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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., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

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., (© 2023. The Author(s).)

Background: Diagnostic delays in cancers are frequent in developing countries due to poor health infrastructure. Existing literature from developed countries suggests that diagnostic interval in bone sarcomas is primarily dictated by tumour biology with no impact on survival. This study evaluates the social and biological determinants of the diagnostic interval in bone sarcomas in a resource-challenged setting and assesses its impact on treatment outcomes., Methods: A retrospective single-institutional study was conducted on patients with high-grade bone sarcomas recorded in the sarcoma clinic database between 2003 and 2018. Baseline clinical characteristics and treatment outcomes were recorded. Logistic regression was performed to assess the impact of baseline clinical and social characteristics (distance from treating centre and rural vs. urban residence) on the diagnostic interval. Further, the impact of diagnostic interval on histologic response to neoadjuvant chemotherapy, amputation requirement in extremity sarcomas and survival was evaluated., Results: A total of 1227 patients were included for analysis. The median diagnostic interval was 4 months (3-7 months). Age above 18 years, Ewing sarcoma (ES) diagnosis, absence of fever at presentation and tumour size above 7.5 cm were predictors of a longer diagnostic interval (>4 months). The length of the diagnostic interval did not impact amputation requirement or survival outcomes. However, the proportion of patients with good necrosis post-neoadjuvant chemotherapy was lower among patients with longer diagnostic intervals (25% vs. 34·16%; p-value = .04)., Conclusion: Tumour characteristics rather than social factors determined the diagnostic interval. Diagnostic interval did not impact survival outcomes even in a resource-constrained setting., (© 2022 Wiley Periodicals LLC.)

Background: Early prediction of response to neoadjuvant chemotherapy (NACT) is important to aid personalized treatment in osteosarcoma. Diffusion-weighted Intravoxel Incoherent Motion (IVIM) MRI was used to evaluate the predictive value for response to NACT and survival outcome in osteosarcoma., Methods: Total fifty-five patients with biopsy-proven osteosarcoma were recruited prospectively, among them 35 patients were further analysed. Patients underwent 3 cycles of NACT (Cisplatin + Doxorubicin) followed by surgery and response adapted adjuvant chemotherapy. Treatment outcomes were histopathological response to NACT (good-response ≥ 50% necrosis and poor-response < 50% necrosis) and survival outcome (event-free survival (EFS) and overall survival (OS)). IVIM MRI was acquired at 1.5T at baseline (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Quantitative IVIM parameters (D, D*, f & D*.f) were estimated using advanced state-of-the-art spatial penalty based IVIM analysis method bi-exponential model with total-variation penalty function (BETV) at 3 time-points and histogram analysis was performed., Results: Good-responders: Poor-responders ratio was 13 (37%):22 (63%). EFS and OS were 31% and 69% with 16.27 and 25.9 months of median duration respectively. For predicting poor-response to NACT, IVIM parameters showed AUC = 0.87, Sensitivity = 86%, Specificity = 77% at t0, and AUC = 0.96, Sensitivity = 86%, Specificity = 100% at t1. Multivariate Cox regression analysis showed smaller tumour volume (HR = 1.002, p = 0.001) higher ADC-25 th -percentile (HR = 0.047, p = 0.005) & D-Mean (HR = 0.1, p = 0.023) and lower D*-Mean (HR = 1.052, p = 0.039) were independent predictors of longer EFS (log-rank p-values: 0.054, 0.0034, 0.0017, 0.0019 respectively) and non-metastatic disease (HR = 4.33, p < 10 -3 ), smaller tumour-volume (HR = 1.001, p = 0.042), lower D*-Mean (HR = 1.045, p = 0.056) and higher D*.f-skewness (HR = 0.544, p = 0.048) were independent predictors of longer OS (log-rank p-values: < 10 -3 , 0.07, < 10 -3 , 0.019 respectively)., Conclusion: IVIM parameters obtained with a 1.5T scanner along with novel BETV method and their histogram analysis indicating tumour heterogeneity were informative in characterizing NACT response and survival outcome in osteosarcoma., (© 2022. The Author(s).)

Osteosarcoma is a rare malignancy; however, it is still the most common primary bone tumor in adolescents and young adults. Chemotherapy improves survival indubitably in osteosarcoma; nevertheless, the concern is the stagnant progress since the last several decades. There are a handful of active agents and unresolved issues, especially in choosing the ideal chemotherapy regimen. The oncology community is in equipoise regarding the position of high-dose methotrexate (HDMTX), mandatory or adjunct. The choice of therapy becomes widely relevant, including in low- and middle-income countries (LMIC), where HDMTX administration brings additional complexities. Research into novel non-HDMTX-based protocols adapted to the available resources is pivotal in improving disease outcomes, especially in LMIC. The current review focuses on real-world challenges in decision-making and provides a comprehensive overview of the evolution of treatment protocols in LMIC., (© 2021 Wiley Periodicals LLC.)

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., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. Each author certifies that neither he, nor any member of his immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2021 by the Association of Bone and Joint Surgeons.)

Background and Objectives: Local control of disease is one of the main goals of osteosarcoma management. We conducted a retrospective evaluation of 95 operated cases of osteosarcoma over 7 years to know about the factors associated with local recurrence in resource-challenged environment of the developing world., Methods: The factors which were evaluated and compared between local recurrence and non-local recurrence groups included demographic profile, site of tumor, whether biopsy done outside, type of surgery (limb salvage or amputation), presence of pathological fracture, vicinity of neurovascular bundle, tumor volume, histological subtype, chemotherapy induced necrosis, surgical margins, and delay in surgery. The time to local recurrence after surgery was also noted in the local recurrence group., Results: At a mean follow-up of 2.8 years, biopsy done from outside the treating center and delay in surgery after completion of neo-adjuvant chemotherapy emerged as significant risk factors for local recurrence. Most of the local recurrences (80%) occurred within 12 months of the primary surgery., Conclusions: Lack of financial resources and availability of few tertiary care centers dealing with musculoskeletal oncology in the developing countries, lead to overburden with a long waiting list for tumor surgery making the scenario different from the Western world., (© 2017 Wiley Periodicals, Inc.)

Background: Studies of baseline prognostic factors in patients with localized osteosarcoma treated without high dose methotrexate are limited., Methods: This is single-institutional review of localized osteosarcoma patients treated without high dose methotrexate between June 2003-December 2012. A multivariate analysis of impact of baseline and treatment characteristics on outcome was performed and a prognostic model was developed based solely on baseline factors for predicting event-free survival (EFS) and overall survival (OS)., Results: Of 237 patients with median age of 17 years (range 2-66 yrs), neoadjuvant chemotherapy (NACT) was administered in 220 (92.82%) patients. Post NACT, 200/237 (84.38%) patients underwent surgery. At 30 months median follow-up, 5-year EFS and OS were 36.60 ± 0.03%, and 50.33 ± 0.04%, respectively. In multivariate analysis, baseline factors including duration of symptom >4 months (P < 0.001) and good performance status (PS) (P < 0.001) predicted better EFS whereas good PS (P = 0.01) and normal serum alkaline phosphatase (SAP) (P = 0.03) predicted better OS. The 5-year EFS without any risk factor (symptom duration <4 months, PS>1) was 58.7 ± 0.1%, with either one factor 31.5 ± 0.1% and with both factors 21.9 ± 0.1%. The 5-year OS without any risk factor (PS>1, elevated SAP) was 66.9 ± 0.1%, with either one factor 57.9 ± 0.1% and with both factors 25.6 ± 0.1%., Conclusions: This prognostic model assists in categorizing risk-groups within localized osteosarcoma., (© 2015 Wiley Periodicals, Inc.)

Purpose: A prospective study was undertaken to evaluate the diagnostic and prognostic significance of serum levels of vascular endothelial growth factor (VEGF) in patients with primary localised osteosarcoma., Methods: Serum VEGF levels were measured by an enzyme-linked immunosorbent assay (ELISA) in blood samples collected prechemotherapy, postchemotherapy, and postsurgery in 40 patients with histologically proven primary osteosarcoma. Comparison was made between serum VEGF level of healthy controls (n = 10) and prechemotherapy patient sera to evaluate its diagnostic potential. Serum VEGF levels of patients with and without metastasis were compared. Immunohistochemical staining was done to establish the correlation between serum and tissue VEGF expression. The Kaplan-Meier curve was used for survival analysis, Results: No significant relationship was observed between serum VEGF levels and age, gender, tumour size, local recurrence or histopathological subtypes of osteosarcoma. We observed significantly raised mean serum VEGF in patient sera compared with healthy controls (p = 0.001). Significant fall in mean serum VEGF level was observed following chemotherapy (p = 0.001). Patients who developed metastases had significantly higher serum VEGF levels compared with the nonmetastatic group (P = 0.001). Serum VEGF levels correlated well with VEGF expression in tissues., Conclusion: Serum VEGF levels might prove to be of diagnostic, predictive and prognostic value in patients with primary osteosarcoma, although further studies with larger sample size and longer follow-up is needed to support the hypothesis.

Background: The current standard for neoadjuvant chemotherapy (NACT) response evaluation in osteosarcoma is histopathologic necrosis (HN). However, it is accessible only after NACT completion and may get affected by confounding factors. Thus, noninvasive surrogate such as (18)Fluorine-Fluorodeoxyglucose-positron emission tomography-computerized tomography (PET-CT) scan would be useful to individualize therapy., Methods: Thirty-one treatment naive osteosarcoma patients evaluated prospectively by PET-CT scan preceding and after 3 cycles of NACT and surgery during 2006 to 2008. Various anatomic and metabolic parameters of PET-CT scan were compared with HN (good response ≥90% HN) as reference standard. Receiver operating characteristic curves were generated to assess the best threshold and predictability., Results: Median age was 17 years; 25 were male patients and 23 were nonmetastatic. Ten cases were good, whereas 21 cases were poor histologic responders. PET-CT parameters including post-NACT (2) and pre-NACT (1) standard uptake value (SUV)max ratio (SUV2:SUV1), SUV2, pre-NACT and post-NACT volumes (V1and V2), change in V after NACT, pre-NACT and post-NACT metabolic burden (MB) and change in MB after NACT correlated with HN. Two independent predictors were identified in stepwise multivariable analysis; if V1 ≤300 mL and SUV2:SUV1 ≤0.48, observed good histologic response proportions was 83%, whereas if V1 >300 mL and SUV2:SUV1 >0.48, it was 0%., Conclusions: NACT response can be predicted reliably by PET-CT scan early in disease course (even at baseline) and PET-CT parameters correlate well with HN. MB seems to be sensitive substitute for response evaluation. Independent predictors may have wider clinical applications if further validation can be done.

Background: Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy., Objective: To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease., Materials and Methods: Thirty-one treatment-naïve osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out., Results: Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume., Conclusion: In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma.

Purpose: Measurement of tumor angiogenesis by qualitative analysis of dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI), and its association with diffusion-weighted (DW)-MRI and glucose metabolism using positron emission tomography-computerized tomography (PET-CT) scan has not been explored in osteosarcoma. Present study was aimed to evaluate the potential of these surrogates., Patients and Methods: Thirty-one treatment naive patients with osteosarcoma underwent MRI and PET-CT preceding and following three cycles of neoadjuvant chemotherapy (NACT) and surgery. Time intensity curves (TICs) representing low microvascular permeability is persistent type while that of high permeability are plateau and washout types. Vascular endothelial growth factor (VEGF) expression was assessed in biopsy and resected specimens by immunohistochemistry. The sample was considered VEGF positive when intensive positive staining of VEGF was observed in >10% of the tumor cells in biopsy or resection specimens., Results: TIC could correctly identify all 28 VEGF positive samples at baseline and 24/25 (96%) of VEGF positive samples and 5/6 (83%) of VEGF negative samples after NACT. The change in curve pattern from washout/plateau to persistent type was in agreement with corresponding decrease in microvascular permeability, that is, VEGF expression. For persistent type of TIC, mean change in VEGF was 73.3 +/- 43.2% and for plateau and washout type of TIC it was 19.54 +/- 45% and 16.66 +/- 28.86%, respectively (P

Background: The vascular endothelial growth factor (VEGF) pathway is the key regulator of angiogenesis. In osteosarcoma baseline VEGF is of proven prognostic value but prognostic potential of post-NACT VEGF expression is largely unexplored., Procedure: Treatment naive patients with osteosarcoma were subjected to initial staging workup followed by three cycles of neoadjuvant chemotherapy (NACT) and surgery; resected tumors were assessed for histological necrosis by Huvos grading. Initial biopsy and resected tumor specimens post-NACT were examined for VEGF expression by immunohistochemistry. Positive VEGF expression was considered when intensive positive staining was observed in >10% of the tumor cells. VEGF expression at baseline was compared with grade of tumor; pre-NACT and post-NACT VEGF expression were compared with histological necrosis. Receiver operating characteristic curves were generated to assess best threshold and predictability., Results: A total of 31 patients were recruited with median age of 17 years (range 5-66 years); male/female ratio was 25:6; 23 patients (74%) were non-metastatic. At baseline, there was 90% concordance between positive VEGF expression and higher histological grade (28/31); baseline VEGF expression did not correlate well with stage and histological necrosis. Twenty-one (67%) were poor and 10 (33%) were good histologic responders; post-NACT VEGF expression as well as VEGF change following NACT significantly correlated with histological necrosis., Conclusion: Positive VEGF expression in surviving tumor cells post-NACT in resected tumors appears to be an important negative prognostic factor in osteosarcoma which may help future therapies to be identified according to the angiogenic potential of the disease.

Background: There is controversy regarding the patterns and prognostic significance of Her-2/neu and p-53 expression in osteosarcoma. Further, their combined expression has not been studied., Procedure: Prechemotherapy biopsy specimens of 63 osteosarcoma patients from June 2004 to August 2006 were analyzed for Her-2/neu and p-53 using immunohistochemistry and compared with grade, stage, and morphologic subtype of tumor., Results: There were 59 high-grade tumors; 32 of 63 had metastases. Histopathologic types included 36 of 63 osteoblastic and 18 of 63 chondroblastic subtypes. Male sex (P=0.045) and chondroblastic type (P=0.004) were associated with metastatic disease. Her-2/neu cytoplasmic staining was seen in 30 of 63 (47.1%) cases, 4 of 30 had additional membranous staining, 17 of 30 were metastatic, and 29 of 30 were high-grade tumors. Staining grade was 3+ in 10 of 30 samples whereas staining intensity 3+ was observed in 26 of 30 samples. Her-2/neu 3+ staining grade was significantly associated with chondroblastic subtype (6/18, P=0.026). P-53 staining was seen in 20 of 63 (31.74%) cases (all high grade), of which 11 were metastatic. Staining grades 3+ and 4+ were seen in 16 of 20 samples whereas staining intensity 3+ in 13 of 20 samples. P-53 expression was higher in chondroblastic (7/18, P value was not significant) and fibroblastic (3/3, P<0.05) subtypes. Coexpression of Her-2/neu and p-53 was seen in 10 cases (15.87%); 3 of 10 cases showed Her-2/neu membranous staining (P=0.01)., Conclusions: Her-2/neu (47.1%), p-53 (31.74%), and their combined expression (15.87%) were not related to grade or stage of tumor. Chondroblastic subtype was associated with staining grade 3+ of Her-2/neu staining whereas coexpression of Her-2/neu and p-53 was significantly associated with membranous Her-2/neu staining.

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.

Introduction: The outcomes of osteosarcoma in low middle income countries (LMICs) are different due to patients presenting in advanced stages, resource constraints and the use of non-high-dose-methotrexate (HDMTX)-based regimens. This study derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol. Materials and methods: A retrospective study including osteosarcoma patients enrolled for treatment at a single tertiary care centre in India between 2003-19 was conducted. Baseline biologic and social characteristics were extracted from medical records and survival outcomes were noted. The cohort was randomised into a derivation and validation cohort. Multivariable Cox regression was used to identify baseline characteristics that were independently prognostic for survival outcomes in the derivation cohort. A score was derived from the prognostic factors identified in the derivation cohort and further validated in the validation cohort with estimation of its predictive ability. Results: 594 patients with osteosarcoma were eligible for inclusion in the study. Around one-third of the cohort had metastatic disease with 59% of the patients residing in rural areas. The presence of metastases at baseline (HR 3.39; p<0.001; score=3), elevated serum alkaline phosphatase (SAP) >450 IU/L (HR 1.57; p=0.001; score=1) and baseline tumour size > 10 cm (HR 1.68; p<0.001; score=1) were identified to be independent factors predicting inferior event free survival (EFS) and were included in development of the prognostic score. Patients were categorized as low risk (score 0), intermediate risk (score 1-3) and high risk (4-5). Harrell's cindices for the score were 0.682, 0.608 and 0.657 respectively for EFS in the derivation, validation and whole cohort respectively. The timed AUC of ROC was 0.67 for predicting 18-month EFS in the derivation, validation and whole cohorts while that for 36-month EFS were 0.68, 0.66 and 0.68 respectively. Conclusions: The study describes the outcomes among osteosarcoma patients from an LMIC treated uniformly with a non-HDMTX-based protocol. Tumor size, baseline metastases and SAP were prognostic factors used to derive a score with good predictive value for survival outcomes. Social factors did not emerge as determinants of survival. [ABSTRACT FROM AUTHOR]

It has been indicated in several instances that tall stature is also an important risk factor in the development of osteosarcoma. This relationship between height and osteosarcoma is substantiated even more by the increasing evidences being put forth in the recent literature on dependence of certain tumors on the growth factors and their receptors, acting through autocrine or paracrine mechanisms. There has been no study on the Indian population that attempts to define such a relationship. The primary objective of this study was to define relationship between height of patients and osteosarcoma at the time of diagnosis in the Indian population. Retrospective data was collected from the old hospital records. Height of patients at the time of diagnosis was compared with expected height of patients of the same age with reference to the standardized growth charts provided by the Indian Academy of Paediatrics. Out of 98 patients, there were 65 male and 33 female patients with M: F ratio being 1.97:1. The mean age at diagnosis was 17 (SD = 8) years with range of 5–55 years (median = 17 years). Height of the patients at the time of diagnosis was 155.18 (SD = 15.47) cm with range of 115 cm–184 cm (median = 159 cm). Overall, patients with Osteosarcoma were found to be shorter than the expected height deduced from the national growth charts. When patients were divided into two groups of those who were of growing age and those who had completed growth, results were similar. The observation that majority of patients with osteosarcoma in our study were stunted, is an important finding. It could be deduced from this observation that these patients are unable to mount the usual biological response to the overstimulated growth as part of tumorigenesis in osteosarcoma. This could point to a different scenario in the Indian population and more studies need to be carried out with larger number of patients to further elaborate on this observation. [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]

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]