Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB) who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

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Factors predicting recurrence after curative resection for rectal cancer: a 16-year study

World Journal of Surgical Oncology ◽

10.1186/s12957-019-1718-1 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 4

Author(s):

Waad Farhat ◽

Mohamed Azzaza ◽

Abdelkader Mizouni ◽

Houssem Ammar ◽

Mahdi ben Ltaifa ◽

...

Keyword(s):

Prognostic Factors ◽

Recurrence Rate ◽

Cox Regression ◽

Survival Curve ◽

Rectal Adenocarcinoma ◽

Distal Margin ◽

Curative Surgery ◽

Factors Affecting ◽

Cox Regression Analysis ◽

Kaplan Meier

Abstract Background The recurrence after curative surgery of the rectal adenocarcinoma is a serious complication, considered as a failure of the therapeutic strategy. The aim of this study was to identify the different prognostic factors affecting the recurrence of adenocarcinoma of the rectum. Methods A retrospective analysis of patients operated for adenocarcinoma of the rectum between January 2000 and December 2015 was conducted. The study of the recurrence rate and prognostic factors was performed through the Kaplan Meier survival curve and the Cox regression analysis. Results During the study period, 188 patients underwent curative surgery for rectal adenocarcinoma, among which 53 had a recurrence. The recurrence rate was 44.6% at 5 years. The multivariate analysis identified four parameters independently associated with the risk of recurrence after curative surgery: a distal margin ≤ 2 cm (HR = 6.8, 95% CI 2.7–16.6, 6), extracapsular invasion of lymph node metastasis (HR = 4.4, 95% CI 1.3–14), tumor stenosis (HR = 4.3, 95% CI 1.2–15.2), and parietal invasion (pT3/T4 disease) (HR = 3, 95% CI 1.1–9.4). Conclusion The determination of the prognostic factors affecting the recurrence of rectal adenocarcinoma after curative surgery allows us to define the high-risk patients for recurrence. Trial registration ClinicalTrials.gov Identifier: NCT03899870. Registered on 2 February 2019, retrospectively registered.

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IMUP and GPRC5A: Two Newly Identified Risk Score Indicators in Pancreatic Ductal Adenocarcinoma

10.21203/rs.3.rs-895660/v1 ◽

2021 ◽

Author(s):

Rong Wei ◽

Zixin Zeng ◽

Ningning Shen ◽

Ziyue Wang ◽

Honghong Shen ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Cells ◽

Cox Regression ◽

Bioinformatic Analysis ◽

Cancer Development ◽

Local Hospital ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Key Genes ◽

The Difference

Abstract Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan-Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over 8-fold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the >8-fold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan-Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 64 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

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Assessment of Response to Chemotherapy in Pancreatic Cancer with Liver Metastasis: CT Texture as a Predictive Biomarker

Diagnostics ◽

10.3390/diagnostics11122252 ◽

2021 ◽

Vol 11 (12) ◽

pp. 2252

Author(s):

Sihang Cheng ◽

Zhengyu Jin ◽

Huadan Xue

Keyword(s):

Pancreatic Cancer ◽

Liver Metastasis ◽

Cox Regression ◽

Imaging Biomarkers ◽

Cox Regression Analysis ◽

Recist 1.1 ◽

Kaplan Meier ◽

Texture Parameters ◽

Choi Criteria ◽

Response To Chemotherapy

In this paper, we assess changes in CT texture of metastatic liver lesions after treatment with chemotherapy in patients with pancreatic cancer and determine if texture parameters correlate with measured time to progression (TTP). This retrospective study included 110 patients with pancreatic cancer with liver metastasis, and mean, entropy, kurtosis, skewness, mean of positive pixels, and standard deviation (SD) values were extracted during texture analysis. Response assessment was also obtained by using RECIST 1.1, Choi and modified Choi criteria, respectively. The correlation of texture parameters and existing assessment criteria with TTP were evaluated using Kaplan-Meier and Cox regression analyses in the training cohort. Kaplan-Meier curves of the proportion of patients without disease progression were significantly different for several texture parameters, and were better than those for RECIST 1.1-, Choi-, and modified Choi-defined response (p < 0.05 vs. p = 0.398, p = 0.142, and p = 0.536, respectively). Cox regression analysis showed that percentage change in SD was an independent predictor of TTP (p = 0.016) and confirmed in the validation cohort (p = 0.019). In conclusion, CT texture parameters have the potential to become predictive imaging biomarkers for response evaluation in pancreatic cancer with liver metastasis.

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Prior Therapy With Pegylated-Interferon Alfa-2b Improves the Efficacy of Adjuvant Pembrolizumab in Resectable Advanced Melanoma

Frontiers in Oncology ◽

10.3389/fonc.2021.675873 ◽

2021 ◽

Vol 11 ◽

Author(s):

Dong-Dong Jia ◽

Yanling Niu ◽

Honglin Zhu ◽

Sizhen Wang ◽

Tonghui Ma ◽

...

Keyword(s):

Adjuvant Therapy ◽

Cox Regression ◽

Objective Response ◽

Pegylated Interferon ◽

Recurrence Rates ◽

Cox Regression Analysis ◽

Prior Therapy ◽

Kaplan Meier ◽

Melanoma Patients ◽

The Impact

Combination immunotherapy can overcome the limited objective response rates of PD-1 blockade. Interferon alpha (IFN-α) has been proven to be effective in modulating immune responses and may enhance the clinical responses to PD-1 blockade. According to clinical practice guidelines, IFN-α was recommended as adjuvant therapy for stage IIB/C melanoma patients. However, the impact of prior IFN-α therapy on the efficacy of subsequent PD-1 blockade in melanoma has not been previously reported. Therefore, we performed a retrospective analysis for melanoma patients and addressed whether prior IFN-α therapy enhanced adjuvant pembrolizumab as later-line treatment. Fifty-six patients with resectable stage III/IV melanoma who received adjuvant therapy with pembrolizumab were retrospectively enrolled in this study. Notably, 25 patients received adjuvant pegylated IFN-α (PEG-IFN-α) in the prior line of treatment while 31 patients did not receive prior PEG-IFN-α therapy. Cox regression analysis showed that prior PEG-IFN-α therapy was associated with the efficacy of later-line adjuvant pembrolizumab (hazard ratio=0.37, 95% CI 0.16-0.89; P = 0.026). The recurrence rates after treatment with adjuvant pembrolizumab were significantly reduced in the prior PEG-IFN-α group (P < 0.001). The Kaplan-Meier analysis also showed that recurrence-free survival (RFS) after adjuvant pembrolizumab therapy was prolonged by prior PEG-IFN-α treatment (median RFSPem 8.5 months vs. 4.5 months; P = 0.0372). These findings indicated that prior PEG-IFN-α could enhance the efficacy of adjuvant pembrolizumab. The long-lasting effects of PEG-IFN-α provide a new rationale for designing combination or sequential immunotherapy.

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IMUP and GPRC5A: two newly identified risk score indicators in pancreatic ductal adenocarcinoma

Cancer Cell International ◽

10.1186/s12935-021-02324-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Rong Wei ◽

Guoye Qi ◽

Zixin Zeng ◽

Ningning Shen ◽

Ziyue Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Cells ◽

Cox Regression ◽

Bioinformatic Analysis ◽

Cancer Development ◽

Local Hospital ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Key Genes ◽

The Difference

Abstract Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan–Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22,491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over eightfold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the > eightfold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan–Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 62 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

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Surgical Outcomes of Vaginal or Cervical Melanoma

Frontiers in Surgery ◽

10.3389/fsurg.2021.771160 ◽

2022 ◽

Vol 8 ◽

Author(s):

Hui Tian ◽

Xuan Wang ◽

Bin Lian ◽

Lu Si ◽

Min Gao ◽

...

Keyword(s):

Adjuvant Therapy ◽

Proportional Hazards ◽

Cox Regression ◽

Radical Resection ◽

Cox Proportional Hazards ◽

Cox Regression Analysis ◽

Resection Group ◽

Kaplan Meier ◽

Significant Difference ◽

Peking University

Objective: To evaluate the effectiveness of radical resection compared with non-radical resection for vaginal or cervical melanoma.Methods: We retrospectively analysed the clinical data of post-operative patients with primary lower genital tract melanoma hospitalised at Peking University Cancer Hospital between Jan 2014 and Dec 2020. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Kaplan–Meier method-plotted survival curves and univariate and multivariate Cox proportional hazards regression models were used to identify the factors associated with RFS and OS, and to calculate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs).Results: A total of 80 patients were included. Thirty-one patients had received non-radical resection, and 49 patients had received radical resection. The median patient age was 55.5 (IQR 45.3–60.0) years. Sixty-two (77.5%) patients had vaginal melanoma. Sixty-four patients (80.0%) had received post-operative adjuvant therapy. The median follow-up time was 36.0 months (95% CI 10.1–62.1 months). Sixty-four patients developed recurrence, and 44 patients died. The median RFS (mRFS) was 6.0 months (95% CI 3.4–8.6 m), and the RFS for the radical resection group was longer than that for the non-radical resection group (9.5 vs. 5.3 m), with no significant difference (P > 0.05). The median OS (mOS) was 25.9 months (95% CI 14.4–37.4 m). The mOS was 24.6 months (95% CI 10.3–38.9 m) and 25.9 months (95% CI 10.9–40.9 m) in the non-radical resection group and the radical resection group, respectively. Multivariate Cox regression analysis showed that surgical approach, infiltration depth of the tumour, lymph node metastasis, and post-operative adjuvant therapy were independent risk factors for RFS and that post-operative adjuvant therapy was an independent risk factor for OS.Conclusion: By performing multivariate analysis, which corrected for potential confounding factors, we identified surgical procedures that were associated with RFS, and we found that RFS and OS in patients with vaginal melanoma and cervical melanoma benefitted from post-operative adjuvant therapy.

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The role of TP, TS, and DPD as potential predictors of outcome following capecitabine plus oxaliplatin (XELOX) versus bolus 5-fluorouracil/leucovorin (5-FU/LV) as adjuvant therapy for stage III colon cancer: Biomarker findings from study NO16968 (XELOXA).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3578 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3578-3578

Author(s):

Hans-Joachim Schmoll ◽

Josep Tabernero ◽

Jean Alfred Maroun ◽

Filippo G. De Braud ◽

Timothy Jay Price ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Therapy ◽

Cox Regression ◽

Dihydropyrimidine Dehydrogenase ◽

Disease Free Survival ◽

Stage Iii ◽

Study Endpoint ◽

Primary Study ◽

Cox Regression Analysis ◽

Stage Iii Colon Cancer

3578 Background: In NO16968, XELOX was superior in terms of disease-free survival (DFS) and overall survival (OS) to bolus 5-FU/LV as adjuvant therapy for stage III colon cancer (Schmoll et al. ASCO GI 2012). Three key enzymes appear to have the potential to predict efficacy and/or safety of fluoropyrimidine-based treatment: thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD). We evaluated the association between baseline TP, TS and DPD and outcome (DFS and OS). Methods: Pts with stage III colon cancer received either XELOX (8 cycles, 24w) or bolus 5-FU/LV (Mayo Clinic, 6 cycles, 24w; Roswell Park, 4 cycles, 32w). The primary study endpoint was DFS; secondary endpoints included OS. TP, TS and DPD expression levels were determined in formalin-fixed, paraffin-embedded tissues by RT-PCR, and the median used as a cut-off point: high (above median) vs. low (below median). Results: The biomarker population included 498 (26%) of 1886 pts entered (XELOX, n=242; 5-FU/LV, n=256). Baseline demographics, tumor characteristics, cancer history and efficacy (DFS and OS) were similar to those in the main study population. Cox regression analysis for DFS (Table). In the XELOX group pts with low DPD and TP levels and a high TP/DPD ratio appeared to have significantly better DFS; this effect was not observed with 5-FU/LV. Subgroup analysis shows that the difference between XELOX and 5-FU/LV was also higher in pts with low DPD levels. Conclusions: These exploratory findings suggest that tumor DPD and TP RNA levels could be used to predict outcomes of adjuvant treatment with fluoropyrimidine/oxaliplatin combinations, and should be validated prospectively. Analysis of the current dataset is ongoing and further details on potential biomarkers will be available. [Table: see text]

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Factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e15712 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e15712-e15712

Author(s):

Mridula Krishnan ◽

Lakshmi Manogna Chintalacheruvu ◽

Nicholas B George ◽

Carlos J Silva ◽

Nabin Khanal ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Stage Iii ◽

Factors Affecting

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The Role of Chemotherapy in the Survival Benefits of Patients Aged Older Than 40 Years With Osteosarcoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211066195 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110661

Author(s):

Zhiyou Cao ◽

Yuelin Zhang ◽

Qiang Xu ◽

Xiaolong Yu ◽

Xuqiang Liu ◽

...

Keyword(s):

Regression Analysis ◽

Survival Benefit ◽

Cox Regression ◽

Rank Test ◽

Cancer Specific Survival ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Stratified Analysis ◽

The Impact ◽

Grade Iii

Objectives: The value of chemotherapy in the survival benefits of patients aged > 40 years with osteosarcoma is controversial. We aimed to explore the impact of chemotherapy on the survival benefits of patients aged >40 years with osteosarcoma. Methods: The Surveillance, Epidemiology, and End Results database was used to select eligible patients. The selected patients were divided into the chemotherapy and non-chemotherapy groups. Logistic regression analysis was performed to investigate the potential factors contributing to the selection of chemotherapy. The overall survival (OS) and cancer-specific survival (CSS) of the two groups were compared using the Kaplan–Meier method with a log-rank test. Cox proportional risk models were used to determine the prognostic factors for OS and CSS. Stratified analysis was performed according to tumour grade and stage. Results: A total of 1032 eligible patients were included in our analysis. Of these, 586 and 446 patients were in the chemotherapy and nonchemotherapy groups, respectively. Multivariate logistic analysis indicated that grade III/IV and distant stage were associated with chemotherapy. Kaplan–Meier plots showed that patients did not achieve an improved OS or CSS after receiving chemotherapy. Cox regression analysis indicated that age > 60 years, axial, grade III/IV, and regional and distant stage were independent risk factors for poor prognosis in both OS and CSS. Stratified analysis revealed a survival benefit from chemotherapy in patients with grade III/IV and distant stage. Conclusions: Chemotherapy did not significantly improve OS and CSS in patients aged > 40 years with osteosarcoma. In this age group, survival benefit from chemotherapy was observed in patients with high-grade tumours (grade III/IV) and metastasis (distant stage).

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Development of a Gene Risk Signature for Patients of Pancreatic Cancer

Journal of Healthcare Engineering ◽

10.1155/2022/4136825 ◽

2022 ◽

Vol 2022 ◽

pp. 1-8

Author(s):

Tao Liu ◽

Long Chen ◽

Guili Gao ◽

Xing Liang ◽

Junfeng Peng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Regression Analysis ◽

Cox Regression ◽

Roc Curves ◽

Cancer Prognosis ◽

Cox Regression Analysis ◽

Clinical Biomarkers ◽

Kaplan Meier ◽

Malignant Solid Tumor ◽

Patient Prognosis

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

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