[Reirradiation of recurrent breast carcinoma]. / Réirradiation des récidives de carcinomes mammaires.

Approximately 10 to 15% of patients with breast cancer will have a local recurrence after initial conservative treatment or mastectomy. Total mastectomy has historically been the standard treatment for local recurrence. However, the question of reirradiation may arise as part of a second conservative treatment in conjunction with segmentectomy or in the case of chest wall recurrence to improve local control. Different modalities are available: brachytherapy, external beam radiotherapy with or without hyperthermia. Although the carcinologic results are encouraging, this complex situation requires rigorous patient selection and technical requirements to achieve the best local control and limit toxicity events. This article presents a review of the literature on the different indications and techniques for reirradiation of ipsilateral recurrent breast cancer, with the aim of providing decision support in clinical practice.

[Practice-changing trials: Urological radiation oncology]. / Essais qui changent les pratiques : cancers urologiques.

Herein, we provide a non-exhaustive selection of the main clinical trials presented in 2023-2024 related to radiation-oncology used in the treatment of urological cancers including prostate cancer (radiotherapy of localized prostate cancer, post-prostatectomy irradiation, reirradiation, biochemical recurrence following local treatment, radiotherapy for metastatic cancer), muscle invasive bladder cancer and primary kidney cancer.

News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?

Trimodal therapy consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy, has emerged as a valuable therapeutic alternative to radical cystectomy in patients with muscle invasive bladder cancer. Concomitant radiosensitising chemotherapy is a component of trimodality increasing locoregional control compared to radiotherapy alone. The combinations 5-fluorouracil with mitomycin or cisplatin are the best supported in the literature. Gemcitabine appears to be a feasible and promising alternative. There is considerable international heterogeneity in terms of dose, volumes and fractionation. The most commonly used regimens are moderately hypofractionated (55Gy in 20 fractions over 4 weeks) and normofractionated (64Gy in 32 fractions) regimens. Radiotherapy for bladder cancer is an effective and evolving treatment, with current technical developments, and studies of new combinations with systemic treatments underway.

[Update of guidelines of the AFSOS, SFRO, SFH, SFNCM, SFCE, GFRP for the management of radio-induced nausea and vomiting]. / Actualisation du référentiel AFSOS, SFRO, SFH, SFNCM, SFCE, GFRP : nausées et vomissements radio-induits.

BACKGROUND: Radiation-induced nausea and vomiting have mutiple clinical consequences: delay or refusal of irradiation (decreased antineoplastic efficacy of irradiation), altered quality of life, dehydration, malnutrition, interruption of treatment, decompensation of comorbidities and aspiration. These guidelines aim at defining good clinical practices for management of radiation-induced nausea and vomiting (RINV). METHODS: AFSOS, SFRO, SFH, SFNEP, SFCE and GFRP applied an expert consensus methodology to propose updated guidelines. RESULTS: RINV are underdiagnosed and undertreated. Assessment of the emetogenic risk depends on two main factors: 1) the irradiated anatomical localization and 2) the associated concomitant chemotherapy. In case of exclusive radiotherapy, primary antiemetic prophylaxis depends on the emetogenic risk of irradiated anatomical localization. Primary antiemetic prophylaxis is initiated at the onset of irradiation and continues until 24h after the end of the irradiation. In the case of concomitant radiochemotherapy, the emetogenic risk is generally higher for chemotherapy and the primary antiemetic prophylaxis corresponds to that of chemo-induced nausea and vomiting. In the case of persistence of these symptoms, subject to a well-conducted treatment, a rigorous diagnostic procedure must be carried out before being attributed to radiotherapy and precise evaluation of their impact. Remedial treatments are less well codified. CONCLUSION: It is essential to know and good management practices for radiation-induced nausea and vomiting.

Personalizing radiotherapy with adaptive radiotherapy: Interest and challenges.

Adaptive radiotherapy (ART) is a recent development in radiotherapy technology and treatment personalization that allows treatment to be tailored to the daily anatomical changes of patients. While it was until recently only performed "offline", i.e. between two radiotherapy sessions, it is now possible during ART to perform a daily online adaptive process for a given patient. Therefore, ART allows a daily customization to ensure optimal coverage of the treatment target volumes with minimized margins, taking into account only the uncertainties related to the adaptive process itself. This optimization appears particularly relevant in case of daily variations in the positioning of the target volume or of the organs at risk (OAR) associated with a proximity of these volumes and a tenuous therapeutic index. ART aims to minimize severe acute and late toxicity and allows tumor dose escalation. These new achievements have been possible thanks to technological development, the contribution of new multimodal and onboard imaging modalities and the integration of artificial intelligence tools for the contouring, planning and delivery of radiation therapy. Online ART is currently available on two types of radiotherapy machines: MR-linear accelerators and recently CBCT-linear accelerators. We will first describe the benefits, advantages, constraints and limitations of each of these two modalities, as well as the online adaptive process itself. We will then evaluate the clinical situations for which online adaptive radiotherapy is particularly indicated on MR- and CBCT-linear accelerators. Finally, we will detail some challenges and possible solutions in the development of online ART in the coming years.

Role of stereotactic radiotherapy in the management of small-cell lung cancer.

Small-cell lung cancer is the most aggressive form of lung neoplasia, treated in recent decades with chemoradiotherapy in case of limited stage and chemotherapy alone at the metastatic stage. In the last few years, the advent of immunotherapy has changed the landscape in the treatment of non-small-cell lung cancer, and to a lesser degree in small-cell lung cancer. Despite the recent advances in research, small-cell lung cancer is still considered an aggressive and lethal disease characterized by high recurrence or metastatic potential. As stereotactic radiotherapy has established itself as the standard of care in the early stage of inoperable non-small-cell lung cancer and in metastatic disease to treat brain and extracranial metastases, these same issues now arise in the management of small-cell lung cancer. This article aims to review the current knowledge and the potential of stereotactic radiotherapy in small-cell lung cancer.

Preoperative stereotactic radiotherapy for the management of brain metastases.

Traditionally, postoperative whole-brain radiation therapy (WBRT) has been used for resected brain metastases, reducing local and intracerebral relapses. However, WBRT is associated with cognitive deterioration. Postoperative stereotactic radiotherapy (SRT) has emerged due to its neurocognitive preservation benefits. Despite its advantages, postoperative SRT has several drawbacks, including difficulties in target volume delineation, increased risk of radionecrosis (RN) and leptomeningeal disease (LMD), and prolonged treatment duration. Preoperative SRT has been proposed as a potential alternative, offering promising results in retrospective studies. Retrospective studies have suggested that preoperative SRT could achieve high local control rates with fewer LMD and RN rates compared to postoperative SRT. However, preoperative SRT is primarily based on retrospective data, and no phase 2/3 trials have been published to date. Ongoing clinical trials are expected to provide further insights into the efficacy and safety of preoperative SRT, addressing key questions regarding fractionation, dose, and timing relative to surgery.

Delineation of target volume by radiation therapists during online adaptive radiation therapy: What authorization?

The evolution of radiation therapy techniques goes hand in hand with the evolution of the profession of radiation therapist. In the particular context of online adaptive radiotherapy based on cone beam computed tomography images, delegation of certain tasks from the physician to the radiation therapist is possible within the framework of a cooperation protocol. This delegation requires prior theoretical and practical training. It enriches the practice of radiation therapists by allowing them to acquire new skills and greater autonomy. It foreshadows access for radiation therapists to advanced practice.

[Events and errors in radiation oncology: Conciliating perspectives to support care]. / Survenue d'un évènement ou d'une erreur en oncologie radiothérapie : concilier les perspectives pour préserver le soin.

The term "event" covers a wide range of concrete situations in radiation oncology, from particularly intense radiation-related side effects to the possibility of technical or human error. Although quality procedures are an integral part of radiotherapy oncology department operations ensuring the analysis and prevention of such events, their occurrence during radiation treatment still has a significant impact on patients and their experience of the treatment process, as well as on health professionals. These practical, emotional and symbolic impacts are all the greater when the event occurs in the aftermath of an error. The ethical approach therefore comprises three essential stages: recognizing the event as such, informing those involved of the event and, finally, creating conditions for the continuation of care. Each of these stages is marked by specific issues and questions, requiring a complex ethical approach that constantly involves reconciling the possible divergent perceptions of patients and health professionals. The occurrence of an event can also lead to a genuine crisis of confidence with multiple dimensions, which health professionals will also have to face and to support. Finally, the occurrence of an event calls into question not only our responsibility towards patients, but also our ideal of control. We need to criticize our culture of performance, rethink our approach to events and errors, and see them also as opportunities for positive change.

Impact of kV-cone beam computed tomography dose on DNA repair mechanisms: A pilot study.

PURPOSE: In head and neck squamous cell carcinoma (HNSCC), early complications of the radiotherapy (RT) are observed from the beginning of the treatment to a few months after its end. During external radiotherapy treatment, several patient-dependent parameters can cause a modification of the dose distribution compared to the planned distribution due to variation in patient positioning, anatomy, or intra-fractional movements for example. To verify these parameters during treatment sessions, one of the most commonly used solutions is the cone-beam computed tomography (CBCT). Nowadays, the use of CBCT may constitutes a significant part of the total dose at the end of treatment (up to 10 cGy per session) and more often the volume irradiated by imaging is larger than the one irradiated by the treatment, leading to unintentional irradiation of nearby organs. In this study, we asked whether the imaging low dose added to a following fraction dose (2Gy) may affect the biological response in terms of DNA repair. MATERIAL AND METHODS: Using an IVInomad dosimeter and scintillating fiber probes specially designed for this exploratory study, we exposed fibroblasts cells from head and neck cancer (HNC) patients to a CBCT dose followed by a radiotherapy fraction dose. DNA double strand breaks and DNA repair were assessed by immunofluorescence using the biomarkers gamma H2AX (γH2AX) and pATM. RESULTS: The median dose of CBCT was measured between 17 to 21 mGy per session. The kinetics of both biomarkers were found to be strongly dependent on the individual factor in radiosensitive patients. For HNC patients, a prior CBCT dose applied few minutes before the 2Gy dose may have a sublinear effect on the DNA repair mechanisms and potentially on observed health tissue toxicity. CONCLUSION: The preliminary results obtained highlight the importance of individual and tissue factors for recognizing and repairing DSB during a treatment by radiotherapy using CBCT.

Radiation-induced lymphocyte apoptosis assay: Primetime for routine clinical use?

The impact of curative radiotherapy mainly depends on the total dose delivered to the tumor. However, despite recent technological advances, the dose delivered to surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In the same population treated at one center with the same technique, individual radiosensitivity clearly exists, particularly in terms of late side effects that are, in principle, non-reversible. This article details the history of the radiation-induced lymphocyte apoptosis assay, from preclinical data to multicenter clinical trials. It puts the performance of such assays into perspective to define the optimal clinical situations for its use in daily practice.

Towards clinical application of ultra-high dose rate radiotherapy and the FLASH effect: Challenges and current status.

Ultra-high dose rate external beam radiotherapy (UHDR-RT) uses dose rates of several tens to thousands of Gy/s, compared with the dose rate of the order of a few Gy/min for conventional radiotherapy techniques, currently used in clinical practice. The use of such dose rate is likely to improve the therapeutic index by obtaining a radiobiological effect, known as the "FLASH" effect. This would maintain tumor control while enhancing tissues protection. To date, this effect has been achieved using beams of electrons, photons, protons, and heavy ions. However, the conditions required to achieve this "FLASH" effect are not well defined, and raise several questions, particularly with regard to the definition of the prescription, including dose fractionation, irradiated volume and the temporal structure of the pulsed beam. In addition, the dose delivered over a very short period induces technical challenges, particularly in terms of detectors, which must be mastered to guarantee safe clinical implementation. IRSN has carried out an in-depth literature review of the UHDR-RT technique, covering various aspects relating to patient radiation protection: the radiobiological mechanisms associated with the FLASH effect, the used temporal structure of the UHDR beams, accelerators and dose control, the properties of detectors to be used with UHDR beams, planning, clinical implementation, and clinical studies already carried out or in progress.

Combination of radiotherapy and immunotherapy in duality with the protumoral action of radiation.

Radiotherapy is widely used to treat various cancers. Its combination with immune checkpoint inhibitors is intensively studied preclinically and clinically. Although the first results were very encouraging, the number of patients who respond positively remains low, and the therapeutic benefit is often temporary. This review summarizes how radiation can stimulate an antitumor immune response and its combination with immunotherapy based on inhibiting immune checkpoints. We will provide an overview of radiotherapy parameters that should be better controlled to avoid downregulating the antitumor immune response. The low response rate of combining radiotherapy and immunotherapy could, at least in part, be caused by the stimulation of cancer cell invasion and metastasis development that occur at similar doses and number of radiation fractions. To end on a positive note, we explore how a targeted inhibition of the inflammatory cytokines induced by radiation with a cyclooxygenase-2 inhibitor could both support an antitumor immune response and block radiation-induced metastasis formation.

[Borderlines and malignant phyllodes tumors of the breast: From the anatomopathological challenge to the standard of care]. / Tumeurs phyllodes borderlines et malignes du sein : du défi anatomopathologique à l'élaboration d'un standard de prise en charge.

Phyllodes tumors, borderline (BPT) and malignant (MPT), represent a rare group of fibroepithelial breast tumors. Due to their rarity, their treatment remains poorly codified. The precise incidence of these tumors remains unknown. TPMs represent half of breast sarcomas and 1 % of breast tumors. Their treatment at the localized stage is based on surgery, that can be conservative surgery or a mastectomy. The impact of oncoplastic techniques and immediate breast reconstruction is not documented. The excision margins of the BPT and MPT must be free, a wider margin can provide a benefit in local recurrence but in also overall survival in the case of TPM. The optimal width of the excision margin is not known. In the event of positive margins, a second surgery could make up the result of an insufficient first surgery. Chemotherapy does not seem to provide any benefit on recurrence-free survival, but the available data are particularly weak. The data on adjuvant radiotherapy are more important. This allows better local control in the event of breast-conserving surgery. The benefit of post-mastectomy radiotherapy is less documented but can be considered in cases of poor prognostic factors. The management of TPM at the metastatic stage is based on the use of chemotherapy (anthracyclines, Ifosfamide) and local treatment of metastases in cases of oligometastatic disease. Due to the rarity of these tumors, it is essential that their management be discussed within a network of qualified professionals (NETSARC+).

A multidisciplinary view of FLASH irradiation.

The delivery of ultra-high dose rates of radiation, called FLASH irradiation or FLASH-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of FLASH-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the FLASH effect and the ongoing developments to bring this new modality to patient treatment.

Practice-changing trials on breast cancer.

There is new data in the fractionation modalities and these are the really the practice-changing trials of last years: can we use hypo fractionated whole breast radiotherapy in patients presented with ductal carcinoma in situ? Can we realize hypofractionated whole breast radiotherapy with simultaneous integrated boost? What about hypofractionated irradiation after mastectomy with reconstruction? Can we do hypofractionation to lymph nodes without risk of increased toxicity? The purpose of this work is to respond with the last evidence-based recently presented or published data.

Committee of the new positions of the Société française de radiothérapie oncologique: Toward an advanced practice master in radiotherapy.

In 2022, the radiation therapist committee of the Association française du personnel paramédical d'electroradiologie médicale (AFPPE, French association of paramedical electroradiology technicians), the Société française de radiothérapie oncologique (SFRO, French society of radiation oncology) and the Syndicat national des radiothérapeutes oncologue (SNRO, national syndicate of radiation oncologists) have been committed to working on the development of advanced practice roles. The objective of this article is to report the activities that should be in the scope of radiation therapists advanced practice and describe the competences required for these activities. This work was carried out by six radiation therapists, six radiation oncologists and one medical physicist representatives of the French national societies for each professional group. First, a basic list of activities was established and then competences were identified for groups of activities. In total, the list includes five core competences, nine competences and nine groups of activities that can be divided into the four pillars of advanced practice. The nine groups of activities can be presented in seven different dimensions including patient care and support, treatment planning, treatment imaging and delivery, management and consultancy, quality and risk management, research and innovation, education and training. The French advanced practice competences framework was developed with a multidisciplinary group to move forward the project of a master degree in advanced practice in radiation therapy in France.

Prediction of radiotherapy toxicity: 20 years of COPERNIC radiosensitivity diagnosis procedure.

PURPOSE: Since 2004, in the frame of the care pathway, our Research Unit has replied to the demand of expertise of radiation oncologists about the individual radiosensitivity of some of their patients. This procedure, called COPERNIC, is based on a skin biopsy and the radiation-induced nucleoshuttling of the ATM protein (the RIANS model), a major actor of DNA break repair and signaling. In 2016, with the first 117COPERNIC fibroblast lines, we obtained a significant correlation between the maximum number of the nuclear ATM foci, pATMmax, and the CTCAE severity grade of the post-radiotherapy tissue reactions. In this study, we propose to verify the validity of our previous findings with a new COPERNIC data subset obtained in the 2014-2024 period. MATERIALS AND METHODS: We applied a standard immunofluorescence technique to quiescent COPERNIC fibroblasts to assess, after 2Gy, the level of micronuclei, γH2AX and pATM foci. The 117 COPERNIC data published in 2016 were considered as the reference data subset. A new COPERNIC data subset composed of 133fibroblast cell lines was considered as the validating data subset. RESULTS: Our data showed that spontaneous or residual micronuclei levels, and residual γH2AX foci levels cannot predict CTCAE grades. Conversely, the linear formula linking the maximal number of pATM foci and the corresponding CTCAE grade and obtained in 2016 from the reference data subset fitted well the validating data. CONCLUSIONS: The maximal number of pATM foci appears to be one of the most reliable biomarkers for predicting post-radiotherapy radiotoxicity.

Outcomes of adjuvant lymph node field radiotherapy and immunotherapy for stage III melanoma.

PURPOSE: With the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma. PATIENTS AND METHODS: This retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence. RESULTS: Thirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8-45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7% for the patients receiving immunotherapy alone (95% CI: 42.5-82.5%) and 83.3% for those receiving radiotherapy and immunotherapy (95% CI: 48.2-95.6%; P=0.131). The locoregional progression rate was 24% in patients receiving immunotherapy and 8% in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6% of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events. CONCLUSION: In patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies.

Voice quality after surgery or radiotherapy for glottic T1 squamous cell carcinoma: Results of the VOQUAL study.

PURPOSE: Many series have compared voice quality after radiotherapy or surgery for cT1 glottic carcinoma. Different meta-analyses identify better results for radiotherapy while others do not identify any difference, some finally find a superiority of surgery. The purpose of this study was to compare the voice quality in the long term of patients who underwent transoral surgery versus exclusive irradiation for the treatment of cT1 glottic carcinoma. MATERIAL AND METHODS: The VOQUAL study was a pilot comparative multicenter cross-sectional study. The primary endpoint was the Voice Handicap Index comparison between two groups (radiotherapy or surgery). The voice assessment also consisted in the heteroevaluation of voice quality by the Grade, Roughness, Breathness, Asthenia, and Strain rating scale reported by Hirano. RESULTS: The study included 41 adult patients with cT1 carcinoma of the vocal cord treated by cordectomy or exclusive radiation in two oncologic centers. The median Voice Handicap Index value was 20 [8; 32.5] in the surgery group and 10 [4; 18.5] in the radiotherapy group. There was no statistically significant difference between the median values and the various components F, P and E of the questionnaire (P=0.1585). The median value of the numeric dysphonia Grade, Roughness, Breathness, Asthenia, and Strain scale was 2 [0; 5] in the surgery group and 2 [0.25; 3.75] in the radiotherapy group. There was no statistically significant difference between these values (P=0.78). CONCLUSION: Our study did not show any significant difference on the primary endpoints of Voice Handicap Index and Grade, Roughness, Breathness, Asthenia, and Strain scores. LEVEL OF EVIDENCE: III. CLINICAL TRIAL REGISTRATION: The VOQUAL study was registered on the ClinicalTrials.gov platform under the number NCT04447456, in July 2020.