A. McWilliam

The Future of Image-guided Radiotherapy

Dose-escalated radiotherapy using increasingly conformal techniques from three-dimensional conformal radiotherapy to step-and-shoot intensity-modulated radiotherapy (IMRT) through to volumetric-modulated arc therapy (VMAT) has been shown to improve outcomes in a number of different solid tumours [1e5]. This has been achieved while minimising the potential toxicity to surrounding normal tissue. However, the accuracy of radiotherapy delivery is limited by volume delineation, set-up error and intra-/inter-fraction organ deformation, motion and rotation. These uncertainties are reduced using optimal planning and image-guided radiotherapy (IGRT). The use of cone-beam computed tomography (CBCT) has improved the precision of radiotherapy, enabled the safe delivery of stereotactic ablative body radiotherapy and can produce results comparable with surgery [6]. Despite the successive incremental improvements in radiotherapy, the limitation of CBCT is that there is loss of image quality compared with the planning scan and it is suboptimal for many tissues [7]. Magnetic resonance imaging (MRI) provides improved soft-tissue contrast in many parts of the body and offers far superior in-room imaging for radiotherapy. Although other MRI guidance technology exists [8], at present only the MRlinear accelerator (MR-linac) is available in the UK. The MRlinac combines a 1.5T magnet with a linac. This allows diagnostic quality images to be taken during radiotherapy treatment with the potential for real-time adaptive planning and delivery. University Medical Centre Utrecht developed the prototype [9,10] with further advances made in collaboration with commercial partners, Elekta AB and Philips. The international MR-linac Consortiumwas formed

The impact of continuously-variable dose rate VMAT on beam stability, MLC positioning, and overall plan dosimetry

A recent control system update for Elekta linear accelerators includes the ability to deliver volumetric‐modulated arc therapy (VMAT) with continuously variable dose rate (CVDR), rather than a number of fixed binned dose rates (BDR). The capacity to select from a larger range of dose rates allows the linac to maintain higher gantry speeds, resulting in faster, smoother deliveries. The purpose of this study is to investigate two components of CVDR delivery — the increase in average dose rate and gantry speed, and a determination of their effects on beam stability, MLC positioning, and overall plan dosimetry. Initially, ten VMAT plans (5 prostate, 5 head and neck) were delivered to a Delta4 dosimetric phantom using both the BDR and CVDR systems. The plans were found to be dosimetrically robust using both delivery methods, although CVDR was observed to give higher gamma pass rates at the 2%/2 mm gamma level for prostates (p < 0.01). For the dual arc head‐and‐neck plans, CVDR delivery resulted in improved pass rates at all gamma levels (2%/2 mm to 4%/4 mm) for individual arc verifications (p < 0.01), but gave similar results to BDR when both arcs were combined. To investigate the impact of increased gantry speed on MLC positioning, a dynamic leaf‐tracking tool was developed using the electronic portal imaging device (EPID). Comparing the detected MLC positions to those expected from the plan, CVDR was observed to result in a larger mean error compared to BDR (0.13 cm and 0.06 cm, respectively, p < 0.01). The EPID images were also used to monitor beam stability during delivery. It was found that the CVDR deliveries had a lower standard deviation of the gun‐target (GT) and transverse (AB) profiles (p < 0.01). This study has determined that CVDR may offer a dosimetric advantage for VMAT plans. While the higher gantry speed of CVDR appears to increase deviations in MLC positioning, the relative effect on dosimetry is lower than the positive impact of a flatter and more stable beam profile. PACS numbers: 87.56.bd; 87.55.km; 87.55.Qr

An automated workflow for patient-specific quality control of contour propagation.

Contour propagation is an essential component of adaptive radiotherapy, but current contour propagation algorithms are not yet sufficiently accurate to be used without manual supervision. Manual review of propagated contours is time-consuming, making routine implementation of real-time adaptive radiotherapy unrealistic. Automated methods of monitoring the performance of contour propagation algorithms are therefore required. We have developed an automated workflow for patient-specific quality control of contour propagation and validated it on a cohort of head and neck patients, on which parotids were outlined by two observers. Two types of error were simulated-mislabelling of contours and introducing noise in the scans before propagation. The ability of the workflow to correctly predict the occurrence of errors was tested, taking both sets of observer contours as ground truth, using receiver operator characteristic analysis. The area under the curve was 0.90 and 0.85 for the observers, indicating good ability to predict the occurrence of errors. This tool could potentially be used to identify propagated contours that are likely to be incorrect, acting as a flag for manual review of these contours. This would make contour propagation more efficient, facilitating the routine implementation of adaptive radiotherapy.

The suitability of common metrics for assessing parotid and larynx autosegmentation accuracy

Contouring structures in the head and neck is time-consuming, and automatic segmentation is an important part of an adaptive radiotherapy workflow. Geometric accuracy of automatic segmentation algorithms has been widely reported, but there is no consensus as to which metrics provide clinically meaningful results. This study investigated whether geometric accuracy (as quantified by several commonly used metrics) was associated with dosimetric differences for the parotid and larynx, comparing automatically generated contours against manually drawn ground truth contours. This enabled the suitability of different commonly used metrics to be assessed for measuring automatic segmentation accuracy of the parotid and larynx. Parotid and larynx structures for 10 head and neck patients were outlined by five clinicians to create ground truth structures. An automatic segmentation algorithm was used to create automatically generated normal structures, which were then used to create volumetric-modulated arc therapy plans. The mean doses to the automatically generated structures were compared with those of the corresponding ground truth structures, and the relative difference in mean dose was calculated for each structure. It was found that this difference did not correlate with the geometric accuracy provided by several metrics, notably the Dice similarity coefficient, which is a commonly used measure of spatial overlap. Surface-based metrics provided stronger correlation and are, therefore, more suitable for assessing automatic segmentation of the parotid and larynx. PACS number(s): 87.57.nm, 87.55.D, 87.55.Qr.Contouring structures in the head and neck is time‐consuming, and automatic segmentation is an important part of an adaptive radiotherapy workflow. Geometric accuracy of automatic segmentation algorithms has been widely reported, but there is no consensus as to which metrics provide clinically meaningful results. This study investigated whether geometric accuracy (as quantified by several commonly used metrics) was associated with dosimetric differences for the parotid and larynx, comparing automatically generated contours against manually drawn ground truth contours. This enabled the suitability of different commonly used metrics to be assessed for measuring automatic segmentation accuracy of the parotid and larynx. Parotid and larynx structures for 10 head and neck patients were outlined by five clinicians to create ground truth structures. An automatic segmentation algorithm was used to create automatically generated normal structures, which were then used to create volumetric‐modulated arc therapy plans. The mean doses to the automatically generated structures were compared with those of the corresponding ground truth structures, and the relative difference in mean dose was calculated for each structure. It was found that this difference did not correlate with the geometric accuracy provided by several metrics, notably the Dice similarity coefficient, which is a commonly used measure of spatial overlap. Surface‐based metrics provided stronger correlation and are, therefore, more suitable for assessing automatic segmentation of the parotid and larynx. PACS number(s): 87.57.nm, 87.55.D, 87.55.Qr

Using the Malthus programme to predict the recruitment of patients to MR-linac research trials in prostate and lung cancer

In this study, we used evidence-based mathematical modelling to predict the patient cohort for MR-linac to assess its feasibility in a time of austerity. We discuss our results and the implications of evidence-based radiotherapy demand modelling tools such as Malthus on the implementation of new technology and value-based healthcare.

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected.

Benefit of using motion compensated reconstructions for reducing inter-observer and intra-observer contouring variation for organs at risk in lung cancer patients

BACKGROUND AND PURPOSE In lung cancer patients, accuracy in contouring is hampered by image artefacts introduced by respiratory motion. With the widespread introduction of 4DCT there is additional uncertainty caused by the use of different reconstruction techniques which will influence contour definition. This work aims to assess both inter- and intra-observer contour variation on average and motion compensated (mid-position) reconstructions. MATERIAL AND METHODS Eight early stage non-small cell lung cancer patients that received 4DCT were selected and these scans were reconstructed as average and motion compensated datasets. 5 observers contoured the organs at risk (trachea, oesophagus, proximal bronchial tree, heart and brachial plexus) for each patient and each reconstruction. Contours were compared against a STAPLE volume with distance to agreement metrics. Intra-observer variation was assessed by redelineation after 4 months. RESULTS The inter-observer variation was significantly smaller using the motion compensated datasets for the trachea (p = 0.006) and proximal bronchial tree (p = 0.004). For intra-observer variation, a reduction in contour variation was seen across all organs at risk in using motion compensated reconstructions. CONCLUSIONS This work shows that there is benefit in using motion compensated reconstructions for reducing both inter-observer and intra-observer contouring variations for organs at risk in lung cancer patients.

Technical Note: Investigating the impact of field size on patient selection for the 1.5T MR-Linac

Purpose: The 1.5 T Elekta MR‐Linac, due to the construction of the system will have a maximum radiation field size in the superior‐inferior patient direction of 22 cm at isocentre. The field size may impact on the patient groups which can be treated on the system. This technical note aims to address the question of which treatment sites will be affected by field size limitations on the MR‐Linac. Methods: Using historical data for 11 595 cases over 2 yr treated at the authors’ institution, the proportion of plans that would fit the MR‐Linacs field size was determined for eleven patient groups. In addition, cervix plans were analyzed to determine the length of the two Clinical Target Volumes (CTVs) and any overlap between them. Results: With a 1 cm margin to allow for online plan adaption, 80% of all plans would be suitable for the MR‐Linac due to the field size. This percentage increases to 100% for smaller tumor volumes such as prostate and brain. However, for cervix and three dose‐level head and neck plans the percentage becomes 61% and 66%, respectively. Conclusion: The maximum radiation field size of the MR‐Linac in the superior‐inferior patient direction is 22 cm. With a 1 cm margin approximately 80% of all plans would be suitable for the MR‐Linac with the available field size, decreasing to 61% for larger tumor volumes. For cervix patients this may motivate investigations into treating each CTV with a separate isocentre, allowing for careful control of matching fields.

Changes in prostate apparent diffusion coefficient values during radiotherapy after neo-adjuvant hormones

Background: Changes in prostate cancer apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) provide a noninvasive method for assessing radiotherapy response. This may be attenuated by neoadjuvant hormone therapy (NA-HT). We investigate ADC values measured before, during and after external beam radiotherapy (EBRT) following NA-HT. Methods: Patients with ⩾T2c biopsy-proven prostate cancer receiving 3 months of NA-HT plus definitive radiotherapy were prospectively identified. All underwent ADC-MRI scans in the week before EBRT, in the third week of EBRT and 8 weeks after its completion. Imaging was performed at 1.5 T. The tumour, peripheral zone (PZ) and central zone (CZ) of the prostate gland were identified and median ADC calculated for each region and time point. Results: Between September and December 2014, 15 patients were enrolled (median age 68.3, range 57–78) with a median Gleason score of 7 (6–9) and prostate-specific antigen (PSA) at diagnosis 14 (3–197) ng/ml. Median period of NA-HT prior to first imaging was 96 days (69–115). All patients completed treatment. Median follow up was 25 months (7–34), with one patient relapsing in this time. Thirteen patients completed all imaging as intended, one withdrew after one scan and another missed the final imaging. PZ and CZ could not be identified in one patient. Median tumour ADC before, during and post radiotherapy was 1.24 × 10−3 mm2/s (interquartile range 0.16 × 10−3 mm2/s), 1.31 × 10−3 mm2/s (0.22 × 10−3 mm2/s), then 1.32 × 10−3 mm2/s (0.13 × 10−3 mm2/s) respectively (p > 0.05). There was no significant difference between median tumour and PZ or CZ ADC at any point. Gleason score did not correlate with ADC values. Conclusions: Differences in ADC parameters of normal and malignant tissue during EBRT appear attenuated by prior NA-HT. The use of changes in ADC as a predictive tool in this group may have limited utility.

Assessing MR-linac radiotherapy robustness for anatomical changes in head and neck cancer

The MR-Linac will provide excellent soft tissue contrast for on-treatment imaging. It is well known that the electron return effect (ERE) results in areas of increased and decreased dose at air/tissue boundaries, which can be compensated for in plan optimisation. However, anatomical changes may affect the quality of this compensation. In this paper we aim to quantify the interaction of anatomical changes with ERE in head and neck (H&N) cancer patients. Twenty patients treated with either 66 Gy or 60 Gy in 30 fractions were selected. Ten had significant weight-loss during treatment requiring repeat CT (rCT) and ten had PTVs close to the sinus cavity. Plans were optimised using Monaco to meet the departmental dose constraints and copied to the rCT and re-calculated. For the sinus patients, we optimised plans with full and empty sinus at both 0 T and 1.5 T. The effect of the opposite filling state was next evaluated. No clinically relevant difference between the doses in the PTV and OARs were observed related to weight-loss in 0 T or 1.5 T fields. Variable sinus filling caused greater dosimetric differences near the walls of the sinus for plans optimised with a full cavity in 1.5 T, indicating that optimising with an empty sinus makes the plan more robust to changes in filling. These findings indicate that current off-line strategies for adaptive planning for H&N patients are also valid on an MR-linac, if care is taken with sinus filling.