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Background Prostate cancer oligometastatic disease can be treated using stereotactic body radiotherapy (SBRT) in order to postpone start of systemic treatments such as androgen deprivation therapy (ADT). 68Ga-PSMA-PET/CT imaging allows for diagnosis of oligometastases at lower PSA values. We analysed a cohort of patients with prostate cancer lymph node oligometastases detected on PSMA-PET/CT. Materials and methods Ninety patients with metachronous oligometastatic prostate cancer received SBRT for 1-3 lymph node metastases diagnosed on 68Ga-PSMA-PET/CT. The primary end point was progression free survival (PFS), with disease progression defined as occurrence of either target lesion progression, new metastatic lesion or biochemical progression. Secondary outcomes were biochemical PFS (BPFS), ADT-free survival (ADT-FS), toxicity and quality of life (QoL). Baseline patient characteristics were tested for association with PFS and a preliminary risk score was created. Results Median follow-up was 21 months (interquartile range 10-31 months). Median PFS and BPFS were 16 and 21 months, respectively. Median ADT-FS was not reached (73% (95%-CI 62-86%) at 24 months). In multivariable analysis, younger age, higher PSA prior to SBRT and extrapelvic location were associated with shorter PFS. Grade 1 fatigue was the most predominant acute toxicity (34%). Highest grade toxicity was grade 2 for acute and late events. QoL analysis showed mild, transient increase in fatigue at 1-4 weeks after SBRT. Conclusion A median PFS of 16 months was attained after SBRT for patients with PSMA-PET positive oligometastatic lymph nodes from prostate cancer. Higher pre-SBRT PSA, younger age and extrapelvic location were found to be predictors of shorter PFS.

BACKGROUND AND PURPOSE The aim of this study was to determine the feasibility of hypofractionated schedules for metastatic bone/bone marrow lesions in children and to investigate dosimetric differences to the healthy surrounding tissues compared to conventional schedules. METHODS 27 paediatric patients (mean age, 7 years) with 50 metastatic bone/bone marrow lesions (n = 26 cranial, n = 24 extra-cranial) from solid primary tumours (neuroblastoma and sarcoma) were included. The PTV was a 2 mm expansion of the GTV. A prescription dose of 36 and 54 Gy EQD2α/β=10 was used for neuroblastoma and sarcoma lesions, respectively. VMAT plans were optimized for each single lesion using different fractionation schedules: conventional (30/20 fractions, V95% ≥ 99%, D0.1cm3 ≤ 107%) and hypofractionated (15/10/5/3 fractions, V100% ≥ 95%, D0.1cm3 ≤ 120%). Relative EQD2 differences in OARs Dmean between the different schedules were compared. RESULTS PTV coverage was met for all plans independently of the fractionation schedule and for all lesions (V95% range 95.5-100%, V100% range 95.1-100%), with exception of the vertebrae (V100% range 63.5-91.0%). For most OARs, relative mean reduction in the Dmean was seen for the hypofractionated plans compared to the conventional plans, with largest sparing in the 5 fractions (< 43%) followed by the 3 fractions schedule (< 40%). In case of PTV overlap with an OAR, a significant increase in dose for the OAR was observed with hypofractionation. CONCLUSIONS For the majority of the cases, iso-effective plans with hypofractionation were feasible with similar or less dose in the OARs. The most suitable fractionation schedule should be personalised depending on the spatial relationship between the PTV and OARs and the prescription dose.

Purpose: To describe experience with partial nephrectomy combined with brachytherapy as part of the local management of bilateral Wilms tumor (WT) including a review of the available literature.Results (methods and case description): Between 2011 and 2014, three highly selected patients (age nine months, 16 months, and 4 years) with bilateral WT (two synchronous and one metachronous) underwent enucleation and perioperative brachytherapy to the tumor bed. With a minimum follow-up of 5 years, all three patients are in continuous complete remission with preserved kidney function.Conclusions: Although nephron sparing surgery aiming at tumor free-margins remains the gold standard for bilateral WT, tumor enucleation followed by brachytherapy may be considered in carefully selected patients at high risk for end-stage kidney failure. Given the rarity and complexity of the procedure, concentration of care of such patients is mandatory.

Purpose At our department, MR-guided stereotactic body radiation therapy (SBRT) using the 1.5T MR-linac system (Unity, Elekta AB, Stockholm, Sweden) has been initiated for patients with lymph node oligometastases. Superior soft tissue contrast and the possibility for online plan adaptation on the Unity may allow for hypofractionated treatment. The purpose of this study was to investigate the dosimetric feasibility and compare the plan quality of different hypofractionated schemes. Methods and materials Data was used from 12 patients with single lymph node oligometastases (10 pelvic, 2 para-aortic), which were all treated on the Unity with a prescribed dose of 5x7 Gy to 95% of the PTV. Hypofractionation was investigated for 3x10 Gy and 1x20 Gy schemes (all 60 Gy BED α/β = 10). The pre-treatment plans were evaluated based on dose criteria and plan quality. If all criteria were met, the number of online adapted plans which also met all dose criteria was investigated. For pre-treatment plans meeting the criteria for all three fractionation schemes, the plan quality after online adaptation was compared using the four parameters described in the NRG-BR001 phase 1 trial. Results Pre-treatment plans met all clinical criteria for the three different fractionation schemes in 10, 9 and 6 cases. 50/50, 45/45 17/30 of the corresponding online adapted plans met all criteria, respectively. Violations were primarily caused by surrounding organs at risk overlapping or adjacent to the PTV. The 1x20 Gy treatment plans were, in general, of lesser quality than the 5x7 Gy and 3x10 Gy plans. Conclusion Hypofractionated radiotherapy for lymph node oligometastases on the 1.5T MR-linac is feasible based on dose criteria and plan quality metrics. The location of the target relative to critical structures should be considered in choosing the most suitable fractionation scheme. Especially for single fraction treatment, meeting all dose criteria in the pre-treatment situation does not guarantee that this also applies during online treatment.

Background and purpose Patients were treated at our institute for single and multiple lymph node oligometastases on the 1.5T MR-linac since August 2018. The superior soft-tissue contrast and additional software features of the MR-linac compared to CBCT-linacs allow for online adaptive treatment planning. The purpose of this study was to perform a target coverage and dose criteria based evaluation of the clinically delivered online adaptive radiotherapy treatment compared with conventional CBCT-linac treatment. Materials and methods Patient data was used from 14 patients with single lymph node oligometastases and 6 patients with multiple (2–3) metastases. All patients were treated on the 1.5T MR-linac with a prescribed dose of 5 × 7 Gy to 95% of the PTV and a CBCT-linac plan was created for each patient. The difference in target coverage between these plans was compared and plans were evaluated based on dose criteria for each fraction after calculating the CBCT-plan on the daily anatomy. The GTV coverage was evaluated based on the online planning and the post-delivery MRI. Results For both single and multiple lymph node oligometastases the GTV V35Gy had a median value of 100% for both the MR-linac plans and CBCT-plans pre- and post-delivery and did not significantly differ. The percentage of plans that met all dose constraints was improved from 19% to 84% and 20% to 67% for single and multiple lymph node cases, respectively. Conclusion Target coverage and dose criteria based evaluation of the first clinical 1.5T MR-linac SBRT treatments of lymph node oligometastases compared with conventional CBCT-linac treatment shows a smaller amount of unplanned violations of high dose criteria. The GTV coverage was comparable. Benefit is primarily gained in patients treated for multiple lymph node oligometastases: geometrical deformations are accounted for, dose can be delivered in one plan and margins can be reduced.

Background and purpose: Whole bladder radiotherapy is challenging due to inter- and intrafraction size and shape changes. To account for these changes, currently a Library of Plans (LoP) technique is often applied, but daily adaptive radiotherapy is also increasingly becoming available. The aim of this study was to compare LoP with two magnetic resonance imaging guided radiotherapy (MRgRT) strategies by comparing target coverage and volume of healthy tissue inside the planning target volume (PTV) for whole bladder treatments.Methods and materials: Data from 25 MRgRT lymph node oligometastases treatments (125 fractions) were used, with three MRI scans acquired at each fraction at 0, 15 and 30 min. Bladders were delineated and used to evaluate three strategies: 1) LoP with two plans for a 15 min fraction, 2) MRgRT15min for a 15 min fraction and 3) MRgRT30min for a 30 min fraction. The volumes of healthy tissue inside and bladder outside the PTV were analyzed on the simulated post-treatment images.Results: MRgRT30min had 120% and 121% more healthy tissue inside the PTV than LoP and MRgRT15min. For LoP slightly more target outside the PTV was found than for MRgRT30min and MRgRT15min, with median 0% (range 0-23%) compared to 0% (0-20%) and 0% (0-10%), respectively.Conclusions: Taking into account both target coverage and volume of healthy tissue inside the PTV, MRgRT15min performed better than LoP and MRgRT30min for whole bladder treatments. A 15 min daily adaptive radiotherapy workflow is needed to potentially benefit from replanning compared to LoP.

Prostate cancer oligometastatic disease can be treated using stereotactic body radiotherapy (SBRT) in order to postpone start of systemic treatments such as androgen deprivation therapy (ADT). 68Ga-PSMA-PET/CT imaging allows for diagnosis of oligometastases at lower PSA values. We analysed a cohort of patients with prostate cancer lymph node oligometastases detected on PSMA-PET/CT.Ninety patients with metachronous oligometastatic prostate cancer received SBRT for 1-3 lymph node metastases diagnosed on 68Ga-PSMA-PET/CT. The primary end point was progression free survival (PFS), with disease progression defined as occurrence of either target lesion progression, new metastatic lesion or biochemical progression. Secondary outcomes were biochemical PFS (BPFS), ADT-free survival (ADT-FS), toxicity and quality of life (QoL). Baseline patient characteristics were tested for association with PFS and a preliminary risk score was created.Median follow-up was 21 months (interquartile range 10-31 months). Median PFS and BPFS were 16 and 21 months, respectively. Median ADT-FS was not reached (73% (95%-CI 62-86%) at 24 months). In multivariable analysis, younger age, higher PSA prior to SBRT and extrapelvic location were associated with shorter PFS. Grade 1 fatigue was the most predominant acute toxicity (34%). Highest grade toxicity was grade 2 for acute and late events. QoL analysis showed mild, transient increase in fatigue at 1-4 weeks after SBRT.A median PFS of 16 months was attained after SBRT for patients with PSMA-PET positive oligometastatic lymph nodes from prostate cancer. Higher pre-SBRT PSA, younger age and extrapelvic location were found to be predictors of shorter PFS.

Highlights • The Elekta Unity MR-linac adaptive radiotherapy concept is explained. • The adapt to shape and adapt to position workflows are compared. • Different methods for dose re-calculation and optimization are discussed. • Full online re-planning is the most robust adaptive planning method for the Unity. • Faster methods are available, but should be dosimetrically explored per use case., Background and purpose The promise of the MR-linac is that one can visualize all anatomical changes during the course of radiotherapy and hence adapt the treatment plan in order to always have the optimal treatment. Yet, there is a trade-off to be made between the time spent for adapting the treatment plan against the dosimetric gain. In this work, the various daily plan adaptation methods will be presented and applied on a variety of tumour sites. The aim is to provide an insight in the behavior of the state-of-the-art 1.5 T MRI guided on-line adaptive radiotherapy methods. Materials and methods To explore the different available plan adaptation workflows and methods, we have simulated online plan adaptation for five cases with varying levels of inter-fraction motion, regions of interest and target sizes: prostate, rectum, esophagus and lymph node oligometastases (single and multiple target). The plans were evaluated based on the clinical dose constraints and the optimization time was measured. Results The time needed for plan adaptation ranged between 17 and 485 s. More advanced plan adaptation methods generally resulted in more plans that met the clinical dose criteria. Violations were often caused by insufficient PTV coverage or, for the multiple lymph node case, a too high dose to OAR in the vicinity of the PTV. With full online replanning it was possible to create plans that met all clinical dose constraints for all cases. Conclusion Daily full online replanning is the most robust adaptive planning method for Unity. It is feasible for specific sites in clinically acceptable times. Faster methods are available, but before applying these, the specific use cases should be explored dosimetrically.

Highlights • An international survey assessed the potential role of MRgRT in pediatrics. • The Dutch National cohort has been used to put results into a clinical perspective. • A potential toxicity/outcome benefit is expected for 55%/24% of primary sites. • A potential toxicity/outcome benefit is expected for 62%/38% of metastatic sites. • Consortium-based collaboration is essential to validate expectations., Background and purpose Magnetic resonance guided radiotherapy (MRgRT) has been successfully implemented for several routine clinical applications in adult patients. The purpose of this study is to map the potential benefit of MRgRT on toxicity reduction and outcome in pediatric patients treated with curative intent for primary and metastatic sites. Materials and methods Between May and August 2020, a survey was distributed among SIOPE- and COG-affiliated radiotherapy departments, treating at least 25 pediatrics patients annually and being (candidate) users of a MRgRT system. The survey consisted of a table with 45 rows (clinical scenarios for primary (n = 28) and metastatic (n = 17) tumors) and 7 columns (toxicity reduction, outcome improvement, PTV margin reduction, target volume daily adaptation, online re-planning, intrafraction motion compensation and on-board functional imaging) and the option to answer by ‘yes/no’ . Afterwards, the Dutch national radiotherapy cohort was used to estimate the percentage of pediatric treatments that may benefit from MRgRT. Results The survey was completed by 12/17 (71% response rate) institutions meeting the survey inclusion criteria. Responders indicated an ‘expected benefit’ from MRgRT for toxicity/outcome in 7% (for thoracic lymphomas and abdominal rhabdomyosarcomas)/0% and 18% (for mediastinal lymph nodes, lymph nodes located in the liver/splenic hilum, and liver metastases)/0% of the considered scenarios for the primary and metastatic tumor sites, respectively, and a ‘possible benefit’ was estimated in 64%/46% and 47%/59% of the scenarios. When translating the survey outcome into a clinical perspective a toxicity/outcome benefit, either expected or possible, was anticipated for 55%/24% of primary sites and 62%/38% of the metastatic sites. Conclusion Although the benefit of MRgRT in pediatric radiation oncology is estimated to be modest, the potential role for reducing toxicity and improving clinical outcomes warrants further investigation. This fits best within the context of prospective studies or registration trials.

Highlights • Recently, highly-conformal target volumes for flank delineation were defined. • Delineation variation of this target volume was assessed in an international setting. • Ten radiation oncologist delineated the GTV and CTV of six individual cases. • ‘Unacceptable’ delineation variation was found in a large number of participants. • This indicates the need for central target volume review before radiotherapy onset., Background and purpose Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance. Materials and methods Six pediatric renal cancer cases were transferred to ten radiation oncologists from seven European countries (‘participants’). These participants delineated the pre- and postoperative Gross Tumor Volume (GTVpre/post), and Clinical Target Volume (CTV) during two test phases (case 1–2 and 3–4), followed by guideline refinement and a quality assurance phase (case 5–6). Reference target volumes (TVref) were established by three experienced radiation oncologists. The Dice Similarity Coefficient between the reference and participants (DSCref/part) was calculated per case. Delineations of case 5–6 were graded by four independent reviewers as ‘per protocol’ (0–4 mm), ‘minor deviation’ (5–9 mm) or ‘major deviation’ (≥10 mm) from the delineation guideline using 18 standardized criteria. Also, a major deviation resulting in underestimation of the CTVref was regarded as an unacceptable variation. Results A total of 57/60 delineation sets were completed. The median DSCref/part for the CTV was 0.55 without improvement after sequential cases (case 3–4 vs. case 5–6: p = 0.15). For case 5–6, a major deviation was found for 5/18, 12/17, 18/18 and 4/9 collected delineations of the GTVpre, GTVpost, CTV-T and CTV-N, respectively. An unacceptable variation from the CTVref was found for 7/9 participants for case 5 and 6/9 participants for case 6. Conclusion This international multicenter delineation exercise demonstrates that the new consensus for highly-conformal postoperative flank target volume delineation leads to geometrical variation among participants. Moreover, standardized review showed an unacceptable delineation variation in the majority of the participants. These findings strongly suggest the need for additional training and centralized pre-treatment review when this target volume delineation approach is implemented on a larger scale.

To study radiotherapy-related adverse effects, detailed dose information (3D distribution) is needed for accurate dose-effect modeling. For childhood cancer survivors who underwent radiotherapy in the pre-CT era, only 2D radiographs were acquired, thus 3D dose distributions must be reconstructed from limited information. State-of-the-art methods achieve this by using 3D surrogate anatomies. These can lack personalization and lead to coarse reconstructions. We present and validate a surrogate-free dose reconstruction method based on Machine Learning (ML). Abdominal planning CTs ($n$=142) of recently-treated childhood cancer patients were gathered, their organs at risk were segmented, and 300 artificial Wilms' tumor plans were sampled automatically. Each artificial plan was automatically emulated on the 142 CTs, resulting in 42,600 3D dose distributions from which dose-volume metrics were derived. Anatomical features were extracted from digitally reconstructed radiographs simulated from the CTs to resemble historical radiographs. Further, patient and radiotherapy plan features typically available from historical treatment records were collected. An evolutionary ML algorithm was then used to link features to dose-volume metrics. Besides 5-fold cross-validation, a further evaluation was done on an independent dataset of five CTs each associated with two clinical plans. Cross-validation resulted in Mean Absolute Errors (MAEs) $\leq$0.6 Gy for organs completely inside or outside the field. For organs positioned at the edge of the field, MAEs $\leq$1.7 Gy for D$_{mean}$, $\leq$2.9 Gy for D$_{2cc}$, and $\leq$13% for V$_{5Gy}$ and V$_{10Gy}$, were obtained, without systematic bias. Similar results were found for the independent dataset. Our novel, ML-based organ dose reconstruction method is not only accurate but also efficient, as the setup of a surrogate is no longer needed., Comment: M. Virgolin and Z. Wang share first authorship

Metàstasis; Pediatria; Radioteràpia Metástasis; Pediatría; Radioterapia Metastases; Paediatrics; Radiotherapy Purpose/objective About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries. Materials/methods Radiotherapy guidelines for metastatic sites (bone, brain, distant lymph nodes, lung and liver) in eight European protocols for rhabdomyosarcoma, non-rhabdomyosarcoma soft-tissue sarcoma, Ewing sarcoma, neuroblastoma and renal tumours were reviewed. SIOPE centres irradiating ≥50 children annually were invited to participate in an online survey. Results Radiotherapy to at least one metastatic site was recommended in all protocols, except for high-risk neuroblastoma. Per protocol, dose prescription varied per site, and information on delineation and treatment planning/delivery was generally missing. Between July and September 2019, 20/27 centres completed the survey. Around 14% of patients were deemed to have DM from ST at diagnosis, of which half were treated with curative intent. A clear cut-off for a maximum number of DM was not used in half of the centres. Regardless of the tumour type and site, conventional radiotherapy regimens were most commonly used to treat DM. When stereotactic radiotherapy was used, a wide range of fractionation regimens were applied. Conclusion Current radiotherapy guidelines for DM do not allow a consistent approach in a multicentre setting. Prospective (randomised) trials are needed to define the role of radical irradiation of DM from paediatric ST. Stichting Kinderen Kankervrij [project no. 343]. KiKa (Children Cancer Free) foundation, grant number 343 and title: Towards optimization of radiotherapy techniques for metastatic lesions in children stage IV disease. The funding source had no role in the study design, collection, analysis and interpretation of data, writing of this manuscript or the decision to submit the article for publication.

BACKGROUND AND PURPOSE Vacuum cushion immobilization is commonly used during stereotactic body radiotherapy (SBRT) to reduce intrafraction motion. We investigated target and bony anatomy intrafraction motion (translations and rotations) during online adaptive SBRT on an MR-linac for pelvic/para-aortic lymph node metastases with and without vacuum cushion. MATERIALS AND METHODS Thirty-nine patients underwent 5x7 Gy SBRT on a 1.5T MR-linac, 19 patients were treated with vacuum cushion, 19 without and 1 patient sequentially with and without. Intrafraction motion was calculated for target lymph nodes (GTVs) and nearby bony anatomy, for three time intervals (pre-position verification (PV), pre-post, PV-post, relating to the online MRI scans) per treatment fraction. RESULTS Vacuum cushion immobilization significantly reduced anterior-posterior translations for the pre-PV and pre-post intervals, for bony anatomy and pre-post interval for GTV (p

Online adaptive radiotherapy using the 1.5 Tesla MR-linac is feasible for SBRT (5 × 7 Gy) of pelvic lymph node oligometastases. The workflow allows full online planning based on daily anatomy. Session duration is less than 60 min. Quality assurance tests, including independent 3D dose calculations and film measurements were passed.

A. P. Schrier-Uijl1, P. S. Kroon2, D. M. D. Hendriks3, A. Hensen2, J. Van Huissteden4, P. A. Leffelaar5, F. Berendse1, and E. M. Veenendaal1 1Nature Conservation and Plant Ecology, Wageningen University, Droevendaalse steeg 3a, 6708 PD Wageningen, the Netherlands 2Energy Research Centre of the Netherlands (ECN), Department of Air Quality and Climate Change, 1755 LE Petten, the Netherlands 3Deltares, Department of Soil and Groundwater Systems, Princetonlaan 6, 3584 CB Utrecht, the Netherlands 4Hydrology and Geo-Environmental Sciences, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands 5Plant Production Systems, Wageningen University, P.O. Box 430, 6700 AK, Wageningen, the Netherlands

The superior soft tissue contrast provided by magnetic resonance (MR) images on the 1.5T MR-linac allows for the incorporation of patient anatomy information. In this retrospective case study, we present the simulated dosimetric effects and timings of full online replanning as compared to the five plan adaptation methods currently available on the 1.5T MR-linac treatment system. For this case, it is possible to create treatment plans with all six methods within a time slot suitable for an online treatment procedure. However, large dosimetric differences between the plan adaptation methods and full online replanning are present with regards to target coverage and dose to organs at risk (OARs).

Background. In radiotherapy, the magnitude of respiratory-induced tumor motion is often measured using a single four-dimensional computed tomography (4DCT). This magnitude is required to determine the internal target volume. The aim of this study was to compare the magnitude of respiratory-induced motion of pancreatic tumors on a single 4DCT with the motion on daily cone beam CT (CBCT) scans during a 3–5-week fractionated radiotherapy scheme. In addition, we investigated changes in the respiratory motion during the treatment course.Material and methods. The mean peak-to-peak motion (i.e. magnitude of motion) of pancreatic tumors was measured for 18 patients using intratumoral gold fiducials visible on CBCT scans made prior to each treatment fraction (10–27 CBCTs per patient; 401 CBCTs in total). For each patient, these magnitudes were compared to the magnitude measured on 4DCT. Possible time trends were investigated by applying linear fits to the tumor motion determined from daily CBCTs as a function of treatment day.Results. We found a significant (p ≤ 0.01) difference between motion magnitude on 4DCT and on CBCT in superior-inferior, anterior-posterior and left-right direction, in 13, 9 and 12 of 18 patients, respectively. In the anterior- posterior and left-right direction no fractions had a difference ≥ 5 mm. In the superior-inferior direction the difference was ≥ 5 mm for 17% of the 401 fractions. In this direction, a significant (p ≤ 0.05) time trend in tumor motion was observed in 4 of 18 patients, but all trends were small (− 0.17–0.10 mm/day) and did not explain the large differences in motion magnitude between 4DCT and CBCT.Conclusion. A single measurement of the respiratory-induced motion magnitude of pancreatic tumors using 4DCT is often not representative for the magnitude during daily treatment over a 3–5-week radiotherapy scheme. For this patient group it may be beneficial to introduce breath-hold to eliminate respiratory-induced tumor motion.

PURPOSE: Online 1.5T MR imaging on the MR-linac gives better target visualization compared to CBCT and facilitates online adaptive treatment strategies including daily replanning. In this simulation study, the dosimetric impact of online replanning was investigated for SBRT of lymph node oligometastases as a method for correcting for inter-fraction anatomical changes. METHODS: Pre-treatment plans were created for 17 pelvic and para-aortic lymph nodes, with 3 and 8 mm PTV margins reflecting our clinical practice for lymph nodes with good and poor visibility on CBCT. The dose-volume parameters of the pre-treatment plans were evaluated on daily anatomy as visible on the repeated MRIs and compared to online replanning. RESULTS: With online MRI-based replanning significant dosimetric improvements are obtained for the rectum, bladder, bowel and sigmoid without compromising the target dose. The amount of unintended violations of the dose constraints for target and surrounding organs could be reduced by 75% for 8 mm and 66% for 3 mm PTV margins. CONCLUSION: The use of online replanning based on the actual anatomy as seen on repeated MRI compared to online position correction for lymph node oligometastases SBRT gives beneficial dosimetric outcomes and reduces the amount of unplanned violations of dose constraints.

Eddy covariance (EC) technique is often used to determine greenhouse gas exchange at the earth's surface. In general, the instruments involved have a limited high frequency response which reduces the ability to detect the contribution to the flux of small eddies and in addition sensor separation gives high frequency losses. These missing contributions cause an EC flux underestimation which increases for higher values of the stability parameter z/L . Corrections can be performed based on the (empirical) Kaimal co-spectra; however, these were derived using instruments with a limited frequency response. In this study, the validity of the Kaimal spectrum during stable atmospheric conditions is assessed using laser Doppler anemometry (LDA) measurements of the vertical wind velocity at 1 m height during several stable nights at Cabauw in the Netherlands. LDA provides a means to determine the entire turbulent energy spectrum, i.e., from the production scale down to the dissipation scale. Since the measured spectra are found to be in good agreement with the Kaimal spectra, we assume that the Kaimal co-spectra are valid as well. Next, the effect of high frequency correction based on Kaimal co-spectra is assessed using 1 month of EC flux data of CH 4 and N 2 O measured by quantum cascade laser (QCL) spectrometry at Reeuwijk in the Netherlands. After correction, the cumulative emissions increased about 15% for both gases. This underlines the importance of correcting for high frequency losses.

The uncertainty in eddy covariance (EC) flux measurements is assessed for CH4 and N2O using data measured at a dairy farm site in the Netherlands in 2006 and 2007. An overview is given of the contributing uncertainties and their magnitude. The relative and absolute uncertainty of a 30 min EC flux are estimated for CH4 and N2O using N = 2185 EC fluxes. The average absolute uncertainty and its standard deviation are 500 +/- 400 ng C m(-2) s(-1) for CH4 and 100 +/- 100 ng N m(-2) s(-1) N2O. The corresponding relative uncertainties have 95% confidence interval ranging from 20% to 300% for CH4 and from 30% to 1800% for N2O. The large relative uncertainties correspond to relatively small EC fluxes. The uncertainties are mainly caused by the uncertainty due to one-point sampling which contributes on average more than 90% to the total uncertainty. The other 10% includes the uncertainty in the correction algorithm for the systematic errors. The uncertainty in a daily and monthly averaged EC flux are estimated for several flux magnitude ranges. The daily and monthly average uncertainty are smaller than 25% and 10% for CH4 and smaller than 50% and 10% for N2O, respectively, based on fluxes larger than 100 ng C m(-2) s(-1) and 15 ng N m(-2) s(-1). (C) 2009 Elsevier B.V. All rights reserved. (Less)

Annual terrestrial balances of methane (CH4) and nitrous oxide (N2O) are presented for a managed fen meadow in the Netherlands for 2006, 2007 and 2008, using eddy covariance (EC) flux measurements. Annual emissions derived from different methods are compared. The most accurate annual CH4 flux is achieved by gap filling EC fluxes with an empirical multivariate regression model, with soil temperature and mean wind velocity as driving variables. This model explains about 60% of the variability in observed daily CH4 fluxes. Annual N2O emissions can be separated into background emissions and event emissions due to fertilization. The background emission is estimated using a multivariate regression model also based on EC flux data, with soil temperature and mean wind velocity as driving variables. The event emissions are estimated using emission factors. The minimum direct emission factor is derived for six fertilization events by subtracting the background emission, and the IPCC default emission factor of 1% is used for the other events. In addition, the maximum direct emission factors are determined for the six events without subtracting the background emission. The average direct emission factor ranges from 1.2 to 2.8%, which is larger than the IPCC default value. Finally, the total terrestrial greenhouse gas balance is estimated at 16 Mg ha-1 year-1 in CO2-equivalents with contributions of 30, 25 and 45% by CO2, CH4 and N2O, respectively.

Closed (non-steady state) chamber measurements are often used to determine the gas exchange of N2O. Many researchers have addressed the underestimation of the emission estimates obtained from closed chamber measurements when using linear regression methods. However, the linear regression method is still usually applied to derive the flux. The importance of using non-linear regression methods is demonstrated with data from four fertilizing events each consisting of 1 month of automatic chamber measurements at Cabauw in the Netherlands in the period from July 2005 to July 2006. It is presented that the cumulative emission estimates with the exponential regression method are close to the cumulative emissions estimates with the intercept method. The linear estimates differ by up to 60% of the estimates with the exponential method. The performance of each method is validated using a C2H6 tracer and a goodness-of-fit analysis. The goodness-of-fit is much better for the exponential than the linear regression method. The systematic error due to linear regression is of the same order as the estimated uncertainty due to temporal variation. Therefore, closed-chamber data should be tested for non-linearity and an appropriate method should be used to calculate the flux.

An intercomparison is made of the Net Ecosystem Exchange of CO2, NEE, for eight Dutch grassland sites: four natural grasslands, two production grasslands and two meteorological stations within a rotational grassland region. At all sites the NEE was determined during at least 10 months per site, using the eddy-covariance (EC) technique, but in different years. The NEE does not include any import or export other than CO2. The photosynthesis-light response analysis technique is used along with the respiration-temperature response technique to partition NEE into Gross Primary Production (GPP) and Ecosystem Respiration (Re) and to obtain the eco-physiological characteristics of the sites at the field scale. Annual sums of NEE, GPP and Re are then estimated using the fitted response curves with observed radiation and air temperature from a meteorological site in the centre of The Netherlands as drivers. These calculations are carried out for four years (2002–2005). Land use and management histories are not considered. The estimated annual Re for all individual sites is more or less constant per site and the average for all sites amounts to 1390±30 gC m−2 a−1. The narrow uncertainty band (±2%) reflects the small differences in the mean annual air temperature. The mean annual GPP was estimated to be 1325 g C m−2 a−1, and displays a much higher standard deviation, of ±110 gC m−2 a−1 (8%), which reflects the relatively large variation in annual solar radiation. The mean annual NEE amounts to –65±85 gC m−2 a−1. From two sites, four-year records of CO2 flux were available and analyzed (2002–2005). Using the weather record of 2005 with optimizations from the other years, the standard deviation of annual GPP was estimated to be 171–206 gC m−2 a−1 (8–14%), of annual Re 227–247 gC m−2 a−1 (14–16%) and of annual NEE 176–276 gC m−2 a−1. The inter-site standard deviation was higher for GPP and Re, 534 gC m−2 a−1 (37.3%) and 486 gC m−2 a−1 (34.8%), respectively. However, the inter-site standard deviation of NEE was similar to the interannual one, amounting to 207 gC m−2 a−1. Large differences occur due to soil type. The grasslands on organic (peat) soils show a mean net release of CO2 of 220±90 g C m−2 a−1 while the grasslands on mineral (clay and sand) soils show a mean net uptake of CO2 of 90±90 g C m−2 a−1. If a weighing with the fraction of grassland on organic (20%) and mineral soils (80%) is applied, an average NEE of 28 ±90 g C m−2 a−1 is found. The results from the analysis illustrate the need for regionally specific and spatially explicit CO2 emission estimates from grassland.

BACKGROUND: Despite local control now exceeding 90% with image-guided adaptive brachytherapy (IGABT), regional and distant metastases continue to curb survival in locally advanced cervical cancer. As regional lymph nodes often represent first site of metastatic spread, improved nodal control could improve survival. The aim of this study was to examine optimal volume and dose of external beam radiotherapy (EBRT) to maximize regional control including dose contribution from IGABT. MATERIAL AND METHODS: In total 139 patients from the EMBRACE study were analyzed. Individual nodal dose was determined by dose-maps from EBRT and IGABT. All PET/CT scans were re-evaluated and nodal maximal standard uptake value (SUVmax) was determined. Nodal failures were registered to planning scans and related to boosted nodes and treated volume. Relation between SUVmax and nodal control as well as the pattern of regional nodal failure were analyzed. RESULTS: Eighty-four patients were node positive. Nine patients had all metastatic nodes surgically removed. Seventy-five patients had 209 nodes boosted with EBRT. Median nodal boost dose was 62 Gy EQD2 (53-69 Gy EQD2). Median SUVmax was 6 (2-22). No patients had persistent nodal disease, but six patients recurred in a boosted node. SUVmax was significantly higher in nodes that recurred (p = 0.02). However, there was no correlation to nodal dose or volume. Twenty-one patients had a nodal failure including para-aortic nodal (PAN) metastases above the irradiated volume. Nine patients had a PAN-only failure. Patients receiving ≤ 4 cycles of weekly cisplatin had higher risk of nodal failure (p < 0.01). CONCLUSION: Current RT practice provides a high level of control in both boosted nodes and the elective irradiated regional target. However, a high nodal SUVmax is a negative prognostic predictor for nodal control. Attention should be raised to administration of a complete schedule of concurrent chemotherapy as well as treatment of para-aortic nodes.