Chin J Cancer Res

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib

doi: 10.21147/j.issn.1000-9604.2023.05.09

ObjectiveCurrently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis.MethodsWe enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox’s proportional hazard model. Efficacy was analyzed by logistic-regression models.ResultsAmong 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003−0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs. 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024−11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs. 68.2%, OR=4.535; 95% CI: 1.285−16.011; P=0.019) compared to poorly-defined margins.ConclusionsThese pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.

关键词: Neuroendocrine tumors, liver metastases, computed tomography, surufatinib

Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

doi: 10.21147/j.issn.1000-9604.2024.01.09

ObjectiveThere is an ongoing debate about whether the management of gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) should follow the guidelines of small-cell lung cancer (SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.MethodsWe recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing (NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC (LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.ResultsWe recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas. Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC (TERT amplification), colorectal NEC (KRAS mutation), and bile tract NEC (ARID1A mutation). The gene disparities between small-cell NEC (SCNEC) and large-cell NEC (LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in 22.2% of the patients, and they had longer progression-free survival (PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40 (0.21−0.75), P=0.006].ConclusionsThis work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

关键词: Neuroendocrine carcinoma, gastroenteropancreatic, lung, genetic alterations, molecular markers

Genomic dissection of gastrointestinal and lung neuroendocrine neoplasm

doi: 10.21147/j.issn.1000-9604.2019.06.08

ObjectiveNeuroendocrine neoplasms (NENs) are relatively rare and heterogeneous malignancies with two major subtypes: low-grade neuroendocrine tumor (NET) and high-grade neuroendocrine carcinoma (NEC). Comprehensive molecular characterization of NENs is needed to refine our understanding of the biological underpinnings of different NEN subtypes and to predict disease progression more accurately.MethodsWe performed whole-exome sequencing (WES) of NEN samples from 49 patients (25 NETs and 24 NECs) arising from the stomach, intestines or lung. Clinicopathologic features were assessed and associated with molecular events.ResultsNENs generally harbor a low mutation burden, with TP53 being the top mutated gene found in 31% of patients. Consistent with other studies, p53 signaling pathway dysfunction is significantly enriched in NECs compared to NETs (P<0.01). Other than TP53, tissue type-specific mutation profiles of NENs were observed in our cohort compared to those reported in pancreatic NETs. Importantly, we observed significant genomic instability, with increased copy number alterations observed across the NEN genome, which was more profound in NECs and independently correlated with poor overall survival (OS) (P<0.001). NECs could be further stratified into two molecular subtypes based on OS (P<0.001) and the chromosomal instability score (CIS). Interestingly, we discovered that the gain of whole chromosome 5 occurred at the early stage of NEN development, followed by the loss of 5q exclusively in NECs (P<0.001). ConclusionsThese findings provide novel insights into the molecular characteristics of NENs and highlight the association of genomic stability with clinical outcomes.

关键词: Neuroendocrine carcinoma, whole-exome sequencing, chromosomal instability

Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening: A cross-sectional population-based analysis

doi: 10.21147/j.issn.1000-9604.2021.04.08

ObjectiveIntegration of risk stratification into fecal immunochemical test (FIT) might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer (CRC) screening. A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment (QRA) and FIT, FIT-only and QRA-only strategies in a CRC screening program in China.MethodsThe study included 29,626 individuals aged 40−74 years and invited to participate in a CRC screening program in China. Participants were first invited to undertake QRA and one-time FIT (OC-sensor). Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy. Participation, detection rate, and resource demand for colonoscopy were calculated and compared.ResultsOf the 29,626 invitees, 20,203 completed the parallel combination, 8,592 completed the QRA-only, and 11 completed the FIT-only strategy. For the parallel combination, FIT-only, and QRA-only strategies, the overall positivity rates were 10.2% (2,928/28,806), 5.4% (1,096/20,214), and 6.8% (1,944/28,795), respectively; the yield of advanced neoplasm per 10,000 invitees were 46.9 [95% confidence interval (95% CI): 39.8−55.4], 36.8 (95% CI: 30.5−44.4), and 12.2 (95% CI: 8.8−16.8), respectively; the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7% (95% CI: 4.0%−5.6%), 9.9% (95% CI: 8.3%−11.9%), and 1.9% (95% CI: 1.3%−2.6%), respectively; the number of colonoscopies required to detect one advanced neoplasm was 11.4 (95% CI: 9.8−13.4), 5.7 (95% CI: 4.8−6.7), and 28.4 (95% CI: 20.7−39.2), respectively.ConclusionsThe parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.

关键词: Colorectal neoplasm, screening, fecal immunochemical test, risk stratification

Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

doi: 10.21147/j.issn.1000-9604.2017.06.13

Objective To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs), and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases. Methods Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016, and received transarterial embolization (TAE) in the hepatic tumor or hepatic arterial infusion chemotherapy (HAIC). All patients received 179 times of the intervention therapy in total. Results Blood supplies were identified in the 50 cases with angiography, which showed that 35 cases had abundant vessels, while 15 cases had poor blood supply. Twenty-two cases were found either collateral blood supply, or portal vein invasion or arterial-portal vein fistula. The best curative efficacy was complete remission (CR) in 4 cases, partial remission (PR) in 28 cases and stable disease (SD) in 18 cases during the process of treatment. The angiography (P=0.047) and the frequency of intervention (P=0.037) showed significantly statistical difference with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor. Conclusions Interventional treatment is safe and effective for GEP-NETs, and is beneficial to patients with main hepatic metastases after endocrine therapy.

关键词: Gastroenteropancreatic neuroendocrine tumors, hepatic metastasis, angiography, interventional treatment, retrospective analysis

Utility of CT in differentiating liver metastases of well-differentiated gastroenteropancreatic neuroendocrine neoplasms from poorly-differentiated neuroendocrine neoplasms

doi: 10.21147/j.issn.1000-9604.2018.01.04

Objective To determine the capability of dynamic enhanced computed tomography (CT) to differentiate liver metastases (LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Methods Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model. Results The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well- and poorly-differentiated GEP-NENs in terms of feeding arteries (36.4% vs. 75.0%, χ²=8.061, P=0.005), intratumoral neovascularity (18.2% vs. 59.4%, χ²=9.047, P=0.003), lymphadenopathy (27.3% vs. 81.2%, χ²=15.733, P<0.001), tumor-to-aortic ratio in the hepatic arterial and portal venous phase (T-A/AP: 0.297±0.080 vs. 0.251±0.059, t=2.437, P=0.018; T-A/PVP: 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003) and tumor-to-liver ratio in the hepatic arterial phase (T-L/AP: 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006). The LMs of poorly-differentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval (95% CI), 0.018–0.646], lymphadenopathy (P=0.001, OR=0.055, 95% CI, 0.009–0.323) and T-A/PVP (P=0.004, OR=5.3E–5, 95% CI, 0.000–0.044) were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs. Conclusions Dynamic enhanced CT features (intratumoral neovascularity, lymphadenopathy and T-A/PVP) are useful in the pathological classification of LMs of GEP-NENs.

关键词: Diagnosis, gastroenteropancreatic neuroendocrine neoplasm, neoplasm grading, tomography, X-ray computed

Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions: Findings from Global Burden of Disease Study

doi: 10.21147/j.issn.1000-9604.2021.01.02

ObjectiveChina is one of the countries with the heaviest burden of gastric cancer (GC) in the world. Understanding the epidemiological trends and patterns of GC in China can contribute to formulating effective prevention strategies.MethodsThe data on incidence, mortality, and disability-adjusted life-years (DALYs) of GC in China from 1990 to 2019 were obtained from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of disease burden of GC, and the package Nordpred in the R program was used to perform an age-period-cohort analysis to predict the numbers and rates of incidence and mortality in the next 25 years.ResultsThe number of incident cases of GC increased from 317.34 thousand in 1990 to 612.82 thousand in 2019, while the age-standardized incidence rate (ASIR) of GC decreased from 37.56 per 100,000 in 1990 to 30.64 per 100,000 in 2019, with an EAPC of −0.41 [95% confidence interval (95% CI): −0.77, −0.06]. Pronounced temporal trends in mortality and DALYs of GC were observed. In the next 25 years, the numbers of new GC cases and deaths are expected to increase to 738.79 thousand and 454.80 thousand, respectively, while the rates of incidence and deaths should steadily decrease. The deaths and DALYs attributable to smoking were different for males and females.ConclusionsIn China, despite the fact that the rates of GC have decreased during the past three decades, the numbers of new GC cases and deaths increased, and will continue to increase in the next 25 years. Additional strategies are needed to reduce the burden of GC, such as screening and early detection, novel treatments, and the prevention of risk factors.

关键词: Gastric cancer, disease burden, temporal trend, risk factor, prediction

Expressions of Thymidylate Synthase,Thymidine Phosphorylase, Class III β-tubulin, and Excision Repair Cross-complementing Group 1predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin

doi: 10.1007/s11670-011-0288-8

ObjectiveToevaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin.MethodsThe clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically.ResultsThe median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361).ConclusionTUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.

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主管单位：	中国科学院
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