The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients.

PURPOSE: Multiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. METHODS/MATERIALS: The KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. RESULTS: The KIM localisation accuracy was 0.2±0.9 mm (left-right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and -0.1◦±0.8◦ (left-right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. CONCLUSIONS: This work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

Evaluating the utility of knowledge-based planning for clinical trials using the TROG 08.03 post prostatectomy radiation therapy planning data.

Background and purpose: Poor quality radiotherapy can detrimentally affect outcomes in clinical trials. Our purpose was to explore the potential of knowledge-based planning (KBP) for quality assurance (QA) in clinical trials. Materials and methods: Using 30 in-house post-prostatectomy radiation treatment (PPRT) plans, an iterative KBP model was created according to the multicentre clinical trial protocol, delivering 64 Gy in 32 fractions. KBP was used to replan 137 plans. The KB (knowledge based) plans were evaluated for their ability to fulfil the trial constraints and were compared against their corresponding original treatment plans (OTP). A second analysis between only the 72 inversely planned OTPs (IP-OTPs) and their corresponding KB plans was performed. Results: All dose constraints were met in 100% of KB plans versus 69% of OTPs. KB plans demonstrated significantly less variation in PTV coverage (Mean dose range: KB plans 64.1 Gy-65.1 Gy vs OTP 63.1 Gy-67.3 Gy, p < 0.01). KBP resulted in significantly lower doses to OARs. Rectal V60Gy and V40Gy were 17.7% vs 27.7% (p < 0.01) and 40.5% vs 53.9% (p < 0.01) for KB plans and OTP respectively. Left femoral head (FH) V45Gy and V35Gy were 0.4% vs 7.4% (p < 0.01) and 7.9% vs 34.9% (p < 0.01) respectively. In the second analysis plan improvements were maintained. Conclusions: KBP created high quality PPRT plans using the data from a multicentre clinical trial in a single optimisation. It is a powerful tool for utilisation in clinical trials for patient specific QA, to reduce dose to surrounding OARs and variations in plan quality which could impact on clinical trial outcomes.

Comprehensive nodal breast VMAT: solving the low-dose wash dilemma using an iterative knowledge-based radiotherapy planning solution.

INTRODUCTION: Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low-dose wash. METHODS: Forty CLN-breast patient data sets were utilised to develop a knowledge-based planning (KBP) VMAT model, which limits low-dose wash using iterative learning and base-tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP-generated ipsilateral VMAT (ipsi-VMAT) plans against the benchmarked hybrid (h)-VMAT (departmental standard) and bowtie-VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ-at-risk (OAR), remaining-volume-at-risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated. RESULTS: Ipsi- and bowtie-VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h-VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral-lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low-dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient-specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review. CONCLUSIONS: A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low-dose wash associated with increased second malignancy risk.

Rolling out RapidPlan: What we've learnt.

INTRODUCTION: RapidPlan (RP), a knowledge-based planning system, aims to consistently improve plan quality and efficiency in radiotherapy. During the early stages of implementation, some of the challenges include knowing how to optimally train a model and how to integrate RP into a department. We discuss our experience with the implementation of RP into our institution. METHODS: We reviewed all patients planned using RP over a 7-month period following inception in our department. Our primary outcome was clinically acceptable plans (used for treatment) with secondary outcomes including model performance and a comparison of efficiency and plan quality between RP and manual planning (MP). RESULTS: Between November 2017 and May 2018, 496 patients were simulated, of which 217 (43.8%) had an available model. RP successfully created a clinically acceptable plan in 87.2% of eligible patients. The individual success of the 24 models ranged from 50% to 100%, with more than 90% success in 15 (62.5%) of the models. In 40% of plans, success was achieved on the 1st optimisation. The overall planning time with RP was reduced by up to 95% compared with MP times. The quality of the RP plans was at least equivalent to historical MP plans in terms of target coverage and organ at risk constraints. CONCLUSION: While initially time-consuming and resource-intensive to implement, plans optimised with RP demonstrate clinically acceptable plan quality, while significantly improving the efficiency of a department, suggesting RP and its application is a highly effective tool in clinical practice.

Parotid sparing in RapidPlan Oropharynx models: To split or not to split.

INTRODUCTION: Differences in knowledge and experience, patient anatomy and tumour location and manipulation of inverse planning objectives and priorities will lead to a variability in the quality of radiation planning. The aim of this study was to investigate whether parotid glands should be treated as separate or combined structures when using knowledge-based planning (KBP) to create oropharyngeal plans, based on the dose they receive. METHOD: Two separate RapidPlan (RP) models were created using the same 70 radical oropharyngeal patients. The 'separated model' divided the parotids into ipsilateral and contralateral structures. The 'combined model' did not separate the parotids. The models were independently validated using 20 patients not included in the models. The same dose constraints and priorities were applied to planning target volumes (PTVs) and organs at risk (OARs) for all plans. An auto-generated line objective and priority was applied in both models, with parotid mean dose and V50 doses evaluated and compared. RESULTS: Plans optimised using the combined model resulted in lower ipsilateral mean doses and lower V50 doses in 80% and 75% of cases, respectively. Fifty-five per cent of plans produced lower mean doses for the contralateral parotid when optimised using the combined model, while lower V50 doses were evenly split between the models. CONCLUSION: Combining the data for both parotids into one RP model resulted in better ipsilateral parotid sparing. Results also suggest that a combined parotid model will spare dose to the contralateral parotid; however, further investigation is required to confirm these results.

Validation of the 8th edition UICC/AJCC TNM staging system for HPV associated oropharyngeal cancer patients managed with contemporary chemo-radiotherapy.

BACKGROUND: To compare outcomes of high-risk human papilloma virus-related oropharyngeal squamous cell carcinoma (HPV OPSCC) treated with modern radiation treatment (RT) and daily image-guidance, staged with the 7th versus the 8th Edition (Ed) Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM staging systems. METHODS: All eligible patients with HPV OPSCC treated definitively over a 10-year period (2007-2016) at a single institution were included. Protocols consisting of either RT or chemo-radiation (CRT) (weekly cisplatin or cetuximab) +/- neoadjuvant chemotherapy for those with bulky disease were used. All patients were Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) staged at baseline and at intervals for up to 2 years post-treatment. Patients received parotid-sparing intensity modulated or volumetric modulated arc therapy with simultaneous integrated boost to either 70Gy in 35 fractions or 66Gy in 30 fractions. The overall survival (OS) was determined for each stage using the 7th Ed and subsequently with the updated 8th Ed staging system. RESULTS: One hundred fifty-three patients were analysed. Patient stage groupings varied between the 7th and 8th Eds respectively; Stage I (0.7% vs 64.7%), Stage II (8.5% vs 22.2%), stage III (21.6% vs 12.4%) and stage IV (69.3% vs 0.7%). In the 7th Ed, the 5 year probability of OS for stages I to III was 90%, versus stage IV 85.5%. There was no statistically significant difference between the staging groups (p = 0.85). In the 8th Ed there was a statistically significant difference in 5 year OS for stage I and stage II disease (96.9% vs 77.1% respectively; p < 0.0001), but not between stage II and III disease (p = 0.98). CONCLUSIONS: The new 8th Ed UICC/AJCC TNM staging system better discriminates between stage I and Stage II HPV OPSCC with respect to OS compared with the 7th Ed staging system. Further investigation is required for stage III or IV patients.

Advanced Renal Cell Cancer and Low-Dose Palliative Radiation Treatment: A Case of a Substantial and Sustained Treatment Response.

Clear cell carcinoma is the most common form of renal cell carcinoma (RCC). Metastatic RCC is poorly responsive to treatment and has a bleak prognosis. Newer systemic agents have improved outcomes. Furthermore, their interaction with radiation treatment (RT) may provide further therapeutic options. RCC is considered to be radioresistant, however we report the case of a patient with progression on targeted therapy and immunotherapy who achieved a substantial and sustained local, and possibly abscopal, response to low dose palliative radiation therapy.

Feasibility of and rectal dosimetry improvement with the use of SpaceOAR® hydrogel for dose-escalated prostate cancer radiotherapy.

INTRODUCTION: The aim of this study was to investigate the feasibility of injecting a temporary spacer between the rectum and the prostate and to quantify the degree of rectal dosimetric improvement that might result. METHODS: Ten patients underwent CT and MRI before and after injection of 10 cc of hydrogel and at completion of radiotherapy. Hydrogel was injected under general anaesthetic using a transperineal approach. The primary endpoints were perioperative toxicity and rectal dosimetry (V80, V75, V70, V65, V40 and V30). Secondary endpoints were acute gastrointestinal toxicity during and 3 months following radiotherapy and the stability of the hydrogel. Treatment for all patients was planned incorporating volumetric modulated arc therapy with a D95 of 80 Gy in 40 fractions to the prostate and proximal seminal vesicles on both the pre- and post-hydrogel scans. Toxicity was scored with the Common Terminology Criteria, v. 3.0. RESULTS: In the first 24 h, two patients described an increase in bowel movement frequency. The comparison plans had identical prescription doses. Rectal doses were significantly lower for all hydrogel patients for all dose endpoints (V80 = 7% vs. 0.1%, V75 = 10.3% vs. 1.1%, V70 = 13.2% vs. 2.7%, V65 = 15.8% vs. 4.6%, V40 = 35.2% vs. 23.3%, V30 = 52.6% vs. 38.5%; P < 0.001). Post-treatment MRI showed gel stability. Grade 1 bowel toxicity was reported in six patients during radiotherapy and two patients at 3 months' follow-up. No Grade 2 or Grade 3 acute bowel toxicity was reported. CONCLUSION: SpaceOAR hydrogel was successfully injected in 10 patients with minimal side effects. Rectal dosimetry was significantly improved in all patients. This study has been extended to 30 patients with longer follow-up planned.

Health-related quality of life using intensity-modulated radiation therapy for post-prostatectomy radiotherapy.

INTRODUCTION: Post-prostatectomy radiotherapy (PPRT) with intensity-modulated radiation therapy (IMRT) has the potential to decrease toxicity by reducing dose to surrounding structures. We assessed its impact on health-related quality of life (HRQoL). METHODS: PPRT patients were enrolled in a prospective HRQoL database. To be eligible, patients were required to be treated with IMRT and have a minimum of 15-month follow up. HRQoL was assessed at baseline, 3, 9 and 15-24 months using the Expanded Prostate Cancer Index Composite questionnaire. Higher scores reflected better HRQoL. Results were analysed as both population means and as individual scores where a moderate change was 10-20 points and a substantial change was >20 points. RESULTS: There were 64 patients eligible and 83% of the cohort received salvage radiotherapy. Prescribed dose was 64 Gy in 32 fractions for adjuvant and 66 Gy in 33 fractions for salvage IMRT. Mean function scores for urinary, bowel and sexual domains were similar at baseline and 15 months (83.5, 94.2 and 16.9 vs. 82.2, 93.1 and 14.3, respectively). Mean global physical functioning (51.0 vs. 48.1) and mental functioning (51.6 vs. 54.2) showed no difference over time. Individual patient scores by 2 years showed a >20-point deterioration in urinary (12.5%), bowel (1.6%), sexual function (9.4%), physical functioning (3.1%) and mental functioning (1.6%). CONCLUSION: This report on HRQoL following post-prostatectomy IMRT demonstrates no variation in mean scores in any domain and only 1.6% of patients reporting a greater than 20-point deterioration between baseline and 15-24 months in bowel function.