Purpose or Objective: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit.However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy.In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy.Material and Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection.The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact.We developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols.The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma.Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm.This was reduced to 2.8 mm when both techniques were employed.Tumors were not visualized in clinical CBCT images of human subjects.Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects.Different patients were found to require different contrast injection protocols to maximize tumor contrast. Conclusion:Localization of the tumor during treatment is the weak link in IGRT for liver.Respiration managed contrast enhanced CBCT provides a possible solution.Simulation tools for optimal contrast injection, recommended margins for interfraction motion and additional benefits from patient specific tracer kinetics determined from DCE-CT are presented.

The purpose of this study was to quantify the impact of inter-fraction modifications of bladder during RT of prostate cancer on bladder dose surface maps (DSM). Eighteen patients treated with daily image-guided Tomotherapy and moderate hypofractionation (70-72.8Gy at 2.5-2.6Gy/fr in 28 fractions and full bladder) were considered. Bladder contours were delineated on co-registered daily Megavoltage CT (MVCT) by a single observer and copied on the planning CT to generate dose-volume/surface histograms (DVH/DSH) and bladder DSMs. Discrepancies between planned and daily absorbed doses were analyzed through the average of individual systematic errors, the population systematic errors and the population random errors for the DVH/DSHs and DSMs. In total, 477 DVH/DSH and 472 DSM were available. DSH and DVH showed small population systematic errors of absolute surfaces (<3.4cm(2)) and volumes (<8.4cm(3)) at the highest doses. The dose to the posterior bladder base assessed on DSMs showed a mean systematic error below 1Gy, with population systematic and random errors within 4 and 3Gy, respectively. The region surrounding this area shows higher mean systematic errors (1-3Gy), population systematic (8-11Gy) and random (5-7Gy) errors. In conclusion, DVH/DSH and DSMs are quite stable with respect to inter-fraction variations in the high-dose region, within about 2cm from bladder base. Larger systematic variations occur in the anterior portion and cranially 2.5-3.5cm from the base. Results suggest that dose predictors related to the high dose area (including the trigone dose) are likely to be sufficiently reliable with respect to the expected variations due to variable bladder filling.

A prospective multi-centric study (DUE01) was activated in 2010 with the aim to develop predictive models of urinary toxicity and erectile dysfunction after high dose radiotherapy (RT) for prostate cancer. Aim of current analysis was to localize dose regions on bladder surface significantly correlated with acute urinary toxicity, defined by an IPSS > = 15 at RT end. Data of 264 patients (pts) were available; a previous analysis showed correlation between bladder dose-surface/volume histograms (DSH/DVH) and acute toxicity in the group treated with hypo-fractionation (HYPO, n = 124). Current analysis was focused on a homogeneous group of 58 pts treated with Tomotherapy and HYPO (2.5-2.65 Gy/fx, 70-74 Gy) in two Institutes with none/mild symptoms before RT (IPSS < 15). Normalized dose-surface maps (DSMs) of all pts were generated with dedicated software by unfolding the bladder: its contour was cut anteriorly at the points intersecting the sagittal plane passing through its center of mass. DSMs had a resolution of 1mm (cranial-caudal direction), were normalized in the axial direction and were aligned at the bladder base, at the posterior central point, generating a common frame for all pts. Average DSMs of pts with and without toxicity and the corresponding dose difference map (DDM) were calculated. Pixel-by-pixel two-sided t-tests were performed to compare DSMs of pts with/without toxicity: the resulting p-values map was used for identifying the regions better discriminating between pts with/without toxicity. Twenty-two out of 58 pts (38%) experienced acute toxicity (IPSS ≥ 15) at RT end. As expected, average DSMs showed larger areas covered by intermediate-high doses (50-70 Gy) in pts with toxicity. DDM showed larger differences in the anterior area of bladder surface, from its base up to about 20 mm in cranial direction (> 5 Gy), while no significant differences were found for the posterior surface, included in the high-dose region. The areas showing the lowest p-values (p < 0.05) were found at 5-10 mm from bladder base, in the anterior-lateral bladder surface. Based on this result, the % of bladder circumference included in the high-intermediate doses (50-70 Gy, L%50-70 Gy) in the slices at 5-10 mm from bladder base had a higher power in discriminating between pts with and without toxicity: the average L%50 Gy and L%70 Gy at 7 mm from the base were 80% vs 68% and 36% vs 31% for pts with/without toxicity, respectively. DSMs allowed the identification of specific regions of bladder whose sparing seems to be correlated with a decreased risk of patient-reported acute urinary toxicity in a homogeneous group of pts treated with HYPO: the sparing of the anterior surface of bladder in the region near the bladder base might have the potential of significantly reducing toxicity. Further investigation is warranted to confirm/extend these findings to late symptoms.

S4702nd ESTRO Forum 2013 0.43±0.13cm and 0.47±0.16cm were observed for the GTV and parotids respectively.The comparison between planned, delivered and adaptive dose has been summarized in Table 1. Conclusions:The results obtained using SA software are encouraging.The accuracy of SA, for different quality images (KVCT and MVCT), is good, allowing a saving in process time.Furthermore, the SA tool, combined with an in house software, could enable the estimation of the cumulative dose actually delivered to the patients due to anatomical changes.However, the not optimal quality of MVCT images could limit our observations, therefore further analysis are needed to confirm these preliminary results.

Introduction: Treatment plan evaluation requires knowledge of the effect of the plan, not only on the intended target, but also the surrounding normal tissues that are unavoidably irradiated. Recent literature has provided estimations of tolerance doses and proposed dose-volume constraints for many of the organs at risk. However, very few of these recommendations have been independently validated. This study details how constraints proposed for the rectum were tested using data from the RT01 randomised prostate radiotherapy trial. Method: An independent validation of the rectal dose-volume constraints used in the CHHiP trial and proposed recently by Fiorino et al. was performed. The constraints were applied retrospectively to the treatment plans collected from the RT01 trial. Odds ratios (OR) were calculated to compare the reported incidence of specific late rectal toxicity end points in the group of patients whose treatment plan met a specified dose-volume constraint compared to the group of patients who failed that constraint. Results: Statistically significant ORs were observed for every constraint tested (except 75 Gy) for at least one clinical end point. For the CHHiP constraints between 60 and 70 Gy, the ORs calculated for rectal bleeding (RMH score defined in protocol) exceeded 2.5 (P!0.02). Similarly the ORs for CHHiP constraints between 30 and 65 Gy exceeded 2.4 (P!0.021) for urgency (UCLA PCI). The Fiorino constraints between 40 and 60 Gy resulted in ORs O2 (P!0.02) for loose stools (UCLA PCI) Conclusion: Implementing rectal dose-volume constraints from 30 Gy up to the prescription dose will result in a decrease in the incidence of late rectal toxicity. Constraints for doses as low as 30 Gy were statistically significant, further challenging the concept that the rectum is a serial structure where the maximum dose to the organ is the only consideration.

As revealed by previous theoretical studies, targeted radionuclide therapy (TRT) that relies on a single beta-emitting radioisotope is likely to be inappropriate for clinical scenarios such as disseminated malignancy. For a patient with a vast number of tumours and metastases of largely differing sizes a high level of therapeutical efficiency might be achieved only for a restricted range of tumour sizes. This is due to the limited range of beta-electrons in human tissue, essentially causing the therapeutical impact to vary tremendously with tumour size. The dependence of curability on the tumour dimension is expected to be significantly altered if a radionuclide cocktail, consisting of a long-range and a short-range beta-emitter, such as (32)P and (33)P, is involved in the treatment. In this study, a radiation transport simulation was performed, using the MCNP4c2 Monte Carlo code, in order to investigate the relationship between tumour control probability (TCP) and tumour size, associated with concurrent use of (32)P and (33)P. Two different models of intratumoural distribution of cumulated activity were taken into account. One simulated an ideal radionuclide uptake in tumour tissue and the other referred to a limited radiotracer penetration. The results were examined in comparison to tumours targeted with pure (32)P, (33)P and (131)I. For both uptake scenarios a considerable reduction of the overall variation of TCP and thus an increasing chance of achieving tumour cure was observed for tumour sizes ranging from microscopic dimensions up to macroscopic diameters, if the targeted radionuclide treatment relies on a (32)P/(33)P cocktail. It was revealed that particular attention has to be given to the ratio of the (32)P and (33)P specific cumulated activities (SCA) in the tumour, since this is a significant determinant of the resulting behaviour of tumour control probability as the tumour diameter varies. This study suggests that a 32P/33P approach is more applicable to diseases that involve a variety of tumours and metastases differing in size.

Purpose: Application of an image guided 4D Monte Carlo framework to the evaluation of intra/inter fraction motion effects between patient organ‐movement and dynamic delivery effects Materials & Methods: An IGMC toolkit that accounts for time‐dependent geometries of organ motion and dynamic delivery and provides accurate dosimetry was developed for lung cancer patients. Fluence calculation for VARIAN‐2100C/D photon accelerator is performed with EGSnrc and for patient dose calculation we use dose‐planning‐method. The time dependent beam delivery information is obtained from the treatment‐planning program in the form of MLC leaf‐sequencing files, while the organ motion pattern was obtained with the use of RPM signal and 4D‐CT. A voxel displacement map is used to quantify the motion of the organ in the voxelized geometry. The study was performed for lung patient for several breathing phases. The data analysis was performed with the freely available package VODCA. Results: Differences between the conventional CORVUS dose plan and the Monte Carlo dose results suggest that Monte Carlo dose calculation is vital for assessing effects in lung tissue. For the free breathing CT, CORVUS was under‐dosing the lung‐tumor by approximately 3Gy. When accounting for temporal effects, comparison between IGMC dose distributions for free breathing, inhale and exhale phases, show that dose coverage of the primary/secondary tumors was significant worse in the inhale phase relative to the exhale/free‐breathing phases. For inhale phase, 5–10% of the volume was receiving 10Gy less than in exhale or free‐breathing phases, leading to large cold spots inside the tumor. This is mainly due to the motion of the diaphragm, which subsequently moves the tumor in the superior‐inferior by more than 2 cm. Conclusions: Image guided 4DMC methods can significantly improve the planning of lung tumor treatments by accurately modeling the motion of the tumors and large heterogeneity in the tumor region. Supported NIH/NCI‐R01/CA111590.