Cancer Medicine最新文献

Background: Medical images play an important role in diagnosis and treatment of pediatric solid tumors. The field of radiology, pathology, and other image-based diagnostics are getting increasingly important and advanced. This indicates a need for advanced image processing technology such as Deep Learning (DL).

Aim: Our review focused on the use of DL in multidisciplinary imaging in pediatric surgical oncology.

Methods: A search was conducted within three databases (Pubmed, Embase, and Scopus), and 2056 articles were identified. Three separate screenings were performed for each identified subfield.

Results: In total, we identified 36 articles, divided between radiology (n = 22), pathology (n = 9), and other image-based diagnostics (n = 5). Four types of tasks were identified in our review: classification, prediction, segmentation, and synthesis. General statements about the studies'' performance could not be made due to the inhomogeneity of the included studies. To implement DL in pediatric clinical practice, both technical validation and clinical validation are of uttermost importance.

Conclusion: In conclusion, our review provided an overview of all DL research in the field of pediatric surgical oncology. The more advanced status of DL in adults should be used as guide to move the field of DL in pediatric oncology further, to keep improving the outcomes of children with cancer.

Background: This study investigated and compared the impact of financial toxicity (FT) on the health-related quality of life (HRQoL) and financial well-being of cancer patients and survivors in the United Kingdom (UK) and United States (US).

Methods: UK & US participants (n = 600) completed an online questionnaire that consisted of a validated FT instrument (COmprehensive Score for financial Toxicity-COST), a standardised HRQoL instrument (EQ-5D-5L) and questions related to their financial well-being. Tobit regression models and descriptive statistics plus χ² tests were used to analyse the association between FT and (i) HRQoL whilst controlling for sociodemographic characteristics; and (ii) financial well-being.

Results: In the UK, health utilities of participants with no assessed experience of FT, mild FT, and moderate/severe FT were 0.81, 0.66, and 0.41, respectively, compared to 0.88, 0.71, and 0.53 in the US. Among those with moderate/severe FT, US participants had significantly higher health utilities compared to their peers in the UK (Mann Whitney test, p = 0.0369). In a pooled analysis of UK and US and after controlling for sociodemographic and clinical characteristics, mild and moderate/severe FT was negatively associated with health utilities (β coff = -0.13, 95% CI: -0.18, -0.08 and β coff = -0.28, 95% CI: -0.34, -0.21, respectively). Over half (54%) of US participants with FT were in debt with median (IQR) debt at I$11,500 (23,000), compared to 32% in the UK with median (IQR) debt at I$ 7200 (12,960). US participants with FT were 2.48 times more likely to be in debt than UK participants with FT (OR = 2.48, 95% CI: 1.46-4.21).

Conclusions: FT is associated with poorer financial well-being and HRQoL among cancer patients/survivors in the US and UK. The impact of FT on financial well-being is larger in the US while the impact on HRQoL is worse in the UK. Further studies using prospective data are required to investigate the nature and extent of these relationships.

Background: Single antigen (Ag)-targeted immunotherapies for acute lymphoblastic leukemia (ALL) are highly effective; however, up to 50% of patients relapse after these treatments. Most of these relapses lack target Ag expression, suggesting targeting multiple Ags would be advantageous.

Materials & methods: The multi-Ag immune responses to ALL induced by transducing cell lines with xenoAgs green fluorescent protein and firefly luciferase was elucidated using flow cytometry, ELISA, and ELISpot assays.

Results: In our model, leukemia responsiveness correlates with in vivo CD4+ T cell activation and DC maturation, supporting a role for DC licensing. In contrast, tolerance is characterized by in vivo increased expression of negative immune checkpoints (IC) which may suppress rather than license DC. In vitro assays confirm the ability of CD4+ T cells from leukemia-responsive mice to promote robust maturation of naïve bone marrow DC in the presence of non-immunogenic leukemia antigens.

Conclusion: Together these findings support a CD4+ T cell-mediated mechanism of DC licensing to promote multi-Ag immune responses that may augment current targeted immunotherapies and avoid relapses in treated children with ALL.

Objective: Endometrial cancer is one of the few cancers for which mortality is still increasing. A lack of treatment options remains a major challenge, particularly for some subtypes of the disease. GZD824, also known as olverembatinib, is a multi-kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR-ABL inhibitor. This study aimed to investigate the pre-clinical efficacy of GZD824 for the treatment of EC.

Methods: Here, we undertook pre-clinical evaluation of GZD824 in seven endometrial cancer cell lines (HEC-1-A, HEC-1-B, MFE296, RL95-2, Ishikawa, KLE and ARK-1), one normal immortalised endometrium derived cell line (E6E7hTERT) and primary mesothelial and fibroblast cells isolated from normal omentum samples.

Results: GZD824 inhibited the proliferation of all endometrial cancer cell lines, which were significantly more sensitive to GZD824 compared to normal cells (p = 0.030). GZD824 significantly inhibited migration in Ishikawa (endometrioid) and ARK1 (serous) endometrial cancer cell lines and significantly inhibited invasion in the ARK1 cells. Whole transcriptome regulation following two doses (0.1 and 1 μM) of GZD824 in Ishikawa and ARK1 cells was investigated via RNA-seq, and key components of enriched pathways were investigated at the translational level. Key pathways altered included ROR1/Wnt, GCN2-ATF4, epithelial to mesenchymal transition (EMT) and PI3K-AKT.

Conclusion: Together, these studies support further investigation of GZD824 as a potential therapeutic agent in endometrial cancer, potentially in combination with immune checkpoint inhibitors.

Background: The role of the immune system in cancer defense is likely underappreciated. While there has been longstanding interest in the role of atopic diseases in cancer, only a few studies have tested this hypothesis.

Methods: We analyzed data from 202,055 women participating in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHS II) to explore whether asthma is associated with breast cancer. We used Cox proportional hazards models to link physician-diagnosed asthma with subsequent incidence of breast cancer.

Results: Across the two cohorts, we identified 18,403 cases of physician-diagnosed asthma. During 4,393,760 person-years of follow-up, 11,096 incident cases of breast cancer were diagnosed. In NHS, women with asthma had a covariate-adjusted hazard ratio of 0.92 (95% CI: 0.86-0.99) to develop breast cancer compared to women without asthma; the respective HR in NHS II was 0.93 (0.84-1.03), and 0.92 (0.87-0.98) in the pooled analysis. Among never-smokers, the HR for breast cancer was 0.91 (0.81-1.02) in NHS, 0.81 (0.70-0.93) in NHS II, and 0.86 (0.77-0.97) combined. In two large prospective cohorts of women, participants with asthma had a somewhat lower risk of breast cancer. An active immune system may provide protection from breast cancer.

Conclusions: In these longitudinal studies, women with asthma had a somewhat lower risk of breast cancer. This association was most pronounced among never smokers. An active immune system may provide protection from breast cancer.

Aim: This study aimed to determine the maximum tolerated dose (MTD) of the urokinase plasminogen activator (uPA) inhibitor upamostat (LH011) in combination with gemcitabine for locally advanced unresectable or metastatic pancreatic cancer.

Method: Seventeen patients were enrolled and received escalating doses of oral LH011 (100, 200, 400, or 600 mg) daily alongside 1000 mg/m² of gemcitabine. Safety profiles, tumor response (including response rate and progression-free survival), pharmacokinetics, and changes in CA199 and D-dimer levels were assessed.

Results: During the study period (Day0-Day49), no patients achieved partial response. Stable disease (SD) was observed in 12 patients (70.6%), while four patients (23.5%) experienced progressive disease (PD). One patient withdrew due to a serious adverse event (SAE) on D47. Pharmacokinetic analysis revealed a dose-related increase in LH011 and its metabolite WX-UK1 exposure from 100 to 400 mg but not in the 600 mg group. Hematological toxicity, mainly attributable to gemcitabine, was the predominant grade 3 or 4 adverse event, with additional occurrences of loss of appetite, rash, and interstitial lung disease. Sinus bradycardia possibly linked to LH011 rather than gemcitabine was noted. The MTD was not reached.

Conclusion: Combining LH011 at doses ranging from 100 to 600 mg with gemcitabine every 21 days demonstrated manageable safety and tolerability. However, tumor response did not significantly differ among the dose groups, suggesting the need for further investigation.

Trial registration: NCT05329597.

Background: Numerous studies have explored the role of vitamin D in various cancers; however, its impact on advanced biliary tract cancers (BTC) within a prospective cohort remains to be investigated. This preplanned subgroup analysis of the NIFTY trial evaluated the prognostic implications of serum vitamin D levels in patients with advanced BTC undergoing second-line chemotherapy.

Methods: From the 174 patients in the NIFTY trial, a total of 173 patients (99.4%) were included in this analysis comparing a liposomal irinotecan plus 5-FU/leucovorin group (n = 87) and a 5-FU/leucovorin alone group (n = 86). Baseline serum 25-hydroxyvitamin D (25(OH)D) levels, an indicator of vitamin D status, were analyzed for their association with baseline characteristics and overall survival (OS) in patients undergoing second-line chemotherapy. Multivariable Cox proportional hazards regression and a restricted cubic spline function were used to assess the association with OS.

Results: There were no significant associations between baseline characteristics and serum 25(OH)D levels. Baseline serum 25(OH)D levels were not associated with OS in either the multivariable Cox proportional hazard regression or restricted cubic spline analysis. In the subgroup analysis, however, higher serum 25(OH)D levels were significantly associated with poorer OS in female patients, while no significant association was observed in male patients, indicating a significant interaction by sex. Additionally, a marginally significant interaction was observed between body mass index and serum 25(OH)D levels for OS, with higher levels associated with better OS in patients who were underweight.

Conclusions: Our preplanned subgroup analysis of the NIFTY trial indicates that the serum 25(OH)D levels did not have a significant effect on OS in the overall patient population with advanced BTC. However, higher serum 25(OH)D levels were associated with worse OS in female patients, underscoring the need for further investigation into the role of vitamin D in BTC.

Background: By simultaneously staining multiple immunomarkers on a single tissue section, multiplexed immunohistochemistry (mIHC) enhances the amount of information that can be observed in a single tissue section and thus can be a powerful tool to visualise cellular interactions directly in the tumour microenvironment. Performing mIHC remains technically and practically challenging, and this technique has many limitations if not properly validated. However, with proper validation, heterogeneity between histopathological images can be avoided.

Aims: This review aimed to summarize the currently used methods and to propose a standardised method for effective mIHC.

Materials and methods: An extensive literature review was conducted to identify different methods currently in use for mIHC.

Results: Guidelines for antibody selection, panel design, antibody validation and analytical strategies are given. The advantages and disadvantages of each method are discussed.

Conclusion: This review summarizes widely used pathology imaging software and discusses the potential for automation of pathology image analysis so that mIHC technology can be a truly powerful tool for research as well as clinical use.

Objective: The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early-stage MCC, prompted this study.

Methods: A systematic review and meta-analysis of randomized and non-randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease-specific survival (DSS), and/or disease-free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.

Results: Forty-nine studies representing 46,215 participants were included in the meta-analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62-0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I² = 94%, 95% CI, 93.0-95.5). Both LR (HR = 1.52, 95% CI, 0.37-6.19) and RR (HR = 0.41, 95% CI, 0.09-1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24-1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13-0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E-value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.

Conclusions: Although adjuvant RTx improves survival and recurrence outcomes among early-stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.