Purpose The expanded HILUS study showed that bronchial dose and bronchial tumor compression are risk factors for bronchopulmonary bleedings after stereotactic body radiation therapy of centrally located lung tumors. In the current analysis of the same cohort, the aim was to identify the dose-volume histogram (DVH) parameter that best predicts fatal bronchopulmonary bleeding and to develop a predictive model for this endpoint. Methods and Materials The HILUS cohort included 230 patients with 238 central targets treated with stereotactic body radiation therapy of 7 Gy × 8 to the periphery of the planning target volume, where 21 patients developed grade-5 bronchopulmonary bleeding. Cox regression-based normal-tissue complication probability models were developed, accounting for the dose to the main and intermediate bronchi and bronchial tumor compression. Three alternative DVH parameters were explored: the dose to a certain volume (Dv), the volume receiving a certain dose (Vd), and the equivalent uniform dose. Internal validation was performed with the bootstrap method. Results The best fits of the bivariable normal-tissue complication probability models included bronchial tumor compression in combination with the DVH parameters of D0.31 cm3, V82Gy,EQD2 (equivalent dose in 2-Gy fractions), and equivalent uniform dose with n = 0.024, respectively. This indicates that a high dose to a small volume may lead to grade-5 bronchopulmonary bleeding. The probability of fatal bleeding at 2 years without bronchial tumor compression was 10% for a D0.31 cm3 of 107 Gy3 EQD2, and 20% at 165 Gy3 EQD2, whereas the probability with bronchial tumor compression was 10% at 0 Gy3 and 20% at 58 Gy3 EQD2. The model showed good discrimination and calibration. Conclusions Bronchial tumor compression is a strong predictor for grade-5 bleeding, and the most relevant dose parameter appears to be the dose to a small volume of the main and intermediate bronchi.

PURPOSE:To provide case-based, practical examples outlining step-by-step calculations and documentation for reirradiation (reRT) evaluation. The representative examples demonstrate the application of the Reirradiation Collaborative Group (ReCOG) consensus for dosimetric assessment and reporting in reRT and illustrate how these standards can be implemented in clinical practice. METHODS AND MATERIALS:Two spine reRT cases were selected. Cumulative organ-at-risk doses were assessed using 3 approaches: direct point dose summation, point dose summation within overlap regions, and image registration-based 3-dimensional dose summation. Step-by-step calculations were performed for each approach, and new dose objectives for subsequent planning iterations were derived and compared. RESULTS:The example reRT cases detail the special medical physics consult process, highlighting different cumulative dose estimation strategies depending on the availability of voxel-based equieffective dose calculation and visualization tools. Selection of an assessment strategy should balance clinical resources with patient-specific considerations. Calculation and visualization of equieffective dose distributions facilitate cumulative dose assessment and strengthen image registration-based methods. If 3-dimensional equieffective dose calculation is not available, anatomically corresponding volumes and doses in each plan contributing to the cumulative dose in the areas of overlap can be determined manually to improve the accuracy of point dose-based summation. CONCLUSIONS:The case examples demonstrate how to apply the ReCOG consensus for dosimetric assessment and reporting in reRT and illustrate multiple strategies for cumulative dose evaluation. This work supports patient care and contributes to enhancing the field's knowledge and delivery of safer reRT.

This study presents the results of a multicentre external dosimetry audit conducted as part of the PROTECT trial, involving nine European radiotherapy centres delivering proton and photon treatments. A dosimetry equipment vendor performed beam output audits at participating sites, verifying the absorbed dose-to-water measurements. Measurements used reference conditions based on the IAEA TRS-398, with ionization chambers traceable to primary standards. The audit compared local centre measurements to independent assessments, finding all within the acceptable 3% agreement threshold. The study is part of the successful implementation of a comprehensive, multicentre QA programme in the PROTECT trial.

Background and purpose:Dose accumulation in reirradiation can contribute to both treatment outcomes and safe cumulative doses. We demonstrated consensus strategies on dose accumulation for three clinical reirradiation scenarios. Materials and methods:For a lung patient, prescription, point and volumetric-based dose accumulations were generated, while isodose transfer also highlighted a visual approach. In a head and neck case, three-dimensional conformal radiotherapy (3DRT) fields were reconstructed from treatment records. For a brachytherapy gynaecological case, isodose transfer and full volumetric dose accumulation were generated. For pertinent organs at risk (OARs) equieffective doses (EQD2Gy) enabled comparisons between the different methods. Results:Large variations in cumulative EQD2Gy values in the lung case were calculated. Assuming prescription EQD2Gy, values were 181.9, 161.4 and 154.6 Gy to the spinal canal, brachial plexus and pericardium. Median cumulative point EQD2Gy values for these organs were 15.9, 81.9, 66.6 Gy and similarly, volumetric dose values were 13.9, 68.9 and 55.2 Gy respectively. The head and neck re-simulation showed significant process limitations, especially for brainstem (11.8 - 34.4 Gy EQD2Gy). For the brachytherapy case, cumulative EQD2Gy values were similar across direct point and volumetric dose summation (88.5 vs 88.0 Gy for bladder; 83.6 vs 80.0 Gy for rectum). Conclusions:Different reirradiation dose accumulation strategies can lead to significant variations in reported OAR cumulative dose. Prescription and point-based dose methods tend to overestimate cumulative dose, which could justify their application in time critical situations, but may limit treatment options. More advanced volumetric-based methods demonstrated improved consistency in cumulative dose reporting.

BACKGROUND:Novel cone-beam computed tomography (CBCT) has become available on standard C-arm linacs, making it widely applicable in photon-based radiotherapy. PURPOSE:To evaluate CT number stability of novel CBCT systems installed on seven C-arm linacs within a single institution, across CBCT systems and over time, and to assess the CBCT-based dose calculation accuracy in head-and-neck, lung, and pelvic cancer patients. METHODS:A Gammex Advanced Electron Density phantom (Sun Nuclear) was scanned at installation of eleven CBCT imaging panels at seven TrueBeam C-arm linacs (Varian Medical Systems, A Siemens Healthineers Company), and after three and six months. Three CBCT protocols were evaluated, a head protocol (tube voltage of 100 kVp, iterative reconstruction, denoted iCBCT), a thorax protocol (tube voltage of 125 kVp; filtered back projection with Feldkamp-Davis-Kress (FDK) algorithm), and a pelvis protocol (tube voltage of 125 kVp; iCBCT). Fifteen tissue-equivalent phantom inserts were scanned individually, placed centrally in the phantom. The mean CT number was extracted, and CT number stability was assessed across imaging panels and timepoints. CT number stability was compared to a previous CBCT detector model. Moreover, routine measurements using four inserts were performed until 18 months after installation. Conversion curves for mass density estimation were generated, following a consensus guide. The spread of the curves due to CT number variation across imaging panels was assessed. Treatment plans created on planning CT (pCT) scans of 10 head-and-neck, 22 lung, and 15 pelvic cancer patients were recalculated on CBCT scans, selected to match the anatomy seen on the pCT. Dose-volume parameters for targets and organs-at-risk were compared between pCT and CBCT. RESULTS:The CT numbers were consistent across the imaging panels and over time for iCBCT reconstruction, but to a lesser degree for FDK reconstruction. The CT number variation increased with the density of the phantom inserts. Still, for the high-density bone insert the range/interquartile range of the CT numbers across imaging panels were 51/29 HU (head protocol), 140/41 HU (thorax protocol), and 27/16 HU (pelvis protocol). For the longitudinal measurements, the median differences were 4 HU, -9 HU, and -8 HU after three months and -8 HU, -32 HU, and -26 HU after six months, for the head, thorax, and pelvis protocol, respectively. For the routine measurements, no clear time dependence was seen for the CT number differences. It was found that a single conversion curve per CBCT protocol could be used for all imaging panels. For iCBCT, median dose differences between pCT and CBCT were within 0.5% for head-and-neck and pelvis and 1.5% for lung, while FDK lung was within 2.5%. The largest deviations with iCBCT were -1.3% for head-and-neck, -1.1% for pelvis, and -3.8% for thorax, but -18.0% for thorax FDK. CONCLUSIONS:The CT number stability was sufficient to allow for a single conversion curve per CBCT protocol to be applied across all CBCT imaging panels. A high dose calculation accuracy was found for 36 patients with iCBCT scans, while larger deviations were seen for eleven thorax FDK scans.

Background and purpose:Safe delivery of high-dose reirradiation depends on robust evaluation of previously delivered dose on current patient anatomy. This study aims to assess the variability of 1) rigid (RIR) and deformable (DIR) image registration, and 2) dose-mapping based on RIR or DIR, as part of the pre-trial quality assurance for CURE Lung, a Scandinavian thoracic reirradiation trial. Materials and methods:Seven lung cancer cases, treated with curatively intended reirradiation near a previously irradiated region, were distributed to six Danish centres. Organs-at-risk (OARs) were delineated on CT images of previous (CTprev) and current treatment (CTcurrent). RIR and DIR from CTprev to CTcurrent were performed for all cases at each centre, and doses were mapped from CTprev to CTcurrent using both methods. Mapped and current physical doses were converted to equieffective doses (EQD2), and cumulative EQD2-doses were generated on CTcurrent. Inter-centre variation was assessed using volume coefficients and distance measurements. A linear mixed-effects model tested the effect of registration method on OAR alignment, near-maximum and volumetric EQD2-dose constraints from CURE Lung, and variability in DVH bands. Results:DIR significantly reduced the geometrical variations for all OARs, with mean surface distances <4.4 mm. Near-maximum EQD2-doses overall had less variability with DIR compared to RIR. No significant differences were found for the full DVH bands. Conclusion:DIR provides significantly better consistency in transfer of OAR from CTprev to CTcurrent and reduces variability in EQD2-dose evaluations compared to RIR. This supports preferential use of DIR for reirradiation planning in lung cancer.

As cancer survivors live longer, technologies improve, and reirradiation (reRT) becomes more common, standardised methods for the assessment and reporting of cumulative radiation doses are needed to allow treatment optimisation and integration with other medical specialties managing these complex patients. This consensus statement, developed by an international collaboration of radiation oncologists, physicists, and other experts in the Reirradiation Collaborative Group, proposes a framework for consistent evaluation, documentation, reporting, and clinical decision making in reRT. This paper outlines practical strategies for dose accumulation from multiple courses of radiation therapy with the use of both image registration-based and point dose-based methods, accounting for uncertainties in data availability, physiological organ recovery, and anatomical changes. The emphasis of the consensus statement is on institutional workflows, improved software tools, and better capture of longitudinal patient outcomes. We also highlight the need for improved biological models, data infrastructure, and cross-specialty collaboration. Ultimately, reRT is framed as a transformative challenge for oncology, demanding interdisciplinary innovation across science, clinical care, and health systems. Widespread adoption of these recommendations could accelerate progress toward improved outcomes for patients receiving reRT worldwide.

Background and purpose: Prophylactic cranial irradiation (PCI) is part of standard treatment for patients with limited disease small cell lung cancer (LD-SCLC), treated with curative intent. However, doubt has been raised about the efficacy of PCI in a modern clinical setting. Therefore, we examined factors impacting PCI receival, the cumulative incidence of symptomatic brain metastases, and overall survival (OS) with and without PCI. Patient/material and methods: Records of 190 patients with LD-SCLC consecutively treated between 2012 and 2021 at our institution were reviewed. Patients were grouped based on whether they received PCI (PCI, n = 119) or not (no PCI, n = 71). Baseline characteristics, Kaplan-Meier estimates of OS, and cumulative incidence of symptomatic brain metastases were compared for the two groups. Results: PCI no patients were older, had a poorer performance status, were more often treated in 2018–2021 and had more frequently a brain magnetic resonance imaging (MRI) at the time of diagnosis. No PCI median OS was 19 months compared to 24 months for PCI, not significantly different (p = 0.40). During follow-up 54 patients (28.4%) developed symptomatic brain metastases, with no statistically significant difference in the numbers of patients with, and cumulative incidence of, symptomatic brain metastases between the two groups (p = 0.35 and p = 0.21, respectively). Interpretation: Despite patients not receiving PCI being older and in poorer performance status, no statistically significant difference in OS or cumulative incidence of brain metastasis were observed compared to patients who received PCI. This supports uncertainty regarding the role of PCI.

Background and purpose: Reirradiation has seen increased interest and clinical use; however, robust data on patient numbers and treatment indications are missing. As a precursor to a prospective national reirradiation registry, a comprehensive national audit of reirradiation was performed. Patients/materials and methods: Radiotherapy retreatment courses in 2023 were audited by all (eight) radiotherapy centres in Denmark. Six centres extended the evaluation to include 2021–22, and three of these also evaluated preceding years. Reirradiation was defined according to the ESTRO/EORTC consensus (i.e. treatment volume overlap or cumulative dose toxicity risk) using 3 months threshold between the primary and reirradiation courses. Reirradiation courses were further stratified into curative/ablative and palliative treatments by prescription dose. Results: The total number of radiotherapy patients at Danish centres in 2023 was 17,424. Of these, 3,163 received retreatment, including 1,471 reirradiation courses (1,035 palliative; 436 curative/ablative). From 2014 to 2023, absolute numbers for both retreatment and reirradiation increased. We found large variation in prescription doses and fractionation schedules used for reirradiation. Widely used palliative prescriptions were 8Gy/1 fraction (F), 20Gy/4F and 30Gy/10F; stereotactic prescriptions of 20Gy/1F or 27Gy/3F in brain and 45Gy/3F in lung; and a variety of curative treatments schedules. Palliative reirradiations were primarily thoracic (29%), spine (25%), and abdominal/pelvic (22%) and curative/ablative reirradiations were primarily breast (29%) and lung stereotactic (23%). Interpretation: This is the first comprehensive national audit of reirradiation, demonstrating an increasing number of patients being treated, using a wide variety of dose prescriptions and fractionation schedules.

BACKGROUND AND PURPOSE:The NIELS trial will examine if inhomogeneous dose-escalated radiotherapy up to a mean dose of 80 Gy in 40 fractions (fx), twice-daily delivered (BID), for patients with limited disease small cell lung cancer can improve overall survival. Because of the inherent risks of dose-escalation, pre-trial QA is particularly important. This study aims to examine the feasibility of the NIELS trial planning approach in a multicenter setting. MATERIALS AND METHODS:The NIELS trial will randomize patients between standard dose radiotherapy (60 Gy/40fx BID) and inhomogeneous dose-escalated radiotherapy (up to 80 Gy/40fx BID). Five representative patient cases were distributed to seven Nordic centers for pre-trial QA planning of a standard and an escalated dose plan. Targets for escalation were primary tumor (GTVp) and involved lymph nodes (GTVn). We evaluated inter-center variation in achievable dose-escalation and doses to organs at risk (OAR). RESULTS:All targets could be escalated beyond the standard dose, with a median mean dose of 79.6 Gy [76.9-81.0] and 75.8 Gy [68.3-81.1] for GTVp and GTVn. Some targets could not be fully escalated due to OAR proximity. Three separate breaches of mandatory OAR constraints were observed in 35 escalated dose plans. There was a statistical difference in mean lung dose between standard and escalated plans, though clinically small, with a median inter-patient difference of 0.3 Gy. There were no differences in mean doses to the heart and esophagus. CONCLUSION:Inhomogeneous dose-escalation as planned in the NIELS trial is feasible, and the dose-escalation can be performed respecting the OAR constraints in a multi-center setting.

INTRODUCTION:High-dose lung cancer reirradiation is promising but associated with high toxicity risk. Development of and adherence to consensus guidelines will support safe use. MATERIALS AND METHODS:Literature review and live workshops were conducted to develop treatment planning guidelines in preparation for the Scandinavian CURE Lung trial. Relevant OARs, dose metrics, constraints, and priorities were considered. For six high-dose reirradiation lung cancer cases, the physical 3D dose distribution of previous treatment was mapped to current CT. The cases were distributed to eight radiotherapy centres, which optimised plans on current CT respecting equieffective cumulative dose constraints. Mapped previous dose and current dose were rescaled to EQD2Gy (α/β = 3 Gy, spinal cord: α/β = 2 Gy), summed by each centre, and reviewed centrally. After cases 1-4 were completed, prioritisation between OAR constraints and target coverage was clarified. RESULTS:Consensus agreement on guidelines for treatment planning, equieffective cumulative dose constraints, and priorities was established. For cases 1-3, centres complied with constraints. For case 4, covering PTV while respecting OAR constraints was difficult, and major variations were identified, underscoring the need for clearer prioritisation guidance. Consensus was reached to prioritise OAR constraints, and centres re-optimised case 4 accordingly. For cases 5 and 6, all centres underdosed PTV, to comply with OAR constraints. Generally, considerable variation in cumulative OAR doses was observed. CONCLUSIONS:A treatment planning protocol was developed. The pre-trial multi-centre treatment planning study identified and resolved key missing guidance to facilitate common conception of consensus guidelines. Feasibility and compliance with the proposed equieffective cumulative dose constraints were established.

Robust quality assurance (QA) of clinical trials in radiotherapy (RT) is paramount for minimising uncertainties in treatment delivery, thereby strengthening the statistical power of the study and increasing the likelihood of accurately answering the research question. As RT techniques evolve and become more complex, establishing an appropriate QA program for a specific clinical trial becomes increasingly challenging, highlighting the importance of clear and standardised recommendations. This study provide such recommendations for Principal Investigators (PIs) to consider when planning and conducting RT Quality Assurance (RTQA) for clinical trials. They arise from experiences with RTQA in the clinical trials conducted in the Danish Multidisciplinary Cancer Groups (DMCGs). The recommendations include a checklist to guide PIs in developing an effective RTQA program.

BACKGROUND:Independent secondary dose calculation (ISDC) is becoming increasingly important for patient specific quality assurance. The most widely used analytical algorithms in ISDC are becoming challenged by Monte Carlo systems, which offer a potentially higher accuracy. PURPOSE:Quantify the benefit of Monte Carlo over analytical algorithms, and of customized beam models over generic beam models, in terms of clinically relevant parameters, action level, and workload. METHODS:A set of 100 patients across 20 case classes, all planned with Acuros XB (Siemens Healthineers) was analyzed with Mobius3D (M3D) (Siemens Healthineers) and SciMoCa (Radialogica LLC), both with custom beam models (SMCcbm) and generic beam models (SMCgen). Gamma pass rate (GPR) and mean target dose difference |ΔD| action levels were determined for various rates of QA failures. RESULTS:At a workload of < 10%, the action level for M3D was GPR (3%, 3 mm) < 90% and |ΔD| > 4.5%. For SMCgen, the action level was GPR (2%, 2 mm) < 95% and |ΔD| > 1.5%. For SMCcbm, it was GPR (2%, 1 mm) < 95% and |ΔD | > 1%. The combination of both criteria reduced the workload to < 5%. SMC failures could be traced back to differences in the patient density model of Acuros XB. Some M3D failures could be traced back to the handling of tissue heterogeneities. The different performance between SMCcbm and SMCgen was due to one (of three) generic beam models. CONCLUSION:Monte Carlo allows substantially stricter acceptance criteria and is sensitive enough to capture TPS commissioning errors. Generic beam models must be validated thoroughly before being put to use in ISDC.

Background and purpose: Reirradiation is becoming more frequent in clinical practice. However, workflows and practices vary widely between clinics, as general guidelines are scarce or lacking in practical detail. This paper presents comprehensive national Danish consensus recommendations covering all steps of the reirradiation workflow. The aim is to standardise and improve reirradiation treatment quality and provide guidance for much-needed large-scale clinical trials. Methods: An expert panel was formed comprising physicians, clinical physicists, and clinical researchers from all Danish radiotherapy centres. An in-person 2-day workshop was followed by multiple online meetings. Recommendations were based on expert consensus, supported by review of existing literature, and were reviewed by all Danish Multidisciplinary Cancer Groups before publication. Results: Reirradiation cases should be designated clearly as such at each workflow step. Review of patient cases at multidisciplinary reirradiation conferences is encouraged. Immobilisation, positioning, and motion management should resemble that of previous treatment(s) as closely as possible. Information on previous dose should be used in planning and evaluation. The degree of complexity (e.g. summation of dose maxima, rigid/deformable image registration, 3D dose accumulation) should reflect the clinical situation as well as the extent/quality of available information. Dose should always be converted to an equieffective dose before summation. Daily image-guidance and regular evaluation of delivered dose are recommended. We provide guidance on quality assurance of dose mapping and guidelines for clinical reirradiation trials. Interpretation: We present national consensus guidelines for site-independent reirradiation treatment workflows. The guidelines have been approved by the site-specific Danish Multidisciplinary Cancer Groups.