Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial.

BACKGROUND AND PURPOSE: Partial breast irradiation (PBI)has beenthe Danish Breast Cancer Group(DBCG) standard for selected breast cancer patients since 2016 based onearlyresults from the DBCG PBI trial.During trial accrual, respiratory-gated radiotherapy was introduced in Denmark. This study aims to investigate the effect of respiratory-gating on mean heart dose (MHD). PATIENTS AND METHODS: From 2009 to 2016 the DBCG PBI trial included 230 patientswith left-sided breast cancer receiving external beam PBI, 40 Gy/15 fractions/3 weeks.Localization of the tumor bed on the planning CT scan, the use of respiratory-gating, coverage of the clinical target volume (CTV), and doses to organs at risk were collected. RESULTS: Respiratory-gating was used in 123 patients (53 %). In 176 patients (77 %) the tumor bed was in the upper and in 54 patients (23 %) in the lower breast quadrants. The median MHD was 0.37 Gy (interquartile range 0.26-0.57 Gy), 0.33 Gy (0.23-0.49 Gy) for respiratory-gating, and 0.49 Gy (0.31-0.70 Gy) for free breathing, p < 0.0001. MHD was < 1 Gy in 206 patients (90 %) and < 2 Gy in 221 patients (96 %). Respiratory-gating led to significantly lower MHD for upper-located, but not for lower-located tumor beds, however, all MHD were low irrespective of respiratory-gating. Respiratory-gating did not improve CTV coverage or lower lung doses. CONCLUSIONS: PBI ensured a low MHD for most patients. Adding respiratory-gating further reduced MHD for upper-located but not for lower-located tumor beds but did not influence target coverage or lung doses. Respiratory-gating is no longer DBCG standard for left-sided PBI.

MR-guided stereotactic radiotherapy of infra-diaphragmatic oligometastases: Evaluation of toxicity and dosimetric parameters.

BACKGROUND AND PURPOSE: The SOFT trial is a prospective, multicenter, phase 2 trial investigating magnetic resonance (MR)-guided stereotactic ablative radiotherapy (SABR) for abdominal, soft tissue metastases in patients with oligometastatic disease (OMD) (clinicaltrials.gov ID NCT04407897). We present the primary endpoint analysis of 1-year treatment-related toxicity (TRAE). MATERIALS AND METHODS: Patients with up to five oligometastases from non-hematological cancers were eligible for inclusion. A risk-adapted strategy prioritized fixed organs at risk (OAR) constraints over target coverage. Fractionation schemes were 45-67.5 Gy in 3-8 fractions. The primary endpoint was grade ≥ 4 TRAE within 12 months post-SABR. The association between the risk of gastrointestinal (GI) toxicity and clinical and dosimetric parameters was tested using a normal tissue complication probability model. RESULTS: We included 121 patients with 147 oligometastatic targets, mainly located in the liver (41 %), lymph nodes (35 %), or adrenal glands (14 %). Nearly half of all targets (48 %, n = 71) were within 10 mm of a radiosensitive OAR. No grade 4 or 5 TRAEs, 3.5 % grade 3 TRAEs, and 43.7 % grade 2 TRAEs were reported within the first year of follow-up. We found a significant association between grade ≥ 2 GI toxicity and the parameters GI OAR D0.1cc, D1cc, and D20cc. CONCLUSION: In this phase II study of MR-guided SABR of oligometastases in the infra-diaphragmatic region, we found a low incidence of toxicity despite half of the lesions being within 10 mm of a radiosensitive OAR. GI OAR D0.1cc, D1cc, and D20cc were associated with grade ≥ 2 GI toxicity.

Recommendation on the technical and dosimetric data to be included in stereotactic body radiation therapy clinical trial publications based on a systematic review.

The results of phase II and III trials on Stereotactic Body Radiation Therapy (SBRT) increased adoption of SBRT worldwide. The ability to replicate clinical trial outcomes in routine practice depends on the capability to reproduce technical and dosimetric procedures used in the clinical trial. In this systematic review, we evaluated if peer-reviewed publications of clinical trials in SBRT reported sufficient technical data to ensure safe and robust implementation in real world clinics. Twenty papers were selected for inclusion, and data was extracted by a working group of medical physicists created following the ESTRO 2021 physics workshop. A large variability in technical and dosimetric data were observed, with frequent lack of required information for reproducing trial procedures. None of the evaluated studies were judged completely reproducible from a technical perspective. A list of recommendations has been provided by the group, based on the analysis and consensus process, to ensure an adequate reproducibility of technical parameters in primary SBRT clinical trials. Future publications should consider these recommendations to assist transferability of the clinical trial in real world practice.

A temporally and spatially explicit, data-driven estimation of airborne ragweed pollen concentrations across Europe.

Ongoing and future climate change driven expansion of aeroallergen-producing plant species comprise a major human health problem across Europe and elsewhere. There is an urgent need to produce accurate, temporally dynamic maps at the continental level, especially in the context of climate uncertainty. This study aimed to restore missing daily ragweed pollen data sets for Europe, to produce phenological maps of ragweed pollen, resulting in the most complete and detailed high-resolution ragweed pollen concentration maps to date. To achieve this, we have developed two statistical procedures, a Gaussian method (GM) and deep learning (DL) for restoring missing daily ragweed pollen data sets, based on the plant's reproductive and growth (phenological, pollen production and frost-related) characteristics. DL model performances were consistently better for estimating seasonal pollen integrals than those of the GM approach. These are the first published modelled maps using altitude correction and flowering phenology to recover missing pollen information. We created a web page (http://euragweedpollen.gmf.u-szeged.hu/), including daily ragweed pollen concentration data sets of the stations examined and their restored daily data, allowing one to upload newly measured or recovered daily data. Generation of these maps provides a means to track pollen impacts in the context of climatic shifts, identify geographical regions with high pollen exposure, determine areas of future vulnerability, apply spatially-explicit mitigation measures and prioritize management interventions.

Expanded HILUS Trial: A Pooled Analysis of Risk Factors for Toxicity From Stereotactic Body Radiation Therapy of Central and Ultracentral Lung Tumors.

PURPOSE: Stereotactic body radiation therapy for tumors near the central airways implies high-grade toxic effects, as concluded from the HILUS trial. However, the small sample size and relatively few events limited the statistical power of the study. We therefore pooled data from the prospective HILUS trial with retrospective data from patients in the Nordic countries treated outside the prospective study to evaluate toxicity and risk factors for high-grade toxic effects. METHODS AND MATERIALS: All patients were treated with 56 Gy in 8 fractions. Tumors within 2 cm of the trachea, the mainstem bronchi, the intermediate bronchus, or the lobar bronchi were included. The primary endpoint was toxicity, and the secondary endpoints were local control and overall survival. Clinical and dosimetric risk factors were analyzed for treatment-related fatal toxicity in univariable and multivariable Cox regression analyses. RESULTS: Of 230 patients evaluated, grade 5 toxicity developed in 30 patients (13%), of whom 20 patients had fatal bronchopulmonary bleeding. The multivariable analysis revealed tumor compression of the tracheobronchial tree and maximum dose to the mainstem or intermediate bronchus as significant risk factors for grade 5 bleeding and grade 5 toxicity. The 3-year local control and overall survival rates were 84% (95% CI, 80%-90%) and 40% (95% CI, 34%-47%), respectively. CONCLUSIONS: Tumor compression of the tracheobronchial tree and high maximum dose to the mainstem or intermediate bronchus increase the risk of fatal toxicity after stereotactic body radiation therapy in 8 fractions for central lung tumors. Similar dose constraints should be applied to the intermediate bronchus as to the mainstem bronchi.

Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline.

PURPOSE: This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent. METHODS: ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology. RESULTS: Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation. CONCLUSIONS: Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances.

Interfractional dose accumulation for MR-guided liver SBRT: Variation among algorithms is highly patient- and fraction-dependent.

BACKGROUND AND PURPOSE: Daily plan adaptations could take the dose delivered in previous fractions into account. Due to high dose delivered per fraction, low number of fractions, steep dose gradients, and large interfractional organ deformations, this might be particularly important for liver SBRT. This study investigates inter-algorithm variation of interfractional dose accumulation for MR-guided liver SBRT. MATERIALS AND METHODS: We assessed 27 consecutive MR-guided liver SBRT treatments of 67.5 Gy in three (n = 15) or 50 Gy in five fractions (n = 12), both prescribed to the GTV. We calculated fraction doses on daily patient anatomy, warped these doses to the simulation MRI using seven different algorithms, and accumulated the warped doses. Thus, we obtained differences in planned doses and warped or accumulated doses for each algorithm. This enabled us to calculate the inter-algorithm variations in warped doses per fraction and in accumulated doses per treatment course. RESULTS: The four intensity-based algorithms were more consistent with planned PTV dose than affine or contour-based algorithms. The mean (range) variation of the dose difference for PTV D95% due to dose warping by these intensity-based algorithms was 10.4 percentage points (0.3 to 43.7) between fractions and 8.6 (0.3 to 24.9) between accumulated treatment doses. As seen by these ranges, the variation was very dependent on the patient and the fraction being analyzed. Nevertheless, no correlations between patient or plan characteristics on the one hand and inter-algorithm dose warping variation on the other hand was found. CONCLUSION: Inter-algorithm dose accumulation variation is highly patient- and fraction-dependent for MR-guided liver SBRT. We advise against trusting a single algorithm for dose accumulation in liver SBRT.

Volume matters: Breast induration is associated with irradiated breast volume in the Danish Breast Cancer Group phase III randomized Partial Breast Irradiation trial.

PURPOSE: The relation between breast induration grade 2-3 at 3 years after radiation therapy and irradiated breast volume was investigated for patients in the Danish Breast Cancer Group (DBCG) Partial Breast Irradiation (PBI) trial. METHODS Treatment plan data was obtained from the Danish radiotherapy plan database. Dosimetric parameters for breast and organs at risk were determined. Breast induration data was obtained from the DBCG database. The volume of the whole breast (CTVp_breast) treated to various dose levels was determined for treatment plans in both arms. Logistic regression was used to assess the frequency of induration on breast volume irradiated to ≥40 Gy. RESULTS PBI and WBI was given to 433 and 432 patients, respectively. Median and interquartile ranges (IQR) for CTVp_breast were 710 mL (467-963 mL; PBI) and 666 mL (443-1012 mL; WBI) (p = 0.98). Median and IQR for CTVp_breast treated to ≥40 Gy was 24.9% (18.6-32.6%; PBI) and 59.8% (53.6-68.5%; WBI). Grade 2-3 induration was observed in 5% (PBI) and 10% (WBI) of the patients. A dose-response relationship was established between irradiated breast volume and frequency of breast induration. From the model, 5% and 10% risks of breast induration were observed for ≥40 Gy delivered to CTVp_breast volumes of 177 mL (95%CI, 94-260 mL) and 426 mL (95%CI, 286-567 mL), respectively. CONCLUSION The frequency of breast induration increased significantly with increasing irradiated breast volume, strongly favouring small volumes and PBI. Thus, treated breast volume - not the breast size itself - is the risk factor for induration. This is the first report directly linking the 40 Gy irradiated breast volume to breast induration.

Partial Breast Irradiation Versus Whole Breast Irradiation for Early Breast Cancer Patients in a Randomized Phase III Trial: The Danish Breast Cancer Group Partial Breast Irradiation Trial.

PURPOSE: On the basis of low risk of local recurrence in elderly patients with breast cancer after conservative surgery followed by whole breast irradiation (WBI), the Danish Breast Cancer Group initiated the noninferiority external-beam partial breast irradiation (PBI) trial (ClinicalTrials.gov identifier: NCT00892814). We hypothesized that PBI was noninferior to WBI regarding breast induration. METHODS: Patients operated with breast conservation for relatively low-risk breast cancer were randomly assigned to WBI versus PBI, and all had 40 Gy/15 fractions. The primary end point was 3-year grade 2-3 breast induration. RESULTS: In total, 865 evaluable patients (434 WBI and 431 PBI) were enrolled between 2009 and 2016. Median follow-up was 5.0 years (morbidity) and 7.6 years (locoregional recurrence). The 3-year rate of induration was 9.7% for WBI and 5.1% for PBI (P = .014). Large breast size was significantly associated with induration with a 3-year incidence of 13% (WBI) and 6% (PBI) for large-breasted patients versus 6% (WBI) and 5% (PBI) for small-breasted patients. PBI showed no increased risk of dyspigmentation, telangiectasia, edema, or pain, and patient satisfaction was high. Letrozole and smoking did not increase the risk of radiation-associated morbidity. Sixteen patients had a locoregional recurrence (six WBI and 10 PBI; P = .28), 20 patients had a contralateral breast cancer, and eight patients had distant failure (five WBI and three PBI). A nonbreast second cancer was detected in 73 patients (8.4%), and there was no difference between groups. CONCLUSION: External-beam PBI for patients with low-risk breast cancer was noninferior to WBI in terms of breast induration. Large breast size was a risk factor for radiation-associated induration. Few recurrences were detected and unrelated to PBI.

Accuracy and consistency of intensity-based deformable image registration in 4DCT for tumor motion estimation in liver radiotherapy planning.

We investigate the accuracy of intensity-based deformable image registration (DIR) for tumor localization in liver stereotactic body radiotherapy (SBRT). We included 4DCT scans to capture the breathing motion of eight patients receiving SBRT for liver metastases within a retrospective clinical study. Each patient had three fiducial markers implanted. The liver and the tumor were delineated in the mid-ventilation phase, and their positions in the other phases were estimated with deformable image registration. We tested referenced and sequential registrations strategies. The fiducial markers were the gold standard to evaluate registration accuracy. The registration errors related to measured versus estimated fiducial markers showed a mean value less than 1.6mm. The positions of some fiducial markers appeared not stable on the 4DCT throughout the respiratory phases. Markers' center of mass tends to be a more reliable measurement. Distance errors of tumor location based on registration versus markers center of mass were less than 2mm. There were no statistically significant differences between the reference and the sequential registration, i.e., consistency and errors were comparable to resolution errors. We demonstrated that intensity-based DIR is accurate up to resolution level for locating the tumor in the liver during breathing motion.

Synthetic 4DCT(MRI) lung phantom generation for 4D radiotherapy and image guidance investigations.

PURPOSE: Respiratory motion is one of the major challenges in radiotherapy. In this work, a comprehensive and clinically plausible set of 4D numerical phantoms, together with their corresponding "ground truths," have been developed and validated for 4D radiotherapy applications. METHODS: The phantoms are based on CTs providing density information and motion from multi-breathing-cycle 4D Magnetic Resonance imagings (MRIs). Deformable image registration (DIR) has been utilized to extract motion fields from 4DMRIs and to establish inter-subject correspondence by registering binary lung masks between Computer Tomography (CT) and MRI. The established correspondence is then used to warp the CT according to the 4DMRI motion. The resulting synthetic 4DCTs are called 4DCT(MRI)s. Validation of the 4DCT(MRI) workflow was conducted by directly comparing conventional 4DCTs to derived synthetic 4D images using the motion of the 4DCTs themselves (referred to as 4DCT(CT)s). Digitally reconstructed radiographs (DRRs) as well as 4D pencil beam scanned (PBS) proton dose calculations were used for validation. RESULTS: Based on the CT image appearance of 13 lung cancer patients and deformable motion of five volunteer 4DMRIs, synthetic 4DCT(MRI)s with a total of 871 different breathing cycles have been generated. The 4DCT(MRI)s exhibit an average superior-inferior tumor motion amplitude of 7 ± 5 mm (min: 0.5 mm, max: 22.7 mm). The relative change of the DRR image intensities of the conventional 4DCTs and the corresponding synthetic 4DCT(CT)s inside the body is smaller than 5% for at least 81% of the pixels for all studied cases. Comparison of 4D dose distributions calculated on 4DCTs and the synthetic 4DCT(CT)s using the same motion achieved similar dose distributions with an average 2%/2 mm gamma pass rate of 90.8% (min: 77.8%, max: 97.2%). CONCLUSION: We developed a series of numerical 4D lung phantoms based on real imaging and motion data, which give realistic representations of both anatomy and motion scenarios and the accessible "ground truth" deformation vector fields of each 4DCT(MRI). The open-source code and motion data allow foreseen users to generate further 4D data by themselves. These numeric 4D phantoms can be used for the development of new 4D treatment strategies, 4D dose calculations, DIR algorithm validations, as well as simulations of motion mitigation and different online image guidance techniques for both proton and photon radiation therapy.

The HILUS-Trial-a Prospective Nordic Multicenter Phase 2 Study of Ultracentral Lung Tumors Treated With Stereotactic Body Radiotherapy.

INTRODUCTION: Stereotactic body radiation therapy of thoracic tumors close to the central airways implies risk of severe toxicity. We report a prospective multicenter phase 2 trial for tumors located less than or equal to 1 cm from the proximal bronchial tree with primary end point of local control and secondary end point of toxicity. METHODS: Stereotactic body radiation therapy with 7 Gy × 8 was prescribed to the 67% isodose encompassing the planning target volume. The patients were stratified to group A (tumors ≤ 1 cm from the main bronchi and trachea) or group B (all other tumors). Risk factors for treatment-related death were tested in univariate analysis, and a logistic regression model was developed for fatal bronchopulmonary bleeding versus dose to the main bronchi and trachea. RESULTS: A total of 65 patients (group A/group B, n = 39/26) were evaluated. The median distance between the tumor and the proximal bronchial tree was 0 mm (0-10 mm). The 2-year local control was 83%. Grade 3 to 5 toxicity was noted in 22 patients, including 10 cases of treatment-related death (bronchopulmonary hemorrhage, n = 8; pneumonitis, n = 1; fistula, n = 1). Dose to the combined structure main bronchi and trachea and tumor distance to the main bronchi were important risk factors. Dose modeling revealed minimum dose to the "hottest" 0.2 cc to the structure main bronchi and trachea as the strongest predictor for lethal bronchopulmonary hemorrhage. CONCLUSIONS: On the basis of the presented data, 7 Gy × 8, prescribed to the planning target volume-encompassing isodose, should not be used for tumors located within 1 cm from the main bronchi and trachea. Group B-type tumors may be considered for the treatment on the basis of an individual risk-benefit assessment and a maximum dose to the main bronchi and trachea in the order of 70 to 80 Gy (equivalent dose in 2 Gy fractions).

Dosimetric influence of deformable image registration uncertainties on propagated structures for online daily adaptive proton therapy of lung cancer patients.

PURPOSE: A major burden of introducing an online daily adaptive proton therapy (DAPT) workflow is the time and resources needed to correct the daily propagated contours. In this study, we evaluated the dosimetric impact of neglecting the online correction of the propagated contours in a DAPT workflow. MATERIAL AND METHODS: For five NSCLC patients with nine repeated deep-inspiration breath-hold CTs, proton therapy plans were optimised on the planning CT to deliver 60 Gy-RBE in 30 fractions. All repeated CTs were registered with six different clinically used deformable image registration (DIR) algorithms to the corresponding planning CT. Structures were propagated rigidly and with each DIR algorithm and reference structures were contoured on each repeated CT. DAPT plans were optimised with the uncorrected, propagated structures (propagated DAPT doses) and on the reference structures (ideal DAPT doses), non-adapted doses were recalculated on all repeated CTs. RESULTS: Due to anatomical changes occurring during the therapy, the clinical target volume (CTV) coverage of the non-adapted doses reduces on average by 9.7% (V95) compared to an ideal DAPT doses. For the propagated DAPT doses, the CTV coverage was always restored (average differences in the CTV V95 < 1% compared to the ideal DAPT doses). Hotspots were always reduced with any DAPT approach. CONCLUSION: For the patients presented here, a benefit of online DAPT was shown, even if the daily optimisation is based on propagated structures with some residual uncertainties. However, a careful (offline) structure review is necessary and corrections can be included in an offline adaption.

Intrafractional fiducial marker position variations in stereotactic liver radiotherapy during voluntary deep inspiration breath-hold.

OBJECTIVES: To evaluate intrafractional fiducial marker position variations during stereotactic body radiotherapy (SBRT) in patients treated for liver metastases in visually guided, voluntary deep inspiration breath-hold (DIBH). METHODS: 10 patients with implanted fiducial markers were studied. Respiratory coaching with visual guidance was used to ensure comfortable voluntary breath-holds for SBRT imaging and delivery. Three DIBH CTs were acquired for treatment planning. Pre- and post-treatment CBCTs were acquired for each of the three treatment fractions. Per-fraction marker position was evaluated on planar 2D kV images acquired during treatment fractions for 4 of the 10 patients. RESULTS: The median difference in marker position was 0.3 cm (range, 0.0-0.9 cm) between the three DIBH CTs and 0.3 cm (range, 0.1 to 1.4 cm) between pre- and post-treatment CBCTs. The maximum intrafractional variation in marker position in craniocaudal (CC) direction on planar kV images was 0.7 to 1.3 cm and up to 1.0 cm during a single DIBH. CONCLUSION: Difference in marker position of up to 1.0 cm was observed during a single DIBH despite use of narrow external gating window and visual feedback. Stability examination on pre-treatment DIBH CTs was not sufficient to guarantee per-fraction stability. Evaluation of differences in marker position on pre- and post-treatment CBCT did not always reveal the full magnitude of the intrafractional variation. ADVANCES IN KNOWLEDGE: To increase treatment accuracy, it is necessary to apply real-time monitoring of the tumour or a reliable internal surrogate when delivering liver SBRT in voluntary DIBH.

Delineation of whole heart and substructures in thoracic radiation therapy: National guidelines and contouring atlas by the Danish Multidisciplinary Cancer Groups.

BACKGROUND AND PURPOSE: This study presents Danish consensus guidelines for delineation of the heart and cardiac substructures across relevant Danish Multidisciplinary Cancer Groups. MATERIAL AND METHODS: Consensus guidelines for the heart and cardiac substructures were reached among 15 observers representing the radiotherapy (RT) committees of four Danish Multidisciplinary Cancer Groups. The guidelines were validated on CT scans of 12 patients, each with five independent contour sets. The Sørensen-Dice similarity coefficient (DSC), the distance between the centers of the arteries and the mean surface distance were used to evaluate the inter-observer variation. RESULTS: National guidelines for contouring the heart and cardiac substructures were achieved. The median DSC was 0.78-0.96 for the heart and the four cardiac chambers. For the four substructures of the left ventricle, the median DSC was 0.35-0.57. The coronary arteries were contoured in ten segments, with the best agreement for the left anterior descending coronary artery segments, with a median distance between the arteries ranging from 2.4-4.4 mm. The median variation was 3.7-12.8 mm for the right coronary artery segments and 3.7-6.2 mm for the left circumflex coronary artery segments, with the most pronounced inter-observer variation in the distal segment for all three coronary arteries. CONCLUSION: National guidelines for contouring the heart and cardiac substructures were developed across relevant Danish Multidisciplinary Cancer Groups, where RT dose to the heart is of concern. The inter-observer contour overlap was best for the heart and chambers and decreased for smaller structures.

Deformable image registration uncertainty for inter-fractional dose accumulation of lung cancer proton therapy.

BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) patients show typically large anatomical changes during treatment, making recalculation or adaption necessary. For report and review, the applied treatment dose can be accumulated on the reference planning CT using deformable image registration (DIR). We investigated the dosimetric impact of using six different clinically available DIR algorithms for dose accumulation in presence of inter-fractional anatomy variations. MATERIALS AND METHODS: For seven NSCLC patients, proton treatment plans with 66 Gy-RBE to the planning target volume (PTV) were optimised. Nine repeated CTs were registered to the planning CT using six DIR algorithms each. All CTs were acquired in visually guided deep-inspiration breath-hold. The plans were recalculated on the repeated CTs and warped back to the planning CT using the corresponding DIRs. Fraction doses warped with the same DIR were summed up to six different accumulated dose distributions per patient, and compared to the initial dose. RESULTS: The PTV-V95 of accumulated doses decreased by 16% on average over all patients, with variations due to DIR selection of 8.7%. A separation of the dose effects caused by anatomical changes and DIR uncertainty showed a good agreement between the dose degradation caused by anatomical changes and the dose predicted from the average of all DIRs (differences of only 1.6%). CONCLUSION: The dose degradation caused by anatomical changes was more pronounced than the uncertainty of employing different DIRs for dose accumulation, with averaged results from several DIRs providing a good representation of dose degradation caused by anatomy. However, accumulated dose variations between DIRs can be substantial, leading to an additional dose uncertainty.