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Purpose This study aimed to quantify the coverage probability for esophageal cancer radiotherapy as a function of a preset margin for online MR-guided and (CB)CT-guided radiotherapy. Methods Thirty esophageal cancer patients underwent six T2-weighted MRI scans, 1 prior to treatment and 5 during neoadjuvant chemoradiotherapy at weekly intervals. Gross tumor volume (GTV) and clinical target volume (CTV) were delineated on each individual scan. Follow-up scans were rigidly aligned to the bony anatomy and to the clinical target volume itself, mimicking two online set-up correction strategies: a conventional CBCT-guided set-up and a MR-guided set-up, respectively. Geometric coverage probability of the propagated CTVs was assessed for both set-up strategies by expanding the reference CTV with an isotropic margin varying from 0 mm to 15 mm with an increment of 1 mm. Results A margin of 10 mm could resolve the interfractional changes for 118 out of the 132 (89%) analyzed fractions when applying a bone-match registration, whereas the CTV was adequately covered in 123 (93%) fractions when the registration was directly performed at the CTV itself (soft-tissue registration). Closer analyses revealed that target coverage violation predominantly occurred for distal tumors near the junction and into the cardia. Conclusion Online MR-guided soft-tissue registration protocols exhibited modest improvements of the geometric target coverage probability as compared to online CBCT-guided bone match protocols. Therefore, highly conformal target irradiation using online MR-guidance can only be achieved by implementing on-table adaptive workflows where new treatment plans are daily generated based on the anatomy of the day.

Background: Neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer causes tumor regression during treatment. Tumor regression can induce changes in the thoracic anatomy, with smaller target vol...

Purpose To assess the dosimetric benefits of online MR-guided radiotherapy (MRgRT) for esophageal cancer patients and to assess how these benefits could be translated into a local boosting strategy to improve future outcomes. Methods Twenty-nine patients were in-silico treated with both a MRgRT regimen and a conventional image guided radiotherapy (IGRT) regimen using dose warping techniques. Here, the inter and intrafractional changes that occur over the course of treatment (as derived from 5 MRI scans that were acquired weekly during treatment) were incorporated to assess the total accumulated dose for each regimen. Results A significant reduction in dose to the organs-at-risk (OARs) was observed for all dose–volume-histogram (DVH) parameters for the MRgRT regimen without concessions to target coverage compared to the IGRT regimen. The mean lung dose was reduced by 28%, from 7.9 to 5.7 Gy respectively and V20Gy of the lungs was reduced by 55% (6.3–2.8%). A reduction of 24% was seen in mean heart dose (14.8–11.2 Gy), while the V25Gy of the heart was decreased by 53% (14.3–6.7%) and the V40Gy of the heart was decreased by 69% (3.9–1.2%). In addition, MRgRT dose escalation regimens with a boost up to 66% of the prescription dose to the primary tumor yielded approximately the same dose levels to the OARs as from the conventional IGRT regimen. Conclusion This study revealed that MRgRT for esophageal cancer has the potential to significantly reduce the dose to heart and lungs. In addition, online high precision targeting of the primary tumor opens new perspectives for local boosting strategies to improve outcome of the local management of this disease.

Purpose This study assessed the margins needed to cover tumor intrafraction motion during an MR-guided radiotherapy (MRgRT) dose-escalation strategy in intermediate risk rectal cancer. Methods Fifteen patients with rectal cancer were treated with neoadjuvant short-course radiotherapy, 5x5 Gy, according to an online adaptive workflow on a 1.5 T MR-linac. Per patient, 26 3D T2 weighted MRIs were made; one reference scan preceding treatment and five scans per treatment fraction. The primary tumor was delineated on each scan as gross tumor volume (GTV). Target coverage margins were assessed by isotropically expanding the reference GTV until more than 95% of the voxels of the sequential GTVs were covered. A margin with a coverage probability threshold of 90% was defined as adequate. Intra- and interfraction margins to cope with the movement of the GTV in the period between scans were calculated to indicate the target volume margins. Furthermore, the margin needed to cover GTV movement was calculated for different time intervals. Results The required margins to cover inter- and intrafraction GTV motion were 17 mm and 6 mm, respectively. Analysis based on time intervals between scans showed smaller margins were needed for adequate GTV coverage as time intervals became shorter, with a 4 mm margin required for a procedure of 15 min or less. Conclusion The shorter the treatment time, the smaller the margins needed to cover for the GTV movement during an online adaptive MRgRT dose-escalation strategy for intermediate risk rectal cancer. When time intervals between replanning and the end of dose delivery could be reduced to 15 min, a 4 mm margin would allow adequate target coverage.

Purpose This study aimed to assess the smallest clinical target volume (CTV) to planned target volume (PTV) margins for esophageal cancer radiotherapy using daily online registration to the bony anatomy that yield full dosimetric coverage over the course of treatment. Methods 29 esophageal cancer patients underwent six T2-weighted MRI scans at weekly intervals. An online bone-match image-guided radiotherapy treatment of five fractions was simulated for each patient. Multiple conformal treatment plans with increasing margins around the CTV were created for each patient. Then, the dose was warped to obtain an accumulated dose per simulated fraction. Full target coverage by 95% of the prescribed dose was assessed as a function of margin expansion in six directions. If target coverage in a single direction was accomplished, then the respective margin remained fixed for the subsequent dose plans. Margins in uncovered directions were increased in a new dose plan until full target coverage was achieved. Results The smallest set of CTV-to-PTV margins that yielded full dosimetric CTV coverage was 8 mm in posterior and right direction, 9 mm in anterior and cranial direction and 10 mm in left and caudal direction for 27 out of 29 patients. In two patients the curvature of the esophagus considerably changed between fractions, which required a 17 and 23 mm margin in right direction. Conclusion Accumulated dose analysis revealed that CTV-to-PTV treatment margins of 8, 9 and 10 mm in posterior & right, anterior & cranial and left & caudal direction, respectively, are sufficient to account for interfraction tumor variations over the course of treatment when applying a daily online bone match. However, two patients with extreme esophageal interfraction motion were insufficiently covered with these margins and were identified as patients requiring replanning to achieve full target coverage.

Objective This study was conducted in order to determine the optimal timing of diffusion-weighted magnetic resonance imaging (DW-MRI) for prediction of pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. Methods Patients with esophageal adenocarcinoma or squamous cell carcinoma who planned to undergo nCRT followed by surgery were enrolled in this prospective study. Patients underwent six DW-MRI scans: one baseline scan before the start of nCRT and weekly scans during 5 weeks of nCRT. Relative changes in mean apparent diffusion coefficient (ADC) values between the baseline scans and the scans during nCRT (ΔADC(%)) were compared between pathologic complete responders (pCR) and non-pCR (tumor regression grades 2–5). The discriminative ability of ΔADC(%) was determined based on the c-statistic. Results A total of 24 patients with 142 DW-MRI scans were included. pCR was observed in seven patients (29%). ΔADC(%) from baseline to week 2 was significantly higher in patients with pCR versus non-pCR (median [IQR], 36% [30%, 41%] for pCR versus 16% [14%, 29%] for non-pCR, p = 0.004). The ΔADC(%) of the second week in combination with histology resulted in the highest c-statistic for the prediction of pCR versus non-pCR (0.87). The c-statistic of this model increased to 0.97 after additional exclusion of patients with a small tumor volume (n = 3) and tumor histology of the resection specimen other than adenocarcinoma or squamous cell carcinoma (n = 1). Conclusion The relative change in tumor ADC (ΔADC(%)) during the first 2 weeks of nCRT is the most predictive for pathologic complete response to nCRT in esophageal cancer patients. Key Points • DW-MRI during the second week of neoadjuvant chemoradiotherapy is most predictive for pathologic complete response in esophageal cancer. • A model including ΔADCweek 2was able to discriminate between pathologic complete responders and non-pathologic complete responders in 87%. • Improvements in future MRI studies for esophageal cancer may be obtained by incorporating motion management techniques.

Aim To assess changes in tumor volume during neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer with weekly MRI. Background & Methods Neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer can cause tumor regression, however data on the magnitude of the volumetric changes during nCRT are scarce. Tumor regression can induce changes in the thoracic anatomy, with smaller target volumes and displacement of organs at risk (OARs) in close proximity to the tumor target as a result. Adaptation of the radiotherapy treatment plan according to volumetric changes during treatment might reduce dose to the OARs while maintaining adequate target coverage. In the current study patients with histologically proven esophageal cancer undergoing nCRT for esophageal cancer underwent 6 MRI scans: 1 scan prior to nCRT and 5 weekly scans during treatment. Tumors were delineated on T2 weighted images by two gastrointestinal radiation oncologists and volumetric changes were assessed. Results A total of 164 MRI scans of 28 patients were included. The mean tumor volume at baseline was 45ml (SD ± 23ml). Tumor volume regression started after the first week of nCRT and appeared to be a linear process with significant declines in tumor volume every subsequent week (p-values Conclusion This study shows a significant linear decrease in tumor volume after the first week of nCRT for esophageal cancer on weekly MRI. These findings suggest the possible benefit of radiotherapy plan adaptations during nCRT.

Herbivores are reported to slow down as well as enhance nutrient cycling in grasslands. These conflicting results may be explained by differences in herbivore type. In this study we focus on herbivore body size as a factor that causes differences in herbivore effects on N cycling. We used an exclosure set-up in a floodplain grassland grazed by cattle, rabbits and common voles, where we subsequently excluded cattle and rabbits. Exclusion of cattle lead to an increase in vole numbers and a 1.5-fold increase in net annual N mineralization at similar herbivore densities (corrected to metabolic weight). Timing and height of the mineralization peak in spring was the same in all treatments, but mineralization in the vole-grazed treatment showed a peak in autumn, when mineralization had already declined under cattle grazing. This mineralization peak in autumn coincides with a peak in vole density and high levels of N input through vole faeces at a fine-scale distribution, whereas under cattle grazing only a few patches receive all N and most experience net nutrient removal. The other parameters that we measured, which include potential N mineralization rates measured under standardized laboratory conditions and soil parameters, plant biomass and plant nutrient content measured in the field, were the same for all three grazing treatments and could therefore not cause the observed difference. When cows were excluded, more litter accumulated in the vegetation. The formation of this litter layer may have added to the higher mineralization rates under vole grazing, through enhanced nutrient return through litter or through modification of microclimate. We conclude that different-sized herbivores have different effects on N cycling within the same habitat. Exclusion of large herbivores resulted in increased N annual mineralization under small herbivore grazing.