Laura Tuomikoski

Adaptive radiotherapy strategies for pelvic tumors – a systematic review of clinical implementations

Abstract Introdution: Variation in shape, position and treatment response of both tumor and organs at risk are major challenges for accurate dose delivery in radiotherapy. Adaptive radiotherapy (ART) has been proposed to customize the treatment to these motion/response patterns of the individual patients, but increases workload and thereby challenges clinical implementation. This paper reviews strategies and workflows for clinical and in silico implemented ART for prostate, bladder, gynecological (gyne) and ano-rectal cancers. Material and methods: Initial identification of papers was based on searches in PubMed. For each tumor site, the identified papers were screened independently by two researches for selection of studies describing all processes of an ART workflow: treatment monitoring and evaluation, decision and execution of adaptations. Both brachytherapy and external beam studies were eligible for review. Results: The review consisted of 43 clinical studies and 51 in silico studies. For prostate, 1219 patients were treated with offline re-planning, mainly to adapt prostate motion relative to bony anatomy. For gyne 1155 patients were treated with online brachytherapy re-planning while 25 ano-rectal cancer patients were treated with offline re-planning, all to account for tumor regression detected by magnetic resonance imaging (MRI)/computed tomography (CT). For bladder and gyne, 161 and 64 patients, respectively, were treated with library-based online plan selection to account for target volume and shape variations. The studies reported sparing of rectum (prostate and bladder cancer), bladder (ano-rectal cancer) and bowel cavity (gyne and bladder cancer) as compared to non-ART. Conclusion: Implementations of ART were dominated by offline re-planning and online brachytherapy re-planning strategies, although recently online plan selection workflows have increased with the availability of cone-beam CT. Advantageous dosimetric and outcome patterns using ART was documented by the studies of this review. Despite this, clinical implementations were scarce due to challenges in target/organ re-contouring and suboptimal patient selection in the ART workflows.

Absorbed doses behind bones with MR image‐based dose calculations for radiotherapy treatment planning

PURPOSE Magnetic resonance (MR) images are used increasingly in external radiotherapy target delineation because of their superior soft tissue contrast compared to computed tomography (CT) images. Nevertheless, radiotherapy treatment planning has traditionally been based on the use of CT images, due to the restrictive features of MR images such as lack of electron density information. This research aimed to measure absorbed radiation doses in material behind different bone parts, and to evaluate dose calculation errors in two pseudo-CT images; first, by assuming a single electron density value for the bones, and second, by converting the electron density values inside bones from T(1)∕T(2)∗-weighted MR image intensity values. METHODS A dedicated phantom was constructed using fresh deer bones and gelatine. The effect of different bone parts to the absorbed dose behind them was investigated with a single open field at 6 and 15 MV, and measuring clinically detectable dose deviations by an ionization chamber matrix. Dose calculation deviations in a conversion-based pseudo-CT image and in a bulk density pseudo-CT image, where the relative electron density to water for the bones was set as 1.3, were quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms. RESULTS The calculations revealed that the applied bulk density pseudo-CT image causes deviations up to 2.7% (6 MV) and 2.0% (15 MV) to the dose behind the examined bones. The corresponding values in the conversion-based pseudo-CT image were 1.3% (6 MV) and 1.0% (15 MV). The examinations illustrated that the representation of the heterogeneous femoral bone (cortex denser compared to core) by using a bulk density for the whole bone causes dose deviations up to 2% both behind the bone edge and the middle part of the bone (diameter <2.5 cm), but in the opposite directions. The measured doses and the calculated ones in the standard CT image were within 0.4% (through gelatine only) and 0.9% (behind bones). CONCLUSIONS This study indicates that the decrease in absorbed dose is not dependent on the bone diameter with all types of bones. Thus, performing dose calculation in a pseudo-CT image by assuming a single electron density value for the bones can lead to a substantial misrepresentation of the dose distribution profile. This work showed that dose calculation accuracy can be improved by using a pseudo-CT image in which the electron density values have been converted from the MR image intensity values inside bones.

Implementation of adaptive radiation therapy for urinary bladder carcinoma: Imaging, planning and image guidance

Abstract Background. Adaptive radiation therapy (ART) for urinary bladder cancer has emerged as a promising alternative to conventional RT with potential to minimize radiation-induced toxicity to healthy tissues. In this work we have studied bladder volume variations and their effect on healthy bladder dose sparing and intrafractional margins, in order to refine our ART strategy. Material and methods. An online ART treatment strategy was followed for five patients with urinary bladder cancer with the tumors demarcated using Lipiodol®. A library of 3–4 predefined treatment plans for each patient was created based on four successive computed tomography (CT) scans. Cone beam CT (CBCT) images were acquired before each treatment fraction and after the treatment at least weekly. In partial bladder treatment the sparing of the healthy part of the bladder was investigated. The bladder wall displacements due to bladder filling were determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment planning CT scans. An ellipsoidal model was applied in order to find the theoretical maximum values for the bladder wall displacements. Moreover, the actual bladder filling rate during treatment was evaluated using the CBCT images. Results. In partial bladder treatment the volume of the bladder receiving high absorbed doses was generally smaller with a full than empty bladder. The estimation of the bladder volume and the upper limit for the intrafractional movement of the bladder wall could be represented with an ellipsoidal model with a reasonable accuracy. Observed maximum growth of bladder dimensions was less than 10 mm in all three orthogonal directions during 15 minute interval. Conclusion. The use of Lipiodol contrast agent enables partial bladder treatment with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder model can be used for the estimation of the bladder volume changes and the upper limit of the bladder wall movement during the treatment fraction.

Influence of MRI-based bone outline definition errors on external radiotherapy dose calculation accuracy in heterogeneous pseudo-CT images of prostate cancer patients

Abstract Background. This work evaluates influences of susceptibility-induced bone outline shift and perturbations, and bone segmentation errors on external radiotherapy dose calculation accuracy in magnetic resonance imaging (MRI)-based pseudo-computed tomography (CT) images of the male pelvis. Material and methods. T1/T2*-weighted fast gradient echo, T1-weighted spin echo and T2-weighted fast spin echo images were used in bone detection investigation. Bone edge location and bone diameter in MRI were evaluated by comparing those in the images with actual physical measurements of fresh deer bones positioned in a gelatine phantom. Dose calculation accuracy in pseudo-CT images was investigated for 15 prostate cancer patients. Bone outlines in T1/T2*-weighted images were contoured and additional segmentation errors were simulated by expanding and contracting the bone contours with 1 mm spacing. Heterogeneous pseudo-CT images were constructed by adopting a technique transforming the MRI intensity values into Hounsfield units with separate conversion models within and outside of bone segment. Results. Bone edges and diameter in the phantom were illustrated correctly within a 1 mm-pixel size in MRI. Each 1 mm-sized systematic error in bone segment resulted in roughly 0.4% change to the prostate dose level in the pseudo-CT images. The prostate average (range) dose levels in pseudo-CT images with additional systematic bone segmentation errors of −2 mm, 0 mm and 2 mm were 0.5% (−0.5–1.4%), −0.2% (−1.0–0.7%), and −0.9% (−1.8–0.0%) compared to those in CT images, respectively, in volumetric modulated arc therapy treatment plans calculated by Monte Carlo algorithm. Conclusions. Susceptibility-induced bone outline shift and perturbations do not result in substantial uncertainty for MRI-based dose calculation. Dose consistency of 2% can be achieved reliably for the prostate if heterogeneous pseudo-CT images are constructed with ≤± 2 mm systematic error in bone segment.

A comparison between two clinically applied plan library strategies in adaptive radiotherapy of bladder cancer

BACKGROUND AND PURPOSE The predominant approach to clinically applied adaptive radiotherapy (ART) for bladder cancer is daily selection of treatment plans from a plan library. In this study we have compared two clinical strategies for creating multiple planning target volumes (PTV) for ART of bladder cancer. MATERIAL AND METHODS Online ART delivering 60 Gy in 30 fractions to the whole bladder was simulated for ten patients using two methods of creating plan libraries. In the RepeatCT method four planning CT scans were acquired at 15-min intervals, generating four CTVs with different bladder volumes. In the RepeatCBCT method one planning CT and four daily cone-beam CT images were combined using Boolean operators to form three composite CTVs. Plan selection rates and PTV volumes were evaluated, with the selected volumes averaged across 30 treatment fractions (PTV(mean)). RESULTS The PTV(mean) volume was on average 80 cm(3) smaller (p<0.001) in the RepeatCT method than in the RepeatCBCT method. Compared to the non-adaptive treatment, the PTV(mean) was reduced by 46% (range 33-53%, RepeatCT) and 36% (range 27-44%, RepeatCBCT). CONCLUSIONS Both methods reduced the PTV(mean) volume compared to the non-adaptive approach, but the reduction was larger using the strategy with repeat planning CT imaging. However, the strategy with combined CT and repeat CBCT imaging produced a more adequate range of PTV volumes.

Toward a more patient-specific model of post-radiotherapy saliva secretion for head and neck cancer patients

ABSTRACT Background. Reduction of saliva secretion is a common side effect following radiotherapy (RT) for cancer of the head and neck region. The aim of this study is to predict the post-RT salivary function for individual patients prior to treatment and to recognise possible differences in individual radiosensitivity. Material and methods. A predictive model for post-RT salivary function was validated for 64 head and neck cancer patients. The input parameters for the model were salivary excretion fraction (sEF) measured by 99mTc-pertechnetate scintigraphy, total stimulated salivary flow and mean absorbed dose for the major salivary glands. SEF values after RT relative to the baseline before RT (rEF) were compared among the patients using the distance ΔrEF between single gland rEF and the corresponding expected value at the dose response curve. Results. A significant correlation (R = 0.86, p = 0.018) was found between the modelled and the measured values of stimulated salivary flow six months after RT. The average prediction error for the saliva flow rate was 6 ml/15 min. A linear relationship between ΔrEF for the left and the right parotid glands was observed both six (R = 0.53) and 12 (R = 0.79) months after RT. The average of absolute values of ΔrEF was 0.20 for parotid glands and 0.22 for submandibular glands. Conclusions. The salivary flow model was validated for 64 patients. The results imply, that one explanation for the discrepancies between the predicted and the measured salivary flow rate values and the common variations found in ΔrEF for the parotid glands may be differences in patients’ individual response to radiation. However, quantitative extraction of individual radiosensitivity would require further studies in order to take it into account in predictive models.

Diffusion-weighted magnetic resonance imaging for evaluation of salivary gland function in head and neck cancer patients treated with intensity-modulated radiotherapy

BACKGROUND AND PURPOSES Permanent xerostomia as a result of radiation-induced salivary gland damage remains a common side effect of radiotherapy (RT) of the head and neck. The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing the post-RT salivary gland function in patients with head and neck cancer (HNC). MATERIALS AND METHODS In this prospective study, 20 HNC patients scheduled for bilateral neck chemoradiotherapy (CRT) with weekly cisplatin went through diffusion-weighted magnetic resonance imaging (DW-MRI) and salivary gland scintigraphy (SGS) prior to and at a mean of six months after completing the treatment. The changes in apparent diffusion coefficient (ADC) before and after treatment were compared with ejection fraction (EF) measured with SGS and the radiation dose absorbed by the salivary glands. RESULTS As a result of gustatory stimulation with ascorbic acid, the ADC showed a biphasic response with an initial increase and subsequent decrease. This pattern was seen both before and after RT. Post-RT ADC increased as a function of RT dose absorbed by the salivary glands. A moderate statistical correlation between pre- and post-RT ADCs at rest and EF measured with SGS was found. CONCLUSIONS DW-MRI seems a promising tool for detection of physiological and functional changes in major salivary glands after RT.

Marginal miss or radioresistance? The pattern of local recurrence after operation and 3D planned radiation treatment in soft tissue sarcoma of the extremities and the limb girdles; an analysis based on image fusion

Abstract Background. Most local recurrences have developed in the clinical target volume in previously published series after combined modality treatment for soft tissue sarcoma. However, marginal misses were seen in almost 20% of the patients. The aim of the present study was to determine the location of the recurrence and the total dose at the centre point of the local recurrence for future radiation therapy planning. Material and methods. We included only patients with images in digital form, during 1999–2006 (n = 17), treated for soft tissue sarcoma with combined surgical therapy and radiotherapy at Helsinki University Central Hospital. Image fusion was used to determine the location of the recurrence in relation to radiation therapy target. Results. In the present study utilising digital image fusion, in patients with 3D CT-based radiation treatment planning the risk of marginal miss was low as only one patient of 17 relapsed outside the target. Estimated mean radiation dose at the site of local recurrence was 49.1 Gy in patients with positive margins and 48.1 Gy in patients with negative margins. Conclusion. The risk of marginal miss in soft tissue sarcoma is low after modern 3D planned radiation treatment combined with surgery. More generous use of boost might improve in-target local control.

SP-0392: Overview of clinical practice of ART for pelvic tumours

S183 ______________________________________________________________________________________________________ The project BioQuaRT has been funded within the European Metrology Research programme EMRP. The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union. The project MITRA has been funded by the Italian Istituto Nazionale di Ficica Nucleare (INFN). References: [1] S. Pszona et al., Nucl. Instrum. and Meth. A 447, 601 (2000) [2] V.Conte et al., New J. Phys. 14, 093010, (2012) [3] G. Garty et al., Radiat. Prot. Dosim. 99, 325 (2002) [4] B. Grosswendt, Radiat. Prot. Dosim. 110, 789 (2004) [5] H Palmans, H Rabus, et al., Br. J. Radiol. 87: 20140392 (2015) [6] http://www.ptb.de/emrp/bioquart.html [7] http://www.lnl.infn.it/~microdos/MITRA.html [8] D. Moro et al., INFN-LNL-Report 239, 178-179 (2013) [9] G. Hilgers et al., INFN-LNL-Report 240, 129-130 (2014) [10] G. Hilgers et al., HIL Annual Report 2013, 46-48 (2014) [11] T. Friedrich et al., Journal of Radiation Research 54, 494-514 (2013) [12] https://www.gsi.de/bio-pide

SU‐E‐J‐54: Bone Detection in MR Images and Absorbed Dose in a Material Behind Bones in Radiotherapy

PURPOSE To determine whether bones could be localized accurately by using MR images only in radiotherapy treatment planning. Furthermore, to measure absorbed dose in a material behind different parts of the bone, and to evaluate dose calculation error in a pseudo-CT image by assuming a single electron density for the bones. METHODS A dedicated phantom was constructed using fresh deer bones and gelatine. The accuracy of the bone edge location and the bone diameter in MR images were evaluated by comparing those in the images with the actual measures. The absorbed dose behind the bones was measured by a matrix detector at 6 and 15 MV. Thedose calculation error in the bulk density pseudo-CT image was quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms (TPSs: Xio 4.60 and Monaco 3.00, Elekta CMS Software). RESULTS The examination of bone position revealed that the bones can be localized within a 1-mm-pixel-size in the MR images. The measured dose behind less than 2.5-cm-thick femur indicated that the absorbed dose behind the middle part of the bone is approximately one percentage unit (6 MV: 1.3%, 15 MV: 0.9%) smallerthan that of the physically narrower bone edge. The calculations illustrated that the bulk density pseudo-CT image used causes errors up to nearly 2% to the dose behind the middle part, but also, the edge of the femur. CONCLUSIONS This research ascertains that the bone localization is not a restrictive issue for radiotherapy treatment planning by using MR imageonly. The work indicates also that the decrease in absorbed dose is not necessarily dependent on the diameter of the bone. Future research shouldinvestigate the generation of more complex pseudo-CT images and the dosecalculations by using these. Supported by Elekta.