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.

[Dose optimization in 3D pulsed dose rate brachytherapy for patients with locally advanced cervical cancer: A French multicenter phase II trial]. / Optimisation de la curiethérapie utérovaginale de débit pulsé des cancers du col utérin localement évolués : résultats finaux du PHRC Tridicol.

PURPOSE: We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers. MATERIAL AND METHODS: Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy. RESULTS: The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications. CONCLUSION: HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Rectal cancer radiotherapy.

We present the updated recommendations of the French society of oncological radiotherapy for rectal cancer radiotherapy. The standard treatment for locally advanced rectal cancer consists in chemoradiotherapy followed by radical surgery with total mesorectal resection and adjuvant chemotherapy according to nodal status. Although this strategy efficiently reduced local recurrences rates below 5% in expert centres, functional sequelae could not be avoided resulting in 20 to 30% morbidity rates. The early introduction of neoadjuvant chemotherapy has proven beneficial in recent trials, in terms of recurrence free and metastasis free survivals. Complete pathological responses were obtained in 15% of tumours treated by chemoradiation, even reaching up to 30% of tumours when neoadjuvant chemotherapy is associated to chemoradiotherapy. These good results question the relevance of systematic radical surgery in good responders. Personalized therapeutic strategies are now possible by improved imaging modalities with circumferential margin assessed by magnetic resonance imaging, by intensity modulated radiotherapy and by refining surgical techniques, and contribute to morbidity reduction. Keeping the same objectives, ongoing trials are now evaluating therapeutic de-escalation strategies, in particular rectal preservation for good responders after neoadjuvant treatment, or radiotherapy omission in selected cases (Greccar 12, Opera, Norad).

[Impact of reconstructive or minimal invasive surgery on the assessment of current definitions of postoperative clinical target volume for head and neck cancers]. / Impact de la chirurgie reconstructrice avec lambeaux et de la chirurgie mini-invasive sur la définition du volume cible anatomoclinique des cancers de la sphère ORL.

Advances in the reconstructive surgery and minimally invasive endonasal endoscopic surgery of head and neck is poorly evaluated in terms of their impact on radiotherapy planning and outcomes. These surgical advances have resulted in reduced morbidity with equivalent or better tumor control. In the absence of a recommendation on how to delineate target volumes in patients with flaps or to consider margins after endoscopic endonasal surgery, radiotherapy practices are inevitably heterogeneous. Efforts are needed to increase the therapeutic index of postoperative radiotherapy in these situations. We analysed the rare existing literature and outlined a preliminary basis for a recommendation. Strengthening of multidisciplinarity to accurately define target volumes in these complex and relatively new situations, and "delineation concertation meetings" between radiologists, surgeons and radiation oncologists could probably contribute to improved outcomes.

[Anal canal cancer: In the era of intensity-modulated radiotherapy, outstanding issues]. / Cancer du canal anal : à l'ère de la radiothérapie conformationnelle avec modulation d'intensité, questions en suspens.

Intensity-modulated radiotherapy makes possible to optimize the irradiation and spare normal tissues. The toxicity remains important with concomitant chemotherapy often associated. The improvement of MRI and PET-CT define more precisely the target volumes, which need a higher dose, but necessitates to respect the rules of contouring. The treatment is uniform whatever the stage but should be individualized based on clinical stage and tumor response. New paradigms concern biology, staging, volumes and doses, fractionation and combined treatments.

[Radiotherapy of rectal carcinoma]. / Radiothérapie des cancers du rectum.

Indications, doses and techniques of conformal radiotherapy for rectal carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

[Head and neck adaptive radiotherapy: A tool for the detection of patients requiring adaptive radiotherapy]. / Radiothérapie adaptative des cancers ORL : un outil permettant d'identifier les patients nécessitant une adaptation de leur traitement.

PURPOSE: The purpose of this work was to implement a simple dosimetric alert tool in a retrospective study for six patients suffering from head and neck cancer to detect when a patient might require an adaptive radiotherapy. MATERIALS AND METHODS: The dosimetric tool generates a 3D cartography of two dosimetric complementary information: a dose variation tolerance map and a dose differential map. The tolerance map is calculated on the initial scanner (CTinit) using the planned dose distribution. It shows for each voxel of each delineated volume the availability for local dose variations during the course of radiotherapy without exceeding the dose threshold. The differential dose map is generated on the tomographic image CBCT (CBCTtreatment). It shows dose variations between the planned and the actual delivered dose distribution for each voxel. By comparing both maps, when a voxel presents a value superior to the corresponding dose variation tolerance, an alert is generated and the anatomical areas concerned are visually indicated to the physician. RESULTS: The application of the dosimetric tool on six patients with head and neck cancers reveals the ability of the tool to detect cases requiring a new treatment plan. Two patients whose the tumour shrinkage produced an increase of the delivered dose to the spinal cord beyond 45 Gy have been detected. CONCLUSION: The development of the dosimetric tool allows the automatic detection, with no delineation needs, of patients suffering from head and neck cancers requiring an adaptive strategy.

[Radiochemotherapy for esophageal cancer: which nodes should be irradiated?]. / Chimioradiothérapie des cancers de l'œsophage : quelles aires ganglionnaires faut-il irradier ?

Esophageal cancer has a high likelihood of distant lymphatic spread even at an early stage. Radiotherapy plays a major role in the management of localized or locally-advanced esophageal cancer with a regional or distant lymph node involvement. Radiotherapy can sterilize micrometastatic nodes and cancer cells in transit in the peri-esophageal fat that are not removed by surgery. After preoperative chemoradiotherapy followed by monobloc esophagectomy including lymph node dissection above and below the diaphragm, the locoregional failure rate was around 3% in the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study Group (CROSS) trial. This is significantly lower than that observed with surgery alone or following exclusive chemoradiotherapy delivering 50 Gy over 5 weeks. Patterns of failure usually combine local and nodal failure. These results suggest that: (1) radiotherapy plays a major role in the management of micrometastatic nodes that are not removed by surgery; (2) the total dose of radiotherapy without surgery may be too low to control macroscopic disease. Better knowledge of regional failure sites and the enhancement of clinical practices through homogenized nodal radiotherapy could lead to a decrease in regional relapses, but at the expense of irradiated volumes greater than the macroscopic tumor volume. Intensity-modulated radiotherapy or volumetric modulated arctherapy makes it possible to increase mediastinal irradiated volumes while effectively protecting healthy tissues.

[Reirradiations of head and neck cancers: state of the concept and ways of development]. / Ré-irradiations des cancers de la tête et du cou : état du concept et voies de développement.

The treatment of local recurrence or second primary developed in irradiated area in the field of head and neck carcinoma, should be planned and organized through multidisciplinary discussions. The outcome of such a clinical situations benefits from second line and advanced technology treatments. Only a few patients are amenable to salvage surgery, hence radiation therapy, combined or not with chemotherapy, takes a major role in these indications. This overview of the literature describes recent development in this field, aiming to improve local control while the sparing of organ at risk remains an important goal. Radiation therapy is currently implementing major new technologies set to improve external beam irradiation with new concepts on dose, fractionation, intensity modulated radiation therapy and stereotactic approach - as well as in brachytherapy. Apart from dedicated studies, the great heterogeneity of the treated patients should be underlined and taken into consideration. However, current data confirm the feasibility of reirradiation with acceptable local control and toxicity.

Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience.

BACKGROUND: Adalimumab may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis who had secondary failure to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab in patients with ulcerative colitis who previously responded to infliximab, and then lost response or became intolerant. METHODS: We report our single-centre experience in 13 patients. The patients received a loading dose of 160 mg of adalimumab subcutaneously in week 0, followed by 80 mg at week 2 and then 40 mg every other week starting at week 4. The primary efficacy measure was the proportion of patients on adalimumab therapy during the study. RESULTS: Median duration of follow-up was 42 weeks (range, 10-100). The mean number of adalimumab infusions was 21 (range, 5-50). The probability of maintaining adalimumab was 92.3%, 84.6%, 60.6% and 32.5% at 1, 3, 6 and 23 months respectively. Six of 13 patients (46.2%) underwent colectomy during the study. No serious toxicities occurred in the study. CONCLUSION: Adalimumab is well-tolerated and may be effective in maintaining clinical remission in a subgroup of patients with ulcerative colitis and lost response or intolerance to infliximab, potentially avoiding colectomy in about half of the patients.

[Helminths and inflammatory bowel diseases]. / Helminthes et maladies inflammatoires chroniques intestinales.

The current etiologic model of inflammatory bowel diseases proposes a genetically predisposed host responding to a variety of environmental triggers by exhibiting an abnormal immune response to normal luminal flora. Crohn's disease is common in highly industrialized western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. From this observation grew the hygiene hypothesis, which states that our failure to be exposed to previously common infectious agents alters the immune repertoire established in childhood. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Crohn's disease involves over reactive T-helper (Th1) pathways, and helminths blunt Th1 responses, inducing production of Th2 cytokines. Helminths also induce regulatory T cells to maintain host mucosal homeostasis. Thus, there is an immunological basis to expect that exposure to helminths such as Trichuris suis will prove beneficial in Crohn's disease. Exposure to helminths may be effective in treating inflammatory bowel diseases and was well tolerated, according to the results of few studies. Its long-term safety remains unknown.