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Abstract: Background: The simultaneous integrated boost (SIB) technique with dose per fraction slightly higher than 2Gy offers the advantages of shortening the treatment time and increasing the biologically equivalent dose to the tumor. This study was designed to evaluate the feasibility of a dose-escalating radiotherapy treatment by using a SIB-IMRT approach in patients with early and moderately advanced head and neck cancers. Materials and methods: Fifty-seven consecutive patients with pharyngo-laryngeal T2N0 or T2N1, or laryngeal T3N0 SCC were included. The therapeutic PTVs were treated according to three consecutive dose levels i.e., 69Gy in 30 fractions of 2.3Gy (dose level I), 72Gy in 30 fractions of 2.4Gy (dose level II) or 75Gy in 30 fractions of 2.5Gy (dose level III). The prophylactic PTVs received a dose of 55.5Gy delivered in 30 fractions of 1.85Gy. The primary endpoint of the study was acute toxicity assessed during treatment and during the first 3months following the completion of radiotherapy. The secondary endpoints included loco-regional control, disease-free survival, overall survival and late toxicity at 2years of follow-up. The study design allowed patients to be enrolled in the second dose level group if no more than 10% of grade 4 acute toxicity was observed on the first dose level group within 3months after the completion of IMRT, and so on for the third level group. Results: Forty-four men and 13 women were included in the trial. The majority of them presented with oropharyngeal cancer (53%) and laryngeal cancer (33%). Only 3 patients developed grade 4 acute mucositis during treatment, one in each dose level. Thirty-two patients (56%) experienced grade 3 toxicity, mostly dermatitis and mucositis, without any significant difference between the groups. Late grade 1 and 2 xerostomia was seen in 53% and 33% of patients, respectively. Transient grade 4 late toxicity was observed in 16% of all patients and was equally distributed among the groups. The 2-year loco-regional control was 82% for all 3 groups (79% dose level I, 88% dose level II, 79% dose level III). The 2-year overall survival was 89% for dose level I and II, and 95% for dose level III. Conclusions: This dose escalation SIB-IMRT protocol was safe and effective as the sole treatment of early and moderately advanced SCC of head and neck. No toxicity difference was observed between the groups. [Copyright &y& Elsevier]

Abstract: Purpose: This work describes the clinical validation of an automatic segmentation algorithm in CT-based radiotherapy planning for prostate cancer patients. Material and methods: The validated auto-segmentation algorithm (Smart Segmentation, version 1.0.05) is a rule-based algorithm using anatomical reference points and organ-specific segmentation methods, developed by Varian Medical Systems (Varian Medical Systems iLab, Baden, Switzerland). For the qualitative analysis, 39 prostate patients are analysed by six clinicians. Clinicians are asked to rate the auto-segmented organs (prostate, bladder, rectum and femoral heads) and to indicate the number of slices to correct. For the quantitative analysis, seven radiation oncologists are asked to contour seven prostate patients. The individual clinician contour variations are compared to the automatic contours by means of surface and volume statistics, calculating the relative volume errors and both the volume and slice-by-slice degree of support, a statistical metric developed for the purposes of this validation. Results: The mean time needed for the automatic module to contour the four structures is about one minute on a standard computer. The qualitative evaluation using a score with four levels (“not acceptable”, “acceptable”, “good” and “excellent”) shows that the mean score for the automatically contoured prostate is “good”; the bladder scores between “excellent” and “good”; the rectum scores between “acceptable” and “not acceptable”. Using the concept of surface and volume degree of support, the degree of support given to the automatic module is comparable to the relative agreement among the clinicians for prostate and bladder. The slice-by-slice analysis of the surface degree of support pinpointed the areas of disagreement among the clinicians as well as between the clinicians and the automatic module. Conclusion: The efficiency and the limits of the automatic module are investigated with both a qualitative and a quantitative analysis. In general, with efficient correction tools at hand, the use of this auto-segmentation module will lead to a time gain for the prostate and the bladder; with the present version of the algorithm, modelling of the rectum still needs improvement. For the quantitative validation, the concept of relative volume error and degree of support proved very useful. [Copyright &y& Elsevier]

Abstract: Background and purposes: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing radiotherapy for prostate cancer requires a standardisation of target delineation as well as clinical quality assurance procedures. Patients and methods: Pathological and imaging studies provide valuable information on tumour extension. In addition, clinical investigations on patient positioning and immobilisation as well as treatment verification data offer an abundance of information. Results: Target volume definitions for different risk groups of prostate cancer patients based on pathological and imaging studies are provided. Available imaging modalities, patient positioning and treatment preparation studies as well as verification procedures are collected from literature studies. These studies are summarised and recommendations are given where appropriate. Conclusions: On behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group this article presents a common set of recommendations for external beam radiotherapy of patients with prostate cancer. [Copyright &y& Elsevier]

Life expectancy of patients treated for brain tumors has lengthened due to the therapeutic improvements. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. Technical evolutions aim at enhancing the therapeutic ratio. Sparing of the healthy tissues has been improved using various approaches; however, few dose constraints have been established regarding brain structures associated with cognitive functions. The aims of this literature review are to report the main brain areas involved in cognitive adverse effects induced by radiotherapy as described in literature, to better understand brain radiosensitivity and to describe potential future improvements. [ABSTRACT FROM AUTHOR]

• The RIS development area was almost always in full beam. • Reassuringly, new RT techniques such as VMAT should not have an impact on the incidence of RIS. • Patients developing RIS in low dose areas may have an individual predisposition. The Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS. Patient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated. The mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2–32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS. This study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years. [ABSTRACT FROM AUTHOR]

• In total, more than 4000 adult patients are currently treated with PT across Europe annually. • CNS and HNC tumours are the most frequently treated tumour sites. • Most centres use national or institutional guidelines for selecting patients for PT. • Treatments are usually reimbursed by national health care systems. • Most patients are included in prospective data registries and clinical trials. Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres. We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT. Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%). Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT. [ABSTRACT FROM AUTHOR]

• Our GORTEC internationally-reviewed consensus showed that the flap-tissue junction should be considered at higher risk of tumor spread compared to other areas of the flap. • Surgeons should report the placement of flaps more accurately and consider clip placement to guide radiotherapy planning. • The risks of radiation-induced atrophy, fibrosis, and osteoradionecrosis should be considered during radiotherapy optimization. Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns. [ABSTRACT FROM AUTHOR]

Background and purpose To evaluate clinical results and safety of a dose adaptive protocol based on tumor volume coverage and critical structure constraints, for the treatment of skull base chordomas. Material and methods Between May 2006 and October 2012, 106 patients with skull base chordoma were treated by combined photon and proton irradiation. Prescribed dose levels were 68.4, 70.2, 72 and 73.8 Gy(RBE) in once daily fractionation of 1.8 Gy(RBE). Dose level and dosimetric constraints to organs at risk depended on postoperative residual Gross Tumor Volume (GTV) coverage. Local control (LC) and overall survival (OS) were evaluated using the Kaplan–Meier method. Results With a median follow-up of 61 months, the 2-year, 4-year, and 5-year LC rates were 88.6%, 78.3%, and 75.1%, respectively. GTV > 25 mL ( p  = 0.034 , HR = 2.22; 95%CI 1.06–4.62) was an independent unfavorable prognostic factor of LC. The 2-year, 4-year, and 5-year OS rates were 99%, 90.2%, and 88.3%, respectively. Grade 3–5 late toxicity was observed in 7 patients, resulting in 93% 5-year freedom from high-grade toxicity. Conclusions This study suggests that the probability of LC of skull base chordomas depends on postoperative GTV. The dose adaptive protocol achieves acceptable local control. Future studies should investigate whether further dose escalation to doses in excess of 74 Gy(RBE) would achieve better results. [ABSTRACT FROM AUTHOR]

The ACCIRAD project, commissioned by the European Commission (EC) to develop guidelines for risk analysis of accidental and unintended exposures in external beam radiotherapy (EBRT), was completed in the year 2014. In 2015, the “General guidelines on risk management in external beam radiotherapy” were published as EC report Radiation Protection (RP)-181. The present document is the third and final report of the findings from the ACCIRAD project. The main aim of this paper is to describe the key features of the risk management process and to provide general guidelines for radiotherapy departments and national authorities on risk assessment and analysis of adverse error-events and near misses. The recommendations provided here and in EC report RP-181 are aimed at promoting the harmonisation of risk management systems across Europe, improving patient safety, and enabling more reliable inter-country comparisons. [ABSTRACT FROM AUTHOR]

Abstract Purpose Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Grégoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy. Method For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus. Results This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively. Conclusion Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi-institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma. [ABSTRACT FROM AUTHOR]

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

Purpose To describe the current status of implementation of European directives for risk management in radiotherapy and to assess variability in risk management in the following areas: 1) in-country regulatory framework; 2) proactive risk assessment; (3) reactive analysis of events; and (4) reporting and learning systems. Material and Methods The original data were collected as part of the ACCIRAD project through two online surveys. Results Risk assessment criteria are closely associated with quality assurance programs. Only 9/32 responding countries (28%) with national regulations reported clear “requirements” for proactive risk assessment and/or reactive risk analysis, with wide variability in assessment methods. Reporting of adverse error events is mandatory in most (70%) but not all surveyed countries. Conclusions Most European countries have taken steps to implement European directives designed to reduce the probability and magnitude of accidents in radiotherapy. Variability between countries is substantial in terms of legal frameworks, tools used to conduct proactive risk assessment and reactive analysis of events, and in the reporting and learning systems utilized. These findings underscore the need for greater harmonisation in common terminology, classification and reporting practices across Europe to improve patient safety and to enable more reliable inter-country comparisons. [ABSTRACT FROM AUTHOR]

Introduction The delineation of Clinical Target Volume (CTV) is a critical step in radiotherapy. Several guidelines suggest different subvolumes and anatomical boundaries in rectal cancer (RC), potentially leading to a misunderstanding in the CTV definition. International consensus guidelines (CG) are needed to improve uniformity in RC CTV delineation. Material and methods The 7 radiation oncologist experts defined a roadmap to produce RC CG. Step 1: revision of the published guidelines. Step 2: selection of RC cases with different clinical stages. Step 3: delineation of cases using Falcon following previously published guidelines. Step 4: meeting in person to discuss the initial delineation outcome, followed by a CTV proposal based on revised and if needed, adapted anatomical boundaries. Step 5: peer review of the agreed consensus. Step 6: peer review meeting to validate the final outcome. Step 7: completion of RC delineation atlases. Results A new ontology of structure sets was defined and the related table of anatomical boundaries was generated. The major modifications were about the lateral lymph nodes and the ischio-rectal fossa delineation. Seven RC cases were made available online as consultation atlases. Conclusion The definition of international CG for RC delineation endorsed by international experts might support a future homogeneous comparison between clinical trial outcomes. [ABSTRACT FROM AUTHOR]

Purpose To determine whether post-implant MRI-based dosimetry of the Dominant Intra-prostatic Lesion (DIL) could best predict the occurrence of PSA bounce after prostate brachytherapy. Methods and materials We selected 66 patients with a low risk prostate cancer treated with 125 I prostate brachytherapy as monotherapy. Post-implant dosimetry based on day 30 CT-scan and multiparametric MRI co-registration was generated: planned D 90, D 95, V 100, V 150 values were calculated for each DIL. Bounce was defined as a PSA elevation ⩾0.2 ng/mL from the previous baseline value followed by a decrease to or below the prior nadir with no additional treatment. Results After a median follow-up of 35.5 months (range 13.2–72.5), a PSA bounce occurred in 24 (36.4%) patients. The mean planned D 90 of the DIL was significantly lower in bouncers: 196 ± 61 Gy vs. 234 ± 62 Gy, p = 0.018. The mean planned V 150 of the DIL was 56 ± 32% for bouncers while it was 75 ± 30% for non-bouncers, p = 0.026. Conclusion A lower planned D 90 or V 150 in the DIL were predictive of PSA bounce after prostate brachytherapy. PSA bounce could be caused by delayed cell death related to sublethal damage accumulation in the tumor. [ABSTRACT FROM AUTHOR]

Purpose The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes. Methods Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists. Results Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1 mm axial slices. The atlas can also be obtained in DICOM-RT format on request. Conclusion Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers. [ABSTRACT FROM AUTHOR]

Purpose To retrospectively analyze the efficacy of 36 Gy of elective node irradiation and report patterns of recurrence in patients with anal cancer treated by chemoradiation with the same radiotherapy (RT) treatment scheme. Methods and materials Between January1996 and December 2013, 142 patients with anal squamous cell cancer were scheduled to receive a dose of 36 Gy of elective node irradiation (ENI) to the inguinal area and whole pelvis over 4 weeks followed after a 2-week gap by a boost dose of 23.4 Gy over 17 days to the macroscopic disease. Mitomycin C combined with fluorouracil, capecitabin or cisplatin was given at day 1 of each sequence of RT. Results Disease stages were I: 3, II: 78, III A : 23, III B : 38. Compliance rates were 97.2% with RT and 87.9% with chemotherapy. After a median follow up of 48 months [3.6–192], estimated 5-year overall survival and colostomy-free survival were 75.4% and 85.3% respectively. Eleven patients (7.7%) never achieved a complete response, 15 had a local component of recurrence and 5 a regional one. One patient had failure in the common iliac node area outside the treatment fields. The inguinal control rate was 98.5%. The 5-year tumor and nodal control rates were 81.5% and 96.0%, respectively. Conclusion Chemoradiation with a dose of 36 Gy ENI achieved excellent nodal control. However, it is necessary to improve the 5-year control rate of the primary tumor. Omitting the gap and using additional doses per fraction or hyper-fractionation are to be explored. [ABSTRACT FROM AUTHOR]

Background and purpose We aimed to evaluate the patterns of loco-regional failure (LRF) after exclusive chemoradiotherapy (eCRT) for esophageal cancer with respect to planned dose and/or the incidental (unplanned) dose outside target volumes. Materials and methods Co-image registration of CT or 18 F-FDG PET-CT at the time of failure (tf) and at the time of CRT (t0) was performed in 34 patients with LRF. Dosimetric parameters with regard to local failure (LF), nodal failure (NF) and involved nodal stations (NS) were derived. Results Twenty-two patients (64.7%) had LF, the majority of which (95.5%) were located at the epicenter of the GTV of the primary tumor. The mean doses recalculated to the NS at tf were more likely to be lower than the planned dose delivered to the PTV at t0: D mean = 33.9 ± 20.8 Gy vs 52.2 ± 8.5 Gy ( p = 0.0009), D 95% = 27.5 ± 21 Gy vs 46.1 ± 4.8 Gy ( p = 0.004). Among the 12 patients with NF outside the elective nodal irradiation (ENI) volume, D mean of NS outside the ENI was significantly lower (19.4 ± 21.4 Gy) than the D mean of NS with failure within the ENI (45.1 ± 6.1 Gy, p = 0.01). Conclusion Loco-regional failure after exclusive chemoradiotherapy for esophageal cancer may be due to an inadequately low dose. [ABSTRACT FROM AUTHOR]

Disconnected cancer research data management and lack of information exchange about planned and ongoing research are complicating the utilisation of internationally collected medical information for improving cancer patient care. Rapidly collecting/pooling data can accelerate translational research in radiation therapy and oncology. The exchange of study data is one of the fundamental principles behind data aggregation and data mining. The possibilities of reproducing the original study results, performing further analyses on existing research data to generate new hypotheses or developing computational models to support medical decisions (e.g. risk/benefit analysis of treatment options) represent just a fraction of the potential benefits of medical data-pooling. Distributed machine learning and knowledge exchange from federated databases can be considered as one beyond other attractive approaches for knowledge generation within “Big Data”. Data interoperability between research institutions should be the major concern behind a wider collaboration. Information captured in electronic patient records (EPRs) and study case report forms (eCRFs), linked together with medical imaging and treatment planning data, are deemed to be fundamental elements for large multi-centre studies in the field of radiation therapy and oncology. To fully utilise the captured medical information, the study data have to be more than just an electronic version of a traditional (un-modifiable) paper CRF. Challenges that have to be addressed are data interoperability, utilisation of standards, data quality and privacy concerns, data ownership, rights to publish, data pooling architecture and storage. This paper discusses a framework for conceptual packages of ideas focused on a strategic development for international research data exchange in the field of radiation therapy and oncology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In 2011 the European Commission launched a tender to develop guidelines for risk analysis of accidental and unintended exposures in external beam radiotherapy. This tender was awarded to a consortium of 6 institutions, including the ESTRO, in late 2011. The project, denominated “ACCIRAD”, recently finished the data collection phase. Data were collected by surveys administered in 38 European countries. Results indicate non-uniform implementation of event registration and classification, as well as incomplete or zero implementation of risk assessment and events analysis. Based on the survey results and analysis thereof, project leaders are currently drafting proposed guidelines entitled “Guidelines for patient safety in external beam radiotherapy – Guidelines on risk assessment and analysis of adverse-error events and near misses”. The present article describes the aims and current status of the project, including results of the surveys. [ABSTRACT FROM AUTHOR]

Introduction One of the goals of Quality Assurance in Radiotherapy (QART) is to reduce the variability and uncertainties related to treatment planning and beam delivery. The purpose of this study was to assess the outcome impact and cost-effectiveness (CE) of various QART levels for a head and neck (H&N) cancer study. Materials and methods QART levels were defined as: basic QART with a dummy run (level 2), level 2 plus prospective Individual Case Reviews (ICRs) for 15% of patients (level 3) and level 2 plus prospective ICRs for all patients (level 4). The follow-up of patients was modeled using a multi-state model with parameters derived from EORTC, TROG and RTOG prospective studies. Individual patient data, linking QART results with outcome, were retrieved from the TROG database. Results for each QART level were expressed as percentage of mortality and local failure at 5 years. Results Quality-of-life-adjusted and recurrence-free survival increased with increasing QART levels. The increase of all these metrics was more sizeable with an increased QART level from 2 or 3 to 4. The estimated quality-adjusted-life-years (QALYs) for an increase of QART levels of 3-4 and 2-4 were 0.09 and 0.15, respectively. The incremental CE ratio was €5525 and €3659 Euros per QALY for these QART levels. Compared to QART level 2 or 3, level 4 was cost-effective. Conclusions Increasing QART levels resulted in better patient outcome in this simulated study. The increased complexity of the QART program was also cost-effective. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The purpose of this study was to describe the pattern of nodal relapse with 18F-fluoro-choline (FCH) Positron Emission Tomography/Computerized Tomography (PET/CT) in prostate cancer patients after radiotherapy. Materials and methods: Eighty-three patients had a FCH PET/CT at time of biochemical failure. Of 65 patients with positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy with or without a prior radical prostatectomy. Each FCH positive node was assigned to a lymph node station with respect to the CTV defined by the RTOG guidelines (CTVRTOG). 3D mapping was performed after each node was manually placed in a reference planning CT scan after automatic co-registration of the two scans based on bone anatomy. Eighteen patients (58%) underwent focal salvage FCH PET-guided stereotactic radiotherapy with no hormones. Results: Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had ⩾2 positive nodes on FCH PET/CT (OR=8.75, [95% CI: 1.38–54.80], p =0.020). Relapses that occurred outside the CTVRTOG involved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2–L3. Conclusion: 3D mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2–L3 safely to cover 95% of nodal stations at risk of an occult relapse. [Copyright &y& Elsevier]

Abstract: In 2003, a panel of experts published a set of consensus guidelines for the delineation of the neck node levels in node negative patients (Radiother Oncol, 69: 227–36, 2003). In 2006, these guidelines were extended to include the characteristics of the node positive and the post-operative neck (Radiother Oncol, 79: 15–20, 2006). These guidelines did not fully address all nodal regions and some of the anatomic descriptions were ambiguous, thereby limiting consistent use of the recommendations. In this framework, a task force comprising opinion leaders in the field of head and neck radiation oncology from European, Asian, Australia/New Zealand and North American clinical research organizations was formed to review and update the previously published guidelines on nodal level delineation. Based on the nomenclature proposed by the American Head and Neck Society and the American Academy of Otolaryngology-Head and Neck Surgery, and in alignment with the TNM atlas for lymph nodes in the neck, 10 node groups (some being divided into several levels) were defined with a concise description of their main anatomic boundaries, the normal structures juxtaposed to these nodes, and the main tumor sites at risk for harboring metastases in those levels. Emphasis was placed on those levels not adequately considered previously (or not addressed at all); these included the lower neck (e.g. supraclavicular nodes), the scalp (e.g. retroauricular and occipital nodes), and the face (e.g. buccal and parotid nodes). Lastly, peculiarities pertaining to the node-positive and the post-operative clinical scenarios were also discussed. In conclusion, implementation of these guidelines in the daily practice of radiation oncology should contribute to the reduction of treatment variations from clinician to clinician and facilitate the conduct of multi-institutional clinical trials. [Copyright &y& Elsevier]

Abstract: Purpose: This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area. Patients and methods: Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients. Results: Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1year, NS). Sixteen patients experienced clinical grade ⩾3 late toxicities (>6months), 11 in R-RT arm and five in Ch-T arm. Conclusions: Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC. [Copyright &y& Elsevier]

Abstract: Background and purpose: We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas. Methods: Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20mg/m2). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60mg/m2), every 3weeks. Patients had to receive LHRH agonist during 3years. Results: The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3–4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced a grade 3 toxicity, and 15 patients experienced a grade 2 toxicity. With a median follow-up of 54months, the 5-year clinical disease-free survival was 66.72% and the 5-year survival was 92.15%. Conclusions: 3D-CRT with androgen deprivation and concurrent weekly docetaxel, followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III randomized trial. [Copyright &y& Elsevier]

Abstract: The past decade has provided many technological advances in radiotherapy. The European Institute of Radiotherapy (EIR) was established by the European Society of Therapeutic Radiology and Oncology (ESTRO) to provide current consensus statement with evidence-based and pragmatic guidelines on topics of practical relevance for radiation oncology. This report focuses primarily on 3D CT-based in-room image guidance (3DCT-IGRT) systems. It will provide an overview and current standing of 3DCT-IGRT systems addressing the rationale, objectives, principles, applications, and process pathways, both clinical and technical for treatment delivery and quality assurance. These are reviewed for four categories of solutions; kV CT and kV CBCT (cone-beam CT) as well as MV CT and MV CBCT. It will also provide a framework and checklist to consider the capability and functionality of these systems as well as the resources needed for implementation. Two different but typical clinical cases (tonsillar and prostate cancer) using 3DCT-IGRT are illustrated with workflow processes via feedback questionnaires from several large clinical centres currently utilizing these systems. The feedback from these clinical centres demonstrates a wide variability based on local practices. This report whilst comprehensive is not exhaustive as this area of development remains a very active field for research and development. However, it should serve as a practical guide and framework for all professional groups within the field, focussed on clinicians, physicists and radiation therapy technologists interested in IGRT. [Copyright &y& Elsevier]

Abstract: Background and purpose: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on ‘Multidisciplinary Rectal Cancer Treatment: Looking for an European Consensus’ (EURECA-CC2) was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO), and European Society of Therapeutic Radiation Oncology (ESTRO). Methods: Consensus was achieved using the Delphi method. The document was available to all Committee members as a web-based document customized for the consensus process. Eight chapters were identified: epidemiology, diagnostics, pathology, surgery, radiotherapy and chemotherapy, treatment toxicity and quality of life, follow-up, and research questions. Each chapter was subdivided by a topic, and a series of statements were developed. Each member commented and voted, sentence by sentence thrice. Sentences upon which an agreement was not reached after voting round # 2 were openly debated during a Consensus Conference in Perugia (Italy) from 11 December to 13 December 2008. A hand-held televoting system collected the opinions of both the Committee members and the audience after each debate. The Executive Committee scored percentage consensus based on three categories: “large consensus”, “moderate consensus”, and “minimum consensus”. Results: The total number of the voted sentences was 207. Of the 207, 86% achieved large consensus, 13% achieved moderate consensus, and only 3 (1%) resulted in minimum consensus. No statement was disagreed by more than 50% of the members. All chapters were voted on by at least 75% of the members, and the majority was voted on by >85%. Conclusions: This Consensus Conference represents an expertise opinion process that may help shape future programs, investigational protocols, and guidelines for staging and treatment of rectal cancer throughout Europe. [Copyright &y& Elsevier]

Abstract: Purpose: The Gastro-Intestinal Working Party of the EORTC Radiation Oncology Group (GIWP-ROG) developed guidelines for target volume definition in neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction (GEJ) and the stomach. Methods and materials: Guidelines about the definition of the clinical target volume (CTV) are based on a systematic literature review of the location and frequency of local recurrences and lymph node involvement in adenocarcinomas of the GEJ and the stomach. Therefore, MEDLINE was searched up to August 2008. Guidelines concerning prescription, planning and treatment delivery are based on a consensus between the members of the GIWP-ROG. Results: In order to support a curative resection of GEJ and gastric cancer, an individualized preoperative treatment volume based on tumour location has to include the primary tumour and the draining regional lymph nodes area. Therefore we recommend to use the 2nd English Edition of the Japanese Classification of Gastric Carcinoma of the Japanese Gastric Cancer Association which developed the concept of assigning tumours of the GEJ and the stomach to anatomically defined sub-sites corresponding respectively to a distinct lymphatic spread pattern. Conclusion: The GIWP-ROG defined guidelines for preoperative irradiation of adenocarcinomas of the GEJ and the stomach to reduce variability in the framework of future clinical trials. [Copyright &y& Elsevier]

Abstract: Introduction: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. Materials and methods: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. Results: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. Conclusions: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques. [Copyright &y& Elsevier]

Abstract: Purpose. To analyse clinical and dosimetric characteristics with regard to clinical constraints in head and neck cancer patients treated with intensity-modulated radiotherapy (IMRT). Materials and methods. Between August 2001 and July 2005, 75 patients with non-metastatic head and neck cancers were treated with IMRT with curative intent. Dose–volume histograms (DVH) drawn up from inverse dosimetry were analysed and compared to the prescription according to the clinical presentation of the disease. Results. For bilateral irradiation, the mean doses delivered to the contralateral and ipsilateral parotid glands were, respectively, 28.1 and 26.3Gy. Dose constraints to the submandibular glands were only respected for the contralateral gland during unilateral irradiation. For tumors located in paranasal sinuses, the maximal dose to the contralateral and ipsilateral optic nerves remained significantly lower than the constraint doses while the constraints for the anterior part of the eyes could not be respected. Conclusions. Significant differences were observed concerning respect of the constraints applied to the parotid or to the submandibular glands for medial tumors. The respect of constraints for the organs at risk critically depends on the location and size of the primary tumor and on the definition of the CTV. The clinical impact has to be further evaluated. [Copyright &y& Elsevier]

Abstract: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing post-operative radiotherapy for prostate cancer requires a standardisation of the target volume definition and delineation as well as standardisation of the clinical quality assurance procedures. Recommendations for this are presented on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group and in addition to the already published guidelines for radiotherapy as the primary treatment. [Copyright &y& Elsevier]

: Background and purposeWe retrospectively analysed our experience of contact therapy alone and/or combined with interstitial brachytherapy as exclusive treatment of low lying rectal tumours.: Patients and methodsFrom 1971 to 2001, 124 patients (103 adenocarcinomas, 21 villous tumours) were treated by contact therapy alone or combined with interstitial brachytherapy. All patients were staged according to the Dijon classification. The average size of the lesions was 2.4 cm (max 7 cm), clinical aspect was polypoı¨d in 75% of the cases, flat in 17%. Sixty four patients received contact therapy in three fractions and 44 patients received four fractions, for an average delivered dose of 95 Gy. Interstitial brachytherapy boost delivered 24 Gy on a reference isodose of 55 cGy/h in 10 patients.: ResultsThe local control was 83% for T1 and 38% for T2 tumours (P=0.004). For mobile tumours, the local control rate is 76%, significantly higher than for tumours with impaired mobility (55%, P=0.03). Thirty-nine patients experienced a local failure (31%). For patients amenable to surgery, a Miles procedure was performed in 25 patients. Ultimate local control rate is 93% for T1, 69% for T2 (P<0.05), 15 patients failed despite treatment for local recurrence (15%). No significant differences were observed in a comparison of adenocarcinoma and villous tumours according to initial and ultimate local control. The mean disease free survival rate for the whole population is 66 months. The 5-year disease free survival for T1a and T1b is, respectively, 82 and 78%, 40 and 25% for T2a and T2b, respectively. The overall 5-year survival for the whole group is 62.4%. At the end of the treatment, 75% of the patients described a very good sphincter function. No deleterious effect on continence was reported during the follow-up.: ConclusionsThe control rate for T1 rectal cancer treated with contact therapy with or without brachytherapy is comparable to surgical series. The sphincter was preserved in 80% of the patients. Radiotherapy remains an efficient and cheap alternative to surgery, mainly for old and fragile patients, or refusing colostomy. The results of these approaches for tumors larger than 3 cm (T2) are not satisfactory. For patients not amenable to surgery, external beam radiation therapy and/or combined modality with chemoradiation should be discussed to increase the loco-regional control rate. A careful selection of patients based on rectal examination and trans-rectal ultrasound could select more accurately patients amenable to such an approach. [Copyright &y& Elsevier]

Background and purpose: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals—the so-called Brussels guidelines from Gre´goire et al., and the so-called Rotterdam guidelines from Nowak et al.—emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies.Materials and methods: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck.Results and conclusions: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described. [Copyright &y& Elsevier]

Abstract: To evaluate the impact of PTV reduction when delivering image-guided IMRT (IG-IMRT) for patients with prostate cancer. Between 2001 and 2007, 165 men were treated with daily IG-IMRT using a 3D ultrasound-based system. Median dose prescribed to the prostate was 78Gy [74Gy–78Gy]. Patients were stratified regarding the CTV to the PTV margin: group A (n =87)=5mm or group B (n =78)=10mm. Late toxicity was scored using the CTC v3.0 scale. Biochemical progression-free survival (bPFS) was calculated using the Phoenix definition. Grade 2 genitourinary toxicity was 7.0% for group A and 6.6% for group B (p =1.00). Grade 2 gastrointestinal toxicity was 1.2% and 2.6% (p =0.38). With a median follow-up of 38.3months [5.25–87.3], bPFS at 3years was 92.5% [82.4%–96.9%] in group A and 94.3% [85.5%–97.8%] in group B (p =0.84). IG-IMRT yielded very low rates of late toxicity. Margin had impact neither on short-term bPFS nor late toxicity. [Copyright &y& Elsevier]

Abstract: The Sonarray ultrasound system is a non-invasive technique allowing real-time prostate localization. Since 2003, it has been used in our department before intensity modulated radiation therapy for prostate cancer. We reported both setup errors and organ motion detected by Sonarray system and the accuracy of this ultrasound imaging dedicated to radiotherapy. [Copyright &y& Elsevier]