Age-related Disparities in Pan-Cancer Mortality and Causes of Death: Analysis of Surveillance, Epidemiology, and End Results (SEER) Data.

Comprehensive analysis of mortality and causes of death (COD) in cancers was of importance to conduct intervention strategies. The current study aimed to investigate the mortality rate and COD among cancers, and to explore the disparities between age. Initially, cancer patients diagnosed between 2010 and 2019 from the surveillance, epidemiology, and end results (SEER) database were extracted. Then, frequencies and percentage of deaths, and mortality rate in different age groups were calculated. Meanwhile, age distribution of different COD across tumor types was illustrated while the standardized mortality ratios (SMR) stratified by age were calculated and visualized. A total of 2,670,403 death records were included and digestive system cancer (688,953 death cases) was the most common primary cancer type. The mortality rate increased by 5.6% annually in total death, 4.0% in cancer-specific death and 10.9% in non-cancer cause. As for cancer-specific death, the age distribution varied among different primary tumor types due to prone age and prognosis of cancer. The top five non-cancer causes in patients older than 50 were cardiovascular and cerebrovascular disease, other causes, COPD and associated conditions, diabetes as well as Alzheimer. The SMRs of these causes were higher among younger patients and gradually dropped in older age groups. Mortality and COD of cancer patients were heterogeneous in age group due to primary tumor types, prone age and prognosis of cancer. Our study conducted that non-cancer COD was a critical part in clinical practice as well as cancer-specific death. Individualized treatment and clinical intervention should be made after fully considering of the risk factor for death in different diagnosis ages and tumor types.

Ten-year retrospect of the investigation of proximal limbs metastasis in cancer: a multi-center study on survival outcome, limb function status and surgical procedures analysis.

BACKGROUND: The aim of study was to evaluate survival outcome and limb function in cancer patients with proximal limbs metastasis. Associated factors on survival outcome and limb function were identified. The comparative analysis between intramedullary nailing and prosthesis surgery in cancer patients with proximal limb metastasis was performed. METHODS: In this five-center retrospective study, patients diagnosed with limbs metastasis were collected. Descriptive statistics was used and log-rank test was performed to analyze the survival in subgroups. The Cox proportional hazards regression analysis was performed to identify the independent prognostic factors. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate limb function after surgery, and t test or analysis of variance (ANOVA) was utilized in subgroup analysis. RESULTS: A total of 316 patients with limb metastasis were included with mean age at 61.0 years. The most common primary tumor was breast, followed by renal cancer and lung cancer. The median overall survival was 24.0 months and the 1-, 3- and 5-year survival rates were 86.9%, 34.7% and 6.8%, respectively. Primary tumor type, visceral metastasis and chemotherapy were proved to be the independent prognostic factors. The mean Musculoskeletal Tumor Society (MSTS) score was 20.5, significant difference was observed in subgroup of solitary/multiple bone metastasis, with/without pathological fracture, and type of surgery. CONCLUSION: The present study concluded that primary tumor type, visceral metastasis and chemotherapy were three factors affecting the survival of patients. Compared with intramedullary nailing, the patients underwent prosthesis surgery showed better limb function, this procedure should be encouraged in patients with indication.

Clinicomics-guided distant metastasis prediction in breast cancer via artificial intelligence.

BACKGROUND: Breast cancer has become the most common malignant tumour worldwide. Distant metastasis is one of the leading causes of breast cancer-related death. To verify the performance of clinicomics-guided distant metastasis risk prediction for breast cancer via artificial intelligence and to investigate the accuracy of the created prediction models for metachronous distant metastasis, bone metastasis and visceral metastasis. METHODS: We retrospectively enrolled 6703 breast cancer patients from 2011 to 2016 in our hospital. The figures of magnetic resonance imaging scanning and ultrasound were collected, and the figures features of distant metastasis in breast cancer were detected. Clinicomics-guided nomogram was proven to be with significant better ability on distant metastasis prediction than the nomogram constructed by only clinical or radiographic data. RESULTS: Three clinicomics-guided prediction nomograms on distant metastasis, bone metastasis and visceral metastasis were created and validated. These models can potentially guide metachronous distant metastasis screening and lead to the implementation of individualized prophylactic therapy for breast cancer patients. CONCLUSION: Our study is the first study to make cliniomics a reality. Such cliniomics strategy possesses the development potential in artificial intelligence medicine.

Effects of kojic acid on changes in the microstructure and myofibrillar protein of duck meat during superchilled storage.

This study investigated the effect of 0.8% (m/v) kojic acid treatment on changes in the microstructure and myofibrillar protein of duck meat covered with oxygen-permeable polyvinylchloride (PVC) film (9 ± 0.5 µM) during superchilled storage (-1.65 ± 0.5°C). The superchilled samples exhibited wider gaps between muscle fibers at 5 weeks storage compared with kojic acid-treated groups. Based on the variation of water status, the water-holding capacity decreased significantly (p < 0.05), and bound water and immobilized water were gradually converted into free water during superchilled storage. For kojic acid-treated samples, however, no major changes were observed with respect to muscle structure, water status, and protein degradation at 6 weeks. The 0.8% (m/v) kojic acid treatment increased the water-holding capacity, reduced carbonyl content and protein degradation, and decreased the α-helix contents loss of myofibrillar proteins. Kojic acid treatment effectively protected myofibrillar protein structure from being destroyed during superchilled storage, suggesting that this method was a good way to reduce protein oxidation and prolonged its shelf life.

Association between malnutrition and leucopenia in patients with osteosarcoma.

Background and aim: Leucopenia (LP) greatly limits the efficacy of chemotherapy in osteosarcoma patients. This study aimed to evaluate the nutritional status of osteosarcoma patients before chemotherapy, assess the risk of LP during the perichemotherapy period, and explore the association between malnutrition and LP. Materials and methods: This study retrospectively analyzed osteosarcoma patients treated in the Tianjin Medical University Cancer Institute and Hospital, China, between January 2009 and December 2020 according to the inclusion and exclusion criteria. Malnutrition in adolescents (5 to 19 years old) and adults (≥20 years old) was diagnosed using WHO AnthroPlus software (version 1.0.4) and Global Leadership initiative on Malnutrition (GLIM), respectively. According to the diagnostic criteria of LP in CTCAE 5.0, patients were divided into the LP group and the non-LP group. Results: A total of 245 osteosarcoma patients were included. The incidence of malnutrition was 49.0%, and the incidence of LP was 51.8%. The incidence of malnutrition in adolescent patients was 53.1%, and their incidence of LP was 55.2%; the incidence of malnutrition in adult patients was 43.1%, and their incidence of LP was 47.1%. Logistic regression analysis showed that malnutrition before chemotherapy was an independent risk factor for the occurrence of LP after chemotherapy (OR = 6.85, 95% CI = 2.16-25.43; and OR = 35.03, 95% CI = 6.98-238.46 in mildly and severely malnourished young patients; OR = 6.06; 95% CI = 1.43-30.16; and OR = 38.09, 95% CI = 7.23-285.78 in mildly and severely malnourished adult patients, respectively). The results showed that age and nutritional status had a joint effect on the occurrence of LP. Conclusion: The nutrition status of osteosarcoma patients before chemotherapy is significantly correlated with the occurrence and severity of LP during peri-chemotherapy period. During osteosarcoma chemotherapy, necessary nutritional support should be given to patients of different ages to correct their malnutrition status in a timely manner, ultimately improving the efficacy of chemotherapy and the prognosis of patients.

The 100 most cited papers on bone metastasis: A bibliometric analysis.

Background: Over the past few decades, a vast number of articles focused on bone metastasis have been published. Bibliometric analysis is helpful to determine the qualities and characteristics and to reveal the influential articles in this field. Methods: All the databases in Web of Science were utilized to identify articles published from 1961 to 2020. The top 100 most cited articles on bone metastases were involved for degree centrality analysis and analyses on publication time and citations, journals, authors, geographical distribution, research institutions, and research keywords. Results: The selected articles were published mainly from 1986 to 2015. The 100 most cited articles were selected from a total of 67,451 citations out of 90,502 publications with a density of 50.239 citations/year. Citations per article ranged from 357 to 2167. The leading country was USA, followed by Canada and United Kingdom. The most frequently studied themes were clinical management of bone metastasis from different malignancy origins. A co-authorship analysis revealed an intense collaborative activity between countries and institutions. Conclusions: This study identified the top 100 most cited articles on bone metastasis. Publication time, area, and theme distribution were thoroughly analyzed. The present study highlighted some of the most influential contributions to the field. Clinical and academic communities have shown a sustained interest in the management of bone metastasis.

Non-cancer Causes of Death Following Initial Synchronous Bone Metastasis in Cancer Patients.

Purpose: To investigate the non-cancer causes of death (COD) in cancer patients with synchronous bone metastasis (BM) that is based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: The retrospective cohort study included malignant cancer patients with synchronous BM diagnosed from 2010 to 2018 in the SEER database. The frequencies and proportion of non-cancer COD were calculated and analyzed in different genders, ages, and races subgroups. Results: A total of 97,997 patients were deceased and included into the current study and 6,782 patients were died of non-cancer causes with a male predominance (N = 4,515, 66.6%). Around half of deaths (N = 3,254, 48.0%) occurred within 6 months after diagnosis while 721 patients were deceased after 3 years. Lung and bronchus cancer, prostate cancer, breast cancer, kidney and renal pelvis cancer, and liver cancer were proved to be the top five cancer types resulting in non-cancer caused death. Cardiovascular and cerebrovascular diseases were the leading non-cancer cause of death (N = 2,618), followed by COPD and associated conditions (N = 553) and septicemia, infectious and parasitic diseases (N = 544). Sub-analyses stratified by gender, age and race were performed and the similar results with slightly difference were observed. Conclusions: Cardiovascular and cerebrovascular diseases were the main non-cancer cause of death in cancer patients with synchronous BM. Other non-cancer causes included COPD, septicemia, infectious and parasitic diseases, and so on. These findings should be considered by physicians. Physicians can counsel cancer patients with BM regarding survivorship with death causes screening and focus on prevention of non-cancer deaths.

Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy.

PURPOSE: To explore the trends of plasma drug concentration changes after high-dose methotrexate (MTX) treatment of osteosarcoma (OS), analyse the risk factors for leukopenia (LP) after MTX treatment, and establish a LP prediction nomogram. METHODS: A total of 35 OS patients at Tianjin Medical University Cancer Institute and Hospital between 2017 and 2021 were collected (the construction cohort). Another 12 OS patients between 2019 and 2021 in P.A. Hertsen Moscow Oncology Research Center were involved (the external validation cohort). Peripheral venous blood MTX concentration (CMTX) was monitored at 0h, 6h, 24h, 48h and 72h after MTX administration. The characteristics were collected: age, sex, body surface area, lesion site, pathological subtype, pathological fractures, American Joint Committee on Cancer (AJCC) clinical stage, MTX dose, tumour necrosis, Ki-67 index, erythrocyte count, haemoglobin count, white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin concentration, creatinine, alkaline phosphatase, and lactate dehydrogenase. Logistic regression analysis was used to determine the risk factors for LP occurrence. Significant factors were used to construct the prediction nomogram. RESULTS: A total of 128 MTX chemotherapy cycles from 35 OS patients were included. Female, Ki-67>20%, CMTX>112µmol/L at 6h, PLT, and AST were risk factors for post-chemotherapy LP occurrence. The LP prediction nomogram was created and validated. CONCLUSIONS: Female, CMTX at 6h, Ki-67 index, AST and PLT before MTX treatment were risk factors for LP in OS patients who received MTX treatment. The established nomogram can guide personalized LP prediction in OS patients receiving MTX chemotherapy.

Evaluating Osteogenic Differentiation of Osteoblastic Precursors Upon Intermittent Administration of PTH/IGFBP7.

Parathyroid hormone (PTH) 1-34 is the first anabolic agent approved for the treatment of osteoporosis. Preclinical evidence shows a potential association between PTH and osteosarcoma. The mechanisms mediating the bone- and neoplasm-forming effects of PTH remain incompleted understood, few studies on the role of Insulin-like growth factor-binding protein 7 (IGFBP7) in mediating the anabolic effects of PTH has been reported. Intermittent PTH administration was found to increase the expression of IGFBP7 in mesenchymal stem cells (MSCs) and pre-osteoblasts. The results indicated that the anabolic effects of PTH were interrupted when knockdown of IGFBP7, while supplementation with IGFBP7 protein could enhance the bone-forming efficacy of PTH and regulate the signaling pathways. Moreover, bone healing was accelerated by the administration of IGFBP7 along with PTH in a mouse model of fracture. The obtained results proved that IGFBP7 was necessary for the anabolic effects of PTH, and combined administration of PTH and IGFBP7 showed stronger bone-forming effects relative to administration of PTH alone.

A Predictive Nomogram for Early Death in Pheochromocytoma and Paraganglioma.

Background: Pheochromocytoma (PHEO) and paraganglioma (PGL) are relatively rare neuroendocrine tumors. The factors affecting patients with early death remain poorly defined. We aimed to study the demographic and clinicopathologic pattern and to develop and validate a prediction model for PHEO/PGL patients with early death. Methods: Data of 800 participants were collected from the Surveillance Epidemiology and End Results (SEER) database as a construction cohort, while data of 340 participants were selected as a validation cohort. Risk factors considered included the year of diagnosis, age at diagnosis, gender, marital status, race, insurance status, tumor type, primary location, laterality, the presence of distant metastasis. Univariate and multivariate logistic regressions were performed to determine the risk factors. R software was used to generate the nomogram. Calibration ability, discrimination ability, and decision curve analysis were analyzed in both construction and validation cohorts. Results: PHEO and PGL patients accounted for 54.3% (N=434) and 45.7% (N=366), respectively. More than half of tumors (N=401, 50.1%) occurred in the adrenal gland, while 16.9% (N=135) were in aortic/carotid bodies. For the entire cohort, the median overall survival (OS) was 116.0 (95% CI: 101.5-130.5) months. The multivariate analysis revealed that older age (versus age younger than 31; age between 31 and 60: OR=2.03, 95% CI: 1.03-4.03, P=0.042; age older than 60: OR=5.46, 95% CI: 2.68-11.12, P<0.001), female gender (versus male gender; OR=0.59, 95% CI: 0.41-0.87, P=0.007), tumor located in aortic/carotid bodies (versus tumor located in adrenal gland; OR=0.49, 95% CI: 0.27-0.87, P=0.015) and the presence of distant metastasis (versus without distant metastasis; OR=4.80, 95% CI: 3.18-7.23, P<0.001) were independent risk factors of early death. The predictive nomogram included variables: age at diagnosis, gender, primary tumor location, and distant metastasis. The model had satisfactory discrimination and calibration performance: Harrell's C statistics of the prediction model were 0.733 in the construction cohort and 0.716 in the validation cohort. The calibration analysis showed acceptable coherence between predicted probabilities and observed probabilities. Conclusions: We developed and validated a predictive nomogram utilizing data from the SEER database with satisfactory discrimination and calibration capability which can be used for early death prediction for PHEO/PGL patients.

Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcomas (STS) with recurrence and metastatic potential. We aimed to investigate the risk factors for developing distant metastases (DM) and to identify the prognostic factors in patients with DM. METHODS: Based on the Surveillance, Epidemiology, and End Result (SEER) database, MPNST patients diagnosed between 2010 and 2016 were extracted in our study. The logistic regression model was performed for predicting DM development while the Cox proportional hazard regression model was conducted for revealing the prognostic factors. RESULTS: Eventually, 764 patients diagnosed with MPNSTs were included with 109 cases presenting with metastases at initial diagnosis. Larger tumor size and lymph node metastases were independent risk factors for developing DM. The median overall survival (OS) for patients with metastases was 8.0 (95% CI: 6.1-9.9) months. Multiple metastatic sites and no surgical treatment were prognostic factors for worse survival. Tumors located in non-head and neck region were related with better survival. CONCLUSIONS: The incidence of DM was 14.3% with a dismal median OS of 8.0 months for metastatic MPNSTs. More evaluation should be applied for patients with large tumor size and lymph metastases. Tumors located in head and neck region and the presence of multiple metastases predicted worse survival outcome. Surgical treatment can significantly improve the survival of MPNST patients with distant metastasis.

Survival and risk factors in patients with liposarcoma with distant metastasis.

BACKGROUND: The distant metastasis in liposarcoma is not thoroughly investigated. Based on a large cohort, we attempted to evaluate the survival in liposarcoma patients with distant metastasis and to reveal the risk factors. METHODS: The records of liposarcoma patients with or without distant metastasis were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2010 to 2016. Survival was calculated by the Kaplan-Meier method. Cox hazard regression was scheduled to investigate prognostic factors for liposarcoma patients with distant metastasis. Risk factors for metastasis were identified by the logistic regression analysis. RESULTS: A total of 227 liposarcomas with distant metastasis were identified in 4,181 patients. The 5-year survival rate for patients with and without metastasis was 12.1% (95% CI: 5.0%-19.0%) and 75.4% (95% CI: 73.6%-77.2%), respectively. Age ≥60 years (HR=1.73; 95% CI: 1.11-2.69) and surgery (HR=0.26; 95% CI: 0.17-0.41) were independent prognostic factors for patients with metastasis. The annual incidence of distant metastasis was from 3.76% to 7.3%. Liposarcoma in trunk (OR=1.69; 95% CI: 1.02-2.79), myxoid type (OR=2.65; 95% CI: 1.16-6.05), grade III (OR=2.62; 95% CI: 1.17-5.88), grade IV (OR=4.07; 95% CI: 1.84-9.00), T2 stage (OR=2.71; 95% CI: 1.15-6.40), and N1 stage (OR=9.44; 95% CI: 4.63-19.26) were associated with the development of metastasis. Homogeneous and heterogeneous factors were found for patients with different metastatic organs. CONCLUSIONS: The survival was significantly dismal in liposarcoma patients with distant metastasis. The risk and prognostic factors provide a reference to clinical screening and prevention for distant metastasis in liposarcoma.

A Population-Based Analysis of Distant Metastasis in Stage IV Gastric Cancer.

BACKGROUND Distant metastasis (DM) is a crucial problem in management of patients with gastric cancer. Identification of the risk factors for development of DM and the prognostic factors for patients with DM is essential in development of individualized treatment of patients at the advanced stage with specific metastasis. MATERIAL AND METHODS Records of patients with gastric cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival duration of patients with specific DM was estimated, and the prognostic factors were investigated using the Cox proportional hazard regression model. The logistic regression model was used to reveal the inherent risk factors for development of DM. RESULTS Eventually, 32.6% (11,918 out of 36,588) of gastric cancer patients were diagnosed with DM between 2010 and 2015, among whom 5,361, 1,778, 1,495, and 231 patients were diagnosed with liver, lung, bone, and brain metastasis, respectively. The median overall survival for patients with DM was 5.0 (95% CI: 4.8-5.2) months, with a 5-year survival rate of 3.9%. Primary tumor site, histology types, tumor grade, T stage, N stage, surgery, chemotherapy, and the number of metastases were associated with worse survival. Younger age and higher tumor grade were positively associated with the development of DM. CONCLUSIONS Initial DM was found in 32.6% of patients with gastric cancer. Homogenous and heterogenous predictive factors were identified for patients with a specific metastatic site, which can be used in targeted screening and individualized treatment.

Analysis of Homogeneous and Heterogeneous Factors for Bone Metastasis in Esophageal Cancer.

BACKGROUND Esophageal cancer is a common cancer worldwide. We performed the present study to assess the homogeneous and heterogeneous risk and prognostic factors of bone metastasis (BM) in esophageal cancer patients using data extracted from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIAL AND METHODS Data from patients with esophageal cancer in the SEER database from 2010 to 2016 were extracted to reveal the risk factors for BM through univariable and multivariable logistic regression. Cox hazard regression analysis was used to evaluate the prognostic factors in esophageal cancer patients with BM from 2010 to 2015. RESULTS A total of 2075 (8.0%) patients with initial bone metastasis were diagnosed from among 25 955 patients with esophageal cancer from 2010 to 2016. Male sex, T4 stage, brain metastasis, and liver metastasis were common risk factors for the occurrence and prognosis of BM. Patients with age younger than 67 years, grade III, higher N stage (N1, N2, and N3), histological subtype of esophageal adenocarcinoma or others, and lung metastasis were also more likely to experience bone metastasis, while unmarried patients were associated with shorter survival. CONCLUSIONS The prevalence of initial bone metastasis was approximately 8.0% in esophageal cancer patients. More attention should be paid to patients with revealed risk and prognostic factors because these factors can guide individualize bone metastasis screening and treatment of esophageal cancer patients.