A tool to predict survival in stage IV entero-pancreatic NEN.
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ABSTRACT: Purpose
Well-differentiated stage IV neuroendocrine neoplasms (NEN) have an extremely heterogeneous, unpredictable clinical behavior. Survival prognostic markers, such as the recently proposed NEP-Score, would be very useful for better defining therapeutic strategies. We aim to verify NEP-Score applicability in an independent cohort of stage IV well-differentiated (WD) gastroentero-pancreatic (GEP) NEN, and identify a derivate prognostic marker taking into account clinical and pathological characteristics at diagnosis.Methods
Age, site of primary tumor, primary tumor surgery, symptoms, Ki67, timing of metastases of 27 patients (10 females; mean age at diagnosis 60.2 ± 2.9 years) with stage IV WD GEP NEN were evaluated to calculate the NEP-Score at the end of follow-up (NEP-T). We calculated the NEP-Score at diagnosis (NEP-D), which does not consider the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF) and an NEP-Score threshold was investigated to predict survival.Results
Mean NEP-T and mean NEP-D were significantly lower in 15 live patients as compared to 12 deceased patients (p < 0.01) at EOF. We identified an NEP-D = 116 as the cutoff that significantly predicts survival. No gender differences were identified.Conclusions
In our series, we confirmed NEP-Score applicability. In addition, we propose NEP-D as a simple, quick and cheap prognostic score that can help clinicians in decision making. NEP-D threshold can predict NEN aggressiveness and may be used to define the best personalized therapeutic strategy.
SUBMITTER: Tarquini M
PROVIDER: S-EPMC8124053 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSeveral risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far.Patients and methodsA retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method.ResultsTwo hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively.ConclusionIn stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:409-415Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.
| S-EPMC5388376 | biostudies-literature
Project description:To develop clinical nomograms for prediction of overall survival (OS) and cancer-specific survival (CSS) in patients with stage IV tongue squamous cell carcinoma (TSCC) after surgery based on the Surveillance, Epidemiology, and End Results (SEER) program database.We collected data of resected stage IV TSCC patients from the SEER database, and divided them into the training set and validation set by 7:3 randomly. Kaplan-Meier analysis and Cox regression analysis were adopted to distinguish independent risk factors for OS and CSS. Clinical nomograms were constructed to predict the 3-year and 5-year probabilities of OS and CSS for individual patients. Calibration curves and Harrell C-indices were used for internal and external validation.A total of 1550 patients with resected stage IV TSCC were identified. No statistical differences were detected between the training and validation sets. Age, race, marital status, tumor site, AJCC T/N/M status, and radiotherapy were recognized as independent prognostic factors associated with OS as well as CSS. Then nomograms were developed based on these variables. The calibration curves displayed a good agreement between the predicted and actual values of 3-year and 5-year probabilities for OS and CSS. The C-indices predicting OS were corrected as 0.705 in the training set, and 0.664 in the validation set. As for CSS, corrected C-indices were 0.708 in the training set and 0.663 in the validation set.The established nomograms in this study exhibited good accuracy and effectiveness to predict 3-year and 5-year probabilities of OS and CSS in resected stage IV TSCC patients. They are useful tools to evaluate survival outcomes and helped choose appropriate treatment strategies.
| S-EPMC6616315 | biostudies-literature
Project description:Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -β), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.
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Project description:Background Since numerous retrospective studies and prospective trials have shown divergent results, whether the surgical excision of the primary tumor results in survival benefits for de novo stage IV breast cancer patients is inconclusive. Consequently, we need a prediction model of prognosis, judge the efficiency of breast surgery, and identify the advanced breast cancer patients who would benefit from surgery. Methods We analyzed the data of 2,747 metastatic breast cancer patients (the surgery group) and 4,508 patients (the non-surgery group) from the Surveillance, Epidemiology, and End Results (SEER) database during 2010–2015. Propensity score matching (PSM) was used to attain a balance between the covariates of both groups. We then assessed the potential risk factors for the breast cancer-specific survival (BCSS) of patients in the non-surgery group by Cox regression and constructed a nomogram to predict BCSS. All the patients were classified into different risk groups based on the median risk score obtained from the nomogram. The hazard ratios of BCSS and overall survival (OS) of patients in the two groups were calculated. Results After PSM, 2,288 patients severally in the two groups (the surgery group and the non-surgery group) were enrolled in the study. A nomogram incorporating 13 potential risk factors (i.e., age, race, cohabitation status, income, tumor grade, histotype, tumor size, lymph node status, molecular subtype, metastasis to brain, liver, lung, and chemotherapy) was constructed using the data of patients in the non-surgery group. The C statistics for the internal (patients in the non-surgery group) and external (patients in the surgery group) validation of the nomogram were 0.70 [95% confidence interval (CI), 0.69–0.71] and 0.73 (95% CI, 0.72–0.74), respectively. In the low-risk group, patients in the surgery group had lower risks of breast cancer-specific mortality (BCSM) (hazard ratio =0.53; 95% CI, 0.47–0.59; P for interaction =0.014) and overall mortality (OM) (hazard ratio =0.52; 95% CI, 0.46–0.58; P for interaction =0.002) than those in the non-surgery group. Conclusions Breast surgery might improve the survival of metastatic breast cancer patients in the low-risk group. The established nomogram could provide a reference for clinicians in enabling personalized treatment among advanced breast cancer patients.
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Project description:BackgroundRecent studies have shown patient-derived tumor organoids can predict the drug response of patients with cancer. However, the prognostic value of patient-derived tumor organoid-based drug tests in predicting the progression-free survival of patients with stage IV colorectal cancer after surgery remains unknown.ObjectiveThis study aimed to explore the prognostic value of patient-derived tumor organoid-based drug tests in patients with stage IV colorectal cancer after surgery.DesignRetrospective cohort study.SettingsSurgical samples were obtained from patients with stage IV colorectal cancer at the Nanfang Hospital.PatientsA total of 108 patients who underwent surgery with successful patient-derived tumor organoid culture and drug testing were recruited between June 2018 and June 2019.InterventionsPatient-derived tumor organoid culture and chemotherapeutic drug testing.Main outcomes measuresProgression-free survival.ResultsAccording to the patient-derived tumor organoid-based drug test, 38 patients were drug sensitive and 76 patients were drug resistant. The median progression-free survival was 16.0 months in the drug-sensitive group and 9.0 months in the drug resistant group ( p < 0.001). Multivariate analyses showed that drug resistance (HR, 3.38; 95% CI, 1.84-6.21; p < 0.001), right-sided colon (HR, 3.50; 95% CI, 1.71-7.15; p < 0.001), mucinous adenocarcinoma (HR, 2.47; 95% CI, 1.34-4.55; p = 0.004), and non-R0 resection (HR, 2.70; 95% CI, 1.61-4.54; p < 0.001) were independent predictors of progression-free survival. The new patient-derived tumor organoid-based drug test model, which includes the patient-derived tumor organoid-based drug test, primary tumor location, histological type, and R0 resection, was more accurate than the traditional clinicopathological model in predicting progression-free survival ( p = 0.001).LimitationsA single-center cohort study.ConclusionsPatient-derived tumor organoids can predict progression-free survival in patients with stage IV colorectal cancer after surgery. Patient-derived tumor organoid drug resistance is associated with shorter progression-free survival, and the addition of patient-derived tumor organoid drug tests to existing clinicopathological models improves the ability to predict progression-free survival.
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Project description:ObjectivesTo construct a nomogram model that combines clinical characteristics and radiomics signatures to preoperatively discriminate pancreatic ductal adenocarcinoma (PDAC) in stage I-II and III-IV and predict overall survival.MethodsA total of 135 patients with histopathologically confirmed PDAC who underwent contrast-enhanced CT were included. A total of 384 radiomics features were extracted from arterial phase (AP) or portal venous phase (PVP) images. Four steps were used for feature selection, and multivariable logistic regression analysis were used to build radiomics signatures and combined nomogram model. Performance of the proposed model was assessed by using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was applied to analyze overall survival in the stage I-II and III-IV PDAC groups.ResultsThe AP+PVP radiomics signature showed the best performance among the three radiomics signatures [training cohort: area under the curve (AUC) = 0.919; validation cohort: AUC = 0.831]. The combined nomogram model integrating AP+PVP radiomics signature with clinical characteristics (tumor location, carcinoembryonic antigen level, and tumor maximum diameter) demonstrated the best discrimination performance (training cohort: AUC = 0.940; validation cohort: AUC = 0.912). Calibration curves and DCA verified the clinical usefulness of the combined nomogram model. Kaplan-Meier analysis showed that overall survival of patients in the predicted stage I-II PDAC group was longer than patients in stage III-IV PDAC group (p<0.0001).ConclusionsWe propose a combined model with excellent performance for the preoperative, individualized, noninvasive discrimination of stage I-II and III-IV PDAC and prediction of overall survival.
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Project description:The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53-1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24-3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.
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Project description:BackgroundDue to the relatively insidious early symptoms of lung adenocarcinoma (LUAD), most LUAD patients are at an advanced stage at the time of diagnosis and lose the best chance of surgical resection. Mounting evidence suggested that the tumor microenvironment (TME) was highly correlated with tumor occurrence, progress, and prognosis. However, TME in advanced LUAD remained to be studied and reliable prognostic signatures based on TME in advanced LUAD also had not been well-established. This study aimed to understand the cell composition and function of TME and construct a gene signature associated with TME in advanced LUAD.MethodsThe immune, stromal, and ESTIMATE scores of each sample from The Cancer Genome Atlas (TCGA) database were, respectively, calculated using an ESTIMATE algorithm. The LASSO and Cox regression model were applied to select prognostic genes and to construct a gene signature associated with TME. Two independent datasets from the Gene Expression Omnibus (GEO) were used for external validation. Twenty-two subsets of tumor-infiltrating immune cells (Tiics) were analyzed using the CIBERSORT algorithm.ResultsFavorable overall survival (OS) and progression-free survival (PFS) were found in patients with high immune score (p = 0.048 and p = 0.028; respectively) and stromal score (p = 0.024 and p = 0.025; respectively). Based on the immune and stromal scores, 453 differentially expressed genes (DEGs) were identified. Using the LASSO and Cox regression model, a seven-gene signature containing AFAP1L2, CAMK1D, LOXL2, PIK3CG, PLEKHG1, RARRES2, and SPP1 was identified to construct a risk stratification model. The OS and PFS of the high-risk group were significantly worse than that of the low-risk group (p < 0.001 and p < 0.001; respectively). The receiver operating characteristic (ROC) curve analysis confirmed the good potency of the seven-gene signature. Similar findings were validated in two independent cohorts. In addition, the proportion of macrophages M2 and Tregs was higher in high-risk patients (p = 0.041 and p = 0.022, respectively).ConclusionOur study established and validated a seven-gene signature associated with TME, which might serve as a prognosis stratification tool to predict survival outcomes of advanced LUAD patients. In addition, macrophages M2 polarization may lead to worse prognosis in patients with advanced LUAD.
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Project description:Introduction Cancer cachexia, found in more than a third of patients with NSCLC, directly leads to functional and survival detriments. As screening and interventions for cachexia and NSCLC improve, deficits in health care access and quality among patients disadvantaged by racial-ethnic and socioeconomic factors must be addressed. Methods We retrospectively evaluated 957 patients diagnosed with having stage IV NSCLC between 2014 and 2020 in Dallas, Texas. Cachexia was retrospectively assessed by applying criteria for substantial unintentional weight loss in the time leading up to cancer diagnosis. Nonparametric, parametric, multivariate logistic regression, and Kaplan-Meier analyses were conducted to evaluate for variables potentially associated with cachexia incidence and survival. Results In multivariate analysis including age, sex, comorbidities, body mass index, risk behaviors, and tumor characteristics, Black race and Hispanic ethnicity were independently associated with more than a 70% increased risk of presenting with cachexia at the time of NSCLC diagnosis (p < 0.05). When private insurance status was included as a covariate, this association was diminished for Hispanic patients only. Black patients presented with stage IV disease at an average of approximately 3 years younger than White patients (Kruskal-Wallis p = 0.0012; t test p = 0.0002). Cachexia status at diagnosis consistently predicted for survival detriments, further highlighting the importance of addressing differential cachexia risk across racial-ethnic groups. Conclusions Fundamentally, our findings reveal elevated cachexia risk in Black and Hispanic patients with stage IV NSCLC with associated survival detriments. These differences are not fully accounted for by traditional determinants of health and suggest novel avenues for addressing oncologic health inequities.
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