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Summary Background /Objective: As a new immune-nutritional marker, the controlled nutritional status (CONUT) score has been reported to predict the prognosis of cancer patients. We aimed to elucidate the prognostic value of preoperative CONUT score in pancreatic cancer patients undergoing radical surgery, and to construct a nomogram based on CONUT score to predict individual survival. Methods Preoperative CONUT scores were calculated prospectively in 382 patients with pancreatic cancer who underwent radical surgery. Evaluated the relationship between CONUT score and pancreatic cancer prognosis. Cox proportional hazard models were used to determine predictors of survival and a new nomogram was established to predict pancreatic cancer overall survival (OS). Results The area under curve of CONUT score was higher than other immune-nutritional indexes. The OS of the high-CONUT group were significantly lower than that of low-CONUT group. Multivariate analysis showed that CONUT score, gender, AJCC stage, complications and reoperation were independent prognostic factors for OS. Nomogram based on these variables has better discriminant ability in predicting survival compared with other traditional staging systems. Conclusions Preoperative CONUT score is an effective independent predictor of OS in pancreatic cancer patients undergoing radical surgery. This new CONUT based nomogram provides accurate, individualized survival prediction for pancreatic cancer.

Shengwei Tian,1,2,* Si Sun,1,2,* Weipu Mao,1,2,* Siwei Qian,1,2 Lei Zhang,1,2 Guangyuan Zhang,1,2 Bin Xu,1,2 Ming Chen1– 3 1Department of Urology, Zhongda Hospital, Southeast University, Nanjing, 210009, People’s Republic of China; 2Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, People’s Republic of China; 3Department of Urology, Nanjing Lishui District People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Xu; Ming ChenDepartment of Urology, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, People’s Republic of ChinaTel +86-18012949196; +86-13913009977Email njxb1982@126.com; mingchenseu@126.comBackground: The aim of this study was to establish a nomogram model to evaluate the prognosis of early-onset kidney cancer (EOKC) in terms of overall survival (OS) and cancer-specific survival (CSS).Methods: Patients with EOKC diagnosed between 2004 and 2015 were collected from Surveillance, Epidemiology and End Results (SEER) and randomly assigned to the training and validation set at a ratio of 2 to 1. Important variables for constructing nomograms were screened by univariate and multivariate Cox analysis. The nomogram model was evaluated using concordance index (C-index), decision curve analysis (DCA) curves, and receiver operating characteristic (ROC) curves.Results: A total of 12,526 EOKC patients were included in the study. OS nomogram was constructed based on gender, age, race, grade, AJCC stage, TNM stage, histology, chemotherapy and radiotherapy. CSS nomogram was constructed based on listed above except gender. In the external validation, the C-index for the OS nomogram was 0.855 (95% CI 0.834– 0.976), and the C-index for the CSS nomogram was 0.938 (0.925– 0.951). High-quality calibration curves were noted in both OS and CSS nomogram models. ROC and DCA curves showed that nomograms had better predictive performance than TNM stage and SEER stage.Conclusion: The nomogram model provides an applicable tool for evaluating the OS and CSS prognosis of EOKC.Keywords: early-onset kidney cancer, nomogram, OS, CSS, SEER

Version 7/7/2020 with edit Triple-Negative Breast Cancer in New Orleans – part deaux Objectives: To update our previously reported findings with more current data from SEER 18 registries to compare race-specific incidence rates of triple-negative breast cancer (TNBC) in New Orleans (NO) and Louisiana (LA) with other SEER metro areas and identify the predictors of TNBC. Background: We previously reported significantly increased incidence rates of TNBC in black women (BW) in NO and LA than other SEER metro areas. Methods: We analyzed tumor characteristics of invasive female breast cancers diagnosed from 2011-2017 from SEER 18 for BW and white women (WW). We compared LA data with SEER 18 and metropolitan areas (Atlanta, Detroit, Los Angeles and San Francisco) as we did with our previous data set. Predictors of TNBC in NO and LA were identified in multivariate logistic regression adjusting for age, BMI, poverty, insurance, tumor size, Bloom-Richardson grade and AJCC stage. Results: The overall incidence rate of TNBC in BW was again significantly higher in NO (29.8 per 100,000) than any metro area and the SEER metro areas combined (23.9 per 100,000). Detroit again had the second highest rate (27.2) followed by San Francisco/Oakland (23.8) Los Angeles (22.3) and Atlanta (22.1). The multivariable analysis showed that younger age, large tumor size, high grade were associated with increased risk of TNBC in BW. Conclusions: The incidence rates of TNBC in BW in NO continue to be consistently higher compared to LA and other SEER 18 metro areas. This data reiterates the importance of ongoing translational research to broaden the understanding and optimize the treatment of this aggressive disease, especially in this vulnerable population. Citation Format: Michelle M Loch, Mei-Chin Hsieh, Thomas Reske, Vivien Chen, Xiao-Cheng Wu. Triple negative breast cancer in New Orleans, part deux [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-40.

The purpose of our study was to establish a reliable and practical nomogram based on significant clinical factors to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with germ cell testicular cancer (GCTC). Patients diagnosed with GCTC between 2004 and 2015 were obtained from the SEER database. Nomograms were constructed using the R software to predict the OS and CSS probabilities and the constructed nomograms were validated and calibrated. A total of 22,165 GCTC patients were enrolled in the study, including the training cohort (15,515 patients) and the validation cohort (6,650 patients). In the training cohort, multivariate Cox regression showed that age, race, AJCC stage, SEER stage and surgery were independent prognostic factors for OS, while age, race, AJCC stage, TM stage, SEER stage and radiotherapy were independent prognostic factors for CSS. Based on the above Cox regression results, we constructed prognostic nomograms of OS and CSS in GCTC patients and found that the OS nomograms had higher C-index and AUC compared to TNM stage in the training and validation cohorts. In addition, in the training and external validation cohorts, the calibration curves showed a good consistency between the predicted and actual 3-, 5- and 10-year OS and CSS rates of the nomogram. The current prognostic nomogram can provide a personalized risk assessment for the survival of GCTC patients.

Background The TNM system of the International Union for Cancer Control/American Joint Committee on Cancer (UICC/AJCC) and the Japanese Gastric Cancer Association (JGCA) systems are the most used lymph node (LN) staging systems in gastric cancer. This study estimated the influence of anatomic location-based node stations on survival and proposed a new staging method based on both the number and anatomical distribution of metastatic LNs (mLNs). Methods Stage I–III gastric cancer patients with radical gastrectomy were retrospectively evaluated. Overall survival (OS) was estimated in 1786 patients with UICC/AJCC stage N1–N3b disease and compared with estimates obtained using JGCA group 1–3 mLN staging. Results The OS of UICC/AJCC stage N1–N3b patients with group 2 JGCA mLNs was significantly worse than that of patients with only group 1 mLNs. The OS of the patients with group 2 mLNs was similar to that of patients with group 1 mLNs but in the next more advanced UICC/AJCC-N stage. The OS of patients with group 3 mLNs was worse than that of patients with any UICC/AJCC-N stage and was similar to that of N3b patients with group 2 mLNs. A new pathological node (pN) staging classification was developed that advanced the N-staging of patients with group 2 mLNs. It was a better indicator of prognosis than the eighth UICC/AJCC-N and the thirteenth JGCA group staging systems. Conclusions A simple, accurate pN staging system including both the number and location of mLNs had improved homogeneity, discriminatory ability, and gradient monotonicity.

BACKGROUND The adjuvant treatment for patients with resected pancreatic cancer (PC) is not yet standardized. Because the prognosis differs according to the American Joint Committee on Cancer (AJCC) stage, a tailored approach to establish more aggressive treatment plans in high-risk patients is necessary. However, studies comparing the efficacy of adjuvant treatment modalities according to the AJCC stage are largely lacking. AIM To compare the efficacy of chemotherapy and chemoradiation therapy according to AJCC 8th staging system in patients with PC who underwent surgical resection. METHODS A total of 335 patients who underwent surgical resection and adjuvant treatment for PC were included. Patients were divided into three groups: Chemoradiation therapy (CRT) group, systemic chemotherapy (SCT) group and combined treatment of chemoradiation plus chemotherapy therapy (CRT-SCT) group. The primary outcomes were differences in overall survival (OS) between the three groups. The secondary outcomes were differences in recurrence-free survival, recurrence pattern and adverse events between the three groups. RESULTS Patients received CRT (n = 65), SCT (n = 62) and CRT-SCT (n = 208). Overall median OS was 33.3 mo (95% confidence interval (CI): 27.4-38.6). In patients with stage I/II, the median OS was 27.0 mo (95%CI: 2.06-89.6) in the CRT group, 35.8 mo (95%CI: 26.9-NA) in the SCT group and 38.6 mo (95%CI: 33.3-55.7) in the CRT-SCT group. Among them, there was no significant difference in OS between the three groups. In 59 patients with stage III, median OS in the SCT group [19.0 mo (95%CI: 12.6-NA)] and the CRT-SCT group [23.4 mo (95%CI: 22.0-44.4)] was significantly longer than that in the CRT group [17.7 mo (95%CI: 6.8-NA); P = 0.011 and P < 0.001, respectively]. There were no significant differences in incidence of locoregional and distant recurrences between the three groups (P = 0.158 and P = 0.205, respectively). Incidences of grade 3 or higher hematologic adverse events were higher in the SCT and CRT-SCT groups than in the CRT group. CONCLUSION SCT and CRT-SCT showed significantly longer OS and recurrence-free survival than CRT in patients with AJCC stage III, while there was no significant difference in OS between the CRT, SCT and CRT-SCT groups in patients with AJCC stage I/II. Different adjuvant therapy according to AJCC stage can be applied in patients with PC.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with high mortality. Identifying patients at risk of distant metastasis assists with management and prognostication. We aimed to define the relationship between volume, survival, and risk of distant metastases. METHODS: A retrospective review of all patients with SNMM treated at a single institution over a 21-year period was conducted. Tumor volume was calculated using cross-sectional imaging and survival analysis was performed. RESULTS: Sixty-one patients were included. Tumor volume was predictive of local progression free survival (LPFS) (p=0.032), distant metastases free survival (DMFS) (p=0.002), and overall survival (OS) (p=0.022). It was a better predictor than AJCC stage and T-classification. Tumor volume equal to or greater than 5cm(3) was associated with a significantly worse DMFS and OS (p=0.022 and 0.009, respectively). CONCLUSION: Calculation of tumor volume assists in quantifying the risk of distant metastases and death in SNMM.

Purpose In this study, we established the inflammatory factor grade system (IFGs) based on the hepatocellular carcinoma (HCC) microenvironment to investigate the role of inflammatory factor grade (IFG) in predicting the prognosis of patients with American Joint Committee on Cancer (AJCC) stage I-II. Patients and methods We enrolled 87 HCC patients with AJCC stage I-II who underwent R0 resection between 2000 and 2012 and had paraffin-embedded specimens. Immunohistochemistry (IHC) was performed to investigate the expression of 12 inflammatory factors and then to establish the IFGs (grade A or B) based on the IHC data. Subsequently, Kaplan-Meier and Cox univariate/multivariate survival analyses were performed to examine the potential prognostic significance. Results Higher IFG (IFG-B) is significantly associated with greater tumor size (P=0.037), and IFG-B predicts a worse disease-free survival (DFS, P

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P, Patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages.

The FGD3 gene works as a cell migration inhibitor and seems to be a promising indicator of outcome in some human cancers including breast. In this study, we analysed for the first time the prognostic role of FGD3 in young breast cancer patients. We studied the relationship between traditional prognostic factors, FGD3 expression and outcome in ≤40 years breast cancer patients. We found that lower FGD3 expression decreased the probability of disease-free survival (p = 0.042) and overall survival (p = 0.007). In a multivariate analysis for overall survival AJCC stage (p = 0.005) and FGD3 expression (p = 0.03) resulted independent prognostic factors. Low FGD3 expression increased the risk of death from disease (HR 5.73, p = 0.03). Moreover, low FGD3 expression was associated with more widespread lymph node involvement (p = 0.04) and a lower FGD3 staining intensity was found in positive-lymph-node patients vs negative (p = 0.003) and in patients with ≥10 involved lymph nodes vs p = 0.05). Our results suggest FGD3 to be a significant independent prognostic factor in young breast cancer patients in terms of disease-free survival and overall survival. A lower expression increased the risk of recurrence and death from disease and was associated with widespread lymph node metastases.

Background Combined hepatocellular‐cholangiocarcinoma (CHC) is a heterogeneous group of primary liver cancers characterized by the coexistence of both hepatic and biliary cellular contents. The aim of this study was to compare CHC and intrahepatic cholangiocarcinoma (ICC) and investigate the treatment and survival of patients with CHC. Methods Data on CHC and ICC, including clinicopathological characteristics, treatments, and survival outcomes were extracted from the SEER database between 2004 and 2016. Univariate and multivariate analyses of all data were performed to identify the risk factors associated with survival outcomes. The overall survival (OS) rates of CHC patients who underwent hepatic resection (HR) or liver transplantation (LT) were also assessed before and after propensity score matching. Results A total of 1066 consecutive patients who had been diagnosed with CHC (n = 286) or ICC (n = 780) were identified. The mean age of the CHC cohort was 60.8±10.7 years old. Among the CHC group, a large proportion of the patients were men and of White ethnicity (73.1% and 71.3%, respectively). The majority of tumors were poorly differentiated (37.8%), while the most common AJCC stage at presentation was stage I (31.4%). Multivariable analysis of all CHC patients revealed that only tumor size, M1 stage, AJCC stage IIIC, AJCC stage IV, surgery, and chemotherapy were significantly associated with OS. The OS was comparable with the ICC in the initial 36 months and better in the subsequent follow‐up after treatment. Surgery was associated with better survival outcomes, whether in the early or advanced stages. Regarding the specific types of surgery, the OS rates were similar in selected patients following HR or LT. Conclusion In patients with CHC, surgical intervention resulted in better long‐term survival outcomes than nonsurgical treatments. The OS rate of CHC patients compared with that of ICC patients was discriminated before and after a 3‐year follow‐up.

Objective: To develop and validate ubiquitination-related molecular subtypes and a novel prognostic index using ubiquitination-related genes (URGs) for patients with bladder cancer (BCa).Materials and Methods: We downloaded the clinical data and transcriptome data of BCa from TCGA and GEO database. Consensus clustering analysis was conducted to identify ubiquitination-related molecular subtypes for BCa. Besides, we performed univariate and multivariate Cox regression analysis to develop a novel prognostic URGs-related index for BCa. We conducted internal and external verification in TCGA cohort and GEO cohort, respectively. Furthermore, the associations of ubiquitination-related molecular subtypes and prognostic index with tumor immune environment were also investigated.Results: A total of four ubiquitination-related molecular subtypes of BCa were finally identified. These four molecular subtypes had significantly different clinical characteristics, prognosis, PD-L1 expression level and tumor microenvironment. Besides, we developed a novel prognostic index using six URGs (including HLA-A, TMEM129, UBE2D1, UBE2N, UBE2T and USP5). The difference in OS between high and low-risk group was statistically significant in training cohort, testing cohort, and validating cohort. The area under ROC curve (AUC) for OS prediction was 0.736, 0.723, and 0.683 in training cohort, testing cohort, and validating cohort, respectively. Multivariate survival analysis showed that this index was an independent predictor for OS. This prognostic index was especially suitable for subtype 1 and 3, older, male, high grade, AJCC stage III-IV, stage N0, stage T3-4 BCa patients.Conclusions: This study identified a total of four ubiquitination-related molecular subtypes with significantly different tumor microenvironment, prognosis, clinical characteristics and PD-L1 expression level. Besides, a novel ubiquitination-related prognostic index for BCa patients was developed and successfully verified, which performed well in predicting prognosis of BCa.

Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p &lt, 0.001) and overall survival (OS) (p &lt, 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p &lt, 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

Introduction The role of postoperative radiation (PR) in treating mammary ACC is poorly defined. This study evaluated the impact of PR on survival outcomes for mammary ACC and the extent of utilization. Methods Patients who underwent surgery for mammary ACC from 2005 to 2015 in SEER database were analyzed. KM analyses of OS and DSS were done for PR versus no PR. Cox hazard regression models were used to determine predictors of OS and DSS. Results Of the 488 patients, 244 underwent PR. The PR group was younger, but other variables were similar between the 2 groups. OS was better for PR (p = 0.029). 10-year DSS was better for PR group by an absolute value of 6 % but did not reach statistical significance (p = 0.537). Age, radiation, nodal metastasis, and grade III/IV were independent predictors of OS while grade III/IV and AJCC stage III/IV independently predicted DSS. Conclusion PR improves OS for mammary ACC, but this study did not show increased utilization. Radiation should be considered after surgery for mammary ACC, particularly for patients with independent predictors of OS., Highlights • The role of postoperative radiation (PR) in the management of mammary adenoid cystic carcinoma (ACC) is still poorly defined. • Postoperative radiation improves OS for mammary ACC. • Despite previous studies demonstrating benefits of PR, this study did not show increased use of the treatment modality. • PR should be considered for mammary ACC, particularly for patients with negative independent predictors of OS.

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

Background Gene expression profiling (GEP) has been integrated into cancer treatment decision‐making in multiple neoplasms. We prospectively evaluated the prognostic utility of the 31‐GEP test (DecisionDx‐Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB). Methods One hundred fifty‐nine patients (age 26‐88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing. GEP results were reported as low‐risk Class 1 (subclasses 1A and 1B) or high‐risk Class 2 (subclasses 2A and 2B). Statistical analyses were performed with chi‐square analysis, t tests, log‐rank tests, and Cox proportional hazard models. Recurrence‐free survival (RFS) and distant metastasis‐free survival (DMFS) were estimated using Kaplan‐Meier method. Results Median follow‐up was 44.9 months for event‐free cases. Median Breslow thickness was 1.4 mm (0.2‐15.0 mm). There were 117 Class 1 and 42 Class 2 patients. Gender, age, Breslow thickness, ulceration, SNB positivity, and AJCC stage were significantly associated with GEP classification (P

Colorectal cancer (CRC) remains a major public health burden worldwide, despite increased knowledge on its pathogenesis and advances in therapy. We aimed to evaluate a new histological grading system based on poorly differentiated clusters (PDCs) counting – the PDCs grade (PDCs-G), and its clinicopathological and prognostic significance, compared to the World Health Organisation (WHO) grading system (WHO grade). We reviewed 71 surgical resection specimens for CRC from the Emergency County Hospital “Pius Brînzeu” Timisoara. The cases were graded using the WHO grade and the PDCs-G, with further analysis of their association with the other recognised prognostic parameters. Using the WHO grade, 9% of the analysed cases were G1, 80% G2, 11% G3, and none of the tumours was graded G4, while in the PDCs-G 16% were G1, 45% G2, and 39% G3. In multivariate analysis PDCs-G was significantly associated with the American Joint Committee on Cancer stage of the disease (AJCC stage) (p = 0.0003), depth of invasion (pT) (p = 0.0084), nodal status (LNM) (p < 0.0001), lymphovascular invasion (LVI) (p < 0.0001), perineural invasion (PNI) (p < 0.0052), and tumour border configuration (p < 0.0001). The novel grading system based on PDCs counting is an additional histological tool in the evaluation of CRC and a promising new prognostic factor for these patients.

Introduction: Male breast cancer (MBC) is a rare tumor with few cases for research. Using the Surveillance, Epidemiology, and End Results program database, we carried out a competing risk analysis in patients with primary nonmetastatic MBC and built a predictive nomogram. Materials and Methods: We extracted primary nonmetastatic MBC patients according to the inclusion and exclusion criteria. Cumulative incidence function (CIF) and proportional subdistribution hazard model were adopted to explore risk factors for breast cancer-specific death (BCSD) and other cause-specific death (OCSD). Then we built a nomogram to predict the 3-year, 5-year and 8-year probabilities of BCSD and OCSD. C-indexes, Brier scores and calibration curves were chosen for validation. Results: We identified 1,978 nonmetastatic MBC patients finally. CIF analysis showed that the 3-year, 5-year and 8-year mortalities were 5.2%, 10.6% and 16.5% for BCSD, and 6.1%, 9.6% and 14.4% for OCSD. After adjustment of Fine and Gray models, black race, PR (-), advanced T/N/grade and no surgery were independently associated with BCSD. Meanwhile, elderly, unmarried status, advanced AJCC stage and no chemotherapy resulted in OCSD more possibly. A graphic nomogram was developed according to the coefficients from the Fine and Gray models. The calibration curves displayed exceptionally, with C-indexes nearly larger than 0.700 and Brier scores nearly smaller than 0.100. Conclusion: The competing risk nomogram showed good accuracy for predictive prognosis in nonmetastatic MBC patients. It was a useful implement to evaluate crude mortalities of BCSD and OCSD, and help clinicians to choose appropriate therapeutic plans.

Background HER2+ and hormone receptor (HoR)‐negative breast cancer usually associated with poor outcome. However, it remained elusive for the prognosis of small (T1a‐T1c) HER2+/HoR‐ breast cancer. The present study retrospectively analyzed the Surveillance, Epidemiology, and End Results (SEER) database to explore the clinicopathological characteristics and prognosis of T1a‐T1c HER2+/HoR‐ breast cancer. Material and Methods Data for patients diagnosed with either HER2‐/HoR+or HER2+/HoR‐ T1a‐T1c breast cancer between 2010 and 2012 were obtained from SEER program. Survival analyses were conducted by Kaplan‐Meier method and Cox proportion hazard regression. Results Totally, 2648 HER2+/HoR‐ and 56387 HER2‐/HoR+T1a‐T1c breast cancer patients were enrolled. There was a clear trend that tumor size had a positive correlation with advanced AJCC stage (P

We aimed to explore the clinicopathological features and survival-related factors for intrahepatic cholangiocarcinoma (ICC). Eligible data were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015. Totally, 4595 ICC patients were collected with a male to female ratio of nearly 1:1. The higher proportion of ICC patients was elderly, tumor size ≥ 5 cm and advanced AJCC stage. Most patients (79.2%) have no surgery, while low proportion of patients receiving radiotherapy (15.1%). The median survival was 7.0 months (range 0–153 months). The 5-year CSS and OS rates were 8.96% and 7.90%. Multivariate analysis found that elderly age (aged ≥ 65 years old), male, diagnosis at 2008–2011, higher grade, tumor size ≥ 5 cm, and advanced AJCC stage were independent factors for poorer prognosis; while API/AI (American Indian/AK Native, Asian/Pacific Islander) race, married, chemotherapy, surgery and radiotherapy were independent favorable factors in both CSS and OS. Furthermore, stratified analysis found that chemotherapy and radiotherapy improved CSS and OS in patients without surgery. Age, sex, race, years of diagnosis, married status, grade, tumor size, AJCC stage, surgery, chemotherapy and radiotherapy were significantly related to prognosis of ICC. Chemotherapy and radiotherapy could significantly improve survival in patients without surgery.

PurposeTo analyze the potential prognostic factors of epithelial ovarian cancer (EOC) in women aged under 35 compared to those aged 60–79.MethodsCases 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.ResultsSixteen 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.ConclusionEOC 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.

This study aimed to explore the association of tumor sidedness with the prognosis of patients with colon signet ring cell carcinoma (SRCC). Eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with left-sided colon SRCC and those with right-sided lesions. A total of 2660 patients were included, among them, 1983 (74.5%) had right-sided colon SRCC. Compared to patients with left-sided colon SRCC, those who had the right-sided colon SRCC showed higher proportion of white race, female, aged ≥ 65 years, receiving total colectomy and ≥ 4 regional lymph node dissection; while had lower proportion of advanced AJCC stage. Besides, right-sided patients exhibited superior 5-year CSS (32.74% vs. 25.89%, P = 0.001) and OS (27.38% vs. 23.02%, P = 0.024) rates compared with left-sided ones. Multivariate analysis revealed that tumor sidedness was an independent prognostic factor. To be specific, patients with right-sided colon SRCC showed better CSS (HR: 0.873; 95% CI 0.777–0.981; P = 0.023) and OS (HR: 0.838; 95% CI 0.753–0.965; P = 0.002). Moreover, subgroup analysis demonstrated superior CSS and OS for right-sided patients in most subgroups. Tumor sidedness was an independent prognostic indicator for colon SRCC. Besides, patients with right-sided colon SRCC have superior prognosis than those with left-sided lesions.

Background Malignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed. Methods A retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973–2016). Results Data for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P 44 years and AJCC stage III and IV were associated with poor DSS. Conclusion MTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient’s age and AJCC stage was independent predictor of DSS.

Background: This study aimed to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in small intestinal gastrointestinal stromal tumors (SI GISTs). Methods: Patients diagnosed with SI GISTs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further randomly divided into training and validating cohorts. Univariate and multivariate Cox analyses were conducted in the training set to determine independent prognostic factors to build nomograms for predicting 3- and 5-year OS and CSS. The performance of the nomograms was assessed by using the concordance index (C-index), calibration plot, and the area under the receiver operating characteristic curve (AUC). Results: Data of a total of 776 patients with SI GISTs were retrospectively collected from the SEER database. The OS nomogram was constructed based on age, surgery, imatinib treatment, and American Joint Committee for Cancer (AJCC) stage, while the CSS nomogram incorporated age, surgery, tumor grade, and AJCC stage. In the training set, the C-index for the OS nomogram was 0.773 (95% confidence interval [95% CI]: 0.722–0.824) and for the CSS nomogram 0.806 (95% CI: 0.757–0.855). In the internal validation cohort, the C-index for the OS nomogram was 0.741, while for the CSS nomogram, it was 0.819. Well-corresponded calibration plots both in OS and CSS nomogram models were noticed. The comparisons of AUC values showed that the established nomograms exhibited superior discrimination power than the 7th Tumor-Node-Metastasis staging system. Conclusion: Our nomogram can effectively predict 3- and 5-year OS and CSS in patients with SI GISTs, and its use can help improve the accuracy of personalized survival prediction and facilitate to provide constructive therapeutic suggestions.

The aim of our study was to explore the value of the 8th edition TNM staging system on evaluating the prognosis of colorectal carcinoid. Colorectal carcinoid patients between 1988 and 2015 were selected in the Surveillance, Epidemiology, and End Results Program (SEER) database for analysis. About 4286 patients with colorectal carcinoid tumors were identified, of which were carcinoid tumor NOS (n = 1726), neuroendocrine carcinoma (NEC) (n = 1346) and other carcinoid tumor (OCT) (n = 591). Worsening 10‐year CSS rates with increasing N status, M status, and SEER historic stage were demonstrated across all three above groups (all P, For all carcinoid tumors, detailed 8th AJCC categories of advanced stages conferred increased HRs with overlapping CIs. However, in the early and middle status, HRs did not increase with the increase of stages, or there was no difference in HRs between adjacent stages. More optimized staging methods should be developed and validated in the future.

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.

PURPOSE: Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. METHODS: Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. RESULTS: In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m(2) difference in BMI = 0.85, 95% CI 0.75–0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35 kg/m(2) vs. 18.5–24.9 kg/m(2) = 4.74, 95% CI 1.78–12.59). CONCLUSIONS: Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

Current staging paradigms from the American Joint Committee on Cancer (AJCC) staging system for upper urinary tract carcinomas treat locoregionally advanced (T4 and N+) and metastatic (M1) patients as a single entity (stage IV). The current study proposes a modification of the AJCC staging system where these 2 entities are separated.The Surveillance, Epidemiology, and End Results (SEER) database (2004-2014) was accessed through SEER*Stat program. Overall survival (OS) analyses according to AJCC and modified staging systems were conducted through Kaplan-Meier analysis. Moreover, cancer-specific survival analysis was conducted through a Cox proportional hazard model.OS was compared according to AJCC and modified AJCC staging systems. The P value for OS trend for both staging systems was .0001. This was also found when OS was stratified by the site of the primary (renal pelvis vs. ureter) as well as when stratified by the staging approach (pathologic vs. clinical) (P .0001). Cancer-specific Cox proportional hazard analysis (adjusted for age, grade, histology, and surgical treatment) was conducted for both staging systems. Pairwise hazard ratio comparisons between different stage categories for both staging systems were significant (P .0001). The c index for cancer-specific survival for the AJCC staging system was 0.706 with standard error 0.006 (95% confidence interval, 0.695-0.717), while the c index for cancer-specific survival for the modified AJCC staging system was 0.714 with standard error 0.006 (95% confidence interval, 0.702-0.725).Dividing stage IV upper urinary tract carcinomas into locoregionally advanced and metastatic disease subcategories improves the prognostic utility of the staging system compared to the current AJCC staging system. Given the limitations of a SEER-based study, this concept needs to be externally validated in various settings.

Conjunctival squamous cell carcinoma (SCC) is the most common tumor of conjunctival epithelium. It is associated with risk of permanent visual impairment and has the capability to recur, metastasize, and cause death. Deregulation of cell cycle control has been reported in a number of malignancies. The aim of the present study was to assess expression of G1/S cell cycle regulatory proteins [retinoblastoma protein (pRb)/P16/cyclin D1] in conjunctival SCC. Forty-four prospective cases of conjunctival SCC from a tertiary eye care referral center in northern India were included in this study. American Joint Committee on Cancer (AJCC) staging was performed and patients were followed up for 46±3.2 months. pRb loss was seen in 87% and overexpression of p16 and cyclin D1 in 36% and 66%, respectively. Kaplan-Meier analysis revealed reduced disease-free survival in patients with pRb loss (P=0.006). On univariate analysis, pRb loss (P=0.02), orbital invasion (P=0.03), and AJCC stage ≥T3 (P=0.03) emerged as significant high-risk features. On multivariate analysis pRb loss emerged as the most significant poor prognostic indicator in conjunctival SCC cases. Our findings suggest pRb loss to be a useful indicator of aggressive behavior and is recommended for identifying high-risk conjunctival SCC patients.

Background: Renal cell carcinoma (RCC) is considered the commonest and most fatal malignant neoplasm of the kidney. Distant metastases are found in 30% of RCC patients at diagnosis, which is considered an important sign of predic-tion of patients' prognosis. So trying to clarify molecular mechanisms of metastases in RCC could help to discover a recent therapeutic target to decrease and control distant metastases and subsequently might improve patients prognosis.Aim of the Study: Was to assess the EZH2 & Twist-1 combined expressions in RCC tissues with different histopatho-logical subtypes and to correlate their expression with clin-icopathological parameters.Material and Methods: We have assessed expression of EZH2 & Twist-1 in tissue by using immunohistochemistry in 50 paraffin blocks of RCC different histopathological subtypes, analyzed correlations between the levels of combined expres-sions and clinicopthological data. Results: Increased EZH2 expression was positively asso-ciated with advanced AJCC stage, Lymph Node (L.N) metas-tases (p=0.006), higher grade (p

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is undefined among the different macroscopic types. This study evaluated the viability of the American Joint Committee on Cancer (AJCC) 8th edition staging classification for different macroscopic types. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 2,679 eligible patients with an estimated 199 periductal infiltrating type of ICC (ICC-PI) patients and 2,480 mass-forming type of ICC (ICC-MF) patients. After conducting a multivariate Cox analysis, we found that the AJCC 8th edition staging system was suitable for ICC-MF patients but not for ICC-PI patients according to cancer-specific survival (CSS) and overall survival (OS). The main reason was the similar hazard ratio (HR) between the ICC-PI patients with stage I and stage II disease according to CSS (HR:0.969, P = 0.949) and OS (HR:0.832, P = 0.703). Moreover, we found that ICC-PI patients in AJCC stage I had a similar HR as ICC-MF patients in AJCC stage II according to CSS (HR: 1.208, P = 0.475) and OS (HR:1.206, P = 0.456). Therefore, we suggested that ICC-PI patients may be defined as T2, which is classified as stage II disease. This suggestion for the AJCC 8th edition staging system would be more suitable for different macroscopic types of ICC but requires further verification in prospective clinical trials.

// Martha L. Slattery 1 , Andrew J. Pellatt 2 , Frances Y. Lee 2 , Jennifer S. Herrick 3 , Wade S. Samowitz 4 , John R. Stevens 5 , Roger K. Wolff 6 and Lila E. Mullany 7 1 Department of Medicine, University of Utah, Salt Lake City, Utah, USA 2 Tulane Medical School, New Orleans, Louisiana, USA 3 Department of Medicine, University of Utah, Salt Lake City, Utah, USA 4 Department of Pathology, University of Utah, Salt Lake City, Utah, USA 5 Department of Mathematics and Statistics, Utah State University, Logan, Utah, USA 6 Department of Medicine, University of Utah, Salt Lake City, Utah, USA 7 Department of Medicine, University of Utah, Salt Lake City, Utah, USA Correspondence to: Martha L. Slattery, email: marty.slattery@hsc.utah.edu Keywords: colorectal cancer, miRNAs, survival, stage, prognosis Received: May 16, 2017 Accepted: July 25, 2017 Published: August 03, 2017 ABSTRACT Half of miRNAs expressed in colorectal tissue are expressed < 50% of the population. Many infrequently expressed miRNAs have low levels of expression. We hypothesize that less frequently expressed miRNAs, when expressed at higher levels, influence both disease stage and survival after diagnosis with colorectal cancer (CRC); low levels of expression may be background noise. We examine 304 infrequently expressed miRNAs in 1893 population-based cases of CRC with paired carcinoma and normal mucosa miRNA profiles. We evaluate miRNAs with disease stage and survival after adjusting for age, study center, sex, MSI status, and AJCC stage. These miRNAs were further evaluated with RNA-Seq data to identify miRNA::mRNA associations that may provide insight into the functionality of miRNAs. Eleven miRNAs were associated with advanced disease stage among colon cancer patients ( Q value = 0.10). Eight infrequently expressed miRNAs influenced survival if highly expressed in overall CRC. Of these, five increased likelihood of dying if they were highly expressed, i.e. miR-124-3p, miR-143-5p, miR-145-3p, miR31-5p, and miR-99b-5p, while three were associated with better survival if highly expressed, i.e. miR-362-5p, miR-374a-5p, and miR-590-5p. Thirteen miRNAs infrequently expressed in colon-specific carcinoma tissue were associated with CRC survival if highly expressed. Evaluation of miRNAs::mRNA associations showed that mRNA expression influenced by infrequently expressed miRNA contributed to networks and pathways shown to influence disease progression and prognosis. Our large study enabled us to examine the implications of infrequently expressed miRNAs after removal of background noise. These results require replication in other studies. Confirmation of our findings in other studies could lead to important markers for prognosis.

// Ze-Tian Shen 1 , Han Zhou 1 , Ao-Mei Li 1 , Bing Li 1 , Jun-Shu Shen 1 and Xi-Xu Zhu 1 1 Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China Correspondence to: Xi-Xu Zhu, email: simon_doctor@163.com Keywords: intrahepatic cholangiocarcinoma, stereotactic body radiotherapy, CyberKnife, unresectable, Synchrony Received: December 05, 2016 Accepted: July 18, 2017 Published: August 07, 2017 ABSTRACT Stereotactic body radiation therapy (SBRT) has been an emerging non-invasive treatment modality for patients with intrahepatic cholangiocarcinoma (ICC) when surgical treatment cannot be applied. The CyberKnife ® is a SBRT system that allows for real-time tracking of the tumor. The purpose of this study was to evaluate the clinical outcomes and prognostic factors for ICC patients receiving this treatment. Twenty-eight patients with ICC were enrolled in the present study. The median prescription dose was 45 Gy (range, 36-54 Gy), fractionated 3 to 5 times with a 70% to 92% isodose line. Local control, overall survival, progression-free survival and toxicity were studied. The median follow-up time was 16 months (3-42 months). Based on modified Response Evaluation and Criteria in Solid Tumors (mRECIST), response rate and disease control rate of SBRT in ICC were 46.4% (13/28) and 89.3% (25/28), respectively. Median overall survival was 15 months (95% CI, 7.22-22.78). 1- and 2-years survival rates were 57.1% and 32.1%, and 1- and 2- years Progression-free Survival rates were 50.0 % and 21.4 %. Multivariate analysis revealed that number of lesions (solitary vs. multiple nodules), CA19-9 levels (≤37 U/mL vs. 37-600/>600) and TNM stage (AJCC stage) were independent prognostic factors for ICC patients treated with SBRT. Toxicity was mostly transient and tolerable. No greater than grade 3 toxicity was observed. These results suggested that CyberKnife SBRT might be a good alternative treatment for unresectable ICC.

It has been reported that younger patients with non-small cell lung cancer (NSCLC) tend to have a better prognosis. Yet, few studies have focused on the clinicopathological characteristics and prognosis of young small cell lung cancer (SCLC), especially for patients with age < 50. In our study, we used Surveillance, Epidemiology, and End Results (SEER) population-based data and identified 16503 patients with SCLC including 711 patients aged < 50, 3338 patients aged 50–59, 5937 patients aged 60–69, 4649 patients aged 70–79 and 1868 patients aged ≥ 80 between 2010 and 2013. The Kaplan-Meier methods was used to develop the survival curve, and the results showed that the SCLC patients with aged < 50 tended to a better over survival (OS) and cancer specific survival (CSS) (all, P < 0.001). In addition, Cox regression model was used to analyze survival prognosis factors and perform subgroup analysis. The results showed that age was an independent prognostic factor for CSS (P < 0.001). Importantly, we found that for the patients with AJCC stage III subgroup, the age < 50 had apparent CSS benefit compared with any other age group (all, P < 0.01). Interestingly, for the patients with no surgery, radiation and no radiation subgroup, the age < 50 had no apparent CSS benefit only compared with age 50–59 (all, P > 0.05). In conclusion, our study demonstrated that the SCLC patients with aged < 50 tended had a better survival benefit, especially for patients with AJCC stage III.

Background The purpose of this study was to test the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting recurrence risk of major salivary gland carcinoma in an Asian cohort. Methods We retrospectively enrolled 149 patients who had undergone intended curative resections for major salivary gland carcinoma between 2007 and 2012. The performance of the MSKCC nomogram and the American Joint Committee on Cancer (AJCC) seventh staging system in predicting recurrence risk was compared. Results The MSKCC nomogram and the AJCC staging system both accurately predicted the 5-year recurrence probabilities, with the concordance index (c-index = 0.82; 95% confidence interval [CI], 0.75–0.89 vs c-index, 0.77; 95% CI, 0.68–0.87; p = .45) in patients with major salivary gland carcinomas after curative surgeries. Comparing to the actual observed events, the calibration plot indicated that the MSKCC nomogram accurately estimated the recurrence in low-risk groups but tended to overestimate in high-risk groups. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the prediction was very good for patients with AJCC stages I and II disease (c-index = 0.92 and 0.90, respectively) and modest for those of AJCC stages III and IVa (c-index = 0.51 and 0.62, respectively). Conclusion The MSKCC nomogram and the AJCC staging system each had its value in predicting recurrence of major salivary gland cancers. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the MSKCC nomogram was more accurate in predicting recurrence risks in those patients with AJCC stage I and II diseases than those with late-stage diseases. © 2017 Wiley Periodicals, Inc. Head Neck 39: 860–867, 2017

Introduction Intraductal papillary mucinous neoplasm (IPMN) is a field defect disease of pancreas that has malignant potential. Many studies have recommended surgery as the preferred treatment. We investigated whether a total pancreatectomy (TP) can improve patient prognosis compared to a pancreatoduodenectomy (PD) and the indications for each approach. Patients and methods We obtained data of 548 malignant IPMN patients who underwent either a TP or a PD from SEER database. The survival rates were analyzed using the Kaplan–Meier method and a Cox regression model. Cases were subdivided to investigate the advantages of each procedure. Results The surgical procedures (PD and TP) did not significantly affect either cancer-specific survival (CSS) times or overall survival (OS) times in both Kaplan–Meier analysis and Cox regression (Kaplan–Meier: P CSS = 0.919, P OS = 0.996; Cox: P CSS = 0.735, P OS = 0.820). In the subgroup analyses, patients in stage T4 and AJCC stage III in the TP group had a longer survival time than did those in the PD group (33 months vs 14 months), but not significant (T4: P CSS = 0.124, AJCC III: P CSS = 0.102). In addition, PD had the trend to be better for poorly differentiated patients (P os = 0.055) and older patients. Conclusion TP did not offer any significant OS and CSS benefits as compared to PD. However, for patients in stage T4 and AJCC stage III, TP may extend survival time in some degree. In older or histologically poorly differentiated patients, PD may be preferable to TP. The results are rational, but still warrant further verification due to limited sample volumes of specific subgroups.

Aims Recently, lymph-node ratio (LNR) has emerged as a prognostic tool in staging rectal cancer. Studies to date have demonstrated threshold values above and below which survival is differentially altered. Neoadjuvant therapy significantly reduces the number of lymph node retrieved. The aim of the present study was to determine the effect of neoadjuvant therapy on LNR and its prognostic properties. Methods Consecutive patients who underwent curative rectal cancer resections in a single institution from 2007 to 2010 were reviewed. LNR was stratified into five subgroups of 0, 0.01–0.17, 0.18–0.41, 0.42–0.69 and 0.7–1.0 based on a previous study. The effect of neoadjuvant therapy on lymph node retrieval, LNR, locoregional (LR) and systemic recurrence (SR), disease-free (DFS) and overall survival (OS) was compared between patients who did (Neoadjuvant) and did not (Surgery Alone) receive neoadjuvant therapy. Results Neoadjuvant and Surgery Alone groups were comparable in gender, age and tumour stage. The number of lymph nodes retrieved were significantly lower in the Neoadjuvant group ( p p = 0.36). There was no statistical difference in the DFS and OS between the Neoadjuvant and Surgery Alone groups at the various LNR cut off values in patients with AJCC Stage 3 tumours. Conclusions LNR ratio remains unaltered despite reduced lymph node retrieval after neoadjuvant therapy in rectal cancer. LNR may therefore be a more reliable prognostic indicator in this subgroup of patients.

Purpose The treatment of advanced gallbladder cancer (GBC) remains controversial. Therefore, the purpose of this study was to explore treatment choices for advanced GBC. Methods We identified four different treatments from the surveillance, epidemiology, and end results (SEER) database: surgery, chemotherapy (CT), surgery and chemotherapy (Surgery + CT), and no surgery/no chemotherapy (No surgery/No CT). Kaplan‐Meier method and Cox proportional hazards regression method were used to determine the risk factors for overall survival (OS) and cancer‐specific survival (CSS). In addition, patients in AJCC stages III and IV stage were matched with 1:1 propensity score matching (PSM) for diagnosis age, race, marital status, histological type, tumor grade, and treatment pattern to decrease the possibility of selection bias. Results A total of 288 AJCC stage III patients and 4239 AJCC stage IV patients with advanced GBC were identified from the SEER database between 2004 and 2015. Treatment pattern was an independent risk factor for patients with advanced GBC. For all patient, AJCC stage III patients and AJCC stage IV patients, “Surgery + CT” treatment minimized the OS and CSS in advanced GBC patients. In addition, after the PSM analysis, the “Surgery + CT” treatment still significantly decreased patient OS and CSS. Conclusions “Surgery + CT” treatment can provide survival benefits for patients with advanced GBC. In addition, “Surgery + CT” treatment was not fully utilized and may further improve the survival rate of GBC patients., Surgery and chemotherapy (Surgery + CT) can provide survival benefits for patients with advanced gallbladder cancer (GBC). The treatment of “Surgery + CT” is not fully utilized, and the combined use of “Surgery + CT” can improve the survival rate of GBC patients.

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.

Scalp and neck melanomas (SNMs) have a relatively poor prognosis compared to other sites, and represent an anatomically challenging area for detection. The aim of this study was to identify the role of the hairdresser in detection of SNMs. A tertiary surgical oncology institutional database was retrospectively reviewed for all patients undergoing resection of a scalp, posterior neck, or retro auricular invasive primary melanoma between 2008 and 2014. SNMs accounted for 128 melanoma patients during the study period, with median age 66 years, 88 % male, and median Breslow thickness 1.55 mm. Hairdressers detected 10 % of all SNMs, with hairdresser-detected SNMs presenting 13 years younger (53 vs. 66 years, P = 0.015), and with a trend towards lower Breslow depth (1.15 vs. 1.63) and more frequent discovery in AJCC Stage Ia or Ib (66.7 % vs. 44.8 %) than otherwise-detected SNMs. Women with SNMs were 1.8-fold more likely than men to have their SNMs detected by a hairdresser (P = 0.001), and presented at higher AJCC clinical stage than men and required wider surgical resection margins (P = 0.011). Women with hairdresser-detected SNMs were younger, with lower Breslow thickness and lower AJCC Clinical Stage than women with otherwise-detected SNM. This study suggests that hairdressers play a critical role in detection of invasive primary scalp and neck melanoma, accounting for 10 % of all melanomas referred to a tertiary surgical oncology center. Quality improvement initiatives aimed at increasing early detection of scalp and neck melanoma should include members of the cosmetology community.

// Ellis Patrick 1, 6, 7, 8, 10 , Sarah-Jane Schramm 2, 3 , John T. Ormerod 1, 9 , Richard A. Scolyer 4, 5 , Graham J. Mann 2, 3 , Samuel Mueller 1, * , Jean Y.H. Yang 1, 3, * 1 School of Mathematics and Statistics, The University of Sydney, Sydney, Australia 2 The Westmead Millennium Institute for Medical Research, The University of Sydney, Sydney, Australia 3 Melanoma Institute Australia, The University of Sydney, Sydney, Australia 4 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia 5 Discipline Pathology, Sydney Medical School, The University of Sydney, Sydney, Australia 6 Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA 7 Harvard Medical School, Boston, MA, USA 8 Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA 9 ARC Centre of Excellence for Mathematical & Statistical Frontiers 10 Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA * These authors have contributed equally to this work Correspondence to: Jean Y.H. Yang, email: jean.yang@sydney.edu.au Keywords: biomarker, classification, cancer, pathology, prognosis Received: March 12, 2016 Accepted: September 26, 2016 Published: November 08, 2016 ABSTRACT Cancer research continues to highlight the extensive genetic diversity that exists both between and within tumors. This intrinsic heterogeneity poses one of the central challenges to predicting patient clinical outcome and the personalization of treatments. Despite progress in some individual tumor types, it is not yet possible to prospectively, accurately classify patients by expected survival. One hypothesis proposed to explain this is that the prognostic classifiers developed to date are insufficiently sensitive and specific; however it is also possible that patients are not equally easy to classify by any given biomarker. We demonstrate in a cohort of 45 AJCC stage III melanoma patients that clinico-pathologic biomarkers can identify those patients that are most likely to be misclassified by a molecular biomarker. The process of modelling the classifiability of patients was then replicated in a cohort of 49 stage II breast cancer patients and 53 stage III colon cancer patients. A multi-step procedure incorporating this information not only improved classification accuracy but also indicated the specific clinical attributes that had made classification problematic in each cohort. These findings show that, even when cohorts are of moderate size, including features that explain the patient-specific performance of a prognostic biomarker in a classification framework can improve the modelling and estimation of survival.

Fibrolamellar carcinoma (FLC) and conventional hepatocellular carcinoma (HCC) share the same American Joint Committee on Cancer (AJCC) staging. The worse survival with HCC is attributed to the underlying cirrhosis.The aim of this study was to compare stage-matched prognosis after resection of FLC and non-cirrhotic HCC. Outcomes after resection of 65 consecutive patients with FLC and 158 non-cirrhotic patients with HCC were compared. Patients were staged according to the 7th edition AJCC staging. The AJCC stage distributions for FLC and HCC demonstrated a predominance of stage IV disease in FLC and stage I in HCC (FLC stage I—23 %, II—15 %, III—15 %, IV—46 % vs. HCC stage I—42 %, II—32 %, III—20 %, IV—6 %, p

Objective Application of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of lepidic adenocarcinomas in conjunction with American Joint Committee on Cancer (AJCC) staging has been challenging. We aimed to compare IASLC/ATS/ERS and AJCC classifications, to determine if they could be integrated as a single staging system. Methods We reviewed patients from 2001-2013 who had AJCC stage I lepidic adenocarcinomas, and categorized them according to IASLC/ATS/ERS guidelines: adenocarcinoma in situ (AIS); minimally invasive adenocarcinoma (MIA); or invasive adenocarcinoma (IA). We integrated the 2 classification systems by separating AIS and MIA as being stage 0, and routinely classifying IA as stage I. Results Median follow-up was 52 months in 138 patients. The IASLC/ATS/ERS classification demonstrated a higher disease-free survival (DFS) in AIS (100%) and MIA (96%) versus IA (80%) ( P = .022), and higher overall survival (OS): 100% for AIS and MIA, versus 90% for IA ( P = .049). The AJCC classification identified a DFS of 87% and an OS of 94% for stage I patients. Integration of the 2 systems demonstrated higher DFS in stage 0 (98%) versus I (80%) ( P = .006), and higher OS: 100% for stage 0 versus 90% for stage I ( P = .014). Conclusions The IASLC/ATS/ERS classification better discriminates AIS and MIA compared with current AJCC staging; however, integration suggests that these categories may be collectively classified in AJCC staging, based on similarly favorable outcomes and distinctive survival rates.

// Xiaoqiang Li 1, 2, * , Shuang Liu 1, 2, * , Hui Li 1, 2, * , Lei Guo 1, 2 , Bo Zhang 1, 2 , Zhenhai Lin 3 , Jubo Zhang 4 , Qinghai Ye 1, 2 1 Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China 2 Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R. China 3 Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China 4 Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China * These authors contributed equally to this work Correspondence to: Qinghai Ye, e-mail: ye.qinghai@zs-hospital.sh.cn Jubo Zhang, e-mail: zhang.jubo@zs-hospital.sh.cn Keywords: hepatocellular carcinoma, hepatic pedicle clamping, hepatectomy, tumour stage, prognosis Received: January 17, 2016 Accepted: February 28, 2016 Published: March 24, 2016 ABSTRACT Intermittent hepatic pedicle clamping (HPC) is often performed during hepatectomy. Whether it affects the long-term prognosis of hepatocellular carcinoma (HCC) patients is still controversial. This study evaluated the impact of HPC in patients with different stages of HCC. The study included 1401 patients who underwent hepatectomy in the primary cohort with 129 AJCC stage IIIB HCC patients; there were 80 AJCC stage IIIB HCC patients in the validation cohort. In each cohort, patients were placed in the long-term HPC (LTHPC) group or the short-term HPC (STHPC) group based on the cut-off time of HPC estimated by the receiver-operating characteristic (ROC) curve. Although HPC did not show significant effects on the prognosis of stage I–IIIA HCC patients in the primary cohort, 1−, 3−, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates of stage IIIB HCC patients who received LTHPC (HPC time > 12 minutes) were significantly higher than those with STHPC (HPC time ≤ 12 minutes or received no HPC), similar in the validation cohort. Multivariate analysis demonstrated HPC time was an independent protective factor for RFS and OS in stage IIIB HCC patients. Herein, we report that proper HPC improved the postoperative prognosis of stage IIIB HCC patients and served as an independent protective factor.

Aim: To investigate outcomes in unresectable hepatocellular carcinoma (HCC) patients stratified by sociodemographic and clinical factors in a population study. Materials & methods: Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed in 2000–2011. Overall survival (OS) was stratified using patient sociodemographic characteristics and American Joint Commission on Cancer (AJCC) staging. Log-rank test and Cox proportional hazard models were used to identify prognostic factors of OS. Results: In patients with AJCC stage I and II unresectable HCC, prolonged OS was correlated with being married, younger age, ethnicity, geographic location, living in large urban areas, being insured and higher income and education levels. Conclusion: In AJCC stage I and II unresectable HCC patients with favorable sociodemographic factors, prolonged OS maybe in part related to better access to cancer-directed therapy.

e16052 Background: To assess microsatellite instability (MSI) and KRAS mutation prevalence, discrepancies and their impact on outcome in AJCC stage IV colorectal adenocarcinoma (colorectal cancer; CRC). Methods: The 2010-2016 United States National Cancer Database was queried for stage IV CRC patients > 18yo and information on MSI and KRAS mutation. Microsatellite status was stratified as stable microsatellites (MSS, including low instability) and microsatellite instability high (MSI-H). KRAS status was stratified as mutation and wildtype. Prevalence and discrepancies were evaluated according to patient demographics, US geography and CRC factors. Overall survival (OS) was assessed using Cox proportional hazards models adjusting for age, gender, race, comorbidities, metastatic burden, CRC treatment, treatment center type, and year of CRC diagnosis. A priori, a statistical interaction test between microsatellite status, KRAS status and primary CRC site was planned. Results: Microsatellite/KRAS status was available for n = 10,844/n = 25,712 patients, respectively. OS was assessed in n = 5,904 patients with data on both microsatellite and KRAS status, and follow-up. Overall prevalence of MSI-H was 3.1% and KRAS mutation 42.4%. Microsatellite and KRAS status varied according to primary CR site, as presented in Table. Further variation was evident according to US-geography, with MSI-H rates ranging from 1.6% to 4.1%, and KRAS mutation rates ranging from 41.1% to 44%. On multivariable analyses, longer OS was observed in patients with KRAS wildtype versus mutation (HR = 0.91, 95% CI: 0.85-0.97 p = 0.004), MSS versus MSI-H (HR = 0.75, 95% CI: 0.62-0.9, p = 0.003), and left-sided versus right-sided CRC (HR = 0.65, 95% CI: 0.6-0.7, p < 0.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (interaction p = 0.002). Conclusions: Depending on its primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, MSI-H and primary CRC sidedness independently affect overall survival and interact with distinct prognostic profiles. Generically classifying adenocarcinomas of different site as “CRC” might deprecate this diversity. [Table: see text]

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

Background BRAF and MEK inhibitors dabrafenib (D) and trametinib (T) have transformed BRAFV600-mutant melanoma patients’ (pts) treatment. In a large prospective trial of pts treated with combination D+T, which also included pts with brain metastasis (BM), we assessed factors associated with progression and stratified the population into risk groups using regression tree analysis (RTA). Methods This phase IIIb single arm, open label, multicenter, French study included in 40 centers pts with histologically confirmed unresectable stage IIIc or IV BRAFV600-mutant melanoma. Selection criteria allowed presence of BM, ECOG ≤2, previous advanced melanoma treatments (except BRAFi+MEKi combination). Progression-free survival (PFS) was estimated using the Kaplan Meier analysis and modeled with multivariate Cox regression model. Risk subgroups were identified using an exponential RTA. Significance was set at p Results Between March 2015 and November 2016, 914 pts were screened and 856 received at least 1 dose of D+T. Overall, 92% of pts had AJCC stage IV melanoma, 38% ECOG ≥1 and 32% BM. Among the 587 pts with known LDH at baseline, 38% had >ULN. Median PFS was 8.02 months (95%CI, 7.33-8.77). Significant independent factors associated with lower PFS were ECOG ≥1, elevated serum LDH, ≥3 metastatic sites, and presence of BM (Table). Pts with Table . 1338P Multivariate Cox proportional hazards analysis of PFS by prognostic factors - All Subjects Treated Population (N = 856) N (%) HR 95% CI p value LDH at baseline * 366 (42.8) 1 (=reference) - - [1 - 2[ ULN 160 (18.7) 1.64 [1.26 - 2.14] 0.0003 ≥2 ULN 61 (7.1) 2.45 [1.70 - 3.53] Missing 269 (31.4) 1.34 [1.05 - 1.71] 0.0167 ECOG * 0 531 (62.0) 1 (=reference) - - 1 242 (28.3) 1.49 [1.19 - 1.87] 0.0005 ≥2 83 (9.7) 2.32 [1.69 - 3.19] Metastatic sites * 344 (40.2) 1 (=reference) - - ≥3 445 (52.0) 1.61 [1.28 - 2.02] Missing 67 (7.8) 1.05 [0.63 - 1.74] 0.8494 Presence of brain metastasis * No 579 (67.6) 1 (=reference) - - Yes 275 (32.1) 1.38 [1.11 - 1.71] 0.0043 Missing 2 (0.23) - - - * Factors included in the RTA. Conclusions This is to date the largest prospective study in advanced BRAFV600-mutant melanoma pts treated with D+T. The study was carried out in conditions close to the real-world. We confirm findings of registration trials that LDH, ECOG and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor. Editorial acknowledgement Jone Iriondo-Alberdi (PhD) from ITEC Services. Legal entity responsible for the study Novartis Pharma S.A.S. (France). Funding Novartis Pharma S.A.S. (France). Disclosure P. Saiag: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Bristol-Myers Squibb; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck Sharp & Dohme ; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche-Genentech; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Novartis. C. Robert: Advisory / Consultancy: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Merck Sharp & Dohme ; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Participation to Boards and Steering Committees: Pierre Fabre. J.J. Grob: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp & Dohme ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Incyte. L. Mortier: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: GSK/Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Leo; Honoraria (self): Merck Serono; Honoraria (self): Sanofi; Honoraria (self): Pierre Fabre; Honoraria (self): Novartis. C. Lebbe: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Merck Sharp & Dohme ; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): Merck; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte. S. Mansard: Advisory / Consultancy: Novartis. F. Grange: Advisory / Consultancy: Novartis. E. Neidhardt: Travel / Accommodation / Expenses: BMS. T. Lesimple: Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: Incyte; Advisory / Consultancy: Pierre Fabre; Research grant / Funding (self): Roche. C. Bedane: Advisory / Consultancy: Novartis. S. Dalac-Rat: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: Pierre Fabre. C. Nardin: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD. A. Szenik: Full / Part-time employment: Novartis. A. Denden: Full / Part-time employment: Novartis. C. Dutriaux: Honoraria (self), Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.