imaging for patient positioning will be outlined and indications will be given what the potential of integrated radiotherapy/online MRI systems is., (Copyright © 2015. Published by Elsevier GmbH.)

Background and Purpose: The Facility Questionnaire (FQ) of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group (EORTC-ROG) evaluates the human, technical and organizational resources at each EORTC member institution. The purpose of this study is to use the FQ database to assess the improvement of radiation therapy (RT) structures and resources within the EORTC compared to the previous surveys performed by our group., Material and Methods: We report the content of the current FQ database, completed online by 156 EORTC candidate member institutions from 22 countries between February 2011 and February 2013. Results are compared to FQ-published data from 1992 and 2007., Results: The average number of patients per year per EORTC institution is 2381 (range 350-12,000) an 18.2% increase compared to the 2007 figures. From 2007 to 2013 the average number of radiation oncologists, physicists and radiation technologists per EORTC institution has increased by 27% (from 8.5 to 10.8), 41% (from 5.2 to 7.4) and 38% (from 26.1 to 36.1) respectively. Consequently the number of patients per year per radiation oncologist has decreased from 258 to 243, for physicists from 426 to 354 and for radiation technologists from 107 to 86. One hundred and forty-six (94%) and 101 (65%) institutions can now deliver IMRT and SBRT, compared to 77 (79%) and 53 (54%) in 2007., Conclusions: The standards set by the EORTC-ROG are met by a continually improving number of institutions, helping to safeguard use of advanced technologies in EORTC-ROG clinical trials., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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 ≥6 years) 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 3 years 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 V75 Gy (OR=1.07). In multivariate analysis, ≥G1 linc was associated with V40 Gy (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 3 years after RT (OR=16.3)., Conclusions: Long-term (median: 7 years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3 years after RT. Linc was associated with several risk factors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Set-up errors represent a source of uncertainty in head and neck (H&N) cancer radiotherapy. The present study evaluated set-up accuracy with the use of cone-beam computed tomography (CBCT) in order to establish the proper clinical target volume (CTV) to planning target volume (PTV) margins to be adopted., Methods: Local set-up accuracy was analysed for 44 H&N cancer patients since the implementation of CBCT. An on-line correction protocol was adopted, with the first 3 scans used to correct systematic errors with a 3-mm action level. The overall mean displacement (M), the population systematic (Σ) and random (σ) errors and the 3D vector length were calculated. PTV margins were calculated according to the van Herk formula (2.5Σ + 0.7σ)., Results: A total of 420 CBCT scans were analysed. A systematic correction was needed in 43% of patients. The value of M was <1 mm in all directions; the values of Σ and σ ranged over 1-1.2 and 1.4-1.9 mm, respectively. Pre-correction PTV margins were 3.48, 4.08 and 4.33 mm along the 3 axes. The PTV margins calculated after online correction were <2.5 mm in all directions., Conclusions: Kilovoltage CBCT is effective in evaluating set-up accuracy in H&N patients. CTV-PTV margins of 5 mm are safe and are currently adopted at our centre; however, some special situations, such as re-irradiation or the close proximity of organs at risk and high-dose regions, could benefit from daily image registration and lower (i.e., 3 mm) margins.

Intensity Modulated Radiation Therapy (IMRT) is a complex treatment modality that requires pre-treatment patient-specific quality control (QC) in order to assess a correct treatment delivery. The aim of this work is to investigate pre-treatment patient-specific per-field QCs performed with an on-board EPID at the gantry angle of 0° and at the treatment ones, and to asses if measurements executed at 0° are able to guarantee a correct treatment. Ten patients with prostate cancer were evaluated. Two "verification" plans were created for each patient in order to calculate the dose at the EPID surface: one with all fields positioned at 0° and one with all fields at the actual treatment angles. EPID's mechanical shifts due to gravity effects were always taken into account and corrected. 0 and no-0 plans were compared using a gamma-index method (3%, 3 mm). The gamma index was found dependent on gantry angles but the difference between 0 and no-0 samples was small (-0.3% mean value) and the criteria of acceptability of the gamma method was always satisfied for every field delivered at angles different from 0. Therefore patient-specific pre-treatment QCs should be done at treatments angles, but, if periodical quality assurance is performed on dynamic MLC for different gantry angles, this requirement was shown not strictly mandatory and pre-treatment IMRTQC can be reasonably executed at 0° angles too., (Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions., Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for ≤3 years after RT) of 586 patients were available. The peak incontinence (P&#95;INC) and two longitudinal definitions (chronic incontinence [C&#95;INC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M&#95;INC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P&#95;INC (Grade 2 or greater), C&#95;INC, and M&#95;INC of ≥1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models., Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M&#95;INC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P&#95;INC, M&#95;INC ≥1, and C&#95;INC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P&#95;INC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C&#95;INC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of ≥80% was predictive of a M&#95;INC of ≥1 (OR, 3.8; p = .008) and of C&#95;INC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor) correlated highly with both C&#95;INC and M&#95;INC ≥1. The predictive values of the models for C&#95;INC (area under the curve, 0.83) and M&#95;INC ≥1 (area under the curve, 0.73) were greater than the ones for P&#95;INC (area under the curve, 0.62) and more reliable (p = .0001-.0003 against p = .02). Nomograms for the two longitudinal definitions were derived., Conclusions: The longitudinal definitions of fecal incontinence (C&#95;INC and M&#95;INC ≥1) were helpful in accounting for both the persistence and the severity of the incontinence. A significant fraction of peak events was consequential to acute incontinence, and a longer duration of symptoms mainly depended on the rectal dose bath (percentage of rectal volume receiving >40 Gy), and pretreatment clinical factors., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 36 months 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), V75 Gy (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 V75 Gy 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 © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer., Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events)., Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy., Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 TD(50)s: the ratio of TD(50)s 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 TD(50)=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 © 2011 Elsevier Ireland Ltd. All rights reserved.)

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 36 months 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 36 months. Bleeding was mainly correlated with V75 Gy 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 V75 Gy<5% and, in the case of patients previously submitted to abdominal/pelvic surgery, V70 Gy<15-20%. Faecal incontinence seems to be mainly a consequential effect after acute toxicity.

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.

Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with > or =70 Gy conformal radiotherapy., Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered., Results: Of 1,132 patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p = 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea., Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for particular symptoms.

Background and Purpose: Intensity modulated radiation therapy offers a dose distribution improvement by modulating the two-dimensional X-ray fluence. This increases the treatment complexity from the planning phase to the verification one. Pre-treatment dosimetric verifications of each treatment field are strictly necessary, films and EPIDs are generally used for this purpose. In this paper we investigated the dosimetric characteristics of a commercially available fluoroscopic EPID "I'mRT QA" (Scanditronix-Wellhöfer) (I-QA) based on charge-coupled device camera (CCD) and we present a new method for optimising the EPID's response., Materials and Methods: I-QA is an optically sealed EPID and it is designed for on-line two-dimensional measurements of relative dose distribution. Dose profiles measured in water with diodes and dose distributions measured in water-equivalent phantoms with films were compared with those obtained with the I-QA for homogeneous and intensity modulated 6 and 18 MV photon beams., Results and Conclusions: I-QA measurements depend on the field size and on the two-dimensional energy spectrum of the beam. The incoming beam was modified positioning a series of lead and plastic (RW3) slabs above the fluorescent screen to obtain a homogeneous response of the I-QA over the whole sensitive area. The thickness of lead and RW3 sheets was optimised to get the best matching between diodes, films and the I-QA measurements for each energy. Gamma index evaluations showed a correspondence between I-QA measurements and diode ones within 3% or 2 mm for homogeneous and simple modulated fields, and within 5% or 3mm for complex modulated fields.

X-ray and light field alignment evaluation is carried out during linac quality assurance programs. In this paper, we compare the size of the light field measured by a photodiode and by a more traditional visual observation with the size of the x-ray field. The comparison between actual light field size, measured with the photodiode, and light field size measured by human eye allow us to verify the reliability of human eye in the evaluation of this parameter. The visual field is always larger than real light field; however, it agrees better with the x-ray field. It matches the light field if we take into account the 25% (+/- 1%) of the decrement line of the maximum central lightening; however, this method simulates better the actual field employed in radiation treatments.

Introduction: Digital radiographic systems permit to optimize execution, depiction and storage of radiological images. Since a Regius 336 digital system (Konica Corp., Tokyo, Japan) devoted to chest radiography was recently installed in the Radiology Department of S. Anna Hospital in Como, Italy, we investigated its performance relative to image quality., Material and Methods: Konica Regius 336 is a computed radiography system made of a phosphorescence detector plate which is scanned with an infrared semiconductor laser beam. The radiographic image obtained from the detector is subjected to image processing, which allows a stable output and the nonlinear curve typical of conventional radiographic systems. Image quality was assessed based on the following parameters: dose, contrast, noise, and spatial resolution. As reference, we assessed the same parameters on a Cronex 88 analogic chest-changer (DuPont Pharma, North Billerica, Mass, USA)., Results: The Regius 336 air kerma values were always higher than the analogic ones (about 10%), both with and without a chest phantom; noise was also greater than in analogic images, sometimes even doubled. The optical densities of a step wedge and the spatial resolution of the digital chest-changer are independent of the X-ray tube voltage consequent to broader optical latitude. Inversely, the analogic images of the wedges show great optical density variability as a function of the X-ray tube voltage (in a range of 2). The modulation transfer functions of the two systems have the same trend., Discussion and Conclusions: The performance of the Konica Regius 336 is nearly equivalent to that of an analogic system. The main advantages of the digital system are a standard output, lower consumption of radiographic films, higher productiveness and better image quality standard level.

Purpose: The aim of this paper is to compare the EC-L Kodak system for radiation therapy beam localization with a conventional one that could be daily employed in a radiotherapy department., Background: The main purpose of portal images is to verify the treatment volume in actual clinical conditions. Low contrast is the main constraint affecting portal film image., Methods: Kodak proposes a new imaging system (film and cassette) characterized by contrast enhancement as imaging standard for radiotherapy. The evaluation of system contrast was carried out by using a step-wedge consisting in 4 60 x 60 mm plexiglas steps and an anthropomorphic phantom. Portal films were exposed to a 6 MV photon beam by a linear accelerator (Varian Clinac 1800) with a 250 x 340 mm field size at the 1000 mm source film distance. The 2 imaging system performances were evaluated analyzing the image optical density., Results: The use of the Kodak system results in a real contrast improvement, so it is satisfactory to describe the field placement as to the region of interest., Conclusions: The most critical characteristic attaining this method regards low contrast, i. e. the small optical density difference existing between different anatomical regions on the film. Since radiographic techniques can significantly influence quality of portal films, the adequate choice of film and screen combination, as well as the exposure technique is particularly useful in a radiotherapy quality assurance program.

Introduction: In vivo dosimetry allows to verify dose delivering accuracy in radiotherapy treatments. Exit dose measurements add more information about delivered dose than entrance dose evaluations., Materials and Methods: Commercial semiconductor diodes are used for exit dose measurements. The diodes are calibrated by comparison with an ionization chamber at a reference condition. Diode reading was compared with the dose measured by the ionization chamber at the exit point. The exit point is defined as the point on the central axis of the beam, at a distance equal to the maximum dose from the exit surface of a homogeneous water-like phantom. As clinical irradiation conditions are always different from reference conditions, exit dose correction factors have been investigated as a function of phantom thickness, field size at the isocenter, source-surface distance, wedge and tray. Measurements have been performed by irradiating a set of p-type semiconductor detectors with 6 MV photon beam (four diodes--mod. EDP10--Scanditronix) and 18 MV photon beam (three diodes--mod. EDP20--Scanditronix) from a Clinac 1800 linear accelerator (Varian, Palo Alto, CA, USA)., Results: The most relevant exit dose correction factors are related to field size and phantom thickness for 6 MV photons. The variation of these factors as a function of field size may be greater than 1% with a standard deviation of the same order. On the contrary, the correction factors for field, thickness and tray photons are negligible for 18 MV., Conclusions: Applying exit dose correction factors may require a great effort, particularly when many silicon diodes must be used. The actual effectiveness of each calibration factor is evaluated through the statistical analysis of experimental data. In this way, the usefulness of correction factor calculation, as depending from both experimental conditions and diode responses, can be derived from its effects on the exit dose value.

Introduction: Shaped fields are widely used in radiotherapy to protect critical organs and to avoid unnecessary normal tissue irradiation. The most common system for photon beam shaping consists in a low melting point alloy. We studied the air bubbles which can occur during alloy cooling with both new and remelted alloys and when different cooling techniques are chosen., Material and Methods: Forty cone samples (18 of remelted alloy and 22 of new alloy) were prepared to evaluate the frequence of air bubble recurrence, with reproducible geometric sizes (height = 70 mm, major base surface diameter = 60 mm, minor base surface diameter = 40 mm). Air bubble sizes and dose inhomogeneity were evaluated by reproducing 60Co radiograph of each sample (two orthogonal projections: 6 x 7 cm). The samples were cooled at a constant temperature, following three different modalities: high (25 degrees C), medium (5 degrees C), low (-20 degrees C) temperature. Owing to the small geometrical magnification, air bubble sizes were determined by measuring their surface on samples lateral projections, taking into account the sight detectable bubble edges., Results: Up to 300 mm2 lateral surface bubbles are always present in all castings. Casting inhomogeneities can produce a film-density inhomogeneity ranging from 9% to 40%. The spatial distribution of bubbles seems to be random., Conclusions: Bubble recurrence is independent of both the metal alloy (repeatedly used castings) and the different block cooling modalities. The effect of air bubbles on the shielded areas dose inhomogeneity is generally of no relevant importance. However, these inhomogeneities can produce hot spots which must be taken into accurate consideration only in the particular treatments where critical small size organ dose sparing represents a basic issue (i.e. the shielding of eye lens).

Introduction: The evaluation of effective doses in nuclear medicine investigations is generally referred to the average man, with no relevant associated diseases, during standard examinations. The effective dose in nuclear medicine examinations can be measured directly with ICRP 68. In clinical practice, the many variables related to patients characteristics and examination type may cause major differences between practical and theoretical doses. Thus, we investigated the factors which may affect internal irradiation in some of the most common nuclear medicine investigations., Materials and Methods: We analyzed the most frequent examinations carried out on 177 patients in the Nuclear Medicine Department of S. Anna Hospital, namely thyroid scintigraphy, total body bone scan, dynamic and static renal scintigraphy. The administered activity data were analyzed as a function of the withdrawn activity and that remaining in the syringe after i.v. administration and of time delays, and then they were submitted to statistical analysis (mean, standard deviation, 95% confidence range)., Results: Equivalent and effective dose changes had no correlation with patient anatomy and associated diseases on the basis of history alone, while radiopharmaceutical preparation and administration methods exhibited a real influence on effective dose: the difference between nominal and administered activity ranged 11-14.5%., Conclusions: The patients submitted to nuclear medicine investigations receive an effective dose ranging from < .5 mSv to > 4 mSv in total body scan. Our results, related to the different examination techniques, represent a confident evaluations of patient doses, as required by the relevant normative law.

A quick formula is proposed for calculating equivalent squares of irregularly shaped photon fields. No complex calculations are required. Three different energies (60Co; 6 MV and 18 MV x-rays) were investigated. Comparison with results utilizing the Clarkson technique (60Co) and with experimental measurements (6 MV and 18 MV x-rays) indicates that the method is accettable in a wide variety of clinical situations. The applied procedure introduces an indetermination lower than 4%, with maximum absolute percentage errors of 3%, 2.7%, and 3.6% for 6 MV, 18 MV, and 60Co photon fields respectively.

We illustrate a radiotherapy treatment chart elaborated to fulfil the necessity for clarity in reporting information about radiotherapeutic treatment. The schematic configuration of the chart results from the experience and the cooperation of physicists, physicians and technicians, and an effort has been made to satisfy Levels 2/3 of the ICRU 50 recommendations. The chart has been divided into four sections corresponding to different kinds of information: a cover sheet, a section containing data about the treatment planning geometry and the console parameters adopted, a section showing dosimetric data, and a section showing treatment data. The chart seems to give a good level of accuracy in reporting treatment plan information.