Chinese Journal of Cancer Research最新文献

Objective: Immune effector cell-associated hematotoxicity (ICAHT), characterized by prolonged cytopenia and delayed hematopoietic recovery, is a common complication following chimeric antigen receptor T (CAR-T) cell therapy. However, the applicability of existing predictive models, CAR-HEMATOTOX (CAR-HT) for lymphoma, acute lymphoblastic leukemia-HEMATOTOX (ALL-HT) for B-ALL, and the early ICAHT prediction model (eIPM), remains uncertain across different hematologic malignancies.

Methods: We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June 2025, including B-ALL (n=62), T-ALL/non-Hodgkin's lymphoma (NHL) (n=25), and multiple myeloma (MM, n=32). The CAR-HT, ALL-HT, and eIPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.

Results: Grade 3 ICAHT occurred in 32.3% of B-ALL, 40.0% of T-ALL/NHL, and 25.0% of MM patients, while grade 4 rates were 33.9%, 20.0%, and 6.3%, respectively. CAR-HT classified 67.2% of patients as high-risk, and ALL-HT identified 56.3% of ALL/NHL patients as high-risk. In both models, high-risk groups experienced significantly more prolonged neutropenia than low-risk groups (CAR-HT: 17.7 vs. 5.3 d, P<0.001; ALL-HT: 21.3 vs. 7.7 d, P<0.001). Both eIPMpre and eIPMpost strongly correlated with grade 3-4 ICAHT (P<0.001). Importantly, survival analysis showed that eIPMpre stratification distinguished outcomes: 1-year overall survival (OS) was 65% in medium+high-risk vs. 84% in low-risk patients (P=0.006), and 1-year disease-free survival (DFS) was 44% vs. 73% (P<0.001). Similar predictive accuracy was observed with eIPMpost.

Conclusions: The CAR-HT, ALL-HT, and eIPM models consistently identify patients at high risk for severe ICAHT across B-ALL, T-ALL/NHL, and MM. Among these, the eIPM stands out as a promising universal tool for survival prediction. These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.

Objective: Microscopically positive resection margins (R1) in gastric cancer have been associated with poor outcomes, but evidence regarding its prognostic significance across different stages remains inconsistent. This study investigated the impact of R1 resection on survival outcomes and evaluated the prognostic significance of detailed pathological characteristics of margin involvement.

Methods: This retrospective study analyzed 10,165 patients who underwent curative-intent gastrectomy for gastric cancer between 2007 and 2021. Propensity score matching was performed at a 1:3 ratio between R1 (n=45) and R0 (n=130) cases. For R1 margins, detailed pathological assessment included involvement length, proportion, depth, and histological features. Survival outcomes were evaluated across all stages, and the impact of subsequent resection was analyzed.

Results: After propensity score matching, R1 resection showed significantly lower 5-year overall survival rates compared to R0 resection across all stages (stage I: 60.0% vs. 90.9%, P=0.008; stage II: 40.0% vs. 83.3%, P=0.001; stage III: 20.0% vs. 35.4%, P<0.001). In R1 cases, tumor involvement length ≤1 cm (P<0.001), proportion ≤10% (P=0.012), and mucosal-only involvement (P=0.004) were associated with better survival. Patients who underwent subsequent resection to achieve R0 status showed better survival than those with persistent R1 resection (53.8% vs. 26.7%, P<0.001) and comparable survival to matched R0 cases (53.8% vs. 46.9%, P=0.320).

Conclusions: R1 resection significantly impairs survival across all stages of gastric cancer, with the extent and depth of microscopic involvement influencing prognosis. When R1 status is discovered postoperatively, subsequent resection should be considered to improve survival outcomes.

Acute graft-versus-host disease (aGVHD) is an important complication which critically impacts the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation. Increasing evidence suggests that dysbiosis of the gut microbiota plays a key role in aGVHD pathogenesis. The biological process involves compromised intestinal barrier integrity, amplified inflammation driven by the translocation of microbial products like lipopolysaccharide, and finally the dysregulated immune response centralized by T cell activation and differentiation. Meanwhile, certain microbial metabolites such as short-chain fatty acids and secondary bile acids exert protective effects. The clinical relevance of these findings is underscored by studies establishing that specific gut microbial signatures, such as low diversity and single pathogen dominance, independently predict aGVHD morbidity and mortality. From a therapeutic perspective, the microbiome has emerged as an important therapeutic target for aGVHD. Fecal microbiota transplantation has shown significant efficacy in clinical trials for prophylaxis and treatment of aGVHD, providing definitive proof-of-concept for ecological restoration. This review synthesizes these foundational mechanistic insights, from metabolic disruption to host-microbe crosstalk at the mucosal barrier, and details the rapidly advancing clinical landscape of microbiome-targeted diagnostics and therapeutics for aGVHD.

Objective: This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography (LDCT) scans, thereby addressing overdiagnosis in lung cancer screening.

Methods: In this retrospective study, 628 patients with pulmonary nodules who underwent three LDCT scans followed by surgical resection were categorized into invasive carcinoma (n=155) and non-invasive nodule (n=473) groups on the basis of pathological diagnosis. This derivation aimed to identify risk factors and construct a multivariate logistic model. The predictive performance was externally validated in two independent cohorts (retrospectively designed, n=252; prospectively designed, n=269). The discrimination and calibration of the model were evaluated using area under the curve (AUC), and calibration plots. Decision curve analysis (DCA) was further performed to evaluate the net benefit in practical clinical scenarios.

Results: The model, termed multiple CTs-invasive lung cancer (MCT-ILC), incorporated eleven factors encompassing nodule features at baseline and feature variability during follow-up. The standard deviation of diameter variability (SD_diameter) was the most reliable predictor, with an odds ratio [95% confidence interval (95% CI) of 7.35 (5.32-10.16) (P<0.001). AUCs with 95% CIs for the MCT-ILC model were 0.912 (0.864-0.960) and 0.906 (0.833-0.979) in the two testing cohorts and were superior to those for the model containing only features at baseline (P_Delong=0.002 and 0.021, respectively). For calibration, the Brier scores of the MCT-ILC model were 0.091 (95% CI: 0.064-0.118) and 0.078 (95% CI: 0.055-0.101) in the two test sets. The decision curve image showed that the MCT-ILC model was the only model that maintained positive net benefits across the entire threshold range. Furthermore, the MCT-ILC model score could classify more than 90% of patients with invasive nodules into the high-risk group.

Conclusions: The MCT-ILC model could assess pulmonary nodule invasiveness, potentially mitigating overdiagnosis in lung cancer screening.

Objective: This study aims to estimate the thyroid cancer (TC) burden and trends from 1990 and 2021 among working-age population (WAP), at the global, regional, and national levels.

Methods: Based on the Global Burden of Disease 2021 study, this cross-sectional study included data on TC incidence and mortality for WAP aged 15-64 years across 204 countries and territories from 1990 to 2021. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of TC were used to estimate the disease burden. Temporal trends of ASIR and ASMR were estimated by average annual percentage changes (AAPCs) based on age-period-cohort models. Relative inequality of TC burden across 204 countries was estimated by the slope index of concentration index.

Results: Globally, ASIR of TC increased from 2.27 per 100,000 population to 3.41 per 100,000 population from 1990 to 2021, with AAPC of 1.59% [95% confidence interval (95% CI): 1.54, 1.64]; in contrast, ASMRs were stable at 0.31 per 100,000 population. Females had a higher disease burden than males, and adults aged 45-64 years accounted for more than 55% of the TC cases. Across regions and countries, North Africa and Comoros experienced the highest increase in ASIR, with AAPCs of 2.97% and 7.73%, respectively. All socio-demographic index (SDI) regions experienced a significant increase in ASIR, and regions with high and high-middle SDI experienced a significant decrease in ASMR. Global ASIR burden and ASMR burden were revealed to be concentrated mainly in higher-SDI and lower-SDI countries, respectively, with the concentration index in both sexes of 0.16 (95% CI: 0.13, 0.19) and -0.14 (95% CI: -0.18, -0.10) in 2021.

Conclusions: Over the past three decades, the incidence burden of TC among the global WAP remarkably increased. International and regional policies for TC controls are supposed to be updated timely, to handle the current increasing burden and geographic disparities among WAP.

Objective: Acute myeloid leukemia (AML) patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene (FLT3-ITD) receiving tyrosine kinase inhibitors maintenance after allogeneic hematopoietic stem cell transplantation (allo-HSCT) demonstrated improved survival outcomes, however, some still experienced relapse during the maintenance. This study aimed to explore risk factors which might be indicators for poor survival after allo-HSCT in this population.

Methods: We consecutively enrolled FLT3-ITD AML patients undergoing transplantation at three centers. By integrating genetic profiles with clinical information, we assessed their impact on transplant outcomes.

Results: A total of 196 patient were eligible in the analysis, among whom 14% harbored myelodysplasia-related (MR) mutations, including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and ZRSR2. Co-mutant MR was independently associated with poorer overall survival (OS) [hazard ratio (HR): 2.4, 95% confidence interval (95% CI): 1.1-5.3, P=0.030]. DNMT3A co-mutations strongly predicted adverse survival and relapse [OS: HR: 2.1, 95% CI: 1.0-4.3, P=0.045; relapse-free survival (RFS): HR: 2.2, 95% CI: 1.1-4.1, P=0.017; cumulative incidence of relapse (CIR): HR: 2.3, 95% CI: 1.1-4.8, P=0.030]. Compared to patients with negative measurable residual disease (MRD) complete remission (CR), no significant differences were observed in CR patients with positive MRD, while those without CR exhibited significantly inferior outcomes (P=0.003).

Conclusions: Patients with myelodysplasia-related gene mutations (MRmut) and/or DNMT3A mutations experienced inferior outcomes after transplantation, requiring further exploration. Furthermore, similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.

Objective: Pancreatic cancer is a global health challenge, yet the Western Pacific Region (WPR) lacks comprehensive analysis of its burden and human resources for health (HRH) distribution. This study aims to assess trends in pancreatic cancer and HRH density in the WPR and investigate their relationship.

Methods: Pancreatic cancer data from GBD 2021 and annual HRH density from GBD 2019 were analyzed. Joinpoint regression was used to analyze temporal trends of pancreatic cancer burden and HRH density across 31 countries of the WPR. Spearman's rank correlation analysis and generalized linear models were applied to investigate the association between HRH density and pancreatic cancer burden.

Results: From 1990 to 2021, pancreatic cancer incidence in the WPR increased by 209%, from 59,766 to 184,612 cases, with a 201% rise in mortality and a 152% increase in disability-adjusted life years (DALYs). In 2021, smoking and high fasting plasma glucose were major risk factors, responsible for 16.43% and 23.29% of deaths, respectively. HRH density was positively correlated with the age-standardized incidence (P=0.767), death (P=0.752), and DALYs (P=0.726) rates of pancreatic cancer, and in 2019, most countries' HRH densities were below the Universal Health Coverage targets.

Conclusions: Despite improvements in HRH, notable distribution inequalities and shortages persist, limiting capabilities in pancreatic cancer diagnosis and treatment. The positive association between burden and HRH density reflects improved diagnostics from HRH growth but persistent treatment insufficiency due to shortages, and suggests that targeted HRH investment, strengthened primary care, and integration of palliative care are crucial to alleviating the burden.

Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CAR-T) therapy represent pivotal treatments for hematologic malignancies, each with distinct strengths and limitations. ASCT reduces tumor burden through myeloablative conditioning but remains susceptible to relapse, while CAR-T therapy precisely targets malignant cells but encounters challenges, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and limited persistence. Emerging evidence suggests that combining ASCT with CAR-T therapy yields synergistic effects. ASCT reshapes the immune microenvironment, lowers immunosuppressive cells and CRS risk, while CAR-T eliminates residual disease and promotes immune recovery. Clinical trials in relapsed/refractory B-cell lymphomas and multiple myeloma demonstrate complete remission rates (CRR) of 72%-100% and two-year progression-free survival (PFS) rates of 59%-83%, with severe CRS/ICANS incidences below 10%. However, the precise mechanisms underlying this synergy, optimal timing of CAR-T infusion after ASCT, and ideal dosing regimens require further definition. Future research should prioritize large-scale, randomized controlled trials and establish standardized protocols for toxicity management to maximize therapeutic benefits. By integrating the complementary strengths of ASCT and CAR-T, this combination strategy represents a promising approach for improving outcomes in high-risk hematologic malignancies; however, additional studies are necessary to validate its efficacy and expand its clinical applicability.

Objective: Heterogeneity in the evidence of association between lifestyle factors and breast cancer (BC) incidence hampers initiatives to modify BC risk. This overview aims to synthesise evidence from systematic reviews (SRs) to inform lifestyle-related modifications for BC prevention.

Methods: We systematically searched (MEDLINE, EMBASE, and CINAHL) from January 2013 to August 2023 for SRs of the association between lifestyle factors [alcohol consumption, physical activity (PA), body mass index (BMI), smoking, breastfeeding, oral contraception (OC), hormone replacement therapy (HRT), and sedentary behavior (SB)] and BC incidence. A narrative data synthesis was performed.

Results: Sixty-six SRs met the eligibility criteria. Evidence from 40 SRs indicated consistent associations between the risk of BC and postmenopausal BMI increase (relative risk increase: 2%-21%), use of HRT (risk increase: 23%-33%), smoking (risk increase: 4%-86%), and alcohol consumption (risk increase: 4%-61%). Additionally, evidence from 23 SRs suggested protective associations with PA (risk decrease: 10%-39%), breastfeeding (risk decrease: 9%-53%), and healthy lifestyle scores (protective about 20%-26%). However, inconsistent and/or statistically non-significant associations were found between BC incidence and premenopausal BMI increase [relative risk (RR): 0.78-1.08], SB (RR: 1.01-1.20), and OC use [odds ratio (OR): 1.01-1.35].

Conclusions: This overview identifies lifestyle factors associated with BC incidence, highlighting both harmful and protective factors. Our summary findings can support information and interventions related to modifying these factors, including limiting alcohol and smoking, or avoiding postmenopausal BMI increase and HRT.