The 50 most-cited articles in Radiotherapy and Oncology, 2020

BACKGROUND: Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS: A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS: Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular…

Artificial Intelligence (AI) is currently being introduced into different domains, including medicine. Specifically in radiation oncology, machine learning models allow automation and optimization of the workflow. A lack of knowledge and interpretation of these AI models can hold back wide-spread and full deployment into clinical practice. To facilitate the integration of AI models in the radiotherapy workflow, generally applicable recommendations on implementation and quality assurance (QA) of AI models are presented. For commonly used applications in radiotherapy such as auto-segmentation, automated treatment planning and synthetic computed tomography (sCT) the basic concepts are discussed in depth. Emphasis is put on the commissioning, implementation and case-specific and routine QA of AI models needed for a methodical introduction in clinical practice.

Background and purpose Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan ( 10 B) for recurrent or locally advanced head and neck cancer. Materials and methods In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan ( 10 B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan ( 10 B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). Results Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior…

BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC,…

Plan evaluation is a key step in the radiotherapy treatment workflow. Central to this step is the assessment of treatment plan quality. Hence, it is important to agree on what we mean by plan quality and to be fully aware of which parameters it depends on. We understand plan quality in radiotherapy as the clinical suitability of the delivered dose distribution that can be realistically expected from a treatment plan. Plan quality is commonly assessed by evaluating the dose distribution calculated by the treatment planning system (TPS). Evaluating the 3D dose distribution is not easy, however; it is hard to fully evaluate its spatial characteristics and we still lack the knowledge for personalising the prediction of the clinical outcome based on individual patient characteristics. This advocates for standardisation and systematic collection of clinical data and outcomes after radiotherapy. Additionally, the calculated dose distribution is not exactly the dose delivered to the patient due to uncertainties in the dose calculation and the treatment delivery, including variations in the…

Background and purpose FLASH radiotherapy, a technique based on delivering large doses in a single fraction at the micro/millisecond timescale, spares normal tissues from late radiation-induced toxicity, in an oxygen-dependent process, whilst keeping full anti-tumor efficiency. We present a theoretical model taking into account the kinetics of formation and decay of reactive oxygen species, in particular of organic peroxyl radicals RO O . formed by addition of O 2 to primary carbon-centred radicals R . and known to play a major role at the origin radio-induced complications. Materials and methods The model focuses on the time-dependent evolution of radiolytic products in living matter exposed to continuous irradiation at dose-rates in the range 1 0 - 3 - 1 0 7 G y · s - 1 . The 9 differential rate equations resulting from the radiolytic and enzymatic reactions network were solved using the published values of these reactions rate constants in a cellular environment. Results The model suggests a correlation between the area-under-the-curve of time-evolving \[ R O O . \] and the…

BACKGROUND AND PURPOSE: Access to healthcare data is indispensable for scientific progress and innovation. Sharing healthcare data is time-consuming and notoriously difficult due to privacy and regulatory concerns. The Personal Health Train (PHT) provides a privacy-by-design infrastructure connecting FAIR (Findable, Accessible, Interoperable, Reusable) data sources and allows distributed data analysis and machine learning. Patient data never leaves a healthcare institute. MATERIALS AND METHODS: Lung cancer patient-specific databases (tumor staging and post-treatment survival information) of oncology departments were translated according to a FAIR data model and stored locally in a graph database. Software was installed locally to enable deployment of distributed machine learning algorithms via a central server. Algorithms (MATLAB, code and documentation publicly available) are patient privacy-preserving as only summary statistics and regression coefficients are exchanged with the central server. A logistic regression model to predict post-treatment two-year survival was trained and…

INTRODUCTION: The presence of previously unnoticed bilateral macroscopic salivary gland locations in the human nasopharynx was suspected after visualization by positron emission tomography/computed tomography with prostate-specific membrane antigen ligands (PSMA PET/CT). We aimed to elucidate the characteristics of this unknown entity and its potential clinical implications for radiotherapy. MATERIALS AND METHODS: The presence and configuration of the PSMA-positive area was evaluated in a retrospective cohort of consecutively scanned patients with prostate or urethral gland cancer (n = 100). Morphological and histological characteristics were assessed in a human cadaver study (n = 2). The effect of radiotherapy (RT) on salivation and swallowing was retrospectively investigated using prospectively collected clinical data from a cohort of head-neck cancer patients (n = 723). With multivariable logistic regression analysis, the association between radiotherapy (RT) dose and xerostomia or dysphagia was evaluated. RESULTS: All 100 patients demonstrated a demarcated bilateral…

PURPOSE: To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT. MATERIAL AND METHODS: Five low and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom. RESULTS: Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The…

BACKGROUND AND PURPOSE: Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). MATERIALS AND METHODS: HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan-Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. RESULTS: (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by…

Radiotherapy treatment planning studies contribute significantly to advances and improvements in radiation treatment of cancer patients. They are a pivotal step to support and facilitate the introduction of novel techniques into clinical practice, or as a first step before clinical trials can be carried out. There have been numerous examples published in the literature that demonstrated the feasibility of such techniques as IMRT, VMAT, IMPT, or that compared different treatment methods (e.g. non-coplanar vs coplanar treatment), or investigated planning approaches (e.g. automated planning). However, for a planning study to generate trustworthy new knowledge and give confidence in applying its findings, then its design, execution and reporting all need to meet high scientific standards. This paper provides a 'quality framework' of recommendations and guidelines that can contribute to the quality of planning studies and resulting publications. Throughout the text, questions are posed and, if applicable to a specific study and if met, they can be answered positively in the provided…

BACKGROUND AND PURPOSE: For skull base tumors, target definition is the key to safe high-dose treatments because surrounding normal tissues are very sensitive to radiation. In the present work we established a joint ESTRO ACROP guideline for the target volume definition of skull base tumors. MATERIAL AND METHODS: A comprehensive literature search was conducted in PubMed using various combinations of the following medical subjects headings (MeSH) and free-text words: "radiation therapy" or "stereotactic radiosurgery" or "proton therapy" or "particle beam therapy" and "skull base neoplasms" "pituitary neoplasms", "meningioma", "craniopharyngioma", "chordoma", "chondrosarcoma", "acoustic neuroma/vestibular schwannoma", "organs at risk", "gross tumor volume", "clinical tumor volume", "planning tumor volume", "target volume", "target delineation", "dose constraints". The ACROP committee identified sixteen European experts in close interaction with the ESTRO clinical committee who analyzed and discussed the body of evidence concerning target delineation. RESULTS: All experts agree that…

BACKGROUND AND PURPOSE: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group (GHG) is a collaborative group of Radiation Therapy Quality Assurance (RTQA) Groups harmonizing and improving RTQA for multi-institutional clinical trials. The objective of the GHG OAR Working Group was to unify OAR contouring guidance across RTQA groups by compiling a single reference list of OARs in line with AAPM TG 263 and ASTRO, together with peer-reviewed, anatomically defined contouring guidance for integration into clinical trial protocols independent of the radiation therapy delivery technique. MATERIALS AND METHODS: The GHG OAR Working Group comprised of 22 multi-professional members from 6 international RTQA Groups and affiliated organizations conducted the work in 3 stages: (1) Clinical trial documentation review and identification of structures of interest (2) Review of existing contouring guidance and survey of proposed OAR contouring guidance (3) Review of survey feedback with recommendations for contouring guidance with standardized OAR nomenclature. RESULTS:…

PURPOSE: The delineation of the clinical target volume (CTV) is a crucial, laborious and subjective step in cervical cancer radiotherapy. The aim of this study was to propose and evaluate a novel end-to-end convolutional neural network (CNN) for fully automatic and accurate CTV in cervical cancer. METHODS: A total of 237 computed tomography (CT) scans of patients with locally advanced cervical cancer were collected and evaluated. A novel 2.5D CNN network, called DpnUNet, was developed for CTV delineation and further applied for CTV and organ-at-risk (OAR) delineation simultaneously. Comprehensive comparisons and experiments were performed. The mean Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (95HD) and subjective evaluation were used to assess the performance of this method. RESULTS: The mean DSC and 95HD values were 0.86 and 5.34 mm for the delineated CTVs. The clinical experts' subjective assessments showed that 90% of the predicted contours were acceptable for clinical usage. The mean DSC and 95HD values were 0.91 and 4.05 mm for bladder, 0.85 and 2.16…

PURPOSE: In the Netherlands, head and neck cancer (HNC) patients qualify for intensity modulated proton therapy (IMPT) based on model-based selection (MBS). The aim of this study was to evaluate the first experience in MBS of HNC patients. METHODS: Patients who were subjected to MBS (Jan 2018-Sep 2019) were evaluated. A VMAT plan was created for all patients with optimal sparing of organ at risks (OARs) in normal tissue complication probability (NTCP) models for a number of toxicities. An IMPT plan was created only for those with NTCP difference (ΔNTCP) between VMAT and best-case scenario for proton (assuming 0 Gy dose for all OARs in IMPT plan) that exceeded any ΔNTCP-thresholds defined in Dutch National Indication Protocol. These patients qualified for a robust IMPT-plan creation with similar target doses and subsequent plan comparison. RESULTS: Of 227 patients, 141 (62%) qualified for plan comparison, of which 80 (35%) were eventually selected for proton therapy. Most patients were selected based on the ΔNTCP for dysphagia-related toxicities. The selection rate was higher among…

BACKGROUND AND PURPOSE: Daily online adaptation of the clinical target volume (CTV) using MR-guided radiotherapy enables margin reduction of the planning target volume (PTV). This study describes the implementation and initial experience of MR-guided radiotherapy on the 1.5T MR-linac and evaluates treatment time, patient compliance, and target coverage, including an initial assessment of margin reduction. MATERIALS AND METHODS: Patients were treated on a 1.5T MR-linac (7MV, FFF). At each fraction a 3D T2 weighted (T2w) MR-sequence was acquired on which the CTV was adapted after a deformable registration of the contours from the pre-planning CT scan. Based on the new contours a full online replanning was done after which a new 3D T2w MR-sequence was acquired for position verification. A 5 field Intensity Modulated Radiotherapy (IMRT) plan was delivered. RESULTS: Forty-three patients with rectal cancer were treated with 25 Gy in 5 fractions of which 18 with reduced margins. In total, 204 of 215 fractions were delivered on the MR-linac all of which obtained a clinically acceptable…

PURPOSE: The POP-ART RT study aims to determine to what extent and how intrafractional real-time respiratory motion management (RRMM), and plan adaptation for interfractional anatomical changes (ART) are used in clinical practice and to understand barriers to implementation. Here we report on part II: ART using more than one plan per target per treatment course. MATERIALS AND METHODS: A questionnaire on the current practice of ART, wishes for expansion or implementation, and barriers to implementation was distributed worldwide. Four types of ART were discriminated: daily online replanning, online plan library, protocolled offline replanning (all three based on a protocol), and ad-hoc offline replanning. RESULTS: The questionnaire was completed by 177 centres from 40 countries. ART was used by 61% of respondents (31% with protocol) for a median (range) of 3 (1-8) tumour sites. CBCT/MVCT was the main imaging modality except for online daily replanning (11 users) where 10 users used MR. Two thirds of respondents wished to implement ART for a new tumour site; 40% of these had plans to…

To enable accurate magnetic resonance imaging (MRI)-based dose calculations, synthetic computed tomography (sCT) images need to be generated. We aim at assessing the feasibility of dose calculations from MRI acquired with a heterogeneous set of imaging protocol for paediatric patients affected by brain tumours. Sixty paediatric patients undergoing brain radiotherapy were included. MR imaging protocols varied among patients, and data heterogeneity was maintained in train/validation/test sets. Three 2D conditional generative adversarial networks (cGANs) were trained to generate sCT from T1-weighted MRI, considering the three orthogonal planes and its combination (multi-plane sCT). For each patient, median and standard deviation (σ) of the three views were calculated, obtaining a combined sCT and a proxy for uncertainty map, respectively. The sCTs were evaluated against the planning CT in terms of image similarity and accuracy for photon and proton dose calculations. A mean absolute error of 61 ± 14 HU (mean±1σ) was obtained in the intersection of the body contours between CT and sCT.…

Quantitative imaging biomarkers show great potential for use in radiotherapy. Quantitative images based on microscopic tissue properties and tissue function can be used to improve contouring of the radiotherapy targets. Furthermore, quantitative imaging biomarkers might be used to predict treatment response for several treatment regimens and hence be used as a tool for treatment stratification, either to determine which treatment modality is most promising or to determine patient-specific radiation dose. Finally, patient-specific radiation doses can be further tailored to a tissue/voxel specific radiation dose when quantitative imaging is used for dose painting. In this review, published standards, guidelines and recommendations on quantitative imaging assessment using CT, PET and MRI are discussed. Furthermore, critical issues regarding the use of quantitative imaging for radiation oncology purposes and resultant pending research topics are identified.

BACKGROUND AND PURPOSE: To investigate the feasibility of synthesizing computed tomography (CT) images from magnetic resonance (MR) images using generative adversarial networks (GANs) for nasopharyngeal carcinoma (NPC) intensity-modulated radiotherapy (IMRT) planning. MATERIALS AND METHODS: Conventional T1-weighted MR images and CT images were acquired from 173 NPC patients. The MR and CT images of 28 patients were randomly chosen as the independent tested set. The remaining images were used to build a conditional GAN (cGAN) and a cycle-consistency GAN (cycleGAN). A U-net was used as the generator in cGAN, whereas a residual-Unet was used as the generator in cycleGAN. The cGAN was trained using the deformable registered MR-CT image pairs, whereas the cycleGAN was trained using the unregistered MR and CT images. The generated synthetic CT (SCT) images from cGAN and cycleGAN were compared with the true CT images with respect to their Hounsfield Unit (HU) discrepancy and dosimetric accuracy for NPC IMRT plans. RESULTS: The mean absolute errors within the body were 69.67 ± 9.27 HU and…

Despite of the predominant role of chemotherapy and surgery in pancreatic ductal adenocarcinoma (PDAC), radiotherapy (RT) still has a place in multimodal management of this disease where local tumour sequelae are fatal in about 40% of the patients. RT (chemoradiotherapy and stereotactic body radiotherapy) is used and investigated in the non-metastatic setting as part of definitive treatment strategies, in (neo)adjuvant settings and for locally recurrent disease. The ACROP committee was delegated by ESTRO to recommend target volume delineation for these clinical situations. The guidelines of this document are a result of a structured evaluation of the best available evidence by a panel of international experts in the field. Guidance for treatment planning including diagnostic imaging is provided. Recommendations are given for GTV delineation. The role and the definition of CTV volumes are critically discussed. Aspects of motion management and patient positioning are taken into account for PTV definition. Furthermore, aspects of delineation of organs at risk and of dose constraints…

The rapid spread of COVID19 infection across the globe is causing a health care emergency. Our aim is to assist discussion about the risks and benefits to facilitate decision-making regarding radiotherapy for rectal cancer patients. In our roles as clinicians and as experts who have conducted clinical trials evaluating the role of radiotherapy in rectal cancer, we present our assessment of treatment options that should be considered by health care professionals in the setting of the COVID 19 pandemic. We want to minimize the risks to our patients whilst aiming to maintain cancer outcomes. We have used the European Society for Medical Oncology (ESMO) rectal cancer guidelines as a framework to describe our recommendations [[1]Glynne-Jones R. Wyrwicz L. Tiret E. et al.Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2017; 28 (iv22-iv40)Abstract Full Text Full Text PDF Scopus (1109) Google Scholar] (Fig. 1). ESMO Guideline: TME without pre-operative radiotherapy is recommended in most cases. Recommendation: We strongly support the use of…