Upright patient positioning for pelvic radiotherapy treatments.

Radiotherapy is typically delivered in supine position. However, upright positioning may affect organ volume, positioning, and movement, compared to supine/prone positioning which might have beneficial impacts. In this study, we report patient positioning data in an upright positioning system designed by Leo Cancer Care®. Sixteen patients with pelvic tumors were included in this study. They had 3 setups in an upright position: an initial setup with acquisition of reference optical images, and 2 repositioning setups. The intra-fraction motion was assessed during two 20-minute chair rotation sessions. The patient comfort in supine and upright position was assessed with a 5-point Likert scale questionnaire. Eight women and 8 men treated on regular linacs between October 2021 and June 2022 were included. Their median age and weight were 62.5 years (35 to 81 years) and 75.1 kg (41 to 107 kg). The inter-fraction shift means were -0.5 mm (SD = 2.5), -0.4 mm (SD = 1.3) and -0.9 mm (SD = 2.7) in left-right (LR), antero-posterior (AP), and cranio-caudal (CC) directions, respectively. The intrafraction shifts after 20 min were 0.0 mm (SD = 1.5), 0.2 mm (SD = 1.1) and 0.0 mm (SD = 0.3) in LR, CC, and AP directions, respectively. Average global comfort was 4.1 (3 to 5) for the upright position and 3.9 (2 to 5) for the supine position. In conclusion, the first study on pelvic cancer patients positioned in upright position on a chair is promising, and it opens a potential new direction for the treatment of cancer patients. Evaluation of thoracic and head and neck tumors is ongoing, and imaging with vertical CT is expected to start soon.

A Critical Review of the Antimicrobial and Antibiofilm Activities of Green-Synthesized Plant-Based Metallic Nanoparticles.

Metallic nanoparticles (MNPs) produced by green synthesis using plant extracts have attracted huge interest in the scientific community due to their excellent antibacterial, antifungal and antibiofilm activities. To evaluate these pharmacological properties, several methods or protocols have been successfully developed and implemented. Although these protocols were mostly inspired by the guidelines from national and international regulatory bodies, they suffer from a glaring absence of standardization of the experimental conditions. This situation leads to a lack of reproducibility and comparability of data from different study settings. To minimize these problems, guidelines for the antimicrobial and antibiofilm evaluation of MNPs should be developed by specialists in the field. Being aware of the immensity of the workload and the efforts required to achieve this, we set out to undertake a meticulous literature review of different experimental protocols and laboratory conditions used for the antimicrobial and antibiofilm evaluation of MNPs that could be used as a basis for future guidelines. This review also brings together all the discrepancies resulting from the different experimental designs and emphasizes their impact on the biological activities as well as their interpretation. Finally, the paper proposes a general overview that requires extensive experimental investigations to set the stage for the future development of effective antimicrobial MNPs using green synthesis.

Management of oropharyngeal squamous cell carcinoma.

This article reviews the various treatment options, by primary or postoperative external radiotherapy and by brachytherapy for the p16-negative oropharyngeal squamous cell carcinoma. Dose levels, fractionation and association with systemic treatments are presented. The need for neck node dissection post local treatment is discussed, as well as specificities for the management of p16-positive tumours. Guidelines for target volume selection and delineation are thoroughly elaborated. Last, the management by radiotherapy of locoregional recurrences is discussed.

Management and work-up procedures of patients with head and neck malignancies treated by radiation.

Radiotherapy alone or in association with systemic treatment plays a major role in the treatment of head and neck tumours, either as a primary treatment or as a postoperative modality. The management of these tumours is multidisciplinary, requiring particular care at every treatment step. We present the update of the recommendations of the French Society of Radiation Oncology on the radiotherapy of head and neck tumours from the imaging work-up needed for optimal selection of treatment volume, to optimization of the dose distribution and delivery.

Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.

Clinical implementation of deep-learning based auto-contouring tools-Experience of three French radiotherapy centers.

Deep-learning (DL)-based auto-contouring solutions have recently been proposed as a convincing alternative to decrease workload of target volumes and organs-at-risk (OAR) delineation in radiotherapy planning and improve inter-observer consistency. However, there is minimal literature of clinical implementations of such algorithms in a clinical routine. In this paper we first present an update of the state-of-the-art of DL-based solutions. We then summarize recent recommendations proposed by the European society for radiotherapy and oncology (ESTRO) to be followed before any clinical implementation of artificial intelligence-based solutions in clinic. The last section describes the methodology carried out by three French radiation oncology departments to deploy CE-marked commercial solutions. Based on the information collected, a majority of OAR are retained by the centers among those proposed by the manufacturers, validating the usefulness of DL-based models to decrease clinicians' workload. Target volumes, with the exception of lymph node areas in breast, head and neck and pelvic regions, whole breast, breast wall, prostate and seminal vesicles, are not available in the three commercial solutions at this time. No implemented workflows are currently available to continuously improve the models, but these can be adapted/retrained in some solutions during the commissioning phase to best fit local practices. In reported experiences, automatic workflows were implemented to limit human interactions and make the workflow more fluid. Recommendations published by the ESTRO group will be of importance for guiding physicists in the clinical implementation of patient specific and regular quality assurances.

Head and neck proton therapy in France: A missed opportunity or a challenge in front of us?

Following major advances of the best of photon-techniques such as intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT) and, to arrive soon, magnetic resonance (MR)-linac radiotherapy, there are still substantial opportunities in the treatment of head and neck cancers to further reduce the toxicity burden. Proton therapy represents another attractive option in this high-quality and highly competitive precision radiotherapy landscape. Proton therapy holds promises to reduce toxicities and to escalate the dose in radioresistant cases or cases where dose distribution is not satisfactory with photons. However, the selection of patients for proton therapy needs to be done using evidence-based medicine to build arguments in favor of personalized precision radiation therapy. Referral to proton therapy versus IMRT or SBRT should be registered (ProtonShare® platform) and envisioned in a formalized clinical research perspective through randomized trials. The use of an enrichment process using a model-based approach should be done to only randomize patients doomed to benefit from proton. To tackle such great opportunities, the French proton therapy challenge is to collaborate at the national and international levels, and to demonstrate that the extra-costs of treatment are worth clinically and economically in the short, mid, and long-term. In parallel to the clinical developments, there are still preclinical issues to be tackled (e.g., proton FLASH, mini-beams, combination with immunotherapy), for which the French Radiotransnet network offers a unique platform. The current article provides a personal view of the challenges and opportunities with a focus on clinical research and randomized trial requirements as well as the needs for strong collaborations at the national and international levels for PT in squamous cell carcinomas of the head and neck to date.

Quality assurance of radiotherapy in the ongoing EORTC 1420 "Best of" trial for early stage oropharyngeal, supraglottic and hypopharyngeal carcinoma: results of the benchmark case procedure.

INTRODUCTION: The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS). MATERIALS AND METHODS: Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV). RESULTS: 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD). CONCLUSIONS: This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients' clinical outcome.

Independent external validation using the EORTC HNCG-ROG 1219 DAHANCA trial data of NTCP models for acute oral mucositis.

PURPOSE: To externally validate previously published Normal Tissue Complication Probability (NTCP) models developed by separate teams for grade 3 oral mucositis (g3OM). MATERIALS AND METHODS: Two models were validated: a logistic model, based on 144 head and neck cancer (HNC) patients receiving induction chemotherapy followed by chemo-IMRT; a multivariable logistic model for prediction of g3OM for 253 patients receiving radical treatment for the head and neck squamous cell carcinoma (HNSCC). The EORTC HNCG-ROG 1219 DAHANCA trial dataset, consisting of 169 patients was used as the validation cohort. This cohort was treated with accelerated fractionated chemo-IMRT, with/without the hypoxic radiosensitizer Nimorazole for HNSCC. External validity was assessed using the scaled Brier score. Calibration was assessed in terms of calibration curves as well as measures of mean and weak calibration. Hosmer-Lemeshow was used for goodness-of-fit test. Discrimination was calculated using the area under the receiver operating curve (AUC-ROC). RESULTS: The prevalence of g3OM in the validation cohort (35.5%) was similar to that of two development cohorts, i.e. 38.7% and 31.9% for Bhide logistic and Otter multivariable logistic models respectively. The scaled Brier scores showed good overall model performance. Perfect calibration was observed in the prevalence range of 20% to 40%. AUC-ROC was acceptable in external validation (0.67). The Hosmer-Lemeshow test showed good agreement between predicted and observed outcomes for two models. CONCLUSION: The NTCP models were validated and lead to valid predictions in a wide range of diverse treatment techniques and patient characteristics, also when Nimorazole is added as hypoxic radiosensitizer.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer.

BACKGROUND: Second primary cancers (SPCs) are diagnosed in over 5% of patients after a first primary cancer (FPC). We explore here the impact of immune checkpoint inhibitors (ICIs) given for an FPC on the risk of SPC in different age groups, cancer types and treatments. PATIENTS AND METHODS: The files of the 46 829 patients diagnosed with an FPC in the Centre Léon Bérard from 2013 to 2018 were analyzed. Structured data were extracted and electronic patient records were screened using a natural language processing tool, with validation using manual screening of 2818 files of patients. Univariate and multivariate analyses of the incidence of SPC according to patient characteristics and treatment were conducted. RESULTS: Among the 46 829 patients, 1830 (3.9%) had a diagnosis of SPC with a median interval of 11.1 months (range 0-78 months); 18 128 (38.7%) received cytotoxic chemotherapy (CC) and 1163 (2.5%) received ICIs for the treatment of the FPC in this period. SPCs were observed in 7/1163 (0.6%) patients who had received ICIs for their FPC versus 437/16 997 (2.6%) patients receiving CC and no ICIs for the FPC versus 1386/28 669 (4.8%) for patients receiving neither CC nor ICIs for the FPC. This reduction was observed at all ages and for all histotypes analyzed. Treatment with ICIs and/or CC for the FPC are associated with a reduced risk of SPC in multivariate analysis. CONCLUSION: Immunotherapy with ICIs alone and in combination with CC was found to be associated with a reduced incidence of SPC for all ages and cancer types.

Time of PTV is ending, robust optimization comes next.

Continuous improvements have been made in the way to prescribe, record and report dose distributions since the therapeutic use of ionizing radiations. The international commission for radiation units and measurement (ICRU) has provided a common language for physicians and physicists to plan and evaluate their treatments. The PTV concept has been used for more than two decades but is becoming obsolete as the CTV-to-PTV margin creates a static dose cloud that does not properly recapitulate all planning vs. delivery uncertainties. The robust optimization concept has recently emerged to overcome the limitations of the PTV concept. This concept is integrated in the inverse planning process and minimizes deviations to planned dose distribution through integration of uncertainties in the planning objectives. It appears critical to account for the uncertainties that are specific to protons and should be accounted for to better exploit the clinical potential of proton therapy. It may also improve treatment quality particularly in hypofractionated photon plans of mobile tumors and more widely to photon radiotherapy. However, in contrast to the PTV concept, a posteriori evaluation of plan quality, called robust evaluation, using error-based scenarios is still warranted. Robust optimization metrics are warranted. These metrics are necessary to compare PTV-based photon and robustly optimized proton plans in general and in model-based NTCP approaches. Assessment of computational demand and approximations of robust optimization algorithms along with metrics to evaluate plan quality are needed but a step further to better prescribe radiotherapy may has been achieved.

[Impact of reconstructive or minimal invasive surgery on the assessment of current definitions of postoperative clinical target volume for head and neck cancers]. / Impact de la chirurgie reconstructrice avec lambeaux et de la chirurgie mini-invasive sur la définition du volume cible anatomoclinique des cancers de la sphère ORL.

Advances in the reconstructive surgery and minimally invasive endonasal endoscopic surgery of head and neck is poorly evaluated in terms of their impact on radiotherapy planning and outcomes. These surgical advances have resulted in reduced morbidity with equivalent or better tumor control. In the absence of a recommendation on how to delineate target volumes in patients with flaps or to consider margins after endoscopic endonasal surgery, radiotherapy practices are inevitably heterogeneous. Efforts are needed to increase the therapeutic index of postoperative radiotherapy in these situations. We analysed the rare existing literature and outlined a preliminary basis for a recommendation. Strengthening of multidisciplinarity to accurately define target volumes in these complex and relatively new situations, and "delineation concertation meetings" between radiologists, surgeons and radiation oncologists could probably contribute to improved outcomes.

Do all the linear accelerators comply with the ICRU 91's constraints for stereotactic body radiation therapy treatments?

Recent technological developments in linear accelerators (linacs) and their imaging systems have made it possible to routinely perform stereotactic radiotherapy (SRT) treatments. To ensure the security and quality of the treatments, national and international recommendations have been written. This review focuses on the recommendations of the report 91 of the International Commission on Radiation Units (ICRU) on stereotactic treatments with small photon beams and proposes to answer the question of the eligibility of the commercially available accelerators for the treatment of extra-cranial SRT (SBRT). The ICRU 91 report outlines important features needed to respect the constraints, which are high intensity photon beam, integrated image-guidance, high mechanical accuracy of the linac, multileaf collimator with reduced leaf width, bundled motion management and bundled 6 Dimensional "robotic" couch tabletop. Most of the contemporary linacs meet these recommendations, in particular, stereotactic dedicated linacs, or modern gantry-based linacs equipped with 3 dimensional cone-beam CT imaging and 2D-stereoscopic planar imaging. Commercially available ring-based linacs have some limitations: they offer only coplanar treatments, and couch movements are limited to translations and, some have limited imaging equipment and no ability to manage intrafraction motion. However, for performing SBRT, non-coplanar irradiations are not mandatory, contrarily to intracranial stereotactic irradiations. Furthermore, patients' rotations can be corrected, thanks to real-time adaptive radiotherapy available on MRI-linacs. Finally, significant improvements are expected in the short term to compensate the weaknesses of the current devices.

Volumetric and dosimetric comparison of two delineation guidelines for the radiation treatment of laryngeal squamous cell carcinoma.

PURPOSE: Three methods have been recently proposed for the delineation of the primary tumor clinical target volume (CTV-P) in Head and Neck Cancers: the anatomic method popularized in the French literature by Lapeyre et al. the geometric methods proposed by the DAHANCA group, and more recently the international guidelines promoted by Grégoire et al. integrating the latter two. The aim of this study was to perform a volumetric and dosimetric comparison of the French and the International consensus methods in laryngeal SCC. PATIENTS AND METHODS: Two radiation oncologists independently delineated the high dose and low dose primary tumor CTV in four patients with T2 or T3 N0-M0 laryngeal SCC following either the so-called French guidelines or the International guidelines. For the 4 cases, the GTV was delineated by a single radiation oncologist. Nodal CTVs were delineated by one radiation oncologist for the 4 cases using International guidelines. Dose optimization was then performed with VMAT (MONACO version 5.11) using 6 MeV photons. Differences in target volumes and dose distributions in OARs and PTVs were then evaluated with various metrics such as the DICE Similarity Coefficient and the homogeneity index. RESULTS: Major differences were observed in the CTV delineation between the 2 delineation methods for the low dose volumes and to a lower extend for the high dose volumes. These differences translated into variations in dose distribution favoring the International guidelines for decreasing dose to various OARs. Such differences toned down when dose distribution on the primary tumors PTVs and nodal PTVs were combined. CONCLUSION: This study demonstrated large differences in CTV delineation between the 2 delineation guidelines. Such differences translated into differences in dose distribution.

Radiomics: Principles and radiotherapy applications.

Radiomics is defined as the extraction of a large quantity of quantitative image features. The different radiomic indexes that have been proposed in the literature are described as well as the various factors that have an impact on the robustness of these indexes. We will see that several hundred quantitative features can be extracted per lesion and imaging modality. The ever-growing number of features studied raises the question of the statistical method of analysis used. This review addresses the research supporting the clinical use of radiomics in oncology in the staging of disease, discrimination between healthy and pathological tissues, the identification of genetic features, the prediction of patient survival, the response to treatment, the recurrence after radiotherapy and chemoradiotherapy and the side effects. Based on the existing literature, it remains difficult to identify features that should be used for current clinical practice.

Multi-modal imaging for dose planning and its benefits: the paradigm of head and neck tumours.

The ultimate goal of any radiotherapy is to eradicate the disease without inflicting damage on the normal tissues surrounding the tumours, which could be responsible for late treatment morbidity. To achieve this objective, the first step is to precisely select and delineate the target volumes to which a given dose will be prescribed. This step requires the use of multi-modal images from clinical examination to anatomical and molecular images. Imaging examination will be used not only to delineate the boundaries of the tumour volume, but also to assess tumour heterogeneity and, possibly, to guide a heterogeneous dose prescription (i.e. the so-called 'dose painting' approach). Last, re-imaging the patient during treatment to assess variation of the tumour volume during radiotherapy may also be performed in the framework of adaptive treatment. Over the last decade, a lot of information has been gathered on the use of multi-modal imaging for dose planning, and its potential and technical difficulties have been identified. During the lecture, the speaker will review the state-of-the-art of multi-imaging for treatment, using head and neck tumours as a paradigm, emphasising what should be considered as routine practice and what should still be viewed as research questions. © 2018 ICRP. Published by SAGE.