Chinese journal of cancer research = Chung-kuo yen cheng yen chiu最新文献

Objective: To describe the contemporary trends in total, inpatient, and outpatient expenditure on major subtypes of cancer in different classifications of hospitals in mainland China.

Methods: Home page of Inpatient Medical Records (HIMRs) and Hospital Annual Reports (HARs) were used to estimate hospital care expenditure on cancer. Inpatient payments and their share of cancer were calculated with the top-down method. Kriging spatial interpolation methods were used at the county level and summed at the province level. Outpatient expenditure was estimated with inpatient expenditure and the ratios of outpatient to inpatient payments in specialized cancer hospitals, stratified by province. Total expenditure on cancer was the sum of both payments. Log-linear regression was applied to estimate annual percentage change (APC) of expenditure.

Results: Total expenses for cancer of Chinese residents reached up to 304.84 billion Chinese Yuan (CNY) in 2017, accounting for 5.8% of the total health expenses (THE). After adjusting for consumer price index (CPI), medical expenses for cancer have increased from 63.30 billion CNY in 2008 to 249.56 billion CNY in 2017 [APC: 15.2%, 95% confidence interval (95% CI): 13.4%-17.0%]. The APC was slightly higher than THE around 2013, while was lower after 2013. During 2008-2017, the ratio of inpatient to outpatient costs for cancer decreased from 4.3:1 to 3.8:1. The inpatient payments for cancer mainly happened in grade 3 general hospitals, East China, and among lung, colorectal, and stomach cancer; while the fastest increase was found in West China, and among thyroid, prostate, and colorectal cancer.

Conclusions: During 2008-2017, the rapid growth trend of medical expenses for cancer has been effectively controlled with the continuous deepening of medical reform and improvements of residents' health care. More attention should be paid to potential increases of medical costs caused by technological progress and demand release. Socialized and multi-channel insurance financing modes should be explored in the future.

Objective: Benefits of adjuvant treatment in pT1N1 gastric cancer (GC) remain controversial. Additionally, an effective biomarker for early GC is the need of the hour. The prognostic and predictive roles of single patient classifier (SPC) were validated in stage II/III GC. In this study, we aimed to elucidate the role of SPC as a biomarker for pT1N1 GC.

Methods: The present retrospective biomarker study (NCT03485105) enrolled patients treated for pT1N1 GC between 1996 and 2012 from two large hospitals (the Y cohort and S cohort). For SPC, mRNA expression of four classifier genes (GZMB, WARS, SFRP4 and CDX1) were evaluated by real-time reverse transcription-polymerase chain reaction assay. The SPC was revised targeting pT1 stages and the prognosis was stratified as high- and low-risk group by the expression of SFRP4, a representative epithelial-mesenchymal transition marker.

Results: SPC was evaluated in 875 patients (n=391 and 484 in the Y and S cohorts, respectively). Among 864 patients whose SPC result was available, 41 (4.7%) patients experience GC recurrence. According to revised SPC, 254 (29.4%) patients were classified as high risk [123 (31.5%) and 131 (27.1%) in the Y and S cohorts, respectively]. The high risk was related to frequent recurrence in both Y and S cohort (log-rank P=0.023, P<0.001, respectively), while there was no difference byGZMB and WARS expression. Multivariable analyses of the overall-cohort confirmed the high risk of revised SPC as a significant prognostic factor [hazard ratio (HR): 4.402 (2.293-8.449), P<0.001] of GC. A significant difference was not detected by SPC in the prognosis of patients in the presence and absence of adjuvant treatment (log-rank P=0.670).

Conclusions: The present study revealed the revised SPC as a prognostic biomarker of pT1N1 GC and suggested the use of the revised SPC for early-stage GC as like stage II/III.

Objective: To forward the magnetic resonance imaging (MRI) based distance between the deepest tumor invasion and mesorectal fascia (DMRF), and to explore its prognosis differentiation value in cT3 stage rectal cancer with comparison of cT3 substage.

Methods: This was a retrospective, multicenter cohort study including cT3 rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by radical surgery from January 2013 to September 2014. DMRF and cT3 substage were evaluated from baseline MRI. The cutoff of DMRF was determined by disease progression. Multivariate cox regression was used to test the prognostic values of baseline variables.

Results: A total of 804 patients were included, of which 226 (28.1%) developed progression. A DMRF cutoff of 7 mm was chosen. DMRF category, the clock position of the deepest position of tumor invasion (CDTI) and extramural venous invasion (EMVI) were independent predictors for disease progression, and hazard ratios (HRs) were 0.26 [95% confidence interval (95% CI), 0.13-0.56], 1.88 (95% CI, 1.33-2.65) and 1.57 (95% CI, 1.13-2.18), respectively. cT3 substage was not a predictor for disease progression.

Conclusions: The measurement of DMRF value on baseline MRI can better distinguish cT3 rectal cancer prognosis rather than cT3 substage, and was recommended in clinical evaluation.

In the last decade, the focus of computational pathology research community has shifted from replicating the pathological examination for diagnosis done by pathologists to unlocking and discovering "sub-visual" prognostic image cues from the histopathological image. While we are getting more knowledge and experience in digital pathology, the emerging goal is to integrate other-omics or modalities that will contribute for building a better prognostic assay. In this paper, we provide a brief review of representative works that focus on integrating pathomics with radiomics and genomics for cancer prognosis. It includes: correlation of pathomics and genomics; fusion of pathomics and genomics; fusion of pathomics and radiomics. We also present challenges, potential opportunities, and avenues for future work.

More than 600,000 people are diagnosed with esophageal cancer (EC) every year globally, and the five-year survival rate of EC is less than 20%. Two common histological subtypes of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have great geographical variations in incidence rates. About half of the world's EC was diagnosed in China and a majority of which belong to ESCC. Globally, the overall incidence rate of EC is decreasing. In some high-risk Asian regions, such as China, the incidence rate of ESCC has generally declined, potentially due to economic growth and improvement of diet habits. In some European high-income countries and the United States, the decline is mainly attributed to the decrease in smoking and drinking. The risk factors of EC are not well understood, and the importance of environmental and genetic factors in the pathogenesis is also unclear. The incidence and mortality of advanced EC can be reduced through early diagnosis and screening. White light endoscopy is still the gold standard in the current screening technology. This article reviews the epidemiology, risk factors, and screening strategies of EC in recent years to help researchers determine the most effective management strategies to reduce the risk of EC.

Objective: To develop and validate a radiomics prognostic scoring system (RPSS) for prediction of progression-free survival (PFS) in patients with stage IV non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy.

Methods: In this retrospective study, four independent cohorts of stage IV NSCLC patients treated with platinum-based chemotherapy were included for model construction and validation (Discovery: n=159; Internal validation: n=156; External validation: n=81, Mutation validation: n=64). First, a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography (CT) images of each patient. Then, a radiomics signature was constructed using the least absolute shrinkage and selection operator method (LASSO) penalized Cox regression analysis. Finally, an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.

Results: The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts (All P<0.05). On the multivariable analysis, independent factors for PFS were radiomics signature, performance status (PS), and N stage, which were all selected into construction of RPSS. The RPSS showed significant prognostic performance for predicting PFS in discovery [C-index: 0.772, 95% confidence interval (95% CI): 0.765-0.779], internal validation (C-index: 0.738, 95% CI: 0.730-0.746), external validation (C-index: 0.750, 95% CI: 0.734-0.765), and mutation validation (C-index: 0.739, 95% CI: 0.720-0.758). Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness (All P<0.05).

Conclusions: This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stage IV NSCLC patients treated with platinum-based chemotherapy, which holds promise for guiding personalized pre-therapy of stage IV NSCLC.

Objective: The predictive effect of preoperative chemoradiotherapy (CRT) is low and difficult in guiding individualized treatment. We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT.

Methods: From April 2012 to April 2019, 95 patients with locally advanced gastric cancer who received preoperative concurrent CRT and who were enrolled in three prospective studies were included. All patients were stage T_3/4N₊. Local control, distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were evaluated. Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses. The down-staging depth score (DDS), which is a novel method of evaluating CRT response, was used to predict long-term outcomes.

Results: The median follow-up period for survivors was 30 months. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve predicted by the DDS was 0.728, which was better than the pathological complete response (pCR), histological response and ypN0. Decision curve analysis further affirmed that DDS had the largest net benefit. The DDS cut-off value was 4. pCR and ypN0 were associated with OS (P=0.026 and 0.049). Surgery and DDS are correlated with DMFS, DFS and OS (surgery: P=0.001, <0.001 and <0.001, respectively; and DDS: P=0.009, 0.013 and 0.032, respectively). Multivariate analysis showed that DDS was an independent prognostic factor of DFS (P=0.021).

Conclusions: DDS is a simple, short-term indicator that was a better surrogate endpoint than pCR, histological response and ypN0 for DFS.

Objective: Patient-derived xenograft (PDX) models provide a promising preclinical platform for hepatocellular carcinoma (HCC). However, the molecular features associated with successful engraftment of PDX models have not been revealed.

Methods: HCC tumor samples from 76 patients were implanted in immunodeficient mice. The molecular expression was evaluated by immunohistochemistry. Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test. The independent prediction parameters were identified by logistic regression analyses.

Results: The engraftment rate for PDX models from patients with HCC was 39.47% (30/76). Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates. Tumors with poor differentiation and vascular invasion were related to engraftment success. The positive expression of CK19, CD133, glypican-3 (GPC3), and Ki67 in tumor samples was associated with engraftment success. Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment. Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates, with 71.9% in GPC3⁺/Ki67⁺ tumors, 30.8% in GPC3^-/Ki67⁺ tumors, 15.0% in GPC3⁺/Ki67^- tumors, and 0 in GPC3^-/Ki67^- tumors.

Conclusions: Successful engraftment of HCC PDXs was significantly related to molecular features. Tumors with the GPC3⁺/Ki67⁺ phenotype were the most likely to successfully establish HCC PDXs.

Objective: To validate the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.

Methods: Data were collected from the China Pancreas Data Center (CPDC) for patients with resected PDAC in 2016 and 2017, and cancer-specific survival (CSS) was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors. The recursive partitioning analysis (RPA), Kaplan-Meier method, and log-rank test were performed on the training dataset to generate a proposed modification for the 8th TNM staging system utilizing the preoperative carbohydrate antigen (CA)19-9 level. Validation was performed for both staging systems in the validation cohort.

Results: A total of 1,676 PDAC patients were retrieved, and the median CSS was significantly different between the 8th TNM groupings, with no significant difference in survival between stage IB and IIA. The analysis of T and N stages demonstrated a better prognostic value in the N category. Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors. All patients with CA19-9 >500 U/mL had similar survival, and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III. The modified staging system had a better performance for predicting CSS than the 8th AJCC staging scheme.

Conclusions: The 8th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients, and the N category has a better prognostic value than the T category. Our modified staging system has superior accuracy in predicting survival than the 8th AJCC TNM staging system.

Objective: Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer (mCRC) worldwide and was approved in China in 2010. However, there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC. This observational, phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.

Methods: Between September 2013 and November 2016, patients with histologically confirmed mCRC were enrolled in a prospective, multicenter, observational, non-interventional phase IV trial at 26 centers across China. Eligible patients received different chemotherapeutic regimens combined with bevacizumab. The efficacy and safety data in the intention-to-treat study population were analyzed.

Results: A total of 611 patients were included in the efficacy analysis. The median overall survival and median progression-free survival was 18.00 and 10.05 months, respectively. The objective response rate was 21.00% and disease control rate was 89.40%. In subgroup analyses, the survival differences were observed according to metastatic status, duration of treatment and elevation in blood pressure. A total of 613 patients were evaluable for safety assessments. And 569 (92.82%) patients reported at least one adverse event (AE), and 151 (24.63%) experienced grade 3 or higher AEs. The incidence of bevacizumab-associated AEs of special interest was reported in 31 (5.06%) patients with hypertension (n=12), abscesses and fistulae (n=7), bleeding (n=6), proteinuria (n=3), gastrointestinal perforation (n=2) and venous thrombotic events (n=1).

Conclusions: This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety. Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.