Chinese Journal of Cancer Research最新文献

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive (CLDN18.2-positive) gastric cancer (GC) vary in different clinical studies, making it difficult to optimize anti-CLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.

Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01 clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells (2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells (2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.

Results: CLDN18.2 was expressed in 57.6% (cut-off: 2+, 40%) and 48.9% (cut-off: 2+, 70%) of patients. Programmed death-ligand 1 (PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score (CPS)≥1, CLDN18.2 (cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2 (cut-off: 2+, 70%)] of patients. CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction (non-GEJ), and diffuse phenotype (P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC (both P<0.05). Uterine adnexa metastasis (P<0.001) was more frequent and liver metastasis (P<0.001) was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival (irPFS) were inferior in the CLDN18.2-positive group.

Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.

Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.

Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0).

Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Objective: There 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.

Methods: We 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.

Results: We 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].

Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

The prevalence of colorectal cancer (CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum (F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However, little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis (CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC. Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

Objective: This study aims to provide an analysis of the current status and trends of lung cancer incidence and mortality rates in China, comparing trends with those in the United States (U.S.).

Methods: Data on lung cancer incidence and mortality rates spanning 2000 to 2018 were extracted from the China Cancer Registry Annual Report and the Surveillance, Epidemiology, and End Results database for China and the U.S., respectively. Crude incidence and mortality rates were calculated by sex and age, with age-standardized incidence rates (ASIR) and mortality rates (ASMR) calculated using the Segi-Doll world standard population. Trend analyses employed Joinpoint regression models to determine average annual percentage change (AAPC). The study also assessed the proportion of new cases and deaths by sex and age.

Results: In 2018, the ASIR of lung cancer for males in China was 50.72 per 100,000 and the ASMR was 39.69 per 100,000, the ASIR for females was 26.25 per 100,000 and the ASMR was 15.24 per 100,000. Both ASIR and ASMR were higher in males and the highest in the population aged 65 years and older, with the lowest among those aged 20-49 years. In China, female ASIR demonstrated an increasing trend (AAPC: 1.16%), while ASMR decreased in both sexes (AAPCs: -0.48% for males, -1.00% for females). The U.S. exhibited decreasing trends in both ASIR and ASMR across sexes and age groups.

Conclusions: The study identified an increasing trend in lung cancer incidence among females and a decreasing mortality trend in both sexes in China. These trends are likely linked to factors such as smoking prevalence, advancements in cancer screening, and improved medical care. The findings underscore the need for tailored lung cancer prevention measures in China, particularly the reinforcement of anti-smoking policies.

Objective: Cervical squamous intraepithelial lesion (SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment.

Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses ("diagnosis", "initial treatment", "chemoradiotherapy", "follow-up" and "recurrence/progression/metastasis") to estimate the total costs. The median and interquartile range (IQR) of total costs (including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated.

Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL (LSIL) (n=549), high-grade SIL (HSIL) (n=803), cervical cancer stage IA (n=226), IB (n=610), IIA (n=487), IIB (n=282), III (n=452) and IV (n=62). In urban areas, the estimated total costs of LSIL and HSIL were [Formula: see text]1,637.7 (IQR: [Formula: see text]956.4-[Formula: see text]2,669.2) and [Formula: see text]2,467.1 (IQR: [Formula: see text]1,579.1-[Formula: see text]3,762.3), while in rural areas the costs were [Formula: see text]459.0 (IQR: [Formula: see text]167.7-[Formula: see text]1,330.3) and [Formula: see text]1,230.5 (IQR: [Formula: see text]560.6-[Formula: see text]2,104.5), respectively. For patients with cervical cancer stage IA, IB, IIA, IIB, and III-IV, the total costs were [Formula: see text]15,034.9 (IQR: [Formula: see text]11,083.4-[Formula: see text]21,632.4), [Formula: see text]19,438.6 (IQR: [Formula: see text]14,060.0-[Formula: see text]26,505.9), [Formula: see text]22,968.8 (IQR: [Formula: see text]16,068.8-[Formula: see text]34,615.9), [Formula: see text]26,936.0 (IQR: [Formula: see text]18,176.6-[Formula: see text]41,386.0) and [Formula: see text]27,332.6 (IQR: [Formula: see text]17,538.7-[Formula: see text]44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage.

Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

Objective: The aim of this study was to investigate the factors influencing pathological complete response (pCR) rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab (H) + pertuzumab (P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden (RCB) systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2 (HER2)+ breast cancer was analyzed.

Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery (CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry (IHC) 3+/hormone receptor (HR)-, IHC3+/HR+, IHC2+ in situ hybridization (ISH)+/HR- and IHC2+ ISH+/HR+ groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.

Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals; 18,853 (24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target (H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate (P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0% (κ=0.717, P<0.001).

Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+ breast cancer.

Cancer stands as a prominent public health concern in China, with elusive intervention targets due to unidentified high-risk causal factors for most cancers. Consequently, emphasis has shifted towards screening, diagnosing, and treating early cancer cases within the general population. However, China faces considerable obstacles in its cancer prevention and control efforts, attributing to the complexity and heterogeneity of the occurrence, progression, and prognosis of malignant tumors across populations, time, and regions. Taking esophageal cancer screening practices as an example, this review outlines the importance and assessment of cancer screening, delineating major challenges in China's cancer prevention and control: 1) limited comprehension of cancer's natural history; 2) lack of "China Evidence" supporting screening effectiveness and value; 3) compromised efficiency and accuracy in current screening modality; and 4) insufficient sustainability of the current screening practices and translation of relevant scientific research achievements. To address these challenges, we propose potential coping strategies: 1) establishing tailored technologies and pathways for cancer prevention and control based on population-based and clinical epidemiological studies using high-quality designs; 2) breaking conventional constraints to establish a novel cancer screening strategy aligned with real-world needs; and 3) establishing enhanced communication platforms among scientific research teams, policymakers, and industrial institutions to foster collaboration and innovation.

Objective: The aim of this study was to prospectively compare double-tract reconstruction (DTR) and esophagogastrostomy (EG) after proximal gastrectomy (PG) regarding the incidence of reflux esophagitis, quality of life (QOL), nutritional status and surgical safety.

Methods: This study was a randomized controlled trial. Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group. The characteristics of patients, parameters for surgical safety, incidence of reflux esophagitis, nutrition status and QOL were collected and compared between the two groups. Univariate analysis and multivariate analysis were performed to determine the significant factors affecting the incidence of reflux esophagitis after PG.

Results: Thirty-seven patients of the EG group and 36 patients of the DTR group were enrolled. The incidence of reflux esophagitis was significantly lower in the DTR group than in the EG group (8.3% vs. 32.4%, P=0.019). The DTR group demonstrated a more favorable QOL than the EG group after PG. The nutritional status was balanced within the EG group and the DTR group. The operation time was longer in the DTR group than in the EG group (191 min vs. 221 min, P=0.001), while surgical safety was similar in the two groups.

Conclusions: Our research demonstrated that DTR is superior to EG after PG in terms of the incidence of reflux esophagitis and provides a more satisfactory QOL without increasing surgical complications or sacrificing nutritional status.