Neurological side effects of radiation therapy.

Radiation therapy (RT) is one of the main treatments administered to patients with cancer. The development of technology has improved RT accuracy by allowing more precise delivery of high doses to the target volumes with reduced exposure of healthy tissue. Life expectancy has increased due to these therapeutic advancements and the patients' quality of life remains a major concern. The adverse events related to RT are quite various and most likely will impair essential neurological functions, e.g. cognitive status. This literature review aims to describe the physiopathological processes, the neurological symptoms as well as the local modifications observed in magnetic resonance imaging following RT. The specific therapeutic options and preventive actions will also be discussed.

Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study.

BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.

[Informed consent in radiotherapy care]. / Consentement aux soins en radiothérapie.

Obtaining consent to care requires the radiation oncologist to provide loyal information and to ensure that the patient understands it. Proof of such an approach rests with the practitioner. The French Society for Radiation Oncology (SFRO) does not recommend the signature of a consent form by the patient but recommends that the radiation oncologist be able to provide all the elements demonstrating the reality of a complete information circuit.

Osteosarcomas of the mandible: multidisciplinary management of a rare tumor of the young adult a cooperative study of the GSF-GETO, Rare Cancer Network, GETTEC/REFCOR and SFCE.

BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.

Impact of neoadjuvant chemotherapy on survival in breast cancer patients in daily practice: a population-based study.

This population-based study aimed to describe the effects of neoadjuvant chemotherapy (NC) on survival in breast cancer (BC) patients in daily practice. BC patients treated with NC followed by surgery and radiotherapy, were retrospectively selected from 1982 to 2005 using the Côte d'Or BC registry. These patients were matched for the baseline AJCC (American Joint Committee on Cancer) stage, age at diagnosis, date of diagnosis and oestrogens receptors status to those who had undergone surgery followed by adjuvant chemotherapy and radiotherapy. The prognostic effect of NC on survival in BC patients was assessed with relative survival (RS) analyses. From 1982 to 2005, 210 patients with BC diagnosed in Côte d'Or were treated with NC followed by surgery and radiotherapy. For these patients, mean age at diagnosis was 50 (SD = 11). The main tumour characteristics were clinical AJCC stage 3 (46%) and an advanced Scarff Bloom and Richardson (SBR) stage (80%). Breast conserving surgery was performed in 84 patients (40%), 151 patients (72%) were treated with anthracyclines as the NC and the 5-year RS rate was 71%. Among these patients, 92 (37%) were matched. In this population, multivariate analyses showed that the use of NC did not independently influence RS: relative excess risk = 0.93 (0.50, 1.71).

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.

Hypofractionated postoperative stereotactic radiotherapy for large resected brain metastases.

PURPOSE: The aim of the present retrospective study was to report outcomes after hypofractionated stereotactic radiotherapy (HSRT) for resected brain metastases (BM). PATIENTS AND METHODS: We reviewed results of patients with resected BM treated with postoperative HSRT (3×7.7Gy to the prescription isodose 70%) between May 2013 and June 2020. Local control (LC), distant brain control (DBC), overall survival (OS), leptomeningeal disease relapse (LMDR), and radiation necrosis (RN) occurrence were reported. RESULTS: Twenty-two patients with 23 brain cavities were included. Karnofsky Performance status (KPS) was≥70 in 77.3%. Median preoperative diameter was 37mm [21.0-75.0] and median planning target volume (PTV) was 23 cm3 [9.9-61.6]. Median time from surgery to SRT was 69 days [7-101] and 48% of patients had a local relapse on pre-SRT imaging. Median follow-up was 17.5 months [1.6-95.9]. One and two-year LC rates were 60.9 and 52.2% respectively. One and 2-year DBC rates were 45.5 and 40.9%. Median OS was 16.5 months. Four patients (18.2%) presented LMDR during follow-up. RN occurred in 6 patients (27.2%). Three factors were associated with OS: ECOG-PS (P=0.009), KPS (P=0.04), cystic or solid nature of the metastasis before surgery (P=0.037). Several factors were related to RN occurrence: PTV diameter and volume, Normal brain V21, V21 and V24 isodoses volumes. CONCLUSION: HSRT is the most widely used scheme for larger brain cavities after surgery. The optimal dose and scheme remain to be defined as well as the optimal delay between postoperative SRT and surgery. Dose escalation may be necessary, especially in case of subtotal resection.

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases.

PURPOSE: Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery. PATIENTS AND METHODS: From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3. RESULTS: The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05). CONCLUSION: A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.

Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Management of oropharyngeal squamous cell carcinoma.

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

Hepatic tumours and radiotherapy.

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.

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

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

Radiotherapy for laryngeal cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of laryngeal cancers. Intensity modulated radiotherapy is the standard of care radiotherapy for the management of laryngeal cancers. Early stage T1 or T2 tumours can be treated either by radiotherapy or conservative surgery. For tumours requiring total laryngectomy (T2 or T3), an organ preservation strategy by either induction chemotherapy followed by radiotherapy or chemoradiotherapy with cisplatin is recommended. For T4 tumours, a total laryngectomy followed by radiotherapy is recommended when feasible. Dose regimens for definitive and postoperative radiotherapy are detailed in this article, as well as the selection and delineation of tumour and lymph node target volumes.

[Efficacy and tolerance of salvage curative radiotherapy for patients with cervical relapse of differentiated thyroid carcinoma]. / Efficacité et tolérance de la radiothérapie externe pour les patients atteints d'une récidive d'un carcinome différencié de la thyroïde.

PURPOSE: Radiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin. MATERIAL AND METHODS: This monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma - vesicular or papillary - in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4. RESULTS: Thirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2years was 66.7%. The median LRPFS was 48months [32.9-not reached] and the median overall survival 49months [38.8-not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57-166.78], P=0.00113) and LRPFS (HR: 33.91 [4.46-257.61], P=0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81-99,76], P=0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57-16.66], P=0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P=0.34, LRPFS: P=0.84). The rate of acute grade 3 toxicities was 14%. CONCLUSION: Salvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone.

Radiotherapy for nasopharyngeal cancer.

Nasopharyngeal cancers are a rarity in France. Radiotherapy is the cornerstone of treatment, frequently combined with chemotherapy. The technical modality of radiotherapy is complex in this disease, which is located in the vicinity of numerous organs at risk. In this article, we will present the updated guidelines of the French society for radiation oncology (Société française de radiothérapie oncologique, SFRO) on the indications, and technical details of radiotherapy in nasopharyngeal cancers.

RadioTransNet: Preclinical research network coordinated at the SFRO and SFPM.

The RadioTransNet programme launched under the auspices of French societies for radiation oncology (SFRO) and medical physics (SFPM) was approved by the French national cancer institute (INCa) in December 2018 and is dedicated to proposing a relevant national and transversal structure for preclinical research including translational research in radiation oncology with well-defined priority areas of research. Its activities, coordinated by a scientific committee that includes radiation oncologists, medical physicists, academic biologists, are structured around several main areas, i.e.: target volume definition, interaction of radiation with normal tissues, combined treatments and modern dose calculation approaches. Four work packages have been created in these areas and are associated with other objectives pertaining to fundamental radiobiology, early implementation of new drugs in a preclinical setting, contribution of imaging in this task, research in medical physics including transversal components such as medical oncology, radiology, nuclear medicine and also cost/efficiency evaluation. All these tasks will be included in a national network that uses the complementary expertise provided by partners involved in the scheme. Calls for proposals will be selected by the scientific council to be submitted to INCa and the various academic associations to obtain funding for the human and technical resources required to conduct under optimal conditions projects in preclinical and translational research in radiation-oncology.

Optic nerve motion and gaze direction: Their impact on intraorbital tumor radiotherapy.

PURPOSE: Management of inter- and intra-fraction movements of target volumes and organs at risk (OARs) during radiotherapy is essential. While there is little OAR or target volume movement, the movements and orientation of the eyes can be significant during radiotherapy and they can affect the position of the optic nerve. The objective of the present study was to assess the variations of the optic nerve position due to gaze direction and to discuss their clinical consequences on the radiation treatment of intraorbital tumors. MATERIAL AND METHODS: Three patients without a history of oculomotor nerve palsy underwent six CT acquisitions with a thermoplastic mask: eyes open with different gaze directions (straight ahead, left, right, up, down) and eyes closed. The acquisition with the straight-ahead gaze was chosen as the reference position. Left and right optic nerves were segmented on the six acquisitions, and total volumes and maximum amplitude motions were calculated in three dimensions. RESULTS: Maximum differences were observed while looking left and up, with a median maximum amplitude of 5 and 6mm [range: 2-7mm], respectively. These motions induced a position variation of more than 50% of the volume of the optic nerve (compared to the reference position). Greater variations of motion were observed for the anterior portion of the nerve. The gaze position with the fewest variations compared to the reference position was eyes closed. CONCLUSION: Optic nerve positions vary significantly due to the gaze direction, especially for the anterior portion of the nerve. These variations should be taken into account for the treatment of small intraorbital tumors involving the anterior third of the optic nerve.

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.