AutoLock: a semiautomated system for radiotherapy treatment plan quality control.

A semiautomated system for radiotherapy treatment plan quality control (QC), named AutoLock, is presented. AutoLock is designed to augment treatment plan QC by automatically checking aspects of treatment plans that are well suited to computational evaluation, whilst summarizing more subjective aspects in the form of a checklist. The treatment plan must pass all automated checks and all checklist items must be acknowledged by the planner as correct before the plan is finalized. Thus AutoLock uniquely integrates automated treatment plan QC, an electronic checklist, and plan finalization. In addition to reducing the potential for the propagation of errors, the integration of AutoLock into the plan finalization workflow has improved efficiency at our center. Detailed audit data are presented, demonstrating that the treatment plan QC rejection rate fell by around a third following the clinical introduction of AutoLock.

Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial.

Background: Glioblastoma is a high-grade aggressive neoplasm whose outcomes have not changed in decades. In the current treatment pathway, tumour growth continues and remains untreated for several weeks post-diagnosis. Intensified upfront therapy could target otherwise untreated tumour cells and improve the treatment outcome. POBIG will evaluate the safety and feasibility of single-fraction preoperative radiotherapy for newly diagnosed glioblastoma, assessed by the maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV). Methods: POBIG is an open-label, dual-centre phase I dose and volume escalation trial that has received ethical approval. Patients with a new radiological diagnosis of glioblastoma will be screened for eligibility. This is deemed sufficient due to the high accuracy of imaging and to avoid treatment delay. Eligible patients will receive a single fraction of preoperative radiotherapy ranging from 6 to 14 Gy followed by their standard of care treatment comprising maximal safe resection and postoperative chemoradiotherapy (60 Gy/30 fr) with concurrent and adjuvant temozolomide). Preoperative radiotherapy will be directed to the part of the tumour that is highest risk for remaining as postoperative residual disease (hot spot). Part of the tumour will remain unirradiated (cold spot) and sampled separately for diagnostic purposes. Dose/volume escalation will be guided by a Continual Reassessment Method (CRM) model. Translational opportunities will be afforded through comparison of irradiated and unirradiated primary glioblastoma tissue. Discussion: POBIG will help establish the role of radiotherapy in preoperative modalities for glioblastoma. Trial registration: NCT03582514 (clinicaltrials.gov).

Evaluating the Effectiveness of Deep Learning Contouring across Multiple Radiotherapy Centres.

Background and purpose: Deep learning contouring (DLC) has the potential to decrease contouring time and variability of organ contours. This work evaluates the effectiveness of DLC for prostate and head and neck across four radiotherapy centres using a commercial system. Materials and methods: Computed tomography scans of 123 prostate and 310 head and neck patients were evaluated. Besides one head and neck model, generic DLC models were used. Contouring time using centres' existing clinical methods and contour editing time after DLC were compared. Timing was evaluated using paired and non-paired studies. Commercial software or in-house scripts assessed dice similarity coefficient (DSC) and distance to agreement (DTA). One centre assessed head and neck inter-observer variability. Results: The mean contouring time saved for prostate structures using DLC compared to the existing clinical method was 5.9 ± 3.5 min. The best agreement was shown for the femoral heads (median DSC 0.92 ± 0.03, median DTA 1.5 ± 0.3 mm) and the worst for the rectum (median DSC 0.68 ± 0.04, median DTA 4.6 ± 0.6 mm). The mean contouring time saved for head and neck structures using DLC was 16.2 ± 8.6 min. For one centre there was no DLC time-saving compared to an atlas-based method. DLC contours reduced inter-observer variability compared to manual contours for the brainstem, left parotid gland and left submandibular gland. Conclusions: Generic prostate and head and neck DLC models can provide time-savings which can be assessed with paired or non-paired studies to integrate with clinical workload. Reducing inter-observer variability potential has been shown.

Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer.

Background: Lung cancer survival remains poor. The introduction of Intensity-Modulated Radiotherapy (IMRT) allows treatment of more complex tumours as it improves conformity around the tumour and greater normal tissue sparing. However, there is limited evidence assessing the clinical impact of IMRT. In this study, we evaluated whether the introduction of IMRT had an influence on the proportion of patients treated with curative-intent radiotherapy over time, and whether this had an effect on patient survival. Materials and Methods: Patients treated with thoracic radiotherapy at our institute between 2005 and 2020 were retrospectively identified and grouped into three time periods: A) 2005-2008 (pre-IMRT), B) 2009-2012 (selective use of IMRT), and C) 2013-2020 (full access to IMRT). Data on performance status (PS), stage, age, gross tumour volume (GTV), planning target volume (PTV) and survival were collected. The proportion of patients treated with a curative dose between these periods was compared. Multivariable survival models were fitted to evaluate the hazard for patients treated in each time period, adjusting for PS, stage, age and tumour volume. Results: 12,499 patients were included in the analysis (n=2675 (A), n=3127 (B), and n=6697 (C)). The proportion of patients treated with curative-intent radiotherapy increased between the 3 time periods, from 38.1% to 50.2% to 65.6% (p<0.001). When stage IV patients were excluded, this increased to 40.1% to 58.1% to 82.9% (p<0.001). This trend was seen across all PS and stages. The GTV size increased across the time periods and PTV size decreased. Patients treated with curative-intent during period C had a survival improvement compared to time period A when adjusting for clinical variables (HR=0.725 (0.632-0.831), p<0.001). Conclusion: IMRT was associated with to more patients receiving curative-intent radiotherapy. In addition, it facilitated the treatment of larger tumours that historically would have been treated palliatively. Despite treating larger, more complex tumours with curative-intent, a survival benefit was seen for patients treated when full access to IMRT was available (2013-2020). This study highlights the impact of IMRT on thoracic oncology practice, accepting that improved survival may also be attributed to a number of other contributing factors, including improvements in staging, other technological radiotherapy advances and changes to systemic treatment.

Magnetic resonance-guided radiation therapy: A review.

Magnetic resonance-guided radiation therapy (MRgRT) is a promising approach to improving clinical outcomes for patients treated with radiation therapy. The roles of image guidance, adaptive planning and magnetic resonance imaging in radiation therapy have been increasing over the last two decades. Technical advances have led to the feasible combination of magnetic resonance imaging and radiation therapy technologies, leading to improved soft-tissue visualisation, assessment of inter- and intrafraction motion, motion management, online adaptive radiation therapy and the incorporation of functional information into treatment. MRgRT can potentially transform radiation oncology by improving tumour control and quality of life after radiation therapy and increasing convenience of treatment by shortening treatment courses for patients. Multiple groups have developed clinical implementations of MRgRT predominantly in the abdomen and pelvis, with patients having been treated since 2014. While studies of MRgRT have primarily been dosimetric so far, an increasing number of trials are underway examining the potential clinical benefits of MRgRT, with coordinated efforts to rigorously evaluate the benefits of the promising technology. This review discusses the current implementations, studies, potential benefits and challenges of MRgRT.

The evolving role of radiotherapy in non-small cell lung cancer.

Lung cancer is the most commonly diagnosed cancer and biggest cause of cancer mortality worldwide with non-small cell lung cancer (NSCLC) accounting for most cases. Radiotherapy (RT) plays a key role in its management and is used at least once in over half of patients in both curative and palliative treatments. This narrative review will demonstrate how the evolution of RT for NSCLC has been underpinned by improvements in RT technology. These improvements have facilitated geometric individualization, increasingly accurate treatment and now offer the ability to deliver truly individualized RT. In this review, we summarize and discuss recent developments in the field of advanced RT in early stage, locally advanced and metastatic NSCLC. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NSCLC.

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.

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-Linac's 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.

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.

INTRODUCTION: The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of 'isotoxic' radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable. METHODS AND ANALYSIS: Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years. ETHICS AND DISSEMINATION: The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West-Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally. TRIAL REGISTRATION NUMBER: NCT01836692; Pre-results.