De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Background: Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated. Methods: Patients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1-3, pN0-pN2b; hypopharynx: pT1-2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years. Findings: A total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%-9.2%) in the whole study population and 14.1% (95% CI: 3.8%-23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%-6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%-96%) and overall survival was 94% (95% CI: 90%-98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively. Interpretation: The study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution.

Impact of mediastinal tumor burden and lymphatic spread in locally advanced non-small-cell lung cancer: A secondary analysis of the multicenter randomized PET-Plan trial.

PURPOSE: The aim of this secondary analysis of the prospective randomized phase 2 PET-Plan trial (ARO-2009-09; NCT00697333) was to evaluate the impact of mediastinal tumor burden and lymphatic spread in patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: All patients treated per protocol (n = 172) were included. Patients received isotoxically dose-escalated chemoradiotherapy up to a total dose of 60-74 Gy in 30-37 fractions, aiming as high as possible while adhering to normal tissue constraints. Radiation treatment (RT) planning was based on an 18F-FDG PET/CT targeting all lymph node (LN) stations containing CT positive LNs (i.e. short axis diameter > 10 mm), even if PET-negative (arm A) or targeting only LN stations containing PET-positive nodes (arm B). LN stations were classified into echelon 1 (ipsilateral hilum), 2 (ipsilateral station 4 and 7), and 3 (rest of the mediastinum, contralateral hilum). The endpoints were overall survival (OS), progression-free survival (PFS), and freedom from local progression (FFLP). RESULTS: The median follow-up time (95 % confidence interval [CI]) was 41.1 (33.8 - 50.4) months. Patients with a high absolute number of PET-positive LN stations had worse OS (hazard ratio [HR] = 1.09; 95 % CI 0.99 - 1.18; p = 0.05) and PFS (HR = 1.12; 95 % CI 1.04 - 1.20; p = 0.003), irrespective of treatment arm allocation. The prescribed RT dose to the LNs did not correlate with any of the endpoints when considering all patients. However, in patients in arm B (i.e., PET-based selective nodal irradiation), prescribed RT dose to each LN station correlated significantly with FFLP (HR=0.45; 95 % CI 0.24-0.85; p = 0.01). Furthermore, patients with involvement of echelon 3 LN stations had worse PFS (HR = 2.22; 95 % CI 1.16-4.28; p = 0.02), also irrespective of allocation. CONCLUSION: Mediastinal tumor burden and lymphatic involvement patterns influence outcome in patients treated with definitive chemoradiotherapy for locally advanced NSCLC. Higher dose to LNs did not improve OS, but did improve FFLP in patients treated with PET-based dose-escalated RT.

Implementation of PET/CT in radiation oncology-a patterns-of-care analysis of the German Society of Nuclear Medicine and the German Society of Radiation Oncology.

BACKGROUND: The use of positron-emission tomography (PET)/computed tomography (CT) in radiation therapy (RT) has increased. Radiation oncologists (RadOncs) have access to PET/CT with a variety of tracers for different tumor entities and use it for target volume definition. The German Society of Nuclear Medicine (DGN) and the German Society of Radiation Oncology (DEGRO) aimed to identify current patterns of care in order to improve interdisciplinary collaboration. METHODS: We created an online survey on participating RadOncs' use of PET tracers for different tumor entities and how they affect RT indication, dose prescription, and target volume definition. Further topics were reimbursement of PET/CT and organizational information (fixed timeslots and use of PET with an immobilization device [planning/RT-PET]). The survey contained 31 questions in German language (yes/no questions, multiple choice [MC] questions, multiple select [MS] questions, and free-text entry options). The survey was distributed twice via the DEGRO member mailing list. RESULTS: During the survey period (May 22-August 7, 2023) a total of 156 RadOncs (13% of respondents) answered the survey. Among these, 59% reported access to diagnostic PET/CT within their organization/clinic and 24% have fixed timeslots for their patients. 37% of survey participants can perform RT-PET and 29% have the option of providing a dedicated RT technician for planning PET. Besides [18F]-fluorodeoxyglucose (FDG; mainly used in lung cancer: 95%), diagnostic prostate-specific membrane antigen (PSMA)-PET/CT for RT of prostate cancer is routinely used by 44% of participants (by 64% in salvage RT). Use of amino acid PET in brain tumors and somatostatin receptor PET in meningioma is low (19 and 25%, respectively). Scans are reimbursed through private (75%) or compulsory (55%) health insurance or as part of indications approved by the German Joint Federal Committee (Gemeinsamer Bundesausschuss; 59%). 98% of RadOncs agree that PET impacts target volume definition and 62% think that it impacts RT dose prescription. DISCUSSION: This is the first nationwide survey on the role of PET/CT for RT planning among RadOncs in Germany. We find high acceptance of PET results for treatment decisions and target volume definition. Planning PET comes with logistic challenges for different healthcare settings (e.g., private practices vs. university hospitals). The decision to request PET/CT is often based on the possibility of reimbursement. CONCLUSION: PET/CT has become an important tool for RadOncs, with several indications. However, access is still limited at several sites, especially for dedicated RT-PET. This study aims to improve interdisciplinary cooperation and adequate implementation of current guidelines for the treatment of various tumor entities.

Dose prescription for stereotactic body radiotherapy: general and organ-specific consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery.

PURPOSE AND OBJECTIVE: To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. MATERIALS AND METHODS: Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80%, 60-79%, < 60% for high, intermediate, and poor consensus, respectively). Post-first round statements were refined in a live discussion for the second round of the Delphi process. RESULTS: Experts consented on a total of 14 OA and 17 OS statements regarding SBRT of primary and secondary lung, liver, pancreatic, adrenal, and kidney tumors regarding dose prescription, target coverage, and organ at risk dose limitations. Degree of consent was ≥ 80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to the upper abdomen. In round 2, the degree of consent was ≥ 80 to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation to liver metastases after chemotherapy (47%) or single-fraction SBRT for kidney primaries (13%). In round 2, no statement had 60-79% consensus. CONCLUSION: In 29 of 31 statements a high consensus was achieved after a two-tier Delphi process and one statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for SBRT dose prescription. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization of SBRT practice and facilitates dose prescription and reporting in clinical trials investigating SBRT.

Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results.

INTRODUCTION: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. METHODS: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. RESULTS: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. CONCLUSIONS: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.

Development and evaluation of two open-source nnU-Net models for automatic segmentation of lung tumors on PET and CT images with and without respiratory motion compensation.

OBJECTIVES: In lung cancer, one of the main limitations for the optimal integration of the biological and anatomical information derived from Positron Emission Tomography (PET) and Computed Tomography (CT) is the time and expertise required for the evaluation of the different respiratory phases. In this study, we present two open-source models able to automatically segment lung tumors on PET and CT, with and without motion compensation. MATERIALS AND METHODS: This study involved time-bin gated (4D) and non-gated (3D) PET/CT images from two prospective lung cancer cohorts (Trials 108237 and 108472) and one retrospective. For model construction, the ground truth (GT) was defined by consensus of two experts, and the nnU-Net with 5-fold cross-validation was applied to 560 4D-images for PET and 100 3D-images for CT. The test sets included 270 4D- images and 19 3D-images for PET and 80 4D-images and 27 3D-images for CT, recruited at 10 different centres. RESULTS: In the performance evaluation with the multicentre test sets, the Dice Similarity Coefficients (DSC) obtained for our PET model were DSC(4D-PET) = 0.74 ± 0.06, improving 19% relative to the DSC between experts and DSC(3D-PET) = 0.82 ± 0.11. The performance for CT was DSC(4D-CT) = 0.61 ± 0.28 and DSC(3D-CT) = 0.63 ± 0.34, improving 4% and 15% relative to DSC between experts. CONCLUSIONS: Performance evaluation demonstrated that the automatic segmentation models have the potential to achieve accuracy comparable to manual segmentation and thus hold promise for clinical application. The resulting models can be freely downloaded and employed to support the integration of 3D- or 4D- PET/CT and to facilitate the evaluation of its impact on lung cancer clinical practice. CLINICAL RELEVANCE STATEMENT: We provide two open-source nnU-Net models for the automatic segmentation of lung tumors on PET/CT to facilitate the optimal integration of biological and anatomical information in clinical practice. The models have superior performance compared to the variability observed in manual segmentations by the different experts for images with and without motion compensation, allowing to take advantage in the clinical practice of the more accurate and robust 4D-quantification. KEY POINTS: Lung tumor segmentation on PET/CT imaging is limited by respiratory motion and manual delineation is time consuming and suffer from inter- and intra-variability. Our segmentation models had superior performance compared to the manual segmentations by different experts. Automating PET image segmentation allows for easier clinical implementation of biological information.

A prospective study of immune responses in patients with lung metastases treated with stereotactic body radiotherapy with or without concurrent systemic treatment.

We prospectively evaluated the effects of stereotactic body radiotherapy (SBRT) on circulating immune cells. Patients with oligo-metastatic and oligo-progressive pulmonary lesions were treated with SBRT with (cSBRT) or without (SBRT group) concurrent systemic treatment (chemotherapy or immune checkpoint blockade) using different fractionation regimes. Immunoprofiling of peripheral blood cells was performed at baseline, during, at the end of SBRT, and at the first and second follow-ups. The study accrued 100 patients (80 with evaluable samples). The proportion of proliferating CD8+ T-cells significantly increased after treatment. This increase remained significant at follow-up in the SBRT group, but not in the cSBRT group and was not detected with doses of >10Gy per fraction indicating that lower doses are necessary to increase proliferating T-cells' frequency. We detected no favorable impact of concurrent systemic treatment on systemic immune responses. The optimal timing of systemic treatment may be post-SBRT to leverage the immune-modulating effects of SBRT.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

[Prevention, Diagnosis, Therapy, and Follow-up of Lung Cancer - Interdisciplinary Guideline of the German Respiratory Society and the German Cancer Society - Abridged Version]. / Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms.

The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.

Usability and usefulness of (electronic) patient identification systems-A cross-sectional evaluation in German-speaking radiation oncology departments.

PURPOSE: Patient misidentification in radiation oncology (RO) is a significant concern due to the potential harm to patient health and the burden on healthcare systems. Electronic patient identification systems (ePIS) are increasingly being used as an alternative or supplement to organizational systems (oPIS). The objective of this study was to assess the usability and usefulness of ePIS and oPIS in German-speaking countries. METHODS: A cross-sectional survey was designed by a group of experts from various professional backgrounds in RO. The survey consisted of 38 questions encompassing quantitative and qualitative data on usability, user experience, and usefulness of PIS. It was available between August and October 2022. RESULTS: Of 118 eligible participants, 37% had implemented some kind of ePIS. Overall, 22% of participants who use an oPIS vs. 10% of participants who use an ePIS reported adverse events in terms of patients' misidentification in the past 5 years. Frequent or very frequent drop-outs of electronic systems were reported by 31% of ePIS users. Users of ePIS significantly more often affirmed a positive cost-benefit ratio of ePIS as well as an improvement of workflow, whereas users of oPIS more frequently apprehended a decrease in staffs' attention through ePIS. The response rate was 8%. CONCLUSION: The implementation of ePIS can contribute to efficient PI and improved processes. Apprehensions by oPIS users and assessments of ePIS users differ significantly in aspects of the perceived usefulness of ePIS. However, technical problems need to be addressed to ensure the reliability of ePIS. Further research is needed to assess the impact of different PIS on patient safety in RO.

PET/CT reading for relapse in non-small cell lung cancer after chemoradiotherapy in the PET-Plan trial cohort.

BACKGROUND: Current studies indicate that fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography ([18F]FDG PET/CT) is the most accurate imaging modality for the detection of relapsed locally advanced non-small cell lung cancer (NSCLC) after curatively intended chemoradiotherapy. To this day, there is no objective and reproducible definition for the diagnosis of disease recurrence in PET/CT, the reading of which is relevantly influenced by post radiation inflammatory processes. The aim of this study was to evaluate and compare visual and threshold-based semi-automated evaluation criteria for the assessment of suspected tumor recurrence in a well-defined study population investigated during the randomized clinical PET-Plan trial. METHODS: This retrospective analysis comprises 114 PET/CT data sets of 82 patients from the PET-Plan multi-center study cohort who underwent [18F]FDG PET/CT imaging at different timepoints for relapse, as suspected by CT. Scans were first analyzed visually by four blinded readers using a binary scoring system for each possible localization and the associated reader certainty of the evaluation. Visual evaluations were conducted repeatedly without and with additional knowledge of the initial staging PET and radiotherapy delineation volumes. In a second step, uptake was measured quantitatively using maximum standardized uptake value (SUVmax), peak standardized uptake value corrected for lean body mass (SULpeak), and a liver threshold-based quantitative assessment model. Resulting sensitivity and specificity for relapse detection were compared to the findings in the visual assessment. The gold standard of recurrence was independently defined by prospective study routine including external reviewers using CT, PET, biopsies and clinical course of the disease. RESULTS: Overall interobserver agreement (IOA) of the visual assessment was moderate with a high difference between secure (ĸ = 0.66) and insecure (ĸ = 0.24) evaluations. Additional knowledge of the initial staging PET and radiotherapy delineation volumes improved the sensitivity (0.85 vs 0.92) but did not show significant impact on the specificity (0.86 vs 0.89). PET parameters SUVmax and SULpeak showed lower accuracy compared to the visual assessment, whereas threshold-based reading showed similar sensitivity (0.86) and higher specificity (0.97). CONCLUSION: Visual assessment especially if associated with high reader certainty shows very high interobserver agreement and high accuracy that can be further increased by baseline PET/CT information. The implementation of a patient individual liver threshold value definition, similar to the threshold definition in PERCIST, offers a more standardized method matching the accuracy of experienced readers albeit not providing further improvement of accuracy.

Education and training in radiation protection in Europe: results from the EURAMED Rocc-n-Roll project survey.

PURPOSE: To analyse the existing radiation protection (RP) education and training (E&T) capabilities in the European Union and identify associated needs, problems and challenges. METHOD: An online survey was disseminated via the EURAMED Rocc-n-Roll consortium network and prominent medical societies in the field of radiological research. The survey sections analyse the RP E&T during undergraduate, residency/internship and continuous professional development; RP E&T problems and legal implementation. Differences were analysed by European geographic regions, profession, years of professional experience and main area of practice/research. RESULTS: The majority of the 550 respondents indicated that RP topics are part of undergraduate curricula in all courses for their profession and country (55%); however, hands-on practical training is not included according to 30% of the respondents. The lack of E&T, practical aspects in current E&T, and mandatory continuing E&T were considered the major problems. The legal requirement that obtained higher implementation score was the inclusion of the practical aspects of medical radiological procedures on education (86%), and lower score was obtained for the inclusion of RP E&T on medical and dental school curriculums (61%). CONCLUSIONS: A heterogeneity in RP E&T during undergraduate, residency/internship and continuous professional development is evident across Europe. Differences were noted per area of practice/research, profession, and European geographic region. A large variation in RP E&T problem rating was also obtained.

Systemic immune modulation by stereotactic radiotherapy in early-stage lung cancer.

We performed a prospective study of circulating immune cell changes after stereotactic body radiotherapy (SBRT) in 50 early-stage NSCLC patients. We found no significant increase in CD8+ cytotoxic T lymphocytes at first follow-up (the primary endpoint) but detected a significant increase in expanding Ki-67+CD8+ and Ki-67+CD4+ T-cell fractions in patients treated with 10 Gy or less per fraction. SBRT can induce significant expansion in circulating effector T-cells immediately post-treatment.

Cardiac Function Modifies the Impact of Heart Base Dose on Survival: A Voxel-Wise Analysis of Patients With Lung Cancer From the PET-Plan Trial.

INTRODUCTION: Heart dose has emerged as an independent predictor of overall survival in patients with NSCLC treated with radiotherapy. Several studies have identified the base of the heart as a region of enhanced dose sensitivity and a potential target for cardiac sparing. We present a dosimetric analysis of overall survival in the multicenter, randomized PET-Plan trial (NCT00697333) and for the first time include left ventricular ejection fraction (EF) at baseline as a metric of cardiac function. METHODS: A total of 205 patients with inoperable stage II or III NSCLC treated with 60 to 72 Gy in 2 Gy fractions were included in this study. A voxel-wise image-based data mining methodology was used to identify anatomical regions where higher dose was significantly associated with worse overall survival. Univariable and multivariable Cox proportional hazards models tested the association of survival with dose to the identified region, established prognostic factors, and baseline cardiac function. RESULTS: A total of 172 patients remained after processing and censoring for follow-up. At 2-years posttreatment, a highly significant region was identified within the base of the heart (p < 0.005), centered on the origin of the left coronary artery and the region of the atrioventricular node. In multivariable analysis, the number of positron emission tomography-positive nodes (p = 0.02, hazard ratio = 1.13, 95% confidence interval: 1.02-1.25) and mean dose to the cardiac subregion (p = 0.02, hazard ratio = 1.11 Gy-1, 95% confidence interval: 1.02-1.21) were significantly associated with overall survival. There was a significant interaction between EF and region dose (p = 0.04) for survival, with contrast plots revealing a larger effect of region dose on survival in patients with lower EF values. CONCLUSIONS: This work validates previous image-based data mining studies by revealing a strong association between dose to the base of the heart and overall survival. For the first time, an interaction between baseline cardiac health and heart base dose was identified, potentially suggesting preexisting cardiac dysfunction exacerbates the impact of heart dose on survival.

Education and training in radiation protection in Europe: an analysis from the EURAMED rocc-n-roll project.

BACKGROUND: A Strengths, weaknesses, opportunities and threats analysis was performed to understand the status quo of education and training in radiation protection (RP) and to develop a coordinated European approach to RP training needs based on stakeholder consensus and existing activities in the field. Fourteen team members represented six European professional societies, one European voluntary organisation, two international healthcare organisations and five professions, namely: Medical Physicists; Nuclear Medicine Physicians; Radiologists; Radiation Oncologists and Radiographers. Four subgroups analysed the "Strengths", "Weaknesses", "Opportunities" and "Threats" related to E&T in RP developed under previous European Union (EU) programmes and on the Guidelines on Radiation Protection Education and Training of Medical Professionals in the EU. RESULTS: Consensus agreement identified four themes for strengths and opportunities, namely: (1) existing structures and training recommendations; (2) RP training needs assessment and education & training (E&T) model(s) development; (3) E&T dissemination, harmonisation, and accreditation; (4) financial supports. Weaknesses and Threats analysis identified two themes: (1) awareness and prioritisation at a national/global level and (2) awareness and prioritisation by healthcare professional groups and researchers. CONCLUSIONS: A lack of effective implementation of RP principles in daily practice was identified. EuRnR strategic planning needs to consider processes at European, national and local levels. Success is dependent upon efficient governance structures and expert leadership. Financial support is required to allow the stakeholder professional agencies to have sufficient resources to achieve a pan European radiation protection training network which is sustainable and accredited across multiple national domains.