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Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83 months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7-4.6); median overall survival was 34.3 months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 ( p -value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ceddia, Onesti, Vari, Torchia, Cosimati, Riva, Maccallini, Cerro, Benvenuti, Russillo, Anelli, Sperduti, Biagini and Ferraresi.)

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None of the authors has any interests to report directly related to this manuscript. Outside the scope of this manuscript: Elena Palassini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Giacomo Giulio Baldi, consulting fees from Eli Lilly, Pharmamar, AboutEvents; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, Istituto Gentili; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai. Sara Sulfaro, Marta Barisella, Giuseppe Bianchi, Domenico Campanacci, Marco Fiore, Marco Gambarotti, Massimiliano Gennaro, Carlo Morosi, no conflict of interests to declare. Federico Navarria, travel grants from Pharmamar, Boehringer Ingelheim. Claudia Sangalli, advisory board from Boehringer Ingelheim, Astra Zeneca. Rossella Bertulli, travel grants from PharmaMar. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alexia Bertuzzi, Roberto Biagini, Angela Bonadonna, Antonella Brunello, Dario Callegaro, no conflict of interests to declare. Ferdinando Cananzi, speaking fee from Istituto Gentili. Marco Cianchetti, Paola Collini(,) Danila Comandini, Annalisa Curcio, no conflict of interests to declare. Lorenzo D’Ambrosio, advisory board: PSI CRO Italy, GSK, AstraZeneca, Boehringer Ingelheim, Eisai. Meeting participation: GSK, AstraZeneca, PharmaMar. Martino De Pas, participation on advisory board from Glaxo Smith Kline, Boehringer Ingelheim. Trial support from: Pfizer, BluPrint Medicine, Gilead, Amgen, Merck. Angelo Paolo Dei Tos, no conflict of interests to declare. Virginia Ferraresi, Travel grants from PharmaMar, Gentili, Boehringer Ingelheim. Advisory Board: SERB Pharmaceuticals. Andrea Ferrari, Alessandro Franchi, no conflict of interests to declare. Anna Maria Frezza, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elena Fumagalli, Advisory Board from Deciphera Pharmaceuticals. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Matteo Ghilli, Daniela Greto, no conflict of interests to declare. Giovanni Grignani, advisory board from Pharmamar, Incyte, Merck, Novartis, Deciphera,Bayer. Michele Guida, advisory board from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre. Toni ibrahim, advisory board and consultation fees from Amgen, Glaxosmithkline, PharMamar and Istituto Gentili. Travel grants from Istitaka Gentili and Pharmamar. Marco Krengli, Roberto Luksch, Andrea Marrari, Marinella Mastore, Alessandra Merlini, no conflict of interests to declare. Giuseppe Maria Milano, Advisory board from Bayer, GSK, SERBS Pharmaceuticals. Piera Navarria, Maria Abbondanza Pantaleo, Antonina Parafioriti, no conflict of interests to declare. Ilaria Pellegrini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elisabetta Pennacchioli, Marco Rastrelli, Elisabetta Setola, Salvatore Tafuto, Salvatore Turano, Sergio Valeri, Bruno Vincenzi, Viviana Vitolo, Andrei Ivanescu, Fiammetta Paloschi, no conflict of interests to declare. Paolo Giovanni Casali, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alessandro Gronchi, no conflict of interests to declare. Silvia Stacchiotti, personal financial interests (honoraria, consultancy or advisory role): Aadi, Astex Pharmaceuticals, Bavarian Nordic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Gentili, GSK, Agenus, Ikena, MaxiVAX, Novartis, PharmaMar, Pharma Essentia, Rain Therapeutics, Servier. Support for attending meetings and/or travel Pharmamar; Institutional financial interests: Advenchen, Bayer, Blueprint, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, GSK, Hutchinson, Inhibrx, Karyopharm, Novartis, PharmaMar, Rain Therapeutics, SpringWorks; unpaid Member of the Scientifc Advisory Board of the Chordoma Foundation, Member of the Scientifc Advisory Board of the Desmoid Foundation, Member of the Scientifc Advisory Board of the Epithelioid Hemangioendothelioma Group, Member of the Scientifc Advisory Board of the Leiomyosarcoma Foundation., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Atypical cartilaginous tumour (ACT) and high-grade chondrosarcoma (CS) of long bones are respectively managed with active surveillance or curettage and wide resection. Our aim was to determine diagnostic performance of X-rays radiomics-based machine learning for classification of ACT and high-grade CS of long bones., Methods: This retrospective, IRB-approved study included 150 patients with surgically treated and histology-proven lesions at two tertiary bone sarcoma centres. At centre 1, the dataset was split into training (n = 71 ACT, n = 24 high-grade CS) and internal test (n = 19 ACT, n = 6 high-grade CS) cohorts, respectively, based on the date of surgery. At centre 2, the dataset constituted the external test cohort (n = 12 ACT, n = 18 high-grade CS). Manual segmentation was performed on frontal view X-rays, using MRI or CT for preliminary identification of lesion margins. After image pre-processing, radiomic features were extracted. Dimensionality reduction included stability, coefficient of variation, and mutual information analyses. In the training cohort, after class balancing, a machine learning classifier (Support Vector Machine) was automatically tuned using nested 10-fold cross-validation. Then, it was tested on both the test cohorts and compared to two musculoskeletal radiologists' performance using McNemar's test., Findings: Five radiomic features (3 morphology, 2 texture) passed dimensionality reduction. After tuning on the training cohort (AUC = 0.75), the classifier had 80%, 83%, 79% and 80%, 89%, 67% accuracy, sensitivity, and specificity in the internal (temporally independent) and external (geographically independent) test cohorts, respectively, with no difference compared to the radiologists (p ≥ 0.617)., Interpretation: X-rays radiomics-based machine learning accurately differentiates between ACT and high-grade CS of long bones., Funding: AIRC Investigator Grant., Competing Interests: Declaration of interests Matteo Interlenghi: CTO and employee of DeepTrace Technologies. DeepTrace Technologies is a spin-off of Scuola Universitaria Superiore IUSS, Pavia, Italy; shareholder in DeepTrace Technologies. Christian Salvatore: CEO of DeepTrace Technologies. DeepTrace Technologies is a spin-off of Scuola Universitaria Superiore IUSS, Pavia, Italy; shareholder in DeepTrace Technologies. Isabella Castiglioni: Shareholder in DeepTrace Technologies. All other authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Although patient narratives have been increasingly introduced in various fields of medicine, a standard method in clinical practice is still lacking. The objectives of this pilot study were to evaluate the feasibility and usefulness of a digital narrative diary integrated into the care pathway of patients with bone sarcoma and limb soft tissue sarcoma both from the patients' and the healthcare professionals' (HCPs) perspectives. A digital platform, DNMLAB, was designed to obtain guided narratives from patients during their pathway of care in compliance with confidentiality and data protection laws. The diary was used for patients, often young, facing a rare and impactful disease that is difficult to manage and with few opportunities to share experiences. The multidisciplinary team shared the narratives and integrated them into the patient's treatment pathway. Narrative prompts were adequate for the care pathway. Patients correctly considered the diary as a shared area to think about their condition, and HCPs considered it "a shared area growing at each meeting with the patient". The main advantages reported by patients were increased awareness, the opportunity to express their opinion on cures and important personal needs and the perception of better taking charge (score ≥ 4.6). The main advantages of HCP were improved communication, therapeutic alliance, and deeper knowledge of patients. This study confirmed the authors' previous experiences, showing that a digital narrative process is feasible and useful for oncology clinical practice according to patients and HCPs.

Purpose: To determine diagnostic performance of MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor (ALT) of the extremities., Material and Methods: This retrospective study was performed at three tertiary sarcoma centers and included 150 patients with surgically treated and histology-proven lesions. The training-validation cohort consisted of 114 patients from centers 1 and 2 (n = 64 lipoma, n = 50 ALT). The external test cohort consisted of 36 patients from center 3 (n = 24 lipoma, n = 12 ALT). 3D segmentation was manually performed on T1- and T2-weighted MRI. After extraction and selection of radiomic features, three machine learning classifiers were trained and validated using nested fivefold cross-validation. The best-performing classifier according to previous analysis was evaluated and compared to an experienced musculoskeletal radiologist in the external test cohort., Results: Eight features passed feature selection and were incorporated into the machine learning models. After training and validation (74% ROC-AUC), the best-performing classifier (Random Forest) showed 92% sensitivity and 33% specificity in the external test cohort with no statistical difference compared to the radiologist (p = 0.474)., Conclusion: MRI radiomics-based machine learning may classify deep-seated lipoma and ALT of the extremities with high sensitivity and negative predictive value, thus potentially serving as a non-invasive screening tool to reduce unnecessary referral to tertiary tumor centers., (© 2023. The Author(s).)

Background: Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle owns the remarkable ability to restore tissue damage, but only when limited in size. The current surgical therapies employed in the treatment of this pathology, which particularly affects military personnel, do not yet provide satisfactory results. For this reason, more innovative approaches must be sought, specifically skeletal muscle tissue engineering seems to highlight promising results obtained from preclinical studies in VML mouse model. Despite the great results obtained in rodents, translation into human needs a comparable animal model in terms of size, in order to validate the efficacy of the tissue engineering approach reconstructing larger muscle mass (human-like). In this work we aim to demonstrate the validity of a porcine model, that has underwent a surgical ablation of a large muscle area, as a VML damage model., Results: For this purpose, morphological, ultrasound, histological and fluorescence analyses were carried out on the scar tissue formed following the surgical ablation of the peroneus tertius muscle of Sus scrofa domesticus commonly called mini-pig. In particular, the replenishment of the damaged area, the macrophage infiltration and the vascularization at different time-points were evaluated up to the harvesting of the scar upon six months., Conclusion: Here we demonstrated that following VML damage, there is an extremely poor regenerative process in the swine muscle tissue, while the formation of fibrotic, scar tissue occurs. The analyses performed up to 180 days after the injury revealed the development of a stable, structured and cellularized tissue, provided with vessels and extracellular matrix acquiring the status of granulation tissue like in human., (© 2023. The Author(s).)

Background: The COVID-19 outbreak had a negative psychological impact on cancer patients. In this study, we analyzed emotional distress and quality of life in patients diagnosed with sarcoma during the first year of the pandemic compared to the previous year., Methods: We retrospectively enrolled patients with soft tissue, bone sarcoma, and aggressive benign musculoskeletal diseases diagnosed during the pandemic (COVID group) or the year before (control group) at the IRCCS Regina Elena National Cancer Institute in Rome. Patients who had undergone a psychological assessment with the EORTC QLQ-C30 and the Distress Thermometer at diagnosis were included in the final analysis. We analyzed whether there is a difference in the various domains of quality of life between the two groups and whether there are changes over time in each group., Results: We enrolled 114 patients (72 control group; 42 COVID group), affected by soft tissue (64%), bone sarcoma (29%), and aggressive benign musculoskeletal diseases (7%). We did not observe significant differences in the health-related quality of life domains in the control and COVID groups, except for the financial domain ( p  = 0.039), with 9.7% vs. 23.8% of patients with a score > 0 in the control and COVID groups, respectively. We observed emotional distress at diagnosis in 48.6% of patients in the control group vs. 69.0% in the COVID group ( p = 0.034). In the control group, we observed an improvement in physical function ( p = 0.043) and in QoL ( p = 0.022), while in the COVID group, we observed a deterioration in role function ( p = 0.044) during follow-up. In the COVID group, 22.2% of patients were concerned about COVID-19, 61.1% by tumor, 91.1% stated that the pandemic worsened their subjective perception of cancer, and 19.4% perceived that their quality of care had worsened., Conclusion: We observed a higher level of distress among patients diagnosed during the pandemic compared to the year before, probably due to the increased concern for both infection and cancer, the worsened perception of health status, and the perception of a poorer quality of health care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Onesti, Vari, Minghelli, Nardozza, Rossi, Sperati, Checcucci, Faltyn, Cercato, Cosimati, Salvatori, Biagini, Ciliberto, Ferraresi and Maggi.)

Introduction: Surgery of primary malignant tumors involving the sacroiliac joint requires wide resection, which often interrupts the pelvic ring. Nowadays, restoration of the pelvic ring to provide stability and which technique is most fitting remain subject to debate. The aim of this study is to evaluate the results of pelvic reconstruction with pedicle screw instrumentation and tibial allograft following Enneking Type I-IV resections., Patients and Methods: All patients who underwent reconstruction with tibial allograft, screws and rods after resection of areas I and IV for primary bone tumors between 2017 and 2022 were reviewed. Clinical and radiological characteristics, fusion rate and functional results were analyzed. The MSTS score and the TESS were used to evaluate functional results., Results: Seven patients were included in the study. Chondrosarcoma was the most common histology. Only four patients reported pain. No fractures were observed at tumor diagnosis. Computer-assisted navigation was used in six cases. Reconstruction was performed in four cases with a screw inserted in the homolateral L5 pedicle and in the ischium, in two cases with a screw in the homolateral L4 pedicle and another in the homolateral L5 pedicle, in the last case with two screws inserted in L4 and L5, one screw in the ischium and another one in the residual iliac wing. In this case a contralateral stabilization was also carried out. The spine screws and the iliac screws were connected with a rod. The mean follow-up for all 7 patients was 37 months. One patient (16.6%) died due to general complications not directly related to the surgery; while the others are alive and apparently free of disease. Complete fusion was obtained in four out of seven patients and the average time for fusion was 9 months. The average MSTS score and TESS were 58.7% and 57.8%, respectively., Discussion: The need for reconstruction is thoroughly debated in literature. The advantages of restoring posterior pelvis stability are the prevention of long-term pain associated with limb shortening and secondary scoliosis. Re-establishment of the pelvic ring can be achieved through synthetic, biologic or hybrid reconstructions., Conclusions: More studies that assess the surgical consequences at long-term follow-up and help clarify the indications for reconstruction and the specific technique are necessary to confirm our preliminary results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Three-dimensional (3D) bioprinting is an emerging technology, which turned out to be an optimal tool for tissue engineering approaches. To date, different printing systems have been developed. Among them, the extrusion-based approach demonstrated to be the most suitable for skeletal muscle tissue engineering, due to its ability to produce and deposit printing fibers in a parallel pattern that well mimic the native skeletal muscle tissue architecture. In tissue bioengineering, a key role is played by biomaterials, which must possess the key requisite of 'printability'. Nevertheless, this feature is not often well correlated with cell requirements, such as motives for cellular adhesion and/or absorbability. To overcome this hurdle, several efforts have been made to obtain an effective bioink by combining two different biomaterials in order to reach a good printability besides a suitable biological activity. However, despite being efficient, this strategy reveals several outcomes limitations. We report here the development and characterization of a novel extrusion-based 3D bioprinting system, and its application for correction of volumetric muscle loss (VML) injury in a mouse model. The developed bioprinting system is based on the use of PEG-Fibrinogen, a unique biomaterial with excellent biocompatibility, well-suited for skeletal muscle tissue engineering. With this approach, we obtained highly organized 3D constructs, in which murine muscle progenitors were able to differentiate into muscle fibers arranged in aligned bundles and capable of spontaneously contracting when cultured in vitro . Furthermore, to evaluate the potential of the developed system in future regenerative medicine applications, bioprinted constructs laden with either murine or human muscle progenitors were transplanted to regenerate the Tibialis Anterior muscle of a VML murine model, one month after grafting., (Creative Commons Attribution license.)

Background: Undifferentiated soft-tissue sarcomas (USTS) are one of the most common sarcoma histotypes in adults. The standard of care is surgical excision plus adjuvant radiotherapy, while the use of perioperative chemotherapy is still controversial. The aim of this study was to investigate the value of pre-treatment [18F]FDG PET/CT conventional metrics and textural features in predicting disease-free survival (DFS) and overall survival (OS) in patients with USTS of the limbs and trunk., Methods: [18F]FDG PET/CT scans of 51 consecutive patients with locally advanced USTS were retrospectively evaluated. Conventional and textural PET parameters were analysed and tested as predictive factors for DFS and OS., Results: During a median follow up of 50.7 months, 23 (45.1%) and 29 (56.9%) patients had death or disease progression, respectively. Univariate analysis revealed a significant association for perioperative treatment, PET volumetric parameters and the textural feature GLCM&#95;correlation with DFS and OS. In multivariate analysis, perioperative treatment and GLCM&#95;correlation were the only independent factors, allowing stratification of the population into three different prognostic classes., Conclusion: GLCM&#95;correlation can identify USTS at high risk of relapse and death, thus helping to optimize the perioperative treatment of patients.

Objective: The extent of response to neoadjuvant chemotherapy predicts survival in Ewing sarcoma. This study focuses on MRI radiomics of skeletal Ewing sarcoma and aims to investigate feature reproducibility and machine learning prediction of response to neoadjuvant chemotherapy., Materials and Methods: This retrospective study included thirty patients with biopsy-proven skeletal Ewing sarcoma, who were treated with neoadjuvant chemotherapy before surgery at two tertiary sarcoma centres. 7 patients were poor responders and 23 were good responders based on pathological assessment of the surgical specimen. On pre-treatment T1-weighted and T2-weighted MRI, 2D and 3D tumour segmentations were manually performed. Features were extracted from original and wavelet-transformed images. Feature reproducibility was assessed through small geometrical transformations of the regions of interest mimicking multiple manual delineations, and intraclass correlation coefficient >0.75 defined feature reproducibility. Feature selection also consisted of collinearity and significance analysis. After class balancing in the training cohort, three machine learning classifiers were trained and tested on unseen data using hold-out cross-validation., Results: 1303 (77%) 3D and 620 (65%) 2D radiomic features were reproducible. 4 3D and 4 2D features passed feature selection. Logistic regression built upon 3D features achieved the best performance with 85% accuracy (AUC=0.9) in predicting response to neoadjuvant chemotherapy., Conclusion: Compared to 2D approach, 3D MRI radiomics of Ewing sarcoma had superior reproducibility and higher accuracy in predicting response to neoadjuvant chemotherapy, particularly when using logistic regression classifier., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gitto, Corino, Annovazzi, Milazzo Machado, Bologna, Marzorati, Albano, Messina, Serpi, Anelli, Ferraresi, Zoccali, Aliprandi, Parafioriti, Luzzati, Biagini, Mainardi and Sconfienza.)

A 42-year-old male with left hip pain was diagnosed of several right femoral and tibial bone tumours. All lesions were osteolytic with sclerotic margins. The symptomatic lesion in the proximal femur also showed bone expansion and focal cortical thinning. Whole-body [ 18 F]-fluorodeoxyglucose (FDG) PET/CT and segmental PET/MRI of the left hip and femur were performed for metabolic characterization of the lesions and for biopsy guidance. The lesions showed a heterogenous degree of FDG uptake corresponding to different metabolic stages of the disease. A biopsy of the tumour portion showing the highest FDG uptake revealed a fibrous dysplasia (FD). In conclusion, although generally affecting paediatric and adolescent subjects, polyostotic FD may be detected in the adulthood. Despite the benign nature of the disease, increased glucose metabolism can be seen in some lesions. Hybrid imaging combining morphological and functional information may help guide biopsy and better define the treatment strategy., (© 2022. The Author(s).)

Background: The COVID-19 pandemic led to a rapid reorganization of healthcare activities, leading to reduced access to clinics, interruption of screenings, and treatment schedule modifications in several cancer types. Few data are available on sarcomas. We analyzed COVID-19-related diagnostic delay in a sarcoma referral center in Italy., Methods: We retrospectively enrolled in this study patients with histological diagnosis of soft tissue or bone sarcoma and aggressive benign musculoskeletal diseases obtained during the first year of the pandemic (Covid group) or the year before (Control group) and followed at the Regina Elena National Cancer Institute in Rome. The primary endpoint was the time from the first symptom to histological diagnosis., Results: We evaluated 372 patients, 185 of whom were eligible for primary endpoint analysis (92 patients in the Control group and 93 patients in the Covid group). The patients were affected by soft tissue sarcoma in most cases (63.0% and 66.7% in Covid and Control groups, respectively). We observed a diagnostic delay in the Covid group with a median time from the first symptom to the definitive histological diagnosis of 103.00 days (95% CI 92.77-113.23) vs . 90.00 days (95% CI 69.49-110.51) in the Control group ( p = 0.024), but not a delay in treatment beginning (151 days, 95% CI 132.9-169.1 vs . 144 days, 95% CI 120.3-167.7, respectively, p = 0.208). No differences in stage at diagnosis were observed (12% vs . 16.5% of patients with metastatic disease at diagnosis in the Covid and Control groups, respectively, p = 0.380). Progression-free survival ( p = 0.897) and overall survival ( p = 0.725) were comparable in the subgroup of patients affected by soft tissue sarcoma., Conclusions: A delay in sarcoma diagnosis but not in starting treatment has been observed during the first year of the COVID-19 pandemic. Nevertheless, no difference in stage at diagnosis or in terms of survival has been observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DM declared a past co-authorship with the author SV and a shared parent affiliation with the author AC to the handling editor at the time of review. The author CEO declared past co-authorships with the Editor RG., (Copyright © 2022 Onesti, Vari, Nardozza, Maggi, Minghelli, Rossi, Sperati, Checcucci, Faltyn, Cercato, Cosimati, Biagini, Ciliberto and Ferraresi.)

The use of massive bone allografts after the resection of bone tumours is still a challenging process. However, to overcome some issues related to the processing procedures and guarantee the best three-dimensional matching between donor and recipient, some tissue banks have developed a virtual tissue database based on the scanning of the available allografts for using their 3D shape during virtual surgical planning (VSP) procedures. To promote the use of future VSP bone-shaping protocols useful for machining applications within a cleanroom environment, in our work, we simulate a massive bone allograft machining with two different machines: a four-axes (computer numerical control, CNC) vs. a five-axes (robot) milling machine. The allograft design was based on a real case of allograft reconstruction after pelvic tumour resection and obtained with 3D Slicer and Rhinoceros software. Machining simulations were performed with RhinoCAM and graphically and mathematically analysed with CloudCompare and R, respectively. In this case, the geometrical differences of the allograft design are not clinically relevant; however, the mathematical analysis showed that the robot performed better than the four-axes machine. The proof-of-concept presented here paves the way towards massive bone allograft cleanroom machining. Nevertheless, further studies, such as the simulation of different types of allografts and real machining on massive bone allografts, are needed.

Background: Guidelines for the implementation of narrative medicine in clinical practice exist; however, in Italy, no standard methodology is currently available for the management of oncological patients. Since 2017, at the "Regina Elena" National Cancer Institute, studies using "digital narrative diaries" (DNMLAB platform) have been carried out; this article focuses on a pilot, uncontrolled, real-life study aiming to evaluate the utility of DNM integrated with the care pathway of patients with bone and limb soft tissue sarcomas., Methods: Adult patients completed the diary during treatment or follow-up by writing their narrative guided by a set of narrative prompts. The endpoints were: (a) patients' opinions about therapeutic alliance, awareness, and coping ability; (b) healthcare professionals' (HCPs') opinions about communication, therapeutic alliance, and information collection. Open- and closed-ended questions (Likert score: 1-5) were used to assess the items., Results: At the interim analysis of data from seven patients and five HCPs, DNM was shown to improve: (a) the expression of patients' point of view, the perception of effective taking charge, disease awareness, and self-empowerment (score: 4.8/5); (b) patients' communication, relationships, and illness knowledge (score: 4.6-4.8/5)., Conclusions: The preliminary results supported the need to integrate patients' narratives with clinical data and encourage further research.

Competing Interests: Disclosure PGC has received honoraria for participation in advisory board for Bayer, institutional research funding from Amgen Dompé, Advenchen, Bayer, Blueprint, Deciphera, Eli Lilly, Epizyme, Daiichi, GlaxoSmithKline (GSK), Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks, AROG Pharmaceuticals and Eisai and carried out nonremunerated activities for the Italian Sarcoma Group, European School of Oncology, Federation of Italian Cooperative Groups and Rare Cancers Europe; JYB received research support from Merck Sharp & Dohme (MSD), Roche, GSK, Novartis, Bayer, PharmaMar outside the present work; NA reports nonremunerated leadership and advisory roles for Sociedade Portuguesa de Cirurgia; JB reports no personal financial disclosure, received research grants (institutional) from Eli Lilly, Novartis, Roche, Samsung Bioepis, Paxman Coolers Ltd., Sun Pharma and reports nonremunerated advisory role for Novartis, nonremunerated leadership activities for Immuno-Oncology Society of India, Indian Society of Medical and Paediatric Oncology, Teenage and Young Adult Cancer Foundation and Indian Cooperative Oncology Network; SB has received honoraria for participation in advisory boards for Deciphera, Blueprint Medicines, Lilly, Novartis, Daiichi-Sankyo, Plexxikon, Roche, GSK and reports invited speaker fees from Pfizer and PharmaMar, institutional research grant from Novartis, performed institutional research as principal investigator (PI) for Daiichi-Sankyo, Roche, Deciphera, Lilly, Novartis, Blueprint Medicines, Bristol Myers Squibb (BMS), Incyte and carried out nonrenumerated activities for Federal Institute for Drugs and Medical Devices (BfArm) and is the founding member of German Sarcoma Foundation; RB reports nonrenumerated activities as PI for IRCSS Galeazzi Orthopaedic Institute and IRE-ISG Regina Elena Institute and participation at the Clinical Experience Exchange Meeting, III IDBN National Congress 2019, Italian Association of Medical Oncology (AIOM), IRE-ISG Regina Elena Institute and Lazio Association of Orthopaedic Hospital Traumatologists (A.L.O.T.O.); SBi has received honoraria for participation in advisory boards from Bayer Healthcare, Boehringer Ingelheim, Clinigen, Hoffmann-La Roche, Ipsen, Eli Lilly and Sensorion and reports nonremunerated activities for Bayer and membership of the German Paediatric Oncology Society and European Musculoskeletal Oncology Society; SBon has received honoraria for advisory board from Nanobiotix and as an invited speaker for PharmaMar, trial research grant from the Institut National du Cancer (INCa); IB has received honoraria for participation in advisory boards for Roche, Lilly, Sanofi, Pierre Fabre, Ipsen and as an invited speaker for Amgen, BMS, Novartis, Leo Pharma, AstraZeneca and Genesis and is a member of Board of Directors for Hellenic Society of Medical Oncology, Hellenic Society of Sarcomas and Rare Tumors, Hellenic Oncology Research Group (HORG) and reports PI trial research support from Novartis, BMS, Regeneron, MSD, Lilly and Roche; JVMGB receives royalties from UpToDate and Wolters Kluwer, and direct research funding from TRACON pharmaceuticals; KB has received honoraria for expert testimony and advisory boards for Bayer, invited speaker fees and research grant from Eli Lilly, PI for Deciphera and Novartis; TB has received honoraria for participation in advisory boards for Bayer and Eli Lilly, invited speaker fees from PharmaMar and Novartis; EDÁ has received honoraria for participation in advisory board for Bayer, invited speaker for Lilly, PharmaMar and Roche and institutional research support from Pfizer, Roche and AstraZeneca; APDT has received honoraria for participation in advisory boards for Bayer and Roche, invited speaker for PharmaMar and Novartis; XGDM has received honoraria for participation in advisory boards for Ipsen, EUSAPharma, BMS, Pfizer, Roche and PharmaMar and is an invited speaker for Lilly, Astellas Pharma, Eisai and Pfizer and received institutional research grant from Astra Zeneca; ME has received honoraria for participation in advisory boards for Clinigen and Bayer, consulting fees from Blueprint Medicines, institutional research funding from Novartis; AF has received honoraria for participation in advisory board for Novartis and invited speaker fees for MSD and Amgen; VF has received honoraria for participation in advisory boards and speaker fees for BMS, Novartis and MSD and speaker fees from Pierre Fabre; SG has reported institutional research for Blueprint Medicines and is a member of American Society of Clinical Oncology (ASCO) and AIOM; HG has reported PI research for Daiichi, Deciphera and Novartis and co-ordinating PI for Boehringer Ingelheim and AmMax Bio; FG has received honoraria for participation in advisory board for Amgen and expert testimony for Deciphera, stock ownership for Atlanthera, licencing fees from Zimmer, nonrenumerated activities for 3D-Side and INCa DGOS funding and is a member of the board of NetSarc, the French clinical reference network for soft tissue and visceral sarcomas; GG has received honoraria for participation in advisory boards for Lilly, Eisai, Merck, Bayer and GSK, invited speaker fees from PharmaMar and Novartis and institutional grants from PharmaMar, Bayer and Novartis; RH has received honoraria from GSK; ABH is a member of Board of Directors for EIT Health UK and Ireland and received or currently receives direct research funding as a PI from Roche, performs work in clinical trials or contracted research for the institution and as the Clinical Director of the Oncology and Haematology Directorate, Oxford Cancer Centre; NH has received honoraria as expert testimony and invited speaker from PharmaMar and performs work in clinical trials or contracted research for which the author’s institution received financial support from PharmaMar, Lilly, Adaptimmune Therapeutics, AROG Pharmaceuticals, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint Medicines, Nektar Therapeutics, Forma, Amgen and Daiichi-Sankyo and reports nonremunerated leadership roles for Grupo Español de Investigación en Sarcomas (GEIS) and SELNET and has nonremunerated membership or affiliation with ESMO, Sociedad Española de Oncología Médica (SEOM), ASCO, Connective Tissue Oncology Society (CTOS) and European Organisation for Research and Treatment of Cancer (EORTC); PH has received honoraria for participation in advisory boards for Pfizer, Roche and GSK, invited speaker fees from PharmaMar and Lilly, clinical expert fees from Boehringer Ingelheim and institutional research funding for clinical trials from Siemens, Novartis, Blueprint Medicines and meeting sponsorship from PEKKIP Oncology and reports carrying out nonremunerated activities for the German Sarcoma Foundation (DSS), German Interdisciplinary Sarcoma Group (GISG) and Interdisciplinary Working Party on Sarcomas (IAWS) of the German Cancer Society (DKG) and advisory role for the German Cancer Aid (DKH) Committee on Health Technology Assessment and Sarcoma Patients EuroNet (SPAEN); HJ has received honoraria for participation in advisory boards for Orion Pharma, Neutron Therapeutics and Maud Kuistila Memorial Foundation and had full time or part time employment at Orion Pharma (until 31 August 2020), stocks in Orion Pharma and Sartar Therapeutics; RLJ has received honoraria for expert testimony consultancy for Adaptimmune, Bayer, Boehringer Ingelheim, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daiichi, Deciphera, Immune Design, Lilly, SpringWorks, Tracon, UpToDate, PharmaMar and is on the advisory board for Athenex and received institutional research grant from MSD; CJ has received travel grants from Ipsen and PharmaMar; BK has received honoraria for participation in advisory boards for Bayer, Blueprint Medicines, Boehringer Ingelheim, SpringWorks, GSK and PharmaMar, institutional research support from PharmaMar and SpringWorks and is a member of EORTC and Chair of the EORTC soft tissue and bone sarcoma group (STBSG); AK has received honoraria for participation in advisory boards for Daiichi-Sankyo and Otsuka and invited speaker fees from Novartis, Taiho and Eisai; KK has received honoraria for participation in the advisory board for Bayer and expert testimony for Eli Lilly and Roche; ALC has received honoraria for participation in advisory boards for Deciphera and Lilly and invited speaker fees from PharmaMar and Bayer; EL received honoraria from SpringWorks Therapeutics for scientific advisory board participation and is a member of the European Reference Network GENTURIS; AL has received institutional research grants from Johnson & Johnson, Alphamed, Medacta and ImplanTec and reports nonremunerated activities for European Musculoskeletal Society (EMSOS), Austrian Society of Orthopaedic Surgeons (OGO) and membership of CTOS; AL-P has received honoraria as invited speaker for PharmaMar, institutional research funding from the Spanish Health Ministry, reported nonrenumerated activities as PI for PharmaMar, Cebiotex, Deciphera, Lilly, GSK, Daiichi, Epizyme, Advenchen Laboratories, Novartis, Karyopharm, Blueprint medicines, GEIS and other activity for EORTC; JM-B has received honoraria for expert testimony for Lilly, PharmaMar, Eisai, Bayer, invited speaker fee from PharmaMar and carried out institutional research for PharmaMar, Eisai, Novartis, Immix Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Blueprint Medicines, Deciphera, Nektar Therapeutics, Forma, Amgen, Daiichi-Sankyo, Lilly, AROG Pharmaceuticals, Adaptimmune and GSK; OM has received honoraria for participation in advisory boards for MSD, Megapharm, AstraZeneca, Takeda and ProGenetics and invited speaker fees from MSD and Roche; CM has performed nonremunerated activities for International Cancer Imaging Society and EORTC STBSG; OMi has received honoraria for participation in advisory boards for Bayer, Blueprint Medicines, MSD, Pfizer, invited speaker fees from BMS, Eli-Lilly, Ipsen, Roche and Servier and institutional research for Blueprint Medicines, Bayer, Epizyme and Eli-Lilly; EP has received honoraria for participation in advisory boards for SynOx, Daiichi-Sankyo and Deciphera Pharmaceuticals and invited speaker fees from Peer View Educational; MAP has received honoraria for participation in advisory boards for Roche, invited speaker fees from Eli-Lilly, Pfizer and Novartis and expert testimony from Blueprints Medicine and institutional research grant from Novartis; SP-N has received honoraria for participation in advisory board for Immunocore; PR has received honoraria for participation in advisory boards for Bayer, Clinigen, Roche, MSD, Deciphera, Mundibiopharma, PharmaMar, Blueprint Medicines, invited speaker fees from Lilly, PharmaMar and institutional research for PharmaMar, Karyopharm, SpringWorks, AROG Pharmaceuticals, Blueprint, Deciphera, Amgen, Astellas, Epizyme, Lilly, MSD, Pfizer, Novartis and Philogen and has membership of the German Sarcoma Foundation; PRu has received honoraria for participation in advisory boards for MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, invited speaker fees from MSD, BMS, Pierre Fabre, Merck, Sanofi, Novartis and institutional research funding from Pfizer, BMS and reports carrying out nonremunerated activities for the Polish Society of Surgical Oncology and ASCO; MS has received honoraria for travel grant from PharmaMar and writing engagement for Lilly; SS has reported a research grant from Johnson & Johnson and research funding from Roche Austria; PS has received honoraria for participation in advisory boards for Deciphera, Blueprint Medicines, Boehringer Ingelheim, Ellipses Pharma, Transgene, Exelixis, Medscape, Guided Clarity, Ysios, Modus Outcomes, Studiecentrum voor Kernenergie, Curio Science and institutional honoraria for advisory boards for Blueprint Medicines, Ellipses Pharma, IntelliSphere, expert testimony for Advanced Medical/Teladoc Health and institutional research funding from CoBioRes NV, Eisai, G1 Therapeutics, Novartis and PharmaMar; SSl is the Chair of Centre for Personalised Cancer Treatment and Route Personalised Medicine, Dutch Science Agenda, a member of supervisory board for SkylineDx and Scientific advisory committee Pan-Cancer T BV; SJS has received honoraria for participation in advisory board for GSK; KSH reports nonrenumerated activity for CTOS as President 2020 and membership of the Scandinavian Sarcoma Group; MAJvdS has performed work in clinical trials or contracted research for which the institution received financial support from Daiichi Sankyo, implantcast and CarboFix; WTAvdG has received institutional honoraria for participation in advisory boards of Bayer and GSK, institutional research grants from Novartis and Lilly and performed consultancy work for SpringWorks; WJvH has received institutional honoraria for participation in advisory board for Belpharma, invited speaker fees from Amgen and reports expert testimony for Sanofi and MSD and personal travel grant from Novartis and institutional research grant from BMS; TF reports institutional research funding from the Foundation ARC and Ligue Régionale contre le Cancer and leadership role for ERN GENTURIS; AG has received honoraria for participation in advisory boards for Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks and Nanobiotix and is an invited speaker for Lilly, PharmaMar and reports research grant from PharmaMar; SSta has received honoraria for participation in advisory boards for Bayer, Deciphera, Eli Lilly, Daiichi, MaxiVAX, Novartis, invited speaker fees from GSK and PharmaMar, expert testimony fee from Bavarian Nordic and Epizyme and institutional research funding from Amgen Dompé, Advenchen, Bayer, Blueprint Medicines, Deciphera, Eli Lilly, Epizyme, Daiichi, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks and Hutchinson MediPharma International Inc. and carried out nonremunerated activities for CTOS, Chordoma Foundation, Epithelioid Haemangioendothelioma Foundation, Desmoid Foundation, EORTC STBSG and Italian Sarcoma Group Onlus. AB, AD, AFer, AMF, PJ, DAK, FLG, ABM, MM, CMo, RP, AAS, CS, DS, AT and MU have declared no conflicts of interests.

Competing Interests: Disclosure SJS has received honoraria for participation in advisory board for GlaxoSmithKline (GSK); NA non-remunerated leadership and advisory roles for Sociedade Portuguesa de Cirurgia; JB has no personal financial disclosure, received research grants (institutional) from Eli Lilly, Novartis, Roche, Samsung Bioepis, Paxman Coolers Ltd, Sun Pharma and non-remunerated advisory role for Novartis, non-remunerated leadership activities for Immuno-oncology society of India, Indian Society of Medical and Paediatric Oncology, Teenage and Young Adult Cancer Foundation and Indian cooperative oncology network; SB has received honoraria for participation in advisory boards for Deciphera, Blueprint Medicines, Lilly, Novartis, Daiichi-Sankyo, Plexxikon, Roche, GSK, invited speaker fees from Pfizer and PharmaMar, institutional research grant from Novartis, institutional research as principal investigator (PI) for Daiichi-Sankyo, Roche, Deciphera, Lilly, Novartis, Blueprint Medicines, Bristol Myers Squibb (BMS), Incyte, non-remunerated activities for Federal Institute for Drugs and Medical Devices (BfArm) and founding member of German Sarcoma Foundation; RB reports non-remunerated activities as PI for IRCSS Galeazzi Orthopedic Institute and IRE-ISG Regina Elena Institute, participation at the Clinical Experience Exchange Meeting, III IDBN National Congress 2019, Italian Association of Medical Oncology (AIOM), IRE-ISG Regina Elena Institute and Lazio Association of Orthopaedic Hospital Traumatologists (ALOTO); SBi has received honoraria for participation in advisory boards from Bayer Healthcare, Boehringer Ingelheim, ClinGen, Hofmann La Roche, Ipsen, Eli Lilly and Sensorion, non-remunerated activities for Bayer and membership of the German Pediatric Oncology Society and European Musculoskeletal Oncology Society; JYB received research support from Merck Sharp & Dohme (MSD), Roche, GSK, Novartis, Bayer, PharmaMar outside the present work; SBon has received honoraria for advisory board from Nanobiotix and as invited speaker for PharmaMar, trial research grant from the Institut National du Cancer (INCa); IB has received honoraria for participation in advisory boards for Roche, Lilly, Sanofi, Pierre Fabre, Ipsen, and as invited speaker for Amgen, BMS, Novartis, Leo Pharma, AstraZeneca and Genesis, member of Board of Directors for Hellenic Society of Medical Oncology, Hellenic Society of Sarcomas and Rare Tumors, Hellenic Oncology Research Group (HORG), PI trial research support from Novartis, BMS, Regeneron, MSD, Lilly and Roche; JVMGB receives royalties from UpToDate and Wolters Kluwer, and direct research funding from TRACON pharmaceuticals; KB has received honoraria for expert testimony and advisory boards for Bayer, invited speaker fees and research grant from Eli Lilly, PI for Deciphera and Novartis; TB has received honoraria for participation in advisory boards for Bayer and Eli Lilly, invited speaker fees from PharmaMar and Novartis; EDÁ has received honoraria for participation in advisory board for Bayer, invited speaker for Lilly, PharmaMar and Roche, institutional research support from Pfizer, Roche and AstraZeneca; APDT has received honoraria for participation in advisory boards for Bayer and Roche, invited speaker for PharmaMar and Novartis; XGDM has received honoraria for participation in advisory boards for Ipsen, EUSA Pharma, BMS, Pfizer, Roche and PharmaMar, invited speaker for Lilly, Astellas Pharma, Eisai and Pfizer and institutional research grant from AstraZeneca; ME has received honoraria for participation in advisory boards for Clinigen and Bayer, consulting fees from Blueprint Medicines, institutional research funding from Novartis; AF has received honoraria for participation in advisory board for Novartis and invited speaker fees for MSD and Amgen; VF has received honoraria for participation in advisory boards and speaker fees for BMS, Novartis and MSD and speaker fees from Pierre Fabre; NG has received honoraria as invited speaker for Eisai and reports membership of the European Society for Paediatric Oncology (SIOPE), ACCELERATE, Societe Francaise de lutte contre les cancers et leucemies de l'enfant et de l'adolescent (SFCE) and Groupe Onco- hématologie Adolescents et Jeunes Adultes (GO-AJA); SG has reported institutional research for Blueprint Medicines and member of American Society of Clinical Oncology (ASCO) and AIOM; HG has reported PI research for Daiichi, Deciphera and Novartis, co-ordinating PI for Boehringer Ingelheim and AmMax Bio; FG has received honoraria for participation in advisory board for Amgen and expert testimony for Deciphera, stock ownership for Atlanthera, licensing fees from Zimmer, non-remunerated activities for 3D-Side and INCa DGOS funding and member of the board of NetSarc the French clinical reference network for soft tissue and visceral sarcomas; GG has received honoraria for participation in advisory boards for Lilly, Eisai, Merck, Bayer and GSK, invited speaker fees from PharmaMar and Novartis, institutional grants from PharmaMar, Bayer and Novartis; AG has received honoraria for participation in advisory boards for Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks and Nanobiotix, invited speaker for Lilly, PharmaMar and research grant from PharmaMar; RH has received honoraria from GSK; ABH is a member of Board of Directors for EIT health UK and Ireland, received or currently receives direct research funding as a PI from Roche, performs work in clinical trials or contracted research for the Institution and Clinical Director of the Oncology and Haematology Directorate, Oxford Cancer Centre; SHN reports institutional research role as deputy PI for Eisai, non-remunerated activity for Harmonization International Bones Sarcoma Consortium (HIBISCus), membership of SIOPE, German, Swiss, Austrian Society of Paediatric Oncology and Hematology (GPOH) and German Society of Pediatrics and Adolescent Medicine (DGKJ); NH has received honoraria as expert testimony and invited speaker from PharmaMar, performs work in clinical trials or contracted research for which his/her institution received financial support from PharmaMar, Lilly, Adaptimmune Therapeutics, AROG Pharmaceuticals, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint Medicines, Nektar Therapeutics, Forma, Amgen and Daiichi-Sankyo, non-remunerated leadership roles for Grupo Español de Investigación en Sarcomas (GEIS) and SELNET, and has non-remunerated membership or affiliation with ESMO, Sociedad Española de Oncología Médica (SEOM), ASCO, Connective Tissue Oncology Society (CTOS) and European Organisation for Research and Treatment of Cancer (EORTC); PH has received honoraria for participation in advisory boards for Pfizer, Roche and GSK, invited speaker fees from PharmaMar and Lilly, clinical expert fees from Boehringer Ingelheim, institutional research funding for clinical trials from Siemens, Novartis, Blueprint Medicines and meeting sponsorship from PEKKIP Oncology, non-remunerated activities for the German Sarcoma Foundation (DSS), German Interdisciplinary Sarcoma Group (GISG) and Interdisciplinary Working Party on Sarcomas (IAWS) of the German Cancer Society (DKG), advisory role for the German Cancer Aid (DKH) Committee on Health Technology Assessment and Sarcoma Patients EuroNet (SPAEN); HJ has received honoraria for participation in advisory boards for Orion Pharma, Neutron Therapeutics and Maud Kuistila Memorial Foundation, had full time or part time employment at Orion Pharma, until 31 August 2020, stocks in Orion Pharma and Sartar Therapeutics; RLJ has received honoraria for expert testimony consultancy for Adaptimmune, Bayer, Boehringer Ingelheim, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daiichi, Deciphera, Immune Design, Lilly, SpringWorks, Tracon, UpToDate, PharmaMar, advisory board for Athenex, institutional research grant from MSD; CJ has received travel grants from Ipsen and PharmaMar; LK has received honoraria for participation in advisory boards for Bayer, Novartis and Agios; BK has received honoraria for participation in advisory boards for Bayer, Blueprint Medicines, Boehringer Ingelheim, SpringWorks, GSK and PharmaMar, institutional research support from PharmaMar and SpringWorks, member of EORTC and Chair of the EORTC soft tissue and bone sarcoma group (STBSG); AK has received honoraria for participation in advisory boards for Daiichi-Sankyo and Otsuka and invited speaker fees from Novartis, Taiho and Eisai; KK has received honoraria for participation in advisory board for Bayer and expert testimony for Eli Lilly and Roche; ALC has received honoraria for participation in advisory boards for Deciphera and Lilly, invited speaker fees from PharmaMar and Bayer; EL received honoraria from SpringWorks Therapeutics for scientific advisory board participation and member of the European Reference Network GENTURIS; AL has received institutional research grants from Johnson & Johnson, Alphamed, Medacta and ImplanTec, non-remunerated activities for European Musculoskeletal Society (EMSOS), Austrian Society of Orthopaedic Surgeons (OGO) and membership of CTOS; ALP has received honoraria as invited speaker for PharmaMar, institutional research funding from the Spanish Health Ministry, reported non-remunerated activities as PI for PharmaMar, Cebiotex, Deciphera, Lilly, GSK, Daiichi, Epizyme, Advenchen Laboratories, Novartis, Karyopharm, Blueprint medicines, GEIS and other activity for EORTC; JMB has received honoraria for expert testimony for Lilly, PharmaMar, Eisai, Bayer, invited speaker fee from PharmaMar, institutional research for PharmaMar, Eisai, Novartis, Immix Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Blueprint Medicines, Deciphera, Nektar Therapeutics, Forma, Amgen, Daiichi-Sankyo, Lilly, AROG Pharmaceutcials, Adaptimmune and GSK; OM has received honoraria for participation in advisory boards for MSD, Megapharm, AstraZeneca, Takeda and Progenetics, invited speaker fees from MSD and Roche; CM has performed non-remunerated activities for International Cancer Imaging Society and EORTC STBSG; OMi has received honoraria for participation in advisory boards for Bayer, Blueprint Medicines, MSD, Pfizer, invited speaker fees from BMS, Eli Lilly, Ipsen, Roche and Servier, institutional research for Blueprint Medicines, Bayer, Epizyme and Eli-Lilly; BM has received honoraria from Clinigen as invited speaker; EP has received honoraria for participation in advisory boards for SynOx, Daiichi-Sankyo and Deciphera Pharmaceuticals and invited speaker fees from Peer View Educational; MAP has received honoraria for participation in advisory boards for Roche, invited speaker fees from Eli Lilly, Pfizer, and Novartis, expert testimony from Blueprints Medicine and institutional research grant from Novartis; SPN has received honoraria for participation in advisory board for Immunocore; PR has received honoraria for participation in advisory boards for Bayer, Clinigen, Roche, MSD, Deciphera, Mundibiopharma, PharmaMar, Blueprint Medicines, invited speaker fees from Lilly, PharmaMar, institutional research for PharmaMar, Karyopharm, SpringWorks, AROG Pharmaceuticals, Blueprint, Deciphera, Amgen, Astellas, Epizyme, Lilly, MSD, Pfizer, Novartis and Philogen, membership of German Sarcoma Foundation; PRu has received honoraria for participation in advisory boards for MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, invited speaker fees from MSD, BMS, Pierre Fabre, Merck, Sanofi, Novartis, institutional research funding from Pfizer, BMS and non-remunerated activities for the Polish Society of Surgical Oncology and ASCO; MS has received honoraria for travel grant from PharmaMar and writing engagement for Lilly; SS has reported a research grant from Johnson & Johnson and research funding from Roche Austria; PS has received honoraria for participation in advisory boards for Deciphera, Blueprint Medicines, Boehringer Ingelheim, Ellipses Pharma, Transgene, Exelixis, Medscape, Guided Clarity, Ysios, Modus Outcomes, Studiecentrum voor Kernenergie, Curio Science, institutional honoraria for advisory boards for Blueprint Medicines, Ellipses Pharma, Intellisphere, expert testimony for Advanced Medical/Teladoc Health, institutional research funding from CoBioRes NV, Eisai, G1 Therapeutics, Novartis and PharmaMar; SSl Chair of Centre for Personalised Cancer Treatment and Route Personalised Medicine, Dutch Science Agenda, member of supervisory board for SkylineDX and Scientific advisory committee Pan-Cancer T BV; KSH reports non-remunerated activity for CTOS as President 2020 and membership of the Scandinavian Sarcoma Group; MAJvdS has performed work in clinical trials or contracted research for which the institution received financial support from Daiichi-Sankyo, Implantcast and Carbofix; WTAvdG has received institutional honoraria for participation in advisory boards for Bayer and GSK, institutional research grants from Novartis and Lilly and consultancy work for SpringWorks; WJvH has received institutional honoraria for participation in advisory board for Belpharma, invited speaker fees from Amgen, expert testimony for Sanofi and MSD, personal travel grant from Novartis and institutional research grant from BMS; TF reported institutional research funding from the Foundation ARC and Ligue Régionale contre le Cancer, leadership role for ERN GENTURIS; PGC has received honoraria for participation in advisory board for Bayer, institutional research funding from Amgen Dompé, Advenchen, Bayer, Blueprint, Deciphera, Eli Lilly, Epizyme, Daiichi, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks, AROG Pharmaceuticals and Eisai, non-remunerated activities for the Italian Sarcoma Group, European School of Oncology, Federation of Italian Cooperative Groups and Rare Cancers Europe; SSta has received honoraria for participation in advisory boards for Bayer, Deciphera, Eli Lilly, Daiichi, Maxivax, Novartis, invited speaker fees from GSK and PharmaMar, expert testimony fee from Bavarian Nordic and Epizyme, institutional research funding from Amgen Dompé, Advenchen, Bayer, Blueprint Medicines, Deciphera, Eli Lilly, Epizyme, Daiichi, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks and Hutchinson MediPharma International Inc., non-remunerated activities for CTOS, Chordoma Foundation, Epithelioid Haemangioendothelioma Foundation, Desmoid Foundation, EORTC STBSG and Italian Sarcoma Group Onlus. AMF, AB, SBo, BB, AD, FF, AFer, PJ, DAK, FLG, ABM, MM, CMo, RP, AAS, CS, DS, AT, MU and RL have declared no conflicts of interests.

Purpose: Joint mega-prosthesis after bone tumors, severe trauma or infection is associated with high rates of post-surgical septic complications. A fast-resorbable antibacterial hydrogel coating (DAC®, Defensive Antibacterial Coating) has previously been shown to be able to significantly reduce surgical site infection in various clinical settings. Aim of the present study was to evaluate the safety and efficacy of the DAC hydrogel coating to prevent early periprosthetic joint infection after joint mega-prosthesis., Methods: In this three-centers, case-control study, 43 patients, treated with an antibacterial hydrogel coated mega-prosthesis for oncological (N = 39) or non-oncological conditions (N = 4), were retrospectively compared with 43 matched controls, treated with mega-implants without the coating. Clinical, laboratory and radiographic examinations were performed to evaluate the occurrence of post-surgical infection, complications and adverse events., Results: At a mean follow-up of 2 years, no evidence of infection or adverse events were observed in the DAC-treated group, compared to six cases of post-surgical infection in the control group., Conclusion: This matched case-control study shows that a fast-resorbable, antibiotic-loaded coating can be safely used to protect joint mega-prosthesis, providing a reduction of early surgical site infections with no side effects. Larger prospective trials with longer follow-ups are warranted to confirm this report., Trial Registration: RS1229/19 (Regina Elena National Cancer Institute Experimental Registry Number)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Competing Interests: Disclosure AG has received honoraria for participation in advisory boards for Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks and Nanobiotix, invited speaker for Lilly, PharmaMar and research grant from PharmaMar; APDT has received honoraria for participation in advisory boards for Bayer and Roche, invited speaker for PharmaMar and Novartis; NA Non-remunerated leadership and advisory roles for Sociedade Portuguesa de Cirurgia; JB has no personal financial disclosure, received research grants (institutional) from Eli Lilly, Novartis, Roche, Samsung Bioepis, Paxman Coolers Ltd, Sun Pharma and non-remunerated advisory role for Novartis, non-remunerated leadership activities for Immuno-oncology society of India, Indian society of Medical and Paediatric Oncology, Teenage and Young Adult Cancer Foundation and Indian cooperative oncology network; SB has received honoraria for participation in advisory boards for Deciphera, Blueprint Medicines, Lilly, Novartis, Daiichi-Sankyo, Plexxikon, Roche, GlaxoSmithKline (GSK), invited speaker fees from Pfizer and PharmaMar, institutional research grant from Novartis, institutional research as principal investigator (PI) for Daiichi-Sankyo, Roche, Deciphera, Lilly, Novartis, Blueprint Medicines, Bristol-Myers Squibb (BMS), Incyte, non-remunerated activities for Federal Institute for Drugs and Medical Devices (BfArm) and founding member of German Sarcoma Foundation; RB reports non-remunerated activities as PI for IRCSS Galeazzi Orthopedic Institute and IRE-ISG Regina Elena Institute, participation at the Clinical Experience Exchange Meeting, III IDBN National Congress 2019, Italian Association of Medical Oncology (AIOM), IRE-ISG Regina Elena Institute and Lazio Association of Orthopaedic Hospital Traumatologists (ALOTO); SBI has received honoraria for participation in advisory boards from Bayer Healthcare, Boehringer Ingelheim, Clinigen, Hoffmann-La Roche, Ipsen, Eli Lilly and Sensorion, non-remunerated activities for Bayer and membership of the German Paediatric Oncology Society and European Musculoskeletal Oncology Society; JYB received research support from Merck Sharp & Dohme (MSD), Roche, GSK, Novartis, Bayer, PharmaMar outside the present work; SBon has received honoraria for advisory board from Nanobiotix and as invited speaker for PharmaMar, trial research grant from the Institut National du Cancer (INCa); IB has received honoraria for participation in advisory boards for Roche, Lilly, Sanofi, Pierre Fabre, Ipsen, and as invited speaker for Amgen, BMS, Novartis, Leo Pharma, AstraZeneca and Genesis, member of Board of Directors for Hellenic Society of Medical Oncology, Hellenic Society of Sarcomas and Rare Tumors, Hellenic Oncology Research Group (HORG), PI trial research support from Novartis, BMS, Regeneron, MSD, Lilly and Roche; JVMGB receives royalties from UpToDate and Wolters Kluwer, and direct research funding from TRACON pharmaceuticals; KB has received honoraria for expert testimony and advisory boards for Bayer, invited speaker fees and research grant from Eli Lilly, PI for Deciphera and Novartis; TB has received honoraria for participation in advisory boards for Bayer and Eli Lilly, invited speaker fees from PharmaMar and Novartis; EDÁ has received honoraria for participation in advisory board for Bayer, invited speaker for Lilly, PharmaMar and Roche, institutional research support from Pfizer, Roche and AstraZeneca; XGDM has received honoraria for participation in advisory boards for Ipsen, EusaPharma, BMS, Pfizer, Roche and PharmaMar, invited speaker for Lilly, Astellas Pharma, Eisai and Pfizer and institutional research grant from AstraZeneca; ME has received honoraria for participation in advisory boards for Clinigen and Bayer, consulting fees from Blueprint Medicines, institutional research funding from Novartis as PI; AF has received honoraria for participation in advisory board for Novartis and invited speaker fees for MSD and Amgen; VF has received honoraria for participation in advisory boards and speaker fees for BMS, Novartis and MSD and speaker fees from Pierre Fabre; SG has reported institutional research for Blueprint Medicines and member of American Society of Clinical Oncology (ASCO) and AIOM; HG has reported PI research for Daiichi, Deciphera and Novartis, Co-ordinating PI for Boehringer Ingelheim and AmMax Bio; FG has received honoraria for participation in advisory board for Amgen and expert testimony for Deciphera, stock ownership for Atlanthera, licensing fees from Zimmer, non-remunerated activities for 3D-Side and INCa DGOS funding and member of the board of NetSarc the French clinical reference network for soft tissue and visceral sarcomas; GG has received honoraria for participation in advisory boards for Lilly, Eisai, Merck, Bayer and GSK, invited speaker fees from PharmaMar and Novartis, institutional grants from PharmaMar, Bayer and Novartis; RH has received Honoraria from GSK; ABH is a member of Board of Directors for EIT Health UK and Ireland, received or currently receives direct research funding as a PI from Roche, performs work in clinical trials or contracted research for the Institution and Clinical Director of the Oncology and Haematology Directorate, Oxford Cancer Centre; SHN received invited speaker fee from University Hospital Basel, Switzerland for Swiss sarcoma symposium, reports institutional research role as deputy PI for Eisai, non-remunerated activity for Harmonization International Bones Sarcoma Consortium (HIBISCus), membership of European Society for Paediatric Oncology (SIOP), German, Swiss, Austrian Society of Paediatric Oncology and Hematology (GPOH) and German Society of Pediatrics and Adolescent Medicine (DGKJ); NH has received honoraria as expert testimony and invited speaker from PharmaMar, performs work in clinical trials or contracted research for which his/her institution received financial support from PharmaMar, Lilly, Adaptimmune Therapeutics, AROG Pharmaceutcials, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint Medicines, Nektar Therapeutics, Forma, Amgen and Daiichi-Sankyo, non-remunerated leadership roles for Grupo Español de Investigación en Sarcomas (GEIS) and SELNET, and has non-remunerated membership or affiliation with ESMO, Sociedad Española de Oncología Médica (SEOM), ASCO, Connective Tissue Oncology Society (CTOS) and European Organisation for Research and Treatment of Cancer (EORTC); PH has received honoraria for participation in advisory boards for Pfizer, Roche and GSK, invited speaker fees from PharmaMar and Lilly, clinical expert fees from Boehringer Ingelheim, institutional research funding for clinical trials from Siemens, Novartis, Blueprint Medicines and meeting sponsorship from PEKKIP Oncology, non-remunerated activities for the German Sarcoma Foundation (DSS), German Interdisciplinary Sarcoma Group (GISG) and Interdisciplinary Working Party on Sarcomas (IAWS) of the German Cancer Society (DKG), advisory role for the German Cancer Aid (DKH) Committee on Health Technology Assessment and Sarcoma Patients EuroNet (SPAEN); HJ has received honoraria for participation in advisory boards for Orion Pharma, Neutron Therapeutics and Maud Kuistila Memorial Foundation, had full-time or part-time employment at Orion Pharma, until 31 August 2020, stocks in Orion Pharma and Sartar Therapeutics; RLJ has received honoraria for expert testimony consultancy for Adaptimmune, Bayer, Boehringer Ingelheim, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daiichi, Deciphera, Immunedesign, Lilly, SpringWorks, TRACON, UpToDate, PharmaMar, advisory board for Athenex, institutional research grant from MSD; CJ has received travel grants from Ipsen and PharmaMar; LK has received honoraria for participation in advisory boards for Bayer, Novartis and Agios; BK has received honoraria for participation in advisory boards for Bayer, Blueprint Medicines, Boehringer Ingelheim, SpringWorks, GSK and PharmaMar, institutional research support from PharmaMar and SpringWorks, member of EORTC and Chair of the EORTC soft tissue and bone sarcoma group (STBSG); AK has received honoraria for participation in advisory boards for Daiichi-Sankyo and Otsuka and invited speaker fees from Novartis, Taiho and Eisai; KK has received honoraria for participation in advisory board for Bayer and expert testimony for Eli Lilly and Roche; ALC has received honoraria for participation in advisory boards for Deciphera and Lilly, invited speaker fees from PharmaMar and Bayer; EL received honoraria from SpringWorks Therapeutics for scientific advisory board participation and member of the European Reference Network GENTURIS; AL has received institutional research grants from Johnson & Johnson, Alphamed, Medacta and Implantec, non-remunerated activities for European Musculoskeletal Society (EMSOS), Austrian Society of Orthopaedic Surgeons (OGO) and membership of CTOS; AL-P has received honoraria as invited speaker for PharmaMar, institutional research funding from the Spanish Health Ministry, reported non-remunerated activities as PI for PharmaMar, Cebiotex, Deciphera, Lilly, GSK, Daiichi, Epizyme, Advenchen Laboratories, Novartis, Karyopharm, Blueprint Medicines, GEIS and other activity for EORTC; JMB has received honoraria for expert testimony for Lilly, PharmaMar, Eisai, Bayer, invited speaker fee from PharmaMar, institutional research for PharmaMar, Eisai, Novartis, Immix Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Blueprint Medicines, Deciphera, Nektar Therapeutics, Forma, Amgen, Daiichi-Sankyo, Lilly, AROG Pharmaceuticals, Adaptimmune and GSK; OM has received honoraria for participation in advisory boards for MSD, Megapharm, AstraZeneca, Takeda and Progenetics, invited speaker fees from MSD and Roche; CM has performed non-remunerated activities for International Cancer Imaging Society and EORTC STBSG; OMi has received honoraria for participation in advisory boards for Bayer, Blueprint Medicines, MSD, Pfizer, invited speaker fees from BMS, Eli Lilly, Ipsen, Roche and Servier, institutional research for Blueprint Medicines, Bayer, Epizyme and Eli Lilly; BM has received honoraria from Clinigen as invited speaker; EP has received honoraria for participation in advisory boards for SynOx, Daiichi-Sankyo and Deciphera Pharmaceuticals and invited speaker fees from Peer View Educational; MAP has received honoraria for participation in advisory boards for Roche, invited speaker fees from Eli Lilly, Pfizer and Novartis, expert testimony from Blueprints Medicine and institutional research grant from Novartis; SPN has received honoraria for participation in advisory board for Immunocore; PR has received honoraria for participation in advisory boards for Bayer, Clinigen, Roche, MSD, Deciphera, Mundibiopharma, PharmaMar, Blueprint Medicines, invited speaker fees from Lilly, PharmaMar, institutional research for PharmaMar, Karyopharm, SpringWorks, AROG Pharmaceuticals, Blueprint, Deciphera, Amgen, Astellas, Epizyme, Lilly, MSD, Pfizer, Novartis and Philogen, membership of German Sarcoma Foundation; PRu has received honoraria for participation in advisory boards for MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, invited speaker fees from MSD, BMS, Pierre Fabre, Merck, Sanofi, Novartis, institutional research funding from Pfizer, BMS and non-remunerated activities for the Polish Society of Surgical Oncology and ASCO; MS has received honoraria for travel grant from PharmaMar and writing engagement for Lilly; SS has reported a research grant from Johnson & Johnson and research funding from Roche Austria; PS has received honoraria for participation in advisory boards for Deciphera, Blueprint Medicines, Boehringer Ingelheim, Ellipses Pharma, Transgene, Exelixis, Medscape, Guided Clarity, Ysios, Modus Outcomes, Studiecentrum voor Kernenergie, Curio Science, institutional honoraria for advisory boards for Blueprint Medicines, Ellipses Pharma, Intellisphere, expert testimony for Advanced Medical/Teladoc Health, institutional research funding from CoBioRes NV, Eisai, G1 Therapeutics, Novartis and PharmaMar; SSl Chair of Centre for Personalised Cancer Treatment and Route Personalised Medicine, Dutch Science Agenda, Member of supervisory board for SkylineDX and Scientific advisory committee Pan-Cancer T BV; SSt has received honoraria for participation in advisory board for GSK; KSH reports non-remunerated activity for CTOS as President 2020 and membership of the Scandinavian Sarcoma Group; MAJvdS has performed work in clinical trials or contracted research for which the institution received financial support from Daiichi-Sankyo, Implantcast and Carbofix; WTAvdG has received institutional honoraria for participation in advisory boards of Bayer and GSK, institutional research grants from Novartis and Lilly, and consultancy work for SpringWorks; WJvH has received institutional honoraria for participation in advisory board for Belpharma, invited speaker fees from Amgen, expert testimony for Sanofi and MSD, personal travel grant from Novartis and institutional research grant from BMS; TF reported institutional research funding from the Foundation ARC and Ligue Régionale contre le Cancer, leadership role for ERN GENTURIS; PGC has received honoraria for participation in advisory board for Bayer, institutional research funding from Amgen Dompé, Advenchen, Bayer, Blueprint, Deciphera, Eli Lilly, Epizyme, Daiichi, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks, AROG Pharmaceuticals and Eisai, non-remunerated activities for the Italian Sarcoma Group, European School of Oncology, Federation of Italian Cooperative Groups and Rare Cancers Europe; SSta has received honoraria for participation in advisory boards for Bayer, Deciphera, Eli Lilly, Daiichi, Maxivax, Novartis, invited speaker fees from GSK and PharmaMar, expert testimony fee from Bavarian Nordic and Epizyme, institutional research funding from Amgen Dompé, Advenchen, Bayer, Blueprint Medicines, Deciphera, Eli Lilly, Epizyme, Daiichi, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks and Hutchinson MediPharma International Inc., non-remunerated activities for CTOS, Chordoma Foundation, Epithelioid Haemangioendothelioma Foundation, Desmoid Foundation, EORTC STBSG and Italian Sarcoma Group Onlus; AAS, AB, ABM, AD, AFer, AMF, AT, BB, CMo, CS, DAK, DS, FF, FLG, MM, MU PJ, RP and SBo have declared no conflicts of interests.

Background and aim of the work Proximal humeral fractures incidence in the elderly population is increasing. Treatment management is complicated by fracture complexity and patients' comorbidities. The aim of our prospective study is the outcome evaluation of the role of minimally invasive plate osteosynthesis (MIPO) for elderly patients with a 3- or 4-parts proximal humeral fractures having an intact medial wall.   Methods We included n=42 unilateral 3- and 4-parts proximal humeral fractures treated with MIPO: 20 4-part fractures and 22 were 3-parts fractures were included. 17 patients identified as male and 25 as female (mean age 84yo).  A trans-deltoid approach has been used with minimal surgical exposure and tissue damage to preserve the local tissue for early shoulder mobilization.   Results At follow-up, the DASH recorded mean value was 72, while the Constant mean score was 68. Complications have been recorded in 23,8% of patients with 4-parts fractures having the highest complication frequency. Mean shoulder joint ROM was recorded: anterior elevation 75°, lateral elevation 80°, abduction 90°, intra-rotation 50°, extra-rotation 25°. The following factors were identified influencing the outcome: >8mm calcar fragment, head valgus impaction and periosteal medial hinge preservation.   Conclusions The increase in population longevity matches the increase in complex humeral fracture frequency. We strongly for management consensus for proximal humerus fracture, in a similar way as for neck femoral fractures. MIPO is excellent in reducing soft tissue damage and complications for elderly patients with limited functional demand.

Objective: The application of [ 18 F]FDG PET/CT in predicting histologic response to induction chemotherapy in patients with Ewing sarcoma (EWS) has been proposed using the values of pre-post treatment SUV max as a referral parameter, although with heterogeneous results. The aim of this retrospective study was to evaluate the diagnostic accuracy of [ 18 F]FDG PET/CT volumetric parameters (metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) as compared to SUV max to predict response to chemotherapy and clinical outcome in patients with localised EWS of bone and soft-tissue., Methods: Twenty-eight patients with non-metastatic EWS of bone (n = 20) and soft tissues (n = 8) who underwent a [ 18 F]FDG PET/CT scan before (PET 1 ) and after induction chemotherapy (PET 2 ) were enclosed in the analysis. Values of PET metrics (SUV max , MTV, TLG) at diagnosis and after neoadjuvant chemotherapy as well as the percentage change between PET 1 and PET 2 (ΔSUV, ΔMTV and ΔTLG) were correlated to histological response and to progression-free survival (PFS)., Results: ΔTLG (cut-off: -60%) is the best predictor for histologic response with 100% sensitivity and 77.8% specificity. MTV 1 > 33.4 cm 3 and TLG 1 > 112 were also associated with a favourable histologic response (sensitivity 80% and specificity 77.8% for both). On multivariate analysis, SUV 2 (> 3.3) and ΔTLG (< -18%) were independent predictors of worse PFS., Conclusions: [ 18 F]FDG PET/CT could accurately predict histologic response to neoadjuvant chemotherapy in patients with EWS, also showing a possible prognostic value for future disease relapse., Key Points: • The variation of the PET parameter tumour lesion glycolysis (TLG) can predict the histologic response to induction chemotherapy (sensitivity 100%, specificity 77.8%), in patients with Ewing sarcoma. • The percentage variation of TLG and the value of the SUVmax at PET scan after chemotherapy show a prognostic role for future disease relapse. The combination of both the parameters identifies three prognostic classes of patients with low, intermediate and high risk of disease relapse., (© 2021. European Society of Radiology.)

Introduction: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study., Materials and Methods: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models., Results: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles., Conclusions: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.B. has reported grants from Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft and the European Science Foundation and personal fees from Lilly, Bayer, Pfizer, Novartis, Isofol and Clinigen; E.P. has reported advisory roles for Amgen, Daiichi Sankyo, Eli Lilly, EUSA Pharma and Deciphera, received research support from Bristol Myers Squibb, Pfizer and PharmaMar and received travel support from Lilly, PharmaMar and Takeda; L.K. has reported honoraria from Bayer; P.R. has reported advisory roles for Exactech and Stryker; A.F. has reported honoraria from Ipsen Pharma, PharmaMar and Lilly; P.C. has reported honoraria for the speaker, consultancy or advisory role from Bayer, Deciphera, Eisai, Eli Lilly, Nektar Therapeutics and Pfizer and received research funds from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc., Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer and PharmaMar; P.R. has reported honoraria from Bayer, Clinigen, BMS, Roche, MSD, Deciphera, Novartis, Pfizer, PharmaMar, Lilly and Amgen; I.H., S.F., K.S.H., P.P., S.H.-N., D.M.D., C.B., B.B., E.St., M.G., T.K., M.E., V.F., M.K., R.B., D.B., O.B., A.C., R.S., R.B., T.K., L.H., G.A., B.-N.H., E.Se., A.F., F.K., G.H.-W. and S.S. have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Disclosure SS: Honoraria, consultancy or advisory role: Adaptimmune, Bayer, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, Glaxo, Immune Design, Karyopharm, MaxiVAX, Novartis, PharmaMar; Institutional financial interests: Advenchen, Amgen Dompè, Bayer, Epizyme, Eli Lilly, Daiichi Sankyo, Glaxo, Hutchison MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks. AMF: Institutional financial interests: Advenchen, Amgen Dompè, Bayer, Epizyme, Eli Lilly, Daiichi Sankyo, Glaxo, Hutchison MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks. AC: Advisory board: Angelini Holding S.p.A, Shionogi B.V., L. Molteni & C., Kyowa Kirin S.r.l.; invited speaker King Faisal Specialist Hospital & Research Center. JB: Uncompensated advisory board: Novartis; research funding (institutional) from Eli Lilly, Novartis, Roche, Samsung Bioepis Co. Ltd, Paxman Coolers Ltd, Sun Pharma. SB: Personal fees from Bayer, Deciphera, Lilly, Daiichi Sankyo, Plexxikon, Exelixis, PharmaMar, Lilly, Roche, GlaxoSmithKline (GSK); grants from Incyte, grants and personal fees from Blueprint Medicines, Novartis; research funding (institutional) Pfizer. SB: Research support from Novartis, Incyte, Blueprint Medicines; honoraria or consultation fees from Novartis, Lilly, Pfizer, PharmaMar, Bayer. JYB: Research support and honoraria from Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Roche, Bayer, Novartis, GSK, Deciphera, OSE Pharma, AstraZeneca. Member of the supervisory board: Innate Pharma. SB: Honoraria from PharmaMar. JVMGB: Research funding from TRACON Pharmaceuticals; Royalties from UptoDate and Wolters Kluwer. KB: Advisory: Bayer; expert testimony: Bayer; invited speaker: Lilly; institutional research funding: Lilly. TB: Advisory board from Bayer; honoraria: Novartis, PharmaMar, Eli Lilly. ME: Consultant for Blueprint Medicines; advisory boards for Clinigen and Bayer. AF; Honoraria: Amgen, Lilly, Roche, MSD; research funding; MSD, Roche, Clovis, AstraZeneca. BMS; Abbvie. VF: Consulting or advisory role: BMS, MSD, Novartis; speakers' bureau: BMS, MSD, Novartis, Pierre Fabre. XGdM: Advisory boards for Ipsen, EUSA Pharma, BMS, Pfizer, Roche, PharmaMar; honoraria from Lilly, Astellas Pharma, Eisai, Pfizer. HG: Reports institutional funding from Novartis, Deciphera. FG: Honoraria from Deciphera, Amgen; stock ownership from Atlanthera; royalties from Zimmer. GG: Grants/research supports: PharmaMar, Novartis, Bayer; honoraria or consultation fees: PharmaMar, Bayer, Merck, Eisai, Novartis, Glaxo. NH: Research grants from PharmaMar, Eisai, Immix BioPharma and Novartis; honoraria and travel grants from PharmaMar; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, Adaptimmune Therapeutics, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen and Daiichi Sankyo. PH: Honoraria for consultations and speaker's fees from Roche, GSK, AstraZeneca, Pfizer, PharmaMar, Lilly, Nanobiotix, Novartis, EISAI, Nektar, Sirtex and Pekkip Oncology; research funding and educational grants from Novartis, Siemens, Boehringer, Merck, BLUMedicine and Springer; trial support to my institution by Novartis and Siemens. PH: Advisory roles for Sarcoma UK and National Leiomyosarcoma Foundation; research grants from Sarcoma UK, Desmoid Tumor Research Foundation, Children's Cancer and Leukemia Group and Cancer Research UK, funding from EHE Rare Cancer Charity (UK). HJ: Chair of the Orion Pharma Scientific Advisory Board, chair of Neutron Therapeutics Advisory Board; he has been employed by Orion Pharma, and owns stocks of Orion Pharma and Sartar Therapeutics. RJ: Advisory board Adaptimmune, Athenex, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immune Design, Lilly, Merck, PharmaMar, SpringWorks, TRACON, UptoDate; honoraria: BMS, MSD, Novartis, Pierre Fabre, Merck, Sanofi. CJ: Travel grants from PharmaMar, Ipsen. BK: Reports advisory board Bayer, Blueprint, Boehringer Ingelheim, GSK, PharmaMar, SpringWorks; research funding (institutional) PharmaMar, SpringWorks. AK: Advisory board Otsuka; invited speaker for Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Taiho. ALC: Advisory boards with Lilly, PharmaMar, Deciphera, Blueprint. AL: Reports institutional financial interest, and educational grant from Alphamed, ImplanTec, Johnson & Johnson, Medacta. JMB: Research grants from PharmaMar, Eisai, Immix BioPharma and Novartis; honoraria from PharmaMar, Lilly, Bayer, Eisai, Daichii. Travel grants from PharmaMar; advisory board: Roche, Lilly, PharmaMar; research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, Adaptimmune Therapeutics, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen, Celgene, Pfizer, BMS, and Daiichi Sankyo. OMe: Consultation fees from MSD, AstraZeneca, Takeda, Megapharm, Medison, Progenetics; supported lecture: MSD, AstraZeneca, Roche, BMS. OMi: Consultancy for Amgen, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier, Vifor Pharma; Speakers bureau: Eli Lilly, Roche, Servier; Stock ownership: Amplitude Surgical, Ipsen, Transgene. EP: Advisory boards for Amgen, Daiichi Sankyo, Lilly, Deciphera, EUSA Pharma, and SynOx Therapeutics; research support from BMS, Pfizer, PharmaMar, Daiichi Sankyo, Incyte; travel support from Lilly, PharmaMar and Takeda. MAP: Advisory board Lilly, Pfizer, Roche. SP: Consultant: Deciphera, Daichi Sankyo, Dova, Epizyme, MaxiVAX; Research/Grant Support: Blueprint Medicines, Hutchison MediPharma. SPN: Advisory board for Immunocore. AR: Consulting role with Lilly, Merck, Boehringer Ingelheim; research funding from CASI Pharmaceuticals, Boehringer Ingelheim, Lilly, Novartis, Deciphera, Karyopharm Therapeutics, Pfizer, Roche/Genentech, Boston Biomedical, BMS, MedImmune, Amgen, GSK, Blueprint Medicines, Merck, AbbVie, Adaptimmune. PRe: Advisory roles for Bayer, Clinigen, Roche, MSD, Deciphera, PharmaMar, Mundibiopharma, and speaker's honoraria from Lilly, PharmaMar. BPR: Reports advisory board from Deciphera. PRu: Advisory board MSD, BMS, Merck, Sanofi, Pierre Fabre, Blueprint Medicines; honoraria from BMS, MSD, Novartis, Pierre Fabre, Merck, Sanofi. MS: Travel grant from PharmaMar. SJS: Advisory boards for Lilly and GSK. WDT: Reports fees from Eli Lilly, EMD Serono, Eisai, Mundipharma, C4 Therapeutics, Daiichi Sankyo, Blueprint, GSK, Agios Pharmaceuticals, NanoCarrier, Deciphera; patent Companion Diagnostic for CDK4 inhibitors - 14/854 329 pending to MSKCC/SKI, and patent Enigma and CDH18 as companion Diagnostics for CDK4 inhibition – SKI2016-021-03 pending to MSKCC/SKI and Scientific Advisory Board - Certis Oncology Solutions, Stock Ownership Üo-Founder - Atropos Therapeutics; Stock Ownership/scientific advisory board Innova Therapeutics. WTAWDG: Reports consultancy from SpringWorks to her institute; research grant support from Novartis and Lilly to her institute; advisory for Bayer to her institute. AJW: Consulting: Daiichi Sankyo, Deciphera, Epizyme, Mundipharma; research support to my Institution: Aadi Bioscience, Daiichi Sankyo, Deciphera, Eli Lilly, Karyopharm, Plexxikon. PGC: Honoraria, consultancy or advisory role: Bayer, Deciphera, Eisai, Eli Lilly, Pfizer. Institutional financial interest: Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme, Glaxo, Hutchinson MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar. APDT: Honoraria: Roche, Bayer, Pharmamar, MSD. AG: Compensations for Advisory boards from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, Nanobiotix; honoraria from Lilly and PharmaMar; institutional research grants from PharmaMar. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical management ranges from surveillance or curettage to wide resection for atypical to higher-grade cartilaginous tumours, respectively. Our aim was to investigate the performance of computed tomography (CT) radiomics-based machine learning for classification of atypical cartilaginous tumours and higher-grade chondrosarcomas of long bones., Methods: One-hundred-twenty patients with histology-proven lesions were retrospectively included. The training cohort consisted of 84 CT scans from centre 1 (n=55 G1 or atypical cartilaginous tumours; n=29 G2-G4 chondrosarcomas). The external test cohort consisted of the CT component of 36 positron emission tomography-CT scans from centre 2 (n=16 G1 or atypical cartilaginous tumours; n=20 G2-G4 chondrosarcomas). Bidimensional segmentation was performed on preoperative CT. Radiomic features were extracted. After dimensionality reduction and class balancing in centre 1, the performance of a machine-learning classifier (LogitBoost) was assessed on the training cohort using 10-fold cross-validation and on the external test cohort. In centre 2, its performance was compared with preoperative biopsy and an experienced radiologist using McNemar's test., Findings: The classifier had 81% (AUC=0.89) and 75% (AUC=0.78) accuracy in identifying the lesions in the training and external test cohorts, respectively. Specifically, its accuracy in classifying atypical cartilaginous tumours and higher-grade chondrosarcomas was 84% and 78% in the training cohort, and 81% and 70% in the external test cohort, respectively. Preoperative biopsy had 64% (AUC=0.66) accuracy (p=0.29). The radiologist had 81% accuracy (p=0.75)., Interpretation: Machine learning showed good accuracy in classifying atypical and higher-grade cartilaginous tumours of long bones based on preoperative CT radiomic features., Funding: ESSR Young Researchers Grant., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interest related to this work., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions-pivotal aspects for cell survival and muscle contractile functionalities-together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

The aim of this study was to investigate symptoms, their variation over time and their relationship with quality of life (QoL)/psychological distress in sarcoma patients, as few data regarding QoL and psychological distress in this set of patients are currently available. A total of 188 sarcoma patients from an Italian referral center were involved. Symptoms and financial difficulties were evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire from the first treatment and over the follow-up period, up to 6 years. The authors found that patients with sarcoma experience several symptoms, especially fatigue and pain, which may dramatically worsen QoL and psychological distress. In conclusion, patients with sarcoma often experience fatigue, pain and financial difficulties, which negatively impacts QoL and psychological distress. To ameliorate overall QoL, proper control of symptoms is necessary.

Background and Objectives: The modern approach to primary and secondary muscular skeletal tumors is multidisciplinary. The right combination of chemotherapy, surgery and radiotherapy (RT) makes obtaining local and distant disease control more likely. When surgery is indicated, radiotherapy often has a fundamental role as an adjuvant treatment; however, the titanium alloy instrumentations interfere with Radiotherapy setting, decreasing its effectiveness. It is common opinion that carbon fiber-reinforced devices are convenient in case of adjuvant RT in muscular skeletal oncology. The aim of the study is to support this intuition with experimental data, verifying the more accurate estimation of the delivered dose during RT, comparing Carbon Fiber-Reinforced PEEK (CFRP) plates with titanium-alloy orthopedic devices in order to evaluate their effects on target volume identification and dose distribution for radiation treatment., Methods: Phantoms were then irradiated with a linear accelerator Varian 2100 C/D with photon beams of 6 and 15 MV energies. Absorbed dose in the point of interest was verified by EBT3 gafchromic films above and below the two materials. Images from CT simulations were also analyzed in terms of Hounsfield numbers in patients with titanium and carbon fiber orthopedic implants in the spine or in the femur., Results: For a 6 MV photon beam, the doses measured just under the titanium-alloy plate were less than approximately 20% of the value calculated by the TPS. For a 15 MV beam energy, these differences were slightly lower. Using CFRP plate, the difference between measured and calculated doses was within ±3% for both energies, which was comparable with the statistical uncertainties. In the cases of simulated treatment of humerus titanium implants, the difference varies in range ± 10% with hot spot of + 10% and cold spot of -15%., Conclusions: The use of CFRP for orthopedic devices and implants provides a valuable advantage in identifying the target due to the reduction of artifacts. Clear imaging of the soft tissues surrounding the bone is useful and reduces the discrepancies between calculated/delivered and measured doses, generating a more homogeneous dose distribution. Furthermore, there is a significant benefit in detecting the state of disease in CT imaging during the follow-up of treated patients. In-vivo studies are encouraged to verify whether a more effective radiotherapy leads to a decrease in local recurrence and local progression.

Background: Soft-tissue sarcomas (STS) represent a wide heterogeneous class of rare tumors. The exact role 18 F-fluorodeoxyglucose positron emission/computed tomography ( 18 F-FDG PET/CT) in the evaluation of STS is not well established. The aim of the present study was to evaluate how the use of 18 F-FDG PET/CT in STS could influence patient therapy planning, looking for a possible added value over computed tomography and magnetic resonance imaging-the most used modalities in the study of STS. Differences in SUV max according to histologic subtype and tumor grade were also considered., Methods: a total of 345 consecutive 18 F-FDG PET/CT scans performed for initial staging ( n = 171) or for suspected disease relapse ( n = 174) in 282 patients with STS extracted from the local Information System database were retrospectively reviewed., Results: 18 F-FDG PET/CT altered therapy planning in 80 cases (16.4% for staging and 29.9% in restaging), both for disease upstaging (58.8%) and downstaging (41.2%) Conclusions: 18 F-FDG PET/CT could significantly influence management of patients with STS, particularly for restaging.

The high complexity of multimodality treatment frequently results in undertreatment of elderly sarcoma patients, and this may be one of the factors that influence their prognosis. We describe the real-life approach to a population of patients aged over 70 with both soft tissue (STS) and bone sarcomas (BS) followed by our Sarcoma Disease Management Team from 2012 to 2017. One-hundred and twenty-three patients with a median age of 77 years (range: 70-92) were identified. STS were the most common histological subtypes (94%) and the grade was high in 79/123 patients (64%). At diagnosis, 88% of patients had localized disease (LD) and 12% were metastatic (MD). Overall, 96% of patients with LD underwent surgery, 46/54 (85%) with high grade STS patients underwent complementary radiotherapy, and 10/54 (19%) received adjuvant treatments. Twelve out of 33 patients who relapsed (36%) underwent local therapies. Seventeen (52%) and eight (24%) patients were treated with first-line and second-line medical treatments, respectively. Tolerability to systemic treatments was fairly good. Overall, 21% of the patients with advanced disease were candidates for best supportive care alone. Our case series of elderly patients with both STS and BS shows that personalized multidisciplinary treatment can nevertheless be offered to this frail population in order to control the evolution of disease.

Since the World Health Organization declared the novel coronavirus outbreak a global health emergency, Italy's lockdown was declared on 9 March 2020. Elective orthopedic surgery was forced to stop to allow the healthcare system to face the emergency. However, many orthopedic oncology cases could not be postponed. The aim of this study was to report the experience in managing sarcoma patients and the reorganization of a cancer center in an attempt to maintain it free from COVID-19. A Coronavirus Crisis Unit was established by the health directorate coordination in order to adopt specific procedures. General rules of screening and social distancing were applied in different health settings (entrance check point, hospital inward, outpatient clinic, operative room). Regarding oncologic orthopedics, priority was given to bone and soft tissue sarcomas, metastases and aggressive benign tumors at risk of impending or pathologic fracture. Precise indications were followed to manage first outpatient visits, patients undergoing surgery and follow-up. Meticulous adherence to rules among patients and personnel and collaboration between leadership and medical staff in order to continue to perform multidisciplinary treatment protocols, maintain the availability of infrastructural spaces and source protective equipment, swabs and screening samples have been successful in the aim towards a safe cure for cancer patients.

Objectives: Cartilaginous bone tumors represent a wide variety of neoplasms ranging from benign to extremely aggressive malignant lesions. Unlike other tumors, the biopsy cannot easily predict the histological grade, sometimes not allowing choosing the best therapeutic approach. The aim of the study was to evaluate the ability of 18 F-FDG PET/CT to differentiate enchondroma from chondrosarcoma and to predict the histological grade as compared to biopsy., Methods: 18 F-FDG PET/CT of 95 patients with chondroid lesions were retrospectively evaluated. The best SUV max cutoff to predict the post-surgical histological grade were correlated to those of biopsy and to several radiologic aggressiveness features, which were summarized in the parameter "Radiologic Aggressiveness Score" (AgSCORE)., Results: A concordance between the preoperative biopsy and the definitive histological grade was observed overall in 78.3% of patients, the lowest accuracy (58.6%) being in the identification of intermediate/high-grade chondrosarcoma (G2/G3). The best SUV max cutoff was 2.6 to discriminate enchondroma vs. low-grade chondrosarcoma (sensitivity 0.68, specificity 0.86), 3.7 to differentiate low-grade vs. intermediate/high-grade chondrosarcoma (sensitivity 0.83, specificity 0.84) and 7.7 to differentiate intermediate/high-grade vs. dedifferentiated chondrosarcoma (sensitivity 0.92, specificity 0.9). The AgSCORE also showed a high accuracy to differentiate between G1 and G2/G3 chondrosarcoma (cutoff = 4; sensitivity 0.76; specificity 0.89). An even higher accuracy was observed in those cases in which both SUV max and AgSCORE cutoff were concordant., Conclusions: Results in this large series of patients suggest a potential role of 18 F-FDG PET/CT for histological grading of cartilaginous tumors, thus helping the orthopedic surgeon towards the most appropriate surgical procedure.

Aim: To investigate sarcoma patients' perception of quality of life and psychosocial distress across the different disease's stages. Patients & methods:  Total 329 sarcoma patients were monitored from diagnosis up to a maximum of six consecutive follow-up visits. Results: Functional status worsened over time with the lowest value after surgery and a full recovery not earlier than the second follow-up visit. Married and single patients exhibited similar quality of life pattern. High levels of psychological distress were observed from diagnosis to active treatment periods with a progressive improvement during follow-up. Psychological distress pattern over time varied by marital status and age. Conclusion: Our study suggests the importance of integrating psychosocial care to medical therapy across the entire sarcoma journey.

En-bloc sacrectomy is a highly demanding surgical procedure necessary to obtain wide margin in sacral tumor. The double approach, anterior and posterior approach, is usually preferred for tumors extending proximally to S3 level where iliac internal vessels are at a higher risk for damage during posterior surgery. It can be justified also in selected cases to decrease the risk of posterior approach as in local recurrence or in patients who already underwent laparotomy. Our intent was to apply robotic-assisted techniques for performing anterior preparatory approach for sacrectomy surgery. Between December 2010 and December 2014, three cases of sacrectomies were performed in a previous robotic-assisted preparatory approach to separate the rectum from the tumor. Dissections were successfully performed in all cases close to the pelvic floor. The surgeon was able to position a Gore-Tex spacer between the anterior tumor surface and the rectum in all cases. The anterior dissections were performed with a perfect control of bleeding. No complications related to the anterior approach were reported. Robot-assisted surgery can be considered a valid and minimally invasive technique which allows a safe anterior dissection of the pelvic structures dividing tumors from surrounding tissues. It allows to place a spacer to protect organs during posterior sacral resection performed on the same day or at a later time. Further experiences are advocated to evaluate its efficiency in sacral tumors of greater size.

Interventional radiology provides local management of bone metastases (BM) with a palliative intent in most cases, or with a curative intent in selected patients. Its role has rapidly expanded in the last decade, offering new treatment solutions often in combination with surgery, radiation therapy and medical treatments. The aim of the present paper is to increase awareness, acceptance and adoption of interventional radiology procedures for the treatment of BM; and to present the joint position of the Italian College of Musculoskeletal Radiology and the Italian College of Interventional Radiology.

Although the medical treatments of sarcoma have evolved in the last years, a significant portion of patients develops recurrence after therapies suggesting the need to identify novel targets to improve the treatments. By the use of patient-derived and established cell lines from liposarcoma, as well as specimens from patient biopsies, we found that HMGA1 is involved in the progression of dedifferentiated and myxoid liposarcoma. The immunohistochemical and RT-PCR analyses of 68 liposarcoma specimens revealed a significant high expression of HMGA1, at the protein and RNA levels, both in myxoid and dedifferentiated liposarcoma subtypes compared with differentiated ones. Loss- and gain-of-function experiments by HMGA1-specific depletion and overexpression in dedifferentiated and myxoid liposarcoma cells showed the contribution of this oncogenic factor in cell proliferation, motility, invasion, and drug resistance. The in vitro and in vivo treatment of myxoid liposarcoma with trabectedin, a drug with a potent anti-tumor activity, revealed downregulation of HMGA1, E2F1, and its-downstream targets, vimentin and ZEB1, indicating a critical role of trabectedin in inhibiting the mesenchymal markers of these tumors through the HMGA1/E2F1 axis. These data were also confirmed in patients' tumor biopsies being HMGA1, E2F1, and vimentin expression significantly reduced upon trabectedin therapy, administered as neo-adjuvant chemotherapy. Furthermore, trabectedin treatment inhibits in vitro NFkB pathway in mixoyd liposarcoma sensitive but not in resistant counterparts, and the inhibition of NFkB pathway re-sensitizes the resistant cells to trabectedin treatment. These data support the rational for combining NFkB inhibitors with trabectedin in liposarcoma patients, who have become resistant to the drug.

Objective: The purpose of this study is to verify the effectiveness and complications occurrence of radiofrequency ablation (RFA) in the treatment of osteoid osteoma (OO) in non-operating room anesthesia (N.O.R.A.)., Patients and Methods: From 2014 to 2017, 61 patients affected by OO (40 men and 21 women) with an age of 20.7 years on average (range, 4-51 years; 12 patients aged 20 years or younger) underwent computed tomography-guided percutaneous radiofrequency ablation (RFA) in N.O.R.A. (Non-Operating Room Anesthesia). Lesion sites treated were: femur (27), tibia (22), pelvis (2), talar bone (3), distal radius (1), and humerus (6). Mean follow-up time was 36 months. In each case, anesthesiologic support followed a new protocol (N.O.R.A. protocol), approved by our Institute. Primary success rate, complications, symptom-free intervals, and follow-up results were evaluated., Results: Pain relief (evaluated with Visual Analogue Scale - VAS) was significant in 97% of patients; it disappeared within 24 hours of the procedure in 44 patients, within 3 days in 10 patients, and within 7 days in 7 patients. After 6 months of observation time, 60 of 61 patients were successfully treated and had no more complaints. In 2 patients, two major complications were found: infection of the site treated, healed with antibiotics, and a nerve lesion, healed with steroid therapy. No other complications were observed., Conclusions: RFA is a highly effective, efficient, minimally invasive and safe method for the treatment of OO following N.O.R.A.

Introduction: Core biopsy is today recognized as the gold standard for the diagnosis of bone lesions; unfortunately, when the bone is too solid it can be very difficult to penetrate it; in case of failure, open biopsy is indicated but it is associated with greater contamination and complications. A possible solution is to connect a common orthopedic drill to the core biopsy needle. The aim of the presenting study was to present a technique useful for performing biopsies in case of very strong bone lesions and to evaluate the adequacy and quality of the obtained specimen., Materials and Methods: A standard bone biopsy set was connected to a commercial drill to perform bone biopsies. Data was collected over a 2-year period (2015-2016). Information regarding technical success, diagnostic data and complication rates was all collated to assess the technical feasibility of this technique., Results: Out of 357 bone biopsies, 34 patients underwent the procedure using a common orthopedic drill connected to a core biopsy needle. Diagnostic material was obtained in each patient and the artifacts were considered irrelevant. No major complications occurred in any patient., Discussion: The use of a core biopsy needle connected to a common orthopedic drill facilitates the penetration of thick cortical bone by simply applying continuous speed and pressure; nevertheless, the biopsy needle we use is not designed for a drilling procedure and for this reason it can be damaged, but if the biopsy is performed with particular attention, the mechanical failure can be avoided CONCLUSIONS: Bone biopsy using a commercial hand drill has a technically high success rate with minimal complications. Further studies with more cases are necessary to verify our results., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Limited information is available on the applicative value of liquid biopsy (LB) in rare tumors, including Ewing's sarcoma (ES). The accepted precision diagnostics standards would greatly benefit from a non-invasive LB test monitoring pathognomonic gene rearrangements in the bloodstream., Methods: Tissue and blood samples were collected from six and four ES patients, respectively. Plasma was cleared by two successive rounds of centrifugation and stored frozen until RNA extraction by the QIAmp CNA kit. RNA was retro-transcribed and subjected to real-time quantitative polymerase chain reaction (RT-qPCR) and digital polymerase chain reaction (dPCR). Reactions were set up using two custom primer sets identifying types 1 and 2 EWS-FLI1 fusion transcripts., Results: The two prevalent types of EWS-FLI1 rearrangements could be identified using only two sets of polymerase chain reaction primers, regardless of patient-specific EWS-FLI1 DNA breakpoints. RT-qPCR and dPCR discriminated the two variants in five tumor tissue RNAs and in four circulating tumor RNAs (ctRNAs). Of note, EWS-FLI1 molecular diagnosis was possible using blood samples even when tumor tissue was not available. ctRNA levels correlated ( p < 0.05) with volume-based positron emission tomography (PET) parameters (metabolic tumor volume and total lesion glycolysis), and allowed the fine tracking of disease course after surgery, during adjuvant as well as neoadjuvant chemotherapy, and at follow up in one patient., Conclusions: To our knowledge, this is one of the few single-marker LB assays in solid tumors specifically designed to detect rearranged RNAs in blood, and the first study describing EWS circulating tumor RNAs in ES patients. Altogether, our results support the idea that LB may have a considerable impact on ES patient monitoring and management., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Sarcomas are rare tumors with generally poor prognosis, for which current therapies have shown limited efficacy. Histone deacetylase inhibitors (HDACi) are emerging anti-tumor agents; however, little is known about their effect in sarcomas. By using established and patient-derived sarcoma cells with different subtypes, we showed that the pan-HDACi, ITF2357, potently inhibited in vitro survival in a p53-independent manner. ITF2357-mediated cell death implied the activation of mitochondrial apoptosis, as attested by induction of pro-apoptotic BH3-only proteins and a caspases-dependent mechanism. ITF2357 also induced autophagy, which protected sarcoma cells from apoptotic cell death. ITF2357 activated forkhead box (FOXO) 1 and 3a transcription factors and their downstream target genes, however, silencing of both FOXO1 and 3a did not protect sarcoma cells against ITF2357-induced apoptosis and upregulated FOXO4 and 6. Notably, ITF2357 synergized with Doxorubicin to induce cell death of established and patient-derived sarcoma cells. Furthermore, combination treatment strongly impaired xenograft tumor growth in vivo, when compared to single treatments, suggesting that combination of ITF2357 with Doxorubicin has the potential to enhance sensitization in different preclinical models of sarcoma. Overall, our study highlights the therapeutic potential of ITF2357, alone or in rational combination therapies, for bone and soft tissue sarcomas management.

Introduction: Carbon fiber reinforced (CFR) implants have been proposed for the treatment of fractures or impending fractures of the long bones in the oncology patient. Aim of this study is to present the largest cohort of oncology patients operated by CFR nailing by the Italian Orthopaedic Society (SIOT) Bone Metastasis Study Group., Methods: 53 adult oncology patients were operated on with a CFR-PEEK nail. All the data from adjuvants therapies were collected. Bone callus formation, response to radiotherapy, relapse or progression of the osteolysis were recorded. Hardware survival and failure, breakage and need for implant revision were also analysed., Results: Anatomical implantation of nails include humerus (n = 35), femur (n =11) and tibia (n = 7). The most frequent tumors affecting the bone were myeloma (n = 13), breast (n = 11), lung (n = 8), and renal cell cancer (n = 7). Acrylic cement reinforcement was used in 2 patients. One patient was subjected to electrochemotherapy after nail insertion. Intraoperative and early postoperative complications occurred in 13.2% and 7.54% of patients respectively. Eight patients had local progression and one developed a stress fracture proximally to the distal static screw. Radiographic union occurred in 14 patients; one screw loosening was recorded., Discussion: There is currently a lack of solid evidence on the clinical use of CFR nails in oncologic patients. This is the first and largest study of CFR nailing, with the longest available follow up., Conclusions: Implant related complications and surgery-related morbidity should be taken into account in the decision-making process for the surgical management of these patients. These data can improve the surgeon-patient communication and guide further studies on patients' survival and complications with respect to surgery., (© 2017 Elsevier Ltd. All rights reserved.)

Background: Musculoskeletal sarcomas comprise 1% of all malignancies in adults. Unfortunately, sometimes they are addressed in non-appropriate way requiring a more invasive procedure to achieve radical surgery at a later date. Due to incomplete predictability of their extension, scheduled reconstruction cannot be performed at times, forcing plans to change or clogging up immediate reconstruction. In this paper, the authors provide an insight in the treatment of musculoskeletal sarcomas, particularly focusing on the preoperative planning of reconstructive strategies, which is crucial in order to prevent unpleasant surprises during reconstruction., Methods: Fifty-six consecutive patients requiring reconstructive procedures following the extirpation of tumors were recruited. All data collected during the diagnostic phase were analyzed collectively during a multi-disciplinary meeting where the surgical procedure was planned. A score system was created and results were then classified into "excellent", "good", "sufficient" and "poor"., Results: After a minimum follow up of 12 months, we recorded the following results: excellent in 10 patients (17.9%), good in 28 patients (50%), sufficient in 12 cases (21.4%) and poor in 6 cases (10.7%)., Conclusions: The improvement of treatment and the long-lasting survival in musculoskeletal sarcoma have shifted the goal of therapeutic protocol to obtaining radical tumor removal and maximum functional restoration. When facing unpredictable extension of the resections, reconstruction may be a challenging or even impossible task to fulfil. Only meticulous preoperative planning can prevent surgeons from falling into all sorts of surgical traps following wide resections.

Purpose: Because of the improvement of medical therapy and the corresponding increase in life expectancy, orthopaedic surgeons are obliged to perform more wide resections rather than intramedullary stabilization nailing for patients affected by tumours of the hip compared to the past. Wide resection often causes joint instability, so prosthetic reconstruction presents a higher risk of dislocation than in primary osteoarthritis cases. The aim of the present paper is to classify the indications for the dual mobility cup (DMC) hip prosthesis based on the anatomic structures involved in the disease and to analyse the rationale to reduce the risk of dislocation., Methods: Indications were analyzed and classified based on all the cases in which the DMC prosthesis was used for reconstruction after hip resection in an oncological research hospital., Results: Four classes of indications were identified; for classes I and IV the indication for DMC prosthesis can be considered strong; for classes II and III the indications must be evaluated considering the specific case, based on life expectancy, performance status, presence of osteoarthritis, and availability of adjuvant local therapies. When the DMC prosthesis is indicated, the cup should always be cemented, either alone or with augmentation techniques, to decrease the risk of mobilization due to local disease progression., Conclusions: DMC can be a valid alternative in reconstruction of the hip after tumor removal; nevertheless, prospective, randomized studies are necessary to verify the real dislocation rate based on the entity of resection.

Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient's medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.

Metastases to proximal femur are common and surgery is often suggested to prevent fractures; otherwise it is necessary in cases where this has already occurred. Adjuvant radiotherapy is necessary to reduce the risk of local progression. Nevertheless, the success or failure of radiation therapy treatments depends upon the accuracy in which target identification is correct and dose prescription is fulfilled. Unfortunately, the use of titanium nails consistently limits radiation dose; indeed, the presence of ferromagnetic artifacts interferes with target identification. We present the technique for implant a new carbon fiber nail useful to reduce the ferromagnetic artifacts which allows a better adjuvant radiotherapy.