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Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose).Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built.Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age45yo, PS≥1, pathologic tumor stage≥pT4b,N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors.In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Herein are presented the recommendations from the Société française de radiothérapie oncologique regarding indications and modalities of lung cancer radiotherapy. The recommendations for delineation of the target volumes and organs at risk are detailed.

Introduction Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. Patients and Methods Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. Results The first patient will be enrolled in January 2021, with results expected in 2028.

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.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.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.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.

Organ-sparing strategies in the management of local or locally advanced cancers meet a dual objective: tumor control and preservation of the function of the involved organ. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, bladder-sparing strategies have emerged for the management of urothelial muscle invasive bladder cancer, mostly through trimodal treatment, which consists in maximal trans-urethral resection of bladder tumor, followed by chemo-radiotherapy. This review presents the modalities of trimodal treatment, before exposing the advantages and limitations of this strategy compared to cystectomy among operable patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide similar oncological results among appropriately selected patients. In modern series, the rate of salvage cystectomy is approximately 15% at 5 years; this delayed cystectomy does not seem to be associated with greater morbidity and mortality as compared to upfront cystectomy. Emphasis is placed in the review on quality of life data of these two approaches. In order to optimize the selection of patients eligible to trimodal therapy, the classical predictive factors of response to radio(chemo)therapy are critically analyzed, with the perspective of innovative molecular biomarkers. Finally, a close multidisciplinary collaboration is needed for the choice and the execution of the therapeutic strategy, and the patient should be fully involved in the decision-making process.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council Background Optimal SBRT planning methods for VT ablation are yet to be defined. Purpose To evaluate a multimodal approach for SBRT planning. Methods 30 pts (age 70±10, 90% men, LVEF 26±9%, 67% ICM, 47% NICM or mixed, 1.7±1.2 prior catheter ablations) with drug-refractory VT underwent imaging prior to SBRT. The inHEART technology was used to create image-based 3D models of substrate, cardiac anatomy, and organs at risk (coronaries, phrenic nerve, GI tract, AV node). In MUSIC software (IHU Liryc-Inria), 3D models were fused with prior EP maps, and SBRT targets were interactively drawn in 3D by the referring EP cardiologist. Transmural target volumes and organs at risk were fused with a 4D planning CT and used to plan SBRT in Eclipse (Varian). Results SBRT was delivered on median PTVs of 96[63-149] mL (total dose 25 Gy) with either Truebeam or Edge systems (Varian). Over a median FU of 4[2-8] months, death occurred in 11(37%) pts, due to arrhythmia recurrence in 4(13%). FU at 6 months was available in 14 pts. In these, the median numbers of VT episodes and ICD shocks over the 6 months preceding SBRT were 20[9-27] and 8[5-15], respectively. In the 6 months following SBRT, these decreased to 0[0-30] and 0[0-0], respectively (P Conclusion In patients with severe drug- and catheter ablation-refractory VT, SBRT planning based on 3D image-based models fused with prior EP maps is feasible, and associated with favorable efficacy and safety profiles.

In this work, p-type silicon wafers were electrochemically etched to create nanocrystalline silicon (porous silicon (PS)) films. Different etching periods (5, 10, 15, and 20 minutes) were investigated to see how they affected the development of a nanosized pore array with a constant etching current density (10 mA/cm2). To prevent oxidation, PS samples were stored in methanol after preparation. PS is characterized by X-ray diffraction (XRD), and atomic force microscopy (AFM). At varied etching times (5, 10, 15, and 20 min), the crystallite size as determined by XRD was equal to (66.39, 88.13, 31.2, and 21.21) nm, respectively. The nanometric size was verified via AFM. The porosity of PS increased as the etching time increased; the maximum value was obtained at a 20-minute etching time. The C-V characteristic of PS/Si heterojunction describes control factors like built-in potential (Vbi) and the kind of connection, a linear relationship of 1/C2 with bias voltage indicating that the junction is an abrupt type. Vbi was calculated for PS/p-Si/Al heterojunction at different etching times, and it was between (1.1-1.8) volt. I-V characteristics under illumination showed an enhancement in the efficiency of the PS/Si/Al solar cells. The maximum value of the solar cell efficiency was 6.79% occurs at 15 min time of etching.

Simple Summary Brain metastases are one of the most frequent complications for cancer patients. Stereotactic radiosurgery is considered a cornerstone treatment for patients with limited brain metastases and the ideal dose and fractionation schedule still remain unknown. The aim of this literature review is to discuss the dose-effect relation in brain metastases treated by stereotactic radiosurgery, accounting for fractionation and technical considerations. Abstract For more than two decades, stereotactic radiosurgery has been considered a cornerstone treatment for patients with limited brain metastases. Historically, radiosurgery in a single fraction has been the standard of care but recent technical advances have also enabled the delivery of hypofractionated stereotactic radiotherapy for dedicated situations. Only few studies have investigated the efficacy and toxicity profile of different hypofractionated schedules but, to date, the ideal dose and fractionation schedule still remains unknown. Moreover, the linear-quadratic model is being debated regarding high dose per fraction. Recent studies shown the radiation schedule is a critical factor in the immunomodulatory responses. The aim of this literature review was to discuss the dose–effect relation in brain metastases treated by stereotactic radiosurgery accounting for fractionation and technical considerations. Efficacy and toxicity data were analyzed in the light of recent published data. Only retrospective and heterogeneous data were available. We attempted to present the relevant data with caution. A BED10 of 40 to 50 Gy seems associated with a 12-month local control rate >70%. A BED10 of 50 to 60 Gy seems to achieve a 12-month local control rate at least of 80% at 12 months. In the brain metastases radiosurgery series, for single-fraction schedule, a V12 Gy < 5 to 10 cc was associated to 7.1–22.5% radionecrosis rate. For three-fractions schedule, V18 Gy < 26–30 cc, V21 Gy < 21 cc and V23 Gy < 5–7 cc were associated with about 0–14% radionecrosis rate. For five-fractions schedule, V30 Gy < 10–30 cc, V 28.8 Gy < 3–7 cc and V25 Gy < 16 cc were associated with about 2–14% symptomatic radionecrosis rate. There are still no prospective trials comparing radiosurgery to fractionated stereotactic irradiation.

Resume La radiotherapie stereotaxique des lesions primitives pulmonaires est devenue le traitement de reference des CBNPC de stade precoce T1 T2a N0 chez les patients inoperables. Sa superiorite face a une radiotherapie classique a ete demontree dans l’essai randomise CHISEL, avec un taux de rechutes locales a 2 ans de 14 vs 31 %. Les resultats en terme de controle local > 80-90 % accompagnes de toxicites faibles dans les nombreuses series publiees et les essais prospectifs plaident pour l’expansion de ses indications, jusque-la plutot reservee aux patients fragiles et a haut risque operatoire. Le choix des doses et du fractionnement et la technique de radiotherapie stereotaxique doivent faire l’objet de reflexions tenant compte de la situation clinique du patient, des traitements anterieurs et de la tumeur a traiter (taille et topographie). Les traitements iteratifs, de rattrapage en cas d’echecs d’autres traitements locaux et les reirradiations offrent de nouvelles perspectives pour les patients, remplacant ou retardant l’utilisation d’un traitement systemique. Enfin, l’amelioration des connaissances sur les patterns de reponse sur l’imagerie scanographique et metabolique a contribue a securiser et fiabiliser le suivi des patients.

Resume Le concept de maladie oligometastatique est ne dans les annees 90 afin d’identifier une sous-population de patients dont la maladie metastatique presente une faible charge tumorale (essentiellement du fait d’un faible nombre de metastases , generalement inferieur a 5), et dont l’evolution est plutot indolente. Cette entite a permis de developper de nouvelles approches therapeutiques plus agressives pour ces patients, associant au classique traitement systemique, un traitement local ablatif des lesions secondaires et du primitif, base sur la chirurgie, la radiotherapie classique ou stereotaxique et la radiologie interventionnelle. Applique au cancer bronchique non a petites cellules, cette approche repose essentiellement sur deux essais prospectifs mais dont le niveau de preuve reste encore insuffisant pour la voir proposer comme standard de traitement. Par ailleurs, un des defis majeurs de cette approche consiste a identifier, sur des criteres cliniques, mais egalement biologiques a l’aide de signatures genomiques notamment, les patients oligometastatiques les plus susceptibles de beneficier de ces strategies therapeutiques agressives, afin de ne pas generer inutilement des toxicites des traitements locaux pouvant alterer la qualite de vie des patients.

International audience; Simple Summary: A retrospective multicentric study of 322 patients with head and neck cancers of unknown primary (HNCUP) was performed testing the impact of neck dissection (ND) extent on nodal relapse, progression-free survival and survival. After 5 years, the incidence of nodal relapse was 13.4%, and progression-free survival (PFS) was 59.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective ND or radical/modified ND but survival rates were similar. Patients undergoing lymphadenectomy or ND had significantly better PFS and a lower nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. In HNCUP, ND improves PFS regardless of nodal stage but fails to improve survival. The magnitude of the benefit of ND did not appear to depend on ND extent and decreased with a more advanced nodal stage.Abstract: Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP.Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. Results: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. Conclusion: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage

Radiation therapy (RT) for muscle invasive bladder cancer (MIBC) is challenging, with observed variations in bladder shape and size resulting in inappropriate coverage of the target volumes (CTV). Large margins were historically applied around the CTV, increasing the dose delivered to organs at risk (OAR). With repositioning imaging and visualization of soft tissues during image guided RT, an opportunity to consider these movements and deformations appeared possible with an adaptive RT approach (ART).A bibliographic search on the PubMed database has been done in January 2019. Studies focusing on patients with MIBC, treating on ART, with the objectives of feasibility, clinical and/or dosimetric evaluation and comparison with a standard irradiation technique were eligible. The purpose of this review was to define the different ART techniques used in clinical practice, to discuss their advantages compared to conventional RT in terms of target volume's coverage and OAR dose and to describe their feasibility in clinical practice.A total of 30 studies were selected. The strategies known as "composite offline", "plan of the day" not individualized or individualized, and "re-optimization" have been identified. All the studies have shown a significant benefit of ART in target coverage and dose of OAR, especially the rectum and small bowel. All ART plans produced are not used during RT sessions. Inter-observer variability for the selection of these plans can be observed. The practical implementation within a department required staff education and training, and increases the duration of treatment preparation. The "A-POLO" approach seems to be the most suitable for practice.ART is the technique of choice for bladder cancer RT. The "plan of the day" approach, individualized according to the A-POLO methodology, seems to be the most effective. The emergence of daily re-optimization, especially using MRI-Linac, is promising. The correlation between dosimetric benefits and clinical efficacy and safety results should be demonstrated into future trials.

BACKGROUND: Surgical residency program is considered one of the toughest residency programs, which affects quality of life of the residents during training years. To date, no study has evaluated quality of life among residents, especially surgical residents here in Saudi Arabia. AIM: The objective of this study is to evaluate quality of life among surgical residents. METHODS: The study is a cross-sectional study conducted during September 2018 in King Khalid Hospital at King Abdulaziz Medical City (KAMC) Jeddah, Saudi Arabia. The study utilized the Work-Related Quality of Life, WRQoL, scale which measures perceived quality of life covering six domains: General Well-Being (GWB), Home-Work Interface (HWI), Job and Career Satisfaction (JCS), Control at Work (CAW), Working Conditions (WCS) and Stress at Work (SAW), in addition to demographic questions, asking about (age, gender, marital status, resident level, specialty, BMI, smoking, number of days of exercise per week, hours of sleep per day, on-calls per month, clinics per week, operations per week). RESULTS: Of the 99 surgical residents training at KAMC, 73 residents returned the survey with a response rate of 72.8%. The mean age of the residents was 28 ± 2.1 years with the mean BMI of 25 kg/m2. 54.8% were married, and 42.5% were smokers. Half of the residents (50.7%) working in King Abdulaziz Medical City have low work-related quality of life. In comparison between male and female residents’ overall Quality of life, there was no significant difference between them (p = 0.363). CONCLUSIONS: Our main study finding is that half of the residents (50.7%) working at KAMC has low work-related quality of life, and there is no significant difference between male and female residents. Further studies are needed to determine the causes and improve the work-related quality of life among surgical residents.

(1) Background: To assess the role of postoperative external beam radiotherapy (pEBRT) on locoregional failure (LRF) for patients with locally advanced high-risk non-anaplastic thyroid carcinoma (naTC) at primary event or relapse. (2) Methods: Between 1995 and 2015, postoperative naTC patients with a theoretical indication for EBRT were included based on criteria that were common to American-British-French current guidelines, i.e., pT3-4, pN+, gross or microscopic residual disease. Inverse probability of treatment weighting (IPTW) after multiple imputation was used to reduce selection biases. (3) Results: Of 254 naTC patients, 216 patients underwent pEBRT (106 de novo, 110 at relapse, median dose 60 Gy) and 38 underwent surgery only. pEBRT patients had more gross residual disease, a major prognostic factor (p = 0.027) but less perineural invasion (p = 0.008) or lymphovascular emboli (p = 0.009). pEBRT patients more frequently underwent radioiodine therapy (p = 0.026). The 10-year cumulative incidence of LRF was 56% (95% CI, 32&ndash, 74%) in operated patients, and 23% (95% CI, 17&ndash, 30%) in pEBRT patients. After IPTW method, pEBRT reduced the risk of LRF (hazard ratio 0.30, 95% CI [0.18&ndash, 0.49], p &lt, 0.001), but had no impact on OS. In the pEBRT group, non-Intensity Modulated RadioTherapy (IMRT) plans and interruption of the radiotherapy were associated with poorer survival, while extended versus limited field strategy and dose were not. (4) Conclusions: In naTC patients who have pT3-4, pN+ disease or R1-2 resection, pEBRT improved LRF. Limited-field IMRT is preferred.

Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015.Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival.Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.

Alumina nanoparticles or (Al2O3 NPs) have been prepared by electrolysis method and deposited using drop casting method on glass and porous silicon (PS) substrates as thin films. Electrochemical etching of p-type silicon wafers was used to prepare nanocrystalline porous silicon. The structural and morphological properties of Al2O3 NPs were investigated by XRD, AFM and SEM techniques, respectively. The optical energy band gap of Al2O3 nanostructure (NSs) has been determined from its optical properties and it was around 3.6 eV. TEM has been used to investigate the nanoscale morphology of Al2O3NPs and showed the grains had a spherical shape and it confirmed the nanometric size of the prepared NPs. PS’s XRD pattern revealed that it had a single crystalline structure, whereas it was amorphous for the Al2O3 NSs. The nanometric scale of both Al2O3 NSs and PS was calculated by XRD patterns, it was about 34nm for Al2O3 NPs and about 90 nm for PS. The diffusion effect of the Al2O3NPs on the electrical properties of heterojunctions PS/Si was studied. Photovoltaic characteristics have been reported for Al2O3NPs/PS/Si Photovoltaic device. Ag/Al2O3/PS/Si/Al solar cell parameters were reported the efficiency of solar cell was 11.8% and F.F is 32.08 %. Ag/Al2O3/PS/Si/Al Photodetector heterojunctions have two peaks of response the first one located at 350 nm and the second at 850 nm with maximum responsivity of 0.8A/W.

Resume La lobectomie avec curage ganglionnaire radical reste le traitement de reference du cancer pulmonaire primitif non a petites cellules (NSCLC) de stade I. L’evolution spontanee des tumeurs pulmonaires NSCLC etant tres pejorative, le recours aux traitements locaux non chirurgicaux est une option precieuse pour la prise en charge de ces patients fragiles et non eligibles a une chirurgie. Au cours des dernieres annees, la radiotherapie stereotaxique (SBRT) et les techniques d’ablation percutanee (ou destruction tumorale percutanee) ont progressivement pris toute leur place dans cette indication. Le choix des doses et du fractionnement et de la technique de traitement doivent faire l’objet de reflexions tenant compte de la situation clinique du patient, des traitements anterieurs et de la tumeur a traiter (taille et topographie). Les traitements iteratifs, de rattrapage en cas d’echecs d’une des techniques et les reirradiations offrent de nouvelles perspectives pour les patients, remplacant ou retardant l’utilisation d’un traitement systemique. Enfin, l’interpretation de l’imagerie scanographique et metabolique de suivi s’ameliore continuellement meme si elle reste encore aujourd’hui tres difficile. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Resume La notion de maladie oligometastatique s’applique a une sous-population de patients presentant une faible charge tumorale caracterisee sur le plan clinique par un nombre limite de metastases. La 8e classification TNM differentie ce sous-groupe de patients atteints d’une seule metastase extra-thoracique (stade M1b) des patients presentant plusieurs metastases extrathoraciques dans un ou plusieurs organes (stade M1c). Ces stades oligometastatiques peuvent relever d’approches therapeutiques renforcees combinant traitement systemique et traitement local des lesions secondaires et du primitif bronchique, par la chirurgie, la radiotherapie conventionnelle ou stereotaxique et la radiologie interventionnelle. L’immunotherapie combinee a la radiotherapie est egalement en cours d’evaluation dans cette situation clinique particuliere. L’identification des patients candidats a de telles strategies therapeutiques demeure toutefois difficile puisqu’il ne s’agit pas de surajouter des toxicites a une absence de benefice clinique significatif. A cote des facteurs pronostiques cliniques (PS, stade N, chronologie de survenue et/ou site des metastases…), la determination de biomarqueurs predictifs (micro-ARN, signatures genomiques, statut PDL1…) serait utile a une prise en charge optimisee des patients oligometastatiques. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Image-guided radiotherapy takes place at every step of the treatment in lung cancer, from treatment planning, with fusion imaging, to daily in-room repositioning. Managing tumoral and surrounding thoracic structures motion has been allowed since the routine use of 4D computed tomography (4DCT). The integration of respiratory motion has been made with "passive" techniques based on reconstruction images from 4DCT planning, or "active" techniques adapted to the patient's breathing. Daily repositioning is based on regular images, weekly or daily, low (kV) or high (MV) energy. MRI and functional imaging also play an important part in lung cancer radiation and open the way for adaptative radiotherapy.

Resume Le traitement de reference des carcinomes epidermoides du canal anal localement evolues (stades II et III) est la chimioradiotherapie exclusive. Celle-ci delivre une dose de 45 Gy a raison de cinq fractions de 1,8 Gy par semaine dans un volume pelvien, puis un complement de dose de 14 a 20 Gy dans la tumeur. La chimiotherapie concomitante la plus souvent utilisee comprend une association de 5-fluoro-uracile et de mitomycine-C delivree lors de la premiere et cinquieme semaine d’irradiation. Une couverture optimale des volumes cibles est parfois difficile a obtenir avec une irradiation conformationnelle (jonctions des faisceaux, combinaison d’electrons et photons parfois complexes dans les aires ganglionnaires). La toxicite cutaneomuqueuse et digestive induite par le traitement peut necessiter un intervalle libre avant la realisation du complement d’irradiation. Celui-ci peut avoir un effet deletere sur les resultats s’il est prolonge (plus de 38 jours). Les differentes techniques de radiotherapie conformationnelle avec modulation d’intensite (statique segmentee, dynamique, arctherapie volumique modulee et tomotherapie helicoidale) ont leur interet dans cette localisation. Elles permettent d’obtenir une sterilisation tumorale et ganglionnaire avec une baisse des doses intermediaires et elevees aux organes a risque (intestin grele, perinee/organes genitaux, vessie, moelle osseuse) entrainant une reduction de la toxicite aigue de grade 3 ou plus ainsi qu’une meilleure conservation fonctionnelle du sphincter anorectal. Une description de la realisation de l’arctherapie volumique modulee est presentee dans cet article. Les avantages et inconvenients de cette technique par rapport aux autres y sont discutes.

Objectif de l’etude Les adenopathies cervicales du carcinome primaire inconnu divisent la communaute medicale entre ceux qui favorisent l’irradiation elective unilaterale et ceux qui preconisent l’irradiation bilaterale du cou. Nous voulions evaluer les controles locaux et regionaux et la toxicite apres irradiation cervicale bilaterale ou unilaterale. Materiel et methode Il s’agit d’une etude de cohorte multicentrique retrospective. Les patients atteints de carcinome primaire inconnu sans metastases distantes traites par une irradiation externe entre 2000 et 2015 ont ete inclus. Les patients ont fait l’objet d’un suivi regulier. Resultats Sur les 350 patients de 20 centres selectionnes, 39 (11,5 %) etaient atteints d’un cancer de stade N1, 70 (20,7 %) N2a, 117 (34,5 %) N2b, 24 (7,1 %) N2c et 89 (26,3 %) N3, 222 (70,9 %) d’un ou de plusieurs ganglion(s) en rupture capsulaire, 259 (74,4 %) patients ont eu un curage cervical, 350 (100 %) une irradiation cervicale, dont 61 (17,4 %) unilaterale et 304 (87,6 %) une irradiation des muqueuses. Trente-quatre (9,8 %) et 217 (62,2 %) patients ont ete pris en charge par chimiotherapie respectivement neoadjuvante et concomitante. Le suivi median etait de 37 mois (Ecart interquartile : 24 ; 63). Sur 3 ans, les taux de rechute locale, regionale et locoregionale etaient respectivement de 5,6 % [3,0–8,1], 11,7 % [8,1–15,2] et 15,0 % [10,9–18,8]. Les probabilites de survie globale sur trois ans et de survie specifique etaient respectivement de 80,6 % [75,5–84,8] et 84,7 % [80,6–89,1]. Dans l’analyse multifactorielle, 1) l’irradiation des muqueuses etait le seul facteur pronostique associe a un meilleur taux de controle local ; 2) la dissection du cou, le stade ≥ N2b et l’interruption de la radiotherapie de ≥ 4 jours etaient associes a un moins bon taux de controle regional ; et 3), la TEP-scanographie, le plus grand diametre N, le stade ≥ N2b, l’interruption de la radiotherapie et la chimiotherapie neoadjuvante ont ete associes a une survie specifique plus courte. Conclusion L’irradiation bilaterale semble etre plus efficace sur le controle des tumeurs mais notre etude manque de puissance.

The planning CT allows the delineation of the prostate (clinical target volume, CTV) but with an imprecision at the apex and the inability to visualize the intraprostatic cancer. MRI enables accurate visualization of the prostate outlines and in some extent the intraprostatic tumour (gross tumour volume [GTV]). The integration of MRI data within the CT remains still complex. Analysis of prostatectomy specimen has guided the definition of a CTV beyond the capsule, depending on pretreatment factors. In practice, the CTV can be defined as follows: prostate-only, for good prognosis tumours; prostate (+0 to 5mm margins, excluding the rectum) and seminal vesicles (possibly limited to 2 cm of their proximal region) for intermediate-risk tumours; prostate (+5mm margins) and seminal vesicles for high-risk tumours. The planning target volume (PTV) should be between 5mm and 10mm depending on the space directions, in the absence of image-guidance (IGRT). It could be reduced to 5mm in case of IGRT. In the adjuvant setting after prostatectomy, the definition of the CTV should follow the recommendations from cooperative groups. It takes into account both the analysis of pattern of local recurrence after prostatectomy, but also the specific histological analysis of the surgical specimen of the patient. The corresponding PTV margin is 6 to 8mm.

Introduction L’orbitopathie dysthyroidienne (OD) debute par une phase inflammatoire, suivie d’une installation progressive de fibrose pour aboutir a une phase sequellaire. En cas d’OD moderee a severe en phase inflammatoire, une radiotherapie peut etre envisagee. En phase sequellaire, une decompression orbitaire chirurgicale peut s’averer necessaire s’il existe une gene fonctionnelle ou esthetique. Objectif Determiner l’eventuel impact de la radiotherapie orbitaire sur les resultats de la decompression orbitaire bilaterale en phase sequellaire. Le critere primaire de l’etude etait le gain obtenu sur l’exophtalmie apres chirurgie. Patients et methodes Il s’agit d’une etude observationnelle retrospective, exposes/non exposes selon que les patients avaient beneficie ou non d’une radiotherapie orbitaire avant une chirurgie de decompression. Trente-huit patients avaient recu une radiotherapie (RT+) et 98 n’en avaient pas recu (RT−), entre 1995 et 2016. Resultats Dans le groupe RT+ compare au groupe RT−, il y avait significativement plus d’hommes (29 % versus 12 %, p Conclusion Chez les patients ayant une OD, il n’y a pas d’effet deletere de la radiotherapie orbitaire sur les resultats de la decompression chirurgicale.

Objectif de l’etude Cette etude retrospective nationale a evalue l’apport de la radiotherapie postoperatoire dans les carcinomes thyroidiens differencies de pronostic defavorable. Materiel et methode Les patients etaient eligibles sur ces criteres : carcinomes thyroidiens differencies de stade T3 ou T4, et/ou avec envahissement ganglionnaire avec rupture capsulaire, et/ou en recidive locoregionale, et/ou ne fixant pas l’iode. L’impact de la radiotherapie sur la recidive locoregionale a ete evaluee par un modele de Fine et Gray de maniere a prendre en compte le deces et la recidive metastatique comme evenements competitifs. Des facteurs pronostiques de recidive locoregionale ont ete recherches dans le sous-groupe des patients irradies. Resultats Au total, 254 patients (de 18 centres) ont ete inclus, dont 38 operes non irradies. Le suivi median etait de 78 mois. Les incidences cumulees de recidive locoregionale etaient respectivement a 5 et 10 ans de 18,6 % et 28,1 %. Les probabilites de survie globale a 5 et 10 ans etaient de 78,4 % et 63,0 %. Apres ajustement sur les facteurs de confusion potentiels, la radiotherapie diminuait le risque de recidive locoregionale avec un hazard ratio (HR) de 0,26 et un intervalle de confiance (IC) a 95 % de [0,13 ; 0,54]. A 10 ans, l’incidence cumule de recidive locoregionale etait de 23 % [17 % ; 30 %] pour les patients irradies contre 56 % [32 % ; 74 %] pour les patients non irradies. Apres ajustement sur les facteurs de confusion, la radiotherapie n’apportait pas de benefice de survie globale (HR : 0,82 ; IC95 % : 0,41–1,64). Parmi les patients irradies, la thyroidectomie totale diminuait le risque de recidive locoregionale alors que l’histologie insulaire le majorait. Conclusion La radiotherapie postoperatoire permet d’ameliorer le taux de controle locoregional dans les carcinomes thyroidiens differencies de pronostic defavorable.

International audience; To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was t(end); MR acquisitions performed at t(end-2M), t(end-4M) and t(end-6M) (respectively 2, 4 and 6 months before t(end)) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between a dagger B from t(end-4M) to t(end-2M) and a dagger B from t(end-6M) to t(end-4M). The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. The fraction of hypoperfused tumor volume (F_hP(g)) was a relevant biomarker. A ratio R(F_hP(g)) aeyenaEuroe0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (aeyen0.61) was associated with more relapse at t(end) compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). Iterative analysis of F_hP(g) from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. aEuro cent Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. aEuro cent Biomarkers were assessed through their patterns of variation during the follow-up. aEuro cent The fraction of hypoperfused tumour volume (F_hP (g) ) seemed to be a relevant biomarker. aEuro cent An innovative ratio R(F_hP (g) ) could be an early surrogate marker of relapse. aEuro cent A significant time gain could be achieved in the management of GBM patients.

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed.

Objectifs Les cancers anaplasiques de la thyroide sont des maladies rares et de pronostic tres defavorable, avec une duree mediane de survie de 10 mois. L’objectif de cette etude etait d’evaluer l’impact sur la survie globale de la strategie therapeutique multimodale. Patients et methodes Les dossiers des patients atteints de cancer anaplasique de la thyroide traite a une dose d’au moins 40 Gy dans les centres du groupe du Rare Cancer Network ont ete analyses. Resultats Au total, parmi les 140 cancers anaplasiques de la thyroide, 25 % avaient une double composante differenciee et indifferenciee. Treize patients ont recu une chimiotherapie neoadjuvante (avec differents protocoles), avec 63 % de reponses partielles. Parmi 68 patients ayant ete operes (dont 63 % par thyroidectomie totale, 70 % avec curage ganglionnaire cervical), 18 % ont eu une exerese complete. Quatre-vingt pour cent des patients ont recu une chimioradiotherapie concomitante (y compris par doxorubicine, docetaxel, cisplatine, carboplatine), 80 % des patients ont eu une radiotherapie externe dans de larges volumes, 20 % dans des volumes limites, et une dose mediane de 60 Gy a ete delivree. Les durees medianes de controle locoregional, survie sans metastase et survie globale etaient respectivement de 16, 14 et 17 mois. L’analyse multifactorielle a montre que la chirurgie et une haute dose de radiotherapie etaient des facteurs independants de la survie globale. Les patients ayant recu une radiotherapie conformationnelle avec modulation d’intensite semblent avoir de meilleurs resultats. Conclusion L’etude est en cours, il faut probablement jusqu’a 300 patients pour confirmer l’ordre optimal entre la chirurgie, la chimiotherapie et la radiotherapie.

The planning CT allows the delineation of the prostate (clinical target volume, CTV) but with an imprecision at the apex and the inability to visualize the intraprostatic cancer. MRI enables accurate visualization of the prostate outlines and in some extent the intraprostatic tumour (gross tumour volume [GTV]). The integration of MRI data within the CT remains still complex. Analysis of prostatectomy specimen has guided the definition of a CTV beyond the capsule, depending on pretreatment factors. In practice, the CTV can be defined as follows: prostate-only, for good prognosis tumours; prostate (+0 to 5mm margins, excluding the rectum) and seminal vesicles (possibly limited to 2 cm of their proximal region) for intermediate-risk tumours; prostate (+5mm margins) and seminal vesicles for high-risk tumours. The planning target volume (PTV) should be between 5mm and 10mm depending on the space directions, in the absence of image-guidance (IGRT). It could be reduced to 5mm in case of IGRT. In the adjuvant setting after prostatectomy, the definition of the CTV should follow the recommendations from cooperative groups. It takes into account both the analysis of pattern of local recurrence after prostatectomy, but also the specific histological analysis of the surgical specimen of the patient. The corresponding PTV margin is 6 to 8mm.

Objectif de l’etude Les zones subventriculaires sont considerees comme une source potentielle de cellules souches de glioblastome. L’objet de l’etude etait d’identifier des facteurs pronostiques de survie en lien avec ces zones subventriculaires parmi des patients atteints de glioblastome. Materiels et methodes Quarante-trois patients traites de premiere intention pour un glioblastome dans notre centre entre 2006 et 2010 ont ete identifies. Tous les patients ont recu apres une resection chirurgicale une chimioradiotherapie (protocole de Stupp et al.). Les zones subventriculaires homolaterales, controlaterales et bilaterales ont ete delineees retrospectivement et les histogrammes dose-volume analyses. Une analyse multifactorielle utilisant le modele de Cox a evalue l’impact des differents facteurs pronostiques lies aux zones subventriculaires sur le temps jusqu’a progression et la survie globale. Cette etude a ete approuvee par notre comite d’ethique local. Resultats Le suivi median, la survie globale mediane et le temps jusqu’a progression mediane etaient respectivement de 22,7 mois (7,5–69,7 mois), 22,7 mois (intervalle de confiance a 95 % [IC 95 %] : 14,5–26,2 mois) et 6,4 mois (IC 95 % : 4,4–9,3 mois). En analyse univafactorielle, le contact initial a la zone subventriculaire etait un facteur pronostique defavorable de survie globale (18,7 contre 41,7 mois, p = 0,014) et de temps jusqu’a progression (4,6 contre 12,9 mois, p = 0,002). Les patients dont le volume de zones subventriculaires recevant plus de 20 Gy etait superieur a 84 % avaient un temps jusqu’a progression significativement plus long (17,7 contre 5,2 mois, p = 0,017). Cette couverture de dose etait compatible avec une epargne hippocampique. En analyse multifactorielle, le contact initial a la zone subventriculaire et un volume de zones subventriculaires recevant plus de 20 Gy de moins de 84 % restaient des facteurs pronostiques defavorable de temps jusqu’a progression (respectivement, HR = 3,07, p = 0,012 et HR = 2,67, p = 0,047). Conclusion Nos resultats suggerent qu’un contact tumoral a la SVZ zone subventriculaire, de meme qu’une couverture de dose insuffisante de la zone subventriculaire recevant plus de 20 Gy (moins de 84 %) sont des facteurs defavorables independants de temps jusqu’a progression. Le ciblage de la zone subventriculaire en radiotherapie pourrait donc etre d’un interet crucial pour l’optimisation du traitement des glioblastomes.

Acquired copper deficiency anemia is rare in humans. This report describes a 38-year-old schizophrenic man with metal pica, especially coins, who presented with symptomatic anemia. Two hundred seventy-five coins were surgically removed from the gastrointestinal tract of this patient during the course of his hospitalization. Some of the post-1981 pennies, which consist primarily of zinc, showed severe corrosion because of their prolonged contact with acidic gastric juice. The patient presented with clinical manifestations consistent with the local corrosive as well as the systemic effects of zinc intoxication. His treatment and outcome are presented. The effects of zinc intoxication on hematologic and other organ systems and on copper absorption are discussed.

Objectifs L’objectif etait d’evaluer l’impact des radiations ionisantes sur l’expression d’integrines de choix dans differentes lignees tumorales colorectales humaines, et de correler ces variations avec le profil invasif de ces lignees. Materiels et methodes Trois lignees d’adenocarcinome colorectal ont ete etudiees : SW480, SW620 et HCT116. Les integrines d’interet, definies apres analyse preliminaire par PCR ( polymerase chain reaction ) sur plaques microfluidiques, etaient les suivantes : α1, α2, α5, α6, αv, β1, et β2. Les cellules ont ete irradiees a 10 Gy et l’expression des ARNm des integrines a ete quantifiee pour chaque lignee a 72 heures de l’irradiation par reverse transcription quantitative PCR (RT-qPCR) et comparee a la condition non irradiee. Les profils d’expression des integrines ont ensuite ete correles avec le niveau d’expression de la vimentine, reflet du profil invasif, par RT-qPCR. Resultats L’expression des ARNm des integrines suivantes etait significativement augmentee apres irradiation : α1 pour les lignees SW480 (expression multipliee par 4,04, p = 7 · 10 −6 ) et SW620 (4,51 fois, p = 0,0003) ; α2 pour les trois lignees (SW480 [3,31 fois, p = 0,0002], SW620 [2,74 fois, p = 0,001] et HCT116 [2,43 fois, p = 0,02]) ; α5 pour la lignee SW620 (1,75 fois, p = 0,0006) ; et αv pour la lignee SW480 (2,05 fois, p = 0,03). Il n’y avait pas de modification significative de l’expression des ARNm des integrines α6, β1 et β2. Par ailleurs, SW480 et SW620 avaient un niveau d’expression basal de la vimentine plus eleve que HCT116 (respectivement 17,51 fois plus et 588,13 fois plus que HCT116). Pour la lignee SW620, l’expression de la vimentine etait augmentee apres irradiation (1,84 fois, p = 0,004). Conclusion L’irradiation de lignees colorectales entraine une majoration de l’expression de l’ARNm des integrines α1, α2, α5 et αv. Cette augmentation est plus marquee dans les lignees presentant un niveau d’expression basal de la vimentine eleve et donc probablement un phenotype basal plus invasif. L’analyse de ces resultats suggere un lien etroit entre le pouvoir invasif des cellules d’adenocarcinome rectal et la stimulation radio-induite des voies des integrines, dont l’inhibition pharmacologique pourrait etre etudiee pour contourner la radioresistance de ces tumeurs.

Objectifs L’objectif etait d’evaluer l’apport de l’IRM de perfusion ponderee en T2* dans la prediction des sites de rechute apres chimioradiotherapie de glioblastome multiforme. Patients et methodes Parmi 44 patients ayant recu en premiere intention une irradiation de 60 Gy et du temozolomide pour un glioblastome multiforme et inclus dans un essai clinique prospectif, 15 ayant ete atteints d’une rechute ont fait l’objet de l’analyse. Tous avaient beneficie d’une IRM anatomique, de diffusion et de perfusion, avant la radiotherapie, puis tous les deux mois jusqu’a rechute. L’IRM de la recidive a ete correlee avec les donnees acquises avant le traitement apres recalage rigide. Plusieurs regions d’interet anatomiques ont ete analysees : la prise de contraste initiale, l’hypersignal en FLAIR et le volume traite (la prise de contraste initiale plus 17 mm en incluant l’hypersignal en FLAIR). Deux methodes de seuillage du volume sanguin cerebral relatif ont ete utilisees : seuil d’hyperperfusion de 1,75 (HP1) tire de la litterature et methode de tripartition de l’histogramme de densite de probabilite du volume traite, basee sur un ajustement multigaussien en trois zones pour chaque patient : hypoperfusion excluant les voxels dont un volume sanguin cerebral relatif de moins de 0,2 (hP), normoperfusion et hyperperfusion (HP2). Au total, 2 021 815 voxels ont ete analyses. Resultats Les voxels HP1, hP et HP2 representaient respectivement 22,49 %, 17,25 % et 24,54 % de la prise de contraste, 14,48 %, 25,08 % et 15,29 % de l’hypersignal en FLAIR, et 16,51 %, 21,71 %, et 20,55 % du volume traite. Les valeurs predictives positives (de rechute des voxels HP1, hP et HP2 contenus dans l’hypersignal en FLAIR etaient respectivement de 21,61 %, 13,78 % et 22,83 % (valeurs predictives negatives correspondantes : 82,42 %, 80,50 % et 82,73 %). Les valeurs predictives positives de rechute des voxels HP1, hP et HP2 contenus dans le volume traite etaient respectivement de 9,48 %, 10,92 % et 12,94 % (valeurs predictives positives correspondantes : 88,29 %, 87,14 % et 87,68 %). Conclusion L’IRM de perfusion ponderee en T2* seule ne semble pas pouvoir predire de facon robuste les sites de rechute apres chimioradiotherapie des glioblastomes multiformes dans notre etude, et donc ne pas pouvoir etre utilisee isolement dans une optique d’escalade de dose par « dose painting ». L’apport surajoute de l’IRM de diffusion est a l’etude.