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Purpose: Re-implantation of the tumor bearing autograft following extracorporeal radiation therapy (ECRT) has been established as an oncologically safe biological reconstruction technique following resection of bone sarcomas. However, factors affecting the ECRT graft-host bone incorporation have not been fully investigated. An insight into the factors that influence graft incorporation can circumvent the complications and increase graft survival. Methods: A total of 96 osteotomies in 48 patients with intercalary resections of primary extremity bone sarcomas (mean age 15.8 years, mean follow-up 42.1 months) were analyzed retrospectively for factors ECRT autograft-host bone union. Results: On univariate analysis, age < 20 years, metaphyseal osteotomy site, V-shaped diaphyseal osteotomy, and use of additional plate at diaphyseal osteotomy had a significantly faster time to union, while gender, tumour type, bone involved, resection length, chemotherapy, type of fixation, and use of intra-medullary fibula did not influence union time. In multivariate analysis, V-shaped diaphyseal osteotomy and use of additional plate at diaphyseal ostetomy were the independent factors with favourable time to union. None of the analyzed factors was found to have a significant effect on the union rate. The major complications were non-union in 11.4% patients, graft failure in 2.1%, infection in 12.5%, and soft tissue local recurrences in 14.5% patients. Conclusion: Modified diaphyseal osteotomy and augmentation of the stability of the reconstruction using additional small plates enhance the incorporation of ECRT autograft. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. Methods: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. Results: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. Conclusion: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration. [ABSTRACT FROM AUTHOR]

Surface osteosarcomas are a rare form of osteosarcomas accounting for around 3-6% of all osteosarcomas. Three major groups of surface osteosarcomas are parosteal, periosteal and the high grade surface osteosarcomas. Of these, the parosteal osteosarcoma is the most common. Parosteal and periosteal osteosarcomas are distinct clinical entities and it is important to identify the clinicoradiological differences between the two types. Surface osteosarcomas occur at a later age as compared to conventional osteosarcomas. The classical site is the lower end of the femur followed by the upper end of the tibia and upper end of humerus, in that order. The periosteal variant affects the tibia more commonly than the parosteal variety. Neo‑adjuvant chemotherapy is the standard of care for high grade surface osteosarcomas. Parosteal osteosarcomas, being low grade lesions, can be treated by upfront wide excision without adjuvant systemic therapy. Controversy prevails over the need for chemotherapy in periosteal osteosarcomas, which are intermediate grade lesions. [ABSTRACT FROM AUTHOR]

Background: Skeletal metastases of bone sarcomas are indicators of poor prognosis. Various imaging modalities are available for their identification, which include bone scan, positron emission tomography/CT scan, MRI, and bone marrow aspiration/biopsy. However, there is considerable ambiguity regarding the best imaging modality to detect skeletal metastases. To date, we are not sure which of these investigations is best for screening of skeletal metastasis.Question/purpose: Which staging investigation-18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT), whole-body MRI, or 99mTc-MDP skeletal scintigraphy-is best in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in detecting skeletal metastases in patients with osteosarcoma and those with Ewing sarcoma?Methods: A prospective diagnostic study was performed among 54 of a total 66 consecutive osteosarcoma and Ewing sarcoma patients who presented between March 2018 and June 2019. The institutional review board approved the use of all three imaging modalities on each patient recruited for the study. Informed consent was obtained after thoroughly explaining the study to the patient or the patient's parent/guardian. The patients were aged between 4 and 37 years, and their diagnoses were proven by histopathology. All patients underwent 99mTc-MDP skeletal scintigraphy, 18F-FDG PET/CT, and whole-body MRI for the initial staging of skeletal metastases. The number and location of bone and bone marrow lesions diagnosed with each imaging modality were determined and compared with each other. Multidisciplinary team meetings were held to reach a consensus about the total number of metastases present in each patient, and this was considered the gold standard. The sensitivity, specificity, PPV, and NPV of each imaging modality, along with their 95% confidence intervals, were generated by the software Stata SE v 15.1. Six of 24 patients in the osteosarcoma group had skeletal metastases, as did 8 of 30 patients in the Ewing sarcoma group. The median (range) follow-up for the study was 17 months (12 to 27 months). Although seven patients died before completing the minimum follow-up, no patients who survived were lost to follow-up.Results: With the number of patients available, we found no differences in terms of sensitivity, specificity, PPV, and NPV among the three staging investigations in patients with osteosarcoma and in patients with Ewing sarcoma. Sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 67% (4 of 6 [95% CI 22% to 96%]) and specificities were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 78% (14 of 18 [95% CI 52% to 94%]), respectively, in patients with osteosarcoma. In patients with Ewing sarcoma, sensitivities to detect bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 88% (7 of 8 [95% CI 47% to 100%]), 88% (7 of 8 [95% CI 47% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and specificities were 100% (22 of 22 [95% CI 85% to 100%]), 95% (21 of 22 [95% CI 77% to 100%]), and 95% (21 of 22 [95% CI 77% to 100%]), respectively. Further, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (6 of 6 [95% CI 54% to 100%]), 83% (5 of 6 [95% CI 36% to 100%]), and 50% (4 of 8 [95% CI 16% to 84%]) and the NPVs were 100% (18 of 18 [95% CI 82% to 100%]), 94% (17 of 18 [95% CI 73% to 100%]), and 88% (14 of 16 [95% CI 62% to 98%]), respectively, in patients with osteosarcoma. Similarly, the PPVs for detecting bone metastases for 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy were 100% (7 of 7 [95% CI 59% to 100%]), 88% (7 of 8 [95% CI 50% to 98%]), and 80% (4 of 5 [95% CI 28% to 100%]), and the NPVs were 96% (22 of 23 [95% CI 78% to 100%]), 95% (21 of 22 [95% CI 77% to 99%]), and 84% (21 of 25 [95% CI 64% to 96%]), respectively, in patients with Ewing sarcoma. The confidence intervals around these values overlapped with each other, thus indicating no difference between them.Conclusion: Based on these results, we could not demonstrate a difference in the sensitivity, specificity, PPV, and NPV between 18F-FDG PET/CT, whole-body MRI, and 99mTc-MDP skeletal scintigraphy for detecting skeletal metastases in patients with osteosarcoma and Ewing sarcoma. For proper prognostication, a thorough metastatic workup is essential, which should include a highly sensitive investigation tool to detect skeletal metastases. However, our study findings suggest that there is no difference between these three imaging tools. Since this is a small group of patients in whom it is difficult to make broad recommendations, these findings may be confirmed by larger studies in the future.Level Of Evidence: Level II, diagnostic study. [ABSTRACT FROM AUTHOR]

Abstract: Low grade central osteosarcoma is a rare primary bone tumor. This fibro-osseous lesion shares some radiological and histopathological resemblance with fibrous dysplasia, which is a more common entity. Thus it may be mistaken as fibrous dysplasia and may receive inadequate treatment resulting in a more malignant recurrent bone tumor. We present a case of low grade central osteosarcoma of the right tibia, which was initially treated as fibrous dysplasia with curettage and bone grafting. Three years later the tumor recurred with greater soft tissue and bony involvement but without metastasis. The patient was treated with above knee amputation and has been asymptomatic for the last two years. [Copyright &y& Elsevier]

Résumé: L’ostéosarcome central de faible malignité est une tumeur osseuse primitive rare. En raison de certaines caractéristiques radiographiques et histologiques communes, cette tumeur fibro-osseuse peut être confondue avec la dysplasie fibreuse (lésion osseuse bénigne plus fréquente) et entraîner un traitement inadapté, à l’origine d’une récidive tumorale osseuse de malignité plus élevée. Nous présentons le cas d’un ostéosarcome central de faible malignité du tibia droit, initialement traité comme une dysplasie fibreuse par curetage et greffe osseuse. Trois ans plus tard, la tumeur a récidivé avec un envahissement plus important des parties molles et de l’os, mais sans dissémination métastatique. Le patient a été traité par une amputation au-dessus du genou. Il est resté asymptomatique au cours des deux dernières années. [Copyright &y& Elsevier]

Background: Osteosarcoma is a high grade malignant, osteoid forming, primary bone tumor affecting the metaphysis of long bones. Local recurrence (LR) in osteosarcomas is a sinister. Theoretically, a high tumor volume at the time of presentation will limit surgical margins, involve vital neurovascular bundles and show poor response to chemotherapy thereby causing high rates of amputations (as against limb salvage surgery) and should be associated with poor survival rates. This study evaluated objectively if high tumor volume is a significant predictor of local recurrence (LR) in operated cases of osteosarcomas. Materials and Methods: Operated cases of osteosarcoma (presenting to the Orthopedic outpatient or the Medical Oncology outpatient between January 1, 2004 and January 1, 2011 were included in the study. Their preoperative clinical data and investigations along with the operative notes were traced from the medical/departmental records. Details of chemotherapy received in the neo‑adjuvant and postoperative periods were noted. Besides, all demographic data were also noted. Tumor volume was calculated using the available magnetic resonance images using the formula: ([π/6] × length × width × depth). Post data extraction, patients were divided in two groups, Groups I (without LR) and Group II (with LR). Results: A total of 95 cases of biopsy proven osteosarcomas were identified. Of which 64 were male and 31 females. There were 15 (15.8%) local recurrences. 71% (57/80) patients without LR fell in the age group of 10-20 years, while 66% (10/15) patients with LR were in the age group of 10-20 years. Limb salvage surgery was done in 81.05% (77/95) patients while a total of 18 patients underwent amputation. Of the 80 cases in Group I (without LR), 40 (50%) patients had tumor volume >200 c.c., 30 patients (37.5%) had tumor volume between 50 and 200 c.c. while only 10 patients had tumor volumes <50 c.c. This was in contrast to the tumor volume noted in Group II (with LR) of 15 patients where 8 patients had a tumor volume between 50 and 200 c.c., five had bigger tumor volumes of >200 c.c. and only two patients were smaller in size, with a tumor volume <50 c.c. The mean tumor volume in the group without LR was 406.74 ± 771.67 c.c. as compared with 195.77 ± 226.8 c.c. in the group with local recurrence. Using Mann‑Whitney test, the difference between the two groups was found to be statistically insignificant (P = 1.403). Conclusions: We conclude that high tumor volume is not a significant predictor of LR in osteosarcomas thus patients with high tumor masses should not be denied limb salvage. However, we recommend that the decision on attempting limb salvage should not only be based on the tumor volume alone. [ABSTRACT FROM AUTHOR]