Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical ...routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs.
Radiation oncologists at four Danish cancer centres delineated high, intermediate and elective dose CTVs (CTV1, CTV2 and CTV3, respectively) in a patient-case template (stage IV squamous cell carcinoma of the oropharynx), first using mainly anatomical margins (original standard) and then using concentric geometric expansion (new standard). Each centre made a dummy-run radiotherapy plan based on the delineated CTVs. The difference between the CTV contours and the radiotherapy plans was evaluated across the centres.
Anatomy-based contours were significantly more heterogenous and showed larger volume differences between centres than geometric margins. Dice similarity coefficient increased by 0.29 and mean surface distance decreased by 4mm for CTV1. Use of consistent CTV volumes resulted in more consistent irradiated volumes between centres.
Introduction of geometric margins resulted in more uniform CTV1 and CTV2 delineation. Geometric CTV expansion was easier, left less room for misinterpretation, and resulted in more uniform treatment plans with similar irradiated high and intermediate dose volumes across all centres.
Imaging hypoxia to improve radiotherapy outcome Horsman, Michael R; Mortensen, Lise Saksø; Petersen, Jørgen B ...
Nature reviews. Clinical oncology,
12/2012, Letnik:
9, Številka:
12
Journal Article
Recenzirano
Reduced oxygen levels (hypoxia) is one of the most important factors influencing clinical outcome after radiotherapy. This is primarily because hypoxic cells are resistant to radiation treatment; ...hence, the greater the number of clonogenic cancer stem cells that exist under hypoxia, the lower the local tumour control. Reduced local control will influence overall survival, as may the hypoxic conditions by increasing malignant progression; however, to fight hypoxia, we should first be able to see it. We need noninvasive approaches that can accurately and reliably image hypoxia in tumours, especially using techniques that are routinely available in the clinic, such as PET, MRI and CT. All these imaging methods are already under clinical evaluation in this context. Such data should allow us to identify those patients on an individual basis who have hypoxic tumours and, thus, at the very least should receive some form of hypoxic modifier in conjunction with radiotherapy. Alternatively, the radiation dose could be either increased to the whole tumour or, if the imaging is accurate enough, only to the hypoxic subvolumes. The aim of this Review is to critically assess the potential use of imaging to help improve clinical outcome to radiotherapy.
Purpose:
In this study the authors present a new method for estimation of proton stopping power ratios (SPRs) using dual energy CT (DECT), which is robust toward CT noise. The authors propose a ...parametrization for SPR based directly on the CT numbers in a DECT image set, whereby the intermediate steps of estimating the relative electron density, ρe
, and mean excitation energy, I, are avoided.
Methods:
The SPR parametrization proposed in this study is a purely empirical fit based on the theoretical SPR values for a list of 34 reference human tissues. To investigate the SPR estimation made with this new method the authors performed a calibration and an evaluation with the method. The authors initially calculated CT numbers using CT energy spectrum characterization parameters obtained from calibration based on a Gammex 467 electron density calibration phantom. These CT numbers were fitted to the theoretical SPR for the reference human tissues using the new SPR parametrization presented in this study. The method was evaluated based on theoretical CT numbers for the reference human tissues. The root-mean-square error (RMSE) of the SPR and the proton range error from the continuous slowing down approximation were calculated for the reference human tissues. To test the stability of the parametrization the authors varied the density and elemental composition of the reference human tissues and calculated their new SPR estimates. Further, clinically realistic noise values were added to the theoretical CT numbers to investigate how CT noise affected the estimated water equivalent range through 10 cm of the reference human tissues. All results for the new SPR parametrization were compared to the results obtained using two previously published DECT methods for SPR estimation. Comparisons were also made to a single energy CT (SECT) SPR estimation method, the stoichiometric method, which is commonly used in clinical practise for proton therapy treatment planning.
Results:
The RMSE for the SPR of the 34 reference human tissues using the new SPR parametrization was 0.12%, compared to 0.19% and 0.28% for the two previously published DECT methods. The SPR parametrization was more stable toward variations of the calcium content in the reference human tissues, but less stable toward density variations and changes to the hydrogen content than the two other DECT methods. When adding noise to the theoretical CT numbers the SPR parametrization gave the lowest water equivalent range errors of all four tested SPR estimation methods (maximum error reduced to 0.4 mm). In all cases tested, the new SPR parametrization outperformed the SECT stoichiometric method.
Conclusions:
The new SPR parametrization gave lower RMSEs than the two other published DECT methods, and was in particular more robust against added noise. The method has potential for reducing range uncertainty margins in treatment planning of proton therapy.
Abstract
Background and purpose. Daily organ motion occurring during the course of radiotherapy in the pelvic region leads to uncertainties in the doses delivered to the tumour and the organs at ...risk. Motion patterns include both volume and shape changes, calling for deformable image registration (DIR), in approaches involving dose accumulation and adaptation. In this study, we tested the performance of a DIR application for contour propagation from the treatment planning computed tomography (pCT) to repeat cone-beam CTs (CBCTs) for a set of prostate cancer patients. Material and methods. The prostate, rectum and bladder were delineated in the pCT and in six to eight repeat CBCTs for each of five patients. The pCT contours were propagated onto the corresponding CBCT using the Multi-modality Image Registration and Segmentation application, resulting in 36 registrations. Prior to the DIR, a rigid registration was performed. The algorithm used for the DIR was based on a 'demons' algorithm and the performance of it was examined quantitatively using the Dice similarity coefficient (DSC) and qualitatively as visual slice-by-slice scoring by a radiation oncologist grading the deviations in shape and/or distance relative to the anatomy. Results. The average DSC (range) for the DIR over all scans and patients was 0.80 (0.65-0.87) for prostate, 0.77 (0.63-0.87) for rectum and 0.73 (0.34-0.91) for bladder, while the corresponding DSCs for the rigid registrations were 0.77 (0.65-0.86), 0.71 (0.55-0.82) and 0.64 (0.33-0.87). The percentage of propagated contours of good/acceptable quality was 45% for prostate; 20% for rectum and 33% for bladder. For the bladder, there was an association between the average DSC and the different scores of the qualitative evaluation. Conclusions. DIR improved the performance of pelvic organ contour propagation from the pCT to CBCTs as compared to rigid registration only. Still, a large fraction of the propagated rectum and bladder contours were unacceptable. The image quality of the CBCTs was sub-optimal and the usability of CBCTs for dose accumulation and adaptation purposes is therefore likely to benefit from improved image quality and improvements of the DIR algorithm.
The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins.
In total, 1576 patients completing radical ...primary IMRT for larynx, pharynx, oral cavity HNSCC in three centers in Denmark between 2006 and 2012 were included. CT-verified LRs were analyzed as possible points of recurrence origin and compared between groups of small (0–2.5 mm), larger (>2.5 mm), and anatomical GTV-CTV1 margins. The recurrence point’s position relative to the GTV and 95% prescription dose was evaluated. Overall local control rate was evaluated using Cox uni- and multi-variate analysis.
After a median follow-up of 41 months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7 mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface (p = 0.4) or the dose to LRs (p = 0.2) was detected between the groups. A difference in LC was found univariate between the centers (p = 0.03), but not in multivariate analysis (p = 0.4).
No relation was found between the recurrences’ distributions as function of the margins used at three centers. In multivariate analysis, local control was not influenced by the centers.
In patients with intestinal failure who are receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) inflict health impairment and high costs.
This study investigates ...the efficacy and safety of the antimicrobial catheter lock solution, taurolidine-citrate-heparin, compared with heparin 100 IE/mL on CRBSI occurrence.
Forty-one high-risk patients receiving HPS followed in a tertiary HPS unit were randomly assigned in a double-blinded, placebo-controlled trial. External, stratified randomization was performed according to age, sex, and prior CRBSI incidence. The prior CRBSI incidence in the study population was 2.4 episodes/1000 central venous catheter (CVC) days 95% Poisson confidence limits (CLs): 2.12, 2.71 episodes/1000 CVC days. The maximum treatment period was 2 y or until occurrence of a CRBSI or right-censoring because of CVC removal. The exact permutation tests were used to calculate P values for the log-rank tests.
Twenty patients received the taurolidine-citrate-heparin lock and 21 received the heparin lock, with 9622 and 6956 treatment days, respectively. In the taurolidine-citrate-heparin arm, no CRBSIs occurred, whereas 7 CRBSIs occurred in the heparin arm, with an incidence of 1.0/1000 CVC days (95% Poisson CLs: 0.4, 2.07/1000 CVC days; P = 0.005). The CVC removal rates were 0.52/1000 CVC days (95% Poisson CLs: 0.17, 1.21/1000 CVC days) and 1.72/1000 CVC days (95% Poisson CLs: 0.89, 3.0/1000 CVC days) in the taurolidine-citrate-heparin and heparin arm, respectively, tending to prolong CVC survival in the taurolidine arm (P = 0.06). Costs per treatment year were lower in the taurolidine arm (€2348) than in the heparin arm (€6744) owing to fewer admission days related to treating CVC-related complications (P = 0.02).
In patients with intestinal failure who are life dependent on HPS, the taurolidine-citrate-heparin catheter lock demonstrates a clinically substantial and cost-beneficial reduction of CRBSI occurrence in a high-risk population compared with heparin. This trial was registered at clinicaltrials.gov as NCT01948245.
Dual energy CT (DECT) has been shown, in theoretical and phantom studies, to improve the stopping power ratio (SPR) determination used for proton treatment planning compared to the use of single ...energy CT (SECT). However, it has not been shown that this also extends to organic tissues. The purpose of this study was therefore to investigate the accuracy of SPR estimation for fresh pork and beef tissue samples used as surrogates of human tissues. The reference SPRs for fourteen tissue samples, which included fat, muscle and femur bone, were measured using proton pencil beams. The tissue samples were subsequently CT scanned using four different scanners with different dual energy acquisition modes, giving in total six DECT-based SPR estimations for each sample. The SPR was estimated using a proprietary algorithm (syngo.via DE Rho/Z Maps, Siemens Healthcare, Forchheim, Germany) for extracting the electron density and the effective atomic number. SECT images were also acquired and SECT-based SPR estimations were performed using a clinical Hounsfield look-up table. The mean and standard deviation of the SPR over large volume-of-interests were calculated. For the six different DECT acquisition methods, the root-mean-square errors (RMSEs) for the SPR estimates over all tissue samples were between 0.9% and 1.5%. For the SECT-based SPR estimation the RMSE was 2.8%. For one DECT acquisition method, a positive bias was seen in the SPR estimates, having a mean error of 1.3%. The largest errors were found in the very dense cortical bone from a beef femur. This study confirms the advantages of DECT-based SPR estimation although good results were also obtained using SECT for most tissues.
Purpose
Photon counting detectors (PCDs) are being introduced in advanced x‐ray computed tomography (CT) scanners. From a single PCD‐CT acquisition, multiple images can be reconstructed, each based ...on only a part of the original x‐ray spectrum. In this study, we investigated whether PCD‐CT can be used to estimate stopping power ratios (SPRs) for proton therapy treatment planning, both by comparing to other SPR methods proposed for single energy CT (SECT) and dual energy CT (DECT) as well as to experimental measurements.
Methods
A previously developed DECT‐based SPR estimation method was adapted to PCD‐CT data, by adjusting the estimation equations to allow for more energy spectra. The method was calibrated directly on noisy data to increase the robustness toward image noise. The new PCD SPR estimation method was tested in theoretical calculations as well as in an experimental setup, using both four and two energy bin PCD‐CT images, and through comparison to two other SPR methods proposed for SECT and DECT. These two methods were also evaluated on PCD‐CT images, full spectrum (one‐bin) or two‐bin images, respectively. In a theoretical framework, we evaluated the effect of patient‐specific tissue variations (density and elemental composition) and image noise on the SPR accuracy; the latter effect was assessed by applying three different noise levels (low, medium, and high noise). SPR estimates derived using real PCD‐CT images were compared to experimentally measured SPRs in nine organic tissue samples, including fat, muscle, and bone tissues.
Results
For the theoretical calculations, the root‐mean‐square error (RMSE) of the SPR estimation was 0.1% for the new PCD method using both two and four energy bins, compared to 0.2% and 0.7% for the DECT‐ and SECT‐based method, respectively. The PCD method was found to be very robust toward CT image noise, with a RMSE of 2.7% when high noise was added to the CT numbers. Introducing tissue variations, the RMSE only increased to 0.5%; even when adding high image noise to the changed tissues, the RMSE stayed within 3.1%. In the experimental measurements, the RMSE over the nine tissue samples was 0.8% when using two energy bins, and 1.0% for the four‐bin images.
Conclusions
In all tested cases, the new PCD method produced similar or better results than the SECT‐ and DECT‐based methods, showing an overall improvement of the SPR accuracy. This study thus demonstrated that PCD‐CT scans will be a qualified candidate for SPR estimations.
Background: Proton arc therapy may improve physical dose conformity and reduce concerns of elevated linear energy transfer (LET) and relative biological effectiveness (RBE) at the end of the proton ...range, while offering more degrees of freedom for normal tissue sparing. To explore the potential of proton arc therapy, we studied the effect of increasing the number of beams on physical and biologically equivalent dose conformity in the setting of pediatric brain tumors.
Material and methods: A cylindrical phantom (Ø = 150 mm) with central cylindrical targets (Ø = 25 and 30 mm) was planned with increasing number of equiangular coplanar proton beams (from 3 to 36). For four anonymized pediatric brain tumor patients, two 'surrogate' proton arc plans (18 equiangular coplanar or sagittal beams) and a reference plan with 3 non-coplanar beams were constructed. Biologically equivalent doses were calculated using two RBE scenarios: RBE
1.1
; and RBE
LET
, the physical dose weighted by the LET. For both RBE scenarios, dose gradients were assessed, and doses to cognitive brain structures were reported.
Results: Increasing the number of beams resulted in an improved dose gradient and reduced volume exposed to intermediate LET levels, at the expense of increased low-dose and low-LET volumes. Most of the differences between the two RBE scenarios were seen around the prescription dose level, where the isodose volumes increased with the RBE
LET
plans, e.g. up to 63% in the 3-beam plan for the smallest phantom target. Overall, the temporal lobes were better spared with the sagittal proton arc surrogate plans, e.g. a mean dose of 3.9 Gy compared to 6 Gy in the reference 3-beam plan (median value, RBE
1.1
).
Conclusion: Proton arc therapy has the potential to improve dose gradients to better spare cognitive brain structures. However, this is at the expense of increased low-dose/low-LET volumes, with possible implications for secondary cancer risks.
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