Verification of stereotactic radiotherapy

Investigations have been made into the use of a computer based simulation technique (Monte Carlo (MC)) to ionising radiation transport in order to verify the doses delivered during linear accelerator based stereotactic radiotherapy and radiosurgery. Due to the complex nature of the micro multi-leaf collimators (μMLC) used in this these treatments, a bespoke model of the μMLC was developed and combined with standard component modules to represent the remainder of the linear accelerator. Following validation of the above models, investigations were made into the dosimetry of small fields, defined by the μMLC and measured with a variety of detectors. Comparisons of relative output, profiles and depth doses were made against MC simulations, and a series of correction factors determined, to account for detector geometry and the non water equivalence of materials used in semiconductor detectors. An assessment was then made to determine the smallest fields that can be measured with each detector with confidence. Systems were then developed to independently simulate stereotactic treatments and compare doses simulated with those calculated by the treatment planning system (TPS); excellent agreement between TPS calculations and MC simulations was observed. The application of MC methods to determine the most appropriate treatment tactics and calculation algorithms for stereotactic body radiotherapy in the lung was then investigated with recommendations made on the most appropriate calculation algorithms and beam arrangements for the technique. The doses calculated using the type-b or collapsed cone algorithm agreed most closely with the MC simulation. There was little difference observed between plans using more than four beams in the treatment delivery. Treatment techniques using only three beams or less achieved poorer coverage of the tumour with dose, producing lower doses at the periphery of the tumour near the interface with the surrounding lung tissue, compared to using a greater number of beams. Finally, methods of transit dosimetry using Electronic Portal Imaging Devices were investigated for use in cranial stereotactic radiotherapy. Three methods were investigated based on a full MC simulation of the radiation transport through the patient and on to the imager, prediction of the dose based on a TPS calculation and an approximation of the radiological path length of the central axis of the beams to derive an expected dose at the imager plane. The MC method produced the best agreement at the expense of a longer time to acquire the comparison doses compared to the TPS calculation method. The equivalent path length method showed good agreement (within 3.5%) between delivered and predicted doses but at a single point.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Verification of stereotatic radiotherapy

Investigations have been made into the use of a computer based simulation technique (Monte Carlo (MC)) to ionising radiation transport in order to verify the doses delivered during linear accelerator based stereotactic radiotherapy and radiosurgery. Due to the complex nature of the micro multi-leaf collimators (�MLC) used in this these treatments, a bespoke model of the �MLC was developed and combined with standard component modules to represent the remainder of the linear accelerator. Following validation of the above models, investigations were made into the dosimetry of small fields, defined by the �MLC and measured with a variety of detectors. Comparisons of relative output, profiles and depth doses were made against MC simulations, and a series of correction factors determined, to account for detector geometry and the non water equivalence of materials used in semiconductor detectors. An assessment was then made to determine the smallest fields that can be measured with each detector with confidence. Systems were then developed to independently simulate stereotactic treatments and compare doses simulated with those calculated by the treatment planning system (TPS); excellent agreement between TPS calculations and MC simulations was observed. The application of MC methods to determine the most appropriate treatment tactics and calculation algorithms for stereotactic body radiotherapy in the lung was then investigated with recommendations made on the most appropriate calculation algorithms and beam arrangements for the technique. The doses calculated using the type-b or collapsed cone algorithm agreed most closely with the MC simulation. There was little difference observed between plans using more than four beams in the treatment delivery. Treatment techniques using only three beams or less achieved poorer coverage of the tumour with dose, producing lower doses at the periphery of the tumour near the interface with the surrounding lung tissue, compared to using a greater number of beams. Finally, methods of transit dosimetry using Electronic Portal Imaging Devices were investigated for use in cranial stereotactic radiotherapy. Three methods were investigated based on a full MC simulation of the radiation transport through the patient and on to the imager, prediction of the dose based on a TPS calculation and an approximation of the radiological path length of the central axis of the beams to derive an expected dose at the imager plane. The MC method produced the best agreement at the expense of a longer time to acquire the comparison doses compared to the TPS calculation method. The equivalent path length method showed good agreement (within 3.5%) between delivered and predicted doses but at a single point

Palliative radiotherapy after oesophageal cancer stenting (ROCS): a multicentre, open-label, phase 3 randomised controlled trial

Background: patients with advanced oesophageal cancer have a median survival of 3-6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion.Methods: this was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I-III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (&gt;11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed.Findings: 220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40-1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4-27·7) with usual care and 18·9 weeks (14·7-25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78-1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3-not reached) with EBRT versus 65·9 weeks (52·7-not reached) with usual care (adjusted subhazard ratio 0·52 [95% CI 0·28-0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3-4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care.Interpretation: patients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions.Funding: National Institute for Health Research Health Technology Assessment Programme.</p

Evaluating the application of Pareto navigation guided automated radiotherapy treatment planning to prostate cancer

Background and purpose Current automated planning methods do not allow for the intuitive exploration of clinical trade-offs during calibration. Recently a novel automated planning solution, which is calibrated using Pareto navigation principles, has been developed to address this issue. The purpose of this work was to clinically validate the solution for prostate cancer patients with and without elective nodal irradiation. Materials and methods For 40 randomly selected patients (20 prostate and seminal vesicles (PSV) and 20 prostate and pelvic nodes (PPN)) automatically generated volumetric modulated arc therapy plans (VMATAuto) were compared against plans created by expert dosimetrists under clinical conditions (VMATClinical) and no time pressures (VMATIdeal). Plans were compared through quantitative comparison of dosimetric parameters and blind review by an oncologist. Results Upon blind review 39/40 and 33/40 VMATAuto plans were considered preferable or equal to VMATClinical and VMATIdeal respectively, with all deemed clinically acceptable. Dosimetrically, VMATAuto, VMATClinical and VMATIdeal were similar, with observed differences generally of low clinical significance. Compared to VMATClinical, VMATAuto reduced hands-on planning time by 94% and 79% for PSV and PPN respectively. Total planning time was significantly reduced from 22.2 mins to 14.0 mins for PSV, with no significant reduction observed for PPN. Conclusions A novel automated planning solution has been evaluated, whose Pareto navigation based calibration enabled clinical decision-making on trade-off balancing to be intuitively incorporated into automated protocols. It was successfully applied to two sites of differing complexity and robustly generated high quality plans in an efficient manner

Multi-institutional evaluation of a Pareto navigation gutomated radiotherapy planning solution for prostate cancer

Background: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. Methods: The implemented ‘Pareto Guided Automated Planning’ (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a ‘Protocol Based Automatic Iterative Optimisation’ planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions’ clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. Results: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. Conclusions: PGAP enabled intuitive adaptation of automated protocols to an institution’s planning aims and yielded plans more congruent with the institution’s clinical preference than the locally produced manual clinical plans

Multi-institutional evaluation of a Pareto navigation guided automated radiotherapy planning solution for prostate cancer

Background: Current automated planning solutions are calibrated using trial and error or machine learning on historical datasets. Neither method allows for the intuitive exploration of differing trade-off options during calibration, which may aid in ensuring automated solutions align with clinical preference. Pareto navigation provides this functionality and offers a potential calibration alternative. The purpose of this study was to validate an automated radiotherapy planning solution with a novel multi-dimensional Pareto navigation calibration interface across two external institutions for prostate cancer. Methods: The implemented ‘Pareto Guided Automated Planning’ (PGAP) methodology was developed in RayStation using scripting and consisted of a Pareto navigation calibration interface built upon a ‘Protocol Based Automatic Iterative Optimisation’ planning framework. 30 previous patients were randomly selected by each institution (IA and IB), 10 for calibration and 20 for validation. Utilising the Pareto navigation interface automated protocols were calibrated to the institutions’ clinical preferences. A single automated plan (VMATAuto) was generated for each validation patient with plan quality compared against the previously treated clinical plan (VMATClinical) both quantitatively, using a range of DVH metrics, and qualitatively through blind review at the external institution. Results: PGAP led to marked improvements across the majority of rectal dose metrics, with Dmean reduced by 3.7 Gy and 1.8 Gy for IA and IB respectively (p < 0.001). For bladder, results were mixed with low and intermediate dose metrics reduced for IB but increased for IA. Differences, whilst statistically significant (p < 0.05) were small and not considered clinically relevant. The reduction in rectum dose was not at the expense of PTV coverage (D98% was generally improved with VMATAuto), but was somewhat detrimental to PTV conformality. The prioritisation of rectum over conformality was however aligned with preferences expressed during calibration and was a key driver in both institutions demonstrating a clear preference towards VMATAuto, with 31/40 considered superior to VMATClinical upon blind review. Conclusions: PGAP enabled intuitive adaptation of automated protocols to an institution’s planning aims and yielded plans more congruent with the institution’s clinical preference than the locally produced manual clinical plans

The effect of planning algorithms in oesophageal radiotherapy in the context of the SCOPE 1 trial

Background and purpose In radiotherapy clinical trials multiple centres contribute to patient recruitment. Depending on the calculation algorithm used, the reported dose distributions may differ significantly: broadly, the results for algorithms which do not model lateral electron transport (type a) give less accurate results than the more recently available algorithms that do (type b) when compared to Monte Carlo simulations and measurements. Clinical implementation studies for type b algorithms have yet to be reported for oesophageal radiotherapy. Furthermore, clinical trials must ensure an equivalent effect of the treatment regardless of calculation method. This retrospective planning study aims to define guidance for type b planning in a UK oesophageal clinical trial, to enable acceptable consistency of dose distributions regardless of algorithm, and allow for the improved calculation accuracy of type b to be incorporated into the optimization. Materials and methods Fifteen patient data sets were planned using a single type a algorithm. Plans were recalculated using a single type b algorithm and subsequently re-optimized with the type b in accordance with optimization rules. The changes in absolute dose at the point of prescription for type a were compared to the recalculated type b. Dose–volume data for organs at risk (OARs), and target volumes were compared, and the volume of the planning target volume (PTV) receiving 95% of the prescribed dose (V95%) was compared to the percentage of PTV overlapping with lung. Results Dose at the prescription point decreased by 0.69% on average (SD = 0.71), p = 0.0021, for type b compared to that for type a. For the re-optimized type b, the OAR doses corresponding to the trial dose–volume constraints were maintained within 1.0% of the type a levels on average. Reductions in the mean PTV V95% of 9.3% and 3.8% were observed for the recalculated and re-optimized type b plans, respectively, when compared to the mean PTV V95% for type a. For the re-optimized type b there is a correlation between PTV V95% and the percentage of PTV overlapping lung (R2 = 0.4979). Conclusions Plan optimization with the type b algorithm results in improved PTV V95%. Using our suggested optimization rules, equivalent OAR doses can be maintained with both types. For type b, this requires a measured level of compromise to PTV in low density tissue, quantified by the relationship between PTV V95% and the percentage of PTV in lung