Independent Factor For Overall Survival Research Articles

Predictive Value of Skeletal Muscle Mass in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients Treated With Immune Checkpoint Inhibitors.

BackgroundReduced muscle mass has been associated with increased treatment complications in several tumor types. We evaluated the impact of skeletal muscle index (SMI) on prognosis and immune-related adverse events (IrAEs) in a cohort of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoints inhibitors (ICI).MethodsA single-institutional, retrospective study was performed including 61 consecutive patients of R/M HNSCC diagnosed between July 2015 and December 2018. SMI was quantified using a CT scan at L3 to evaluate body composition. Median baseline SMI was used to dichotomize patients in low and high SMI. Kaplan-Meier estimations were used to detect overall survival (OS) and progression-free survival (PFS). Toxicity was recorded using Common Terminology Criteria for Adverse Event v4.3.ResultsPatients were 52 men (85.2%) with mean of age 57.7 years (SD 9.62), mainly oral cavity (n = 21; 34.4%). Low SMI was an independent factor for OS in the univariate (HR, 2.06; 95% CI, 1.14–3.73, p = 0.017) and multivariate Cox analyses (HR, 2.99; 95% CI, 1.29–6.94; p = 0.011). PFS was also reduced in patients with low SMI (PFS HR, 1.84; 95% CI, 1.08–3.12; p = 0.025). IrAEs occurred in 29 (47.5%) patients. There was no association between low SMI and IrAEs at any grade (OR, 0.56; 95% CI, 0.20–1.54; p = 0.261). However, grades 3 to 4 IrAEs were developed in seven patients of whom three had low SMI.ConclusionsLow SMI before ICI treatment in R/M HNSCC patients had a negative impact on OS and PFS. Further prospective research is needed to confirm the role of body composition as a predictive biomarker in ICI treatment.

Effect of Azacitidine on CD4+CD25+Foxp3+ Regulatory T Cell on Immunity in Myelodysplastic Syndrome Survivors

Background: Immune editing is recognized as important in various pathogenic processes. We previously showed that regulatory T cell (Treg) levels were elevated in MDS with a poor prognosis and that Treg levels decreased with Azacitidine (AZA) treatment and became equivalent to that in the untreated group. In this study, we examined changes in the number of circulating Tregs, T cells, and NK cells in the peripheral blood of patients with MDS treated with AZA, and we evaluated the clinical significance of these findings with survival.Patients and Methods: Patients with MDS and with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) according to the WHO 2008 classification who were initially treated between January 2015 and December 2016 and followed up for more than 6 months were enrolled in the study. AZA was given intravenously at a dose of 75 mg/m2 daily for either 5 or 7 consecutive days every 4 weeks. The response was assessed using the IWG response criteria for MDS. A total of 50 patients with AML-MRC (n=11), refractory anemia with excess blasts (RAEB) (n=8), refractory cytopenia with multilineage dysplasia (RCMD) (n=28), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) (n=12), and refractory anemia with ring sideroblastis (RARS) (n=1) were included in the study. The IPSS was classified as low (n=15) intermediate-1 (n=13), intermediate-2 (n=10), and high (n=13). Twenty-six patients did not require treatment, including a transfusion (untreated group). Twenty-two patients were treated with AZA (AZA group). The remaining patients received conventional chemotherapy. After obtaining informed consent, blood was drawn from all of the patients at initial diagnosis. In the 22 patients treated with AZA, blood was also drawn after 6 completed treatment cycles. CD4+CD25+Foxp3+ Treg cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD3-CD56+ NK cells were analyzed using flow cytometry, and the absolute numbers of these cells were calculated. Overall survival (OS) probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test for univariate analysis.Results: The median age was 74 years (range: 44-93 years), and 35 of the patients were male. The median period of observation was 391 days. In the AZA group, 10 patients died (AZA-ineffective group), and 12 had either a CR, PR, or HI (AZA-effective group). The 2-year OS of the AZA group was 43.7%. The absolute number of Tregs and Treg% values before treatment were not significantly different between the AZA group and the untreated group. The Treg levels in peripheral blood before treatment in the AZA-effective (0.80±0.39%) tended to be lower than that in the AZA-ineffective (1.29±0.82%) group (p=0.076). The CD8+ T cell counts before treatment were moderately higher in the AZA-effective group compared to that in the AZA-ineffective group (385.5 ± 129.0 vs. 195.5 ± 70.0 /μL, p<0.01). Similarly, the CD3-CD56+ NK cell counts before treatment differed significantly between the AZA-effective group (197.4 ± 138.8 /μL) and the AZA-ineffective group (82.3 ± 36.7 /μL) (p=0.015). In a univariate analysis, the MDS patients with elevated NK cells survived longer than the group with reduced NK cells (p=0.013). In a multivariate analysis, the lower percentage of Treg cells and the higher percentage of CD8+T cells before treatment were independent factors for OS (HR, 4.80; p=0.085, HR, 4.13; p=0.040, respectively). In the AZA group, the percentage of CD8+T cells before treatment associated with OS (HR, 39.24; p=0.018). After treatment, the AZA group had an increase in the NK cell counts, which tended to associate with survival (HR 4.29; p=0.067).Conclusions: The number of Tregs in MDS cases requiring treatment was higher than that in MDS cases for which treatment was unnecessary. The prognosis of the patients with high CD8+ T cells counts was better. In contrast, there was an increase in the number of NK cells after AZA treatment, which was found to be associated with an improved prognosis. These results suggest that an immunological mechanism associated with the prognosis of MDS may be enhanced by treatment with AZA. Further examination of this mechanism and of the influence of AZA on the immunological effect are required. DisclosuresNo relevant conflicts of interest to declare.

Mutant p53 and Twist1 Co-Expression Predicts Poor Prognosis and Is an Independent Prognostic Factor in Breast Cancer.

PurposeThe basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.MethodsTwist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.ResultsOf the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.ConclusionsOur results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.

A nomogram based on CENPP expression for survival prediction in breast cancer.

In recent years, it has been found that the expression of 17 centromere proteins (CENPs) was closely related to malignant tumors, however, the role of CENPs in breast cancer (BC) has not been fully investigated. This study intends to investigate the prognostic value of CENPs in BC and establish nomogram based on expression of CENPs to predict BC patients' prognosis. A total of 800 BC patients with complete relevant data were included from the TCGA database and were further randomly divided into training set (N=480) and validation set (N=320). Univariate and multivariate Cox regression analysis were used to screen independent factors for overall survival (OS) prediction of BC patients in the training set. Then, the nomogram was established based on these independent predictors and further validated by receiver-operating characteristic (ROC) curves and calibration plots. The GEPIA and bcGenExMiner v4.4 databases were utilized to analyze mRNA expression of candidate gene in BC patients with different clinicopathological features, respectively. Multivariate Cox regression analysis showed that age, Her2 status, pathologic_T stage, pathologic_M stage and CENPP expression were of independent prognostic value for BC. CENPP was overexpressed in BC tissues (P<0.01) and lower expression of CENPP was associated with worse OS (P=0.005, HR =2.35; 95% CI: 1.30-4.23). We then established a nomogram based on those independent predictors, and the calibration curve demonstrated good fitness of the nomogram for OS prediction. In the training set, the AUCs of 3- and 5-year survival were 0.757 and 0.797, respectively. In the validation set, the AUCs of 3- and 5-year survival were 0.727 and 0.71, respectively. Our study showed that CENPP was a novel prognostic factor for patients with BC, and the established nomogram could provide valuable information on prognostic prediction for patients with BC.

Hepatoma upregulated protein and Ki-67 expression in resectable hepatocellular carcinoma.

Hepatoma upregulated protein (HURP) and Ki-67 have been identified as cancer-related genes involved in cell growth and proliferation. Previous experimental studies have suggested an essential role for HURP expression in liver carcinogenesis. However, data regarding HURP expression in hepatocellular carcinoma (HCC) and its correlation with patient outcomes are limited. In this study, we examined the clinicopathologic features associated with HURP expression in HCC, and compared them to the results of the Ki-67 study. Eighty-seven resected HCC at tumor, node, metastasis (TNM) stages I (n = 28), II (n = 29), and III (n = 30) were evaluated. HURP and Ki-67 expression were assessed by immunohistochemistry. Multivariate analysis was used to examine the prognostic significance of HURP and Ki-67 expression. HURP expression in HCC tissue was observed in 59% of patients and associated with female sex, low white blood cell count, and low platelet count. Ki-67 expression was observed in 67% of patients and associated with younger age, higher serum α-fetoprotein (AFP) levels, and frequent microvascular invasion. Univariate analysis showed that factors related to overall survival were: age >55 years, AFP >20 ng/mL, indocyanine green retention rate at 15 minutes (ICG-15) >15%, tumor size >5 cm, multiple tumors, macrovascular invasion, microvascular invasion, Ki-67 expression, and serum vascular endothelial growth factor >170 pg/mL. HURP expression was not associated with postresection survival. Multivariate analysis indicated that macrovascular invasion, multiple tumors, ICG-15 >15%, and Ki-67 expression were independent factors for overall survival. Multiple tumors and Ki-67 expression were independent factors related to recurrence-free survival. In our study, HURP expression in HCC tissue was not associated with post-resection survival. Ki-67 expression was an independent prognostic factor for survival. Our results suggest that the effect of HURP activity on growth, invasion, and postresection outcome of HCC in actual patients is less than previously demonstrated in experimental studies.

Survival Analysis and Prediction Model for Pulmonary Sarcomatoid Carcinoma Based on SEER Database.

ObjectiveThis study aimed to investigate the incidence of the pulmonary sarcomatoid carcinoma (PSC), to compare the clinical characteristics and overall survival (OS) of patients with PSC and those with other non-small-cell lung cancer (oNSCLC), so as to analyze the factors affecting the OS of patients with PSC and construct a nomogram prediction model.MethodsData of patients with PSC and those with oNSCLC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results database were collected. The age-adjusted incidence of PSC was calculated. The characteristics of patients with PSC and those with oNSCLC were compared, then the patients were matched 1:2 for further survival analysis. Patients with PSC were randomly divided into training set and testing set with a ratio of 7:3. The Cox proportional hazards model was used to identify the covariates associated with the OS. Significant covariates were used to construct the nomogram, and the C-index was calculated to measure the discrimination ability. The accuracy of the nomogram was compared with the tumor–node–metastasis (TNM) clinical stage, and the corresponding area under the curve was achieved.ResultsA total of 1049 patients with PSC were enrolled, the incidence of PSC was slowly decreased from 0.120/100,000 in 2004 to 0.092/100,000 in 2015. Before PSM, 793 PSC patients and 191356 oNSCLC patients were identified, the proportion of male, younger patients (<65 years), grade IV, TNM clinical stage IV was higher in the PSC. The patients with PSC had significantly poorer OS compared with those with oNSCLC. After PSM, PSC still had an extremely inferior prognosis. Age, sex, TNM clinical stage, chemotherapy, radiotherapy, and surgery were independent factors for OS. Next, a nomogram was established based on these factors, and the C-indexs were 0.775 and 0.790 for the training and testing set, respectively. Moreover, the nomogram model indicated a more comprehensive and accurate prediction than the TNM clinical stage.ConclusionsThe incidence of PSC was slowly decreased. PSC had a significantly poor prognosis compared with oNSCLC. The nomogram constructed in this study accurately predicted the prognosis of PSC, performed better than the TNM clinical stage.

Prognostic value of metabolic parameters measured by pretreatment dual-time-point 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with intrahepatic or perihilar cholangiocarcinoma: A STROBE study.

The purpose of this study was to determine the glucose metabolism at delay phase measured by pretreatment dual-time-point 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/ computed tomography (CT) provides prognostic information independent of well-known prognostic factors in patients with intrahepatic or perihilar cholangiocarcinoma (ICC or PCC).From July 2012 to December 2017, 55 patients (men 27, women 28, mean age 68 ± 11 years) with pathologically proven ICC or PCC were enrolled in this retrospective study. The dual-time-point 18F-FDG PET/CT as part of a staging workup was performed in all patients. The patient's data includes age, sex, serum CA19-9, presence of LN or distant metastasis, early SUVmax (early maximum standardized uptake value [eSUV]), delay SUVmax (delay maximum standardized uptake value [dSUV]), retention index of SUVmax (percent change of maximum standardized uptake values [ΔSUV]), neutrophil to lymphocyte ratio (NLR) and histopathology including pCEA, p53, Ki-67 index. The analysis of the relationship between metabolic parameters and survival was done using the Kaplan–Meier curve and Cox proportional hazards regression model.Median survival for all patients was 357 days. Median early and delay SUVmax was 5.2 (range: 2.0–21.4) and 6.5 (range 2.7–24.5), respectively. The overall survival was found to be significantly related to eSUV, dSUV, ΔSUV, age, serum CA19-9 and NLR in univariate analysis. In multivariate analysis, dSUV (P = .014, 95%CI; 1.30–10.7, HR 3.74) and ΔSUVmax (P = .037, 95%CI; 1.05–6.12, HR 2.5) were independent factors of overall survival. Kaplan–Meier curve analysis clearly showed the significant difference of overall survival between 2 groups (high eSUV, low eSUV + high ΔSUV vs low eSUV and ΔSUV, P < .001) among the comparisons of the SUV parameters on FDG PET. In the receiver operating characteristic analysis using combinations of the SUV parameters, the 2 groups [eSUV + ΔSUV (P = .0001, area under the curve [AUC] 0.68) and dSUV + ΔSUV (P = .0002, AUC 0.71)] showed significantly larger AUC than the other groups applying eSUV or dSUV alone (AUC 0.61 and AUC 0.68).dSUV and ΔSUV on pretreatment dual-time-point 18F-FDG PET/CT can be useful parameters in the prediction of survival in patients with ICC or PCC.

Influence of positive margins on tumour recurrence and overall survival after gastrectomy for gastric cancer.

Incidence of positive surgical margins after curative gastrectomy ranges from 1% to 20%. It has been suggested that positive surgical margin is an adverse prognosis factor, with a higher local recurrence and worse overall survival (OS). However, the management of these patients remains unclear. A total of 267 patients who underwent gastrectomy with curative intent between January 2010 and December 2018 in our centre were enrolled in this study. Post-operative histological analysis revealed positive resection margins in 18 patients (8%). Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared. Patients with positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, whole stomach involved and poorly differentiated tumours. Local recurrence was described in 50% of cases with positive margins. The multivariate analysis demonstrated that the TNM stage was the only independent prognostic factor associated with recurrence. OS for positive margins at 1, 3 and 5 years was 75%, 57% and 26%, respectively. The median survival in patients with positive margins was 38.33 versus 81.17 months for R0 patients (p=0.027). Multivariate analysis showed that age (hazard ratio [HR] 1.041, 95% confidence interval [CI] 1.02-1.07, sex (HR 2.00, 95% CI 1.22-3.30) and TNM stage (p < 0.001) were independent factors of OS. Positive resection margin was an indication of advanced and more aggressive disease rather than an independent prognosis factor for OS or recurrence in gastric cancer.

A nomogram combining plasma fibrinogen and systemic immune\u2011inflammation index predicts survival in patients with resectable gastric cancer

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.

The predictive and prognostic value of sex in localized colorectal cancer: a SEER-based analysis.

BackgroundAlthough the influence of sex on different cancer survival has been investigated, the predictive and prognostic value of sex in localized colorectal cancer (CRC) still remain controversial.MethodsSurvival was evaluated in patients who diagnosed with localized CRC in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Overall survival (OS) outcomes were estimated with the Kaplan-Meier method, and multivariable Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsWe obtained a dataset that included 70,836 males and 69,705 females of localized CRC patients. Compared with males, females more often had age ≥75 years (55.1% vs. 44%), right-sided colon cancer (56.8% vs. 45.4%), and more advanced pT stage cancer (75.5% vs. 72%). In addition, we found that females had better OS than males and that sex could be an independent factor of OS in T1-3N0M0 (Stage I-II) colon cancer (regardless of right/left-sided tumour) and T1-2N0M0 (Stage I) rectal cancer (each HR <1, each P<0.05). Although a significant OS benefit was not observed in T3N0M0 rectal cancer in the overall analysis (P=0.183), females who underwent postoperative chemotherapy had better OS than males among T3N0M0 (Stage II) rectal cancer patients significantly (P<0.001).ConclusionsIn our study, sex was shown to be a prognostic factor in localized-CRC. In particular, females may benefit more from postoperative chemotherapy than males with T3N0M0 (Stage II) rectal cancer.

Fluorodeoxyglucose F 18 for the Assessment of Acute Intestinal Graft-versus-Host Disease and Prediction of Response to Immunosuppressive Therapy

Graft-versus-host disease (GVHD) is a common complication that increases morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Fluorodeoxyglucose F 18 (18F-FDG)-positron emission tomography (PET) imaging has been demonstrated to be highly informative for evaluating and mapping of intestinal GVHD. To corroborate and extend existing findings and to investigate whether glucose metabolism assessed by 18F-FDG-PET might be an effective diagnostic tool to predict corticosteroid-refractory acute GVHD and overall survival. In this retrospective analysis, 101 patients with clinically suspected acute intestinal GVHD underwent 18F-FDG-PET between June 2011 and February 2019. Seventy-four of these patients with clinically and/or histologically proven acute intestinal GVHD as well as positive 18F-FDG-PET findings were analyzed in detail to assess the predictive value of 18F-FDG-PET regarding the response to immunosuppressive therapy and survival. Quantitative PET parameters, particularly the maximum standard uptake value (SUVmax), of patients with a fast response (ie, clinical improvement and decreased GVHD activity by at least 1 stage after 1 week of GVHD treatment) or slow/no response (ie, persistent disease activity for more than 1 week or increasing GVHD activity following first-line immunosuppressive therapy) were evaluated. 18F-FDG-PET detected intestinal GVHD with a sensitivity of 93% (95% confidence interval [CI], 85% to 97%) and specificity of 73% (95% CI, 45% to 91%). Patients with a fast response to immunosuppressive therapy had a mean SUVmax of 13.7 (95% CI, 11.0 to 16.5) compared with 7.6 (95% CI, 7.0 to 8.3; P=.005) observed in patients with prolonged or no response. The median overall survival (OS) was 573.0 days (95% CI, 539.5 to 606.5 days) for patients with fast response versus 255 days (95% CI, 161.0 to 349.0 days; P=.009) for patients with slow or no responses. A SUVmax threshold >8.95 applied to 18F-FDG-PET performed within 100 days after transplantation identified patients with a median OS of 390 versus 117 days for patients with SUVmax ≤8.95 (P=.036). SUVmax threshold and donor type were independent factors for OS. Our results indicate that 18F-FDG-PET is highly accurate in identifying patients with acute intestinal GVHD and may predict responses to immunosuppressive therapy as well as survival, particularly when applied within the first 100 days after transplantation. These results provide a strong rationale to integrate PET imaging in future prospective trials evaluating new therapies for acute GVHD.

Novel Nomograms-Based Prediction Models for Patients with Primary Undifferentiated Pleomorphic Sarcomas Resections.

Simple SummaryUndifferentiated pleomorphic sarcomas (UPS) are one of the most common soft tissue sarcomas which have relatively high potentials of recurrence and metastasis. Surgery remains the mainstream treatment for UPS patients. However, in modern medicine, doctors nowadays lack proper models to tell patients the exact prognosis of individuals after they have undergone primary surgery. In this work, we for the first time develop two nomograms that are able to predict 3- and 5-year overall survival (OS) and time to recurrence (TTR) for UPS patients. These nomograms show relatively good accuracy and practicability which may contribute a lot to the modern medical decision-making process.Background: Undifferentiated pleomorphic sarcomas (UPS) were one of the most common soft tissue sarcomas. As UPS had relatively high potentials of recurrence and metastasis, we designed two nomograms to better predict the overall survival (OS) and time to recurrence (TTR) for patients who underwent primary surgery. Methods: The data of UPS patients who underwent primary surgery were extracted from Shanghai Cancer Center, Fudan University. Multivariate analyses were performed using Cox proportional hazards regression to identify independent prognostic factors. Kaplan–Meier analysis was used to compare differences for patients who underwent primary surgery in OS and TTR. Nomograms were designed with the help of R software and validated using calibration curves and receiver operating characteristic curves (ROC). Results: Kaplan–Meier curves showed that patients with older ages (p = 0.0024), deeper locations (p = 0.0422), necrosis (p < 0.0001), G3 French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification (p < 0.0001), higher Ki-67 (p < 0.0001), higher mitotic index (p < 0.0001), R1/R2 resections (p = 0.0002) and higher invasive depth (p = 0.0099) had shorter OS than the other patients while patients with older ages (p = 0.0108), necrosis (p = 0.0001), G3 FNCLCC classification (p < 0.0001), higher Ki-67 (p = 0.0006), higher mitotic index (p < 0.0001) and R1/R2 resections (p < 0.0001) had shorter TTR compared with those without. Multivariate analyses demonstrated that mitotic rates and surgical margin were independent factors for TTR while age and invasive depth were independent factors for OS. Three parameters were adopted to build the nomograms for 3- and 5-year OS and TTR. The Area Under Curve (AUC) of this nomogram at 3- and 5-year TTR reached 0.802, 0.814, respectively, while OS reached 0.718, 0.802, respectively. Calibration curves for the prediction of 3- and 5-year OS and TTR showed excellent agreement between the predicted and the actual survival outcomes. Conclusions: Some important parameters could be used to predict the outcome of individual UPS patients such as mitotic age, rates, surgical margin, and invasive depth. We developed two accurate and practicable nomograms that could predict 3- and 5-year OS and TTR for UPS patients, which could be involved in the modern medical decision-making process.

Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma.

BackgroundIntrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment.MethodsBetween March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups.ResultsICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort.ConclusionsHAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.

A nomogram for predicting overall survival in patients with resected non-small cell lung cancer treated with chemotherapy

BackgroundChemotherapy is a common treatment for patients with resected non-small cell lung cancer (NSCLC). However, there are few models for predicting the survival outcomes of these patients. Here, we developed a clinical nomogram for predicting overall survival (OS) in this cohort.MethodsA total of 16,661 patients with resected NSCLC treated with chemotherapy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified prognostic factors and integrated them into a nomogram. The model was subjected to bootstrap internal validation using the SEER database and external validation using a database in China and the National Cancer Database (NCDB). The model’s predictive accuracy and discriminative ability were tested by calibration and concordance index (C-index).ResultsAge, sex, number of dissected lymph nodes, extent of surgery, N stage, T stage, and grade were independent factors for OS and were integrated into the model. The calibration curves for probability of 1-, 3-, and 5-year OS showed excellent agreement between the predicted and actual survivals. The C-index of the nomogram was higher than that of the Tumor-Node-Metastasis staging system for predicting OS (training cohort, 0.62 vs. 0.58; China cohort, 0.68 vs. 0.63; NCDB cohort, 0.59 vs. 0.57).ConclusionsWe developed a nomogram that can present individual prediction of OS for patients with resected NSCLC who are undergoing chemotherapy. This practical prognostic tool may help clinicians in treatment planning.

Improving biliary stent patency for malignant obstructive jaundice using endobiliary radiofrequency ablation: experience in 150 patients.

Although self-expandable mental stents (SEMS) placement is the standard care for relieving obstructive jaundice caused by unresectable malignant biliary stricture, how to maintain stent potency remains an intractable problem. This study was to evaluate the efficacy and safety of endobiliary radiofrequency ablation (RFA) through percutaneous transhepatic cholangiography (PTC) pathway in treating such patients. Consecutive patients who were performed endobiliary RFA as well as SEMS placement because of unresectable malignant obstructive jaundice in single institution in recent 8years were retrospectively reviewed. As comparison, patients who underwent only percutaneous SEMS placement for unresectable malignant biliary stricture during the contemporary period were reviewed. Stent patency, complications, complications, and overall survival (OS) were investigated and analyzed. One hundred and fifty patients who underwent endobiliary RFA and 127 patients who underwent only stent placement were included in this study. In the study group of endobiliary RFA, 87 patients (58.0%) underwent ablation for 1 time, 49 (32.7%) for 2 times, and 14 (9.3%) for 3 times. Complications related to RFA as well as SEMS placement happened in 113 patients (75.3%), without severe complications that needed emergent surgery or interventional therapy. The median duration of stent patency after ablation was 11.2month, and the median survival time was 12.3month. As comparison, difference was found in the number of interventional procedures and stents placed, duration of initial stent patency, and the incidence of moderate bleeding and pain. In the study group, only the type of tumor that caused biliary obstruction (intrahepatic carcinoma vs. extrahepatic carcinoma) was a poor independent factor (P = 0.035) for recurrent biliary obstruction. Repeated interventional therapy and adoption of subsequent therapy were only independent factors for OS. Endobiliary RFA and SEMS placement is technically safe and feasible for unresectable malignant obstructive jaundice to improve the quality of life and prolong survival.

Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

IntroductionA high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC. MethodsWe retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Optimal cutoff for prediction of response by TMB was determined by receiver operating characteristic analysis, and area under the curve (AUC) was calculated for all 3 biomarkers and combinations. Cox model was used to assess prognostic factors of overall survival (OS) and time to progression (TTP). Survival cutoffs calculated with Kaplan-Meier survival curves were TMB ≥10 mut/Mb, PD-L1 ≥50%, NLR <5, and combined biomarkers. ResultsData from 88 patients treated were analyzed. The optimal TMB cutoff was 9.24 mut/Mb (AUC, 0.62), improving to 0.74 combining all 3 biomarkers. Adjusted Cox model showed that TMB ≥10 mut/Mb was an independent factor of OS (hazard ratio [HR], 0.31; 95% confidence interval; 0.14-0.69; P = .004) and TTP (HR, 0.46; 95% CI, 0.27-0.77; P = .003). The combination of high TMB with positive PD-L1 and low NLR was significantly associated with OS (P = .038) but not TTP. ConclusionsTMB has modest predictive and prognostic power for clinical outcomes after ICI treatment. The combination of TMB, PD-L1, and NLR status improves this power.

A prognostic nomogram based on LASSO Cox regression in patients with alpha-fetoprotein-negative hepatocellular carcinoma following non-surgical therapy

BackgroundAlpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC.MethodsA total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort.ResultsThe C-index of nomogram1was 0.708 (95%CI: 0.673–0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606–0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690–0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691–0.813; AUC: 0.784, 95%CI: 0.709–0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively.ConclusionsNovel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.

Predictive Value of Combined Preoperative Carcinoembryonic Antigen Level and Ki-67 Index in Patients With Gastric Neuroendocrine Carcinoma After Radical Surgery.

PrécisWe present a valid and reproducible nomogram that combined the TNM stage as well as the Ki-67 index and carcinoembryonic antigen levels; the nomogram may be an indispensable tool to help predict individualized risks of death and help clinicians manage patients with gastric neuroendocrine carcinoma.BackgroundTo analyze the long-term outcomes of patients with grade 3 GNEC who underwent curative surgery and investigated whether the combination of carcinoembryonic antigen (CEA) levels and Ki-67 index can predict the prognosis of patients with gastric neuroendocrine carcinoma (GNEC) and constructed a nomogram to predict patient survival.MethodsIn the training cohort, data were collected from 405 patients with GNEC after radical surgery at seven Chinese centers. A nomogram was constructed to predict long-term prognosis. Data for the validation cohort were collected from 305 patients.ResultsThe 5-year overall survival (OS) was worse in the high CEA group than in the normal CEA group (40.5% vs. 55.2%, p = 0.013). The 5-year OS was significantly worse in the high Ki-67 index group than in the low Ki-67 index group (47.9% vs. 57.2%, p = 0.012). Accordingly, we divided the whole cohort into a KC(-) group (low Ki-67 index and normal CEA) and KC(+) group (high Ki-67 index and/or high CEA). The KC(+) group had a worse prognosis than the KC(-) group (64.6% vs. 46.8%, p < 0.001). KC(+) and the AJCC 8th stage were independent factors for OS. Then, we combined KC status and the AJCC 8th stage to establish a nomogram; the C-index and area under the curve (AUC) were higher for the nomogram than for the AJCC 8th stage (C-index: 0.660 vs. 0.635, p = 0.005; AUC: 0.700 vs. 0.675, p = 0.020). The calibration curve verified that the nomogram had a good predictive value, with similar findings in the validation groups.ConclusionsThe nomogram based on KC status and the AJCC 8th stage predicted the prognosis of patients with GNEC well.

Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment

BackgroundThe aim of the present study was to investigate the influence of kinase insert domain containing receptor (KDR) genetic variation on the efficacy of treatment and safety of patients with chemotherapy-refractory metastatic colorectal cancer (CRC) receiving apatinib.MethodsA total of 108 patients with chemotherapy refractory metastatic CRC who were treated with apatinib participated in this study retrospectively. Efficacy of the patients’ treatment was evaluated. Prognosis was carried out and safety profile was documented, respectively. Blood specimens and peripheral blood mononuclear cells (PBMC) of the patients were obtained for the analysis of genetic variation and KDR gene mRNA expression, respectively. The association between genotype status and clinical outcomes was presented.ResultsObjective response rate (ORR) and disease control rate (DCR) of the 108 patients with metastatic CRC receiving apatinib treatment were 5.6% and 69.4%, respectively. Survival analysis results exhibited that the median progression-free survival (PFS) and overall survival (OS) of the 108 patients with metastatic CRC was 3.6 months (95% confidence interval (CI): 3.03–4.17 months) and 8.9 months (95% CI: 7.57–10.23 months), respectively. Subsequently, the analysis of KDR genetic variation indicated that rs2071559 was of clinical significance. The minor allele frequency of rs2071559 was 0.22 and the genotype status corresponded with Hardy-Weinberg equilibrium (P=0.949). Prognosis analysis in a dominant inheritance manner through the combination of patients with TC and CC genotype showed that the median PFS of patients with TT genotype and TC/CC genotype was 4.1 and 3.0 months, respectively (P=0.012). Furthermore, the median OS of patients with the two genotypes was 10.5 and 6.1 months, respectively (P=0.007). Additionally, multivariate Cox regression analysis of OS showed that TC/CC genotype was an independent factor for OS (Hazard ratio (HR)=0.65, P=0.021). Interestingly, mRNA expression analysis suggested that the mRNA expression of KDR in PBMC differed significantly according to rs2071559 genotype status (P<0.001).ConclusionApatinib demonstrated a potentially superior clinical outcome for patients with chemotherapy-refractory metastatic CRC. KDR polymorphism rs2071559 could be used as a potential biomarker for the prognosis evaluation of patients with CRC receiving apatinib therapy.

P36.09 Overexpression of KIAA0101 Promotes the Progression of Non-Small Cell Lung Cancer

Lung cancer ranked as the most common lethal cancer type in the world, with incidence continue rising. KIAA0101, also known as a proliferating cell nuclear antigen (PCNA) binding protein, highly expressed in various types of cancer. However, the prognosis, diagnostic value, and biological function of KIAA0101 have not thoroughly illustrated in non-small lung cancer (NSCLC). We utilized bioinformatics and cell lines to verify the KIAA0101 expression. Functional analyses were conducted to confirm the roles in vitro and vivo. The results identified that KIAA0101 overexpressed in NSCLC tissues and cell lines than normal tissues. High KIAA0101 expression was positively associated with high T stage, nodal invasion, advanced tumor stage, and poor overall survival (OS) (p<0.01). The receiver operating characteristic (ROC) curves showed that KIAA0101 could sufficiently distinguish NSCLC from paired healthy tissues (AUC=0.9691, p<0.0001). The multivariate analysis revealed that KIAA0101 was an independent factor of OS (HR=1.451, 95% CI: 1.073-1.963, p=0.016). Furthermore, KIAA0101 knockdown inhibited the proliferation and migration of NSCLC cells and decreased tumor volume in nude mice.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Tabled 1CharactersiticsUnivariate analysisMultivariate analysisP valueHR95%CIP valueHR95%CIAge (≥60/＜60 years)0.1371.2310.936-1.619Gender (Male/Female)0.0781.2250.977-1.537TNM stage (III-IV/I-II)<0.0012.0811.639-2.642N stage (N1+N2+N3/N0)<0.0011.7081.372-2.1250.0071.4261.102-1.845T stage (T1+T2/T3+T4)<0.0011.9291.480-2.5140.0041.5811.155-2.166M stage (M1/M0)0.0042.1071.268-3.499KIAA0101 expression (High/Low)0.0441.2501.006-1.5530.0491.2491.001-1.559 Open table in a new tab In summary, our findings suggested that KIAA0101 was an influential prognostic and diagnostic factor in NSCLC, and considered to be a potential treating target.