Search

Supplementary Table 1, Figures 1-3 from Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients

Histologic response to chemotherapy for osteosarcoma is one of the most important prognostic factors for survival, but assessment occurs after surgery. Although tumor imaging is used for surgical planning and follow-up, it lacks predictive value. Therefore, a radiomics model was developed to predict the response to neoadjuvant chemotherapy based on pretreatment T1-weighted contrast-enhanced MRI. A total of 176 patients (median age, 20 years [range, 5–71 years]; 107 male patients) with osteosarcoma treated with neoadjuvant chemotherapy and surgery between January 2007 and December 2018 in three different centers in France (Centre Léon Bérard in Lyon, Centre Hospitalier Universitaire de Nantes in Nantes, and Hôpital Cochin in Paris) were retrospectively analyzed. Various models were trained from different configurations of the data sets. Two different methods of feature selection were tested with and without ComBat harmonization (ReliefF and t test) to select the most relevant features, and two different classifiers were used to build the models (an artificial neural network and a support vector machine). Sixteen radiomics models were built using the different combinations of feature selection and classifier applied on the various data sets. The most predictive model had an area under the receiver operating characteristic curve of 0.95, a sensitivity of 91%, and a specificity 92% in the training set; respective values in the validation set were 0.97, 91%, and 92%. In conclusion, MRI-based radiomics may be useful to stratify patients receiving neoadjuvant chemotherapy for osteosarcomas. Keywords: MRI, Skeletal-Axial, Oncology, Radiomics, Osteosarcoma, Pediatrics Supplemental material is available for this article. © RSNA, 2022

Background. The initial management of patients with sarcoma is critical. We used the French National Cancer Institute-funded nationwide sarcoma database NETSARC to report the management and oncologic outcomes in children, adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods. Data from patients with sarcoma are collected, regularly monitored and updated using NETSARC. NETSARC was searched for pediatric (Results. We collected data from 3,972 pediatric and AYA patients with sarcoma diagnosed between 2010 and 2017, including 714 children, 1,290 AYAs treated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed regarding pre-treatment biopsy (Children: 83.5%; AYA in RSC: 85.9%; AYA in non-RSC 48.1%), pre-treatment imaging (Children: 81.2%; AYA in RSC: 86.8%; AYA in non-RSC: 56.5%) and R0 margins (Children: 52%; AYA in RSC 57.6%; AYA in non-RSC: 20.2%) (pConclusions. This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.

Orthopaedic surgery I has a key role on the medical pathway of adolescent and young-adult (AYA) patients with musculo-skeletal tumor from diagnosis, tumor resection, musculo-skeletal immediate or delayed reconstruction, to dealing with late complications and sequelae following reconstruction during childhood. Administrative authorizations, organization by health authorities as well as training courses are quite different for adult and pediatric surgery. However, surgery for musculo-skeletal tumors in AYA patients have neither adult nor pediatric specifities; resection-reconstruction rules and technics are the same for adult or pediatric patients, with nevertheless lower complication rate and more biologic reconstructions for the youngest, and more prosthetic reconstructions for the oldest. Late complications after bone and soft-tissue reconstructions in childhood and musculo-skeletal deformation after surgery and/or radiotherapy in childhood need the vision from "adult" orthopaedic teams for long and very long term success of the surgical project with a good knowledge of pediatric technics previously used. Thus, formal shared time and transition care are necessary between pediatric and adult surgical teams to prepare long-term follow-up of these childhood cancer survivors. Participation to the same specialized Multi-Disciplinary Board, scientific society gathering adult and pediatric surgeons, clinical trials with no age-limitation might help to erase barriers and to ease collaboration between adult and pediatric ortho-oncologic teams.

International audience; Simple Summary As patients with rare cancers face specific problems, reference networks have been developed in several European countries and then at the European level to improve their management. In some cases, the specialized centers belonging to reference networks provide remote services (specialized diagnosis review, discussion in the Multidisciplinary Tumour Board, etc.) to increase access to these services. Using data from the national sarcoma reference network implemented in France (NETSARC+), the IGeAS research program assesses the potential of its organization to address the geographical inequalities in cancer management. We analyze the individual, clinical, and geographical determinants of the overall survival of sarcoma patients in France. We found no association between the overall survival of sarcoma patients and variables measuring their social deprivation, remoteness from reference centers, and geographical context. Following previous results from the research program, this study suggests that reference network organization should be considered to reduce cancer inequalities. The national reference network NETSARC+ provides remote access to specialized diagnosis and the Multidisciplinary Tumour Board (MTB) to improve the management and survival of sarcoma patients in France. The IGeAS research program aims to assess the potential of this innovative organization to address geographical inequalities in cancer management. Using the IGeAS cohort built from the nationwide NETSARC+ database, the individual, clinical, and geographical determinants of the 3-year overall survival of sarcoma patients in France were analyzed. The survival analysis was focused on patients diagnosed in 2013 (n = 2281) to ensure sufficient hindsight to collect patient follow-up. Our study included patients with bone (16.8%), soft-tissue (69%), and visceral (14.2%) sarcomas, with a median age of 61.8 years. The overall survival was not associated with geographical variables after adjustment for individual and clinical factors. The lower survival in precarious population districts [HR 1.23, 95% CI 1.02 to 1.48] in comparison to wealthy metropolitan areas (HR = 1) found in univariable analysis was due to the worst clinical presentation at diagnosis of patients. The place of residence had no impact on sarcoma patients' survival, in the context of the national organization driven by the reference network. Following previous findings, this suggests the ability of this organization to go through geographical barriers usually impeding the optimal management of cancer patients.

Resume Contexte Les reconstructions par prothese massive sont largement repandues apres resection d’une tumeur osseuse. Le design, le mode de fixation et le type de charniere a utiliser font encore debat. Le but de cette etude etait de determiner la survie, les complications et les resultats fonctionnels d’une serie homogene de patients adultes dont le defect osseux suivant l’ablation d’une tumeur du femur distal etait reconstruit par le meme modele d’endoprothese cimentee a charniere fixe avec un suivi minimum de 5 ans. Notre hypothese principale etait que le descellement et l’infection seraient les types d’echec les plus frequents et que ce mode de reconstruction etait fiable dans les resections de femur distal. Patients et methodes Tous les patients adultes de plus de 17 ans avec une reconstruction par prothese massive modulaire Stanmore Mets® cimentee a charniere fixe suivant une resection de femur distal pour une tumeur primitive osseuse dans 4 centres referents francais de 2004 a 2013 ont ete inclus. Les donnees epidemiologiques, le score fonctionnel MSTS, les resultats de l’examen clinique et radiologique, les complications, les courbes de survie avec les types d’echec selon la classification d’Henderson ont ete evalues. Resultats Cent trente-six patients (68 hommes et 68 femmes) d’âge moyen 41,2 [17–77] annees ont ete inclus. Le suivi moyen etait de 81 [61–134] mois. Trente-deux patients (38 %) ont connu 67 complications ayant conduit a une intervention chirurgicale, la plupart infectieuses (n = 28) ou mecaniques (n = 26). La survie prothetique globale etait de 78 %a 5 ans. D’apres la classification d’Henderson, il y a eu 30 echecs prothetiques. Le score moyen MSTS etait de 82 %. Discussion Les resultats sont comparables a la litterature et aux autres modes de reconstruction. Les recentes meta-analyses suggerent que le type de charniere et de fixation des tiges influent peu sur la survie. Des etudes internationales comparatives sont indispensables pour determiner la place exacte de chaque type de reconstruction en fonction du profil du patient. Niveau de preuve IV, serie multicentrique retrospective.

Purpose: The French standard chemotherapy for osteosarcoma combines high-dose methotrexate (HDM) and etoposide–ifosfamide (EI) in children and adolescents, and API-AI (doxorubicin–cisplatin–ifosfam...

Waste workers are exposed to bioaerosols when handling, lifting and dumping garbage. Bioaerosol exposure has been linked to health problems such as asthma, airway irritant symptoms, infectious, gastrointestinal and skin diseases, and cancer. Our objective was to characterize the exposure of urban collectors and drivers to inhalable bioaerosols and to measured the cytotoxic effect of air samples in order to evaluate their health risk. Personal and ambient air sampling were conducted during the summer of 2019. Workers from 12 waste trucks collecting recyclables, organic waste or compost were evaluated. Bacteria and fungi were cultured, molecular biology methods were used to detect microbial indicators, cytotoxic assays were performed and endotoxins and mycotoxins were quantified. Domestic waste collectors were exposed to concentrations of bacteria and endotoxins above the recommended limits, and Aspergillus section Fumigati was detected at critical concentrations in their breathing zones. Cytotoxic effects were observed in many samples, demonstrating the potential health risk for these workers. This study establishes evidence that waste workers are exposed to microbial health risks during collection. It also demonstrates the relevance of cytotoxic assays in documenting the general toxic risk found in air samples. Our results also suggest that exposures differ depending on the type of waste, job title and discharge/unloading locations.

Bone healing in femoral reconstructions using intercalary allografts can be compromised in a tumour context. There is also a high revision rate for non-union, infection, and fractures in this context. The advantages and disadvantages of an associated vascularised fibula graft (VFG) are still a matter of debate.In a multicentre study, we retrospectively analysed 46 allograft reconstructions, operated on between 1984 and 2017, of which 18 were associated with a VFG (VFG+) and 28 without (VFG-), with a minimum follow-up of 2 years. We determined the cumulative probability of bone union as well as the mid- and long-term revision risks for both categories by Kaplan-Meier survival analysis and a multivariate Cox model. We also compared the MSTS scores.Significant differences in favour of VFG+ reconstruction were observed in the survival analyses for the probability of bone union (log-rank, p = 0.017) and in mid- and long-term revisions (log-rank, p = 0.032). No significant difference was observed for the MSTS, with a mean MSTS of 27.6 in our overall cohort (p = 0.060). The multivariate Cox model confirmed that VFG+ was the main positive factor for bone union, and it identified irradiated allografts as a major risk factor for the occurrence of mid- and long-term revisions.Bone union was achieved earlier in both survival and Cox model analyses for the VFG+ group. It also reduced the mid- and long-term revision risk, except when an irradiated allograft was used. In case of a tumour, we thus recommend using VFG+ from a fresh-frozen allograft, as it appears to be a more reliable long-term option.

A biopsy is a prerequisite for the diagnosis and evaluation of musculoskeletal tumors. It is considered that surgical biopsy provides a more reliable diagnosis because it can obtain more tumor material for pathological analysis. However, it is often associated with a significant complication rate. Imaging-guided percutaneous core needle biopsy (PCNB) is now widely used as an alternative to surgical biopsy, it appears to be minimally invasive, possibly with lower complication rates. This study evaluates the diagnostic yield of the preferred use of PCNB in a referral center, its accuracy, and its complication rate. The data relating to the biopsy and the histological analysis were extracted from the database of a bone tumor reference center where PCNB of bone tumors was discussed as a first-line option. 196 bone tumors were biopsied percutaneously between 2016 and 2020. They were located in the axial skeleton in 21.4% (42) of cases, in the lower limb in 58.7% (115), and in the upper limb in 19.9% (39) cases. We obtained a diagnosis yield of 84.7% and a diagnosis accuracy of 91.7%. The overall complication rate of the percutaneous biopsies observed was 1.0% (n = 2), consisting of two hematomas. PCNB performed in a referral center is a safe, precise procedure, with a very low complication rate, and which avoids the need for first-line open surgical biopsy. The consultation between pathologist, radiologist, and clinician in an expert reference center makes this technique an effective choice as a first-line diagnosis tool.

The stemmed acetabular cup (SAC) can be considered in several complicated situations. This type of prosthesis uses the iliac isthmus, which is most often preserved, thus allowing solid anchorage. Its implantation is prone to mechanical complications intraoperatively, such as extra-isthmic effraction, fracture, and early aseptic loosening. The aim of our study was to compare a new technique using a flexible motorized reamer combined with isthmus catheterization (Group A) versus the standard technique deploying a rigid reamer alone (Group B). A retrospective analysis was carried out of the SACs implanted at our hospital. The main evaluation criterion was visualization of extra-isthmic effraction (EIE) of the stem. Fifty-six SACs (Integra Lepine®, Genay, France) were implanted, 31 in group A and 25 in group B. The mean follow-up was 21.6 months ± 22.3. This study found fewer EIEs using a flexible motorized reamer (0 versus 5, p = 0.014), less perioperative bleeding (p = 0.054), and less aseptic loosening in group A (p = 0.034). There was no difference in terms of infection or other mechanical complications post-operatively between the two groups. Using iliac catheterization combined with a flexible motorized reamer when implanting a SAC helps to avoid EIE and it also appears to reduce complications such as peri-operative bleeding and early aseptic loosening. We recommend use of this surgical technique rather than a rigid reamer alone, and this new technique should allow widespread and more accessible use of this specific type of implant.

Complete surgical resection constitutes the mainstay of treatment for locally aggressive, rarely metastazing tumor and low-grade soft tissue sarcomas (LAS). Local relapse is the most common tumor event, especially in the presence of positive margins (R1 margins). The aims of this study are to assess the impact of the national network on patient care and to evaluate the role of immediate re-excision in children, adolescents and young adults with incompletely resected LAS.National retrospective multicenter study of all young patients (≤25 years) included in the Sarcoma "ConticaBase" treated for LAS between 2005 and 2017 for whom pathology/biology review was available via the national NETSARC + network.A total of 96 patients were identified (median age: 16 years). Tumors were localized in 99% of cases (1 N+ tumor). With a median follow-up of 4.7 years (range: 0.1-11.9), eight local relapses and two distant metastases were observed. No patient died. Overall 5-year event-free survival (EFS) was 90.4% [95%CI, 84.3-97]. Five year EFS for R1 patients (n = 51) with (n = 24) and without (n = 27) immediate re-excision was 90.5% [95%CI, 78.8-100.0] and 80.3% [95%CI, 64.7-99.9], respectively (p = 0.34). The 37 patients directly treated in a reference center more commonly had a diagnostic biopsy (78% vs. 21%; p 0.001), more complete surgery (R0: 65% vs. 14%; p 0.001) and less commonly underwent re-excision (16% vs. 54%; p 0.001).This large series indicates that LAS are rare in young patients and have a favorable prognosis. Immediate management in reference centers is associated with better standard of care. The main tumor events are local relapses.

Introduction The capacity of the hydroxyapatite-coated trochanteric screwed plates used with modular hip implants to restore abductor system efficacy after proximal femoral tumor resection has never been assessed. We therefore conducted a retrospective study aiming to: (1) quantitatively evaluate abduction conservation on dynamometry according to use of digastric reinsertion, conserving continuity between the gluteus medius and vastus lateralis muscles, or not, and of standard versus small-offset; (2) assess radiographic trochanteric plate fixation; (3) assess functional scores; and (4) assess complications. Hypothesis Trochanteric reinsertion better conserves abduction strength when reinsertion is digastric. Patients and methods Thirty-one patients undergoing proximal femoral tumor resection between 2006 and 2016 with reconstruction by Stanmore METS™ modular implant with trochanteric plate were included. Twenty-one had digastric fixation between the gluteus medius and vastus lateralis and 10 had simple trochanteric fixation without digastric continuity. Abduction strength was compared between sides on dynamometer. Sixteen patients had full assessment of muscle strength, by a single observer; there were 8 deaths, 5 patients lost to follow-up, and 2 cases of material removal. Results Abduction strength conservation versus the contralateral side was 55.2 ± 23.3% (range, 5.8–86.1%): 66.6 ± 13.0% (46.4–86.1) with versus 36.0 ± 24.7% (5.8–63.2%) without digastric continuity (p = 0.01); severe limp rate was 4/21 when digastric continuity was preserved (19%) versus 6/10 (60%) (p = 0.04), and radiologic trochanteric reinsertion stability rate was 19/21 (90%) versus 4/10 (40%) (p = 0.005). Standard femoral offset conserved greater abduction strength: 64.9 ± 20.0% versus small-offset 45.4 ± 23.2% (p = 0.05). Toronto Extremity Salvage Score (TESS) was 89 ± 9.4%, and Musculoskeletal Tumor Society (MSTS) score 75.4 ± 5.4%. There were 6 complications (19%): 4 infections, 1 dislocation, and 1 plate removal; the single dislocation (3%) was in the digastric conservation group. TESS (90.7 ± 7.8% vs 88.3 ± 4) and MSTS score (75.6 ± 4.0% vs 75.1 ± 3.7) and complications [4/21 (19%) vs 2/10 (20%)] did not differ according to digastric or non-digastric reinsertion (p = 1). Conclusions Abduction strength with a modular implant using a hydroxyapatite-coated trochanteric plate was better conserved by digastric trochanteric reinsertion, resulting in less limping, although the complications rate and functional scores were unaffected. Longer term assessment is needed to confirm this conservation of abduction strength. Level of evidence IV, retrospective study without control group.

Resume Introduction Les plaques trochanteriennes vissees revetues d’hydroxyapatite des protheses modulaires n’ont jamais ete etudiees en ce qui concerne leur capacite a retablir un systeme abducteur efficace dans le cas d’une resection tumorale du femur proximal. Aussi, nous avons mene une etude retrospective ayant pour objectifs : (1) la mesure dynamometrique evaluant quantitativement la conservation de l’abduction en fonction de l’utilisation d’un digastrique (preservation de la continuite entre les tendons du gluteus medius et du vastus lateralis) et du type d’Offset, (2) la fixation radiographique des plaques trochanteriennes, (3) les scores fonctionnels, (4) les complications. Hypothese La reinsertion trochanterienne permet une meilleure conservation de la force en abduction avec une reinsertion en digastrique. Patients et methodes Nous avons examine 31 patients ayant eu une resection carcinologique tumorale femorale proximale entre 2006 et 2016 et ayant eu une reconstruction par une prothese modulaire Stanmore METS™ avec plaque trochanterienne. Vingt-et-un des 31 cas avaient eu la fixation du digastrique entre moyen gluteal et vaste lateral et 10 une fixation trochanterienne simple sans continuite digastrique. La force a ete testee de maniere comparative entre les deux cotes au moyen d’un dynamometre. Seize patients ont pu beneficier d’une investigation complete par un observateur unique de la force musculaire (8 deces, 5 perdus de vue et 2 deposes de materiel). Resultats La conservation de la force en abduction etait de 55,2 ± 23,3 % [5,8–86,1] par rapport au cote controlateral. La force musculaire en abduction par rapport au cote controlateral avec et sans continuite digastrique etait respectivement de 66,6 ± 13,0 % [46,4–86,1] contre 36,0 ± 24,7 % [5,8–63,2] (p = 0,01), la presence d’une boiterie severe dans 4/21 (19 %) contre 6/10 (60 %) (p = 0,04) et la stabilite radiologique de la reinsertion trochanterienne dans 19/21 (90 %) contre 4/10 (40 %) (p = 0,005). L’utilisation d’un modele d’offset femoral Standard augmentait la force d’abduction, avec 64,9 ± 20,0 % par rapport a un offset femoral Small a 45,4 ± 23,2 % (p = 0,05). Nous avons mesure un score Toronto Extremity Salvage Score (TESS) a 89 ± 9,4 % dans cette etude, et un score Musculoskeletal Tumor Society (MSTS) score a 75,4 ± 5,4 %. Nous avons observe 6 complications (19 %) (4 infections, 1 luxation et 1 depose de plaque), la seule luxation (3 %) observee dans le groupe avec conservation digastrique. Les scores TESS (90,7 ± 7,8 % vs 88,3 ± 4 %) et MSTS (75,6 ± 4,0 % vs 75,1 ± 3,7 %) et les complications (4/21 [19 %] vs 2/10 [20 %]) n’etaient pas differents respectivement avec ou sans reinsertion digastrique (p = 1). Conclusions La conservation de la force d’abduction etait meilleure en cas de reinsertion trochanterienne en digastrique par prothese modulaire avec plaque trochanterienne revetue d’hydroxyapatite, se traduisant par un moindre taux de boiterie, mais le taux de complication n’etait pas modifie par la conservation du digastrique de meme que les scores fonctionnels. Une evaluation a plus long terme est necessaire pour valider la conservation de la force d’abduction. Niveau de preuve IV, etude retrospective sans groupe temoin.

Resume Introduction Le Kyste Osseux Anevrysmatique (KOA) est une tumeur benigne qui implique la voie RANK/RANKL. La chirurgie est le traitement de reference, mais comporte certains risques selon la localisation kystique. Le denosumab, anticorps monoclonal humain de type IgG2 ciblant le systeme RANK/RANKL, pourrait avoir une efficacite antiproliferative sur cette tumeur. Le but de l’etude est d’evaluer l’interet du denosumab dans la prise en charge des kystes osseux anevrysmatiques inoperables chez l’enfant. Hypothese Le denosumab est un traitement utilisable chez l’enfant porteur d’un KOA resistant aux traitements dits classiques. Materiel et methode Les dossiers des patients traites par denosumab pour un KOA, dans les 32 centres pediatriques affilies a la SFCE (Societe Francaise du Cancer de l’Enfant) et au GSF-GETO (Groupe sarcome Francais), ont ete revus retrospectivement. Cinq cas ont ete declares, traites entre mars 2015 et juin 2018. La mediane d’âge etait de 8 ans (7–17 ans). Tous les patients presentaient des douleurs, et trois un deficit neurologique. Trois patients ont fait l’objet d’une chirurgie avant traitement, un apres traitement. Un n’a pas ete opere. Ils ont recu des injections mensuelles de denosumab de 70 mg/m2 pendant une duree mediane de 12 mois [4–23 mois]. L’evolution clinique et l’imagerie (scanner, IRM) ont ete analysees. Resultats Des anomalies secondaires du bilan phosphocalcique etaient identifiees pour deux cas. Avec un suivi median de 24 mois [0–28 mois] depuis la mise en route du traitement, les douleurs avaient disparu pour tous les patients, les deficits neurologiques etaient en amelioration. Des modifications radiologiques etaient observees dans tous les cas (remineralisation centrale, recorticalisation). Discussion Le denosumab est une alternative therapeutique pour certains kystes anevrysmatiques inaccessibles a la chirurgie. La toxicite immediate est acceptable. Une etude plus large et un suivi plus long seraient souhaitables pour confirmer cette indication. Niveau de preuve IV.

Background Aneurysmal bone cyst (ABC) is a benign tumour whose progression involves the RANK/RANKL signalling pathway. Surgery is the reference standard treatment but carries risks that vary with the site of the tumour. Denosumab is a human monoclonal IgG2 antibody that targets the RANK/RANKL pathway and may therefore hold promise for inhibiting ABC progression. The objective of this study was to evaluate denosumab use in paediatric patients (younger than 18 years) with ABC and to describe the clinical and radiological outcomes, as well as the side effect profile. Hypothesis Denosumab is a viable option in children with ABC refractory to standard treatments. Material and methods We retrospectively reviewed the medical files of paediatric patients given denosumab to treat ABC in any of 32 centres affiliated with the French Paediatric Cancer Society (Societe Francaise du Cancer de l’Enfant, SFCE) and French Sarcoma Group (Groupe Sarcome Francais, GSF-GETO). We identified 5 patients treated between March 2015 and June 2018. Median age was 8 years (range, 7–17 years). Pain was a symptom in all 5 patients and neurological deficits were present in 3 patients. Surgery was performed in 4 patients, either before (n = 3) or after (n = 1) denosumab therapy; the remaining patient had no surgery. Denosumab was given as monthly injections in a dosage of 70 mg/m2 for a median of 12 months (range, 4–23 months). The clinical outcomes and changes in computed tomography and/or magnetic resonance imaging findings were evaluated. Results Abnormalities in calcium and phosphate levels secondary to the ABC occurred in 2 patients. At median of 24 months (range, 0–28 months) after denosumab initiation, all 5 patients were free of pain, and the neurological deficits in 3 patients had improved. Central remineralisation and cortical reconstitution were demonstrated consistently by the imaging studies. Discussion Denosumab is a viable treatment option in selected paediatric patients with inoperable ABC. The immediate adverse effect profile is acceptable. A larger study with a longer follow-up would be welcome to further assess the contribution of denosumab to the treatment of ABC. Level of evidence IV.

Resume Introduction Qu’elles soient d’origines traumatiques, septiques ou tumorales, les resections de l’humerus proximal imposent une reconstruction complexe du membre superieur. Parmi ces reconstructions, l’utilisation du pilier de scapula vascularise a ete rarement documentee. Cette etude a pour but de decrire la technique chirurgicale d’arthrodese de l’epaule au moyen d’un pilier de scapula vascularise en s’appuyant sur une analyse anatomique du greffon. Materiel et methode Cette etude cadaverique a porte sur 7 epaules de sujets anatomiques distincts. Quatre epaules ont ete injectees au latex afin de decrire la vascularisation du lambeau composite de pilier de scapula. Un travail sur scapula fraiche a ensuite ete realise afin de definir l’orientation optimale du trait d’osteotomie et de la rotation du pilier de la scapula. Chaque segment vasculaire a ete isole et mesure. Trois arthrodeses d’epaules avec lambeau composite de pilier de scapula ont ensuite ete realisees afin de decrire les phases de cette intervention. Resultats L’artere angulaire de la scapula mesurait 8,25 ± 1,5 cm et abordait l’angle du pilier de la scapula 1,6 ± 1,1 cm au-dessus de son rebord antero-inferieur. La longueur moyenne de l’artere circonflexe scapulaire etait de 5,25 ± 1 cm avec une distance entre le bord inferieur de la glene et la terminaison de l’artere circonflexe scapulaire de 3 cm. Le positionnement optimal du greffon etait obtenu avec une osteotomie glenoidienne du pilier horizontale dans le plan frontal et oblique en bas et en avant de 20° dans le plan sagittal, le pilier etant alors tourne de 240° medialement (rotation interne). Discussion L’etude injectee au latex confirme la presence constante d’une double vascularisation du pilier de la scapula provenant de l’artere circonflexe de la scapula et de l’artere angulaire. Bien que sujette a des variations anatomiques, la vascularisation du pilier de la scapula est commune avec celle des muscles grand dorsal et grand rond et peut etre preservee lors du transfert du pilier lors de la reconstruction. La description anatomique d’arthrodese au moyen de ce lambeau composite permet aux operateurs d’anticiper les difficultes operatoires d’ordre techniques et anatomiques rencontrees au cours de cette intervention complexe.

To reply to as yet unmet medical needs to treat osteosarcoma, a form of primary bone cancer, we conceived the 12b80 compound by covalently conjugating antineoplastic compound doxorubicin to a bone targeting hydroxybisphosphonate vector and turned it into a prodrug through a custom linker designed to specifically trigger doxorubicin release in acidic bone tumor microenvironment. Synthesis of 12b80 was thoroughly optimized to be produced at gram scale. 12b80 was evaluated in vitro for high bone support affinity, specific release of doxorubicin in acidic condition, lower cytotoxicity, and cellular uptake of the prodrug. In vivo in rodents, 12b80 displayed rapid and sustained targeting of bone tissue and tumor-associated heterotopic bone and permitted a higher doxorubicin payload in tumor bone environment compared to nonvectorized doxorubicin. Consequently, 12b80 showed much lower toxicity compared to doxorubicin, promoted strong antitumor effects on rodent orthotopic osteosarcoma, displayed a dose-response therapeutic effect, and was more potent than doxorubicin/zoledronate combination.

BackgroundSpatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients.MethodsUsing the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery.ResultsSome clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities.ConclusionsIn the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks’ organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication., Highlights • This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE). • Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN. • Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.

Introduction Pathologic fracture is the most feared complication in long-bone metastasis. Various radiographic tools are available for identifying at-risk patients and guide preventive treatment. The Mirels score is the most frequently studied and widely used, but has been criticized, many patients not being operated on until the actual fracture stage. We therefore conducted a French national multicenter prospective study: (1) to determine the proportion of patients operated on at fracture stage versus preventively; (2) to compare Mirels score between the two; and (3) to identify factors for operation at fracture stage according to Mirels score and other epidemiological, clinical and biological criteria. Hypothesis Simple discriminatory items can be identified to as to complete the Mirels score and enhance its predictive capacity. Material and Methods A non-controlled multicenter prospective study included 245 patients operated on for non-revelatory long-bone metastasis, comparing patients operated on for fracture versus preventively according to body-mass index (BMI), ASA score, Katagiri score items and the 4 Mirels items. Results One hundred and twenty-six patients (51.4%) were operated on at fracture stage: 106 (84.1%) showed high risk on Mirels score (score > 8), and 15 (11.9%) moderate risk (score = 8). On multivariate analysis, 4 independent factors emerged: in increasing order, advanced age (OR = 1.03; 95%CI 1.01–1.06), VAS pain score > 6 (OR = 1.47; 95%CI 1.02–2.11), WHO grade > 2 (OR = 2.74; 95%CI 1.22–6.15), and upper-limb location (OR = 5.26; 95%CI 2.13–12.84). Discussion The present study confirmed that more than half of patients with long-bone metastasis are operated on at actual fracture stage, in agreement with the literature. Several studies highlighted the weakness of the Mirels score as a predictive instrument. Comparison between preventive and fracture-stage surgery showed that upper-limb location, intense pain, advanced age and impaired functional status were associated with fracture-stage surgery, and should be taken into account alongside the original Mirels criteria. This improved scoring instrument remains to be validated in a prospective study. Level of evidence IV, prospective cohort study without control group.

Resume Introduction Les protheses massives a charniere de genou sont utilisees majoritairement pour la reconstruction apres une resection tumorale. Ces protheses peuvent toutefois etre sujettes a des complications, mais cette donnee n’est pas precisee dans la litterature francaise ou alors sur des effectifs et des durees de suivi limites. Aussi nous avons mene une large etude nationale multicentrique retrospective au recul minimal de 5 ans avec pour objectifs : (1) l’analyse comparative de la survie des protheses de reconstruction du femur distal et du tibia proximal ; (2) l’analyse des complications et des echecs. Hypothese Les protheses charniere de reconstruction du femur distal presentaient une survie superieure et des complications moindres que celles de reconstruction du tibia proximal. Materiel et methodes Cent soixante-et-un patients etaient inclus : 118 dans le groupe femur distal et 43 dans le groupe tibia proximal. Les tumeurs resequees etaient majoritairement des osteosarcomes (90 cas) et des chondrosarcomes (31 cas). L’âge moyen etait de 37 ans (12–86). Les complications etaient classees selon Henderson. Un echec etait defini par la necessite d’un changement d’ancrage prothetique ou une amputation. Resultats Au recul moyen de 9 ans (5–23), les taux de survie prothetique etaient plus eleves pour le groupe femur distal avec des valeurs a 5 et 10 ans respectivement de 84 % [IC95 % : 75–89] et 70 % [IC95 % : 59–79] contre 74 % [IC95 % : 69–85] et 43 % [IC95 % : 23–61] pour le groupe tibia proximal (p = 0,02). Les re-operations apres complication etaient le plus souvent liees au descellement aseptique (19 %, 30 cas) et infection profonde (16 %, 25 cas) et concernaient plus frequemment le tibia proximal (65 % vs 43 %) (28 cas vs 51 cas) (OR 2,4 [IC95 % : 1,2–5,1], p = 0,02). Discussion La prothese charniere de reconstruction du genou est une solution therapeutique dans la pathologie tumorale, mais grevee de risques importants de complications (descellements et infections) et un taux d’echec plus important pour les protheses de reconstruction du tibia proximal. Niveau de preuve IV, Serie de cas.