Epidemiology of bone tumors in children and adolescents: a retrospective study of 266 patients in the south of Tunisia.

Although bone tumors (BT) are relatively uncommon among the human neoplasm, they constitute the most frequent tumors in children and adolescents (CAA). Little information is available about the epidemiologic features of BT in CAA. We aimed to present and discuss epidemiological characteristics of BT in CAA in southern Tunisia, regarding the different histological types. This is a retrospective study including cases of BT in CAA collected in the pathology department at the Habib Bourguiba university hospital over a period of 15 years (2006- 2020). A total of 266 BT was diagnosed in our institution (42,7% among all BT in Southern Tunisia) divided into 200 benign bone tumors (BBT) (75,2%) and 66 malignant bone tumors (MBT) (24,8%). The mean age for all BT was 14,2 years (3-20 years) with male predominance (sex ratio: 1,48). The most common tumor was osteochondroma (42.2%) followed by osteosarcoma (14.6%) and Ewing sarcoma (6.4%). For BBT, the most affected age group was the 16 to 20 year - old - group (50,7%) with a male predominance (59.8%) and a predilection for lower limb (66.8%) then the upper limb (16,8%). Osteochondroma was the most common histological type (56.5%) followed by aneuvrysmal cyst (8,5%) and osteoid osteoma (6,5%). For MBT, the mean age was 12,5 years (5-20 years) and the most affected age group was the 11 to 15 year -old -group (59%). Boys were more affected (60.6%), with a preference for the lower limb (57%) followed by the pelvis (15,6%). Osteosarcoma was the most common MBT (60%) followed by Ewing sarcoma (24%). Given their rarity and heterogeneity, the diagnosis of BT is particular in CAA and requires a multidisciplinary approach. The reporting of epidemiological studies remains essential in order to expand our knowledge regarding these uncommon tumors.

Li-Fraumeni-associated osteosarcomas: The French experience.

PURPOSE: Describe clinical characteristics and outcome of Li-Fraumeni syndrome (LFS)-associated osteosarcomas. METHODS: TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) for patients of the same age group. RESULTS: Median age at first osteosarcoma diagnosis was 13.7 years (range: 5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients less than 10 years of age (23% vs. 9%), and when compared with osteosarcomas in patients less than 25 years were characterized by an excess of axial (16% vs. 10%) and jaw sites (15% vs. 3%) and histology with predominant chondroblastic component and periosteal subtypes (17% vs. 1%). Metastases incidence (25%) was as expected in osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%, 95% confidence interval [CI]: 42.6-71.1) were as expected in unselected series of osteosarcomas, whereas the 5-year event-free survival was 36.5% [95% CI: 25.3-52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 43.4% [95% CI: 28.5-57.5]. CONCLUSION: In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype, and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up.

Statistics of bone sarcoma in Japan: report from the population-based cancer registry in Japan.

BACKGROUND: No previous reports have characterized national bone sarcoma profiles overall. We examined the nationwide statistics for bone sarcoma in Japan using data from the National Cancer Registry (NCR), a population-based cancer registry. METHODS: We identified 3,755 patients with bone sarcomas entered in the NCR during 2016-2019 using International Classification of Diseases-Oncology, Third Edition codes for cancer topography and morphology. We extracted data on patient demographics, tumor details (reason for diagnosis, tumor location, histology, extent of disease), hospital volume/type, treatment, and prognosis for each patient. RESULTS: Bone sarcoma showed a slight male preponderance. The age distribution peaked at ages 10-20 and 60-80; approximately 44% of patients were aged over 60 years. Chordoma, chondrosarcoma, and malignant fibrous histiocytoma of bone peaked in the elderly, and Ewing's sarcoma peaked in children. Osteosarcoma had two peaks in Japan as well as in Western countries. The most frequent tumor locations were the limb (45%) and the pelvis (21%). Extent of disease was categorized as: "localized" (39%), "regional" (27%), and "distant" (11%). We found significant associations between overall survival and age, tumor location, facility type, hospital volume, histologic subtype, reason for diagnosis, and extent of disease. The latter had the poorest survival. CONCLUSIONS: This is the first study to outline the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of bone sarcoma in Japan using the NCR. Documenting our data regarding elderly patients' outcomes is essential so other countries showing similar population-aging trends can learn from our experiences. LEVEL OF EVIDENCE: Prognostic studies, Level III.

Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.

BACKGROUND: Canine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation. METHODS: A multi-center sample of childhood osteosarcoma patients and controls underwent genome-wide genotyping and imputation. Ancestry-adjusted SNP associations were calculated within each dataset using logistic regression, then meta-analyzed across the three datasets, totaling 1091 patients and 3026 controls. Ten regions previously associated with canine osteosarcoma risk were mapped to the human genome, spanning ∼6 Mb. We prioritized association testing of 5985 human SNPs mapping to candidate osteosarcoma risk regions detected in Irish wolfhounds, the largest dog breed studied. Secondary analyses explored 6289 additional human SNPs mapping to candidate osteosarcoma risk regions identified in Rottweilers and greyhounds. RESULTS: Fourteen SNPs were associated with human osteosarcoma risk after adjustment for multiple comparisons, all within a 42 kb region of human Chromosome 7p12.1. The lead variant was rs17454681 (OR=1.25, 95 %CI: 1.12-1.39; P=4.1×10-5), and independent risk variants were not observed in conditional analyses. While the associated region spanned 2.1 Mb and contained eight genes in Irish wolfhounds, associations were localized to a 50-fold smaller region of the human genome and strongly implicate GRB10 (growth factor receptor-bound protein 10) in canine and human osteosarcoma predisposition. PheWAS analysis in UK Biobank data identified noteworthy associations of the rs17454681 risk allele with varied measures of height and pubertal timing. CONCLUSIONS: Our comparative oncology analysis identified a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR. Epidemiologists may benefit from leveraging cross-species comparisons to identify haplotypes in highly susceptible but genetically homogenous populations of domesticated animals, then fine-mapping these associations in diverse human populations.

Sex differences in osteosarcoma survival across the age spectrum: A National Cancer Database analysis (2004-2016).

BACKGROUND: Osteosarcoma displays a bimodal peak in incidence in adolescence and later adulthood. Males are more frequently diagnosed with osteosarcoma in both periods. Males have worse survival than females, which is generally poor at 30-70% 5-years post diagnosis, depending on age, but treatment received is often unaccounted for in survival analyses. METHODS: Therefore, we estimated sex differences in survival for children and adults stratifying by treatment received and other disease characteristics using the National Cancer Database (2004-2016, n=9017). We estimated sex differences in long-term survival using Kaplan Meier survival curves and Log-Rank p-values. We also estimated hazard ratios (HR) and 95% confidence intervals (CIs) as the measure of association between sex and death using Cox regression. RESULTS: In all age groups, cases were predominantly male (52-58%). In Kaplan-Meier analyses, males had worse overall survival than females for 0-19, 20-39, and ≥60-year-olds (Log-Rank p<0.05). Females had higher 5- and 10-year survival percentages in all age groups. In adjusted Cox models, males had a higher risk of death among 0-19-year-olds (HRoverall: 1.24, 95% CI: 1.06-1.44; HRnon-metastatic disease: 1.35, 95% CI: 1.12, 1.63, HRlower limb tumors: 1.31, 95% CI: 1.09-1.59). Among 20-39-year-olds, males had an increased risk of death when receiving surgery only (HR: 4.67, 95% CI: 1.44, 15.09). Among those ≥60-year-olds, males had a suggestive increased risk of death overall (HR: 1.17, 95% CI: 0.99-1.39) and a higher risk of death based on some tumor locations, (HRupper limb: 2.52, 95% CI: 1.24, 5.11; HRmidline: 1.36, 95% CI: 1.02, 1.82). CONCLUSIONS: Our findings suggest that the worse survival among young males compared to females with osteosarcoma persisted after accounting for many major disease characteristics, including treatment received. Collectively, our work points toward other unexplored mechanisms beyond treatment, potentially biologic or otherwise, which may be driving the observed sex differences in long-term survival.

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Characteristics and prognostic factors of adult patients with osteosarcoma from the SEER database.

Osteosarcoma is the most common bone malignancy. There are many studies on the prognostic factors of children and adolescents, but the characteristics and prognostic factors of adult osteosarcoma are rarely studied. The aim of this study was to construct a nomogram for predicting the prognosis of adult osteosarcoma. Information on all osteosarcoma patients aged ≥ 18 years from 2004 to 2015 was downloaded from the surveillance, epidemiology and end results database. A total of 70% of the patients were included in the training set and 30% of the patients were included in the validation set. Univariate log-rank analysis and multivariate cox regression analysis were used to screen independent risk factors affecting the prognosis of adult osteosarcoma. These risk factors were used to construct a nomogram to predict 3-year and 5-year prognosis in adult osteosarcoma. Multivariate cox regression analysis yielded 6 clinicopathological features (age, primary site, tumor size, grade, American Joint Committee on Cancer stage, and surgery) for the prognosis of adult osteosarcoma patients in the training cohort. A nomogram was constructed based on these predictors to assess the prognosis of adult patients with osteosarcoma. Concordance index, receiver operating characteristic and calibration curves analyses also showed satisfactory performance of the nomogram in predicting prognosis. The constructed nomogram is a helpful tool for exactly predicting the prognosis of adult patients with osteosarcoma, which could enable patients to be more accurately managed in clinical practice.

Establishment and validation of a competitive risk model for predicting cancer-specific survival in patients with osteosarcoma: a population-based study.

BACKGROUND: Osteosarcoma is the most common primary bone tumor with a poor prognosis. The aim of this study was to establish a competitive risk model nomogram to predict cancer-specific survival in patients with osteosarcoma. METHODS: Patient data was obtained from the Surveillance, Epidemiology, and End Results database in the United States. A sub-distribution proportional hazards model was used to analyze independent risk factors affecting cancer-specific mortality (CSM) in osteosarcoma patients. Based on these risk factors, a competitive risk model was constructed to predict 1-year, 3-year, and 5-year cancer-specific survival (CSS) in osteosarcoma patients. The reliability and accuracy of the nomogram were evaluated using the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration curves. RESULTS: A total of 2900 osteosarcoma patients were included. The analysis showed that age, primary tumor site, M stage, surgery, chemotherapy, and median household income were independent risk factors influencing CSM in patients. The competitive risk model was constructed to predict CSS in osteosarcoma patients. In the training and validation sets, the C-index of the model was 0.756 (95% CI 0.725-0.787) and 0.737 (95% CI 0.717-0.757), respectively, and the AUC was greater than 0.7 for both. The calibration curves also demonstrated a high consistency between the predicted survival rates and the actual survival rates, confirming the accuracy and reliability of the model. CONCLUSION: We established a competitive risk model to predict 1-year, 3-year, and 5-year CSS in osteosarcoma patients. The model demonstrated good predictive performance and can assist clinicians and patients in making clinical decisions and formulating follow-up strategies.

Epidemiology and nomogram of pediatric and young adulthood osteosarcoma patients with synchronous lung metastasis: A SEER analysis.

BACKGROUND: Patients with osteosarcoma and synchronous lung metastasis (SLM) have poor survival. This study aimed to explore the epidemiology data and construct a predictive nomogram to identify cases at risk of SLM occurrence among pediatric and young adulthood osteosarcoma patients. METHODS: All data were extracted from Surveillance, Epidemiology, and End Results 17 registries. The age-standardized incidence rate (ASIR) and annual percentage change was evaluated, and reported for the overall population and by age, gender, race, and primary site. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with SLM occurrence, then significant factors were used to develop the nomogram. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluated the predictive power of the nomogram. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Multivariate Cox analysis was used to determine the prognostic factors. RESULTS: A total of 278 out of 1965 patients (14.1%) presented with SLM at diagnosis. The ASIR increased significant from 0.46 to 0.66 per 1,000,000 person-years from year 2010 to 2019, with an annual percentage change of 3.5, mainly in patients with age 10-19 years, male and appendicular location. All patients were randomly assigned into train cohort and validation cohort with a spilt of 7:3. In the train cohort, higher tumor grade, bigger tumor size, positive lymph nodes and other site-specific metastases (SSM) were identified as significant risk factors associated with SLM occurrence. Then a nomogram was developed based on the four factors. The AUC and calibration curve in both train and validation cohorts demonstrated that the nomogram had moderate predictive power. The median cancer-specific survival was 25 months. Patients with age 20-39 years, male, positive lymph nodes, other SSM were adverse prognostic factors, while surgery was protective factor. CONCLUSIONS: This study performed a comprehensive analysis regarding pediatric and young adulthood osteosarcoma patients had SLM. A visual, clinically operable, and easy-to-interpret nomogram model was developed for predicting the risk of SLM, which could be used in clinic and help clinicians make better decisions.

Multidisciplinary management of adolescents and young adults (AYA) sarcoma: A successful effort of an adult high-volume cancer center.

INTRODUCTION: The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high-volume single center. METHODS: Demographic, clinicopathological data on the diagnosis, treatment and follow-up of all sarcoma patients aged 16-39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late-treatment effects. RESULTS: We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate-high-grade, 24% low-grade STSs. Among BS, 32% were high-grade. Median TTD and TTT were 120 (0-8255) and 7 days (0-83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow-up was 72.9 months(1.6-145), 5-year and 10-year OS were 78.5% and 62%, respectively. Kaplan-Meyer analysis showed a significantly better 5-year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5-year OS was 69.8% versus 82.2%, respectively (p = 0.047). CONCLUSION: Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT.

Risk Factors for Primary Bone Cancer After Childhood Cancer: A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study.

PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship. RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation (Ptrend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.

Outcomes and survival rates of childhood osteosarcoma in Iran, A report from MAHAK Pediatric Cancer Treatment and Research Center, from 2007 to 2020.

Background: Osteosarcoma is one of the most common childhood bone malignancies. Although chemotherapy protocol including methotrexate is an effective treatment for osteosarcoma, some other regimens have excluded it because of its complications. Methods: This retrospective study was conducted on 93 children younger than 15 years old who were diagnosed with osteosarcomafrom March 2007 to January 2020. Two chemotherapy protocols were administrated for patients, namely, DCM protocol (Doxorubicin-Cisplatin-Methotrexate) and German protocol (excluding methotrexate). All statistical analysis was conducted using SPSS-25 software. Results: Among patients, 47.31% were male. Patients' age ranged from 3 to 15 with the mean of 10.41 ± 0.32 years. Femur was the most frequent primary tumor site (59.14%), followed by tibia (22.58%). Metastasis rate at diagnosis was 17.20% in our study. Furthermore, the 5-year overall survival (OS) of total patients was 37.3 ± 7.5%, whereas the 5-year OS of males and females was 33.6 ± 10.9% and 39.8 ± 10.6%, respectively. The 5-year OS of methotrexate regimen was 15.6 ± 9.6%, whereas that of methotrexate-free protocol was 50.2 ± 9.0%. Conclusions: Female patients had better survival rates than males. In addition, the chemotherapy protocol excluding methotrexate significantly increased the overall and event free survival of patients.

Establishment and validation of systematic prognostic nomograms in patients over 60 years of age with osteosarcoma: A multicenter external verification study.

BACKGROUND: The aim of this study was to develop and validate systematic nomograms to predict cancer specific survival (CSS) and overall survival (OS) in osteosarcoma patients aged over 60 years. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) database and identified 982 patients with osteosarcoma over 60 years of age diagnosed between 2004 and 2015. Overall, 306 patients met the requirements for the training group. Next, we enrolled 56 patients who met the study requirements from multiple medical centers as the external validation group to validate and analyze our model. We collected all available variables and finally selected eight that were statistically associated with CSS and OS through Cox regression analysis. Integrating the identified variables, we constructed 3- and 5-year OS and CSS nomograms, respectively, which were further evaluated by calculating the C-index. A calibration curve was used to evaluate the accuracy of the model. Receiver operating characteristic (ROC) curves measured the predictive capacity of the nomograms. The Kaplan-Meier analysis was used for all patient-based variables to explore the influence of various factors on patient survival. Finally, a decision curve analysis (DCA) curve was used to analyze whether our model would be suitable for application in clinical practice. RESULTS: Cox regression analysis of clinical variables identified age, sex, marital status, tumor grade, tumor laterality, tumor size, M-stage, and surgical treatment as prognostic factors. Nomograms showed good predictive capacity for OS and CSS. We calculated that the C-index of the OS nomogram of the training population was 0.827 (95% CI 0.778-0.876), while that of the CSS nomogram was 0.722 (95% CI 0.665-0.779). The C-index of the OS nomogram evaluated on the external validation population was 0.716 (95% CI 0.575-0.857), while that of the CSS nomogram was 0.642 (95% CI 0.50-0.788). Furthermore, the calibration curve of our prediction models indicated the nomograms could accurately predict patient outcome. CONCLUSIONS: The constructed nomogram is a useful tool for accurately predicting OS and CSS at 3 and 5 years for patients over 60 years of age with osteosarcoma and can assist clinicians in making appropriate decisions in practice.

Studies related to osteosarcoma and metabolism from 1990 to 2022: A visual analysis and bibliometric study.

Background: Osteosarcoma is the most common primary bone tumor, its high incidence of metastasis and poor prognosis have led to a great deal of concern for osteosarcoma. In many cancer types, metabolic processes are important for tumor growth progression, so interfering with the metabolic processes of osteosarcoma may be a therapeutic option to stall osteosarcoma progression. A key mechanism of how metabolic processes contribute to the growth and survival of various cancers, including osteosarcoma, is their ability to support tumor cell metabolism. Research related to this field is a direction of great importance and potential. However, to our knowledge, no bibliometric studies related to this field have been published, and we will fill this research gap. Methods: Publications were retrieved on January 1, 2023 from the 1990-2022 Science Citation Index of the Web of Science Core Collection. The Bibliometrix package in R software, VOSviewer and CiteSpace software were used to analyze our research directions and to visualize global trends and hotspots in osteosarcoma and metabolism related research. Results: Based on the search strategy, 833 articles were finally filtered. In this area of research related to osteosarcoma metabolism, we found that China, the United States and Japan are the top 3 countries in terms of number of articles published, and the journals and institutions that have published the most research in this area are Journal of bone and mineral research, Shanghai Jiao Tong University. In addition, Baldini, Nicola, Reddy, Gs and Avnet, Sofia are the top three authors in terms of number of articles published in studies related to this field. The most popular keywords related to the field in the last 30 years are "metabolism" and "expression", which will guide the possible future directions of the field. Conclusion: We used Bibliometrix, VOSviewer, and Citespace to visualize and bibliometrically analyze the current status and possible future hotspots of research in the field of osteosarcoma metabolism. Possible future hotspots in this field may focus on the related terms "metabolism", "expression", and "migraation".

Risk of Cardiovascular Death in Osteosarcoma.

OBJECTIVE: To assess the risk of cardiovascular mortality (CVM) in patients with osteosarcoma. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Orthopaedics, The People's Hospital of Baoan, Shenzhen, Guangdong, China, from 1st January 2019 to 1st January 2022. METHODOLOGY: Data on patients diagnosed with osteosarcoma, between 1975 and 2019, were obtained from the surveillance, epidemiology, and end results (SEER) database. Using the Nelson-Aalen cumulative risk curve to assess the risk of CVM in patients with osteosarcoma. Competing risk models were used for identifying and analysing independent risk factors for CVM in the patients. RESULTS: Data from a total of 1335 patients with osteosarcoma were obtained from the SEER database. The characteristics of patients with osteosarcoma independently related with a high risk of CVM were age over 65 years (HR: 2.528; 95% CI: 1.156 - 5.527), race of other categories (HR: 1.498; 95% CI: 1.044 - 2.151), and exposure radiotherapy (HR: 0.493; 95% CI: 0.244 - 0.998). Receiving chemotherapy was independently associated with a low risk of CVM (HR: 1.911; 95% CI: 1.016 - 3.593). CONCLUSION: Cardiovascular disease death from osteosarcoma was significantly associated with older age at diagnosis, race other class, receiving radiation therapy, and not undergoing chemotherapy. KEY WORDS: Osteosarcoma, Cancer risk factors, Epidemiology.

Risk factors for appendicular osteosarcoma occurrence in large and giant breed dogs in western Canada.

Objective: Risk factors for the development of canine appendicular osteosarcoma (OSA) have been investigated in numerous studies, but with contradictory results. The aim of this study was to analyze weight, age, breed, sex, neuter status, body condition score, and previous lameness in a population of large and giant breed dogs in western Canada with and without appendicular OSA. Animals and procedure: Medical records of 227 large or giant breed dogs diagnosed with appendicular OSA were compared to records from a control population of 454 large and giant breed dogs from the years 2000 to 2020. Results: Gonadectomized dogs, body condition score (BCS), and a history of lameness condition(s) (other than OSA) were associated with increased odds for presentation with OSA. Breeds shown to have increased odds for appendicular OSA occurrence included Rottweilers and Great Danes relative to Labrador retrievers. Conclusion and clinical relevance: Obesity and lameness appear to be independently associated with appendicular osteosarcoma. This study demonstrated that spayed females had the greatest risk compared to other sex and neuter status combinations; further investigation of these factors would be beneficial.

Facteurs de risque d'apparition d'ostéosarcome appendiculaire chez les chiens de grandes races et de races géantes dans l'Ouest canadien. Objectif: Les facteurs de risque de développement de l'ostéosarcome (OSA) appendiculaire canin ont été étudiés dans de nombreuses études, mais avec des résultats contradictoires. Le but de cette étude était d'analyser le poids, l'âge, la race, le sexe, la stérilisation, le score d'état corporel et les boiteries antérieures dans une population de chiens de grande race et de race géante de l'Ouest canadien avec et sans OSA appendiculaire. Animaux et procédure: Les dossiers médicaux de 227 chiens de grande race ou de race géante diagnostiqués avec l'OSA appendiculaire ont été comparés aux dossiers d'une population témoin de 454 chiens de grande race et de race géante des années 2000 à 2020. Résultats: Les chiens gonadectomisés, le score d'état corporel (BCS) et des antécédents de condition(s) de boiterie (autres que l'OSA) étaient associés à une probabilité accrue de présentation d'OSA. Les races dont le risque d'apparition d'OSA appendiculaire était plus élevé comprenaient les Rottweilers et les Grands Danois par rapport aux Labrador retrievers. Conclusion et pertinence clinique: L'obésité et la boiterie semblent être indépendamment associées à l'ostéosarcome appendiculaire. Cette étude a démontré que les femelles stérilisées présentaient le plus grand risque par rapport aux autres combinaisons de sexe et de statut neutre, une enquête plus approfondie sur ces facteurs serait bénéfique.(Traduit par Dr Serge Messier).

Second Primary Malignancies of the Bones and Joints: More Common than Expected in Osteosarcoma Patients.

BACKGROUND: Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults. Second primary malignancies (SPMs) are a potential serious long-term event that can occur in osteosarcoma survivors. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database was queried for all osteosarcoma cases from 2000 through 2015. Standardized incidence ratio (SIR) and absolute excess risk (AER) of SPM per 10,000 persons (AER) relative to representative population-level data were calculated across for various anatomic locations. RESULTS: In total, 3438 patients with osteosarcoma were identified. Of these patients, 79 (2.3%) developed SPMs, with an SIR of 2.84 (95% confidence interval [CI] 2.35 to 3.39, P < 0.0001) and an AER of 44.96. The most common SPMs were tumors of the bones or joints (SIR 73.07, CI, 38.90 to 124.94, P < 0.0001, AER 7.48), tumors of soft tissues including the heart (SIR 15.19, CI, 5.58 to 33.07, P < 0.0001, AER 3.27), and leukemia (SIR 22.28, CI, 15.03 to 31.80, P < 0.0001, AER 16.74). CONCLUSION: The overall incidence of SPMs in osteosarcoma survivors was significantly higher than would otherwise be expected for this population. Considering the occurrence and targeting surveillance for SPM in the osteosarcoma patient population is warranted.

Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma.

PURPOSE: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. METHODS: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. RESULTS: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21-3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01-3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05-6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22-3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. CONCLUSIONS: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. IMPLICATIONS FOR CANCER SURVIVORS: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes.

A longitudinal evaluation on 3-year change of anxiety and depression, and their risk factors among parents of childhood and adolescence patients with resectable osteosarcoma: A cohort study.

Psychological disorders often occur among parents of children with cancer. The current study aimed to explore the longitudinal change of anxiety and depression and their related factors among parents of childhood and adolescence patients with osteosarcoma. A total of 56 childhood and adolescence patients with osteosarcoma who underwent tumor resection and corresponding 104 parents were enrolled. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and HADS-Depression (HADS-D) of parents were evaluated at baseline (the day of patients' hospital discharge), 0.5 year, 1 year, 2 years, and 3 years. From baseline to the 3rd year, HADS-A (from 8.3 ±â€…3.1 to 9.4 ±â€…3.1. P < .001), HADS-D score (from 7.7 ±â€…3.2 to 8.8 ±â€…2.9, P = .001), anxiety rate (from 45.2% to 60.6%, P = .038), depression rate (from 38.5% to 57.7%, P = .002) were elevated; meanwhile, anxiety severity (P = .001) and depression severity (P = .001) were also increased. Furthermore, multivariate logistic regression analysis presented that the role of mother, divorced/widowed marital status, declined family annual income, elevated Enneking stage, and amputation were independently correlated with elevated risk of parents' baseline anxiety or depression (all P < .05). Additionally, declined family annual income, elevated Enneking stage, and amputation were independently correlated with increased risk of parents' 3-year anxiety or depression (all P < .05). Anxiety and depression deteriorate with time in parents of childhood and adolescence patients with osteosarcoma, which are affected by parental role, marital status, family annual income, surgery type, and Enneking stage.