Guidelines for external radiotherapy and brachytherapy procedures: 3rd edition.

The purpose of the first two editions of the guidelines for external radiotherapy procedures, published in 2007 and 2016 respectively, was to issue recommendations aimed at optimising, harmonising and standardising practices. The purpose of this third edition, which includes brachytherapy, is identical while also taking into account recent technological improvements (intensity modulation radiation therapy, stereotactic radiotherapy, and three-dimension brachytherapy) along with findings from literature. Part one describes the daily use of general principles (quality, security, image-guided radiation therapy); part two describes each treatment step for the main types of cancer.

Radiotherapy of lymphomas.

Radiotherapy for Hodgkin lymphomas has evolved a lot over time, but still plays an important role, almost always in addition to chemotherapy, for the management of the early stages. The major objective is to preserve the quality of life of patients who will be cured from this disease in the vast majority of cases. Also, the personalization of the indications for the purpose of de-escalating toxicity is very refined and is essentially based on the pre- and pertherapeutic assessment by FDG-PET. The indications for radiotherapy are more limited for non-Hodgkin lymphomas, but the same principles are found, regardless of the histological type. We present the update of the recommendations of the French society of oncological radiotherapy for radiotherapy of lymphomas, which remains a very evolving field in terms of therapeutic strategy and evaluation.

External irradiation treatment process.

The purpose of this article is to describe the external irradiation process and updated recommendations of the French society for radiation oncology for patient follow-up.

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.

[Proton therapy in France in 2019]. / État des lieux de la protonthérapie en France en 2019.

Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France.

RILA blood biomarker as a predictor of radiation-induced sarcoma in a matched cohort study.

PURPOSE: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT). PATIENTS AND METHODS: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry. RESULTS: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ±â€¯16.0 Gy) and control patients (57.1 ±â€¯15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95%CI [0.221-0.599]. CONCLUSION: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and compared with molecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up.

Prevalence of burnout, depression and job satisfaction among French senior and resident radiation oncologists.

PURPOSE: Cancer caregivers are at high risk of burn-out, with potential severe consequences on professionals' health and on patients' care. We have investigated the prevalence of burn-out and its impact in terms of psychological morbidity among French radiation oncologists. METHODS AND MATERIALS: An anonymous online questionnaire was advertised in all French senior radiation oncologists and residents, including demographical data, job-related stress factors, drug use, the Maslach Burn-out Inventory (MBI) and the General Health Questionnaire (GHQ-12). RESULTS: The response rates were 37% (76 out of 204) for radiation oncologists and 22% (166 out of 751) for residents. Sixty-four (84%) radiation oncology residents and 104 (63%) radiation oncologists met criteria for moderate/severe burn-out (odd ratio 2.1 [95% confidence interval 1.0-4.8], P=0.03). Radiation oncology residents were more prone to depersonalization (P<0.001) and lower personal accomplishment (P<0.001). Burn-out was more frequent in radiation oncologists working for public facilities. Symptoms of depression (GHQ-12≥4) were reported by 42% of residents and 36% of radiation oncologists (P=0.40). Psychological morbidity, suicidal ideation and anxiolytic consumption were more frequent in burnt out responders. CONCLUSION: Our figures are in the highest range of published data. Active screening and prevention of burn-out should be implemented and particularly aimed at radiation oncology residents.

[Siriade 2.0: An e-learning platform for radiation oncology contouring]. / Siriade 2.0 : outil de formation en ligne à la délinéation en radiothérapie.

PURPOSE: In 2008, the French national society of radiation oncology (SFRO) and the association for radiation oncology continued education (AFCOR) created Siriade, an e-learning website dedicated to contouring. MATERIAL AND METHODS: Between 2015 and 2017, this platform was updated using the latest digital online tools available. Two main sections were needed: a theoretical part and another section of online workshops. RESULTS: Teaching courses are available as online commented videos, available on demand. The practical section of the website is an online contouring workshop that automatically generates a report quantifying the quality of the user's delineation compared with the experts'. CONCLUSION: Siriade 2.0 is an innovating digital tool for radiation oncology initial and continuous education.

Breast lymphoma occurring after an invasive ductal breast carcinoma developed in the same area: A case report and literature review.

Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment.

[Stereotactic body radiation therapy for hepatic malignancies: Organs at risk, uncertainties margins, doses]. / Radiothérapie stéréotaxique hépatique : organes à risque, marges d'incertitudes, doses.

Stereotactic body radiation therapy for primary and metastatic hepatic malignancies can be performed in association and/or as an alternative to surgery and radiofrequency. The consequences of the great number of techniques available are heterogeneity in contouring, dose prescription and in determination of dose constraints for organs at risk. The objective of this paper is to improve the quality and safety and to help the diffusion of this technique for a majority of patients. In 2016, the French Society of Radiation Oncology (SFRO) published guidelines for external radiotherapy and brachytherapy ("Recorad"). This paper is an update of these recommendations considering recent publications.

Clinical and diagnosis characteristics of breast cancers in women with a history of radiotherapy in the first 30years of life: A French multicentre cohort study.

PURPOSE: Irradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer. PATIENTS AND METHODS: This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC. RESULTS: A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up. CONCLUSION: Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient's age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage.

Respiratory-gated bilateral pulmonary radiotherapy for Ewing's sarcoma and nephroblastoma in children and young adults: Dosimetric and clinical feasibility studies.

PURPOSE: Bilateral pulmonary radiotherapy in children and young adults aims to reduce the recurrence of lung metastases. The radiation field includes liver tissue, which is sensitive to even low radiation doses. We investigated the feasibility of respiratory gating radiotherapy using voluntary deep inspiration breath hold and its toxicity in these patients. PATIENTS AND METHOD: A retrospective clinical review was conducted for all patients who had undergone bilateral pulmonary radiotherapy, with or without deep inspiration breath hold, treated in our institution between October 1999 and May 2012. A dosimetric study was conducted on seven consecutive children using 4D-scan data on free-breathing and a SpiroDyn'RX-system-scan on deep inspiration breath hold. A radiation treatment of 20Gy was simulated. RESULTS: Concerning the clinical study, seven patients of mean age 11.9 years (range: 4.9-21.1 years) were treated with free-breathing and ten patients of mean age 15.6 years (range: 8.6-19.7 years) were treated with deep inspiration breath hold for mainly Ewing sarcoma and nephroblastoma. Within six months of radiotherapy, all patients experienced mild liver toxicity (grade 1 or 2 altered levels of alanine/aspartate aminotransferase [n=8 of 9] or cholestasis [n=1 of 9]), which resolved completely with no difference between deep inspiration breath hold and free-breathing technique. Over a median follow-up of 2.6 years (range: 0.1-9.3 years), four patients died from disease progression (mean 1.5 years post-radiotherapy [range: 1.1-1.6 years]) and three experienced grade III-V lung toxicity. Concerning the dosimetric study, the irradiated liver volume was significantly lower with deep inspiration breath hold than free-breathing, for each isodose (V5: 73.80% versus 86.74%, P<0.05; V20: 5.70% versus 26.44%, P<0.05). CONCLUSIONS: The dosimetric data of respiratory-gated bilateral pulmonary radiotherapy showed a significantly spare of normal liver tissue. Clinical data showed that this technique is feasible even in young children. However, no liver toxicity difference between deep inspiration breath hold and free-breathing was shown.

[Clinical to target volume margins determination in radiotherapy for anal cancers]. / Détermination des marges du volume cible anatomoclinique au volume cible prévisionnel pour la radiothérapie des cancers du canal anal.

There are very few data on the expansion from the clinical target volume (CTV) to the planning target volume (PTV) in the anal cancer treatment. This article aims to collect the different elements needed for the construction of a PTV from scientific data based on a literature analysis. We reviewed the articles published in the medical literature from the last 20years. They concerned setup errors and internal organ mobility of the different volumes of patients treated by conformational radiotherapy and intensity-modulated radiotherapy (anal canal, meso-rectum, common, intern and extern, inguinal and pre-sacral lymph nodes). CTV to PTV margins admitted in the guidelines and atlas of consensus groups (SFRO, RTOG, AGITG) are from 0.7 to 1cm in all directions, based on expert's opinions but not on scientific data. There are no specific studies on the canal anal mobility. Most of the data are from other pelvis cancers (gynecologic, rectum and prostate). Setup errors can be reduced by daily imaging. Patient repositioning and immobilization modalities are mostly local habits rather than scientific consensus. A three-dimensional 1cm margin is generally admitted. Margins reduction must be careful and has to be assessed.

[Radiotherapy in localized stages of follicular and diffuse non-Hodgkin's lymphomas]. / Radiothérapie des lymphomes malins non hodgkiniens ganglionnaires folliculaires et diffus de stade limité.

Treatment with monoclonal antibodies, especially rituximab, is more and more frequent and questions the interest of radiotherapy in limited stages of diffuse B-cell large cell and follicular non-Hodgkin's lymphomas. From a review of literature, it appears that radiotherapy is of interest in bulky disease, patients with incomplete metabolic response, elderly patients receiving short chemotherapy and those with recurrence after exclusive chemotherapy. Finally, this article gives recommendations on available techniques of radiotherapy and doses to be delivered.

[Radiotherapy of breast cancer]. / Radiothérapie du cancer du sein.

In breast cancer, radiotherapy is an essential component of the treatment. 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. Partial breast irradiation could not be proposed routinely but only in very 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 neo-adjuvant 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 infra-clavicular 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). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. 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 case of 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 radiotherapy.

[Radiotherapy of skin cancers]. / Radiothérapie des cancers cutanés.

The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules.

[The irradiation process]. / Processus du traitement par irradiation.

The purpose of this article is to describe the regulatory framework of the radiotherapy practice in France, the external irradiation and brachytherapy process and the guidelines for patient follow-up.

[Radiotherapy of lymphomas]. / Radiothérapie des lymphomes.

Radiotherapy for Hodgkin's lymphoma has evolved over time but retains a dominant position in the treatment of early stage tumours. Its indications are more limited for non-Hodgkin's lymphomas, but the techniques follow the same principles whatever the histological type. This review presents the French recommendations in terms of preparation and choice of irradiation techniques.

[Guidelines for external radiotherapy and brachytherapy: 2nd edition]. / Recommandations en radiothérapie externe et curiethérapie (Recorad) : 2(e) édition.

In 2007, a first edition was published with the objective to produce guidelines for optimization, harmonization and homogenization of practices in external radiation therapy in France. The second edition, including brachytherapy, has the same objective and takes into account recent technologic improvements (intensity modulation radiation therapy, stereotactic radiotherapy, and 3-dimension brachytherapy) and results of literature. The first part is about daily use of general principles (quality, security, image-guided radiation therapy) and the second is to describe each treatment step in main cancers.

[Frameless set-up with ExacTrac® system for stereotactic radiotherapy of brain metastasis: Descriptive study from five French centres]. / Repositionnement par le système ExacTrac® pour l'irradiation sans cadre invasif de métastases cérébrales en conditions stéréotaxiques : étude descriptive de cinq centres français.

PURPOSE: This study aimed to analyse the positioning protocols with the ExacTrac® system, associated with a dedicated linear accelerator such as Novalis®, for stereotactic treatment of brain metastases in several French centres. MATERIALS AND METHODS: A survey, including three questions about the prescription of irradiation and twenty-one questions about how the ExacTrac® system is used, was sent to nine French centres owning a dedicated Novalis® accelerator. Five centres have accepted to participate in the study. RESULTS: All centres checked the positioning before each treatment's bow, with residual mismatch tolerances of 0.5 to 0.7mm for the translations and 0.5 to 1° for the rotations. All centres except one also realised orthogonal planar images of classic incidences to help operators ensure proper isocentre positioning. Prescribed doses were 20Gy in one fraction, 30Gy and 33Gy in three fractions or 34Gy in four fractions, mainly depending on the size of the lesion. Finally, a physician validated the images at the treatment station before starting the irradiation. CONCLUSIONS: The practices of the different centres concerning the positioning protocols were rather homogeneous, in agreement with the literature data on ExacTrac® system's accuracy, as well as proposed fractionations. The systematic medical validation at the treatment station may, however, be questioned because of the waiting time between the doctor's call and validation itself and because of its usefulness; indeed, corrections by the radiation oncologist are very rare and in some centres, non-existent.