Development of a novel six DNA damage response-related prognostic signature in osteosarcoma.

DNA damage response (DDR) plays a vital role in the development of cancer. Nevertheless, in osteosarcoma, the potential of DDR-related genes (DDRGs) remains unclear. Thus, the current research is intended to investigate the mechanisms of DDRGs in the development of osteosarcoma and to explore potential DDR-related biomarkers in forecasting the prognosis of osteosarcoma patients. The osteosarcoma genomic data from TCGA, GEO and cBioPortal databases were utilized for screening and identification of differentially expressed DDRGs (DEDDRGs). Consensus clustering analysis was performed to identify different subtypes of osteosarcoma based on the expressions of DDRGs. Key DEDRRGs were identified by overlapping DEDRRGs between different subtypes and DEDRRGs between tumor and control samples. Univariate, as well as LASSO regressions, were further applied to obtain robust prognostic signatures. GSVA and ssGSEA analysis were implemented to explore the underlying mechanisms of prognostic DDRG signature in regulating osteosarcoma. In addition, the drug sensitivity of patients in low- and high-risk groups was evaluated using pRRophetic algorithm. A total of 43 key DEDRRGs were identified. Followed by univariate Cox along with LASSO regression analyses, CDK6, CSF1R, EGFR, ERBB4, GATA3 and SOCS1 were identified as prognostic signatures in osteosarcoma. Cox regressions revealed that the risk score was an independent prognostic factor in osteosarcoma.  DDR may affect osteosarcoma via regulating immune microenvironment along with influencing cell proliferation, migration, adhesion and apoptosis. The chemotherapeutic response between patients in low- and high-risk groups was much different. The role of DDRGs in osteosarcoma and identified six DDR-linked biomarkers for forecasting the prognosis of osteosarcoma patients. Our outcomes enhanced the understanding of DDR-related molecular mechanisms involved in osteosarcoma and provided potential therapeutic targets for osteosarcoma patients.

Disparities in incidence and survival for patients with Ewing sarcoma in Florida.

BACKGROUND: Ewing sarcoma (ES) is a malignant bone tumor most commonly affecting non-Hispanic White (NHW) adolescent males, though recognition among Hispanic individuals is rising. Prior population-based studies in the United States (US), utilizing Surveillance, Epidemiology, and End Results (SEER) have shown higher all-cause mortality among White Hispanics, Blacks, and those of low socioeconomic status (SES). Florida is not part of SEER but is home to unique Hispanic populations including Cubans, Puerto Ricans, South Americans that contrasts with the Mexican Hispanic majority in other US states. This study aimed to assess racial/ethnic disparities on incidence and survival outcomes among this diverse Florida patient population. METHODOLOGY: Our study examined all patients diagnosed with osseous ES (2005-2018) in Florida (n = 411) based on the state's population-based cancer registry dataset. Florida Age-adjusted Incidence Rates (AAIRs) were computed by sex and race-ethnicity and compared to the equivalent populations in SEER. Cause-specific survival disparities among Florida patients were examined using Kaplan-Meier analysis. Univariable and multivariable analyses using Cox regression were performed for race/ethnicity, with adjustment for age, sex, year of diagnosis, site of disease, staging, SES, and insurance type. RESULTS: There was a significantly higher incidence of osseous ES in Florida Hispanic males (AAIR 2.6/1,000,000); (95% CI: 2.0-3.2 per 1,000,000; n = 84) compared to the SEER Hispanic males (AAIR 1.2/1,000,000;1.1-1.4 per 1,000,000; n = 382). Older age, distant metastasis, lack of chemotherapy or surgical resection were statistically significant determinants of poor survival while SES, insurance status and race-ethnicity were not. However, among nonmetastatic ES, Florida Hispanics had an increased risk of death compared to Florida NHW (adjusted Hazard Ratio 2.32; 95%CI: 1.20-4.46; p = 0.012). CONCLUSIONS: Florida Hispanic males have a higher-than-expected incidence of osseous ES compared to the US. Hispanics of both sexes show remarkably worse survival for nonmetastatic disease compared to NHW. This disparity is likely multifactorial and requires further in-depth studies.

A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

AIM: To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. METHODS: The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. RESULTS: The median age was 8.5 years (range: 1.5 to 17 y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162 mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. CONCLUSION: Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

Transcriptome and single-cell analysis reveal disulfidptosis-related modification patterns of tumor microenvironment and prognosis in osteosarcoma.

Osteosarcoma (OS) is the most common malignant bone tumor with high pathological heterogeneity. Our study aimed to investigate disulfidptosis-related modification patterns in OS and their relationship with survival outcomes in patients with OS. We analyzed the single-cell-level expression profiles of disulfidptosis-related genes (DSRGs) in both OS microenvironment and OS subclusters, and HMGB1 was found to be crucial for intercellular regulation of OS disulfidptosis. Next, we explored the molecular clusters of OS based on DSRGs and related immune cell infiltration using transcriptome data. Subsequently, the hub genes of disulfidptosis in OS were screened by applying multiple machine models. In vitro and patient experiments validated our results. Three main disulfidptosis-related molecular clusters were defined in OS, and immune infiltration analysis suggested high immune heterogeneity between distinct clusters. The in vitro experiment confirmed decreased cell viability of OS after ACTB silencing and higher expression of ACTB in patients with lower immune scores. Our study systematically revealed the underlying relationship between disulfidptosis and OS at the single-cell level, identified disulfidptosis-related subtypes, and revealed the potential role of ACTB expression in OS disulfidptosis.

[Analysis of 41 cases of non-metastatic Ewing's sarcoma in children]. / 儿童非转移性尤文肉瘤41例分析.

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015.

BACKGROUND: Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015. METHODS: Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program. RESULTS: Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years. CONCLUSIONS: The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.

Development of nomogram and discussion of radiotherapy effect for osteosarcoma survival.

This study aimed to develop a predictive system for prognostic evaluation of osteosarcoma patients. We obtained osteosarcoma sample data from 1998 to 2016 using SEER*Stat software version 8.3.8, and established a multivariable Cox regression model using R-4.0.3 software. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The diagnosis of the model was completed through influential cases, proportionality, and multicollinearity. The predictive ability of the model was tested using area under the curve (AUC), calibration curves, and Brier scores. Finally, the bootstrap method was used to internally verify the model. In total, data from 3566 patients with osteosarcoma were included in this study. The multivariate Cox regression model was used to determine the independent prognostic variables. A nomogram and Kaplan-Meier survival curve were established. The AUC and Brier scores indicated that the model had a good predictive calibration. In addition, we found that the radiotherapy appears to be a risk factor of patients with osteosarcoma and made a discussion. We developed a prognostic evaluation system for patients with osteosarcoma for 1-, 3-, and 5-year overall survival with good predictive ability using sample data extracted from the SEER database. This has important clinical significance for the early identification and treatment of high-risk groups of osteosarcoma patients.

Pleckstrin homology-like domain family A, member 3, a miR-19a-3p-regulated gene, suppresses tumor growth in osteosarcoma by downregulating the Akt pathway.

Pleckstrin homology-like domain family A, member 3 (PHLDA3), is emerging as a critical regulator for multiple cancers. Nevertheless, the expression and role of PHLDA3 in osteosarcoma remain unknown. Herein, we purposed to elucidate the role of PHLDA3 in the progression and chemoresistance of osteosarcoma. According to the bioinformatics analysis, PHLDA3 expression was low in osteosarcoma patients, and low content was linked to poor prognosis. Additionally, activation of PHLDA3 suppressed osteosarcoma cell proliferation, migration, and chemoresistance, whereas PHLDA3 inhibition caused the opposite effects. Mechanistically, our data revealed that PHLDA3 negatively regulates the Akt/GSK3ß signaling cascade in osteosarcoma. Furthermore, we found that miR-19a-3p might exert its oncogenic function by inhibiting PHLDA3 expression in osteosarcoma. These results demonstrated miR-19a-3p/ PHLDA3/ Akt/GSK3ß axis has a pivotal role in osteosarcoma, and PHLDA3 is a prospective therapeutic target for treating osteosarcoma.

Late Mortality in Childhood Cancer Survivors according to Pediatric Cancer Diagnosis and Treatment Era in the Dutch LATER Cohort.

This multi-center cohort-study examined late mortality among 6,165 Dutch five-year childhood cancer survivors diagnosed 1963-2001. Clinical details and cause of death were based on medical records. Mortality was 12-fold that of the general population, with 51.3 additional deaths per 10,000 person-years (21.9 yrs median follow-up). Cumulative mortality 15 yrs post-diagnosis was 6.9%, predominantly from late recurrences; thereafter the absolute contribution of other health outcomes increased. Cumulative all-cause and recurrence-related mortality were highest for Central Nervous System and bone tumor survivors. All-cause, but not subsequent tumor and circulatory disease-related cumulative mortality, was highest for patients diagnosed 1963-1979 vs. later (p-trend <0.001).

Long-term Outcome of Acral Ewing Sarcoma.

BACKGROUND/AIM: Ewing sarcoma is a common primary bone tumor, often located in the distal femur or pelvis. Acral Ewing sarcoma of the upper extremity is exceedingly rare. The aim of this study was to review our institution's experience with the management of rare acral Ewing sarcomas. PATIENTS AND METHODS: We retrospectively reviewed the records of 10 patients with bony Ewing sarcomas located distal to the elbow joint. The group included 9 male and 1 female patient with a mean age at diagnosis of 20±12 years and a mean follow-up of 19 years. RESULTS: All patients presented with a primary complaint of a painful mass. The most common location was the metacarpal (n=4). Patients were treated with chemotherapy and either surgery (n=7) or definitive radiotherapy (n=3). The mean tumor size and necrosis on the resected specimens were 4±1 cm and 87% (range=30-100%), respectively. There was one case of local progression in a patient treated with definitive radiotherapy, which led to an amputation. Four patients developed metastatic disease, most commonly to the lungs. The 5-year survival free of metastatic disease or death due to disease was 55% and 60%, respectively. CONCLUSION: Acral Ewing sarcoma is rare. Combined chemotherapy and surgery lead to definitive local control in all patients, with an acceptable functional outcome.

Efficacy of New Therapies for Relapse After Docetaxel Treatment of Bone Metastatic Castration-resistant Prostate Cancer in Clinical Practice.

BACKGROUND/AIM: To assess the efficacy of novel therapeutic agents, such as androgen receptor axis-targeted agents (ARATs) and cabazitaxel, for relapse of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel in real-world practice, we performed a subanalysis using database from PROSTAT-BSI, a prospective observational study to evaluate the utility of software for quantifying bone metastases on bone scintigraphy. PATIENTS AND METHODS: Patients with clinically relapsed mCRPC after docetaxel treatment who received the new agents (NEW group) and those who did not (standard of care, SOC group) were included; patients who received ARAT before DOC treatment were excluded. Overall survival (OS) after docetaxel treatment was compared between the NEW and SOC groups. RESULTS: Patients in the NEW group had significantly better OS from the start of docetaxel than those in the SOC group (the median OS in NEW and SOC was 28.9 months vs. 14.5 months, respectively). Furthermore, regardless of the time from androgen-deprivation therapy to the start of docetaxel at mCRPC, the NEW group had a better OS from relapse after docetaxel than the SOC group. CONCLUSION: In clinical practice, OS of patients with relapse after docetaxel was significantly improved in the NEW group over the SOC group.

Primary Malignant Osseous Neoplasms in the Hand.

BACKGROUND: Primary malignant osseous neoplasms of the hand are rare malignancies. Comprehensive demographic and survival data regarding primary malignant osseous neoplasms of the hand are lacking in the literature. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified all patients with primary malignant osseous neoplasms of the hand diagnosed between 1983 and 2015. Demographic data were searched for primary osseous neoplasms in the hand and higher incidence of histological subtype. RESULTS: A total of 197 patients were analyzed: 103 patients were diagnosed with histologically low-grade tumor, and 31 were diagnosed with high-grade tumor. Five-year cancer-specific and overall survival rates for the entire cohort were 91.4% and 81.9%, respectively. Histological high tumor grade and regional stage from SEER historic stage data were associated with unfavorable cancer-specific survival. CONCLUSION: Special caution is required if patients have histologically high-grade tumor or tumor extending beyond the periosteum into surrounding joints, as these features worsen cancer-specific mortality.

Predictors and Treatment Outcomes of Pediatric Osteosarcoma in Diverse Socioeconomic Backgrounds in Southeast Asia: A Retrospective Multicenter Study.

BACKGROUND: Pediatric osteosarcoma outcomes among developed and developing countries have not been previously compared. Countries in Southeast Asia (SEA) have a wide variety of socioeconomic statuses. A multi-institutional retrospective study was conducted to determine the prognostic factors and outcomes for pediatric osteosarcoma in SEA. METHODS: Pediatric patients with osteosarcoma treated between 1998 and 2017 in 4 SEA pediatric oncology centers were studied. Countries were classified using the World Bank Atlas method. Kaplan-Meier method and Cox's Proportion Hazard Model were applied to estimate survival outcomes and identify prognostic factors. RESULTS: In all, 149 patients with osteosarcoma with a mean age of 12.48±3.66 years were enrolled. The localized to metastatic disease ratio was 1.5:1. The 5-year overall survival (OS) and event-free survival (EFS) were 53.8% and 42%, respectively. Prognostic factors associated with outcomes were country, stage of disease, MTX-containing regimens, and surgery type (p-value <0.05). In patients with localized disease, EFS was superior with limb-salvage surgery (62%) than amputation or rotationplasty (40%) (p-value 0.009). MTX-containing chemotherapies provided higher OS (45.3%) and EFS (37.9%) than non-MTX regimens (12.3% and 10.7%, respectively) among metastatic patients (p-value 0.004 and 0.005, respectively). Metastatic disease was an independent prognostic factor for death but not relapse outcome.  Conclusion: The disease outcomes in SEA were acceptable compared to developed countries. The stage of disease was the only independent prognostic factor. MTX-containing regimens and limb-salvage surgery should be considered where possible.

Analysis of Related Risk Factors and Prognostic Factors of Gastric Cancer with Bone Metastasis: A SEER-Based Study.

BACKGROUND: Gastric cancer is among the most common malignant tumors at home and abroad, because its early symptoms are mostly insidious, which leads to distant metastasis when gastric cancer is first diagnosed. The common metastatic sites of gastric cancer are mainly the liver, lung, and peritoneum, but bone metastasis is relatively rare, and the prognosis of gastric cancer bone metastasis is very poor. Therefore, this study is built on the SEER database to analyze the related risk factors of gastric cancer bone metastasis and related factors affecting the prognosis of gastric cancer patients, aiming at improving clinicians' understanding of clinical diagnosis and prognosis of bone metastasis of gastric cancer, thus reducing misdiagnosis and missed diagnosis. METHODS: The SEER database was collected to screen out patients with gastric cancer bone metastases and nonbone metastases matched with them from 2010 to 2016, and the Kaplan-Meier method was used to draw survival curves, and the comparison between survival curves was performed by Log-rank test to analyze the overall survival of the two groups of patient's time. Logistic regression analysis was used to analyze the related risk factors of gastric cancer bone metastasis, and the Cox regression proportional hazard model was used to analyze the relationship between gastric cancer bone metastasis and patient prognosis. RESULTS: Using Kaplan-Meier survival curve to analyze the 1, 3, and 5-year survival rates of gastric cancer patients with bone metastasis and non-metastasis groups were 14.2%, 1.8%, 0.6% and 71.4%, 44.3%, 36.4%, respectively; the average survival rate of the metastatic group was The time was 4.0 months (95%CI: 3.475~4.525), and the average survival time of the non-metastatic group was 30.0 months (95%CI: 26.778~33.222). The difference between the two groups was statistically significant (χ 2 = 1076.866, P < 0.001). Multivariate logistic regression analysis showed that race (P = 0.007, OR = 1.296), grade (P < 0.001, OR = 0.575), marital status (P < 0.001, OR = 0.040), tumor size (P = 0.006, OR = 0.752), TNM stage (P < 0.001), T stage (P = 0.023, OR = 0.882), and M stage (P < 0.001, OR = 44.958) are independent risk factors for gastric cancer bone metastasis. The Cox univariate analysis suggests that gastric cancer bone metastasis is a risk factor for the prognosis of gastric cancer patients. The Cox multivariate analysis validates that gastric cancer bone metastasis (HR = 0.584, 95% CI: 0.497~0.688, P < 0.001) is independent of the overall survival rate of gastric cancer patients. CONCLUSIONS: Race, grade, marital status, tumor size, TNM stage, T stage, and M stage are independent risk factors for gastric cancer bone metastasis; and gastric cancer bone metastasis is an independent risk factor that affects the prognosis of gastric cancer patients. Therefore, for such high-risk groups, large range screening of the above indicators can effectively improve the prognosis of gastric cancer patients to a certain extent.

Significance of the neutrophil-to-lymphocyte ratio in predicting the response to neoadjuvant chemotherapy in extremity osteosarcoma: a multicentre retrospective study.

BACKGROUND: At present, no predictive factor has been validated for the early efficacy of neoadjuvant chemotherapy (NACT) in osteosarcoma. The purpose of this study was to investigate the significance of the neutrophil-to-lymphocyte ratio (NLR) in predicting the response to NACT in extremity osteosarcoma. METHODS: Pathological complete response (pCR) was used to assess the efficacy of NACT. Receiver operating characteristic (ROC) curves and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR. Univariate and multivariate analyses using logistic regression models were conducted to confirm the independent factors affecting the efficacy of NACT. RESULTS: The optimal NLR cut-off value was 2.36 (sensitivity, 80.0%; specificity, 71.3%). Univariate analysis revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR. Multivariate analyses confirmed that the NLR before treatment was an independent risk factor for pCR. Compared to patients with a high NLR, those with a low NLR showed a more than 2-fold higher likelihood of achieving pCR (OR 2.82, 95% CI 1.36-5.17, p = 0.02). CONCLUSION: The NLR is a novel and effective predictive factor for the response to NACT in extremity osteosarcoma patients. Patients with a higher NLR showed a lower percentage of pCR after NACT.

The insertion and dysregulation of transposable elements in osteosarcoma and their association with patient event-free survival.

The dysregulation of transposable elements (TEs) has been explored in a variety of cancers. However, TE activities in osteosarcoma (OS) have not been extensively studied yet. By integrative analysis of RNA-seq, whole-genome sequencing (WGS), and methylation data, we showed aberrant TE activities associated with dysregulations of TEs in OS tumors. Specifically, expression levels of LINE-1 and Alu of different evolutionary ages, as well as subfamilies of SVA and HERV-K, were significantly up-regulated in OS tumors, accompanied by enhanced DNA repair responses. We verified the characteristics of LINE-1 mediated TE insertions, including target site duplication (TSD) length (centered around 15 bp) and preferential insertions into intergenic and AT-rich regions as well as intronic regions of longer genes. By filtering polymorphic TE insertions reported in 1000 genome project (1KGP), besides 148 tumor-specific somatic TE insertions, we found most OS patient-specific TE insertions (3175 out of 3326) are germline insertions, which are associated with genes involved in neuronal processes or with transcription factors important for cancer development. In addition to 68 TE-affected cancer genes, we found recurrent germline TE insertions in 72 non-cancer genes with high frequencies among patients. We also found that +/- 500 bps flanking regions of transcription start sites (TSS) of LINE-1 (young) and Alu showed lower methylation levels in OS tumor samples than controls. Interestingly, by incorporating patient clinical data and focusing on TE activities in OS tumors, our data analysis suggested that higher TE insertions in OS tumors are associated with a longer event-free survival time.

Outcomes of Intramedullary Nail Fixation for Metastatic Disease: Impending and Pathologic Fractures.

BACKGROUND/AIM: Intramedullary nail (IMN) fixation has become a treatment mean for impending and pathologic femur fractures. Currently there continues to be a lack of data examining functional outcomes, complications, and survivorship of patients treated with IMNs for metastatic disease of the femur. PATIENTS AND METHODS: We retrospectively identified 183 IMNs placed for impending (n=145) or pathologic (n=38) metastatic fractures from 2010 to 2018. Functional outcomes and complications including blood transfusions, venous thromboembolisms (VTEs) and reoperations were studied. RESULTS: Patients with impending lesions were more likely to be ambulatory at final follow-up (pathologic: 82%, impending: 99%, p<0.0001) and reported greater musculoskeletal tumor society scores (p<0.0001). Likewise, pathologic fractures were associated with greater discharge to non-home locations (p<0.0001) and were more likely to require a postoperative transfusion (pathologic: 66%, impending: 22%, p=0.0001). However, there was no difference in the incidence of VTEs (p=1.00) or reoperations (p=0.69) between cohorts. Patients treated for impending fractures had improved overall survival at 1 year (54% vs. 26%, p<0.0001). CONCLUSION: IMN fixation was durable in impending and pathologic femoral fractures. Early identification of metastases remains critical as patients treated for impending lesions had greater functional outcomes, fewer complications and improved survivorship compared to patients treated for pathologic fractures.

Ra-223 and Ethinylestradiol Combination Therapy in Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Ra-223 is a therapeutic agent for bone metastatic castration-resistant prostate cancer (mCRPC). We examined the efficacy of a treatment method using Ra-223 together with ethinylestradiol (EE). PATIENTS AND METHODS: Patients who received Ra-223 three or more times were included and two groups (with or without EE) were compared retrospectively. RESULTS: Eighteen patients were treated with Ra-223 and EE concomitantly (EstRadium therapy) and 13 patients were treated with Ra-223 alone or Ra-223 and agents other than EE (non-EstRadium therapy). The number of patients with decreased serum prostate-specific antigen level was significantly higher in the EstRadium therapy group than in the non-EstRadium therapy group (p=0.029). CONCLUSION: The combination of Ra-223 and EE, compared to Ra-223 alone, is an effective treatment option for bone mCRPC patients, in terms of PSA response.