Journal of Cancer Research and Clinical Oncology最新文献

Introduction: This retrospective study compared the impact of radiotherapy (RT) and immunotherapy (IO) on survival in patients with stage IV non-small cell lung cancer (NSCLC) following a diagnosis of bone metastasis.

Methods: The TriNetX database (2013-2024) was queried for adults (≥ 18 years) with NSCLC who received IO after diagnosis of bone metastases. Patients were then divided into cohorts based on whether they also received RT after bone metastasis diagnosis.

Results: A risk assessment revealed RT + IO was associated with significantly improved survival at 3 months (92% vs. 86% alive, p < 0.001), 6 months (79% vs. 72%, p = 0.002), and 1 year (59% vs. 54%, p = 0.014). In patients with adenocarcinoma, RT + IO was associated with improved survival at 3 months (92% vs. 88%, p = 0.046) but not at 6 months or 1 year. Similarly, in patients with squamous cell carcinoma, IO + RT was also associated with higher survival (94% vs. 85%, p = 0.040) at 3 months but not at 6 months or 1 year. A Cox proportional hazards model found significant lower hazard of death in the RT + IO group (hazard ratio [HR] = 0.83) and several covariates were associated with higher hazard, including adrenal metastasis (HR = 1.7), liver metastasis (HR = 1.4), lymph node metastasis (HR = 1.3), hypoalbuminemia (< 3.45 g/dL; HR = 1.5), and inpatient or observation care (HR = 1.4).

Discussion: This study highlights the potential importance of combining RT with IO, particularly in the early period after bone metastasis diagnosis.

Purpose: Primary testicular lymphoma (PTL) is a rare but aggressive form of extranodal lymphoma with a high risk of central nervous system (CNS) relapse and poor long-term survival. However, the optimal CNS prophylaxis strategy and effective prognostic models for PTL remain unclear. This study aimed to evaluate the prognostic impact of intrathecal (IT) prophylaxis and to develop a novel, simplified prognostic model in a Chinese multicenter cohort.

Methods: We retrospectively collected data from a total of 55 patients with PTL, treated at three major tertiary hospitals in China. Multivariate Cox regression identified independent prognostic factors for overall survival (OS) and progression-free survival (PFS). A new risk stratification model (BL model, based on B symptoms and LDH levels) was constructed and validated using time-dependent C-index and calibration plots, and compared with the International Prognostic Index (IPI).

Results: IT prophylaxis reduced CNS relapse rates (9.1% vs. 36.4%, p < 0.001) and was independently associated with improved OS (HR = 0.18, p < 0.001) and PFS (HR = 0.21, p < 0.001). The BL model (B symptoms and LDH), demonstrated superior predictive accuracy compared to the IPI, with higher AUCs at 1-, 3-, and 5-year OS (0.883, 0.894, 0.854 vs. 0.656, 0.804, 0.724), and a corrected C-index of 0.798. Calibration analysis confirmed good agreement between predicted and observed survival.

Conclusion: IT prophylaxis significantly improves survival and reduces CNS relapse in PTL. The BL model provides a simple yet effective tool for individualized risk stratification, outperforming IPI and aiding clinical decision-making in PTL.

Background: Although pembrolizumab has been shown to be effective, its high price has prevented it from being widely used. Especially in the real world, the application situation is still uncertain. The purpose of this study was to evaluate the cost-effectiveness of pembrolizumab on the basis of real-world studies, from the perspective of the health care system.

Methods: Retrospectively, 630 patients with advanced NSCLC treated with pembrolizumab (monotherapy or combination chemotherapy) versus chemotherapy alone from January 2020 to December 2022 at a large 3 A hospital in China were included. Confounders between groups were eliminated using propensity score matching analysis. A partitioned survival model was developed to evaluate the cost-effectiveness of pembrolizumab versus chemotherapy for the treatment of advanced NSCLC based on progression-free survival, overall survival, and the incidence of adverse effects in the two matched groups (n = 450 patients). The incremental cost-effectiveness ratio was calculated. The impact of a drug donation program on the cost-effectiveness of pembrolizumab was also evaluated.

Results: Pembrolizumab significantly improved median PFS in patients (15.5 months vs. 8.8 months). The median OS in the Pembrolizumab group has not been reached, while it was 26.2 months in the chemotherapy group. When the drug donation program is not considered, the ICER of pembrolizumab is $146,409.07/QALY. Regardless of whether the willingness-to-pay threshold is set at three times the per capita GDP of China ($36,070.2) or three times the per capita GDP of Guangdong Province ($64,523.8), the use of pembrolizumab is not cost-effective. However, after considering the drug donation program, the ICER decreased to $56,127.74/QALY. Under the willingness-to-pay threshold of three times the per capita GDP of Guangzhou in 2022 ($64,523.8), pembrolizumab became a cost-effective choice.

Conclusion: In the treatment of advanced NSCLC in China, pembrolizumab, particularly when considering the drug donation program, offers better survival outcomes and becomes cost-effective. This highlights the importance of such programs in making high-cost treatments accessible in real-world clinical settings.

Purpose: This study aimed to assess the health-related quality of life (HRQoL) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT), comparing outcomes with the German general population and colorectal cancer (CRC) patients treated with curative intent.

Methods: In a multicenter, cross-sectional study within the "TNTox" study framework (DRKS 00033000), EORTC QLQ-C30 and QLQ-CR29 questionnaires were distributed to LARC patients who had completed TNT. Mean reference values were compared descriptively, and further exploratory comparisons based on clinical features were performed.

Results: The study included responses from 72 patients. Compared to the German general population, a reduction in mean HRQoL across most domains was observed; the strongest effect was observed for role functioning (- 28.7 points, Cohen's d = - 0.95), social functioning (- 25.3 points, d = - 0.89), and for diarrhea (+ 9.9 points, d = 0.80). General HRQoL was similar to that of CRC patients following curative treatment. However, some symptom scores, notably fecal incontinence (+ 13.4 points, d = 0.52), impotence (+ 29.0 points, d = 0.73), and dyspareunia (+ 10.4 points, d = 0.40) appeared to be higher. Significant factors associated with HRQoL included the presence of chronic treatment-related toxicity and duration of TNT; no major differences were observed between patients with or without NOM or stoma.

Conclusion: LARC patients undergoing TNT showed comparable HRQoL outcomes to CRC patients treated with curative intent, but with reductions when compared to the general population. The presence of chronic toxicity significantly impacts HRQoL. Survivors may experience HRQoL impairments post-TNT, underscoring the necessity for ongoing management of chronic toxicity tailored to their needs.

Purpose: Cell growth regulator with EF-hand domain 1 (CGREF1) has been implicated in the upregulation across various cancer types. However, its functional role and clinical relevance in colorectal cancer (CRC) remain poorly characterized. The current study explored the role of CGREF1 in the development and progression CRC.

Methods: Bioinformatics analysis was used to examine the expression of CGREF1 in various malignancies, including CRC. Immunohistochemistry (IHC) and Quantitative real-time PCR (qRT-PCR) were performed to determine the expression of CGREF1 in CRC tissues. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of CGREF1 on the development and progression of CRC.

Results: Bioinformatics analyses confirmed significant upregulation of CGREF1 in multiple malignancies, including CRC. qRT-PCR validated these findings by showing a marked increase in CGREF1 mRNA levels in CRC tissues relative to paired normal adjacent tissues. Consistently, IHC evaluations further corroborated these findings, demonstrating that CGREF1 expression was significantly upregulated in human CRC tissues compared to matched adjacent normal intestinal epithelial tissues. Notably, high expression levels of CGREF1 were significantly correlated with aggressive tumor characteristics and poorer prognostic outcomes in CRC patients. Specifically, CGREF1 expression was markedly elevated in high-grade budding (Bd3), highlighting its potential role in this critical process. Knockdown of CGREF1 in CRC cells significantly attenuated the migration capacity in vitro and in vivo, but did not affect cellular proliferation. Furthermore, knockdown of CGREF1 decreased attenuated F-actin polymerization and reduced pseudopodia formation in CRC cells.

Conclusion: Our findings establish CGREF1 as a critical promoter of CRC migration and a potential prognostic biomarker, providing novel insights into the molecular mechanisms underlying CRC metastasis.

Purpose: While several countries reported an impact of the coronavirus disease (COVID-19) pandemic on cancer incidence in 2020, little is known about trends in the following years. This study examined changes in cancer incidence in Baden-Württemberg between 2015 and 2023.

Methods: Data from the Baden-Württemberg Cancer Registry were used to calculate age-standardized and age-specific incidence rates for all cancers combined and for colorectal, lung, prostate, and breast cancer. Incidence rates for 2020 to 2023 were compared with those from a pre-pandemic reference period (2017-2019) and with expected rates based on modeled trends between 2015 and 2019 using standardized incidence ratios (SIRs).

Results: Among men, the age-standardized overall cancer incidence declined significantly from 734.0 per 100,000 in 2019 to 672.9-681.7 during 2020-2023. In women, incidence declined from 542.2 in 2019 to 504.3-524.4, with statistically significant reductions in 2022 and 2023. Compared to 2017-2019 levels, 14,214 fewer cases (-5.5%) were diagnosed in 2020-2023; relative to model-based expectations, 19,525 fewer cases (-7.6%) were reported. Site-specific analyses showed significantly lower colorectal cancer incidence in both sexes from 2020 onwards (SIRs: 0.81-0.90). For men, part of this decline may reflect a pre-existing downward trend. No significant deviations were found for lung and prostate cancer. Female breast cancer incidence was significantly lower only in 2020 (SIR: 0.93).

Conclusion: Cancer incidence in Baden-Württemberg remained consistently below pre-pandemic and expected levels from 2020 through 2023. Further research is warranted to disentangle potential contributing factors, including post-pandemic effects, competing mortality risks, and migration-related population changes.

Objective: Ubiquitination is integral to the pathogenesis of various tumors. This study sought to elucidate the role and underlying mechanisms of BTRC-mediated ubiquitination and degradation in glioma.

Method: The expression levels of beta-transduced in repeat containing E3 ubiquitin protein ligase (BTRC), nuclear factor of activated T cells 5 (NFAT5) and aquaporin-4 (AQP4) were assessed by RT-qPCR/Western blot. The association and underlying mechanisms of BTRC, NFAT5, and AQP4 were examined through co-immunoprecipitation, cycloheximide chase, and chromatin immunoprecipitation assays. The influence of the BTRC/NFAT5/AQP4 axis on the malignant biological functions of glioma cells and tumor growth was evaluated through a series of in vitro and in vivo experiments.

Results: In glioma cells, BTRC expression was observed to be downregulated. Overexpression of BTRC inhibits proliferation, migration and invasion, while promoting apoptosis in glioma cells. Mechanically, BTRC overexpression facilitates ubiquitination and degradation of NFAT5, thereby inhibiting NFAT5-mediated transcriptional activation of AQP4. Functional recovery assays demonstrated that the overexpression of either AQP4 or NFAT5 counteracted the intervention effect of upregulation of BTRC on the malignant behavior of glioma cells. In vivo animal experiments further confirmed the results of the in vitro experiments, indicating that the overexpression of BTRC inhibits tumor growth through the NFAT5/AQP4 axis.

Conclusion: BTRC negatively modulates the transcription of AQP4 via NFAT5 in glioma cells, thereby influencing their malignant biological functions and tumor growth.

While pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, a small fraction of patients show high microsatellite instability (MSI-H) and may respond to immune checkpoint inhibition. An MSI-H genotype is usually associated with deficiencies in the DNA mismatch-repair mechanism (MMRd). However, discordances between the mismatch-repair status by immunohistochemistry and the microsatellite status by molecular analyses have been noted. To date it is not clear whether PDAC patients with mutations in mismatch repair genes, which result in loss of protein expression (MMRd), who nonetheless retain microsatellite stability (MSS), can profit from checkpoint inhibitor therapy. Here, we present the case of a PDAC patient, diagnosed as MMRd/MSS, who responded to checkpoint inhibitor therapy after failing two lines of chemotherapy. Our data suggest that both MMR and microsatellite status should be determined in PDAC patients and that MMRd status alone, even in an MSS phenotype, can constitute an indication for checkpoint inhibitor therapy.