The role of radiation therapy for de novo metastatic bladder and renal cancers.

Metastatic bladder and renal cancers account respectively for 2.1% and 1.8% of cancer deaths worldwide. The advent of immune checkpoint inhibitors has revolutionized the management of metastatic disease, by demonstrating considerable improvements in overall survival. However, despite initial sensitivity to immune checkpoint inhibitors for most patients, both bladder and renal cancer are associated with short progression-free survival and overall survival, raising the need for further strategies to improve their efficacy. Combining systemic therapies with local approaches is a longstanding concept in urological oncology, in clinical settings including both oligometastatic and polymetastatic disease. Radiation therapy has been increasingly studied with either cytoreductive, consolidative, ablative or immune boosting purposes, but the long-term impact of this strategy remains unclear. This review intends to address the impact of radiation therapy with either curative or palliative intent, for synchronous de novo metastatic bladder and renal cancers.

Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

[Ethical stakes of information in radiation oncology: Thinking the risk and building the therapeutic alliance]. / Enjeux éthiques de l'information en oncologie radiothérapie : penser le risque et construire l'alliance thérapeutique.

Informing patients before receiving radiation therapy is a fundamental ethical imperative. As a condition of the possibility of autonomy, information allows people to make health decisions concerning themselves, which is required by French law. This information includes in particular the potential risks due to radiation therapy. It is therefore necessary to think about what risk is, and how to define and assess it, in order to finally communicate it. The practice of informing people involves many ethical issues relating to the very content of the information, the form in which it is transmitted or even the intention that leads the health professional to say (or not to say) the risk. The transmission of information also questions the way to build a relationship of trust with the patients and how to integrate their own representations about these treatments. Between the risks of paternalism or even defensive medicine, this practice is at the heart of our professional practice.

[Stereotactic body radiation therapy for primary kidney cancer]. / Radiothérapie stéréotaxique des carcinomes rénaux primitifs.

The incidence of primary renal cancer is increasing, particularly in elderly patients who may have comorbidities and/or a surgical contraindications. Stereotactic body radiotherapy has primarily been evaluated retrospectively to date. The most commonly used dose schedules are 40Gy in five fractions, 42Gy in three fractions, and 26Gy in one fraction. The results in terms of local control and toxicity are very encouraging. The advantages of stereotactic body radiotherapy compared to thermal ablative treatments are its non-invasive nature, absence of general anesthesia, ability to treat larger lesions, and those close to the renal hilum. Prospective evaluations are still necessary.

RadioTransNet, Radiotherapy Translational and Preclinical Research Network: Results from the dedicated French cancer institute (INCa) call for projects.

PURPOSE: The RadioTransNet project is a French initiative structuring preclinical and translational research in radiation therapy for cancer at national level. The network's activities are organized around four chosen priorities, which are: target definition, normal tissue, combined treatments and dose modelling. The subtargets linked to these four major priorities are unlimited. They include all aspects associated with fundamental radiobiology, preclinical studies, imaging, medical physics research and transversal components clearly related to these scientific areas, such as medical oncology, radio-diagnostics, nuclear medicine and cost-effectiveness considerations. METHOD: During its first phase of activity, four workshops following the consensus conference model and based on scientific and medical state of the art in radiotherapy and radiobiology were organized on the four above-mentioned objectives to identify key points. Then a road map has been defined and served as the basis for the opening in 2022 of a dedicated call, SEQ-RTH22, proposed by the French cancer national institute (INCa). RESULTS: Four research projects submitted by RadioTransNet partners have been selected to be supported by INCa: the first by Professor Anne Laprie from Oncopole Claudius-Regaud and Inserm ToNic in Toulouse on neurocognition and health after pediatric irradiation, the second submitted by Fabien Milliat from IRSN aims to study decryption and targeting of endothelial cell-immune cells interactions to limit radiation-induced intestinal toxicity, the third project, submitted by Yolanda Prezado from institut Curie-CNRS on proton minibeam radiotherapy as a new approach to reduce toxicity, and the latest project proposed by R. de Crevoisier from centre Eugène-Marquis in Rennes on predictive multiscale models of head and neck radiotoxicity induced for optimized personalized radiation therapy. Topics of each of these projects are presented here. CONCLUSION: RadioTransNet project has been launched in 2018, supported by INCa, in order to structure and promote preclinical research in oncology radiotherapy and to favor collaboration between the actors of this research. INCa relied on RadioTransNet initiatives and activities, resulting in the opening of dedicated call for projects. Beyond its first main goals, RadioTransNet network is able to help to fund the human and technical resources necessary to conduct optimal translational and preclinical research in radiation oncology.

[The morbidity and mortality review meetings in radiotherapy departments: Procedure, implementation and prospects of the "Proust" French national project]. / Revue de morbidité et mortalité en radiothérapie : procédure, implémentation et perspectives du projet national français « Proust ¼.

Radiation-induced acute and late toxicity depends on several parameters. The type, severity and duration of morbidity are mainly related to irradiated volume, total dose and its fractionation and the intrinsic radiosensitivity of the patients. The follow-up of these toxicities is essential. However, unlike many specialties, morbidity and mortality reviews procedures are not developed as part of quality governance programs in radiation therapy departments for the monitoring of toxicity which sometimes hinder the patients' quality of life. One French survey published within the framework of the project entitled Prospective Registration of Morbidity and Mortality, Individual Radiosensitivity and Radiation Technique (Proust), conclude that there was a lack of knowledge of morbidity and mortality reviews and considerable confusion between these reviews and other quality processes without perspective for the local morbidity and mortality reviews development in a large number of the participated centers. In this article, we will discuss the procedure of the "ideal morbidity and mortality reviews" and its implementation through a monocentric experience started in 2015. Thus, the Proust project is a unique opportunity to implement and standardize a national morbidity and mortality reviews implementation in radiation therapy departments by involving the French regions.

Voxel-wise analysis: A powerful tool to predict radio-induced toxicity and potentially perform personalised planning in radiotherapy.

Dose - volume histograms have been historically used to study the relationship between the planned radiation dose and healthy tissue damage. However, this approach considers neither spatial information nor heterogenous radiosensitivity within organs at risk, depending on the tissue. Recently, voxel-wise analyses have emerged in the literature as powerful tools to fully exploit three-dimensional information from the planned dose distribution. They allow to identify anatomical subregions of one or several organs in which the irradiation dose is associated with a given toxicity. These methods rely on an accurate anatomical alignment, usually obtained by means of a non-rigid registration. Once the different anatomies are spatially normalised, correlations between the three-dimensional dose and a given toxicity can be explored voxel-wise. Parametric or non-parametric statistical tests can be performed on every voxel to identify the voxels in which the dose is significantly different between patients presenting or not toxicity. Several anatomical subregions associated with genitourinary, gastrointestinal, cardiac, pulmonary or haematological toxicity have already been identified in the literature for prostate, head and neck or thorax irradiation. Voxel-wise analysis appears therefore first particularly interesting to increase toxicity prediction capability by identifying specific subregions in the organs at risk whose irradiation is highly predictive of specific toxicity. The second interest is potentially to decrease the radio-induced toxicity by limiting the dose in the predictive subregions, while not decreasing the dose in the target volume. Limitations of the approach have been pointed out.

[Understanding/acceptance of radiotherapy: An ethical dilemma resolved by an ethics of care]. / Compréhension/acceptation de la radiothérapie : un dilemme éthique résolu par une éthique de la considération et de la sollicitude.

PURPOSE: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. MATERIALS AND METHODS: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. RESULTS: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. CONCLUSION: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.

A high-performance method of deep learning for prostate MR-only radiotherapy planning using an optimized Pix2Pix architecture.

PURPOSE: The first aim was to generate and compare synthetic-CT (sCT) images using a conditional generative adversarial network (cGAN) method (Pix2Pix) for MRI-only prostate radiotherapy planning by testing several generators, loss functions, and hyper-parameters. The second aim was to compare the optimized Pix2Pix model with five other architectures (bulk-density, atlas-based, patch-based, U-Net, and GAN). METHODS: For 39 patients treated by VMAT for prostate cancer, T2-weighted MRI images were acquired in addition to CT images for treatment planning. sCT images were generated using the Pix2Pix model. The generator, loss function, and hyper-parameters were tuned to improve sCT image generation (in terms of imaging endpoints). The final evaluation was performed by 3-fold cross-validation. This method was compared to five other methods using the following imaging endpoints: the mean absolute error (MAE) and mean error (ME) between sCT and reference CT images (rCT) of the whole pelvis, bones, prostate, bladder, and rectum. For dose planning analysis, the dose-volume histogram metric differences and 3D gamma analysis (local, 1 %/1 mm) were calculated using the sCT and reference CT images. RESULTS: Compared with the other architectures, Pix2Pix with Perceptual loss function and generator ResNet 9 blocks showed the lowest MAE (29.5, 107.7, 16.0, 13.4, and 49.1 HU for the whole pelvis, bones, prostate, bladder, and rectum, respectively) and the highest gamma passing rates (99.4 %, using the 1 %/1mm and 10 % dose threshold criterion). Concerning the DVH points, the mean errors were -0.2% for the planning target volume V95%, 0.1 % for the rectum V70Gy, and -0.1 % for the bladder V50Gy. CONCLUSION: The sCT images generated from MRI data with the Pix2Pix architecture had the lowest image errors and similar dose uncertainties (in term of gamma pass-rate and dose-volume histogram metric differences) than other deep learning methods.

[Crisis situations: Ethical reflection on prioritization of care access in radiation oncology]. / Situations de crise : réflexion éthique sur la priorisation de l'accès aux soins en oncologie radiothérapie.

Understood as a disruption of the conditions of care practice according to established protocols or procedures, crisis situations in radiation oncology departments can have multiple causes. Their seriousness can sometimes impose changes in the decision-making, organizational or technical paradigms. A possible consequence may be the need to make prioritization decisions in access to care, when there is a mismatch between the care needs of a population and the available health resources (whether technical or human). The specificities of care pathways and the wide variety of clinical situations in radiation oncology make these ethical decisions particularly difficult. Anticipation, collegial and multi-professional decision-making procedures or the integration of patient representatives in these prioritization processes are essential tools. Particular attention must be paid to the information to be provided to patients in a concern of transparency and respect. Prioritization situations are real tests for our departments. They go beyond the purely technical aspect of radiation oncology. They can lead to real ethical suffering for health professionals when their values come up against the limits imposed by crisis situations.

Head and neck cancers volume reduction: should we reduce our prophylactic node radiation to spare the antitumor immune response?

Radiotherapy for locally advanced head and neck cancer classically include large prophylactic node volume. However, the use of these large volumes can be responsible for significant toxicity. Furthermore, the disappointing results of radioimmunotherapy combinations in head and neck tumors raise concerns about radiotherapy's potential negative impact on the immune response when large lymph node volumes are treated. Besides, in other tumor locations, such as lung cancers, the volumes of elective irradiation have been considerably reduced, with the same local control as before. This opinion piece reviews the current state of radiation volumes in head and neck cancers, the rationale for these volumes, the potential impact of radiotherapy on immune response, and the volume changes that would improve the efficacy of radioimmunotherapy combinations.

External radiotherapy for prostatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on external radiotherapy of prostate cancer. External radiotherapy is intended for all localized prostate cancers, and more recently for oligometastatic prostate cancers. The irradiation techniques are detailed. Intensity-modulated radiotherapy combined with prostate image-guided radiotherapy is the recommended technique. A total dose of 74 to 80Gy is recommended in case of standard fractionation (2Gy per fraction). Moderate hypofractionation (total dose of 60Gy at a rate of 3Gy per fraction over 4 weeks) in the prostate has become a standard of therapy. Simultaneous integrated boost techniques can be used to treat lymph node areas. Extreme hypofractionation (35 to 40Gy in five fractions) using stereotactic body radiotherapy can be considered a therapeutic option to treat exclusively the prostate. The postoperative irradiation technique, indicated mainly in case of biological recurrence and lymph node involvement, is detailed.

Image-guided radiotherapy.

We present the updated recommendations of the French society for oncological radiotherapy on image-guided radiotherapy (IGRT). The objective of the IGRT is to take into account the anatomical variations of the target volume occurring between or during the irradiation fractions, such as displacements and/or deformations, so that the delivered dose corresponds to the planned dose. This article presents the different IGRT devices, their use and quality control, and quantify the possible additional dose generated by each of them. The practical implementation of IGRT in various tumour locations is summarised, from the different "RecoRad™" guideline articles. Adaptive radiotherapy is then detailed, due to its complexity and its probable development in the next years. The place of radiation technologist in the practice of IGRT is then specified. Finally, a brief update is proposed on the delicate question of the additional dose linked to the in-room imaging, which must be estimated and documented at a minimum, as long as it is difficult to integrate it into the calculation of the dose distribution.

Deep learning methods to generate synthetic CT from MRI in radiotherapy: A literature review.

PURPOSE: In radiotherapy, MRI is used for target volume and organs-at-risk delineation for its superior soft-tissue contrast as compared to CT imaging. However, MRI does not provide the electron density of tissue necessary for dose calculation. Several methods of synthetic-CT (sCT) generation from MRI data have been developed for radiotherapy dose calculation. This work reviewed deep learning (DL) sCT generation methods and their associated image and dose evaluation, in the context of MRI-based dose calculation. METHODS: We searched the PubMed and ScienceDirect electronic databases from January 2010 to March 2021. For each paper, several items were screened and compiled in figures and tables. RESULTS: This review included 57 studies. The DL methods were either generator-only based (45% of the reviewed studies), or generative adversarial network (GAN) architecture and its variants (55% of the reviewed studies). The brain and pelvis were the most commonly investigated anatomical localizations (39% and 28% of the reviewed studies, respectively), and more rarely, the head-and-neck (H&N) (15%), abdomen (10%), liver (5%) or breast (3%). All the studies performed an image evaluation of sCTs with a diversity of metrics, with only 36 studies performing dosimetric evaluations of sCT. CONCLUSIONS: The median mean absolute errors were around 76 HU for the brain and H&N sCTs and 40 HU for the pelvis sCTs. For the brain, the mean dose difference between the sCT and the reference CT was <2%. For the H&N and pelvis, the mean dose difference was below 1% in most of the studies. Recent GAN architectures have advantages compared to generator-only, but no superiority was found in term of image or dose sCT uncertainties. Key challenges of DL-based sCT generation methods from MRI in radiotherapy is the management of movement for abdominal and thoracic localizations, the standardization of sCT evaluation, and the investigation of multicenter impacts.

[Ethical stakes in palliative care in radiation oncology]. / Enjeux éthiques de la pratique des soins à visée palliative en oncologie radiothérapique.

In 2021, the Ethics Commission of the SFRO has chosen the issue of the practice of palliative care in radiotherapy oncology. Radiation oncology plays a central role in the care of patients with cancer in palliative phase. But behind the broad name of palliative radiotherapy, we actually find a large variety of situations involving diverse ethical issues. Radiation oncologists have the delicate task to take into account multiple factors throughout a complex decision-making process. While the question of the therapeutic indication and the technical choice allowing it to be implemented remains central, reflection cannot be limited to these decision-making and technical aspects alone. It is also a question of being able to create the conditions for a singularity focused care and to build an authentic care relationship, beyond technicity. It is through this daily ethical work, in close collaboration with patients, and under essential conditions of multidisciplinarity and multiprofessionalism, that our fundamental role as caregiver can be deployed.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.

Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer.

OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients. MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD > 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs). RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p < 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS. CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.

[Management of image guidance doses delivered during radiotherapy]. / Gestion des doses liées à l'imagerie de positionnement en radiothérapie.

Image-guided radiotherapy (IGRT) has become a standard irradiation technique to improve the clinical outcome of patients in terms of toxicity and local control due to better targeting of radiation during the irradiation fraction. Positioning imaging systems, whether embedded or not, such as kV for 2×2D acquisitions and especially kVCBCT for 3D acquisitions are however irradiating in a large volume including the target volume but also healthy tissue, with a theoretical risk of increased toxicity and second cancer. It therefore appears very important both to optimize the absorbed dose due to IGRT practice but also to report it, especially in case of kVCBCT. The AAPM report published in 2018 (« Image guidance doses delivered during radiotherapy: Quantification, management, and reduction ¼) proposes a management of image guidance doses delivered during radiotherapy. This report is the basis of this focus article that aims at giving orders of magnitude and proposing a management of image guidance doses delivered during radiotherapy in clinical practice. The dose delivered per kVCBCT is about 0.5 to 2 cGy at isocenter according to treatment site. As long as the calculation algorithms are not available in the treatment planning systems, it seems appropriate to use at least the published dose orders of magnitude. This estimate should ultimately allow the clinician to decide on the therapeutic strategy in the event of accumulation of positioning imaging sessions.

[Refractory ventricular tachycardia: Is there a role for radiotherapy?] / Tachycardies ventriculaires réfractaires : quelle place pour la radiothérapie et comment ?

Myocardial scar-related ventricular tachycardia is a serious and potentially life-threatening arrhythmia. The prevention of sudden rhythmic death and ventricular tachycardia recurrence relies on implantable cardioverter defibrillator (ICD), anti-arrhythmic drugs and more recently on radiofrequency catheter ablation. Nevertheless, these approaches have their own risk of adverse events and complications, with a recurrence rate up to 50 % at 2 years. Stereotactic body radiotherapy, delivered in a single dose of 25Gy, has emerged as a new therapeutic tool in the management of highly refractory ventricular tachycardia. In 2017, the very first prospective 5-patient cohort suffering from recurrent ventricular tachycardia on structural heart disease (40 % of ischemic cardiomyopathy) who benefited from cardiac stereotactic body radiotherapy was published. After stereotactic body radiotherapy, the authors observed a strong ventricular tachycardia burden reduction at 12 months, with no major side effects. Since then, around 100 cases have been described in the literature, particularly in the prospective ENCORE-VT study, with positive short- and medium-term outcomes in terms of safety and ventricular tachycardia burden reduction. Recently, another American prospective 5-patient series, published in March 2020, mitigated these results since all patients presented a ventricular tachycardia recurrence at 12 months despite an initial reduction in ventricular tachycardia burden. This article describes the use of stereotactic body radiotherapy in refractory VT, the rationale of the technique, its implementation, preliminary results and potential acute and long-term consequences.

PET and MRI guided adaptive radiotherapy: Rational, feasibility and benefit.

Adaptive radiotherapy (ART) corresponds to various replanning strategies aiming to correct for anatomical variations occurring during the course of radiotherapy. The goal of the article was to report the rational, feasibility and benefit of using PET and/or MRI to guide this ART strategy in various tumor localizations. The anatomical modifications defined by scanner taking into account tumour mobility and volume variation are not always sufficient to optimise treatment. The contribution of functional imaging by PET or the precision of soft tissue by MRI makes it possible to consider optimized ART. Today, the most important data for both PET and MRI are for lung, head and neck, cervical and prostate cancers. PET and MRI guided ART appears feasible and safe, however in a very limited clinical experience. Phase I/II studies should be therefore performed, before proposing cost-effectiveness comparisons in randomized trials and before using the approach in routine practice.