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.

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.

Utilisation of Pareto navigation techniques to calibrate a fully automated radiotherapy treatment planning solution.

BACKGROUND AND PURPOSE: Current automated radiotherapy planning solutions do not allow for the intuitive exploration of different treatment options during protocol calibration. This work introduces an automated planning solution, which aims to address this problem through incorporating Pareto navigation techniques into the calibration process. MATERIALS AND METHODS: For each tumour site a set of planning goals is defined. Utilising Pareto navigation techniques an operator calibrates the solution through intuitively exploring different treatment options: selecting the optimum balancing of competing planning goals for the given site. Once calibrated, fully automated plan generation is possible, with specific algorithms implemented to ensure trade-off balancing of new patients is consistent with that during calibration. Using the proposed methodology the system was calibrated for prostate and seminal vesicle treatments. The resultant solution was validated through quantitatively comparing the dose distribution of automatically generated plans (VMATAuto) against the previous clinical plan, for ten randomly selected patients. RESULTS: VMATAuto yielded statistically significant improvements in: PTV conformity indices, high dose bladder metrics, mean bowel dose, and the majority of rectum dose metrics. Of particular note was the reduction in mean rectum dose (median 25.1 Gy vs. 27.5 Gy), rectum V24.3Gy (median 41.1% vs. 46.4%), and improvement in the conformity index for the primary PTV (median 0.86 vs. 0.79). Dosimetric improvements were not at the cost of other dose metrics. CONCLUSIONS: An automated planning methodology with a Pareto navigation based calibration has been developed, which enables the complex balancing of competing trade-offs to be intuitively incorporated into automated protocols.

Quality assurance of the SCOPE 1 trial in oesophageal radiotherapy.

BACKGROUND: SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims: 1. To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial. 2. To support the trial's clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. METHODS: A detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre's equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins. RESULTS: 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8-67.8cm3; and PTV volumes 221.9-513.3 cm3. For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial. Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a result of their participation in the SCOPE1 trial. CONCLUSIONS: The SCOPE 1 QA programme outcomes lend support to the trial's clinical conclusions. The range of patient planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource for this to be addressed within future trials. As indicated in questionnaire responses, the QA exercise as a whole has contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of elements of the protocol. TRIAL REGISTRATION: The SCOPE1 trial is an International Standard Randomized Controlled Trial, ISRCTN47718479 .

Prospective review of radiotherapy trials through implementation of standardized multicentre workflow and IT infrastructure.

OBJECTIVE:: We sought to develop a process that would allow us to perform a prospective review of outlining in trials using expert reviewers based in multiple centres. METHODS:: We implemented a specific information technology infrastructure and workflow that could serve all organizations involved in the radiotherapy quality assurance (RTQA) process. RESULTS:: Data were processed and packaged in the computational environment for radiotherapy research (CERR) binary format and securely transmitted to the expert reviewer at the designated remote organization. It was opened and reviewed using the distributed CERR-compiled application, and a standardized report was sent to the respective centre. Centres were expected to correct any unacceptable deviations and resubmit outlining for approval prior to commencing treatment. 75% of reviews were completed and fed back to centres within 3 working days. There were no delays in treatment start date. CONCLUSION:: Our distributed RTQA review approach provides a method of prospective outlining review at multiple centres, without compromising the quality, delaying the start of treatment or the need for significant additional infrastructure resources. Future progress in the area of prospective individual case review will need to be supported by additional resources for clinician time to undertake the reviews. ADVANCES IN KNOWLEDGE:: Trial groups around the world have formulated different approaches to address the need for the prospective review of radiotherapy (RT) data with clinical trials, in line with available resources. We report a UK solution that has allowed the workload for outlining review to be distributed across a wider group of volunteer reviewers without the need for any additional infrastructure costs and has already been adopted within the UK RT trials community.

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma.

BACKGROUND: Both oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal adenocarcinoma, but no randomised study has compared their efficacy and toxicity. This randomised phase II "pick a winner" trial will identify the optimum regimen to take forward to a future phase III trial against neo-adjuvant chemotherapy, the current standard in the UK. METHODS/DESIGN: Patients with resectable adenocarcinoma of the oesophagus or Siewert Type 1-2 gastro-oesophageal junction (GOJ), ≥T3 and/or ≥ N1 are eligible for the study. Following two cycles of induction OXCAP chemotherapy (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m(2) D1-21, q 3 wk), patients are randomised 1:1 to OXCAP-RT (oxaliplatin 85 mg/m(2) Day 1,15,29; capecitabine 625 mg/m(2) twice daily on days of RT; RT-45 Gy/25 fractions/5 weeks) or CarPac-RT (Carboplatin AUC2 and paclitaxel 50 mg/m2 Day 1,8,15,22,29; RT-45 Gy/25 fractions/5 weeks). Restaging CT/PET-CT is performed 4-6 weeks after CRT, and a two-phase oesophagectomy with two-field lymphadenectomy is performed six to eight weeks after CRT. The primary end-point is pathological complete response rate (pCR) at resection and will include central review. Secondary endpoints include: recruitment rate, toxicity, 30-day surgical morbidity/mortality, resection margin positivity rate and overall survival (median, 3- and 5-yr OS. 76 patients (38/arm) gives 90% power and one-sided type 1 error of 10% if patients on one novel treatment have a response rate of 35% while the second treatment has a response rate of 15%. A detailed RT Quality Assurance (RTQA) programme includes a detailed RT protocol and guidance document, pre-accrual RT workshop, outlining exercise, and central evaluation of contouring and planning. This trial has been funded by Cancer Research UK (C44694/A14614), sponsored by Velindre NHS Trust and conducted through the Wales Cancer Trials Unit at Cardiff University on behalf of the NCRI Upper GI CSG. DISCUSSION: Following encouraging results from previous trials, there is an interest in neo-adjuvant chemotherapy and CRT containing regimens for treatment of oesophageal adenocarcinoma. NEOSCOPE will first establish the efficacy, safety and feasibility of two different neo-adjuvant CRT regimens prior to a potential phase III trial. TRIAL REGISTRATION: Eudract No: 2012-000640-10. ClinicalTrials.gov: NCT01843829 .