Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection.

INTRODUCTION: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR). MATERIALS AND METHODS: From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT. RESULTS: Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04). CONCLUSION: In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.

Prognostic Factors for Local Recurrence after Cryoablation of Desmoid Tumors.

PURPOSE: To determine the risk factors for local of adult patients treated for desmoid tumors by cryoablation. MATERIALS AND METHODS: Eighty-four patients treated for nonabdominopelvic desmoid tumors by cryoablation from July 2012 to July 2020 were included in a retrospective study. The population was composed of 64 women (76.19%) and 20 men (23.81%), aged from 16 to 75 years (median, 35 years ± 14.25). Each patient underwent preprocedural gadolinium-enhanced magnetic resonance imaging and was followed up to 36 months with the same technique. Clinical features, such as tumor size and previous treatment, epidemiological features, and the technical parameters of cryoablation, were studied. RESULTS: Local relapse was found in 19 (22.62%) of 84 patients. The 12-, 24-, and 36-month progression-free survival rates were 89% (95% confidence interval [CI], 79-94), 74% (95% CI, 60-83), and 68% (95% CI, 53-79), respectively. In univariate analysis, significant prognostic factors associated with local recurrence were non-abdominal wall location (P = .042), debulking strategy (P = .0105), risk of visceral injury (P = .034) or peripheral nerve injury during cryoablation (P = .033), previous radiation therapy (P = .043), and treatment before 2016 (P = .008). In multivariate analysis, abdominal wall tumors displayed the best outcome, whereas the neck and trunk showed a high rate of recurrence (hazard ratio, 7.307 [95% CI, 1.396-38.261]). CONCLUSIONS: The local recurrence of desmoid tumors after cryoablation depends on a number of prognostic factors, in particular, a non-abdominal wall location of the tumor and previous local treatment such as surgery or radiation therapy.

Overall survival in patients with re-excision of positive microscopic margins of limb and trunk wall soft tissue sarcoma operated outside of a reference center: a nationwide cohort analysis.

BACKGROUND: This French nationwide NETSARC exhaustive prospective cohort aims to explore the impact of systematic re-excision (RE) as adjuvant care on overall survival (OS), local recurrence free survival (LRFS), and local and distant control (RFS) in patients with soft tissue sarcoma (STS) with positive microscopic margins (R1) after initial resection performed outside of a reference center. METHODS: Eligible patients had experienced STS surgery outside a reference center from 2010 to 2017, and had R1 margins after initial surgery. Characteristics and treatment comparisons used chi-square for categorical variables and Kruskall-Wallis test for continuous data. Survival distributions were compared in patients reexcised (RE) or not (No-RE) using a log-rank test. A Cox proportional hazard model was used for subgroup analysis. RESULTS: A total of 1,284 patients had experienced initial STS surgery outside NETSARC with R1 margins, including 1,029 patients with second operation documented. Among the latter, 698 patients experienced re-excision, and 331 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, tumor size, tumor depth, and histotype in the population of patients re-excised (RE) or not (No-RE). The study identified RE as an independent favorable factor for OS (HR 0.36, 95%CI 0.23-0.56, p<0.0001), for LRFS (HR 0.45, 95%CI 0.36-0.56, p<0.0001), and for RFS (HR 0.35, 95%CI 0.26-0.46, p<0.0001). CONCLUSION: This large nationwide series shows that RE improved overall survival in patients with STS of extremities and trunk wall, with prior R1 resection performed outside of a reference center. RE as part of adjuvant care should be systematically considered.

A novel and secure technique of stemmed acetabular cup implantation in complex hip reconstructions: a comparative study and technical note.

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

Percutaneous Cryoablation of Symptomatic Intramuscular Venous Malformation.

PURPOSE: To evaluate the efficacy and safety of cryoablation for venous malformations. MATERIALS AND METHODS: A total of 12 patients with symptomatic intramuscular venous malformations who underwent percutaneous cryoablation between February 2015 and December 2018 were retrospectively studied. The mean age was 42 y (range, 19-58 y). Pain was reported by 11 patients (92%) and swelling by 1 (8%). Pain was assessed with a visual analog scale (VAS) before and after cryoablation. Lesion size was followed with magnetic resonance (MR) imaging at baseline and at 3-mo follow-up. Median initial VAS score was 7 (range, 0-8), and median initial lesion size was 32.5 mm (range, 11-150 mm). RESULTS: The median VAS score at 3 mo was 0 (range, 0-4), and the median lesion size at 3 mo was 0 mm (range, 0-142 mm). Eleven of 12 patients reported an improvement in their pain. MR imaging control showed a treatment scar with no residual lesion in 5 patients and decreased lesion size in 4. No major complications were reported. One minor hematoma and 1 small myositis were noted as defined by Society of Interventional Radiology criteria. CONCLUSIONS: Percutaneous cryoablation is effective and safe for treatment of symptomatic intramuscular venous malformations, with improvement of symptoms.

Contemporary rotating hinge arthroplasty can safely be recommended in complex primary surgery.

PURPOSE: The objective was to evaluate clinical and radiological outcomes, survival rate and complications of primary contemporary rotating hinged total knee arthroplasty (CRH-TKA). METHODS: Through a national multicenter retrospective study (14 centers), 112 primary CRH-TKA performed between 2006 and 2011 were included. Indications were: severe frontal plane deformity (55%), inflammatory, constitutional, congenital or post-trauma arthritis (26%), ligament laxity (10%), primary osteoarthritis (9%). Population was elderly (68 ± 13), sedentary (37.5% with a Devane score ≥ 3) and with important comorbidities (87% with ASA score ≥ 2). A clinical (KSS, Oxford scores) and radiological evaluation (implant loosening), as well as survival and reoperation rates assessment, were performed. RESULTS: At last follow-up (7 ± 3 years), KSS and Oxford scores were 64 ± 43 and 33 ± 10 each with a significant improvement of both scores overtime (respectively, p = 0.047 and p < 0.001). Twenty-eight complications (25%) were reported: 12 infections, 6 stiffness, 5 aseptic loosening and 5 patellofemoral instabilities. All in all, 91% (n = 102) of implants were still sealed and in place, 6% (n = 7) required revision and 3% (n = 3) were loose but could not undergo revision due to weak general health status. Mortality rate (18%, n = 20), linked to comorbidities, was high. CONCLUSION: Clinical outcomes and survival of primary CRH-TKA are acceptable given the difficult and complex clinical situations it faced, but with high infection rate. In primary surgery, for patients with severe deformity, bone loss or ligament laxity, the use of CRH-TKA can be recommended. The choice of these implants must remain cautious and limited to situations not allowing the use of less constrained implants. LEVEL OF EVIDENCE: Retrospective therapeutic and cohort study, Level III; retrospective case series, Level IV.

The Lysine Specific Demethylase-1 Negatively Regulates the COL9A1 Gene in Human Articular Chondrocytes.

Osteoarthritis (OA) is a degenerative disease of the joints which is associated with an impaired production of the cartilage matrix by the chondrocytes. Here, we investigated the role of Lysine-Specific Demethylase-1 (LSD1), a chromatin remodeling enzyme whose role in articular chondrocytes was previously associated with a catabolic activity and which is potentially involved during OA. Following a loss of function strategy and RNA sequencing analysis, we detail the genes which are targeted by LSD1 in human articular chondrocytes and identify COL9A1, a gene encoding the α1 chain of the cartilage-specific type IX collagen, as negatively regulated by LSD1. We show that LSD1 interacts with the transcription factor SOX9 and is recruited to the promoter of COL9A1. Interestingly, we observe that OA cartilage displays stronger LSD1 immunostaining compared with normal, and we demonstrate that the depletion of LSD1 in OA chondrocytes prevents the decrease in COL9A1 following Il-1ß treatment. These results suggest LSD1 is a new regulator of the anabolic activity of articular chondrocytes potentially destabilizing the cartilage matrix, since it negatively regulates COL9A1, a gene encoding a crucial anchoring collagen molecule. This newly identified role played by LSD1 may thus participate in the alteration of the cartilage matrix during OA.

Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone.

BACKGROUND: Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB. METHODS: Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection. RESULTS: Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery (n = 106; 48 %) or had a less morbid procedure (n = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4-28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % (n = 24/25) for patients with planned joint/prosthesis replacement and 86 % (n = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5-17.9] months), local recurrence occurred in 17 (15 %) patients. CONCLUSION: For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.

Territorial inequalities in management and conformity to clinical guidelines for sarcoma patients: an exhaustive population-based cohort analysis in the Rhône-Alpes region.

BACKGROUND: Sarcomas are rare cancers with great variability in clinical and histopathological presentation. The main objective of clinical practice guidelines (CPGs) is to standardize diagnosis and treatment. METHODS: From March 2005 to February 2007, all patients diagnosed with localized sarcoma in the Rhône-Alpes region were included in a cohort-based study, to evaluate the compliance of sarcoma management with French guidelines in routine practice and to identify predictive factors for compliance with CGPs. RESULTS: 634 (71 %) patients with localized sarcoma satisfying the inclusion criteria were included out of 891 newly diagnosed sarcomas. Taking into account initial diagnosis until follow-up, overall conformity to CPGs was only 40 % [95 % confidence interval (CI) = 36-44], ranging from 54 % for gastrointestinal stromal tumor to 36 % for soft tissue sarcoma and 42 % for bone sarcoma. In multivariate analysis, primary tumor type [relative risk (RR) = 4.42, 95 % CI = 2.79-6.99, p < 0.001], dedicated multidisciplinary staff before surgery (RR = 4.19, 95 % CI = 2.39-7.35, p < 0.001) and management in specialized hospitals (RR = 3.71, 95 % CI = 2.43-5.66, p < 0.001) were identified as unique independent risk factors for conformity to CPGs for overall treatment sequence. CONCLUSIONS: With only 40 % of total conformity to CPGs, the conclusions support the improvement of initial sarcoma management and its performance in specialized centres or within specialized dedicated networks.

Improved Metastatic-Free Survival after Systematic Re-Excision Following Complete Macroscopic Unplanned Excision of Limb or Trunk Soft Tissue Sarcoma.

BACKGROUND: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated. METHODS: This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE. RESULTS: Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53-0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE. CONCLUSIONS: RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm.

Evolution of the Surgical Management of Lung Cancer Invading the Spine: A Single Center Experience.

For patients with locally advanced non-small cell lung cancer invading the spine, induction chemoradiotherapy combined with radical en bloc resection is the key to obtaining long-term survival. With time, our operative technique evolved to a two-step surgery as we experienced numerous perioperative complications during one step surgery. The aim of our study was to assess postoperative morbimortality and long-term survival of both techniques. We retrospectively reviewed all patients who underwent en bloc resection for lung cancer invading the spine between October 2012 and June 2020. Every patient underwent induction therapy. Sixteen patients were included: nine patients were operated on with one step surgery, seven patients were operated on with two step interventions. Twenty-five percent of patients had major perioperative complications and 56.2% of patients had major post-operative complications. Patients in the "one step" group tended to have more perioperative complications whereas patients in the "two step" group tended to have more post-operative complications. Overall 3-year survival was 40% in the one-step and 86% in the two-step surgery group. Although our practice has been improved by two-step interventions, post-operative morbidity remains significant. As long term survivals are encouraging, this type of treatment should still be proposed for highly selected patients, in specialized centers.

Long-term outcomes after definitive radiotherapy with modern techniques for unresectable soft tissue sarcoma.

INTRODUCTION: The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option. METHODS: We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p < 0.001). Macroscopically incomplete resection and EQD2 ≥ 64 Gy were associated with better OS (p = 0.016 and p = 0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients. CONCLUSION: In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.

Mid and long-term overall survival after carcinologic resections of thyroid cancer bone metastases.

Background: Bone metastases in thyroid cancer impair the patient's quality of life and prognosis. Interestingly, wide margins resection as the surgical treatment of bone metastases might improve the overall survival (OS). Nonetheless, data are lacking regarding the potential benefits of this strategy. Methods: In order to assess the OS of patients with thyroid cancer after a bone metastases carcinologic resection, a retrospective multicentric study was performed, evaluating the 1, 5, 10 and 15 years-OS along with the potential prognosis associated factors. Results: 40 patients have been included in this multicentric study, with a mean follow-up after surgery of 46.6 ± 58 months. We observed 25 (62.5%) unimestastatic patients and 15 multimetastatic patients (37.5%). The median overall survival after resection was 48 ± 57.3 months. OS at 1, 5, 10, and 15 years was respectively 76.2%, 63.6%, 63.6%, and 31.8%. Survival for patients with a single bone metastasis at 15 year was 82.3%, compared with 0.0% (Log Rank, p = 0.022) for multi-metastatic bone patients. Conclusions: This study advocates for an increased long term 10-year OS in patients with thyroid cancer, after resection of a single bone metastasis, suggesting the benefits of this strategy in this population.

Percutaneous Core Needle Biopsy Can Efficiently and Safely Diagnose Most Primary Bone Tumors.

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

Impact of histological subtype on radiological and pathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: Evaluation of response to neoadjuvant radiotherapy (NART) does not consider soft tissue sarcoma (STS) heterogeneity. We aimed to investigate radiological and pathological response of 4 major histotypes. METHODS: Extremity or trunk STS patients who received 50 Gy NART between 2009 and 2020 were retrospectively included. Relative variation in tumor size (RVTS) and pathological response were reported in the overall population and in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), myxoid liposarcoma (MLS) and synovial sarcoma (SS) patients to identify response modalities of each histotype. RESULTS: Among the 121 included patients, 49, 19, 13 and 11 presented UPS, MFS, MLS and SS. Median RVTS were 0% (IQR -18-+18), +8% (IQR 0-+24), -12% (IQR -20-3) and -11% (IQR -15-9), respectively (p = 0.001). Median viable cells were 10%, 60%, 20% and 70% (p = 0.007). In overall population, pathological complete response and median necrosis were 27.7% and 10% without significant correlation to histotype (p = 0.18 and 0.06). Nineteen (38.8%) UPS specimens presented cysts that were emptied during the sampling process and distorted the microscopic response evaluation. Infiltrative growth pattern was observed in 28% and 38.9% UPS and MFS patients. Five (38.5%) MLS presented mature adipocytes without proven prognostic value. Cysts were observed in 36% of SS specimens. In the absence of initial tumor limits, the great viable cellularity of SS may be overestimated by their nodular aspect. CONCLUSION: After NART, we highlighted disparate response of UPS, frequent progression of MFS, and confirmed MLS and SS radiosensitivity. Response must be interpreted with caution and consider the histotype-specific patterns.

Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution.

Trabectedin was recently approved for patients failing doxorubicin, the standard treatment for advanced/metastatic sarcoma. This retrospective study aimed to compare trabectedin efficacy between compassionate use in unselected patients and clinical trials. From May 1999 to January 2006, 92 patients were treated at the Centre Léon Bérard, either in phase II studies or on a named patient compassionate basis. All cases were retrospectively analyzed to assess trabectedin efficacy in terms of response, progression-free, and overall survival.The objective response rate was 10% (N=9): 4% (N=2) for patients treated in compassionate use program and 16% (N=7) for those in clinical trials (P=0.18); 26 (28%) patients had stable disease for at least 6 months, 11 (23%) in the compassionate group and 15 (33%) in clinical trials. Median progression-free and overall survivals were, respectively, 2.2 [95% confidence interval (CI): 1.9-3.6] and 8.9 (95% CI: 6.4-14.2) months for all patients, 2.3 (95% CI: 1.9-4.3) and 10.4 (95% CI: 6.9-24.2) months for patients in clinical trials and 1.8 (95% CI: 1.4-3.4) and 6.4 (95% CI: 3.3-14.2) months for patients under compassionate treatment. In this retrospective analysis, the reported grade 3-4 toxicities were increased transaminase (34 patients, 37%) and neutropenia (38 patients; 42%). Higher efficacy was observed in phase II studies than with compassionate treatment, but no significant difference remained after adjustment in multivariate analysis for performance status, a well-established prognosis factor. The safety and tolerability of trabectedin shown in clinical trials is confirmed for patients in real-life situation treated in compassionate use programs, but its benefit is higher for patients with performance status 0-1.

Survival and complications in hinged knee reconstruction prostheses after distal femoral or proximal tibial tumor resection: A retrospective study of 161 cases.

INTRODUCTION: Hinged knee megaprostheses are mainly used for reconstruction after tumor resection. They may incur complications, but this has not been assessed in the French literature, except in small series at short follow-up. We therefore conducted a large-scale nationwide multicenter retrospective study with a minimum 5 years' follow-up. The objectives were (1) to compare survival between distal femoral and proximal tibial reconstruction prostheses, and (2) to analyze complications and failure. HYPOTHESIS: Distal femoral hinged reconstruction prostheses show longer survival with fewer complications than proximal tibial prostheses. MATERIAL AND METHODS: One hundred sixty-one patients were included: 118 in the distal femoral group, and 43 in the proximal tibial group. Tumors were mostly osteosarcomas (90 cases) or chondrosarcomas (31 cases). Mean age was 37 years (range, 12-86 years). Complications were assessed on the Henderson classification. Failure was defined by prosthesis anchor exchange or amputation. RESULTS: At a mean 9 years' follow-up (range, 5-23 years), implant survival was longer in the distal femoral group: 5- and 10-year survival, 84% [95% CI, 75-89] and 70% [95% CI, 59-79] versus 74% [95% CI, 69-85] and 43% [95% CI, 23-61] (p=0.02). Revision surgery for complications mainly concerned aseptic loosening (19%, 30 cases) or deep infection (16%, 25 cases) and more often involved the proximal tibia (65% vs. 43%, 28 vs. 51 cases; OR 2.4 [95% CI, 1.2-5.1]; p=0.02). DISCUSSION: Hinged knee reconstruction prosthesis is a solution in tumoral pathology, but with a high risk of complications (loosening and infection) and a higher failure rate in the proximal tibial reconstruction prosthesis. LEVEL OF EVIDENCE: IV, case series.

Long term term follow-up of tyrosine kinase inhibitors treatments in inoperable or relapsing diffuse type tenosynovial giant cell tumors (dTGCT).

RATIONALE: CSF1R tyrosine kinase inhibitors (TKI) and antibodies yield response rates and tumor control in patients with diffuse type tenosynovial giant cell tumors (dTGCT). The long term management of patients with dTGCT treated with TKI is however not known. PATIENTS AND METHODS: We conducted a retrospective single center study on the 39 patients with advanced and/or inoperable dTGCT referred to the Centre Leon Berard for a medical treatment. The clinical characteristics and treatments of patients who had received at least one line of CSF1R TKI or Ab was collected from the electronic patient records and analyzed, after this study was approved by the Institutional Review Board of the Centre Leon Berard. Statistics were conducted using SPSS 23.0. RESULTS: Thirty-nine patients received at least one line of TKI among the 101 patients with histologically confirmed dTGCT refered to this center. Imatinib, nilotinib, pexidartinib, emactuzumab were the most frequently used agents. First line treatment was given for a median duration of 7 months. With a median follow-up from the initiation of TKI of 30 months, the progression-free rate at 30 months is 56% for the 39 patients. 15 patients had recurrent disease after first line CSF1R inhibitor: 12 (80%) received a 2nd line treatment for a median duration of 6 months and a median time to progression (TTP) of 12 months. Six patients had afterwards a recurrent disease and 5 (83%) received a 3rd line treatment for a median duration of 5 months and a median TTP of 9 months. Progression-free rate at 30 months was observed in 3 of 12 (25%) after line 2 and 1 of 5 (20%) after line 3. None of the patients refered died with a median follow-up of 67 months. CONCLUSIONS: CSF1R TKI or Ab provide prolonged tumor control and symptom relief for a majority of patients with inoperable or relapsing dTGCT, in first and subsequent lines. Multiple lines are required for close to 50% of patients with relapsing dTGCT.

Use of a dual mobility socket to manage total hip arthroplasty instability.

UNLABELLED: Unconstrained tripolar hip implants provide an additional bearing using a mobile polyethylene component between the prosthetic head and the outer metal shell. Such a design increases the effective head diameter and therefore is an attractive option in challenging situations of unstable total hip arthroplasties. We report our experience with 54 patients treated using this dual mobility implant in such situations. We ascertained its ability to restore and maintain stability, and examined component loosening and component failure. At a minimum followup of 2.2 years (mean, 4 years; range, 2.2-6.8 years), one hip had redislocated 2 months postoperatively and was managed successfully without reoperation by closed reduction with no additional dislocation. Two patients required revision of the implant because of dislocation at the inner bearing. Technical errors were responsible for these failures. Three patients had reoperations for deep infections. The postoperative radiographs at latest followup showed very satisfactory osseointegration of the acetabular component because no radiolucent line or osteolysis was reported. Use of this unconstrained tripolar design was successful in restoring and maintaining hip stability. We observed encouraging results at short-term followup regarding potential for loosening or mechanical failures. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Free fillet lower leg flap for coverage after hemipelvectomy or hip disarticulation.

INTRODUCTION: Tumor resection is the gold standard treatment for soft tissue and bone sarcomas. In the pelvis, this may require a hemipelvectomy that can compromise primary skin closure. Flaps are essential in this context; however the vascularization of potential pedicled flaps may have been removed during tumor excision. Using healthy tissue from the amputated limb as a free flap is an excellent coverage option. HYPOTHESIS: The free fillet flap from an amputated lower limb is a simple and reliable coverage technique after hemipelvectomy or hip disarticulation. MATERIAL AND METHODS: Seven patients were operated on at three specialty centers: six transpelvic amputations (external hemipelvectomy) and one hip disarticulation. In three cases, the flap consisted of the superficial posterior compartment of the calf area and in the three other cases, the lower leg compartments with the fibula and its intact periosteum. Complications were documented. RESULTS: Clear resection margins were achieved in all patients. The mean follow-up at the final visit was 13 months (range, 6.5 to 21 months). Six patients had complications but only one resulted in loss of the flap. Four patients were able to be fitted with a hip prosthesis. DISCUSSION: The free fillet flap from an amputated lower limb is a reliable coverage technique (86%) after hemipelvectomy or hip disarticulation. In the 16 cases previously reported in the literature, there were no wound-healing failures. Local flaps are often too fragile with insufficient muscular padding. This free flap is the preferred first-line technique as it spares other potential free flaps in case of failure without increasing the morbidity of a procedure that is already extensive. This coverage technique should be one the options considered after external hemipelvectomy. LEVEL OF EVIDENCE: IV, retrospective study.