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.

Epidemiología e imagenología del osteosarcoma y condrosarcoma en el territorio craneofacial. Revisión narrativa / Epidemology and imaging of osteosarcoma and chondrosarcoma in the craniofacial territory. Narrative review

Introducción: El osteosarcoma y el condrosarcoma son lesiones óseas malignas, ubicadas con mayor frecuencia en las extremidades y con menor frecuencia en el territorio craneofacial. No se ha reportado características imagenológicas concretas que diferencien ambas patologías en el territorio craneofacial. El propósito de la presente revisión narrativa es analizar las características epidemiológicas e imagenológicas del osteosarcoma craneofacial (OSCF) y condrosarcoma craneofacial (CSCF).Materiales y métodos:Se analizó la información publicada del OSCF y CSCF entre los años 2011-2021, con un enfoque en el análisis imagenológico.Resultados:El OSCF y CSCF no tienen preferencia clara por sexo. Mientras el OSCF se ubica en huesos de origen membranoso y preferencia entre la tercera y cuarta década de vida, el CSCF se ubica en zonas de origen endocondral y preferencia entre la tercera y sexta década de vida. En el OSCF, se han observado tres patrones de presentación imagenológicos: esclerótico, lítico y mixto, a diferencia del CSCF, en que se ha observado solo el patrón de presentación lítico. Ambas patologías tienen límites infiltrantes. El estudio imagenológico se realiza con tomografía computarizada, resonancia magnética, gammagrafía ósea, tomografía computarizada de fotón único y por emisión de positrones. En ambas patologías es más frecuente la recidiva local que la metástasis.Conclusiones:El OSCF y CSCF tienen características clínicas, epidemiológicas diferentes e imagenológicas similares. Establecer diferencias entre ellas es esencial para una correcta presunción diagnóstica.(AU)

Introduction: Osteosarcoma and chondrosarcoma are malignant lesions which locate most frequently in extremities and less frequently in craniofacial territory. Concrete imaging features in craniofacial territory that identify each pathology have not been reported. The aim of the present narrative review is to analyze the epidemiological and imaging features of the craniofacial osteosarcoma (CFOS) and craniofacial chondrosarcoma (CFCS).Materials and methods:We analyzed the information on CFOS and CFCS published between 2011 and 2021, focused on imaging analysis.Results:CFOS and CFCS do not show sex preference. Whilst CFOS is usually located in bones of membranous origin and is commonly discovered between the third and fourth decade of life, CFCS is usually located in areas of endochondral origin and commonly appears between the third and sixth decade of life. Three radiological presentation patterns are observed in CFOS: sclerotic, lytic and mixed, unlike the CFCS, where only the lytic pattern has been observed. Both pathologies have infiltrated margins. The imaging study is performed with computed tomography, magnetic resonance imaging, bone scintigraphy, single-photon computed tomography and positron emission tomography, among others. Local recurrence is more common than metastasis in both pathologies.Conclusion:CFOS and CFCS have different clinical and epidemiological features but similar imaging features. Stablishing differences between both pathologies is essential to achieve a correct presumptive diagnosis.(AU)

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.

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.

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.

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".

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.

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.

Results of a survey on the treatment of adolescents and young adult (AYA) sarcoma patients in Spain at present time

Introduction We aimed to analyse health care services for adolescents and young adults (AYA) with sarcomas in Spain. Methods A survey was sent to all Spanish cancer centres, including questions about demographic, facilities, and treatment strategies for AYAs with sarcomas in the last 2 years. Results Thirty-five units participated in the survey, 17 paediatric and 15 adult units. There were three specialized AYA units. First line regimen varied depending on whether the treating unit was paediatric or not, for osteosarcomas, rhabdomyosarcomas, and non-rhabdomyosarcomas. By contrast, 91.4% of Ewing sarcomas were treated according to EE2012. In the relapse setting, differences between units were higher in all tumours. Additionally, 48% of the units reported not having trials for this population. Conclusion There are major differences in the treatment of AYAs with sarcomas between adult and paediatric units. Enormous efforts are needed to homogenize treatments and increase the access to innovation. (AU)

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.

Assessing the incidence of osteosarcoma among teriparatide-treated patients using linkage of commercial pharmacy and state cancer registry data, contributing to the removal of boxed warning and other labeling changes.

BACKGROUND: Teriparatide, a recombinant human parathyroid hormone analogue, is associated with increased bone mineral density and a decreased risk of fractures. A dose-dependent increase in the incidence of osteosarcoma was observed in toxicology studies conducted in rats. The primary objective of this study was to estimate the incidence of osteosarcoma over a 10-year period among teriparatide-treated patients versus patients unexposed to teriparatide with osteoporosis and patients in the general population using national pharmacy dispensing data linked with data from participating state cancer registries (SCRs) in the US. METHODS: Patients aged 18 years or older with a dispensed teriparatide prescription formed two different cohorts: Teriparatide-Osteoporosis (Teriparatide-OP) was formed by matching teriparatide patients to unexposed patients with osteoporosis and Teriparatide-General Population (Teriparatide-GP) was formed by matching teriparatide patients to general population patients with a dispensed prescription for a medication other than teriparatide. Matching was performed using select demographics and other variables. Study cohorts were linked to SCR data to ascertain osteosarcoma status. To account for missing outcome data from non-participating SCRs, two analytic approaches were used: the first adjusted the person-time at-risk using a coverage fraction and the second restricted the analyses to patients from states with participating SCRs. RESULTS: There were 18 osteosarcoma cases across four study cohorts: the same three cases in the Teriparatide-OP and Teriparatide-GP cohorts, six cases in the Osteoporosis cohort, and nine cases in the General Population cohort. For the analysis using the coverage fraction the incidence rate ratio (IRR) comparing the Teriparatide-OP and Teriparatide-GP cohorts to the Osteoporosis and General Population cohorts was 1.0 (95% CI: 0.2, 4.5) and 1.3 (95% CI: 0.2, 5.1), respectively. When restricting the analysis to patients from states with participating SCRs, the IRR was 0.6 (95% CI: 0.1, 3.6) and 0.8 (95% CI 0.1, 4.0), respectively. CONCLUSION: The estimates of association between teriparatide and osteosarcoma were imprecise due to the small number of observed osteosarcoma cases. However, the incidence of osteosarcoma observed in each study cohort was within the expected range given background rates for the US general population. The evidence generated by this study, in conjunction with other real-world studies evaluating the risk of osteosarcoma, was used to support changes to the US teriparatide label (including removal of the black box warning regarding potential risk of osteosarcoma) and expand treatment options for patients with osteoporosis.

Descriptive epidemiology of soft tissue and bone sarcomas in Lebanon.

OBJECTIVES: Most epidemiologic studies on soft tissue sarcomas (STS) and bone sarcomas (BS) are performed in western countries, with few in the Middle East and North Africa region. We describe the epidemiology of sarcomas in Lebanon using the medical records database at the American University of Beirut Medical Center (AUBMC). METHODS: This single-center retrospective cohort study included patients with sarcomas registered in the database between 2015 and 2019. Their charts were reviewed for baseline characteristics, tumor biology and location, treatment modalities, recurrence, metastasis, and death. RESULTS: The cohort included 234 patients with STS and 99 patients with BS. Most tumors were <10 cm in size. The most common subtypes were liposarcoma for STS and osteosarcoma for BS. The most common location of STS was the thigh. The most frequent sites of STS metastasis were the lungs. Histological subtype, smoking status, and tumor size and grade were significant for progression-free survival (PFS) in patients with STS. By multivariable analysis, smoking was significantly associated with poorer PFS in STS. For BS, only tumor grade was significant for PFS. CONCLUSION: The epidemiology of sarcomas at AUBMC is similar to that previously reported. Smoking history was associated with poorer survival in patients with STS.

Secondary malignant neoplasms after bone and soft tissue sarcomas in children, adolescents, and young adults.

BACKGROUND: Increased survival in young sarcoma patients comes along with a higher incidence of second malignant neoplasms (SMNs). The incidence, latency, histiotype, and outcome of these patients were analyzed because this information is essential to design evidence-based long-term follow-up care programs for young sarcoma survivors. METHODS: Patients entered on clinical trials or registered in registries with a primary sarcoma in 1 of the cooperative sarcoma study groups in the framework of the Society for Pediatric Oncology and Hematology (GPOH) were screened for SMNs. Descriptive analysis, the Kaplan-Meier method, the Gray model, the Fine-Gray model, and the Cox regression model were used for the statistical analyses. RESULTS: A total of 159 out of 7079 (2.2%) patients were registered with a SMN. Among them, 104 solid SMNs (65%) and 56 hematologic SMNs (35%) occurred. Median latency from first diagnosis of sarcoma to the diagnosis of SMN was 6.8 years (range, 0-26.7 years). Cumulative incidence of SMN was 8.8% after 30 years. Five-year-survival was 67.1% (95% confidence interval [CI], 66.0-68.2) for the 7079 patients and it was 45.1% (95% CI, 36.2-53.6) after the diagnosis of a SMN (subcohort of n = 159 patients). CONCLUSIONS: There is a remarkable high cumulative incidence of SMNs after bone and soft tissue sarcomas in children, adolescents, and young adults. Therefore, effective transition as well as risk adapted long-term follow-up care programs should be developed and offered to young sarcoma survivors. LAY SUMMARY: Bone sarcomas and soft tissue tumors are rare tumors in children, adolescents, and young adults. The treatment varies, but may comprise chemotherapy, surgery, and/or radiotherapy. Developing a subsequent malignant tumor is a long-term risk for the patients. To better characterize this risk, we analyzed the data of 7079 patients (up to 21 years old) with bone sarcomas or soft tissue tumors. Our findings provide a basis to counsel young sarcoma survivors on their individual risk of subsequent malignant tumors. Moreover, these data can help to establish recommendations for aftercare in young sarcoma survivors.