Metastatic lymph node burden impacts overall survival in submandibular gland cancer.

Objective: To assess the effect of the number of positive lymph nodes (LNs) on the overall survival (OS) of patients with submandibular gland cancer (SmGC). Methods: Patients who had undergone neck dissection for SmGC were retrospectively enrolled in this study. The effect of the American Joint Committee on Cancer (AJCC) N stage, the number of positive LNs, LN size, LN ratio, and extranodal extension (ENE) on OS and recurrence-free survival (RFS) was evaluated using Cox analysis. Prognostic models were proposed based on the identified significant variable, and their performance was compared using hazard consistency and discrimination. Results: In total, 129 patients were included in this study. The number of positive LNs rather than LN ratio, LN size, and ENE was associated with OS. A prognostic model based on the number of positive LNs (0 vs. 1-2 vs. 3+) demonstrated a higher likelihood ratio and Harrell's C index than those according to the 7th/8th edition of the AJCC N stage in predicting OS and RFS. Conclusions: The effect of LN metastasis on OS and RFS was mainly determined by the number of positive LNs. A validation of this finding is warranted in adenoid cystic carcinomas that were not included in this study.

Development of a prognostic nomogram and risk stratification system for upper thoracic esophageal squamous cell carcinoma.

Background: The study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC). Methods: Newly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: In this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage. Conclusion: We built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians' abilities to predict individualized survival and facilitate to further stratify the management of patients at risk.

The Natural History of Renal-Cell Carcinoma with Sarcomatoid Differentiation, a Stage-by-Stage Analysis.

BACKGROUND: Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB). MATERIALS AND METHODS: We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC. RESULTS: In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P < .001). CONCLUSION: In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

Prognostic factors of intraductal papillary mucinous neoplasm of the bile duct: analysis based on SEER database / 中华肝胆外科杂志

Objective:To explore prognostic factors of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) patients.Methods:Clinical data on 227 patients with IPMN-B between 2004 and 2015 were retrospectively collected from the surveillance, epidemiology, and end results (SEER) database. There were 126 male and 101 female patients with the age at diagnosis of 69(58, 77) years old. IPMN-B patients were divided into two groups based on whether surgical treatment was performed. There were 129 patients in the surgery group and 98 patients in the non-surgery group. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test was used to compared survival rate. The univariate and multivariate Cox analyses were applied to find independent prognostic factors of the survival in IPMN-B patients.Results:The tumor size of 227 IPMN-B patients from the SEER database was 25(18.5, 45.0) mm. The differences of tumor size, grade of defferentiation, American Joint Committee on Cancer (AJCC) stage, T stage, M stage chemotherapy were statistically significant respectively in surgery group and non-surgery group (all P<0.05). The median overall survival time (OS) of patients with IPMN-B was 14 months and the overall 1-year survival was 53.4%. The median overall survival time of IPMN-B patients in surgery group was 27 months, which was better than 5 months of patients in non-surgery group, and the difference was statistically significant ( P<0.001). Univariate Cox analysis found AJCC stage, T stage, N stage, M stage and surgery were prognostic factors in patients with IPMN-B. Multivariate Cox analysis showed that M1 stage ( HR=2.125, 95% CI: 1.472-3.066, P<0.001) was independent risk factor of prognosis while surgery ( HR=2.983, 95% CI: 2.106-4.224, P<0.001) was independent protective factor of prognosis. Conclusion:The AJCC staging system is an important predictor for evaluating the prognosis of IPMN-B patients. Surgery could significantly improve the prognosis of patients with IPMN-B.

Stage-Specific Survival in Breast Cancer in Chinese and White Women: Comparative Data Analysis.

BACKGROUND: Stage-specific survival, according to the eighth edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging (PPS) on breast cancer (BC), between Chinese and White American women remains unclear. OBJECTIVE: This study aimed to assess stage-specific survival in BC between Chinese and White American women according to the eighth AJCC PPS. METHODS: We included Chinese and White American women with BC diagnosed between 2010 and 2018 from the Surveillance, Epidemiology, and End Results database. A chi-square test, the Kaplan-Meier method, a receiver operating characteristic (ROC) curve, and multivariate Cox proportional hazards models were used for data analysis. RESULTS: We included 376,818 individuals in this study: 369,522 White American and 7296 Chinese. Of them, 149,452 (39.7%) migrated from the seventh AJCC anatomic staging (AS) to the eighth AJCC PPS, 22,516 (6.0%) were upstaged, and 126,936 (33.7%) were downstaged. With a median follow-up duration of 44 months, the 5-year overall survival and cancer-specific survival (CSS) for the entire group were 87.4% and 95.9%, respectively. The seventh AJCC AS (P<.001) and the eighth AJCC PPS (P<.001) could significantly predict the survival outcomes of BC, and multivariate analysis revealed that both staging systems were significant prognostic indicators of CSS. The ROC curve revealed that the PPS had a better discriminating ability than the AS (area under the curve [AUC] 0.769 vs 0.753, P<.001). Similar trends were observed after stratification by the 2 ethnic groups. The eighth AJCC PPS had better discriminating ability than the seventh AJCC AS among both White American (AUC 0.769 vs 0.753, P<.001) and Chinese patients (AUC 0.790 vs 0.776, P<.001). In the seventh AJCC AS, Chinese women had better CSS in stage IA (P=.02), stage IIA (P=.005), and stage IIIB (P=.04) disease than White American women, but no significant CSS was observed in stage IB, IIB, IIIA, and IIIC disease between the 2 ethnic groups. Regarding the eighth AJCC PPS, Chinese women had better CSS in stage IA (P=.002) and IIIA (P=.046) disease than White American women, and CSS was similar in Chinese and White American women in other substages. CONCLUSIONS: The eighth AJCC PPS has a similar discriminative ability between White American and Chinese individuals with BC compared with the seventh AJCC AS. Therefore, the eighth AJCC PPS is also applicable to Chinese individuals with BC.

Tumor size rather than the thyroid invasion affects the prognosis of parathyroid carcinoma without lymph node or distant metastasis.

PURPOSE: This study aimed to explore the prognostic value of thyroid invasion of parathyroid carcinoma without lymph node or distant metastasis. METHODS: Two hundred and nine cases of parathyroid carcinoma from the SEER (1989-2014) were eligible for this study. A Chi-squared test, t test, X-tile, Kaplan-Meier curves, and multivariate Cox proportional hazard regression were used for analysis. RESULTS: Thyroid invasion, sex, race, age, radiation, and surgery were not significantly associated with cancer-specific survival by multivariate analysis. However, tumor size ≥ 4 cm was significantly associated with worse cancer-specific survival (P < 0.001). CONCLUSION: Thyroid invasion, which was the criterion for T1 and T2 staging criteria of parathyroid carcinoma according to the AJCC, did not affect the prognosis of patients with parathyroid carcinoma without local lymph node or distant metastasis. Our study indicates that a tumor size ≥ 4 cm may be an appropriate indicator of T1 and T2 cancer staging.

Lymph node ratio-dependent prognosis stratification and postoperative radiotherapy utilization in T1-2N1 oral cavity carcinoma.

OBJECTIVE: Pathological T1-2N1 oral cavity squamous cell carcinoma (pT1-2N1 OCSCC) is a setting with intermediate prognosis whilst without consensus regarding the utilization of postoperative radiotherapy (PORT). This study aimed to investigate the prognostic value of lymph node ratio (LNR) and to further examine its clinical validity for guiding PORT in pT1-2N1 OCSCC. METHODS: OCSCC patients who received surgery between 2010 and 2015 with at least 6 lymph nodes dissection were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Time-dependent receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff of LNR. Multivariable Cox regression analysis was employed to assess the prognostic value of LNR. Impact of PORT was evaluated in respective subgroups stratified by LNR. RESULTS: A total of 870 OCSCC patients with pT1-2N1 diseases were eligible for analysis. The 5-year overall survival (OS) and disease-specific survival (DSS) was 57.2% and 67.9% respectively. Time-dependent ROC analyses for OS and DSS concordantly revealed 5.5% as the optimal cutoff of LNR. Significantly higher risks of death (HR = 1.610, 95% CI: 1.139-2.276) and disease-specific death (HR = 1.731, 95% CI: 1.101-2.723) were unveiled in patients with LNR > 5.5%. PORT related improvement on OS (5-year rate: 57.6% vs. 47.3%, p = 0.095) and DSS (5-year rate: 71.0% vs. 53.8%, p = 0.030) was only found in LNR > 5.5% subgroup. CONCLUSIONS: LNR > 5.5% is indicative of inferior outcome in pT1-2N1 OCSCC, warranting the utilization of PORT in this sub-setting.

Evaluation and Recommendation of the 8th Edition of American Joint Committee on Cancer (AJCC) Staging System for Intrahepatic Cholangiocarcinoma (ICC) in 820 Patients from the Surveillance, Epidemiology, and End Results (SEER) Database.

BACKGROUND: The AJCC made four changes to T category in the 8th AJCC stage for ICC, but this is a topic of debate. METHODS: Data from 820 patients with ICC were extracted from the SEER database. Survival analysis of the 8th AJCC stage was examined. RESULTS: To verify the four T staging changes by survival analysis: prognosis of patients with tumor size > 5 cm was poorer than that with tumor size ≤ 5 cm (P < 0.05); in N0M0 cohort, there was no significant difference in survival between solitary tumor with vascular invasion and multiple tumors (P = 0.092), tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion (P = 0.470), and tumor with and without periductal invasion (PI) (P = 0.220). The prognosis of patients with ≥ 4 positive lymph nodes was relatively poor compared with 1-3 positive lymph nodes (P = 0.037) and similar to patients with stage IV (8th AJCC, P = 0.585). CONCLUSION: This study found that there was no significant difference in survival between tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion, whereas other T staging changes were effective. The inclusion of the number of positive lymph nodes in the 8th AJCC stage may improve prognostic discrimination in ICC patients.

Impact of perioperative allogeneic blood transfusion on the long-term prognosis of patients with different stage tumors after radical resection for hepatocellular carcinoma.

BACKGROUND: We previously reported that perioperative allogeneic blood transfusion (PABT) did not affect long-term survival after radical resection for hepatocellular carcinoma (HCC). This study aimed to investigate the effects of PABT on the prognosis of HCC patients with different stage tumors. METHODS: Patients with primary HCC who underwent curative liver resection between 2003 and 2012 were retrospectively enrolled and divided into the early-stage (stage I) and non-early-stage (stages II, III and IV) groups. The impacts of PABT on the long-term prognosis of patients in different groups after resection were investigated using propensity score matching (PSM) and multivariable Cox regression analyses. RESULTS: We enrolled 426 HCC patients, including 53 matched pairs of patients with early-stage tumors and 51 matched pairs of patients with non-early-stage tumors. Survival analyses of the patients with early-stage tumors showed that the recurrence-free survival (RFS) and overall survival (OS) rates of the transfusion group were significantly worse than those of the nontransfusion group both before and after PSM. Multivariable Cox analyses identified that PABT was an independent predictor of RFS and OS of the patients with early-stage tumors. However, survival analyses of the propensity-matched patients with non-early-stage tumors showed no significant differences in RFS and OS rates between the transfusion and nontransfusion groups (p = 0.296; p = 0.472). CONCLUSIONS: This study demonstrates that PABT has negative impacts on the long-term prognosis of patients with early-stage tumors after radical resection of HCC but has no impact on the long-term prognosis of patients with non-early-stage tumors.

Clinical Characteristics and Prognosis of AJCC 8th Edition Stage Ⅲ Gallbladder Cancer with Different Subtypes: A Study Based on SEER Database / 肿瘤防治研究

Objective To investigate the clinical characteristics, treatment and prognosis of the eighth edition of AJCC stage Ⅲ gallbladder cancer (GBC). Methods We collected the clinical data and follow-up results of 3485 patients with AJCC 8th stage Ⅲ gallbladder cancer. Kaplan Meier survival curves of ⅢA and ⅢB, T3N0M0 (ⅢA), T1-2N1M0 (ⅢB) and T3N1M0 (ⅢB) were drawn and compared. Single factor analysis and Cox multiple factor regression analysis were used to analyze the relation between clinical characteristics, treatment plan, stage Ⅲ subtype and prognosis. Results One-year survival rate of stage ⅢB gallbladder cancer patients was 49.70%, higher than those of stage ⅢA(36.41%); the 1-year survival rate of stage T1-2N1M0 (ⅢB) gallbladder cancer patients was 65.52%, higher than those of stage T3N0M0 (ⅢA) (36.41%) and stage T3N1M0 (ⅢB) (37.05%). According to Cox multivariate analysis, age, tumor grade, tumor size, operation mode, radiotherapy, chemotherapy, AJCC 8th TNM specific subtype and T stage were independent related factors affecting the prognosis of stage Ⅲ GBC patients (P < 0.01). Conclusion The overall survival of stage ⅢB GBC is better than that of stage ⅢA. The risk of stage Ⅲ GBC death was T1-2N1M0 (ⅢB) < T3N0M0 (ⅢA) < T3N1M0 (ⅢB). Radical cholecystectomy (number of dissected lymph node≥6), radiotherapy and chemotherapy are beneficial to the improvement of prognosis of stage Ⅲ GBC patients.

Staging of T2 and T3 nasopharyngeal carcinoma: Proposed modifications for improving the current AJCC staging system.

OBJECTIVES: We aimed to reconstitute T2 and T3 stage classification in nasopharyngeal carcinoma (NPC) cases and verify its utility in clinical settings. MATERIALS AND METHODS: We enrolled 792 NPC patients. Cox proportional hazards model was used to compare the effect sizes (hazard ratio [HR]) of the cranial structure invasion on survival and select the structures for up-staging or downstaging T2 and T3 NPC. The samples were reclassified and the survival curves for T2 and T3 stages were analyzed. The proposed new staging system was validated on an external sample (n = 433). RESULTS: Thirteen cranial structures were examined. American Joint Committee on Cancer (AJCC) T3 stage patients with the invasion of the base of the sphenoid (HR = 2.58, 95% CI = 1.16-5.77) or base of the pterygoid (HR = 2.00, 95% CI = 0.84-4.77) had significantly lower hazard ratios than T2 stage patients with the invasion of soft tissues in the bilateral parapharyngeal space (HR = 5.26, 95% CI = 2.02-13.68) and single/bilateral carotid sheath (HR = 7.78, 95% CI = 3.06-19.76). T3 stage with the invasion of the above-mentioned bones was reclassified as T2, and T2 stage with the invasion of the above-mentioned soft-tissue structures was reclassified as T3. Survival analysis showed a significant difference between the reclassified T2 and T3 stages (P < 0.001). The results were replicated in the validation samples. CONCLUSION: The proposed staging system for defining T2 and T3 stage NPC appears to be superior to the AJCC 8th edition. It could improve prognosis and optimize the treatment selection.

A validated survival nomogram for early-onset diffuse gastric cancer.

This study aimed to establish and independently validate a prognostic nomogram for individual risk prediction in patients with early-onset diffuse gastric cancer (EODGC). Data for 794 patients with EODGC from the SEER database were randomly assigned to training (N=558) and internal validation (N=236) sets, and data for 82 patients from the Renmin Hospital of Wuhan University (RMHWHU) were used as an independent validation cohort. Our LASSO regression analyses of the training set yielded five clinicopathological features (race, AJCC stage, surgery for primary site, chemotherapy and tumor size), which were used to create a survival nomogram. Our survival nomogram achieved better predictive performance than the AJCC staging system, the current standard. Additionally, the calibration curves of the prognostic nomogram revealed good agreement between the predicted survival probabilities and the ground truth values. Indeed, our nomogram, which estimates individualized survival probabilities for patients with EODGC, shows good predictive accuracy and calibration ability for both the SEER and RMHWHU cohorts. These results suggest that a survival nomogram may be better at predicting OS for EODGC patients than the AJCC staging system.

High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC.

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 (P < .001) and TCGA profile (P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation (P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.

Absolute and relative differential blood count predicts survival of AJCC stage I-II melanoma patients scheduled for sentinel lymph node biopsy.

BACKGROUND/OBJECTIVES: Elevated neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is associated with poor overall survival (OS) in metastatic melanoma patients receiving immunotherapy. However, the impact of peripheral blood cells in patients undergoing sentinel lymph node biopsy (SLNB) is still unclear. This study was intended to characterize the impact of peripheral blood leukocytic cells on overall survival (OS) in melanoma patients undergoing SLNB. METHODS: A total of 1412 AJCC stage I-II melanoma patients scheduled for SLNB at a single institution in the period 2010-2015 with available perioperative blood tests were randomly assigned to two independent cohorts. Associations of peripheral blood leukocytes with OS were analysed using Kaplan-Meier estimator and multivariate Cox proportional hazards model. RESULTS: NLR >4.26, absolute neutrophil count >5800/µL, relative neutrophil count >69.7% and relative lymphocyte count ≤ 17.5% were significantly associated with reduced OS in both cohorts. Absolute monocytes >810/µL, absolute eosinophils ≤200/µL, relative monocytes >6.6%, relative eosinophils ≤2.7% and relative basophils ≤0.6% were significantly associated with reduced OS in one cohort each. On multivariate analysis, a combined score including absolute levels of neutrophils, lymphocytes, monocytes and eosinophils was significantly associated with OS in both cohorts. The hazard ratio of patients with a risk score of 3-4 was 5.42 (95% confidence interval: 1.52-19.42, P = 0.0094) in cohort 1 and 9.42 (2.06-43.06, P = 0.0038) in cohort 2, respectively. CONCLUSIONS: We conclude that peripheral blood leukocytes are independently associated with OS in stage I-II melanoma patients and should be considered as prognostic markers in these patients. Eosinophils and basophils deserve more attention in future investigations.

Histological Characteristics and Early-Stage Diagnosis Are Associated With Better Survival in Young Patients With Epithelial Ovarian Cancer: A Retrospective Analysis Based on Surveillance Epidemiology and End Results Database.

PURPOSE: To analyze the potential prognostic factors of epithelial ovarian cancer (EOC) in women aged under 35 compared to those aged 60-79. METHODS: Cases were retrospectively obtained from SEER database. Clinical characteristics, such as race, histological type, AJCC stage, laterality of tumors, CA125 results, and surgical strategies, were analyzed in < 35 years group and 60-79 years group. Kaplan-Meier survival curves were used to evaluate overall survival (OS) and cause-specific survival (CSS). Cox proportional hazard model was used to identify the predictors for CSS. RESULTS: Sixteen thousand eight hundred forty-seven EOC patients diagnosed in 2004-2015 were identified from SEER database, with 1,015 aged under 35 and 15,833 aged 60-79. In < 35 years group, mucinous (32.2%) was the most common histological type, followed by high-grade serous (26.6%) and endometrioid (18.3%), while in 60-79 years group, high-grade serous (68.3%) represented the leading histological type. Most young women were diagnosed at stage I (57.7%), while most old women were diagnosed at stage (48.1%). Both 5-year OS and 5-year CSS were higher in < 35 years group (5-year OS: 76.00% vs 40.18%, p < 0.001; 5-year CSS: 83.56% vs 55.18%, p < 0.001). The multivariate analysis identified histological type and stage as prognostic factors for CSS in both groups. Endometrioid represented a positive predictor for CSS, while carcinosarcoma and malignant Brenner were related to a worse CSS. (< 35 years group: carcinosarcoma vs endometrioid: HR 5.630, p=0.024; malignant Brenner vs endometrioid: HR 4.005, p < 0.001; 60-79 years group: carcinosarcoma vs endometrioid: HR 3.606, p < 0.001; malignant Brenner vs endometrioid: HR 2.291, p < 0.001). Tumors laterality, CA125 levels, surgery and lymphadenectomy failed to be associated with the CSS in < 35 years group, while found to be independent risk factors in 60-79 years group. CONCLUSION: EOC women aged under 35 had a better survival outcome over EOC women aged 60-79, owing to high proportion of endometrioid and mucinous types in histology, as well as early-stage diagnosis. Identification of histological types and gene profiles should be underscored in young EOC patients.

Establishment and validation of an AJCC stage- and histologic grade-based nomogram for pancreatic neuroendocrine tumors after surgical resection.

BACKGROUND: Development of an accurate model to predict prognosis for patients with pancreatic neuroendocrine tumors (P-NETs) after surgical resection is urgently needed. METHODS: In the present study, we conducted Cox proportional hazards regression to identify critical prognostic factors for P-NETs by analyzing data from 2174 patients in the Surveillance, Epidemiology, and End Results (SEER) database. Based on the results of multivariate analysis, a novel nomogram was established. Finally, the novel nomogram for P-NETs was validated in a cohort of 81 patients from a Chinese institute. RESULTS: In the multivariate analysis, age, tumor location, American Joint Committee on Cancer (AJCC) stage, histologic grade, lymph node ratio (LNR) and tumor size were independent risk factors for overall survival (OS) in P-NET patients who underwent radical resection. A nomogram consisting of age, sex, AJCC stage and histologic grade was found to have a concordance index (C-index) of 0.79 for OS in the SEER database, which was significantly higher than the C-index based on the AJCC stage, European Neuroendocrine Tumor Society (ENETS) stage or histologic grade alone. In the validation cohort, the C-index based on the nomogram reached 0.78 for OS. We also defined high-risk (total points >13.5 based on the nomogram) and low-risk populations (total points <13.5 based on the nomogram) in the validation cohort. We found that the actual 5-year recurrence rate in the high-risk group was significantly higher than that in the low-risk group (80.8% vs 23.4%, P<0.001). Kaplan-Meier analysis showed that the 5-year recurrence-free survival (RFS) in the low-risk group was significantly higher than that in the high-risk group (P<0.001). CONCLUSION: An AJCC stage- and histologic grade-based model was found to be extremely efficient in predicting survival for patients with P-NETs after surgical resection and deserves further evaluation for future clinical applications.

Racial differences in patterns of treatment among men diagnosed with de novo advanced prostate cancer: A SEER-Medicare investigation.

PURPOSE: Approximately 5% of men were initially diagnosed with (also referred to as de novo) advanced stage prostate cancer and experience far poorer survival compared to men diagnosed with local or regionally advanced disease. Given the number of new therapies targeting metastatic and castrate-resistant disease, we sought to describe recent treatment patterns by race for de novo AJCC stage IV prostate cancer. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare files to identify men aged 66 and older diagnosed in 2004-2014 with advanced prostate cancer, and examined patterns of treatment among all patients and stratified by race/ethnicity. RESULTS: There were 8828 eligible patients identified, and non-Hispanic black (NHB) patients were more likely to go without treatment (P < 0.001) compared to non-Hispanic white (NHW) patients, even after accounting for early mortality and TNM stage. The frequency of nearly all forms of treatment was lower among NHB with the exception of orchiectomy, which was significantly higher (10.1% vs 6.1%, P < 0.001), and the use of the progesterone Megace among Medicare Part D enrollees (24.6% vs 15.0%, P < 0.001). CONCLUSIONS: Results from this study of elderly Medicare patients presenting with advanced stage prostate cancer suggest that NHB men are less likely to pursue aggressive treatment options. With the reduction in screening for prostate cancer, presumably tied to USPSTF recommendations, and the increasing incidence of men diagnosed with de novo metastatic disease, understanding drivers of treatment-related decisions are critical in reducing racial disparities in advanced prostate cancer outcomes.

Development and Validation of a Nomogram for Predicting Survival in Male Patients With Breast Cancer.

Male breast cancer (MBC) is rare, and most patients are diagnosed at an advanced stage. We aimed to develop a reliable nomogram to predict breast cancer-specific survival (BCSS) for MBC patients, thus helping clinical diagnosis and treatment. Based on data from the Surveillance, Epidemiology, and End Results (SEER) database, 2,451 patients diagnosed with MBC from 2010 to 2015 were selected for this study. They were randomly assigned to either a training cohort (n = 1715) or a validation cohort (n = 736). The Multivariate Cox proportional hazards regression analysis was used to determine the independent prognostic factors, which were then utilized to build a nomogram for predicting 3- and 5-year BCSS. The discrimination and calibration of the new model was evaluated using the Concordance index (C-index) and calibration curves, while its accuracy and benefits were assessed by comparing it to the traditional AJCC staging system using the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and the decision curve analysis (DCA). Multivariate models revealed that age, AJCC stage, ER status, PR status, and surgery all showed a significant association with BCSS. A nomogram based on these variables was constructed to predict survival in MBC patients. Compared to the AJCC stage, the C-index (training group: 0.840 vs. 0.775, validation group: 0.818 vs. 0.768), the areas under the receiver operating characteristic curve of the training set (3-year AUC: 0.852 vs. 0.778, 5-year AUC: 0.841 vs. 0.774) and the validation set (3-year AUC: 0.778 vs. 0.752, 5-year AUC: 0.852 vs. 0.794), and the calibration plots of this model all exhibited better performance. Additionally, the NRI and IDI confirmed that the nomogram was a great prognosis tool. Finally, the 3- and 5-year DCA curves yielded larger net benefits than the traditional AJCC stage. In conclusion, we have successfully established an effective nomogram to predict BCSS in MBC patients, which can assist clinicians in determining the appropriate therapy strategies for individual male patients.

FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma.

Prognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005-2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III-IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.

High metastatic node number, not extranodal extension, as a node-related prognosticator in surgically treated patients with nodal metastatic salivary gland carcinoma.

BACKGROUND: The prognostic relevance of extranodal extension (ENE) for salivary gland carcinoma (SGC) remains unclear. The present study is undertaken to investigate the predictive significance of pathological nodal parameters in surgically treated patients with nodal metastatic SGC. METHODS: This multicenter cohort included 114 patients with pathologically proven node-positive SGC between 2000 and 2014. Possible correlations of clinicopathological parameters and outcomes were examined. RESULTS: The median follow-up was 69 months (range, 11-173 months). The multivariate analysis identified metastatic node number (1-2 vs 3-6; 1-2 vs ≥7) as an independent predictor for regional control (P = 0.005; P = 0.02), locoregional control (P = 0.008; P = 0.04), distant metastasis-free survival (P = 0.17; P = 0.006), disease-free survival (P = 0.05; P = 0.002), and overall survival (P = 0.18; P = 0.009), whereas ENE was not associated with survival outcomes. CONCLUSIONS: Metastatic node number, not ENE, is an independent node-related prognosticator for SGC. Integration of ENE into the American Joint Committee on Cancer 8th edition staging criteria may not improve prognostic performance.