Diagnosis Of Osteosarcoma Research Articles

Single-Cell Profiling of Tumor Microenvironment Heterogeneity in Osteosarcoma Identifies a Highly Invasive Subcluster for Predicting Prognosis.

Osteosarcoma is the most common malignant bone tumor in adolescents, and metastasis is the key reason for treatment failure and poor prognosis. Once metastasis occurs, the 5-year survival rate is only approximately 20%, and assessing and predicting the risk of osteosarcoma metastasis are still difficult tasks. In this study, cellular communication between tumor cells and nontumor cells was identified through comprehensive analysis of osteosarcoma single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, illustrating the complex regulatory network in the osteosarcoma microenvironment. In line with the heterogeneity of osteosarcoma, we found subpopulations of osteosarcoma cells that highly expressed COL6A1, COL6A3 and MIF and were closely associated with lung metastasis. Then, BCDEG, a reliable risk regression model that could accurately assess the metastasis risk and prognosis of patients, was established, providing a new strategy for the diagnosis and treatment of osteosarcoma.

Long-term survival of two patients with inoperable post-irradiation osteosarcoma treated with carbon-ion radiotherapy: a case report

BackgroundCurative treatment of inoperable post-irradiation sarcoma is often challenging, especially using radiotherapy, wherein curative dose administration is difficult because the organs around the tumor have already been irradiated during the first cancer treatment. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of post-irradiation sarcomas because it allows re-irradiation with high-dose localization properties and also demonstrates higher cytotoxic effects on radioresistant tumors compared with X-rays. This study presents the long-term survival of two patients with inoperable post-irradiation pelvic osteosarcoma treated with C-ion RT after uterine cervical cancer treatment.Case presentationThe durations from prior radiotherapy to the diagnosis of post-irradiation osteosarcoma were 112.8 and 172.2 months, respectively. Both patients received 70.4 Gy (relative biological effectiveness) in 16 fractions of C-ion RT, and chemotherapy was performed before and after C-ion RT. Both patients achieved a complete response 1 year after the initiation of C-ion RT. However, one patient developed single lung metastasis 12.6 months after the initiation of C-ion RT and underwent thoracoscopic lobectomy. After 63.7 and 89.0 months from the initiation of C-ion RT, respectively, the patients were alive with no evidence of local recurrence, other distant metastasis, or fatal toxicities.ConclusionsThe study findings suggest that C-ion RT is a suitable treatment option for inoperable post-irradiation osteosarcoma.

Web-Based Patient Educational Material on Osteosarcoma: Quantitative Assessment of Readability and Understandability.

BackgroundPatients often turn to web-based resources following the diagnosis of osteosarcoma. To be fully understood by average American adults, the American Medical Association (AMA) and National Institutes of Health (NIH) recommend web-based health information to be written at a 6th grade level or lower. Previous analyses of osteosarcoma resources have not measured whether text is written such that readers can process key information (understandability) or identify available actions to take (actionability). The Patient Education Materials Assessment Tool (PEMAT) is a validated measurement of understandability and actionability.ObjectiveThe purpose of this study was to evaluate web-based osteosarcoma resources using measures of readability, understandability, and actionability.MethodsUsing the search term “osteosarcoma,” two independent Google searches were performed on March 7, 2020 (by AGS), and March 11, 2020 (by TRG). The top 50 results were collected. Websites were included if they were directed at providing patient education on osteosarcoma. Readability was quantified using validated algorithms: Flesh-Kincaid Grade Ease (FKGE), Flesch-Kincaid Grade-Level (FKGL). A higher FKGE score indicates that the material is easier to read. All other readability scores represent the US school grade level. Two independent PEMAT assessments were performed with independent scores assigned for both understandability and actionability. A PEMAT score of 70% or below is considered poorly understandable or poorly actionable. Statistical significance was defined as P≤.05.ResultsTwo searches yielded 53 unique websites, of which 37 (70%) met the inclusion criteria. The mean FKGE and FKGL scores were 40.8 (SD 13.6) and 12.0 (SD 2.4), respectively. No website scored within the acceptable NIH or AHA recommended reading level. Only 4 (11%) and 1 (3%) website met the acceptable understandability and actionability threshold. Both understandability and actionability were positively correlated with FKGE (ρ=0.55, P<.001; ρ=0.60, P<.001), but were otherwise not significantly associated with other readability scores. There were no associations between readability (P=.15), understandability (P=.20), or actionability (P=.31) scores and Google rank.ConclusionsOverall, web-based osteosarcoma patient educational materials scored poorly with respect to readability, understandability, and actionability. None of the web-based resources scored at the recommended reading level. Only 4 achieved the appropriate score to be considered understandable by the general public. Authors of patient resources should incorporate PEMAT and readability criteria to improve web-based resources to support patient understanding.

Osteosarcoma of the jaws: A case report.

IntroductionOsteosarcomas of the jaws are very rare accounting for only 6 to 7% of all osteosarcomas and 1% of all head and neck malignancies.The clinicopathological characteristics as well as the radiological characteristics are not specific, which represents a diagnostic dilemma. Indeed, this lesion is often mistaken for benign lesions of the maxillary.Case presentationWe report a case of osteosarcoma of the jaws in a 45 year man who consulted in our service for a simple painless oral swelling evolving since a five months.The lesion was excised and histopathological report confirmed the diagnosis of osteosarcoma of the jaw.DiscussionOsteosarcomas are a rarely progressive tumor in the oral cavity that can show up as a case of a benign process of dental origin. During our practice, we often meet similar cases which are treated by usual medication, while a whole malignant process is in the progress and can be life-threatening. The case we present illustrates this perfectly, and owing to a deep clinical investment, the malignant process was stopped at its start.ConclusionThe objective of presenting this case is to draw the attention of the doctors that any lesions even of benign appearance can hide a malignant process. Consider this point and integrate it into its diagnostic approach should be undertaken and should lead to a deepening of the clinical examination by comparing the clinical, radiological and histological data.

Outpatient Opioid Prescribing Habits in Pediatric Patients With Bone Sarcomas After Undergoing Primary Tumor Resection.

The majority of children with bone sarcomas experience pain. Opioids remain the mainstay treatment of cancer-related pain in children. The patterns of outpatient opioid prescription after surgery for primary bone sarcomas remains unknown. The purpose of this study is to evaluate the patterns of outpatient opioid prescription in patients with bone sarcomas after resection of the primary tumor, and to assess for factors that may lead to increased opioid dosing in these patients. A retrospective chart review of 28 patients with bone sarcomas undergoing primary tumor resection was performed. Demographic, medical, surgical, and pharmacological data was collected from all patients. The total morphine milligram equivalents (MMEs) prescribed after patient discharge were compared at 30-day intervals. The MMEs were then stratified by tumor location, presence of metastasis at time of surgery, and preoperative opioid use. Independent predictors of increased 30-day and total 120-day opioid utilization were evaluated. Patients with preoperative opioid use were prescribed significantly more opioids in every 30-day postoperative interval and for the 120-day total. When stratified by tumor location, patients with primary tumors in the pelvis had significantly greater postoperative opioid utilization when compared with patients with tumors located in the lower and upper extremities during postoperative days 61 to 90 (5970 vs. 1060.4 and 0 MMEs, respectively, P=0.048) and during postoperative days 91 to 120 (6450 vs. 829.6 and 0 MMEs, respectively, P=0.015). Older age, diagnosis of osteosarcoma, increased length of stay postoperatively and presence of metastases were associated with a higher 30-day postoperative opioid utilization. Multiple factors were associated with increased opioid use including preoperative opioid use, longer postoperative stay in the hospital, metastatic disease, and primary sarcomas in the pelvis. The patient's sex, body mass index, race, type of insurance, type of surgery performed, reoperation during the same admission and use of nonopioid adjuvants had no effect on opioid use. The results of this study can be used to stratify the average opioid requirement of pediatric patients undergoing primary bone sarcoma resection. Level IV.

Identification of key serum biomarkers for the diagnosis and metastatic prediction of osteosarcoma by analysis of immune cell infiltration

BackgroundThe role of circular RNAs (circRNAs) and microRNAs (miRNAs) in osteosarcoma (OS) development has not been fully elucidated. Further, the contribution of the immune response to OS progression is not well defined. However, it is known that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. Thus, the aim of this study was to identify novel key serum biomarkers for the diagnosis and metastatic prediction of OS by analysis of immune cell infiltration and associated RNA molecules.MethodsHuman OS differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by analysis of microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Further, characteristic patterns of OS-infiltrating immune cells were analyzed. On this basis, we identified statistically significant transcription factors. Moreover we performed pathway enrichment analysis, constructed protein–protein interaction networks, and devised competitive endogenous RNA (ceRNA) networks. Biological targets of the ceRNA networks were evaluated and potential OS biomarkers confirmed by RT-qPCR analysis of the patients’ serum.ResultsSeven differentially expressed circRNAs, 166 differentially expressed miRNAs, and 175 differentially expressed mRNAs were identified. An evaluation of cellular OS infiltration identified the highest level of infiltration by M0 macrophages, M2 macrophages, and CD8+ T cells, with M0 macrophages and CD8+ T cells as the most prominent. Significant patterns of tumor-infiltrating immune cells were identified by principal component analysis. Moreover, 185 statistically significant transcription factors were associated with OS. Further, in association with immune cell infiltration, hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A were identified as potential novel biomarkers for OS diagnosis. Of these, FAM98A had the most promise as a diagnostic marker for OS and OS metastasis. Most importantly, a novel diagnostic model consisting of these four biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was established with a 0.928 AUC value.ConclusionsIn summary, potential serum biomarkers for OS diagnosis and metastatic prediction were identified based on an analysis of immune cell infiltration. A novel diagnostic model consisting of these four promising serum biomarkers was established. Taken together, the results of this study provide a new perspective by which to understand immunotherapy of OS.

Response to neoadjuvant chemotherapy and survival of children and adolescents with high-grade osteosarcoma treated based on the EURAMOS-1 protocol.

High-grade osteosarcoma is the most common malignant bone tumor in children and adolescents. This study aimed to evaluate the histologic response to neoadjuvant chemotherapy and overall and event-free survival rates in patients < 21 years of age with a diagnosis of conventional osteosarcoma. We conducted an analytical and observational study of a cohort of patients < 21 years old with a diagnosis of conventional osteosarcoma treated with the OS INC-2009 protocol (based on EURAMOS-1). Descriptive analysis was performed, and overall and event-free survival rates were calculated by the Kaplan-Meier method. Between April 2009 and October 2016, 84 patients with conventional osteosarcoma (mean age 13.5 ± 3.2 years) were admitted. Metastatic disease at diagnosis was observed in 36 patients (42.8%). Of the 41 patients who received neoadjuvant chemotherapy (50.6%), 15 (36.6%; confidence interval [95% CI]: 49.9-75.6) were classified as good responders and 26 (63%; 95% CI: 22.5-58.0) as poor responders. The 5-year overall and event-free survival rates in good responders were 88.8% (95% CI: 43.3-98.3) and 81.4% (95% CI: 43.5-95.0); in poor responders it was 66.5% (95% CI: 40.7-83.1) and 31.4% (95% CI: 13.8-50.7), respectively. Good responders' evaluation of histologic response to neoadjuvant chemotherapy showed improved overall and event-free survival rates. Specialized centers with multidisciplinary and comprehensive management are required to make the application of high-toxicity protocols feasible.

Research Progress of Exosome-Loaded miRNA in Osteosarcoma.

Currently, although the improvement of surgical techniques and the development of chemotherapy drugs have brought a certain degree of development to the treatment of osteosarcoma, the treatment of osteosarcoma has many shortcomings, and its treatment is limited. MiRNAs and exosomes can be used as diagnostic tools, and they play an important role in the occurrence and chemotherapy resistance of osteosarcoma. Therefore, providing a new method for the treatment of osteosarcoma is the key to solving this problem. To systematically summarize the research status of exoskeleton drug-loaded miRNA in osteosarcoma, we identified and evaluated 208 studies and found that exosome-carrying miRNA can be used as an index for the diagnosis and prognosis of osteosarcoma and share a certain relationship with chemosensitivity. In addition, exosomes can also be used as a carrier of genetic drugs able to regulate the progression of osteosarcoma. Based on the above findings, we propose suggestions for the future development of this field, aiming to bring new ideas for the early diagnosis and treatment of osteosarcoma.

Serum level of miR-217 predicts prognostic outcome for osteosarcoma patients in China

In this study, we aimed to investigate the expression of miR-217 in osteosarcoma and adjacent tissues, and its relationship with clinical features, and thus provide a scientific basis for the diagnosis and treatment of osteosarcoma. Sixty patients with osteosarcoma who underwent radical osteosarcoma resection in our hospital in China from January to December 2015 were selected. Real-time reverse transcription PCR (qRT-PCR) was used to detect the expression of miR-217 in osteosarcoma and parasarcoma tissues. Its correlation with clinical data and prognosis of patients was analyzed. Our results showed that the average expression level of miR-217 in osteosarcoma tissues (2.94 ± 0.79) was higher than that of parasarcoma tissues (2.14 ± 0.66) (P <0.05). The difference between the expression level of miR-217 in osteosarcoma tissue and pathological grade (P = 0.034) and clinical stage (P = 0.007) was statistically significant. Cox multivariate analysis showed that clinical stage (HR = 4.135, 95% CI = 1.682-6.236) and miR-217 (HR = 3.764, 95% CI = 1.572-5.921) are independent risk factors that affect the prognosis of osteosarcoma (P < 0.05). In conclusion, miR-217 plays a key regulatory role in the occurrence and progression of osteosarcoma. Serum miR-217 levels can predict the prognosis of osteosarcoma patients.

Hsa_circ_0087302, a circular RNA, affects the progression of osteosarcoma via the Wnt/β-catenin signaling pathway.

Osteosarcoma is the most common malignant tumor in adolescent bone malignancies. It has the characteristics of a high metastasis rate, high mortality and poor prognosis. As a subclass of endogenous noncoding RNAs, circRNAs have been identified to be related to the occurrence, development and prognosis of different kinds of cancers, but the mechanism of their effect on osteosarcoma is not clear. In the present study, we identified a novel circRNA, hsa_circ_0087302, by RNA-seq, and we found that it was expressed at low levels in osteosarcoma. Using RT-PCR, we confirmed that the expression of hsa_circ_0087302 in osteosarcoma cells was lower than that in osteoblasts. Functional validation experiments revealed that hsa_circ_0087302 overexpression inhibited proliferation, cell cycle, migration, and invasion in osteosarcoma cells. Furthermore, Western blotting experiments demonstrated that hsa_circ_0087302 affected the expression of cell cycle- and Wnt/β-catenin signaling pathway-related proteins. For the first time, we identified that hsa_circ_0087302 may affect the malignant biological behavior of osteosarcoma cells through the Wnt/β-catenin signaling pathway. In summary, hsa_circ_0087302 may provide a new direction for the diagnosis and treatment of osteosarcoma.

Role of extracellular vesicles in osteosarcoma.

Osteosarcoma is a malignant bone tumor characterized by the direct production of osteoid tissue from tumor cells. Extracellular vesicles are membranous vesicles released by cells into the extracellular matrix, which exist widely in various body fluids and cell supernatants, and stably carry some important signaling molecules. They are involved in cell communication, cell migration, angiogenesis and tumor cell growth. Increasing evidence has shown that extracellular vesicles play a significant role in osteosarcoma development, progression, and metastatic process, indicating that extracellular vesicles can be use as biomarker vehicles in the diagnosis and prognosis of osteosarcoma. This review discusses the basic biological characteristics of extracellular vesicles and focuses on their application in osteosarcoma.

Jaw osteosarcoma and pregnancy: a rare coexistence.

ABSTRACTOsteosarcoma of the jaw represents less than 1% of all head and neck malignancies. This malignancy in pregnant women occurs in one per 1000 deliveries. We report a case of a 29-year-old woman, in the 33rd week of gestation, who presented with an expansive tumor destroying the maxillary alveolar bone, histologically composed of pleomorphic, round, spindle, or epithelioid cells and osteoid/chondroid matrix. Upon final diagnosis of osteosarcoma, the lesion was excised. To the best of our knowledge, only 10 cases of jaw osteosarcoma in pregnant women have been reported to date in the English language literature. The use of ancillary examinations, malignancy diagnosis, and cancer treatment can be challenging during pregnancy. Knowledge about jaw osteosarcoma in pregnancy can increase healthcare providers’ awareness, avoid delays and misdiagnosis and potentially improve maternal and neonatal outcomes.

Osteosarcoma of Jaw Masquerading as Calcifying Epithelial Odontogenic Tumour- A Diagnostic Dilemma

Osteogenic osteosarcoma is the most widely recognised primary malignant bone tumour involving particularly the appendicular skeleton. Osteosarcoma of jaw including maxillary and mandibular osteosarcoma accounts for about 7% of cases. The variants of osteosarcoma involving jaw include- osteosarcoma, Not Otherwise Specified (NOS) Low grade central osteosarcoma; chondroblastic osteosarcoma; parosteal osteosarcoma; periosteal Osteosarcoma. The present case was a 27-year-old male who came to the dental Outpatient Department (OPD) with the complaints of swelling in the upper vestibule and loosening of upper alveolar teeth and was reported as Calcifying Epithelial Odontogenic Tumour (CEOT) on histopathological examination and excision of the lesion was done. After two months the patient again presented with a recurrent lytic and sclerotic lesion involving the left maxillary bone with soft tissue extension in the maxillary sinus. Provisional diagnosis was made as malignant transformation of CEOT and immunohistochemistry was performed for the confirmation of the diagnosis. This case represented the challenges in the diagnosis of osteosarcoma of jaw which can be due to difficult biopsy procedure; limited imaging and challenges in legitimate resection because of the proximity to essential structures and the challenges are being faced to get the optimal treatment of jaw osteosarcoma.

Proximal Tibial Osteosarcoma in Pediatric Patient: A Case Report

Background: The most frequent primary malignant bone tumor in children is osteosarcoma. Patients with osteosarcoma are currently treated with a combination of neoadjuvant and adjuvant chemotherapy as well as surgery, either limb-sparing surgery or limb-ablation surgery. How to manage the remaining bone growth during the limb-sparing procedure in youngsters is one of the challenges. Unfortunately, amputation is still many perform for OS patients. The purpose of this study was to inform and educate doctors about the value of early OS diagnosis and treatment in pediatric patients. Case Presentation: We presented case from a male 16 years old Balinese complaint of pain on her left knee 12 months ago. The pain was continuous and got worse at night. The patient went to a traditional masseuse and was given topical herbal ointment. Three months later, a lump appeared on her knee at the size of a small ball and getting bigger. We did a review slide of the previous biopsy sample by the pathology of anatomy in our hospital. The result came out as osteosarcoma with osteoblastic cells. We performed to amputated the limb-affected tumor following wound care routinely controlled. Results: Intraoperatively, we performed wide excision, without patellar tendon, medial collateral ligament, and cruciate ligament preserve. We amputated the limb-affected tumor. The patient routinely controlled to our outpatient clinic every week. Unfortunately, the patient was died after 3 weeks of admission. Conclusion: To reduce the risk of misdiagnosis or delayed diagnosis of osteosarcoma, every source of knee pain with a mass in pediatric age groups should be thoroughly explored with a high index of suspicion for malignant lesions. Therefore, amputation is a cutting-edge osteosarcoma treatment that can be avoided if the patient can be identified early and treated quickly in pediatric oncology malignant instances. Keywords: osteosarcoma, long bone, diagnosis, tibia, pediatric Correspondence: Komang Septian Sandiwidayat. Oncology Division, Department of Orthopaedic &amp; Traumatology, Sanglah General Hospital, Faculty of Medicine, Udayana University, Bali, Indonesia. Email: drseptianortho@gmail.com. Mobile: 62-821-4725-2042. Indonesian Journal of Medicine (2022), 07(03): 298-305 https://doi.org/10.26911/theijmed.2022.07.03.06

Paraplegia Caused by Multifocal Osteosarcoma With Spinal Lesions.

Multifocal osteosarcoma is a rare condition that may be either synchronous or metachronous. Spine involvement of multifocal osteosarcoma is very rare. Synchronous multifocal osteosarcoma is typically described as the occurrence of tumors at two or more sites in the absence of pulmonary metastases. A 55-year-old man initially presented with low back pain. Multiple osteosclerotic lesions were observed, primarily in the spine and pelvis, as well as in soft tissues. Lung lesions were observed, but they were relatively small at reference. Laboratory tests showed a markedly elevated alkaline phosphatase (ALP) level of 36,416 U/L (normal range, 115-359 U/L). Based upon a diagnosis of osteosarcoma on biopsy, chemotherapy was administered, resulting in a decrease in ALP to 17,833 U/L. Decompression of the symptomatic compressed spinal cord and posterior spinal stabilization of T8-12 were performed. However, progressive extensions of multiple lesions to the spinal canal led to paraplegia with urinary dysfunction. Eleven months after the first visit to our hospital, the patient died due to multiple organ failure. Multifocal osteosarcoma accompanied by spinal lesions may lead to paraplegia, a clinical problem that negatively affects the quality of activities of daily living. 4. Multifocal osteosarcoma accompanied by spinal lesions may lead to paraplegia, a clinical problem that negatively affects the quality of life and activities of daily living.

High grade tibiofibular canine osteosarcoma in a 5-year-old female rottweiler

Osteosarcoma is a common neoplastic condition of the bone mostly affecting the appendicular bones in dogs. A five-year-old female Rottweiler was presented with a swollen left hind limb. Haematology showed mild nonregenerative anaemia, severe leukocytosis, and moderate neutrophilia with-out left shift, monocytosis, and severe lymphopenia. Fine needle aspirate (FNA) cytology revealed oval to spindle cells with marked cellular pleomorphism, anisocytosis, binucleation, and proteinaceous granules in the background while radiographic examination revealed osteolysis of the tibia and fibular with new bone formation. These findings are consistent with osteosarcoma. A diagnosis of osteosarcoma was made, based on the cytology and radiography. Surgical amputation of the complete left limb was carried out. However, the dog died of leptospirosis one month later. Post mortem examination revealed pulmonary metastasis of the osteosarcoma. Histopathology of the limb growth revealed oval to spindle cells with intracytoplasmic eosinophilic materials and osteoid matrix. Diagnosis and treatment of dogs affected by osteosarcoma should be comprehensive and complete, with adequate follow-up. The marked lymphopenia could be associated with poor prognosis, therefore an index for prognosis in osteosarcoma. The mortality, in this case, could have been related to leptospirosis and associated with the immunosuppression from tumour metastasis.

A Novel Pyroptosis-Related Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Osteosarcoma.

Osteosarcoma is a common malignant bone tumor with a propensity for drug resistance, recurrence, and metastasis. A growing number of studies have elucidated the dual role of pyroptosis in the development of cancer, which is a gasdermin-regulated novel inflammatory programmed cell death. However, the interaction between pyroptosis and the overall survival (OS) of osteosarcoma patients is poorly understood. This study aimed to construct a prognostic model based on pyroptosis-related genes to provide new insights into the prognosis of osteosarcoma patients. We identified 46 differentially expressed pyroptosis-associated genes between osteosarcoma tissues and normal control tissues. A total of six risk genes affecting the prognosis of osteosarcoma patients were screened to form a pyroptosis-related signature by univariate and LASSO regression analysis and verified using GSE21257 as a validation cohort. Combined with other clinical characteristics, including age, gender, and metastatic status, we found that the pyroptosis-related signature score, which we named “PRS-score,” was an independent prognostic factor for patients with osteosarcoma and that a low PRS-score indicated better OS and a lower risk of metastasis. The result of ssGSEA and ESTIMATE algorithms showed that a lower PRS-score indicated higher immune scores, higher levels of tumor infiltration by immune cells, more active immune function, and lower tumor purity. In summary, we developed and validated a pyroptosis-related signature for predicting the prognosis of osteosarcoma, which may contribute to early diagnosis and immunotherapy of osteosarcoma.

Construction and Validation of a Potent Epigenetic Modification-Related Prognostic Signature for Osteosarcoma Patients.

Background Increasing evidence has shown that tumorigenesis correlates with aberrant epigenetic factors, such as DNA methylation, histone modification, RNA m6A modification, RNA binding proteins, and transcription factors. However, it is unclear that how epigenetic genes linked with alteration contribute to osteosarcoma's incidence and clinical prognosis. We developed an epigenetic modification-related prognostic model that may improve the diagnosis and prognosis of osteosarcoma. Methods We investigated the epigenetic modification-associated genes and their clinical significance in osteosarcoma in this research. Our gene transcriptome data were obtained from the TARGET database and the GEO database. Bioinformatics techniques were used to investigate their functionalities. The diagnostic and prognostic models were constructed using univariate and multivariate Cox regression. In addition, we developed a nomogram indicating the practicability of the prognostic model described above. Results A risk score model constructed based on four epigenetic modification-related genes (MYC, TERT, EIF4E3, and RBM34) can effectively predict the prognosis of patients with osteosarcoma. Based on the risk score and clinical features, we constructed a nomogram. Conclusion Epigenetic modification-related genes have been identified as important prognostic markers that may assist in osteosarcoma therapy therapeutic decision-making.

Abstract 11127: Clinical Heart Failure Events After Doxorubicin Treatment in High Grade Osteosarcoma Patients

Introduction: Osteosarcoma patients are at high risk of developing an anthracycline-induced cardiomyopathy (AC-CMP) due to their cancer treatment. The purpose of the study was to evaluate incidence of heart failure (HF) in this specific population and to identify predictors of HF. Methods: We conducted a retrospective cohort study at a tertiary sarcoma center (timeframe: 1982-2017) among 400 high grade osteosarcoma patients whom underwent surgery and received chemotherapy. Relevant data on demographics, cardiovascular risk profile, medications, osteosarcoma diagnosis and treatment was acquired from the electronic healthcare records and local oncology clinical registry. The primary endpoint was the composite of initiation of HF medication, hospitalization for HF and ICD implantation as primary prevention of sudden cardiac death in reduced left ventricular function. Results: The median age at sarcoma diagnosis in our cohort was 19 [p25-p75: 15-32] years with a median follow up time of 6 [2-14] years. At baseline, few patients used any medication or had cardiovascular risk factors: resp. 5 (1.3%) and 15 (3.8%). The endpoint occurred in 5.8% (23 patients). In 10 patients (2.5%) an admission for decompensated HF was the first presentation of AC-CMP, and ICD-implantation due to a reduced left ventricular ejection fraction occurred in 4 patients (1%). When sarcoma was diagnosed after 30 years of age, patients had near 5-fold increased risk of reaching the primary endpoint within 10 years after diagnosis (competing risk regression with competing risk of death due to malignancy: SHR 5.8 [2.0-16.9], p =0.001) and the time to a first HF event was shorter than younger patients: 3.4 [0.8-7.9] vs. 11.7 [5.2-16.0] years, p =0.027. Conclusions: The risk of developing HF in sarcoma patients is substantial, which warrants close monitoring during treatment and long term follow-up. Older age at diagnosis is associated with higher risk of developing HF and a shorter duration to events.

CAN SERUM KL-6 LEVEL BE USED AS A MARKER IN LUNG METASTASIS OF BONE SARCOMAS?

Osteosarcoma and Ewing sarcoma are the most common bone sarcomas of the childhood. Kerbs von de Lungren 6 (KL-6) is a glycoprotein that is expressed on type 2 pneumocytes and bronchial epithelium. Serum KL-6 level can increase in many interstitial pulmonary diseas and lung cancers. Aim of the study is to evaluate the predictive value of serum KL-6 level on malign potential of pulmonary nodules in pediatric patients with bone sarcoma with pulmonary metastasis or with vague pulmonary nodules. Blood samples were taken from patients with diagnosis of Ewing sarcoma or osteosarcoma at the time of diagnosis or first relapses. Control group was selected from 42 voluntary children without any chronic or acute diseases associated with lung. Serum of the blood samples were separated and frozen at -70 C˚ and KL-6 level was measured via ELISA method. Thorax computed tomography (CT) images of the patients were analyzed to interpret about pulmonary metastasis. Total 47 patients were included in the study, 19 of the patients were with Ewing sarcoma and 28 with osteosarcoma.Thorax CT revealed pulmonary metastasis in 9 of the patients at first evaluation. KL-6 level of the these patients with pulmonary metastasis was greater than without metastasis (p;0.05) and control group (p;0.019). Patients with pulmonary nodule at any time had significantly higher serum KL-6 level at first evaluation than without metastasis (p; 0.04) and control group (p;0.017). In our study we found serum KL-6 level higher in patients with pulmonary nodules that relevant with pulmonary sarcoma metastasis than patients without metastasis and healthy control group. Our study also revealed that patients that had pulmonary metastasis during their follow-up also had higher KL-6 level at diagnosis. These results should be proven with more number of patients. Measuring KL-6 level may be used as a marker for early diagnosis of pulmonary sarcoma metastasis.