Benchmarking Tests of Contemporary SRS Platforms: Have Technological Developments Resulted in Improved Treatment Plan Quality?

PURPOSE: Stereotactic radiosurgery treatment delivery can be performed with a range of devices, each of which have evolved over recent years. We sought to evaluate the differences in performance of contemporary stereotactic radiosurgery platforms and also to compare them with earlier platform iterations from a previous benchmarking study. METHODS AND MATERIALS: The following platforms were selected as "state of the art" in 2022: Gamma Knife Icon (GK), CyberKnife S7 (CK), Brainlab Elements (Elekta VersaHD and Varian TrueBeam), Varian Edge with HyperArc (HA), and Zap-X. Six benchmarking cases were used from a 2016 study. To reflect the evolution of increasing numbers of metastases treated per patient, a 14-target case was added. The 28 targets among the 7 patients ranged from 0.02 to 7.2 cc in volume. Participating centers were sent images and contours for each patient and asked to plan them to the best of their ability. Although some variation in local practice was allowed (eg, margins), groups were asked to prescribe a specified dose to each target and tolerance doses to organs at risk were agreed upon. Parameters compared included coverage, selectivity, Paddick conformity index, gradient index (GI), R50%, efficiency index, doses to organs at risk, and planning and treatment times. RESULTS: Mean coverage for all targets ranged from 98.2% (Brainlab/Elekta) to 99.7% (HA-6X). Paddick conformity index values ranged from 0.722 (Zap-X) to 0.894 (CK). GI ranged from a mean of 3.52 (GK), representing the steepest dose gradient, to 5.08 (HA-10X). The GI appeared to follow a trend with beam energy, with the lowest values from the lower energy platforms (GK, 1.25 MeV; Zap-X, 3 MV) and the highest value from the highest energy (HA-10X). Mean R50% values ranged from 4.48 (GK) to 5.98 (HA-10X). Treatment times were lowest for C-arm linear accelerators. CONCLUSIONS: Compared with earlier studies, newer equipment appears to deliver higher quality treatments. CyberKnife and linear accelerator platforms appear to give higher conformity whereas lower energy platforms yield a steeper dose gradient.

Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial.

BACKGROUND: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. METHODS: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants. FINDINGS: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group). INTERPRETATION: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits. FUNDING: Cancer Research UK.

Corrigendum to "Surface-guided radiotherapy for lung cancer can reduce the number of close patient contacts without compromising initial setup accuracy" [Tech. Innov. Patient Support Radiat. Oncol. 20 (2021) 61-63].

[This corrects the article DOI: 10.1016/j.tipsro.2021.11.005.].

SEAFARER - A new concept for validating radiotherapy patient specific QA for clinical trials and clinical practice.

BACKGROUND: The quality of radiotherapy delivery has been shown to significantly impact clinical outcomes including patient survival. To identify errors, institutions perform Patient Specific Quality Assurance (PSQA) assessing each individual radiotherapy plan prior to starting patient treatments. Externally administered Dosimetry Audits have found problems despite institutions passing their own PSQA. Hence a new audit concept which assesses the institution's ability to detect errors with their routine PSQA is needed. METHODS: Purposefully introduced edits which simulated treatment delivery errors were embedded into radiation treatment plans of participating institutions. These were designed to produce clinically significant changes yet were mostly within treatment delivery specifications. Actual impact was centrally assessed for each plan. Institutions performed PSQA on each plan, without knowing which contained errors. RESULTS: Seventeen institutions using six radiation treatment planning systems and two delivery systems performed PSQA on twelve plans each. Seventeen erroneous plans (across seven institutions) passed PSQA despite causing >5% increase in spinal cord dose relative to the original plans. Six plans (from four institutions) passed despite a >10% increase. CONCLUSIONS: This novel audit concept evolves beyond testing an institution's ability to deliver a single test case, to increasing the number of errors caught by institutions themselves, thus increasing quality of radiation therapy and impacting every patient treated. Administered remotely this audit also provides advantages in cost, environmental impact, and logistics.

Why all radiotherapy planning studies are wrong but some are useful.

Dosimetry comparison studies of radiotherapy treatment planning are common, but often their limitations are not fully acknowledged. Useful data for the community may be produced, which is reproducible and reliable for implementation by others. However, this will only be achieved by clear and detailed reporting, and by consideration of delivered doses and clinical significance.

Surface-guided radiotherapy for lung cancer can reduce the number of close patient contacts without compromising initial setup accuracy.

Surface-guided radiotherapy (SGRT) can assist with patient setup by providing a real-time feedback mechanism over the whole patient treatment surface. It also has the potential to reduce the number of close contacts between staff and the patient, which is advocated for infection control during the COVID-19 pandemic. Residual translations and rotations (post-CBCT) were acquired following a conventional setup protocol (using permanent marks and lasers) and an SGRT setup protocol. The SGRT protocol resulted in one of the two therapeutic radiographers not having any close contact (<2m) with a patient during setup. Data from 702 imaging sessions showed similar setup accuracy with either protocol, fewer large translations and fewer repeat setup occurrences using the SGRT protocol. The potential of SGRT for infection control should be recognised alongside other benefits.

IPEM code of practice for high-energy photon therapy dosimetry based on the NPL absorbed dose calibration service.

The 1990 code of practice (COP), produced by the IPSM (now the Institute of Physics and Engineering in Medicine, IPEM) and the UK National Physical Laboratory (NPL), gave instructions for determining absorbed dose to water for megavoltage photon (MV) radiotherapy beams (Lillicrap et al 1990). The simplicity and clarity of the 1990 COP led to widespread uptake and high levels of consistency in external dosimetry audits. An addendum was published in 2014 to include the non-conventional conditions in Tomotherapy units. However, the 1990 COP lacked detailed recommendations for calibration conditions, and the corresponding nomenclature, to account for modern treatment units with different reference fields, including small fields as described in IAEA TRS483 (International Atomic Energy Agency (IAEA) 2017, Vienna). This updated COP recommends the irradiation geometries, the choice of ionisation chambers, appropriate correction factors and the derivation of absorbed dose to water calibration coefficients, for carrying out reference dosimetry measurements on MV external beam radiotherapy machines. It also includes worked examples of application to different conditions. The strengths of the 1990 COP are retained: recommending the NPL2611 chamber type as secondary standard; the use of tissue phantom ratio (TPR) as the beam quality specifier; and NPL-provided direct calibration coefficients for the user's chamber in a range of beam qualities similar to those in clinical use. In addition, the formalism is now extended to units that cannot achieve the standard reference field size of 10 cm × 10 cm, and recommendations are given for measuring dose in non-reference conditions. This COP is designed around the service that NPL provides and thus it does not require the range of different options presented in TRS483, such as generic correction factors for beam quality. This approach results in a significantly simpler, more concise and easier to follow protocol.

Results of a multicentre dosimetry audit using a respiratory phantom within the EORTC LungTech trial.

INTRODUCTION: The EORTC 22113-08113 LungTech trial assesses the safety and efficacy of SBRT for centrally located NSCLC. To insure protocol compliance an extensive RTQA procedure was implemented. METHODS: Twelve centres were audited using a CIRS008A phantom. The phantom was scanned using target inserts of 7.5 mm and 12.5 mm radius in static condition. For the 7.5 mm insert a 4DCT was acquired while moving according to a cos6 function. Treatment plans were measured using film and an ionization chamber. Wilcoxon's signed-rank tests were performed to compare the three plans across institutions. A Spearman correlation was calculated to evaluate the influence of factors such as PTV, slice thickness and total number of monitor units on the dosimetric results. RESULTS: The reference output dose median [min, max] variation was 0.5% [-1.1, +1.5]. The median deviations between chamber doses and point-planned doses were 1.8% [-0.1; 6.7] for the 7.5 mm and 1.1% [-2.8; 5.0] for the 12.5 mm sphere in static situation and 3.2% [-3.2; 15.7] for the dynamic situation. Film gamma median pass rates were 92.0% [68.0, 99.0] for 7.5 mm static, 96.2% [73.0, 99.0] for 12.5 mm static and 71.0% [40.0, 99.0] for 7.5 mm dynamic. Wilcoxon's signed-rank tests showed that the dynamic irradiations resulted in significantly lower gamma pass rates compared to the 12.5 mm static plan (p = 0.001). The total number of MUs per plan was correlated to both film and IC results. CONCLUSION: An end-to-end audit was successfully performed, revealing important variations between institutions especially in dynamic irradiations. This shows the importance of dosimetry audits and the potentials for further technique and methodology improvements.

Multi-center evaluation of dose conformity in stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging technique for treating oligometastases, but limited data is available on what plan quality is achievable for a range of modalities and clinical sites. METHODS: SBRT plans for lung, spine, bone, adrenal, liver and node sites from 17 participating centers were reviewed. Centers used various delivery techniques including static and rotational intensity-modulation and multiple non-coplanar beams. Plans were split into lung and other body sites and evaluated with different plan quality metrics, including two which are independent of target coverage; "prescription dose spillage" (PDS) and "modified gradient index" (MGI). These were compared to constraints from the ROSEL and RTOG 0813 clinical trials. RESULTS: Planning target volume (PTV) coverage was compromised (PTV V100% < 90%) in 29% of patient plans in order to meet organ-at-risk (OAR) tolerances, supporting the use of plan quality metrics which are independent of target coverage. Both lung (n = 48) and other body (n = 99) site PDS values agreed well with ROSEL constraints on dose spillage, but RTOG 0813 values were too high to detect sub-optimal plans. MGI values for lung plans were mis-matched to both sets of previous constraints, with ROSEL values too high and RTOG 0813 values too low. MGI values were lower for other body plans as expected, though this was only statistically significant for PTV volumes <20 cm3. CONCLUSIONS: Updated guidance for lung and other body site SBRT plan quality using the PDS and MGI metrics is presented.

Stereotactic radiosurgery for benign brain tumors: Results of multicenter benchmark planning studies.

PURPOSE: Stereotactic radiosurgery (SRS) is strongly indicated for treatment of surgically inaccessible benign brain tumors. Various treatment platforms are available, but few comparisons have included multiple centers. As part of a national commissioning program, benchmark planning cases were completed by all clinical centers in the region. METHODS AND MATERIALS: Four benign cases were provided, with images and structures predelineated, including intracanalicular vestibular schwannoma (VS), larger VS, skull base meningioma, and secreting pituitary adenoma. Centers were asked to follow their local practice, and plans were reviewed centrally using metrics for target coverage, selectivity, gradient falloff, and normal tissue sparing. RESULTS: Sixty-eight plans were submitted using 18 different treatment platforms. Fourteen plans were subsequently revised following feedback, and review of 5 plans led to a restriction of service on 2 platforms (2 centers). Prescription doses were consistent for VS and meningioma submissions, but a wide range of doses were used for the pituitary case. All centers prioritized coverage, with the prescription isodose covering ≥95% of 78/82 target volumes. Lower values may be expected next to air cavities when using advanced algorithms, and in general may be acceptable for some benign lesions. Selectivity was much more variable, and in some cases this was combined with high gradient index and/or >1 mm margin, resulting in large volumes of normal tissue being irradiated. Normal tissue doses were more variable across linear accelerator (LINAC)-based plans than with Gamma Knife or CyberKnife, and dose spillage seemed independent of prescription isodose (inhomogeneity). This may reflect the variety of LINAC-based approaches represented or the necessary tradeoff between different objectives. CONCLUSIONS: These benchmarking exercises have highlighted areas of different clinical practice and priorities and potential for improvement. The subsequent sharing of plan data and margin philosophies between the neurosurgery and oncology communities allowed for meaningful comparison between centers and their peers.

Stereotactic radiosurgery for multiple brain metastases: Results of multicenter benchmark planning studies.

PURPOSE: Stereotactic radiosurgery is indicated for treatment of multiple brain metastases. Various treatment platforms are available, but most comparisons are limited to single-center studies. As part of a national commissioning program, benchmark planning cases were completed by 21 clinical centers, providing a unique dataset of current practice across a large number of providers and equipment platforms. METHODS AND MATERIALS: Two brain metastases cases were provided, with images and structures predrawn, involving 3 and 7 lesions. Centers produced plans according to their local practice, which were reviewed centrally using metrics for target coverage, selectivity, gradient fall-off, and normal tissue sparing. RESULTS: Fifty plans were submitted, using 24 treatment platforms. Eleven plans were revised following feedback, including 2 centers that acquired a new platform; 1 other center accepted a restriction of service. All centers prioritized coverage, with the prescription isodose covering ≥95% of 233 of 235 target volumes. Selectivity was much more variable, especially for smaller lesions, and when combined with poor gradient indices resulted in large volumes of normal tissue being irradiated. Tomotherapy submissions were outliers for either selectivity or gradient index, but other platforms could produce plans with relatively low gradient indices for larger lesion volumes. There was more variation among Varian and Elekta LINAC plans than for Gamma Knife and CyberKnife, and larger differences for smaller targets, both inter- and intratreatment platform. Doses to normal brain and brainstem were highest when margins were applied, but improvements were possible by replanning alone. CONCLUSIONS: Multicenter benchmarking exercises have highlighted some variation in clinical practice and priorities, with a few outliers. Most platforms are able to achieve comparable plans, except for the smallest volumes and when larger planning margins are used. The data will be used to advance standardization and quality improvement of national services and can provide useful guidance for centers worldwide.

Unintended doses in radiotherapy-over, under and outside?

Radiotherapy is a safe treatment; nevertheless, national reporting of serious incidents allows investigation of potential harm to individuals and failing safety culture. UK guidance has previously been limited to overexposures, but underexposures will be included in the new legislation, and positioning errors have also been explicitly included in recent guidance. This commentary reviews current guidance and suggests practical approaches to the additional categories, including the definition of a local error margin.

A virtual dosimetry audit - Towards transferability of gamma index analysis between clinical trial QA groups.

PURPOSE: Quality assurance (QA) for clinical trials is important. Lack of compliance can affect trial outcome. Clinical trial QA groups have different methods of dose distribution verification and analysis, all with the ultimate aim of ensuring trial compliance. The aim of this study was to gain a better understanding of different processes to inform future dosimetry audit reciprocity. MATERIALS: Six clinical trial QA groups participated. Intensity modulated treatment plans were generated for three different cases. A range of 17 virtual 'measurements' were generated by introducing a variety of simulated perturbations (such as MLC position deviations, dose differences, gantry rotation errors, Gaussian noise) to three different treatment plan cases. Participants were blinded to the 'measured' data details. Each group analysed the datasets using their own gamma index (γ) technique and using standardised parameters for passing criteria, lower dose threshold, γ normalisation and global γ. RESULTS: For the same virtual 'measured' datasets, different results were observed using local techniques. For the standardised γ, differences in the percentage of points passing with γ < 1 were also found, however these differences were less pronounced than for each clinical trial QA group's analysis. These variations may be due to different software implementations of γ. CONCLUSIONS: This virtual dosimetry audit has been an informative step in understanding differences in the verification of measured dose distributions between different clinical trial QA groups. This work lays the foundations for audit reciprocity between groups, particularly with more clinical trials being open to international recruitment.

Dependence of volume calculation and margin growth accuracy on treatment planning systems for stereotactic radiosurgery.

OBJECTIVE: Uncertainties in radiotherapy target structures are partly dependent on differences between volume calculation and margin growing methods in treatment planning systems (TPS). These uncertainties are exacerbated with very small structures such as those common in stereotactic radiosurgery. METHODS: Data from a national commissioning programme for SRS was used to assess variation in reported volumes for six benchmark cases, including malignant and benign indications. Reported volumes were compared both with and without any margins added according to local practice. RESULTS: 137 plans were submitted, with a total of 311 structures and covering seven TPS. For volumes < 1 cm3 agreement was within 0.05 cm3, and for volumes > 1 cm3 agreement was within 5%. Systematic differences were seen between TPS, partly because of different methods for calculating the end slice volume. About one third of structures had a margin added, of 1-2 mm. Most TPS over-grew the volumes, compared to the approximation of a perfect sphere, especially Pinnacle and Eclipse. CONCLUSION: Differences between volume calculation methods may lead to 5-10% variation in reported volumes from different TPS. This should be taken into account when comparing multicentre studies, and it is recommended that a minimum volume of 0.05 cm3 be used for any near-point doses to allow more consistent comparisons. When margins are added to small structures, there may be up to 40% difference to nominal margin size. Such differences are still small compared to interobserver variation in delineation. Advances in knowledge: This study quantifies the potential uncertainties in clinical volume calculation and margin growth with small radiosurgical targets.

An external dosimetry audit programme to credential static and rotational IMRT delivery for clinical trials quality assurance.

PURPOSE: External dosimetry audits give confidence in the safe and accurate delivery of radiotherapy. The RTTQA group have performed an on-site audit programme for trial recruiting centres, who have recently implemented static or rotational IMRT, and those with major changes to planning or delivery systems. METHODS: Measurements of reference beam output were performed by the host centre, and by the auditor using independent equipment. Verification of clinical plans was performed using the ArcCheck helical diode array. RESULTS: A total of 54 measurement sessions were performed between May 2014 and June 2016 at 28 UK institutions, reflecting the different combinations of planning and delivery systems used at each institution. Average ratio of measured output between auditor and host was 1.002±0.006. Average point dose agreement for clinical plans was -0.3±1.8%. Average (and 95% lower confidence intervals) of gamma pass rates at 2%/2mm, 3%/2mm and 3%/3mm respectively were: 92% (80%), 96% (90%) and 98% (94%). Moderately significant differences were seen between fixed gantry angle and rotational IMRT, and between combination of planning systems and linac manufacturer, but not between anatomical treatment site or beam energy. CONCLUSION: An external audit programme has been implemented for universal and efficient credentialing of IMRT treatments in clinical trials. Good agreement was found between measured and expected doses, with few outliers, leading to a simple table of optimal and mandatory tolerances for approval of dosimetry audit results. Feedback was given to some centres leading to improved clinical practice.

Dose specification for hippocampal sparing whole brain radiotherapy (HS WBRT): considerations from the UK HIPPO trial QA programme.

OBJECTIVE: The HIPPO trial is a UK randomized Phase II trial of hippocampal sparing (HS) vs conventional whole-brain radiotherapy after surgical resection or radiosurgery in patients with favourable prognosis with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS intensity-modulated radiotherapy (IMRT) in a multicentre trial setting. METHODS: Submitted planning benchmark cases were reviewed using visualization for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines. RESULTS: Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison with those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain. CONCLUSION: Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial, consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of an RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS whole-brain radiotherapy.

Current status of kilovoltage (kV) radiotherapy in the UK: installed equipment, clinical workload, physics quality control and radiation dosimetry.

OBJECTIVE: To assess the status and practice of kilovoltage (kV) radiotherapy in the UK. METHODS: 96% of the radiotherapy centres in the UK responded to a comprehensive survey. An analysis of the installed equipment base, patient numbers, clinical treatment sites, quality control (QC) testing and radiation dosimetry processes were undertaken. RESULTS: 73% of UK centres have at least one kV treatment unit, with 58 units installed across the UK. Although 35% of units are over 10 years old, 39% units have been installed in the last 5 years. Approximately 6000 patients are treated with kV units in the UK each year, the most common site (44%) being basal cell carcinoma. A benchmark of QC practice in the UK is presented, against which individual centres can compare their procedures, frequency of testing and acceptable tolerance values. We propose the use of internal "notification" and "suspension" levels for analysis. All surveyed centres were using recommended Codes of Practice for kV dosimetry in the UK; approximately the same number using in-air and in-water methodologies for medium energy, with two-thirds of all centres citing "clinical relevance" as the reason for choice of code. 64% of centres had hosted an external dosimetry audit within the last 3 years, with only one centre never being independently audited. The majority of centres use locally measured applicator factors and published backscatter factors for treatments. Monitor unit calculations are performed using software in only 36% of centres. CONCLUSION: A comprehensive review of current kV practice in the UK is presented. Advances in knowledge: Data and discussion on contemporary kV radiotherapy in the UK, with a particular focus on physics aspects.