Independent Factor For Overall Survival Research Articles

Serum lactate dehydrogenase as a novel prognostic factor for patients with primary undifferentiated pleomorphic sarcomas.

Among soft tissue sarcomas, undifferentiated pleomorphic sarcoma (UPS) has relatively higher potential of recurrence and metastasis. As serum lactate dehydrogenase (LDH) is associated with tumor progression and unfavorable outcomes in multiple malignancies, we designed this study to explore the relationship between preoperative serum LDH and prognosis in UPS patients. We extracted the data of UPS patients who underwent primary surgery in Shanghai Cancer Center, Fudan University. Receiver-operating characteristic (ROC) curve was used to figure out the best cutoff value of LDH to classify them into high- or low-expression groups. Univariate and multivariate analyses were performed using Cox proportional hazards regression to identify independent prognostic factors. Kaplan-Meier analysis was used to compare differences in overall survival (OS) and time to recurrence (TTR) between patients with high- or low-serum LDH. Multivariate analyses demonstrated that preoperative serum LDH was an independent factor for OS. Kaplan-Meier curves showed that patients with relatively high-serum LDH (P = 0.0004) had poorer OS compared with those with low-serum LDH. There was a trend that patients with relatively high-serum LDH had poorer TTR than those without (P = 0.1249). In addition, there were obvious trends that patients with decreased serum LDH after surgery showed better OS (P = 0.0954) and TTR (P = 0.1720) than those with elevated serum LDH. Moreover, high preoperative serum LDH was associated with female patients (P = 0.0004), positive margin (P < 0.0001), worse survival (P = 0.0061), higher mitotic index (P = 0.0222) and necrosis (P = 0.0225). Preoperative serum LDH is an independent factor for OS in UPS patients, and it correlates with future surgical margin.

Changes in Real-World Outcomes in Patients with Metastatic Renal Cell Carcinoma from the Molecular-Targeted Therapy Era to the Immune Checkpoint Inhibitor Era.

Knowledge of changes in the outcome in patients with metastatic renal cell carcinoma from the molecular-targeted therapy era to the immune checkpoint inhibitor (ICI) era remains limited in the real-world setting. We aimed to clarify outcome changes from the previous molecular-targeted therapy era to the current ICI era in patients with metastatic renal cell carcinoma using multi-institution real-world data. We retrospectively evaluated 415 patients with metastatic renal cell carcinoma who received first-line systemic therapy at five Japanese institutions between January 2008 and August 2021. We divided the patients into two groups based on the treatment era: molecular-targeted therapy era (January 2008-August 2018) and ICI era (September 2018-August 2021). According to the era, progression-free survival, overall survival, and objective response rate from first-line systemic therapy were compared. Overall, 304 (73.3%) and 111 (26.7%) patients were categorized into the molecular-targeted therapy and ICI eras, respectively. The proportion of patients without prior nephrectomy (p=0.0030) or those with low Karnofsky Performance Status scores [≤70] (p=0.0258) were significantly higher in the ICI era group. The patients in the ICI era group had significantly longer overall survival (median: not reached vs 23.2 months, p=0.0001) and a higher objective response rate (47.8% vs 24.7%, p<0.0001) than those in the molecular-targeted therapy era group, and progression-free survival tended to be longer in the ICI era group (median: 13.3 vs 8.75 months, p=0.0579). Multivariate analysis further showed that the treatment era (ICI vs molecular-targeted therapy) was an independent factor for overall survival and objective response (both, p<0.0001). The present multi-institution real-world data showed the improved outcome of previously untreated patients with metastatic renal cell carcinoma in the ICI era group compared with that in the molecular-targeted therapy era group. These findings strongly encourage the use of ICI-based treatment for patients with metastatic renal cell carcinoma in the real-world setting. Further studies with extended follow-up periods are needed to confirm our findings.

Serum alpha-fetoprotein as a predictive biomarker for tissue alpha-fetoprotein status and prognosis in patients with hepatocellular carcinoma.

BackgroundAlpha-fetoprotein (AFP) expression is closely related to hepatocarcinogenesis, and it is an important prognostic factor for hepatocellular carcinoma (HCC). We aimed to investigate the relationship between serum AFP concentration and tissue AFP status and identify the prognostic value of serum and tissue AFP for HCC.MethodsThis is a retrospective review of 248 patients with HCC from January 2012 to December 2018. Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of serum AFP for tissue AFP status. Overall survival (OS) was analyzed using the Kaplan-Meier method and log-rank tests were used for comparison between two groups. Multivariate Cox proportional hazards regression analysis was performed for various risk factors.ResultsThe serum AFP level in patients with tissue AFP-positive HCC was higher than those with tissue AFP-negative HCC (506.7 vs. 7.7 ng/mL, P<0.0001). Youden’s index yielded an optimal cut-off value of serum AFP for tissue AFP status of 92.33 ng/mL with a sensitivity and specificity of 0.84 (95% CI: 0.74–0.90) and 0.88 (95% CI: 0.82–0.92), respectively. Moreover, high serum AFP concentrations (≥92.33 ng/mL) were significantly correlated with positive hepatitis B virus (HBV, P=0.012), tumor size (P=0.025) and histological grade (P=0.001); tissue AFP-positive status was associated with positive HBV (P=0.006), tumor number (P=0.033) and histological grade (P<0.001). Further, serum AFP level ≥92.33 ng/mL and tissue AFP-positive status were associated with poorer OS, and positive HBV (Positive: HR 3.496; 95% CI: 1.349–9.064; P=0.010) and larger tumor size (≥5; HR 2.617; 95% CI: 1.372–4.992; P=0.003) were independent factors of OS.ConclusionsThis study showed that serum AFP level could be a highly predictive biomarker for tissue AFP status in patients with HCC. Furthermore, serum AFP levels ≥92.33 ng/mL and tissue AFP-positive status were associated with poorer OS but were not independent factors of OS.

Clinical Outcomes of MRI-Guided Adaptive Brachytherapy for Each Fraction in Locally Advanced Cervical Cancer: A Single Institution Experience

PurposeThis study aims to evaluate clinical outcomes of MRI-guided adaptive brachytherapy (MR-IGABT) for each brachytherapy fraction in patients with locally advanced cervical cancer (LACC).Methods and MaterialsA retrospective analysis was performed on 97 consecutive patients with LACC treated with 44.0–50.4 Gy external beam radiotherapy (EBRT) ± concurrent platinum-containing chemotherapy followed by 4 × 7 Gy MR-IGABT between September 2014 and April 2019. Intracavitary (IC)/interstitial (IS)/hybrid intracavitary and interstitial (IC/IS) brachytherapy was used in MR-IGABT. Brachytherapy planning and dose reporting followed the GEC-ESTRO recommendations. Clinical outcomes including overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), local control (LC), and treatment-related toxicity evaluated by the RTOG criteria were analyzed. Kaplan–Meier and univariable and multivariable Cox regression analyses were used to analyze the prognostic factor.ResultsMedian follow-up was 21.1 months. Median dose to 90% (D90) of the high-risk clinical target volume (HR-CTV) was 91.7 Gy (range 76.7~107.2 Gy). Two-year OS, CSS, PFS, and LC were 83.5%, 84.1%, 71.1%, and 94.8%, respectively. Four patients (4.1%) suffered from grade 3 late gastrointestinal radiation toxicity, and no other grade 3 or greater radiation toxicity occurred. Initial HR-CTV was an independent factor of OS (p = 0.001, HR = 1.018/cm3), PFS (p = 0.012, HR = 1.012/cm3), and LC (p = 0.011, HR = 1.028/cm3). The HR-CTV D90 (p = 0.044, HR = 0.923/Gy) was an independent factor of PFS. Age was an independent factor of LC (p = 0.010, HR = 1.111/year).ConclusionFor patients with LACC, MR-IGABT was effective and safe. It showed favorable LC, OS, and minimal toxicity. Moreover, initial HR-CTV, HR-CTV D90, and age were significant prognostic factors.

Establishment and validation of a prognostic model based on HRR-related lncRNAs in colon adenocarcinoma

BackgroundColon cancer (CRC) is the second leading cause of cancer-related death, and its 5-year survival rate is very low. Homologous recombination repair (HRR) is deficient in most colon cancer. Some long non-coding RNAs (lncRNAs) participate in tumorigenesis of colon cancer through the HRR pathway. We aim to establish a prognostic model based on the HRR-related lncRNAs, expecting to provide a new strategy for precision treatment development in colon cancer.MethodsPearson’s correlation was used to identify the HRR-related prognostic lncRNAs in the TCGA-COAD cohort. The TCGA-COAD cohort was randomized into the training set and the testing set. LASSO Cox regression was used to establish the model which was analyzed in the training set and validated in the testing set and the entire TCGA-COAD cohort. Finally, we explored the potential biological function of our model.ResultsA prognostic model was established based on nineteen HRR-related lncRNAs in the training set. COAD patients were scored by the uniform formula and divided into high-risk and low-risk groups based on the median risk score. Patients with high-risk scores indicated poor prognosis in the training set, and the result was confirmed in the testing set and the entire TCGA-COAD cohort (all p < 0.01). Multivariable analysis suggested that our model was an independent factor for overall survival in COAD. The area under the curve (AUC) and C-index indicated that our model had better predictive efficiency than other indicators in the TCGA-COAD cohort. Functional enrichment analysis suggested that our model was associated with the MAPK pathway in COAD. Besides, our model was positively correlated with the HRD scores.ConclusionA new prognostic model was established based on nineteen HRR-related lncRNAs which had excellent predictive efficiency on the prognosis of COAD. This prognostic model may provide a new strategy for prognostic prediction of COAD patients.

Prognostic Impact of Baseline Neutrophil-to-Eosinophil Ratio in Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Therapy in Second or Later Lines.

BackgroundInflammation is a crucial component in carcinogenesis. The neutrophil-to-eosinophil ratio (NER) has been studied as a biomarker of prognosis and predictive of response in metastatic renal cell carcinoma (mRCC). In the present study, we evaluated the relevance of baseline NER on the progression-free survival (PFS) and overall survival (OS) outcomes in real-world patients with mRCC treated with nivolumab in second or subsequent lines. We also assessed the association of baseline NER with objective response, as well as with toxicity and histology.MethodsIn this multicenter retrospective analysis of patients with mRCC treated with nivolumab, the last systemic absolute neutrophil and eosinophil count before treatment with nivolumab was used to calculate the NER. An additive Cox proportional hazards model was used to identify the cut-off point for NER considering PFS and the patients were allocated into low and high NER groups. Median OS and median PFS were estimated using the Kaplan-Meier estimator, and survival curves of groups were compared using the log-rank test. Univariable and multivariable Cox regression models were used to study OS and PFS and Fisher’s exact test was performed to evaluate the association of NER with the response, toxicity, and histology.ResultsThe 49 analyzed patients had a median follow-up of nine months. The NER cut-off was established at 48, locating 29 patients in the low NER group (NER < 48) and 20 in the high NER group (NER ≥ 48). Median PFS and median OS were significantly shorter in patients with high NER versus low NER (3 vs. 30 months (p < 0.001) and 6 vs. 24 months (p = 0.002), respectively). Multivariable analyses showed that NER (HR 3.92 (95% CI: 1.66-9.23), p = 0.002) was an independent factor for PFS and that NER (HR 3.85 (95% CI: 1.33-11.17), p = 0.013) and progressive disease (HR 5.62 (95% CI: 1.88-16.83), p = 0.002) were independent factors for OS. NER was significantly associated with objective response rate (ORR) (NER ≥ 48-12.5% vs. NER < 48-87.5%, p = 0.003), immune-related adverse events (irAEs) (NER ≥ 48-10.0% vs. NER < 48-42.9%, p = 0.014), and tumor’s histology as patients of high NER group had more non-clear cell carcinoma than low NER group (35.0% vs. 7.4%, p = 0.017).ConclusionOur real-world data analysis of NER in patients with mRCC confirmed the prognostic value of this biomarker, supporting clinical utility in predicting survival. Results also suggested an association between lower NER and better ORR, and that irAEs occur more frequently in patients with a lower NER. However, further large-scale prospective studies are needed to confirm these findings and to validate this biomarker.

Evaluating the Efficacy of EGFR-TKIs Combined With Radiotherapy in Advanced Lung Adenocarcinoma Patients With EGFR Mutation: A Retrospective Study.

Objective: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been recommended as the first-line treatment for advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation. This study retrospectively evaluated patients’ survival and related prognostic factors from single-center, real-world data. Methods: From January 2015 to December 2020, patients detected with EGFR mutation showing unresectable clinical stages III to IV advanced lung adenocarcinoma and receiving EGFR-TKIs and radiotherapy (RT) were recruited for the study. The overall survival (OS) and progression-free survival (PFS) were statistically analyzed with SPSS 22.0 software. Results: This study included 238 patients who completed their follow-up by December 30, 2020. The 1-, 2-, 3-year and median OS were 84.4%, 59.7%, 38.7%, and 30.3 months for OS, 57.0%, 28.8%, 15.7%, and 14.1 months for progression-free survival (PFS1), and 78.9%, 71.7%, 33.3%, and 25.0 months for PFS2, respectively. Multivariate analysis showed that, the independent factors for OS are age, clinical stage, the sequence of TKI and CT, and the total treatment response, and total response; the independent factors for progression-free survival 1 are clinical stage and total treatment response; the independent factors for PFS2 are clinical stage, type of TKI, sequence of TKI and CT, and total treatment response. The univariate analysis also showed a significant association between RT duration (P = 0.041) and dose (P = 0.026) with PFS1. Conclusion: EGFR-TKIs combined with RT was tolerable and efficient for patients with advanced lung adenocarcinoma. OS and PFS prove CT sequential with TKIs. Better treatment response with CR + PR was associated with a longer duration of OS, PFS1, and PFS2. However, further study is required in a larger sample size to confirm the results.

Addition of thermal ablation to systemic chemotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma: a propensity score matching analysis

ABSTRACT Objectives To retrospectively compare the survival outcomes of thermal ablation plus chemotherapy to those of chemotherapy alone in patients with unresectable intrahepatic cholangiocarcinoma (ICC). Methods 189 patients with unresectable ICC who received thermal ablation plus chemotherapy or chemotherapy alone as the initial treatment were identified . To avoid potential bias, 1:1 matching between groups was performed through propensity score matching. Overall survival (OS) was the primary endpoint. Clinical and tumor factors related to OS were analyzed through univariate and multivariate analyses. Results Of the enrolled patients, 55 received ablation plus chemotherapy, and 134 received chemotherapy alone. The median OS was 16.267 months for patients treated with combined therapy and 6.067 months for patients treated with chemotherapy alone (p = 0.000). The benefit of ablation plus chemotherapy was also preserved in the matched cohort, with a median OS of 15.233 months in the combined treatment group and 7.967 months in the chemotherapy group (p = 0.009). Univariate and multivariate analyses indicated that the type of treatment was an independent factor of OS (p < 0.05). Conclusions The combination of thermal ablation and systemic chemotherapy provides an opportunity to improve the prognosis of patients with unresectable ICC.

Superiority of CRP-albumin-lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma.

We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy. Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin×Lymphocyte)/(CRP×104). Patients with a CALLY index ≥5 (n=200) were compared to those with an index <5 (n=184). Next, validation was performed using 267 patients from three other university hospitals (external validation cohort). The number of TNM Stage III and IV patients was significantly higher in the CALLY <5 group than the ≥5 group (p=0.003). There was a significant difference in the 5-year survival rate (CALLY ≥5: 71% vs. <5: 46%; p<0.001). Multivariate analysis identified the CALLY index as an independent factor of overall survival. Similarly, there was a significant difference in the 5-year survival rate between the CALLY ≥5 (73%) and <5 (48%) groups (p<0.001), and the CALLY index was identified as an independent prognostic factor in the external validation cohort. The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.

Pre-treatment Nutritional Risk Assessment by NRS-2002 Predicts Prognosis in Patients With Advanced Biliary Tract Cancer: A Single Center Retrospective Study.

We investigated the predictors of survival in patients with advanced BTC according to their baseline nutritional status estimated by the Nutritional Risk Screening (NRS)-2002. From September 2006 to July 2017, we reviewed the data of 601 inpatients with BTC. Data on demographic and clinical parameters was collected from electronic medical records, and overall survival (OS) and progression-free survival were analyzed using the Kaplan-Meier method and the stepwise Cox regression analysis. Patients with an NRS-2002 score of ≤ 2, 3, and ≥ 4 were respectively classified as “no risk,” “moderate risk,” “high risk.” Following initial NRS-2002 score, 333 patients (55%) were classified as “no-risk,” 109 patients (18%) as “moderate-risk,” and 159 patients (27%) as “high-risk.” Survival analysis demonstrated significant differences in the median OS: “no-risk”: 12.6 months (95% confidence interval [CI], 11.5–13.7); “moderate-risk”: 6.1 months (95% CI, 4.3–8.0); and “high-risk”: 3.9 months (95% CI, 3.2–4.6) (p < 0.001). NRS-2002 score was an independent factor for OS (hazard ratio [HR], 1.616 for “moderate-risk”, 95% CI, 1.288–2.027, p < 0.001; HR, 2.121 for “high-risk”, 95% CI, 1.722–2.612, p < 0.001), along with liver metastasis, peritoneal seeding, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, cholesterol, carcinoembryonic antigen, and carbohydrate antigen 19-9. In conclusion, baseline NRS-2002 is an appropriate method for discriminating those who are already malnourished and who have poor prognosis in advanced BTC patient. Significance of these results merit further validation to be integrated in the routine practice to improve quality of care in BTC patients.

Prognostic Role of 18F-FDG Positron Emission Tomography in Patients with Resectable Hepatocellular Carcinoma

Introduction: 18F-fluorodeoxyglucose positron emission tomography(18F-FDG PET) could predict tumour biology and aggressive of hepatocellular carcinoma(HCC). We hypothesized that 18F-FDG PET predicted survival of patients with HCC who underwent hepatectomy. Method: This was a retrospective study at a university center in Hong Kong. Data was retrieved from a prospectively entered database. Maximum standard uptake value(SUVmax) of tumor/ normal liver uptake(T/L ratio) was recorded. The PET positivity for overall survival(OS) was determined using T/L ratio by c-statistics using receiver operating characteristic curve. Multivariate analyses with preoperative, pathological variables and PET positivity were performed to determine the prognostic significance of post-hepatectomy OS and recurrence. Results: From 2004 to 2019, 267 patients who had 18F-FDG PET before hepatectomy. The 5-year OS and disease free survival(DFS) were 64.8% and 40.5% respectively. The median follow-up was 45.3 months. Table 1 showed the baseline demographics, operative and pathological characteristics of all patients. The optimal cut-off of T/L ratio was 1.526 based on ROC(AUC 0.674, 95% CI 0.608-0.741, P<0.001). Using a T/L ratio cutoff at 1.526, it was found to be an independent predictor of OS [hazard ratio(HR) 1.762 (1.120-2.773), p=0.014] (Table2) and was associated with a better OS.(Figure1) PET positive HCC were more likely to recur (with 5-year DFS 45.8% vs. 33.1%, p=0.001) and had a shorter DFS (median survival 8.5 vs 50 months, p=0.001).(Figure 2) Conclusion: PET positivity using T/L ratio was an independent factor for OS in HCC patients who underwent hepatectomy. 18F-FDG PET could be explored as a potential radiological biomarkers for HCC aggressiveness.

Pretreatment C-Reactive Protein/Albumin Ratio is Associated With Poor Survival in Patients With 2018 FIGO Stage IB-IIA HPV-Positive Cervical Cancer.

Objectives: The present study aimed to identify the predictive value of inflammatory indexes stratified according to human papillomavirus (HPV) infection status in women with FIGO 2018 stage IB∼IIA cervical cancer. We also explored the influences of HPV infection status on the survival of cervical cancer patients. Methods: We collected data for 583 women with stage IB∼IIA cervical cancer in Sun Yat-sen University Cancer Center between 2009 and 2017. The t-test, chi-squared (χ2) test and Fisher’s exact test were applied to compare the differences of inflammatory indexes and clinicopathological features between HPV-positive and HPV-negative groups. Univariate and multivariate analyses were used to identify clinicopathological factors that were associated with the prognosis of cervical cancer patients. Results: There were no differences in overall survival (OS) and progression-free survival (PFS) between HPV-positive and HPV-negative groups. In HPV-positive group, the maximum tumor size, neoadjuvant chemotherapy and the body mass index (BMI) correlated significantly with C-reactive protein/albumin ratio (CAR). The maximum tumor size and the prognostic nutritional index (PNI) correlated significantly with the platelet-lymphocyte ratio (PLR). The maximum tumor size, neoadjuvant chemotherapy and PLR correlated significantly with PNI. Univariate and multivariate analyses showed that the depth of tumor invasion (HR: 3.651, 95% CI: 1.464–9.103, p = 0.005; HR: 2.478, 95% CI: 1.218–5.043, p = 0.012) and CAR (HR: 5.201, 95% CI: 2.080–13.004, p < 0.0001; HR: 2.769, 95% CI: 1.406–5.455, p = 0.003) were independent predictors of poor OS and PFS. PNI was an independent protective factor of OS (HR: 0.341, 95% CI: 0.156–0.745, p = 0.007). PLR was an independent factor of PFS (HR: 1.991, 95% CI: 1.018–3.894, p = 0.044). In HPV-negative group, BMI correlated significantly with CAR. Only depth of invasion (HR: 9.192, 95% CI: 1.016–83.173, p = 0.048) was the independent predictor of poor OS, and no inflammation indexes were independent predictors of prognosis. Conclusion: In patients with HPV-positive cervical cancer, depth of invasion, PNI and CAR are independent factors of OS, and depth of invasion, PLR and CAR are independent factors for PFS. For patients with HPV-negative disease, no inflammation indexes had predictive value for prognosis. The predictive value of inflammation indexes on prognosis is more significant in patients with HPV-positive cervical cancer. Stratification of HPV infection status promotes a more precise clinical application of inflammation indexes, thus improving their accuracy and feasibility.

Factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer patients

ObjectivesThis study aimed to explore factors associated with immunotherapy respond and survival in advanced non-small cell lung cancer (aNSCLC) patients treated with immune checkpoint inhibitors (ICIs). MethodsA total of 101 patients with aNSCLC receiving ICIs were included. The association between clinical factors and multiple endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) were investigated by multivariate analyses. ResultsMultivariate logistic analyses revealed that clinical stage, lactate dehydrogena (LDH), and any grade immune-related adverse events (irAEs) were independent predictors of ORR, while LDH and ICIs treatment type were independent predictors of DCR. In Multivariate Cox analysis, Eastern Cooperative Oncology Group performance status (ECOG PS), LDH, albumin (Alb), platelet to lymphocyte ratio (PLR), and any grade irAEs were independent factors for OS. Similarly, clinical stage, LDH, Alb, and any grade irAEs were independent factors for PFS. Pre-treatment prognostic score was established based on clinical stage, ECOG PS, LDH, Alb and PLR to classify patients into three groups: the good group (0–1 score), the intermediate group (2 scores) and the poor group (3-4 scores). The immunotherapy response was significantly different in various prognostic groups. Subset analyses showed pre-treatment prognostic score ≥ 3 tended to have a strong negative impact on survival among patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 50%. ConclusionsPre-treatment prognostic score based on clinical stage, ECOG PS, LDH, Alb and PLR may help to identify aNSCLC patients who may benefit from ICIs.

Prognostic significance of pseudocapsule status in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

BackgroundWe sought to determine whether pseudocapsule (PS) features have prognostic implications in patients with metastatic renal cell carcinoma (mRCC).MethodsWe retrospectively reviewed 231 patients diagnosed with mRCC and treated with tyrosine kinase inhibitors; 188 patients with data available regarding the tumor-parenchyma interfacial PS of the primary tumor were enrolled for analysis. PS status was evaluated as intact (grade 0), merely involved (grade 1), penetrated (grade 2), and absent (grade 3). We applied the Kaplan-Meier method and Cox regression model to assess the survival impact.ResultsOf the 188 patients, 19 (10.1%), 61 (32.4%), 96 (51.1%) and 12 (6.4%) had grade 0, 1, 2 and 3 PS, respectively. PS status was significantly associated with histology (P=0.0206), venous tumor embolus (P=0.0511), microvascular invasion (P=0.0108) and microsatellite formation (P=0.0097). Patients without a PS had the worst overall survival (OS), with a 3-year OS rate of 12.7%, whereas the OS rates for grades 0, 1 and 2 were 78.8%, 50.8% and 43.6%, respectively. Adjusted by other variables, grade 3 and grade 2 PS gave rise to a much higher risk of death across the cohort [hazard ratio (HR) =5.217, P=0.0182; HR =3.765, P=0.0281, respectively]. Sarcomatoid change was also an independent factor for OS (HR =2.932, P=0.0075). In contrast, microsatellite formation was not associated with survival in the cohort.ConclusionsPS status has prognostic implications for OS in metastatic renal cancer. The absence of the PS and sarcomatoid change are two pathological features related to an extremely poor prognosis.

High HBXIP expression is related to poor prognosis in HCC by extensive database interrogation.

The involvement of HBXIP in cancer development and cancer cell survival is well known. This work probed the potential of HBXIP as a prognostic biomarker in hepatic cell cancer (HCC). First, pan-cancer analysis of HBXIP expression was conducted using The Cancer Genome Atlas (TCGA) database to validate the expression of HBXIP in different cancers. The GSE14520 (GPL3721 Subset) database was used to validate HBXIP in HCC. The association between survival outcomes and prognostic factors was assessed employing univariate and multivariate survival analyses for TCGA Liver Hepatocellular Carcinoma. The biological function of the HBXIP Gene was annotated by gene set enrichment analysis. The relationship between HBXIP expression and immune cells and immune markers was analyzed from the Gene Expression Profiling Interactive Analysis (GEPIA) database. Malignant tissues demonstrated evident upregulation of HBXIP at transcriptional and protein levels over normal tissues (p < 0.05) with this elevated expression linked to an advanced tumor stage in HCC cohorts. Univariate analysis revealed an evident correlation emerged between prognosis and HBXIP for GSE14520 databases (p < 0.05). The disease-free survival (DFS) and overall survival (OS) (five-year values) were lower in samples demonstrating elevated HBXIP (HR: 2.413; 95% CI 1.601, 3.638; p < 0.001) and (HR: 1.613; 95% CI 1.446, 1.844; p = 0.003), respectively vs. lower HBXIP expression. HBXIP emerged as an independent factor in OS prognosis (HR 2.184; 95% CI 1.495, 3.196; p < 0.001) and DFS (HR 1.764; 95% CI 1.261, 2.466; p < 0.001), respectively according to multivariate analysis. Further, multiple Cox analyses in the validation cohort revealed that independent factors for OS were HBXIP, AJCC T stage, vascular invasion, and tumor status with the C-index score of 0.727 (95% CI, 0.704 to 0.750). HBXIP level showed a significantly positive association with tumor immune cell infiltration, and biomarkers of immune cells; besides, the rectum Rho GTPase effectors signaling pathway was also identified. HCC advancement and survival involves HBXIP, which also emerged as a functional biomarker for HCC survival prediction.

Evaluation of Traditional Prognostic Factors for Stage I-III Colorectal Cancer Patients Who Survived for Over Five Years After Surgery

The aim of this study was to explore the prognostic factors in stage I-III colorectal cancer (CRC) patients who had survived for over five years. A total of 9754 stage I-III CRC patients who received curative surgery in the Department of Colorectal Surgery, Fudan University Shanghai Cancer Center were enrolled in this study. Of them, 3640 patients had survived for over five years after surgery. Univariate and multivariate Cox regression analyses were performed in the entire cohort and those who had survived for over five years. Compared with patients in the entire cohort, patients who had survived for over five years were more likely to be younger, have less disease of signet ring cell histology, perineural invasion and vascular invasion, more well differentiated tumors and stage I disease. In the entire cohort, increased age, signet ring cell, poor differentiation, more advanced pathological stage, perineural invasion and vascular invasion were inversely associated with disease-free survival (DFS) and overall survival (OS) using multivariable Cox regression analyses. Only age, pathological stage and perineural invasion remained significant in patients who had survived for over five years. Moreover, tumor location was an independent factor for OS in this subgroup. Predictors for prognosis of CRC change over time. Age, pathological stage and perineural invasion deserve more attention among patients who have survived for over five years.

Survival analysis in the incident dialysis patients by different modalities

To analysis survival in onset uremic patients who initiating HD or PD dialysis in our dialysis center. Between Jan. 2015 and June. 2018, patients with onset uremia and initiating planned-start dialysis were retrospectively enrolled in this study and followed up to January, 2019. The relationships between the types of dialysis modality and patient prognosis were assessed. A total of 460 patients were included in the final analysis. Of which, 213 patient (46.30%) undergoing PD and 247 patients (53.70%) undergoing HD with arteriovenous fistula. The average follow-up time was 27.9 months. Eighty-seven (18.91%) patients died during the study period. The all-cause mortality was 127 per 1000 person-year. It was 102 per 1000 person-year in the HD group and 171 per 1000 person-year in the PD group (p < 0.01). However, dialysis modality was not an independent predictor for survival. During the first year after dialysis initiation, patient survival was comparable between the PD and HD groups (log-rank p = 0.14). As the dialysis age increased over 1 year, HD patients seemed to have a better survival as compared to that of PD patient (log-rank p < 0.05), especially those older than 65 years and without DN. Though dialysis modality was not an independent factor for overall survival, HD therapy seemed to be more suitable for patients without DN.

1151MO Pathological response is an independent factor of overall survival and disease-free survival after neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase II trial

Major pathological response after neoadjuvant cisplatin-based chemotherapy for early-stage NSCLC has been shown to predict survival. This has not been demonstrated for neoadjuvant immune checkpoint inhibitors. In IONESCO multicenter phase II trial, 3 cycles of durvalumab were administered in stage IB>4cm–IIIA, non N2 resectable NSCLC (TNM 8th edition) before surgery. We report here the updated analysis on disease-free survival (DFS) and overall survival (OS) and their association with residual viable tumor cells (RVT). Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes. Specimens were reviewed for the degree of pathologic response i.e. % of RVT in the primary tumor and in any involved lymph nodes. The relationship between % of RVT as a continuous variable and outcomes (OS and DFS) was analyzed using a Cox regression model including patient characteristics (age, gender, PS, smoking status), histology, PD-L1 tumor proportion score (TPS), stage and surgical procedure. 50 pts were included. 46 were eligible and received durvalumab, 43 operated, 67.4% males, median age, 61 yr; all ECOG PS 0-1; 98% (ex-)smokers; 23 adenocarcinoma, 19 squamous; clinical stages IB/IIA/IIB/IIIA = 5/13/27/1; 15 TPS ≥1%. Median % of RVT was 36.11. Median OS and DFS were not reached; 18-m OS: 89.1% [95% CI: 75.8-95.3] 18-m DFS: 73.7% [95% CI: 58.4-84.1]. In the multivariate prognostic analysis, for increasing value of % of RVT, OS and DFS were poorer (HR [95%CI]: 1.05 [1.00-1.10] p=0.04 and 1.06 [1.01-1.11] p=0.02, respectively). The IFCT-1601 IONESCO trial showed for the first time that the extent of pathological response to a neoadjuvant immune checkpoint inhibitor is an independent prognostic factor of OS and DFS in NSCLC.

Prognostic value of PD-L1 expression on immune cells or tumor cells for locally advanced esophageal squamous cell carcinoma in patients treated with neoadjuvant chemoradiotherapy.

Programmed death-ligand 1 (PD-L1) expression may influence the prognosis of patients with localized esophageal cancer. The current study compared the prognostic value of PD-L1 expression between tumor cells and immune cells. Archival esophageal tumor tissue samples were collected from patients who received paclitaxel and cisplatin-based neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal squamous cell carcinoma (ESCC) in three prospective phase II trials. PD-L1 expression on tumor and immune cells was examined immunohistochemically by using the SP142 antibody and scored by two independent pathologists. The association of PD-L1 expression with patient's outcomes was analyzed using a log-rank test and Cox regression multivariate analysis. A total of 100 patients were included. PD-L1 expression on tumor cells was positive (≥ 1%, TC-positive) in 55 patients; PD-L1 expression on immune cells was high (≥ 5%, IC-high) in 30 patients. TC-positive status was associated with poor overall survival (OS) (HR: 1.63, P = 0.035), whereas IC-high status was associated with improved OS (HR: 0.44, P = 0.0024). Multivariate analysis revealed that TC-positive, IC-high, and performance status were independent prognostic factors for progression-free survival and that IC-high and performance status were independent factors for OS. Furthermore, the combination of IC-high and TC-negative status was associated with the optimal OS, whereas that of TC-positive and IC-low status was associated with the worst OS. PD-L1 expression on tumor and immune cells may have different prognostic value for patients with locally advanced ESCC receiving neoadjuvant CRT. A combination of these two indexes may further improve the prognostic prediction.

Development of a prognostic prediction model based on microRNA-1269a in esophageal cancer.

BACKGROUNDEsophageal cancer (ESCA) is a heterogeneous cancer with variable outcomes that are challenging to predict. MicroRNA (miR)-1269a is a newly discovered non-coding RNA that shows promising prognostic prediction in other cancers, but its clinical value in ESCA remains unclear.AIMTo explore the relationship between miR-1269a and its clinical value and to develop a nomogram to succinctly display this relationship.METHODSWe analyzed the expression of miR-1269a in 125 ESCA tissue samples with complete clinical data and 52 normal tissue samples. We determined the prognostic value of miR-1269a for overall survival (OS) and cancer-specific survival (CSS) and evaluated the association between miR-1269a and clinical variables including tumor location, histologic grade, metastatic stage, and American Joint Committee on Cancer (AJCC) stage using multivariate Cox analysis. Additionally, we developed a nomogram for OS and CSS based on miR-1269a expression using age and AJCC stage and assessed its prognostic performance. Using Gene Ontology and Kyoto Encyclopedia of Gene and Genomes analyses, we predicted the target genes of miR-1269a and analyzed their potential function in caner development.RESULTSThe expression of miR-1269a was significantly higher in ESCA patients than healthy controls. Patients with high expression of miR-1269a showed poor prognosis in OS and CSS, suffered increased rates of low differentiation and metastasis, and exhibited tumor stage T3 + T4, positive lymph stage, and AJCC stage III + IV. The area under the receiver operating characteristic curve of miR-1269a was 0.716 for OS and 0.764 for CSS. Multivariate Cox analysis revealed that AJCC stage and miR-1269a were independent factors for OS and CSS. Combing with age, we constructed a nomogram for prognostic prediction. Additionally, our nomogram showed excellent predictive performance for OS and CSS after 3 years and 5 years and was easy to use. Ultimately, the functional analysis suggested that miR-1269a was mostly involved in the PI3K-AKT signaling pathway.CONCLUSIONmiR-1269a can be used as a potential indicator for the prognosis of ESCA patients. We developed an easy-to-use nomogram with excellent ESCA prognostic prediction for clinical use.