Journal of Cancer Research and Clinical Oncology最新文献

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.

Objective: Oncogenic viruses have been implicated in thyroid carcinogenesis, yet their prevalence and clinicopathological associations remain incompletely understood. Thus, it is crucial to investigate the prevalence of human papillomavirus (HPV), Epstein-Barr virus (EBV), and polyomaviruses (JCV and BKV) in thyroid tumors and assess their association with clinic-pathological characteristics.

Methods: This study included 70 fresh biopsy samples collected from 45 TC patients and 25 patients with benign thyroid tumors, along with 10 normal thyroid tissues. Viral DNA was extracted and screened for HPV, EBV, and polyomaviruses using SYBR Green-based real-time PCR.

Results: HPV, EBV, and polyomaviruses, particularly JCV, were detected at significantly lower frequencies in the normal group when compared to malignant and benign groups (p-value = 0.030, p-value = 0.030, and p-value = 0.001, respectively). In TC patients, HPV common, HPV-16, HPV-6, and HPV-11 positivity was correlated with obesity (p-value < 0.05), polyomaviruses, particularly JCV, with older age (p-value = 0.041 and p-value = 0.011), BKV with larger tumor size (p-value = 0.030), and EBV with family cancer history (p-value = 0.020). In benign tumors, polyomavirus was absent in Hashimoto thyroiditis (p-value = 0.020), BKV was linked to older age (p-value = 0.030), and absence of BKV was associated with COVID-19 vaccination (p-value = 0.046).

Conclusion: The current study is the first of its kind in Egypt to investigate the prevalence of HPV, EBV, and polyomaviruses in thyroid tumors and to examine their associations with certain clinicopathological characteristics. The findings underline the importance of viral profiling in understanding thyroid tumor behavior and influencing cancer risk as well.

Purpose: Physical activity is associated with a lower mortality and recurrence risk in cancer, yet the underlying mechanisms remain unclear. This study aimed to evaluate the effects of running sessions on the tumorigenic potential of prostate cancer cells using a 3D in vitro model.

Methods: Fifteen healthy males completed two outdoor running sessions (5 km and 10 km), interspersed by 1 month of wash-out time. Blood samples were collected before (PRE), immediately after (POST), and 3 h after (POST-3 h) sessions. Human serum (HS) samples were used to stimulate LNCaP and PC3 cell lines in 3D in vitro culture technique. The spheroid formation ability was quantified after 21 days of incubation, using GelCount.

Results: In both prostate cancer cell lines, a reduction in spheroid number was shown, by both running sessions and in all timepoints considered (LNCaP cells: 5 km: - 23.8%; 10 km: - 5.6% POST HS; 5 km: - 37.8%; 10 km: - 34.8% POST-3 h HS; PC3 cells: 5 km: - 14%; 10 km: - 15.9% POST HS; 5 km: - 14.2%; 10 km: - 13% POST-3 h HS). The spheroid volume was reduced by 42.6% (5 km) and 51.1% (10 km) with POST-3 h HS, in LNCaP cells; no significant reduction was observed in PC3 cells. No differences were found between the running sessions, while higher muscle mass, cardiorespiratory fitness and age were associated with greater reductions in spheroid number and volume, especially in LNCaP cells.

Conclusion: Running sessions reduce prostate cancer cell spheroid formation, especially in participants with higher physical fitness. Shorter running distances showed comparable effects to longer ones, highlighting practical implications for real-world exercise prescriptions in oncology.