Improved nationwide survival of sarcoma patients with a network of reference centers.

BACKGROUND: We investigated the impact of the implementation of a network of reference centers for sarcomas (NETSARC) on the care and survival of sarcoma patients in France since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTBs), funded by the French National Cancer Institute (INCa) since 2010. Its aims are to improve the quality of diagnosis and care of sarcoma patients. Patients' characteristics, treatments, and outcomes are collected in a nationwide database. The objective of this analysis was to compare the survival of patients in three periods: 2010-2012 (non-exhaustive), 2013-2015, and 2016-2020. RESULTS: A total of 43 975 patients with sarcomas, gastrointestinal stromal tumors (GISTs), or connective tissue tumors of intermediate malignancy were included in the NETSARC+ database since 2010 (n = 9266 before 2013, n = 12 274 between 2013 and 2015, n = 22 435 in 2016-2020). Median age was 56 years, 50.5% were women, and 13.2% had metastasis at diagnosis. Overall survival was significantly superior in the period 2016-2020 versus 2013-2015 versus 2010-2012 for the entire population, for patients >18 years of age, and for both metastatic and non-metastatic patients in univariate and multivariate analyses (P < 0.0001). Over the three periods, we observed a significantly improved compliance to clinical practice guidelines (CPGs) nationwide: the proportion of patients biopsied before surgery increased from 62.9% to 72.6%; the percentage of patients presented to NETSARC MDTBs before first surgery increased from 31.7% to 44.4% (P < 0.0001). The proportion of patients with R0 resection on first surgery increased (from 36.1% to 46.6%), while R2 resection rate decreased (from 10.9% to 7.9%), with a better compliance and improvement in NETSARC centers. CONCLUSIONS: The implementation of the national reference network for sarcoma was associated with an improvement of overall survival and compliance to guidelines nationwide in sarcoma patients. Referral to expert networks for sarcoma patients should be encouraged, though a better compliance to CPGs can still be achieved.

[Cutaneous and subcutaneous primary leiomyosarcoma: A retrospective cohort of 26 cases examining clinical data and treatments]. / Léiomyosarcome cutané et sous-cutané primitif : une cohorte rétrospective de 26 cas s'intéressant aux données cliniques et aux traitements.

BACKGROUND: Superficial leiomyosarcoma is a rare malignant soft tissue tumor arising from smooth muscle cells, accounting for 2-3% of superficial sarcomas, with limited literature available on the subject. It is typically observed in patients aged 50-60 years and affects both men and women equally in the subcutaneous subtype, whereas the cutaneous subtype predominantly affects men. OBJECTIVE: This study aims to examine the clinicopathological features and therapeutic outcomes of patients with leiomyosarcoma. METHOD: This is a descriptive retrospective study of 26 cases of cutaneous and subcutaneous leiomyosarcomas, with histological confirmation. RESULTS: We identified 10 (38.5%) subcutaneous leiomyosarcomas and 16 (61.5%) cutaneous leiomyosarcomas. The majority of tumors were located in the lower limbs, accounting for 13 (50%) cases. During follow-up, 6 patients experienced recurrence, and 7 developed metastases, including 2 of the 7 patients who had R0 resection margins. Among these, 3 out of the 6 recurrent cases and 3 out of the 7 metastatic cases were subcutaneous leiomyosarcomas. The average time to recurrence was 6.2 years. CONCLUSION: The observed risk of metastases and recurrences, despite clear surgical margins, in both cutaneous and subcutaneous leiomyosarcomas, along with the delayed onset of these events, justifies prolonged patient follow-up. The lungs, bones and liver have been identified as the most common site of metastasis.

[Anatomical basis of gluteus maximus and application as a pedicled cover flap for pelvic tumor resections]. / Bases anatomiques du gluteus maximus et application comme lambeau pédiculé de couverture pour les résections de tumeurs du bassin.

OBJECTIVES: The resection of malignant bone tumors of the pelvis causes significant loss of substances making covering procedures difficult. The gluteus maximus pedicled flap allows some reconstructions, but its use in vascular sacrifice is not clearly established. The objective of our study was to study its vascularization in order to assess the possibility of vascular sacrifice during carcinological resection of a pelvic tumor. METHOD: We first performed a vascular mapping of the gluteus maximus muscle using 3-dimensional (3D) models from CT angiography in patients with Leriche syndrome. These models were compared to a cadaveric dissection of 2 injected muscles. A second 3D modeling from postoperative scans was performed in patients who had a gluteus maximus flap after pelvic carcinological surgery. RESULTS: Ten patients with Leriche syndrome had a 3D model from their scanners. Three distinct arterial systems were identified. Seven patients had a flap from the gluteus maximus muscle, including 3 cases of an Inverted pedicled Hemi Gluteus maximus flap (HGI). According to the modeling, the richness of the vascular network would allow the sacrifice of the superior gluteal pedicle without compromising the viability of this flap. CONCLUSION: Our study made it possible to confirm the richness of the vascular network of the gluteus maximus muscle and to consider the theoretical possibility of sacrificing the superior gluteal pedicle without endangering an HGI pedicled muscle flap.

Surgery in reference centers improves survival of sarcoma patients: a nationwide study.

BACKGROUND: NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. PATIENTS AND METHODS: Patients' characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). RESULTS: Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P < 0.001 for all, with a hazard ratio of 0.681 (95% CI 0.618-0.749) for OS]. CONCLUSION: This nationwide registry of sarcoma patients shows that surgical treatment in a reference center reduces the risk of relapse and death.

Sclerosing Epithelioid Fibrosarcoma (SEF) versus Low Grade Fibromyxoid Sarcoma (LGFMS): Presentation and outcome in the nationwide NETSARC+ series of 330 patients over 13 years.

Sclerosing Epithelioid Fibrosarcoma (SEF) and Low Grade Fibromyxoid Sarcoma (LGFMS) are ultrarare sarcomas sharing common translocations whose natural history are not well known. We report on the nationwide exhaustive series of 330 patients with SEF or LGFMS in NETSARC+ since 2010. PATIENTS AND METHODS: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDTB). Since 2010, (i) pathological review has been mandatory for sarcoma,and (ii) tumour/patients' characteristics have been collected in the NETSARC+ nationwide database. The characteristics of patients with SEF and LGFMS and their outcome are compared. RESULTS: 35/73 (48%) and 125/257(49%) of patients with SEF and LGFMS were female. More visceral, bone and trunk primary sites were observed in SEF (p < 0.001). 30% of SEF vs 4% of LGFMS patients had metastasis at diagnosis (p < 0.0001). Median size of the primary tumor was 51 mm (range 10-90) for LGFMS vs 80 (20-320) for SEF (p < 0.001). Median age for LGFMS patients was 12 years younger than that of SEF patients (43 [range 4-98] vs 55 [range 10-91], p < 0.001). Neoadjuvant treatment was more often given to SEF (16% vs 9%, p = 0.05). More patients with LGFMS were operated first in reference centers (51% vs 26%, p < 0.001). The R0 rate on the operative specimen was 41% in LGFMS vs 16% in SEF (p < 0.001). Median event-free survival (EFS) of patients with SEF and LGFMS were 32 vs 136 months (p < 0.0001). The median overall survival (OS) was not reached. Fifty-months OS was 93% vs 81% for LGFMS vs SEF (p = 0.05). Median OS was 77 months after first relapse, similar for SEF and LGFMS. In multivariate analysis, age, tumor size, metastasis at diagnosis were independent prognostic factors for OS in LGFMS. CONCLUSIONS: Although sharing close molecular alterations, SEF and LGFMS have a different natural history, clinical presentation and outcome, with a higher risk of metastatic relapse in SEF. Survival after relapse is longer than with other sarcomas, and similar for SEF and LGFMS.

Locally recurrent chondrosarcoma of the pelvis and limbs can only be controlled by wide local excision.

AIMS: The purpose of this study was to investigate the potential for achieving local and systemic control after local recurrence of a chondrosarcoma of bone. PATIENTS AND METHODS: A total of 126 patients with local recurrence (LR) of chondrosarcoma (CS) of the pelvis or a limb bone were identified from a prospectively maintained database, between 1990 and 2015 at the Royal Orthopaedic Hospital, Birmingham, United Kingdom. There were 44 female patients (35%) and 82 male patients (65%) with a mean age at the time of LR of 56 years (13 to 96). The 126 patients represented 24.3% of the total number of patients with a primary CS (519) who had been treated during this period. Clinical data collected at the time of primary tumour and LR included the site (appendicular, extremity, or pelvis); primary and LR tumour size (in centimetres); type of operation at the time of primary or LR (limb-salvage or amputation); surgical margin achieved at resection of the primary tumour and the LR; grade of the primary tumour and the LR; gender; age; and oncological outcomes, including local recurrence-free survival and disease-specific survival. A minimum two years' follow-up and complete histopathology records were available for all patients included in the study. RESULTS: For patients without metastases prior to or at the time of local recurrence, the disease-specific survival after local recurrence was 62.5% and 45.5% at one and five years, respectively. After univariable analysis, significant factors predicting disease-specific survival were grade (p < 0.001) and surgical margin (p = 0.044). After multivariable analysis, grade, increasing age at the time of diagnosis of local recurrence, and a greater time interval from primary surgery to local recurrence were significant factors for disease-specific survival. A secondary local recurrence was seen in 26% of patients. Wide margins were a good predictor of local recurrence-free survival for subsequent recurrences after univariable analysis when compared with intralesional margins (p = 0.002) but marginal margins did not reach statistical significance when compared with intralesional margins (p = 0.084). CONCLUSION: In cases of local recurrence of a chondrosarcoma of bone, we have shown that if the tumour is non-metastatic at re-staging, an increase in disease-specific survival and in local recurrence-free survival is achievable, but only by resection of the local recurrence with a wide margin. Cite this article: Bone Joint J 2019;101-B:266-271.

Bone regeneration strategies with bone marrow stromal cells in orthopaedic surgery.

Bone is the most transplanted tissue human with 1 million procedures every year in Europe. Surgical interventions for bone repair are required for varied reasons such as trauma resulting non-union fractures, or diseases including osteoporosis or osteonecrosis. Autologous bone grafting is the gold standard in bone regeneration but it requires a second surgery with associated pain and complications, and is also limited by harvested bone quantity. Synthetic bone substitutes lack the osteoinductive properties to heal large bone defects. Cell therapies based on bone marrow or ex vivo expanded mesenchymal stromal stem cells (MSCs) in association with synthetic calcium phosphate (CaP) bone substitutes may be alternatives to autologous bone grafting. This manuscript reviews the different conventional biological and synthetic bone grafting procedures as well as the more recently introduced cell therapy approaches used in orthopaedic surgery for bone regeneration. Some clinical studies have demonstrated safety and efficacy of these approaches but regeneration of large bone defects remain challenging due to the absence of rapid and adequate vascularisation. Future directions in the field of bone regeneration are presented, such as testing alternative cell sources or in situ fabrication of vascularized bone grafts in patients.

Isolated paralysis of the serratus anterior muscle: surgical release of the distal segment of the long thoracic nerve in 52 patients.

INTRODUCTION: Isolated serratus anterior (SA) paralysis is a rare condition that is secondary to direct trauma or overuse. Patients complain of neuropathic pain and/or muscle pain secondary to overexertion of the other shoulder stabilizing muscles. As the long thoracic nerve (LTN) passes along the thorax, it can be compressed by blood vessels and/or fibrotic tissue. The goal of the current study was to evaluate the outcomes of surgical release of the distal segment of the LTN in cases of isolated SA paralysis. PATIENTS AND METHODS: This was a retrospective study of 52 consecutive cases operated on between 1997 and 2012. The average patient age was 32 years (range 13-70). Patients had been suffering from paralysis for an average of 2 years (range 4-259 months); the paralysis was complete in 52% of cases. Every patient underwent a preoperative electroneuromyography (ENMG) assessment to confirm that only the SA was affected and there were no signs of re-innervation. RESULTS: Every patient had abnormal intraoperative findings. There were no complications. All patients showed at least partial improvement following the procedure. The improvement was excellent or good in 45 cases (86.7%), moderate in 4 cases (7.7%) and slight in 3 cases (5.6%). In 32 cases (61.5%), the winged scapula was completely corrected; it was less prominent in 19 cases and was unchanged in one case. The best outcomes following surgical release occurred in patients who presented without preoperative or neuropathic pain and were treated within 18 months of paralysis. DISCUSSION: Isolated SA paralysis due to mechanical injury resembles entrapment neuropathy. We discovered signs of LTN compression or restriction during surgery. Surgical release of the distal segment of the LTN is a simple, effective treatment for pain that provides complete motor recovery when performed within the first 12 months of the paralysis. LEVEL OF EVIDENCE: IV.