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The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 696 - 701
1 Jun 2023
Kurisunkal V Morris G Kaneuchi Y Bleibleh S James S Botchu R Jeys L Parry MC

Aims. Intra-articular (IA) tumours around the knee are treated with extra-articular (EA) resection, which is associated with poor functional outcomes. We aim to evaluate the accuracy of MRI in predicting IA involvement around the knee. Methods. We identified 63 cases of high-grade sarcomas in or around the distal femur that underwent an EA resection from a prospectively maintained database (January 1996 to April 2020). Suspicion of IA disease was noted in 52 cases, six had IA pathological fracture, two had an effusion, two had prior surgical intervention (curettage/IA intervention), and one had an osseous metastasis in the proximal tibia. To ascertain validity, two musculoskeletal radiologists (R1, R2) reviewed the preoperative imaging (MRI) of 63 consecutive cases on two occasions six weeks apart. The radiological criteria for IA disease comprised evidence of tumour extension within the suprapatellar pouch, intercondylar notch, extension along medial/lateral retinaculum, and presence of IA fracture. The radiological predictions were then confirmed with the final histopathology of the resected specimens. Results. The resection histology revealed 23 cases (36.5%) showing IA disease involvement compared with 40 cases without (62%). The intraobserver variability of R1 was 0.85 (p < 0.001) compared to R2 with κ = 0.21 (p = 0.007). The interobserver variability was κ = 0.264 (p = 0.003). Knee effusion was found to be the most sensitive indicator of IA involvement, with a sensitivity of 91.3% but specificity of only 35%. However, when combined with a pathological fracture, this rose to 97.5% and 100% when disease was visible in Hoffa’s fat pad. Conclusion. MRI imaging can sometimes overestimate IA joint involvement and needs to be correlated with clinical signs. In the light of our findings, we would recommend EA resections when imaging shows effusion combined with either disease in Hoffa’s fat pad or retinaculum, or pathological fractures. Cite this article: Bone Joint J 2023;105-B(6):696–701


Aims. Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. Methods. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Results. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. Conclusion. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142–1149


Bone & Joint 360
Vol. 12, Issue 5 | Pages 39 - 42
1 Oct 2023

The October 2023 Oncology Roundup. 360. looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma


Bone & Joint Research
Vol. 6, Issue 4 | Pages 224 - 230
1 Apr 2017
Cool P Cribb G

Objectives. In this cross sectional study, the impact and the efficacy of a surveillance programme for sarcomas of the extremities was analysed. Methods. All patients who had treatment with curative intent for a high-grade sarcoma and were diagnosed before 2014 were included and followed for a minimum of two years. Results. Of the 909 patients who had a review appointment in 2014, 131 were under review for a high-grade sarcoma of the extremities following treatment with curative intent. Of these patients, three patients died of disease, two patients died of other causes, 12 are alive, with disease, and 114 have no evidence of disease. The surveillance programme accounts for 14% of all review appointments. Four of five patients (80%) who developed local recurrence identified the recurrence themselves. Chest radiographs are adequate in identifying metastatic disease and 11 (73%) of metastases were diagnosed during a routine follow up visit. However, the chance of cure is small and only two patients were referred for a metastatectomy. Of these only one survived for more than two years. The mean time for developing metastatic disease and local recurrence was 2.0 and 3.9 years respectively. Once identified, the mean time to death was 2.1 years for patients with metastatic disease. Conclusions. Surveillance of sarcoma patients makes up a substantial amount of the workload of a sarcoma unit. The chance of cure following identification of local recurrence or metastatic disease, however, is small. Alternative methods of surveillance that allow better evaluation of the patient’s needs are recommended. Cite this article: P. Cool, G. Cribb. The impact and efficacy of surveillance in patients with sarcoma of the extremities. Bone Joint Res 2017;6:224–230. DOI: 10.1302/2046-3758.64.BJR-2016-0253.R1


Bone & Joint 360
Vol. 3, Issue 6 | Pages 26 - 29
1 Dec 2014

The December 2014 Oncology Roundup. 360 . looks at: metaphyseal and diaphyseal osteosarcoma subtly different beasts; sports and endoprosthetic reconstruction of the knee; is curettage without tissue diagnosis sensible in cartilaginous tumours?; autoclaved autograft in bone tumour reconstruction; vascularised graft a step too far in bone defects?; interdigitated neoadjuvant chemoradiotherapy in high-grade sarcoma; predicting life expectancy in patients with painful metastasis; and osteolytic lesions of the hands and feet


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 136 - 136
1 Feb 2004
Escribá-Urios I Majò J Roca D Gracia I Doncel A
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Introduction and Objectives: This study analyses the results of our experience in reconstruction of high-grade sarcomas of the proximal humerus. Materials and Methods: A total of 37 patients were treated from March 1983 to December 2001. Average age was 24 years (19–38), with 21 males and 16 females, all presenting with high-grade sarcomas of the proximal humerus. The primary tumour was osteosarcoma in 49% (n=18) of cases, chondrosarcoma in 22% (n=8), Ewing’s sarcoma in 13% (n=5), parosteal sarcoma in 8% (n=3), malignant fibrous histiocytoma in 5% (n=2), and adamantinoma in 3% (n=1). All cases were classified as Type 1 Malawer resections (intraarticular resections of the proximal humerus). Results: During this period, scapulohumeral or scapulothoracic disarticulation was performed in 32% of cases (12 patients). In the remaining 68% (25 cases), limb salvage surgery was performed (relative limb salvage rate: 67.5%). In terms of reconstruction type, 6 cases received megaprotheses, and the remaining 19 cases received osteoarticular allografts of the humerus. Four of the 25 patients had reconstructions with sufficient follow-up time to be considered survivors without recurrence. Results were “acceptable” based on the Enneking-MTS functional scale (overall movement arcs in all directions between 60–120° with tolerable subluxations.) From a subjective point of view, all the patients obtained good results in terms of physical health and mobility of distal joints. No analysis was done of survival due to the varied nature of the neoplasias and adjuvant therapies. The main complication was fracture of the osteoarticular allograft, which occurred in 4 of 19 cases (21%). Subluxation was practically constant throughout our series but was of relatively minor clinical significance. Discussion and Conclusions: The results obtained in this study in terms of local and functional control are similar to those reported in the literature. In spite of the poor functional results for the shoulder joint, the functional results for distal joints and the cosmetic appearance of the extremity are satisfactory. However, the high rate of allograft fractures forces us to reconsider our reconstruction technique, placing priority on a mixed reconstruction using both allograft and mega-prosthesis


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_III | Pages 438 - 438
1 Jul 2010
Ferrari S Smeland S Bielack S Comandone A Dileo P Picci P Hall KS Eriksson M Honegger H Reichardt P
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EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) is the first prospective multicenter international study for patients 41–65 year old with high-grade bone sarcoma. Patients with HG Osteosarcoma (OS), HG sarcoma NOS (S), Fibrosarcoma, MFH, Leiomyosarcoma, Dedifferentiated Chondrosarcoma (DCh) were included. Chemotherapy: Combinations of cisplatin/doxorubicin (CDP 100mg/m2/ADM 60mg/m2), ifosfamide/CDP(IFO 6g/m2/CDP 100mg/m2) and IFO/ADM (IFO 6g/m2/ADM 60mg/m2) were repeated three times (9 cycles). Surgery was planned after 3 cycles. Methotrexate (8g/m2) was postoperatively added in poor responders. Immediate surgery was allowed and 9 cycles with CDP, ADM, IFO were postoperatively given. At December 2007, 140 patients were registered (median age 51 years). OS (51%), S (16%), and DCh (11%) were the more frequent histotypes. Synchronous metastases in 30 (21%) patients, central location of tumor in 45(32%).Surgical complete remission (SCR) was achieved in 84% of patients, (localized 91%, meta-static 37%) without difference among the histology groups. One surgical-related and one chemotherapy-related death were reported. Grade4 WBC and PLT incidence was 55% and 17%.Renal toxicity and peripheral neurotoxicity were reported in 16% and 20% of patients. With a median follow-up of 25 months (4–68) 3 year OS was 58% (95%CI 48–68%) [7% (95%CI 0–19%) without SCR]. In patients with SCR, 3-year OS and EFS were 46% (95%CI 9–83%) and 0% in case of synchronous metastases and 69% (95%CI58–80%) and 45% (95%CI33–57%) for localized patients; 50% (95%CI 29–71%) and 40% (95%CI 20–59%) for patients with central tumor, 73% (95%CI61–85%) and 44% (95%CI31–57%) for those with extremity tumor; 68% (95%CI 52–83%) and 46% (95%CI 32–54%) for OS, 64% (95%CI 42–85%) and 48% (95%CI 25–71%) for S, 48% (95%CI 13–82%) and 27% (95%CI 1–54%) for DCh. The protocol is feasible, but the chemotherapy-related toxicity is remarkable. Surgical complete remission is the main factor influencing survival. Central location and synchronous metastases are negative prognostic factors, but 50% 3-year OS can be achieved with aggressive local and systemic treatment. Osteosarcoma and high-grade sarcoma NOS benefit from chemotherapy more than patients with dedifferentiated chondrosarcoma


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 187 - 187
1 Feb 2004
Ioannou M Kottakis S Papaggeli E Iakovidou I Ziras N Demertzis N
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Introduction: Limb salvage surgery has all but replaced amputation as the treatment of choice for sarcomas of the extremities. This dramatic change came about as the result of two important developments: effective chemotherapy and precision imaging techniques.In high-grade sarcomas the most significant predictors of survival are the location of the primary lesion, local control of the tumor, and the degree of necrosis in the primary tumor after intravenous neoadjuvant chemotherapy (histologic response). Aim : To detect the response to preoperative chemotherapy and correlate with the biological characteristic of osteosarcoma. Materials and method:19 Patients wih primary osteo-sarcoma were studied (follow up 9 months to 7 years). Response to preoperative chemotherapy is made histologically according to the HUVOS staging system..Combination chemotherapy was used based on the Rosen T-10 protocol (high dose methotrexate) or the platine and adriamycine protocol. Conclusions :The best response to preoperative chemotherapy was found in osteoblastic osteosarcomas (12% grade IV, 33% grade III, 33% grade II and 22% grade I tumor necrosis).Chondroplastic osteosarcomas showed less sensitivity to chemotherapy (o% grade IV, 40 % grade III, 20% grade II and 40% grade I tumor necrosis) and paraosteal and periosteal osteosarcomas were resistant to preoperarive chemotherapy


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_II | Pages 322 - 322
1 May 2010
Jeanrot C Langlais F Huten D
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Competence of the extensor mechanism is the major determinant of functional outcome after resection of the proximal tibia and tumor prosthesis implantation. Restoration of a compromised active extension of the knee and an extension lag still remains a difficult challenge. Various techniques have been proposed in the past twenty years including direct attachment of the patellar ligament to the prosthesis, transposition of the medial gastrocnemius muscle possibly associated with other muscle flaps, transposition of the fibula and combination of these techniques. Transposition of the fibula was first reported by Kotz in 1983 but not sufficiently described, so that surgeons who want to plane and manage such a procedure can have some difficulties. We present our technique of fibula transposition and report the functional results about seven patients treated for high-grade sarcomas of the proximal tibia. Fibula transposition is carried out only if the entire fibula and its soft-tissues can be preserved. Resection of the tumor and reconstruction is carried out using the same anteromedial approach. After implantation of the prosthesis, the fibula and its muscles are mobilized anteriorly in a ‘baionnette’ shape obtained by performing a two-level osteotomy. The peroneal nerve and the anterior tibial vessels are previously identified and released to prevent tension on these structures during transposition. Care must be taken to preserve as much as possible the muscular insertions on the fibula so that probability of bone fusion increases. The biceps tendon and the lateral collateral ligament inserted in the fibular head are sutured to the patellar ligament. The knee is immobilized in a knee-ankle orthosis for 6 weeks. We have performed this technique in seven cases. A medial gastrocnemius muscle flap was associated in 3 cases to cover the prosthesis. Fusion was achieved in all cases. Full active extension was obtained in all cases with an extensor strength rated 5/5. All patients were ambulatory without external support at the last follow up


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 62 - 62
1 Mar 2021
Lee J Perera J Trottier ER Tsoi K Hopyan S
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Paediatric bone sarcomas around the knee are often amenable to either endoprosthetic reconstruction or rotationplasty. Cosmesis and durability dramatically distinguish these two options, although patient-reported functional satisfaction has been similar among survivors. However, the impact on oncological and surgical outcomes for these approaches has not been directly compared. We retrospectively reviewed all wide resections for bone sarcoma of the distal femur or proximal tibia that were reconstructed either with an endoprosthesis or by rotationplasty at our institution between June 2004 and December 2014 with a minimum two year follow-up. Pertinent demographic information, surgical and oncological outcomes were reviewed. Survival analysis was performed using the Kaplan-Meier method with statistical significance set at p<0.05. Thirty eight patients with primary sarcomas around the knee underwent wide resection and either endoprosthetic reconstruction (n=19) or rotationplasty (n=19). Groups were comparable in terms of demographic parameters and systemic tumour burden at presentation. We found that selection of endoprosthetic reconstruction versus rotationplasty did not impact overall survival for the entire patient cohort but was significant in subgroup analysis. Two-year overall survival was 86.7% and 85.6% in the endoprosthesis and rotationplasty groups, respectively (p=0.33). When only patients with greater than 90% chemotherapy-induced necrosis were considered, overall survival was significantly better in the rotationplasty versus endoprosthesis groups (100% vs. 72.9% at two years, p=0.013). Similarly, while event-free survival was not affected by reconstruction method (60.2% vs. 73.3% at two years for endoprosthesis vs rotationplasty, p=0.27), there was a trend towards lower local recurrence in rotationplasty patients (p=0.07). When surgical outcomes were considered, a higher complication rate was seen in patients that received an endoprosthesis compared to those who underwent rotationplasty. Including all reasons for re-operation, 78.9% (n=15) of the endoprosthesis patients required a minimum of one additional surgery compared with only 26.3% (n=5) among rotationplasty patients (p=0.003). The most common reasons for re-operation in endoprosthesis patients were wound breakdown/infection (n=6), limb length discrepancy (n=6) and periprosthetic fracture (n=2). Excluding limb length equalisation procedures, the average time to re-operation in this patient population was 5.6 months (range 1 week to 23 months). Similarly, the most common reason for a secondary procedure in rotationplasty patients was wound breakdown/infection, although only two patients experienced this complication. Average time to re-operation in this group was 23.8 months (range 5 to 49 months). Endoprosthetic reconstruction and rotationplasty are both viable limb-salvage options following wide resection of high-grade bony sarcomas located around the knee in the paediatric population. Endoprosthetic reconstruction is associated with a higher complication rate and may negatively impact local recurrence. Study of a larger number of patients is needed to determine whether the reconstructive choice affects survival


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_II | Pages 106 - 107
1 Apr 2005
Fiorenza F Grimer R Bhangu A Beard J Tillman R Abudu S Carter S
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Purpose: The purpose of this work was to analyse follow-up and prognostic factors in a series of patients treated for soft tissue tumours as a function of the type of facility providing initial care: a supra-regional referral centre (Royal Orthopaedic Hospital, Birmingham), and 38 regional hospitals in the referral area. Material and methods: This series included 260 patients (111 women and 149 men) treated between 1994 and 1996. Mean age at diagnosis was 61 years. Primary care was given to 96 patients (37%) in the referral centre and 164 (63%) in other centres. Minimum follow-up was five years. The risk of local recurrence and survival prognosis were studied by risk factor: grade, localisation (supra versus infra aponeurotic), tumour size, quality of resection margins. Results: High-grade tumours were found in 73% of patients with a supra-aponeurotic localisation in 59%. Mean tumour size was 8.6 cm. Tumours in patients treated in the referral centre were larger (10.3 cm versus 7.5 cm) (p< 0.05). Frequency of local recurrence was 20% for the referral centre versus 37% for the other centres. Overall five-year survival rate was 58% and was correlated with grade, tumour size, and localisation (p< à.05). Overall survival of patients given primary care in the referral centre was not statistically different from those treated in the other centres, but for high-grade tumours (UICC grade III), five-year survival was 41% for the referral centre and 14% for the other centres (p< 0.05). Discussion: Soft tissue sarcomas are rare tumours. For high-grade sarcomas, the rate of recurrence after treatment and the survival rate were better for patients given primary care in the referral centre. The question of centralising patients with this type of disease in referral centres is raised


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_II | Pages 133 - 134
1 Feb 2004
Gracia-Alegría I Pérez-Moreno F Peirò-Ibáñez A Doncel-Cabot A Majò-Buigas J
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Introduction and Objectives: Extraskeletal osseous sarcomas are very rare high-grade tumours. They include osteosarcoma, chondrosarcoma, and Ewing’s soft tissue sarcoma and their respective variants. We present a retrospective study of 25 cases covering the period from December 2002 to January 2003. Materials and Methods: This study of 25 cases shows that this heterogeneous group of soft tissue sarcomas primarily affects adults (mean age 50.68; range 17 to 70 years). The thigh (36.60%) and the elbow-forearm (18.18%) are the most common locations for these tumours. In these cases, 14 chondrosarcomas, 8 osteosarcomas, and 3 Ewing’s sarcomas were diagnosed. Mean follow-up time was 48.9 months with a range of 16 to 197 months. There were 16 surgeries performed with wide or compartmental margins, while in the 5 remaining cases, amputations were performed, and one case of Ewing’s sarcoma of the pelvis was treated by means of chemotherapy and radiation therapy, as it was considered non-resectable. All cases of osteosarcoma and Ewing’s sarcoma were treated by means of pre- and postoperative chemotherapy and postoperative radiation therapy. Results: The postoperative duration of symptoms ranged from 2 weeks to 6 years with a mean of 6 months. Local recurrence following surgery with wide or compartmental margens occurred in 8 cases, representing 35.45% (3 chondrosarcomas, 4 osteosarcomas, and 1 Ewing’s sarcoma). The total number of cases surviving without recurrence is 14 (63.6%), surviving cases with one or more recurrences is 5 (22.72%), one case is alive with metastasis (4.59%), and 3 sarcomas (2 ulcerated upon admission) had disseminated and the patients died (10.05%). Discussion and Conclusions: All these tumours were high-grade sarcomas. The most common metastatic localizations were lungs, regional ganglia, and skeleton. The recommended treatment is surgery with wide or compartmental margins, if possible in the early stages, in conjunction with chemotherapy and radiation therapy. The worst prognosis corresponds to the osteosarcoma


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_I | Pages 52 - 52
1 Jan 2004
Court C Bosca L Molina V Missenard G Nordin J
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Purpose: Surgery is required for primary tumours invading the sacroiliac joint. The purpose of the present work was to analyse results obtained with surgical treatment in order to better ascertain indications. Material and methods: Forty patients (24 men and 16 women), mean age 24 years (range 12–56) underwent surgery for high-grade sarcoma (n=30, osteosarcoma 12, Ewing 13, chondrosarcoma five) or more differentiated tumours (n=10, low-grade S chondrosarcoma five, fibro-sarcoma two, others three). Resection was achieved in 37 cases via two approaches and via a lateral approach in three. Resection involved vertical sacrectomy either via the homolateral foramen (n=27) or via the midline (n=10). Reconstruction consisted in stabilising the iliosa-cral assembly generally associated with vertebral osteo-synthesis, an autologous graft in 36 cases, cement in one, and an allograft in three. Functional outcome was assessed with the MSTS (Enneking). Results: There were three infections (all three with extensive lateral approach) and five cases of postoperative lumbosacral trunk palsy. Late complications were three cases of spondylolisthesis and eight nonunions. Twenty patients died (eight local recurrences, ten metastases, one chemotherapy toxicity, one undetermined cause). Sixteen patients achieved complete remission at six years (follow-up 2–16 years) and four patients were lost to follow-up. Functional outcome was very good in eight, good in ten, fair in twelve, and poor in ten. Survival was 40% among patients with malignant tumours (38 patients) but only 20% for those with osteosarcomas. Discussion: Technical improvements (combined approach rather than wide lateral approach and omentum flap) have allowed a reduction of cutaneous and infectious complications. Mechanical complications can be prevented by systematic lumbosacral fusion on the side opposite the resection reconstruction. This provides good functional results despite sacrificing a hemi-sacral plexus if the lumbo-sacral trunk is preserved. Reconstruction after extension of the resection to the acetabulum raises an unresolved problem and yields mediocre results. The quality of the surgical resection is determinant since risk of local recurrence is 8/100 after a contaminated resection edge. Conclusion: Surgical resection of sacroiliac tumours is a source of numerous complications despite real technical improvements. This approach can be proposed if carcinological resection can be reasonably achieved. Local control is very poor in case of large osteo-osteogenic sarcomas


Bone & Joint Research
Vol. 11, Issue 10 | Pages 715 - 722
10 Oct 2022
Matsuyama Y Nakamura T Yoshida K Hagi T Iino T Asanuma K Sudo A

Aims

Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases.

Methods

We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 41 - 41
1 Jul 2020
Monument M Singla A Affan A Jirik F Hildebrand K Kendal J
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Soft tissue sarcomas (STS) have not demonstrated favourable clinical responses to emerging immunotherapies such as checkpoint inhibitors. Studies in carcinomas and melanoma have demonstrated that tumours lacking T-cell infiltrates are associated with poor responses to immunotherapies. It is postulated that STS lack tumour asscoiated lymphocytes which renders these tumours insensitive to checkpoint inhibitors. Our objective was to develop a novel syngeneic mouse model of STS and characterize the immune phenotype of these tumours. Additionally, we sought to evaluate the therapeutic responses of these sarcomas to checkpoint inhibitors and a Type I interferon agonist. K-ras mutagenesis and p53 deletion was induced using a Lenti-Cre-recombinase injection into the hindlimb of 3 week old C57BL/6 mice. Tumours were harvested and characterized using standard histopathology techniques and whole trascriptome sequencing (RNAseq). Full body necrospy and histopathology was performed to identify metastases. Flow cytometry and immunohistochemistry was used to evaluate tumour immune phenotypes. Tumours were implanted into syngeneic C57BL/6 mice and the therapeutic responses to anti-CTLA4, anti-PD1 and DMXAA (Type I interferon agonist) were performed. Tumour responses were evaluated using bioluminescent imaging and caliper measurements. Soft tissue sarcomas developed in mice within 2–3 months of Lenti-Cre injection with 90% penetrance. Histologic analyses of tumours was consistent with a high-grade myogenic sarcoma characterized by smooth muscle actin, Desmin and Myogenin D positive immunostaining. Using crossplatform normalization protocols, geneexpression signatures of the mouse tumours most closely correlated with human undifferentiated pleomorphic sarcoma (UPS). Collectively, gene expression signatures of this murine sarcoma correlated with all muscle-derived human sarcomas (ERMS, ARMS, Synovial sarcoma, UPS). No lung or other visceral metastases were observed in all mice who developed spontaneous tumours. Immune phenotyping demonstrated a paucity of tumour-infiltrating lymphocytes (TILs, (TAMs). 50% of identified TILs in these murine sarcomas expressed PD-1, yet tumours were not responsive to anti-PD1 therapy or anti-CTLA4 therapy. A single intra tumoural (i.t.) injection of the Type I interferon agonist, DMXAA resulted in 80–90% tumour necrosis 72 hrs post-injection, decreased tumour viability up to 2 weeks post-injection and a marked infiltration of CD8+ T-cells and anitgen presenting dendritic cells and macrophages. Additional longitudinal experiments demonstrate a sustained and progressive anti-tumour effect in 83% (5/6) mice up to 6weeks following a single i.t. injection of DMXAA. All control treated mice (6/6) reached humane endpoint within 14 days. At 3 months post-DMXAA treatment, 4/6 mice were free of disease. We re-injected UPS tumours into these mice and tumours did not grow, suggesting abscopal effects after DMXAA treatment of primary tumours. We have characterized a new orthotopic and syngeneic mouse model of a myogenic soft tissue sarcoma. Like most human STS sub-types, these tumours have an immune inert tumour microenvironment and are not sensitive to checkpoint inhibitors. This model, syngeneic to C56BL/6 mice will enable future opportunities to investigate how various branches of the immune system can be targetted or manipulated to unearth new immunotherapeutic strategies for sarcoma. Using this model we have demonstrated that a single, intra-tumoural injection of a Type I interferon agonist can result in anti-tumour effects, recruit cytotoxic lymphocytes and antigen presenting cells with into the the tumour microenvironment. Abscopal tumour rejection after DMXAA treatement suggest adaptive T-cell responses against UPS are active in this model. Future work is needed to determine if upregulation of Type I inferferon pathways can be used as a therapeutic strategy for sarcoma or as a sensitization strategy for checkpoint inhibitors


Bone & Joint 360
Vol. 12, Issue 4 | Pages 35 - 37
1 Aug 2023

The August 2023 Oncology Roundup360 looks at: Giant cell tumour of bone with secondary aneurysmal bone cyst does not have a higher risk of local recurrence; Is bone marrow aspiration and biopsy helpful in initial staging of extraskeletal Ewing’s sarcoma?; Treatment outcomes of extraskeletal Ewing’s sarcoma; Pathological complete response and clinical outcomes in patients with localized soft-tissue sarcoma treated with neoadjuvant chemoradiotherapy or radiotherapy; Long-term follow-up of patients with low-grade chondrosarcoma in the appendicular skeleton treated by extended curettage and liquid nitrogen; Cancer-specific survival after limb salvage versus amputation in osteosarcoma; Outcome after surgical treatment of dermatofibrosarcoma protuberans: does it require extensive follow-up, and what is an adequate resection margin?; Management of giant cell tumours of the distal radius: a systematic review and meta-analysis.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_I | Pages - 59
1 Mar 2002
Missenard G Mascard E Court C
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Purpose: Use of massive allografts for reconstruction of major bone stock defects remains a controversial issue. We reviewed our experience to compare results with other methods, particularly free vascularised bone transfer reconstructions. Material and method: Between 1983 and 1995, 36 patients (15 men and 21 women) underwent cancerological resection of a long bone shaft for primary malignant tumour. Mean age was 19 years (8–84). The tumour was a high-grade sarcoma in 26 cases, low grade sarcoma in eight and adamantinoma in two. Mean length of resection was 19 cm (14–34). Cryopreserved allografts were used in 24 cases, gamma irradiated allografts in 12. Various osteosynthesis procedures were used, generally combining an axial assembly with a single or dual epiphyseal construct. Localisations were: femur 24, tibia ten and humerus four. All patients were reviewed at a minimum follow-up of five years (range 5–16 years, mean 8 years). Functional outcome was assessed with the Enneking criteria. Bone healing at junctions was considered to be achieved when there was no clinical expression and radiographic images remained unchanged for two years. Results: All immediate complications were infections (one femur four tibias) and required partial or total ablation of the allograft in four cases and amputation in one (tibia). The predominant late complications were late consolidation (n=13) and stress fracture of the allograft (n=6). Six patients died before bone healing and were not retained for analysis. Among the 28 patients retained for analysis (eight excluded: six deaths, one amputation, one total ablation of the allograft), only ten achieved bone healing after one procedure. The other eighteen required on the average four reoperations to achieve consolidation (3–11 procedures for osteosynthesis and new allograft material). All patients had achieved bone healing at last follow-up. Functional outcome was excellent for femurs, good for tibias, and fair for humeri due to the impact on shoulder function. There was no significant difference in consolidation with cryopreserved and irradiated bone material but two irradiated grafts could not be used correctly because they were to friable. Discussion: These more or less satisfactory results must be examined in light of the context. Cancerologicl resection (periosteum + soft tissue), generally combined with adjuvant treatment (chemotherapy for 24 patients and radiotherapy for three), places the patient in conditions highly unfavourable for bone healing. Use of allografts alone, combined with approximate fixation procedures early in our experience, demonstrated the limitations of the technique (only two primary consolidations among 18 patients). However, when the allograft was combined with axial fixation and immediate allograft or allograft after adjuvant treatment, primary consolidation was achieved in 80% of the cases (eight out of ten). All patients who achieved long-term remission conserved a functional limb with relatively preserved bone stock. Conclusion: Despite controversial results, massive allograft reconstructions can provide a useful alternative to fill major bone stock defects of the femur or humerus. For the tibia the risk of infections may require further discussion before determining the best approach. These results should be compared with those in a homogeneous series of patients treated with a vascularised free bone transfer, but to our knowledge no such series is available in the literature


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 425 - 429
1 May 2024
Jeys LM Thorkildsen J Kurisunkal V Puri A Ruggieri P Houdek MT Boyle RA Ebeid W Botello E Morris GV Laitinen MK

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Cite this article: Bone Joint J 2024;106-B(5):425–429.


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1314 - 1320
1 Dec 2023
Broida SE Sullivan MH Barlow JD Morrey M Scorianz M Wagner ER Sanchez-Sotelo J Rose PS Houdek MT

Aims

The scapula is a rare site for a primary bone tumour. Only a small number of series have studied patient outcomes after treatment. Previous studies have shown a high rate of recurrence, with functional outcomes determined by the preservation of the glenohumeral joint and deltoid. The purpose of the current study was to report the outcome of patients who had undergone tumour resection that included the scapula.

Methods

We reviewed 61 patients (37 male, 24 female; mean age 42 years (SD 19)) who had undergone resection of the scapula. The most common resection was type 2 (n = 34) according to the Tikhoff-Linberg classification, or type S1A (n = 35) on the Enneking classification.


Bone & Joint 360
Vol. 12, Issue 3 | Pages 35 - 37
1 Jun 2023

The June 2023 Oncology Roundup360 looks at: A size-based criteria for flap reconstruction after thigh-adductor soft-tissue sarcoma resection; Surgical treatment of infected massive endoprostheses implanted for musculoskeletal tumours; Free vascularized fibula for proximal humerus oncological reconstruction in children; The national incidence of chondrosarcoma of bone; a review; Bone sarcoma follow-up: when do events happen?; Osteosarcomas in older adults: a report from the Cooperative Osteosarcoma Study Group