scholarly journals Osteosarcoma: novel prognostic biomarkers using circulating and cell-free tumour DNA

Author(s):  
Iben Lyskjaer ◽  
Neesha Kara ◽  
Solange De Noon ◽  
Christopher Davies ◽  
Ana Maia Rocha ◽  
...  

Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Despite treatment with curative-intent, many patients die of this disease. Biomarkers for assessment of disease burden and prognoses for osteosarcoma are not available. Circulating-free (cfDNA) and -tumour DNA (ctDNA) are promising biomarkers for disease surveillance in several major cancer types, however only two such studies are reported for OS. In this combined discovery and validation study, we identified four novel methylation-based biomarkers in 171 OS tumours (test set) and comprehensively validated our findings in silico in two independent osteosarcoma sample datasets (n= 162, n=107) and experimentally using digital droplet PCR (ddPCR, n=20 OS tumours). Custom ddPCR assays for these biomarkers were able to detect ctDNA in 40% of pre-operative plasma samples (n=72). ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients who experienced a subsequent relapse post-operatively. Both cfDNA levels and ctDNA detection independently correlated with overall survival, p=0.0015, p=0.0096, respectively. Combining both assays increased the prognostic value of the data. Our findings illustrate the utility of mutation-independent methylation-based markers, broadly applicable ctDNA assays for tumour surveillance and prognostication. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers for predicting clinical outcome of OS.

Author(s):  
G.S. Irvine-Smith ◽  
R.G. Lobetti

Canine osteosarcoma is the most commonly diagnosed primary bone tumour in the dog, affecting mainly large and giant breed dogs with the predilection site being the metaphysis of long bones, specifically the distal radius, proximal humerus, distal femur and proximal tibia and fibula. Treatment options are either palliative or curative intent therapy, the latter limb amputation or limb-sparing surgery together with chemotherapy. This article describes the use of an ipsilateral vascularised ulnar transposition autograft as well as chemotherapy in 2 dogs with osteosarcoma of the distal radius. Both dogs showed minimal complications with the technique and both survived over 381 days following the surgery. Complications seen were loosening of the screws and osteomyelitis. The procedure was well tolerated with excellent limb use. This technique is indicated for use in cases with small tumour size that have not broken through the bone cortex.


2021 ◽  
pp. 112070002110015
Author(s):  
Riccardo Zucchini ◽  
Andrea Sambri ◽  
Claudio Giannini ◽  
Michele Fiore ◽  
Carlotta Calamelli ◽  
...  

Introduction: Periacetabular reconstruction after resection of primary bone tumour is a very demanding procedure. They are frequently associated with scarce functional results and a high rate of complications. We report a series of patients with periacetabular resections for primary bone tumours and reconstruction with a porous tantalum (PT) acetabular cup (AC). Materials and methods: 27 patients (median age 30 years) were included, being affected by primary bone tumours of the pelvis and treated with peri-acetabular resection and reconstruction with a PT AC. The diagnoses were 13 osteosarcomas, 7 chondrosarcomas and 7 Ewing sarcomas. Function was assessed with the Harris Hip Score and complications were classified according to Zeifang. Results: The median follow-up was 70 months. 1 patient required removal of the PT AC because of implant associated infection 55 months after surgery. There was 1 hip dislocation and no case of aseptic loosening. At final follow-up, the median HHS was 81 points (range 48–92). Conclusions: The used PT AC had good medium-term survival rates and good functional results. This technique is a viable reconstructive option after resections of periacetabular primary bone sarcomas.


Sarcoma ◽  
1997 ◽  
Vol 1 (2) ◽  
pp. 75-77 ◽  
Author(s):  
Paul Cool ◽  
Mark Davies ◽  
Rob J. Grimer ◽  
Simon R. Carter ◽  
Roger M. Tillman

2018 ◽  
Vol 100-B (1) ◽  
pp. 101-108 ◽  
Author(s):  
J. D. Stevenson ◽  
V. S. Kumar ◽  
G. L. Cribb ◽  
P. Cool

AimsDislocation rates are reportedly lower in patients requiring proximal femoral hemiarthroplasty than for patients undergoing hip arthroplasty for neoplasia. Without acetabular replacement, pain due to acetabular wear necessitating revision surgery has been described. We aimed to determine whether wear of the native acetabulum following hemiarthroplasty necessitates revision surgery with secondary replacement of the acetabulum after proximal femoral replacement (PFR) for tumour reconstruction.Patients and MethodsWe reviewed 100 consecutive PFRs performed between January 2003 and January 2013 without acetabular resurfacing. The procedure was undertaken in 74 patients with metastases, for a primary bone tumour in 20 and for myeloma in six. There were 48 male and 52 female patients, with a mean age of 61.4 years (19 to 85) and median follow-up of two years (interquartile range (IQR) 0.5 to 3.7 years). In total, 52 patients presented with a pathological fracture and six presented with failed fixation of a previously instrumented pathological fracture.ResultsAll patients underwent reconstruction with either a unipolar (n = 64) or bipolar (n = 36) articulation. There were no dislocations and no acetabular resurfacings. Articular wear was graded using the criteria of Baker et al from 0 to 3, where by 0 is normal; grade 1 represents a narrowing of articular cartilage and no bone erosion; grade 2 represents acetabular bone erosion and early migration; and grade 3 represents protrusio acetabuli. Of the 49 patients with radiological follow-up greater than one year, six demonstrated grade 1 acetabular wear and two demonstrated grade 2 acetabular wear. The remainder demonstrated no radiographic evidence of wear. Median medial migration was 0.3 mm (IQR -0.2 to 0.7) and superior migration was 0.3 mm (IQR -0.2 to 0.6). No relationship between unipolar versus bipolar articulations and wear was evident.ConclusionHemiarthroplasty PFRs for tumour reconstruction eliminate joint instability and, in the short to medium term, do not lead to native acetabular wear necessitating later acetabular resurfacing. Cite this article: Bone Joint J 2018;100B:101–8.


1995 ◽  
Vol 20 (1) ◽  
pp. 5-7 ◽  
Author(s):  
D. A. CAMPBELL ◽  
P. A. MILLNER ◽  
C. R. DREGHORN

Primary bone tumours are rare in the hand and wrist. This 34-year survey of the Leeds Regional Bone Tumour Registry reveals 80 such tumours, representing 3.9% of the total number of bone turnouts in the registry. The large majority of these tumours were benign (86%), and were found predominantly in younger patients. Malignant lesions were found more frequently in older patients. 61% of tumours were found in the metacarpals and proximal phalanges. Two-thirds of patients (67.5%) presented with features of swelling, either with or without pain. We conclude that the information gathered from Bone Tumour Registries is of value in describing tumour characteristics, where such information could not be gathered by personal experience alone.


2018 ◽  
Vol 71 (7) ◽  
pp. 579-583 ◽  
Author(s):  
Wonju Jeong ◽  
Ha-Jeong Kim

Clinical outcome prediction is major concern to patients with cancer. Various molecular markers in various carcinomas have been identified in the past few decades. However, accurate predictors in chondrosarcoma have not been developed, even though chondrosarcoma is the second most common primary bone tumour. Chondrosarcoma is the cartilage-forming malignancy and shows a wide spectrum of clinicopathological behaviours. The majority of chondrosarcoma grows slowly and rarely metastasises, and adequate surgery leads to a good prognosis. However, wide surgical excision is acquired in high-grade chondrosarcoma, because this tumour is highly resistant to chemotherapy and radiotherapy. To decide best therapy, accurate diagnostic markers are also necessary in chondrosarcoma. It is reported that angiogenesis and lymphangiogenesis increase by chondrosarcoma staging, and they are promoted by leptin and adiponectin. Several microRNAs to regulate vascular endothelial growth factor (VEGF)-A and VEGF-C are also reported. Alpha-methylacyl-CoA racemase and periostin are proposed as new biomarkers for differential diagnosis of enchondroma and chondrosarcoma. This review summarises that chondrosarcoma diagnostic markers are currently reported.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5404-5404
Author(s):  
Katie Guo ◽  
Melissa Boileau ◽  
Bernard Fortin ◽  
Francine Aubin ◽  
Tony Petrella ◽  
...  

Abstract Introduction Primary bone lymphoma (PBL) is an uncommon form of lymphoma. Diffuse large B-cell lymphoma (DLBCL) represents the main histology associated with PBL. Clinicopathological understanding and management of PBL rely only on retrospective series. Methods Cases of DLBCL diagnosed by bone biopsy treated in one referring center between 1993 and 2014 were retrospectively reviewed (Montreal, Canada). Bone biopsies done as part of the bone marrow analysis were excluded. Patients files were analyzed to determine if patient had primary bone lymphoma or systemic lymphoma with bony involvement. We excluded patient with distant lymph node or other extranodal involvement. Data on clinical presentation, staging procedures and treatment management including use of radiotherapy was collected. Staging was performed according to WHO classification of soft tissue tumors (2002). Survival time and time to recurrence were calculated from the date of the first documented treatment until recurrence or death with the Kaplan-Meier method. Prognostic factors of recurrence or death were explored with log-rank tests and Cox proportional hazards models. Competing risks analysis was attempted to isolate deaths from lymphoma and death from other causes. Our study was approved by local research and ethic committees. Results We retrieved 42 cases of PBL with a median age of 63 years (23-83) treated between October 1995 and April 2014. We identified 3/14 (21%) GCB and 11/14 (79%) non-GCB subtypes based on the modified Hans algorithm (Meyer et al., JCO 2011). The most common presenting symptom was pain (88%). 12/42 (33%) patients had an IPI score ≥ 3. We identified 18 (43%) stage I, 11 (26%) stage II and 13 (31%) stage IV. 20/42 (48%) had bulky disease (≥ 10cm). Among the 37 patients treated with curative intent, 36 (97%) received CHOP-based regimen and 23 (62%) received rituximab. 30 of these 37 (81%) patients received additional radiotherapy of which 67% received a dose of radiotherapy between 36-50 Gy. Overall response rate for patients treated with curative intent was 86%. With a median follow up of 64.8 months for the whole cohort, the 5- and 10-year overall survival was 73% and 54%, respectively. The 5- and 10-year progression-free survival was 70% and 49% respectively. Age, LDH, stage (I-II vs IV), ECOG (0-1 vs 2-4), IPI (0-2 vs 3-5), use of radiotherapy or addition of rituximab were associated with differences in survival and progression rates that did not reach statistical significance given the limited number of patients in our cohort and the fact that half of the deaths were attributed to other causes. A larger cohort would be required to demonstrate a benefit with rituximab. Response was based on positron emission tomography-computed tomography (TEP-CT) imaging in 12 patients. There was an insufficient number of patients to evaluate the role of adding radiotherapy in patient complete remission defined by PET-CT. Conclusion Our survival rates reproduce published data from series of PBL (Ramadan et al., Ann Oncol 2007; Bruno Ventre et al., Oncologist 2014), although the benefit of adding rituximab did not reach statistical significance in our cohort. The role of radiotherapy in the era of response defined by PET-CT remains to be defined. Disclosures Fleury: Gilead: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Lundbeck: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau.


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