Radiation therapy of the primary tumour and oligometastatic sites in patients with breast cancer with synchronous metastases: A literature review.

De novo metastatic breast cancer represents 5 to 8% of all breast cancers (2500 new cases per year in France). Systemic treatment is the cornerstone of treatment, whereas radiation therapy usually has a palliative intent. Advances in systemic and local treatments (surgery and radiation therapy) have substantially improved overall survival. In the recent breast cancer statistics in the United States, the 5-year relative survival for patients diagnosed during 2012-2018 was 29% for stage IV (Breast Cancer Statistics). Thus, an increasing proportion of metastatic breast cancers present a prolonged complete response to systemic therapy, which raises the question of the impact of local treatment on patient survival. Radiation therapy has shown its value for early breast cancer, but its place in the local management of the primary tumour or oligometastatic sites for de novo metastatic breast cancer remains under debate. This article is a literature review assessing the role of radiation therapy directed to the primary tumour and oligometastatic sites of breast cancer in patients with synchronous metastases, in order to highlight clinicians in their therapeutic decision.

[Predictive factors assessment of pathological response to neoadjuvant radiotherapy of soft tissue sarcomas]. / Évaluation de facteurs prédictifs de réponse pathologique à la radiothérapie néoadjuvante des sarcomes des tissus mous.

PURPOSE: Conserving surgery combined with radiotherapy in presence of local recurrence risk factors is standard treatment of soft tissue sarcomas, a group of rare and heterogeneous tumours. Radiotherapy is performed before or after surgery. In neoadjuvant setting, late radiation-induced toxicity is reduced and pathological response to radiotherapy could be achieved. A complete pathological response to radiotherapy has recently been shown to predict better survival. Our study aims at identifying predictive factors of pathological response to neoadjuvant radiotherapy (clinical, radiological or histological) of soft tissue sarcomas. PATIENTS AND METHODS: Clinical, imaging (MRI: perilesional oedema, necrosis, tumour heterogeneity, vasculonervous relationships) and pathological (pathological subtype, tumour grade, anticipated/obtained resection quality) data were retrospectively collected. Tumour response (imaging and pathological), patient outcome, acute and late radiation-induced toxicity, predictive factors of pathological response to neoadjuvant radiotherapy were studied. The 2-test or exact-Fisher test (qualitative variables) and by Student's t-test or Kruskal-Wallis test (quantitative variables) were used for statistical analysis. RESULTS: From April 2017 to April 2021, neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgical excision was performed to 36 consecutive patients with liposarcomas (n=17/36), or undifferentiated sarcomas (n=8/36). MRI response was complete in 1 patient, partial in 9 patients (n=9/36, 25%), stable in 21 patients (n=21/36, 58%) or in progression in 5 patients (n=5/36, 14%). Pathological response was observed in 22 patients (61%). No grade 3-4 acute radiation-induced toxicity was observed. Regarding late toxicity, 28% of patients had grade 1-2 oedema (n=10/36), 39% had a grade 1 fibrosis (n=14/36), and 30% grade 1 pain (n=11/36). No predictive factors of response to radiotherapy was statistically significant. CONCLUSIONS: Neoadjuvant radiotherapy is well-tolerated. No clinical, radiological or pathological predictive factors was identified for radiotherapy tumour response.

[Breast cancer radiation therapy: Current questions in 2023]. / Radiothérapie des cancers du sein : questions d'actualité en 2023.

Radiation therapy is a corner stone of breast cancer treatment as it has been shown postoperatively that it improves local control and overall survival. In recent years, multidisciplinary therapeutic strategies have evolved considerably for early-stage breast cancer, both surgically and in terms of systemic treatments or radiation therapy. Each of these developments affects other treatment components and open up new questions allowing even more personalized treatments. Essentially normofractionated a few years ago, breast radiation therapy is today very largely moderately or even ultra hypofractionated. De-escalation of the surgery of the axilla has changed the indications for lymph node radiation therapy keeping similar efficacy with reduced toxicity. Indications for radiation therapy after neoadjuvant chemotherapy remain based on pre-chemotherapy staging pending the results of ongoing randomized studies. The addition of a boost to the tumor bed significantly reduces the risk of local recurrence, but the magnitude of this benefit decreases with increasing age. The main risk factors for local recurrence are young age, the associated extended ductal in situ component, hormone receptor negative and high-grade status. The results of the simultaneous integrated boost (SIB) seem similar with normo- or moderately hypofractionated radiation therapy regimen.

[Radiation therapists shortage in France: Organizational consequences and difficulties in deploying new missions and/or tasks delegation]. / Métier de manipulateur en radiothérapie en tension en France : conséquences organisationnelles et difficultés à déployer de nouvelles missions et/ou délégation de tâches.

PURPOSE: Radiation therapists shortage has been evaluated at national level in France, specifically in oncology radiotherapy, in terms of: (i) organizational adaptations, (ii) impact on patients care, and (iii) difficulties in deploying new missions and/or tasks delegation. MATERIALS AND METHODS: French professional organisations representing radiation therapists - SFRO, SNRO and AFPPE - sent their members a national survey (ten questions on 32 items). RESULTS: From 18 November 2022 to 31 December 2022, 55 responses were received (response rate: 31%) from radiotherapy managers or department heads; 51% had a structure comprising three to five treatment rooms (receiving 500 to 1000 patients per year [36%], or 1500 to 2000 patients per year [33%]). Activities performed were intensity-modulated radiotherapy (100%), stereotaxic radiotherapy (85%), brachytherapy (40%), adaptive radiotherapy (34%). These structures described consequences in closing machine time for 25% of them (reduction of the hourly volume greater than 10% in 57%) with the following consequences in the last 6 months: (i) an extension of the period of medical care (78%), a closing of one or more accelerators (50%) and the development of moderate hypofractionation scheme or extreme hypofractionation (50%). In current functioning, linear accelerators can deliver treatments with a team of two radiation therapists per room for a short day (43%) or two to four radiation therapists per room teams for a long day (40%). During the last 6 months, there has been a 10% increase in linear accelerators operating with a single team. (ii) regarding treatment planning: 16.4% reported a decrease in the opening amplitude (less than 20% in 44% of cases, from 20 to 50% in 33 % of cases). The initial scheduling of appointments for radiotherapy sessions was carried out by radiation therapists in 84% of the departments in current functioning (0.1 to 1 FTE dedicated to this activity in 62% of the departments). Over the last 6 months, there has been a clear reduction in the number of dedicated FTEs: [FTE=0.1 to 1]=-8%; [FTE=0]=+7%. (ii) Regarding tasks delegation (excluding the decree on acts and activities carried out by the radiation therapist): organ at risk delineation is partially performed by radiation therapist in 26% of the centres; caregiver support time in 78% (56% totally or 22% partially). This activity has been reduced by 42%. Seventy-five percent of departments want to develop new techniques, patient-centered approaches (44%), implement task delegation (organ at risk delineation: 58%; weekly consultations: 67%; positioning imaging validation: 71%), and 78% of departments are interested in developing advanced radiotherapy practice. However, the number of radiation therapists is considered insufficient in their implementation in 76% of cases (one to two FTE missing for 72% of structures). CONCLUSION: This survey shows a significant impact of radiation therapist shortage in radiotherapy oncology care (treatment delays, access to caregiver support time, workload on treatment teams), and represents a major obstacle to the development of radiotherapy structures.

The 2022 Assisi Think Tank Meeting: White paper on optimising radiation therapy for breast cancer.

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation.

Radiotherapy of breast cancer.

Adjuvant radiotherapy is an essential component of the treatment of breast cancer. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neoadjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra- and infraclavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with or after radiotherapy.

[Treatment of primary disease with irradiation in case of de novo metastatic breast cancer]. / Irradiation de la tumeur primitive en cas de cancer du sein métastatique synchrone.

Synchronous metastatic breast cancer accounts for 5 to 6% of all breast cancers in Western countries, which corresponds to nearly 2500 new cases per year in France. Irradiation of the primary tumour in cases of metastatic disease at diagnosis was historically reserved for palliative indications. However, progress in systemic treatments, a better understanding of the biological basis of metastatic dissemination, the genesis of the concept of oligometastatic disease and ablative treatments directed towards metastases are revolutionizing the management of patients with de novo stage IV breast cancer. Survival of these patients has improved markedly over the years, and several studies have investigated the carcinological benefit of local treatment of the breast tumour in patients with advanced diseases at diagnosis. This article provides an update on the role of irradiation of the primary tumour in breast cancer with synchronous metastases, and discusses its interest through published or ongoing trials.

Radio-induced cardiotoxicity: From physiopathology and risk factors to adaptation of radiotherapy treatment planning and recommended cardiac follow-up.

Cancer and cardiovascular disease (CVD) are the leading cause of mortality worldwide, and breast cancer (BC) the most common malignancy affecting women worldwide. Radiotherapy is an important component of BC treatment and participates in CVD occurrence. It seems, therefore, crucial to gather both radiation oncology and cardiology medical fields to improve the follow-up quality of our BC patients. This review aims at updating our knowledge regarding cardiotoxicities risk factors, and consequently, doses constraints in case of 3D-conformal and IMRT treatment planning. Then we will develop how to reduce cardiac exposure and what kind of cardiac follow-up we could recommend to our breast cancer patients.

[Radiation-oncology horizon 2030: From microbiota to plasma laser]. / Oncologie-radiothérapie horizon 2030 : du microbiote au laser plasma.

Advances in physical, technological and biological fields have made radiation oncology a discipline in continual evolution. New current research areas could be implemented in the clinic in the near future. In this review in the form of several interviews, various promising themes for our specialty are described such as the gut microbiota, tumor organoids (or avatar), artificial intelligence, connected therapies, nanotechnologies and plasma laser. The individual prediction of the best therapeutic index combined with the integration of new technologies will ideally allow highly personalized treatment of patients receiving radiation therapy.

[From fibrogenesis towards fibrosis: Pathophysiological mechanisms and clinical presentations]. / De la fibrogenèse à la fibrose : mécanismes physiopathologiques et présentations cliniques.

Fibrogenesis is a universal and ubiquitous process associated with tissue healing. The impairment of tissue homeostasis resulting from the deregulation of numerous cellular actors, under the effect of specific cytokine and pro-oxidative environments can lead to extensive tissue fibrosis, organ dysfunction and significant morbidity and mortality. This situation is frequent in internal medicine, since fibrosis is associated with most organ insufficiencies (i.e. cardiac, renal, or hepatic chronic failures), but also with cancer, a condition with common pathophysiological mechanisms. Finally, fibrosis is a hallmark of numerous systemic autoimmune diseases such as connective tissue disorders (in particular systemic sclerosis), vasculitides, granulomatoses, histiocytoses, and IgG4-associated disease. Although the process leading to tissue fibrosis may be in part irreversible, new pharmacological approaches or cell therapies bring hope in the field of fibrotic conditions.

[Treatment of oligometastatic or oligoprogression cancer]. / Traitement des oligometastases et oligoprogression.

We propose in this short review to report the impact of stereotactic body radiation therapy (SBRT) in oligometastatic or oligoprogressive cancer patients in terms of metastatic progression-free and global survival, and to identify the place of SBRT in patient's pathway.

[Treatment of primary disease (breast, non-small cell lung and prostate cancers) with irradiation in case of de novo metastatic cancer]. / Traitement de la maladie primitive (cancers du sein, du poumon non à petites cellules et de la prostate), par irradiation, au stade d'emblée métastatique.

The basis of treatment of primary disease in case of metastatic cancer at diagnosis is based on the knowledge of the natural history of the disease, the biology of the primary tumour and its metastases, advances in modern radiotherapy techniques (modulated intensity, stereotactic radiotherapy) in order to improve the survival of patients with advanced disease. The clinical concept of oligometastatic disease at diagnosis has repositioned the interest of local treatment for primitive disease because these patients have a slower evolutionary profile than metastatic disease extended from the outset. This article reviews the indication of radiotherapy as a local treatment for primary cancer in a de novo metastatic diagnosed disease in the case of breast cancer, non-small cell lung cancer and prostate cancer.

[Predictive assays for responses of tumors and normal tissues in radiation oncology]. / Outils pour la prédiction de la réponse tumorale et des tissus sains en oncologie radiothérapie.

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better predict the tumor response but also the radiation-induced late effects.

[Individual modification of the dose, volume and fractionation of breast radiotherapy]. / Personnalisation de la dose, du volume et du fractionnement de la radiothérapie du sein.

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.

The Assisi Think Tank Meeting Survey of post-mastectomy radiation therapy in ductal carcinoma in situ: Suggestions for routine practice.

BACKGROUND: Risk factors for local recurrence after mastectomy in ductal carcinoma in situ (DCIS) emerged as a grey area during the second "Assisi Think Tank Meeting" (ATTM) on Breast Cancer. AIM: To review practice patterns of post-mastectomy radiation therapy (PMRT) in DCIS, identify risk factors for recurrence and select suitable candidates for PMRT. METHODS: A questionnaire concerning DCIS management, focusing on PMRT, was distributed online via SurveyMonkey. RESULTS: 142 responses were received from 15 countries. The majority worked in academic institutions, had 5-20 years work-experience and irradiated <5 DCIS patients/year. PMRT was more given if: surgical margins <1 mm, high-grade, multicentricity, young age, tumour size >5 cm, skin- or nipple- sparing mastectomy. Moderate hypofractionation was the most common schedule, except after immediate breast reconstruction (57% conventional fractionation). CONCLUSIONS: The present survey highlighted risk factors for PMRT administration, which should be further evaluated.

Partial versus whole breast irradiation: Side effects, patient satisfaction and costs.

PURPOSE: Since accelerated partial breast irradiation has demonstrated non-inferiority to whole breast irradiation regarding recurrence rate in patients with early stage breast cancer, our objective was to compare its impact on short-term adverse events, patient satisfaction and costs. MATERIALS AND METHODS: Patients with early stage breast cancer treated by breast-conserving surgery between 2007 and 2012 were included: 48 women who received three-dimensional conformal accelerated partial breast irradiation in a multicentre phase-II trial were paired with 48 patients prospectively treated with whole breast irradiation. Adverse events, and patients' opinions concerning cosmesis, satisfaction and pain, were gathered 1 month after treatment. Direct and indirect costs were collected from the French National Health Insurance System perspective until the end of radiotherapy. RESULTS: When comparing its impact, skin reactions occurred in 37% of patients receiving three-dimensional conformal accelerated partial breast radiotherapy and 60% of patients receiving whole breast irradiation (P=0.07); 98% were very satisfied in the group three-dimensional conformal accelerated partial breast radiotherapy versus 46% in the group treated with whole breast irradiation (P<0.001); direct costs were significantly lower in the group treated with partial breast irradiation (mean cost: 2510€ versus 5479€/patient), due to less radiation sessions. CONCLUSION: In patients with early-stage breast cancer, partial irradiation offered a good alternative to whole breast irradiation, as it was less expensive and satisfactory. These, and the clinical safety and tolerance results, need to be confirmed by long-term accelerated partial breast irradiation results in on-going phase III trials.

Magnetic resonance imaging in breast cancer management in the context of neo-adjuvant chemotherapy.

This review discusses the clinical applications of magnetic resonance imaging (MRI) for the assessment of neo-adjuvant chemotherapy (NAC) indication, axillary lymph node status, preNAC cancer prognosis, early and intermediate response to NAC, and post-NAC residual disease in patients with breast cancer. Contrast-enhanced MRI with analysis of the tumor morphological features and qualitative enhancement kinetics must be considered as the standard method for pre-NAC breast cancer staging and post-NAC residual disease assessment. Diffusion-weighted imaging (DWI) is easy to perform and may increase the specificity of breast MRI for tumor staging, and also for the assessment of tumor multifocality and multicentricity and lymph node status. It also provides an ancillary added value in the early and post-NAC response evaluation. Changes in the functional tumor volume are the main criterion for the early response analysis. Other MRI methods, such as quantitative perfusion analysis, MR spectroscopy and texture analysis, are still under study.

[Modalities and advantages of image guided radiation therapy of breast cancer in adjuvant setting]. / Modalités et intérêt de radiothérapie guidée par l'image pour les cancers du sein en situation adjuvante.

In adjuvant setting, breast cancer radiotherapy volumes include whole mammary gland or chest wall, and when indicated, nodal area such as axilla, supraclavicular, and internal mammary chain. An accurate patients positioning is required due to some geometric complexity of target volumes closed to organs at risk as heart and lung. Image guided radiation therapy allows such accuracy. Here we propose a review on image guided radiotherapy for breast cancer.

[The major debate: Micrometastases and breast cancer - To be for nodal irradiation]. / Le grand débat : cancers du sein pN1mi ­ pour l'irradiation des aires ganglionnaires.

Standard of care in breast cancer management is well-defined. However, some gray zones still exist, in particular adjuvant radiotherapy indications in case of pN1mi breast cancer. Here we propose to define their prognosis, to underpin the benefit of adjuvant treatments in such patients' management and to define lymphedema risk, which is the most common late side effect of locoregional treatments.