[Moderately hypofractionated dose escalation radiotherapy for localized prostate cancer, ESHYPRO: Results of a retrospective single-centre series evaluating safety and efficacy]. / Escalade de dose en radiothérapie modérément hypofractionnée pour les cancers de la prostate localisés, ESHYPRO : résultats d'une série monocentrique rétrospective évaluant la toxicité et l'efficacité.

PURPOSE: Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. MATERIAL AND METHODS: The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost. RESULTS: A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both). CONCLUSION: External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses.

[Proposal for the delineation of postoperative primary clinical target volumes in maxillary sinus and nasal cavity cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers du sinus maxillaire et des cavités nasales.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

Dose-escalation in prostate cancer: Results of randomized trials.

In 1998, an editorial from the International Journal of Radiation Oncology - Biology - Physics (IJROBP) on the occasion of the publication of Phase I by Zelefsky et al. on 3D radiotherapy dose escalation asked the question: "will more prove better?". More than 20 years later, several prospective studies have supported the authors' conclusions, making dose escalation a new standard in prostate cancer. The data from prospective randomized studies were ultimately disappointing in that they failed to show an overall survival benefit from dose escalation. However, there is a clear and consistent benefit in biochemical recurrence-free survival, which must be weighed on an individual patient basis against the potential additional toxicity of dose escalation. Techniques and concepts have become more and more precise, such as intensity modulated irradiation, simultaneous integrated boost, hypofractionated dose-escalation, pelvic irradiation with involved node boost or focal dose-escalation on gross recurrence after prostatectomy. The objective here was to summarize the prospective data on dose escalation in prostate cancer and in particular on recent advances in the field. In 2022, can we finally say that more has proven better?

Histosurgical mapping of endoscopic endonasal surgery of sinonasal tumours to improve radiotherapy guidance.

PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

[Ultra-hypofractionated radiotherapy for the treatment of localized prostate cancer: Results, limits and prospects]. / Radiothérapie en hypofractionnement extrême appliquée au traitement du cancer localisé de la prostate : résultats, limites et perspectives.

Still an emerging approach a few years ago, stereotactic body radiation therapy (SBRT) has ranked as a valid option for the treatment of localized prostate cancer. Inherent properties of prostatic adenocarcinoma (low α/ß) make it the perfect candidate. We propose a critical review of the literature trying to put results into perspective to identify their strengths, limits and axes of development. Technically sophisticated, the stereotactic irradiation of the prostate is well tolerated. Despite the fact that median follow-up of published data is still limited, ultra-hypofractionated radiotherapy seems very efficient for the treatment of low and intermediate risk prostate cancers. Data seem satisfying for high-risk cancers as well. New developments are being studied with a main interest in treatment intensification for unfavorable intermediate risk and high-risk cancers. Advantage is taken of the sharp dose gradient of stereotactic radiotherapy to offer safe reirradiation to patients with local recurrence in a previously irradiated area.

[Proposal for the delineation of postoperative primary clinical target volumes in ethmoid cancers]. / Proposition de délinéation des volumes cibles anatomocliniques postopératoires de la tumeur primitive des cancers de l'ethmoïde.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Nutrients cause grassland biomass to outpace herbivory.

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.

[Patient volume, diagnosis and injury mechanisms in a level 1 trauma center at the beginning of the COVID-19 pandemic in comparison to the mean of the 3 previous years : A retrospective, epidemiological evaluation of 4967 patients]. / Patientenaufkommen, Diagnosen und Verletzungsmechanismen eines überregionalen Traumazentrums mit Beginn der COVID-19-Pandemie im Vergleich zum Mittelwert der 3 Vorjahre : Eine retrospektive, epidemiologische Auswertung von 4967 Patienten.

BACKGROUND: As part of the COVID-19 pandemic, political decisions were made to reduce social interaction and to reduce the number of infections. The aim was to create capacities for the in-hospital care of the patients. OBJECTIVE: The aim of the study was to check whether a reduction in the number of trauma patients compared to the mean of the previous 3 years could be observed. MATERIAL AND METHODS: We retrospectively analyzed all patients who presented in the emergency admission from 1 March to 15 April 2020 with the mean of the patients from the previous 3 years 2017-2019. The age of the patients, time of presentation, diagnoses, whereabouts of the patients, inpatient or outpatient, number and duration of the operative care and required capacity on the normal ward and intensive care units (ICU) were recorded. The injury mechanism was also examined. RESULTS: A total of 4967 patients between 1 March and 15 April were included. On average over the 3 previous years, a total of 1348 patients, i.e. 29.3 patients per day were counted in our emergency room. In 2020 a total of 923, i.e. 20 patients per day (p < 0.01) were counted. On average 227 (24.6%) were admitted to hospital compared to 311.5 (23.1%) in 2020. On average 143 operations were performed compared to 136 in 2020. The days on the ward were reduced from 2442 on average for the previous years, in 2020 to 1172 days by 52.1% (p < 0.01). The number of days on the ICU was 450 days on average in previous years and 303 days in 2020 (-32.7%, p < 0.01). CONCLUSION: The number of patients in the emergency admission was significantly reduced in the observation period in 2020 compared to the mean of the previous 3 years. This directly made resources available for the care of COVID-19 patients.

[Individualization of dose and fractionation of radiotherapy for head and neck cancers]. / Personnalisation de la dose et du fractionnement de la radiothérapie des cancers de la tête et du cou.

Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.

[Oral cavity and pharyngo-laryngeal squamous cell carcinoma. What lymph node volumes to select for external beam radiation therapy?] / Carcinomes épidermoïdes de la cavité buccale et du pharyngo-larynx. Quels volumes ganglionnaires traiter en radiothérapie externe ?

The selection of target volumes for head and neck cancer radiation therapy, particularly prophylactic volumes that reflect infra-clinic spreads, is a complex process. It is based on the knowledge of the natural history of these tumors and must take into consideration the special challenges due to the diversity and complexity of head and neck anatomy. The dosimetric and ballistic precision provided by modern radiation techniques has required strong strategic deliberation to ensure the relevance and reproducibility of target volumes. Specifically, regarding cervical lymph node volumes, two issues emerged. What lymph node area to select depending on the location and the staging of the primary tumor? How to convey that choice in the process of treatment planning and delivery? This debate has been progressively enriched over time resulting in the publication of several international guidelines to standardize the terminology of head and neck lymph node areas and to lay solid science-based foundations to drive practices. This abundance of information makes these guidelines complex, but their accurate understanding is required for adequate usage. We provide an overview of the main published recommendations for the selection of lymph node target volumes when treating oral cavity and pharyngo-laryngeal squamous cell carcinoma with radiation therapy.

[Post-treatment follow-up of head and neck cancer patients]. / Surveillance après traitement d'un cancer cervicofacial.

Post-therapeutic follow-up of patients with head and neck cancer involves numerous professionals. The radiation oncologist should play an active role in this process. His oncological knowledge and technical expertise position him as a cornerstone for the detection of recurrences from the treated tumor, the research of second primary cancers and the screening of potential side-effects induced by the different treatments administered. To improve the benefits/costs ratio and allow good patient-compliance, follow-up programs should be built through close collaboration between the different contributors and planned according to a feasible schedule. Paraclinical exams must be arranged to respond to accurate objectives. Patient-education is essential to ensure the patient's full understanding and active participation. Finally, the transfer of the long-term follow-up of cancer survivors from specialists to primary care physicians is relevant but would require a prospective evaluation of its efficiency for this specific population.

[Head and neck intensity-modulated radiation therapy: Normal tissues dose constraints. Pharyngeal constrictor muscles and larynx]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures : dose de tolérance des tissus sains. Muscles constricteurs du pharynx et larynx.

Radio-induced pharyngolaryngeal chronic disorders may challenge the quality of life of head and neck cancer long survivors. Many anatomic structures have been identified as potentially impaired by irradiation and responsible for laryngeal edema, dysphonia and dysphagia. Some dose constraints might be plausible such as keeping the mean dose to the pharyngeal constrictor muscles under 50 to 55Gy, the mean dose to the supra-glottic larynx under 40 to 45Gy and, if feasible, the mean dose to the glottic larynx under 20Gy. A reduction of the dose delivered to the muscles of the floor of the mouth and the cervical esophagus would be beneficial as well. Nevertheless, the publications available do not provide an extensive enough level of proof. One should consider limiting as low as possible the dose delivered to these structures without compromising the quality of irradiation of the target tumor volumes.

[Intensity-modulated radiotherapy of head and neck cancers: Dose effects on the ocular, orbital and eyelid structures]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures : dose de tolérance de l'œil et des voies optiques.

Radiation-induced damage of ocular, orbital and eyelid structures are mainly reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume relationships are, however, inaccurate due to the small volume of most of the organs at risk involved and limited ability of irradiation techniques to spare these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The ability of newest radiation techniques including IMRT and proton therapy to generate steep dose gradients may yield more accurate models in the future. Some toxicities are severe and irreversible, leading to vision loss, as in the case of radiation-induced optic neuropathy for which curative treatments are suboptimal. Other toxicities can lead to reversible vision loss but can be surgically corrected, as is the case for radiation-induced cataract. In this paper, we will review the dose effects for the ocular; orbital and eyelid structures.

[Intensity-modulated radiotherapy for head and neck cancer. Dose constraint for salivary gland and mandible]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures. Dose de tolérance des tissus sains : glandes salivaires et mandibule.

Intensity-modulated radiation therapy (IMRT) is the gold standard for head and neck irradiation. It allows better protection to the organs at risk such as salivary glands and mandible, and can reduce the frequency of xerostomia, trismus and osteoradionecrosis. At the time of treatment planning, the mean dose to a single parotid gland should be kept below 26Gy, the mean dose to a single submandibular gland below 39Gy, the mean dose to the mandible below 60 to 65Gy and the D2% to a single temporomandibular joint below 65Gy. These dose constraints could be further improved with data extracted from cohorts of patients receiving IMRT exclusively. The dose administered to the target volumes should not be lessened to spare the salivary glands or mandible.

[Intensity-modulated radiotherapy of head and neck cancers. Dose constraint for spinal cord and brachial plexus]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures. Dose de tolérance des tissus sains : moelle épinière et plexus brachial.

Given the ballistic opportunities it offers, intensity-modulated radiotherapy has emerged as the gold standard treatment for head and neck cancers. Protection of organs at risk is one of the objectives of optimization during the planning process. The compliance of dose constraints to the nervous system must be prioritized over all others. To avoid complications, it is recommended to respect a maximum dose of 50Gy to the spinal cord, and 60Gy to the brachial plexus using conventional fractionation of 2Gy per fraction. These constraints can be adapted depending on the clinical situation; they will probably be refocused by the follow-up of the IMRT studies.

[Postoperative external beam radiotherapy for medullary thyroid carcinoma with high risk of locoregional relapse]. / Radiothérapie postopératoire des carcinomes médullaires de la thyroïde à haut risque de rechute locorégionale.

PURPOSE: To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. PATIENTS AND METHODS: Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. RESULTS: Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. CONCLUSION: Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long-term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse.

[Value of neck dissection before definitive radiation therapy for locoregionally advanced squamous cell carcinoma of the head and neck]. / Place du curage ganglionnaire avant radiothérapie exclusive dans la prise en charge des carcinomes épidermoïdes localement évolués des voies aérodigestives supérieures.

PURPOSE: Optimal timing of neck dissection remains debated in the conservative management of patients with locoregionally advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: The files of 63 patients with radiographic evidence of bulky or necrotic nodal metastases treated by up-front neck dissection and definitive radiotherapy between 2000 and 2012 at two institutions were retrospectively reviewed. RESULTS: The primary site was oropharyngeal, hypopharyngeal or laryngeal in 63%, 21% and 13% cases, respectively. Overall, 83% of the tumours were staged pN2b or more. Extracapsular spread was found in 48 cases (77%). After a 48-month median follow-up, the 3-year locoregional control and overall survival were 88% and 68%, respectively. Only one isolated failure occurred in the dissected neck. CONCLUSION: This combination therapy provides a good locoregional tumour control. It should be considered as an option in laryngeal, hypopharyngeal or oropharyngeal squamous cell carcinomas with bulky or necrotic nodal metastases at presentation.