Search

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals., Competing Interests: Declaration of interests RK reports receiving support from the University of Utah Huntsman Cancer Institute for attending meetings and for travel. PGSP declares support from the National Cancer Institute's Radiation Research Program for contributions to this Series paper and for attending meetings and conferences. MM reports receiving grants from the Australian National Health and Medical Research Council for clinical trials paid to his institution; a grant for an investigator-initiated clinical trial that Varian has agreed to, but the payment of this grant is pending; travel support from Varian to deliver a presentation at a national research meeting; and honoraria for lectures from Varian that have been donated to his institution. PK is a recipient of grants from the Australian Government National Health and Medical Research Council and the Cancer Institute NSW Translational Program; has US patents on MRI-LINAC radiotherapy and x-ray-guided radiotherapy; and has stock in SeeTreat. NAM is a recipient of payment for expert testimony as a consultant in a medical legal case whose subject matter was unrelated to the field of research in this manuscript; and has served in a leadership role on the committee of the Radiosurgery Society: the Clinical Working Group of the GRID, LATTICE, Microbeam, and FLASH Working Group. BAJ-F is a recipient of institutional grants from Accuray, the Italian Association for Cancer Research, and the Fondazione Instituto Europeo di Oncologia-Centro Cardiologico Monzino for her institution; has received honoraria from the European Society for Radiotherapy and Oncology for lectures and presentations, from the European School of Oncology and the American Society of Clinical Oncology for lectures and masterclasses, and from Roche, Bayer, Janssen, Carl Zeiss, Accuray, Astellas, Elekta, IBA, Technologie Avanzate, and ACCMED for lectures; and has participated on advisory boards for Janssen, AstraZeneca, and Bayer, and on a steering committee for Seagen. AA reports receiving an Advanced Fellowship from the National Institute for Health Research. F-MSK has received research grants from Varian Medical, Merck, and Shenzhen Science and Technology Commission Programme (KQTD20180411185028798); she has also received a speaker's honorarium from AstreZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Context: Cancer prevalence is increasing, with many patients requiring opioid analgesia. Clinicians need to ensure patients receive adequate pain relief. However, opioid misuse is widespread, and cancer patients are at risk., Objectives: This study aims (1) to identify screening approaches that have been used to assess and monitor risk of opioid misuse in patients with cancer; (2) to compare the prevalence of risk estimated by each of these screening approaches; and (3) to compare risk factors among demographic and clinical variables associated with a positive screen on each of the approaches., Methods: Medline, Cochrane Controlled Trial Register, PubMed, PsycINFO, and Embase databases were searched for articles reporting opioid misuse screening in cancer patients, along with handsearching the reference list of included articles. Bias was assessed using tools from the Joanna Briggs Suite., Results: Eighteen studies met the eligibility criteria, evaluating seven approaches: Urine Drug Test (UDT) (n = 8); the Screener and Opioid Assessment for Patients with Pain (SOAPP) and two variants, Revised and Short Form (n = 6); the Cut-down, Annoyed, Guilty, Eye-opener (CAGE) tool and one variant, Adapted to Include Drugs (n = 6); the Opioid Risk Tool (ORT) (n = 4); Prescription Monitoring Program (PMP) (n = 3); the Screen for Opioid-Associated Aberrant Behavior Risk (SOABR) (n = 1); and structured/specialist interviews (n = 1). Eight studies compared two or more approaches. The rates of risk of opioid misuse in the studied populations ranged from 6 to 65%, acknowledging that estimates are likely to have varied partly because of how specific to opioids the screening approaches were and whether a single or multi-step approach was used. UDT prompted by an intervention or observation of aberrant opioid behaviors (AOB) were conclusive of actual opioid misuse found to be 6.5-24%. Younger age, found in 8/10 studies; personal or family history of anxiety or other mental ill health, found in 6/8 studies; and history of illicit drug use, found in 4/6 studies, showed an increased risk of misuse., Conclusions: Younger age, personal or familial mental health history, and history of illicit drug use consistently showed an increased risk of opioid misuse. Clinical suspicion of opioid misuse may be raised by data from PMP or any of the standardized list of AOBs. Clinicians may use SOAPP-R, CAGE-AID, or ORT to screen for increased risk and may use UDT to confirm suspicion of opioid misuse or monitor adherence. More research into this important area is required., Significance of Results: This systematic review summarized the literature on the use of opioid misuse risk approaches in people with cancer. The rates of reported risk range from 6 to 65%; however, true rate may be closer to 6.5-24%. Younger age, personal or familial mental health history, and history of illicit drug use consistently showed an increased risk of opioid misuse. Clinicians may choose from several approaches. Limited data are available on feasibility and patient experience. PROSPERO registration number. CRD42020163385., (© 2022. The Author(s).)

Proton therapy and MRI-Linacs are two of the most exciting and fast growing technologies in radiation oncology. With over 100 MRI-Linacs and 100 proton therapy centres either in operation or under construction, an integrated approach that brings together the excellent soft tissue imaging of MRI with the superior dose conformity of proton therapy is compelling. The promise of MRI-guided proton therapy has prompted multiple research studies and the building of two pre-clinical experimental systems, taking us closer to realisation of this technology. Patients who would benefit most are those whose cancers have substantial tumour motion or anatomical variation, and those who are currently unable to receive safe dose-escalation due to nearby critical structures. MRI-guided proton therapy could allow more patients with pancreatic cancer, central lung cancer and oligo-metastatic cancers in the upper abdomen (e.g. liver and adrenal) to safely receive escalated curative doses. Head and neck, lung, brain and cervix cancers, where treatment accuracy is affected by inter-fraction tumour changes such as tumour regression or changing oedema, or normal anatomy variations, would also benefit from MRI-guidance. There will be new options to improve cure by functional MRI-guided biologically adapted proton therapy. This review focuses on the clinical aspects of MRI-guided proton therapy. We describe the clinical challenges in proton therapy and the clinical benefits from the addition of MRI-guidance. We provide updates on the design and beam modelling of in-line and perpendicular MRI-guided proton therapy systems, and a roadmap to clinical implementation., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT.

The world is embracing the information age, with real-time data at hand to assist with many decisions. Similarly, in cancer radiotherapy we are inexorably moving toward using information in a smarter and faster fashion, to usher in the age of real-time adaptive radiotherapy. The three critical steps of real-time adaptive radiotherapy, aligned with driverless vehicle technology are a continuous see, think, and act loop. See: use imaging systems to probe the patient anatomy or physiology as it evolves with time. Think: use current and prior information to optimize the treatment using the available adaptive degrees of freedom. Act: deliver the real-time adapted treatment. This paper expands upon these three critical steps for real-time adaptive radiotherapy, provides a historical context, reviews the clinical rationale, and gives a future outlook for real-time adaptive radiotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Compared to conventional linacs with rotating gantries, a fixed-beam radiotherapy system could be smaller, more robust and more cost-effective. In this work, we developed and commissioned a prototype x-ray radiotherapy system utilizing a fixed vertical radiation beam and horizontal patient rotation., Methods: The prototype system consists of an Elekta Synergy linac with gantry fixed at 0° and a custom-built patient rotation system (PRS). The PRS was designed to immobilize patients and safely rotate them about the horizontal axis. The interlocks and emergency stops of the linac and PRS were connected. Custom software was developed to monitor the system status, control the motion of the PRS and modify treatment plans for the fixed-beam configuration. Following installation, the prototype system was commissioned for three-dimensional (3D) conformal therapy based on guidelines specified in AAPM TG-45 and TG-142, with modifications for the fixed-beam geometry made where necessary., Results: The system and control software was tested in a variety of machine states and executed motion, stop and beam gating commands as expected. Interlocks and emergency stops of the linac and PRS were found to correctly stop PRS motion and both kV and MV radiation beams when triggered. For 3D conformal treatments, the prototype system met all AAPM TG-45 and TG-142 specifications for geometric and dosimetric accuracy. Motion of the PRS was within 0.6 ± 0.3 mm and 0.10° ± 0.07° of input values for translation and rotation respectively. The axis of rotation of the PRS was coincident with the radiation beam axis to less than 1 mm. End-to-end treatment verification for 6 MV conformal treatments showed less than 2% difference between planned and delivered dose for all fields., Conclusion: In this work, we have developed and commissioned a radiotherapy system that utilizes a fixed vertical radiation beam and horizontal patient rotation. This system is a proof-of-concept prototype for a fixed-beam treatment system without a rotating gantry. Fixed-beam systems that are smaller and more cost-effective could help in improving global access to radiotherapy., (© 2018 American Association of Physicists in Medicine.)

Purpose: Cancer radiation therapy treatment is performed by delivering a 3D dose distribution to the tumor via the relative rotation between beam and patient. While most modern machines rotate the radiation beam around a still patient, the treatment can also be delivered by rotating the patient relative to a fixed beam. Fixed-beam, patient rotation radiotherapy machines show promise for reducing the size, surface area footprint, and shielding requirements compared with rotating gantry machines. In this Technical Note, we describe the development of a bespoke horizontal patient rotation system for the purposes of a fixed-beam cancer radiotherapy architecture., Methods: A horizontal Patient Rotation System was designed in accordance with the appropriate standards pertaining to performance and safety of medical electrical equipment and medical linear accelerators (ISO 9001, IEC 60601-1, IEC 60601-2-1, ISO 14971, ISO 13485, 21CFR820, IEC 62304, Machinery Directive 98/37/EC). The principal criteria for the design were safety, patient comfort, real-time control and the ability to be integrated with other radiation therapy componentry (including a linear accelerator and kV imaging systems)., Results: A first of its kind device for securing, immobilizing, translating, and rotating patients has been designed and built and tested against 161 different design, safety, and usability specifications. The device has real-time control for all critical applications., Conclusions: We designed and built a bespoke device which can translate and rotate patients 360° around a horizontal axis. The device meets all design and safety criteria with early usability tests indicating a high degree of comfort and utility. The system has been installed in a clinical bunker, integrated with a fixed-beam linear accelerator and is currently being commissioned for the purposes of cancer radiotherapy treatment., (© 2017 American Association of Physicists in Medicine.)

Many low- and middle-income countries, together with remote and low socioeconomic populations within high-income countries, lack the resources and services to deal with cancer. The challenges in upgrading or introducing the necessary services are enormous, from screening and diagnosis to radiotherapy planning/treatment and quality assurance. There are severe shortages not only in equipment, but also in the capacity to train, recruit and retain staff as well as in their ongoing professional development via effective international peer-review and collaboration. Here we describe some examples of emerging technology innovations based on real-time software and cloud-based capabilities that have the potential to redress some of these areas. These include: (i) automatic treatment planning to reduce physics staffing shortages, (ii) real-time image-guided adaptive radiotherapy technologies, (iii) fixed-beam radiotherapy treatment units that use patient (rather than gantry) rotation to reduce infrastructure costs and staff-to-patient ratios, (iv) cloud-based infrastructure programmes to facilitate international collaboration and quality assurance and (v) high dose rate mobile cobalt brachytherapy techniques for intraoperative radiotherapy., (Copyright © 2016 The Royal College of Radiologists. All rights reserved.)

It is arguable that the imaging and delivery hardware necessary for delivering real-time adaptive image-guided radiotherapy is available on high-end linear accelerators. Robust and computationally efficient software is the limiting factor in achieving highly accurate and precise radiotherapy to the constantly changing anatomy of a cancer patient. The limitations are not caused by the availability of algorithms but rather issues of reliability, integration, and calculation time. However, each of the software components is an active area of research and development at academic and commercial centers. This article describes the software solutions in 4 broad areas: deformable image registration, adaptive replanning, real-time image guidance, and dose calculation and accumulation. Given the pace of technological advancement, the integration of these software solutions to develop real-time adaptive image-guided radiotherapy and the associated challenges they bring will be implemented to varying degrees by all major manufacturers over the coming years.

The heterogeneity of human tumour radiation response is well known. Researchers have used the normal distribution to describe interpatient tumour radiosensitivity. However, many natural phenomena show a log-normal distribution. Log-normal distributions are common when mean values are low, variances are large and values cannot be negative. These conditions apply to radiosensitivity. The aim of this work was to evaluate the log-normal distribution to predict clinical tumour control probability (TCP) data and to compare the results with the homogeneous (delta-function with single alpha-value) and normal distributions. The clinically derived TCP data for four tumour types-melanoma, breast, squamous cell carcinoma and nodes-were used to fit the TCP models. Three forms of interpatient tumour radiosensitivity were considered: the log-normal, normal and delta-function. The free parameters in the models were the radiosensitivity mean, standard deviation and clonogenic cell density. The evaluation metric was the deviance of the maximum likelihood estimation of the fit of the TCP calculated using the predicted parameters to the clinical data. We conclude that (1) the log-normal and normal distributions of interpatient tumour radiosensitivity heterogeneity more closely describe clinical TCP data than a single radiosensitivity value and (2) the log-normal distribution has some theoretical and practical advantages over the normal distribution. Further work is needed to test these models on higher quality clinical outcome datasets.

In the era of conformal therapy and intensity-modulated therapy, there is an increased desire to raise tumor dose to facilitate improved survival and decrease normal tissue dose to reduce treatment-related complications. Setup accuracy and internal motion limit our ability to reduce margins. Internal motion has both interfraction and intrafraction components, although only the intrafraction component will be addressed here. Intrafraction motion is significant for lung, liver, and pancreatic radiotherapy and to a lesser extent breast and prostate radiotherapy. A method to explicitly account for intrafraction motion is to temporally adjust the treatment beam based on the tumor position with time such that the motion of the radiation beam is synchronized with the tumor motion. This addition of time into the 3-dimensional treatment process is termed 4-dimensional (4D) radiotherapy. Four-dimensional radiotherapy may allow safe clinical target volume-planning target volume margin reduction to achieve the goals of raised tumor dose and decreased normal tissue dose. This article discusses methodology for 4D CT imaging and 4D treatment planning, with some comments on 4D radiation delivery.

Abstract Background This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. Methods This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. Discussion Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. Trial registration Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.