Cancer Clinical Outcomes Research Articles

Prevalence and associated risk factors of cervical cancer among women in a Nigerian cohort

ABSTRACT Background: Cervical cancer is the fourth most common cancer in women worldwide. This study examined the prevalence of cervical cancer and associated factors among patients in a tertiary health facility in Edo state in Nigeria. Methods: A retrospective descriptive cross-sectional survey design was adopted including 3654 female patients who visited the oncology unit between 2016 and 2021. Their clinical files were selected through purposive sampling, and a validated checklist was used as instrument for data collection. Data analyses included descriptive and inferential statistics and multiple logistics regression. Results: Cervical cancer prevalence was highest in 2021 (10.8%). Oral contraceptives (23.8%), immunosuppression (19.3%), the number of sexual partners (8.3%), lack of human papillomavirus (HPV) vaccination (18.8%), diabetes (13.3%), and cardiovascular diseases (9.4%) were among the factors associated cervical cancer. A significant association (P = 0.000) was observed between risk factors and the clinical outcomes of cervical cancer. Women aged 30–59 were 25% more likely (odds ratio [OR] =1.25; 95% confidence interval [CI] = 0.55–2.86) to survive compared to those aged 60 and above. Women with only secondary education were also less likely (OR = 0.45; 95% CI = 0.21–0.99) to survive compared to those with tertiary education. Finally, multiparous women were less likely to survive compared to nulliparous women (OR = 0.30; 95% CI = 0.005–1.79). Conclusion: These results underscore the rising prevalence of cervical cancer and its association with age, supporting advocacy for increased HPV vaccination efforts targeting young girls before sexual maturity, as well as catchup vaccinations for high-risk older women.

DNA damage response and repair gene mutations predict clinical outcomes in biliary tract cancer.

This study aims to explore the genetic characteristics of biliary tract cancer (BTC), with a particular focus on the impact of DNA damage response and repair (DDR) genes on clinical outcomes. A total of 180 patients with BTC and next-generation sequencing data were retrospectively analyzed. Clinical outcomes were compared between DDR-positive and DDR-negative groups. DDR mutations were found in 28.3% of patients, with ATM (7.8%), BAP1 (5.6%), and BRCA2 (3.3%) being the most common. DDR-positive patients receiving first-line platinum-based chemotherapy (n=73) had a significantly higher objective response rate (50.0% vs. 14.9 %; p=.001), longer median progression-free survival (mPFS) (7.7 vs. 3.8 months; p=.001) and longer median overall survival (28.6 vs. 11.9 months; p<.001). Multivariate analysis confirmed that deleterious DDR gene mutations were independently associated with prolonged mPFS (hazard ratio [HR], 0.37; 95% CI, 0.20-0.67; p<.001) and median overall survival (mOS) (HR, 0.19; 95% CI, 0.08-0.46; p<.001). In 56 patients receiving immunotherapy combined with chemotherapy, DDR-positive patients had a significantly higher overall response rate (45% vs. 8.3%; p=.001), longer mPFS (7.7 vs. 3.8 months; p=.009), and longer mOS (12.7 vs. 8.8 months; p=.011). Multivariate analysis showed that the presence of deleterious DDR gene mutations was associated with significantly longer mPFS (HR, 0.34; 95% CI, 0.16-0.73); p=.005] and mOS (HR, 0.23; 95% CI, 0.08-0.62; p=.004). Deleterious DDR gene mutations are associated with improved clinical outcomes in patients with BTC treated with platinum-based chemotherapy or immunotherapy combined with chemotherapy.

Influence of MRP4 levels on clinical outcomes in biliary tract cancer.

624 Background: Biliary tract cancer (BTC) are rare tumors with a poor prognosis.Multidrug resistance protein 4 (MRP4) is a transmembrane efflux transporter that influences on cellular growth and differentiation. Recent studies have linked high MRP4 levels to increased aggressiveness in pancreatic cancer and other tumor types. This study aimed to evaluate the role of MRP4 in BTC and its association with clinical outcomes in a real-world cohort from endemic areas in Argentina. Methods: We conducted a retrospective analysis of clinical outcomes and MRP4 expression in paraffin-embedded tissue samples from 78 patients with BTC. Immunohistochemistry staining was performed, and MRP4 expression was scored based on staining intensity and the percentage of positive cells. A score exceeding 100 was classified as high MRP4 levels. Statistical analyses included Chi-square, Kaplan-Meier survival curves, and log-rank tests, with significance set as p &lt;0.05 (two-tailed). Results: High MRP4 levels were observed in 46 out of the 78 samples (59%). Patients with gallbladder cancer (n=64) and elevated MRP4 levels had significantly poorer overall survival (OS) compared to those with low MRP4 levels (median 11.3 and 14.5 months, high and low, p =0.038). In the broader BTC cohort evaluable for survival (n=73; 64 gallbladder, 7 cholangiocarcinoma, 1 ampulla of Vater, and 1 biliary undefined) patients with elevated MRP4 levels had non-significant shorter OS (median 12.4 and 13.5 months, high and low, p =0.17). Poorly differentiated tumors were more likely to express high MRP4 levels ( p =0.06). High MRP4 expression was found in 59% of localized stages (0-II) and in 57% of advanced stages (III, IV and relapsed). Conclusions: High MRP4 expression is common in BTC, particularly gallbladder cancer, and could be a marker of poor prognosis. MRP4 levels appear more elevated in poorly differentiated tumors, and are similar in both, early and advanced stages, suggesting its involvement in early tumor progression. Further prospective studies are needed to confirm MRP4 as a biomarker. If MRP4 is a driver gene, targeting with inhibitors could represent a promising therapeutic strategy for these challenging tumors.

Correlation Between PIK3R1 Expression and Cell Growth in Human Breast Cancer Cell Line BT-474 and Clinical Outcomes.

While mutations in the PIK3CA gene play important roles in human breast carcinogenesis, PIK3R1 gene alterations are recognized as actionable mutations for clinical cancer treatment. We aimed to elucidate the role of PIK3R1 in cell proliferation on breast carcinoma and to correlate the PIK3R1 expression with patients' outcome using human tumor tissue arrays. Using human BT-474 (estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)-high) breast carcinoma cell line as in vitro model, the role of PIK3R1 in cell proliferation was elucidated by knock-down of the PIK3R1 gene (ΔPIK3R1) in this cell line. Between January 2000 to December 2015, the records of a cohort of 440 patients in our hospital were retrospectively reviewed, including patients' survival. The correlations between PIK3R1 expression and patient prognosis, such as overall survival (OS) and disease-free survival (DFS), were elucidated by human breast cancer tumor tissue array immunostaining. After the PIK3R1 gene was silenced in the BT-474 line, there was an increased cell number and a decrease in the G0G1-fraction, and increased S-fraction and the S+G2M-fraction for the ΔPIK3R1-BT-474 cell line, as compared to their cell wild type (WT) line. Western blot analysis showed that decreased PIK3R1 protein levels were accompanied by an increase of the p-AKT and p-mTOR proteins in the ΔPIK3R1-BT-474 cell line, compared to the equivalent WT line. Using a human tumor tissue array, patients with high-expressed PIK3R1 protein had better outcomes in terms of DFS and OS, compared to those with low-expressed PIK3R1 protein, when breast cancer was at an early stage (stage I/II), but not across all stages of breast cancer in human patients. We concluded that downregulated PIK3R1 in BT-474 cells resulted in an increased cell growth and upregulated AKT-mTOR signaling. Clinically, the high-expressed PIK3R1 protein in tumors correlates positively with patients' outcome in stage I and II breast cancer.

Can we utilise the circadian clock to target cancer stem cells?

The 24-hourly circadian clock has been implicated in the regulation of multiple cancer hallmarks and characteristics. Cancer stem cells (CSCs) are a small but significant population of cells within many cancers, characterised by their self-renewal and clonogenic capacities. Increasing evidence points to CSCs having prominent roles in metastasis and drug resistance. However, it remains largely unknown how circadian clocks are involved with CSCs and what implications these interactions have for cancer progression and therapeutics. In this review, we examine the growing evidence on the role of circadian clocks in CSCs and discuss the potential therapeutic implications. This opens up new opportunities to target CSCs through various chronotherapeutic approaches, potentially improving clinical cancer outcomes. We propose different scenarios in which targeting circadian clocks in CSCs or their surrounding microenvironment could be developed into effective therapeutic strategies, including: (1) direct pharmacological targeting of core clock molecules, (2) optimising the timing of systemic anticancer therapies, and (3) targeting the neighbouring cells or systemic factors that influence tumour cells in a circadian-dependent manner.

Impact of finasteride on modulating the risk and clinical outcomes of bladder cancer: insights from a comprehensive meta-analysis

PurposeNumerous prior analyses have highlighted a potential link between androgen suppression therapy (AST) and bladder cancer (BCa). However, there is a notable gap in research specifically examining the influence of finasteride on BCa risk and clinical outcomes. This study aimed to evaluate preventive and therapeutic value of finasteride for BCa patients.MethodsThis meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to 20 December 2024, to identify studies that examined the intake of finasteride and its impact on the incidence and clinical prognosis of patients with BCa. Data was extracted for further analysis by two different reviewers who independently examined the titles and abstracts of the included articles. Subgroup analyses and leave-one-out sensitivity analyses, were applied to mitigate the potential confounding factors associated with heterogeneity.ResultsOur investigation revealed that finasteride markedly decreased the likelihood of developing BCa (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63–0.88). Subgroup analyses indicated that the preventive effect of finasteride in BCa incidence were generally consistent, regardless of study region, types of research. Furthermore, no notable disparities were observed in OS, CSS, or RFS between the finasteride group and the control group.ConclusionFinasteride plays a protective role against the progression of BCa, nevertheless, its effects on prognostic outcomes, including OS, CSS, and RFS, remain inconclusive. Additional multi-center prospective studies with long-term follow-up are required to further validate prophylactic role of finasteride on bladder cancer.Systematic review registration numberhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=525046, identifier CRD42024525046.

Low albumin-to-creatinine ratios (ACR) are associated with poor outcomes in cancer patients

BackgroundThe albumin-to-creatinine ratio (ACR) is known to predict prognosis in liposarcoma patients, but its role in other tumors remains unclear. This study aimed to evaluate the prognostic relationship between ACR and common solid tumors.MethodsData from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) between 2013 and 2022 were used to analyze patients under 65 years old with solid tumors. Patients were divided into a training cohort (n = 12,027) and a validation cohort (n = 7,985) using simple random sampling. Correlation analysis, Kaplan–Meier method, and restricted cubic spline analysis were conducted to explore ACR's relationship with overall survival (OS). Multivariable logistic regression assessed associations between ACR and Patient—Generated Subjective Global Assessment (PG-SGA), Length of Stay (LOS), and Karnofsky Performance Status (KPS).ResultsIn Cox regression, higher ACR levels were associated with better OS in solid tumor patients. Specifically, when using the cutoff value with low ACR as the reference, higher ACR levels were significantly associated with improved OS. For nasopharyngeal carcinoma (HR = 0.49, 95% CI: 0.35–0.67, P < 0.001), gastrointestinal tract tumors (HR = 0.84, 95% CI: 0.74–0.95, P = 0.007), and urogenital neoplasms (HR = 0.55, 95% CI: 0.43–0.71, P < 0.001), higher ACR levels were linked to better OS. When ACR was categorized into tertiles, the results were consistent with those observed using the cutoff value. In gastrointestinal tract tumor patients, higher ACR levels were linked to lower PG-SGA scores and improved KPS scores (P < 0.05). In urogenital neoplasm patients, higher ACR levels were associated with improved KPS scores (P < 0.05).ConclusionElevated ACR levels were significantly associated with improved OS in cancer patients, particularly in nasopharyngeal carcinoma, gastrointestinal tract tumors, and urogenital neoplasms. ACR was also linked to better nutritional and functional status, suggesting its potential as a prognostic biomarker.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN). PD-L1DP and SP142SP UCs were associated with more favorable ICB outcomes and increased dendritic-cell (DC) infiltration. SP142 PD-L1 staining co-localized with DC-LAMP, a DC marker, while 22C3 staining was more diffuse. 22C3SP UCs, associated with worse outcomes, were enriched in tumor cell-dominant PD-L1 expression. Multiplex IHC in an independent ICB-treated cohort confirmed that tumor cell-dominant PD-L1 expression was associated with shorter survival. Using different PD-L1 assays, we uncovered that SP142 may preferentially stain PD-L1-expressing DCs, key to orchestrating antitumor immunity, while tumor cell-dominant PD-L1 expression, which underlies a subset of "PD-L1 positive" specimens, is associated with poor ICB outcomes.

Impact of time to treatment initiation on the development of cachexia and clinical outcomes in lung cancer.

Pre-cancer onset of cachexia raises uncertainties regarding the optimal timing for early intervention in lung cancer patients. We aimed to examine changes in physical function, nutritional status, and cachexia incidence in patients with lung cancer from the initial visit to treatment initiation and determine the effect of these changes on lung cancer treatment. This single-center retrospective cohort study enrolled patients suspected of having advanced lung cancer who visited Kansai Medical University Hospital between January and February 2023 and were definitely diagnosed with the disease. Patients were categorized into three groups based on their cachexia status: those with cachexia at initial diagnosis (group C), those who developed cachexia between the initial visit and treatment initiation (group OC), and those without cachexia (group NC). Out of 61 patients, 21 had cachexia at their first outpatient visit (group C). The time between the first visit and treatment initiation was 42.5days. The rate of cachexia in patients with stage IV lung cancer in group OC was significantly higher than that in patients with other stages (P=0.008). Of the 33 patients with advanced lung cancer, 11 received supportive care only. The first-line treatment induction rate for the OC group was low. Half of the patients declined chemotherapy and received the best supportive care; their disease control rate (37.5%) was significantly worse than that of the other groups (P=0.007). Cachexia negatively impacts the effectiveness of initial cancer treatment, necessitating early anti-cachexia interventions at the first clinical visit.

IL-1β in Neoplastic Disease and the Role of Its Tumor-Derived Form in the Progression and Treatment of Metastatic Prostate Cancer.

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β synthesized and secreted by immune cells. Herein, we discuss the importance of IL-1β derived from cancer cells which impacts primary tumors, particularly metastatic lesions, separately from and in addition to its more recognized role in immune-mediated inflammatory events. To this end, we focus on the instrumental contribution of IL-1β in the establishment and progression of advanced prostate adenocarcinoma. Special emphasis is placed on the potential role that the standard-of-care treatment strategies for prostate cancer patients have in unleashing IL-1β expression and production at metastatic sites. We conclude by reviewing the therapeutics currently used for blocking IL-1β signaling and propose a rationale for their concomitant use with standard-of-care treatments to improve the clinical outcomes of advanced prostate cancer.

CD4+FOXP3Exon2+ regulatory T cell frequency predicts breast cancer prognosis and survival.

CD4+FOXP3+ regulatory T cells (Tregs) suppress immune responses to tumors, and their accumulation in the tumor microenvironment (TME) correlates with poor clinical outcome in several cancers, including breast cancer (BC). However, the properties of intratumoral Tregs remain largely unknown. Here, we found that a functionally distinct subpopulation of Tregs, expressing the FOXP3 Exon2 splicing variants, is prominent in patients with hormone receptor-positive BC with poor prognosis. Notably, a comprehensive examination of the TCGA validated FOXP3E2 as an independent prognostic marker in all other BC subtypes. We found that FOXP3E2 expression underlies BCs with defective mismatch repair and a stem-like signature and highlights pathways involved in tumor survival. Last, we found that the TME induces FOXP3E2 through the CXCL12/CXCR4 axis and confirmed the higher immunosuppressive capacity of FOXP3E2+ Tregs derived from patients with BC. Our study suggests that FOXP3E2+ Tregs might be used as an independent biomarker to predict BC prognosis and survival and to develop super-targeted immunotherapies.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC). In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3weeks for 12weeks, followed by sintilimab alone. The primary endpoint was the objective response rate (ORR). Pivotal secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. 205 patients were randomized to receive IBI310-sintilimab (n= 103) or placebo-sintilimab (n= 102). The ORR difference between the IBI310-sintilimab arm (32.3%, 95% confidence interval [CI]: 23.3%-42.5%) and the placebo-sintilimab arm (23.5%, 95% CI: 15.5%-33.1%) was not significant (p= 0.17). IBI310-sintilimab and placebo-sintilimab exhibited median PFS values of 3.6 (95% CI: 2.7-6.3) and 4.2months (95% CI: 2.8-6.2), respectively (hazard ratio [HR]= 0.91, 95% CI: 0.65-1.27; p= 0.58). The median OSs were 13.9months (95% CI: 11.5-25.6) in the IBI310-sintilimab arm and 17.2months (95% CI: 13.7-25.9) in the placebo-sintilimab arm (HR= 1.12, 95% CI: 0.79-1.58; p= 0.54). Adding IBI310 to sintilimab increased the incidence of grade ≥3 treatment-related adverse events (55% versus 19%). Compared to single-agent PD-1/PD-L1 blockade, dual blockade of CTLA-4 and PD-1/PD-L1 did not significantly improve clinical outcomes in R/M CC. This work was funded by Innovent Biologics (Suzhou).

Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer.

To compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on EGFR amplification status. Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least 5 copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp-). Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp- patients (median OS 76 vs. 37 months, p=0.15). Among 572 patients who received anti-EGFR antibody-based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp- patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp- patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344). This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

GTF2I acts as a novel tumor suppressor transcription factor and shows Favorable prognosis in renal cancer.

The role of GTF2I (General Transcription Factor2I) alteration has already been reported in thymic cancer as a valuable biomarker. However, the association of GTF2I mutation with renal cancer for prognosis of immunotherapy is not yet examined. The biologic and oncologic significance of GTF2I in renal cancer was examined at multiomics level such as mutation, copy number alteration, structural variants. The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) were used to retrieve the omics data. The expression of GTF2I mRNA was quite significant in case of renal caner. Correlation among the GTF2I mRNA, mutation, CNA and structural variants was also studied. Interactome of GTF2I was also constructed using STRING database. Gain, amplification, and missense mutation exhibited a positive correlation between GTF2I mRNA expression and non-structural variants. Similarly, GTF2I mRNA expression and copy number alterations from GISTIC were positively correlated. High expression of GTF2I was associated with better overall survival indicating the less aggressive clinical features. Insight Box Investigating GTF2I's complex function as a tumor suppressor transcription factor in renal carcinoma provides fresh insights into its biologic and oncologic importance, especially when considering the prognosis of immunotherapy. Little is known about its possible use as a biomarker for renal cancer. Using a multiomics approach and utilizing information from the Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA), our study clarifies the intricate relationship between mRNA expression, GTF2I changes, and clinical outcomes in renal cancer. Our results indicate that GTF2I expression may be used as a prognostic indicator because it is positively correlated with favorable survival outcomes. Furthermore, the molecular interactions behind GTF2I's functional significance in renal cancer are revealed by interactome analysis utilizing the STRING database, providing important information for further study and treatment approaches.

Proximity Labeling: Precise Proteomics Technology for Mapping Receptor Protein Neighborhoods at the Cancer Cell Surface.

Cell surface receptors are pivotal to cancer cell transformation, disease progression, metastasis, early detection, targeted therapy, drug responses, and clinical outcomes. Since they coordinate complex signaling communication networks in the tumor microenvironment, mapping the physical interaction partners of cell surface receptors in vivo is vital for understanding their roles, functional states, and suitability as therapeutic targets. Yet traditional methods like immunoprecipitation and affinity purification-mass spectrometry often fail to detect key but weak or transient receptor-protein interactions. Proximity labeling, a cutting-edge proteomics technology, addresses these technical challenges by enabling precise mapping of protein neighborhoods around a receptor target on the cell surface of cancer cells. This technique has been successfully applied in vitro and in vivo for proteomic mapping across various model systems. This review explores the fundamental principles, technologies, advantages, limitations, and applications of proximity labeling in cancer biology, focusing on mapping receptor microenvironments. By advancing mechanistic insights into cancer cell receptor signaling mechanisms, proximity labeling is poised to transform cancer research, improve targeted therapies, and illuminate avenues to overcome drug resistance.

Sex Differences in Clinical Features and Survival Outcomes of Esophageal Cancer: A Comparative Study in the Korean Population.

Esophageal cancer is a predominantly male disease. However, the sex differences associated with esophageal cancer have not been thoroughly investigated. This study aimed to evaluate the differences between esophageal cancer in males and females in the Korean population. We assessed patients diagnosed with esophageal cancer between 2005 and 2015 at a tertiary referral center. The clinical features of patients, histopathologic characteristics of tumors, and treatment and survival outcomes were compared between male and female patients. We enrolled 2,068 patients, comprising 1,924 (93.0%) males and 144 (7.0%) females. The median age at diagnosis was younger for females than males (65 vs. 63 years, p=0.004). Squamous cell carcinoma was the predominant pathological type (99.0% in males and 93.1% in females); however, the proportion of adenocarcinoma cases was higher in females than males (0.8% vs. 5.6%, p<0.001). Multivariate analysis indicated favorable overall survival for female patients (hazard ratio [HR], 0.685; 95% confidence interval [CI], 0.548-0.857) and patients with high body mass index (≥25 kg/m², HR, 0.432; 95% CI, 0.355-0.526), and in early tumor stage (Stage 4, HR, 12.684; 95% CI, 7.451-21.591). The 5-year overall survival (44.8% vs. 53.5%, p=0.016) and recurrence-free survival rates (74.0% vs. 84.3%, p=0.036) were higher in females than in males. We found significant sex differences in esophageal cancer among the Korean population, with female patients demonstrating distinct clinical characteristics and more favorable survival outcomes compared to male patients. These findings underscore the importance of considering sex-specific factors in the management and prognosis of esophageal cancer.

Association between C-reactive protein-albumin-lymphocyte index and overall survival in patients with esophageal cancer.

Esophageal cancer is an aggressive malignant tumor with poor prognosis, making early detection and treatment crucial. C-reactive protein-albumin-lymphocyte (CALLY) index is a comprehensive indicator which is involved in the process of metabolism, inflammation and immune reaction, and has been addressed to correlate with clinical outcomes in cancer patients. However, However, the evidence in esophageal cancer remains unclear. This study aims to investigate the association between CALLY index and overall survival of patients with esophageal cancer. This study includes the clinical characteristics of 518 patients with esophageal cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project, and evaluates the correlation between CALLY index and overall survival by COX regression analysis. Time-patient survival trends are verified using Kaplan-Meier method, and cubic spline function. Based on the results of multivariate Cox analysis, a nomogram showing 1, 2, 3, and 5-year survival rates is constructed. Calibration curve and decision curve analysis are used to evaluate the prediction accuracy and practical value of nomogram survival prediction. TNM staging of patients with esophageal cancer is determined according to the pathological examination results of the tumor and surrounding tissues, including the size and depth of the tumor (T), the involvement of lymph nodes (N), and the distant metastasis (M). Multivariate Cox regression analysis demonstrates that CALLY index (HR:0.967, 0.937-0.997, P<0.05), smoking (HR: 1.592, 1.064-2.380, P<0.05), TNM staging (HR: 1.595, 1.120-2.270, P<0.05) are independent prognostic factors for survival of patients with esophageal cancer. Patients with high CALLY index has the lower risk of death than those with low CALLY index (HR: 0.54, 0.36-0.80, P<0.05). The nomogram model including CALLY index shows better prediction ability than traditional TNM staging system. CALLY index is independently positive associated with overall survival in patients with esophageal cancer and nomogram model displays superiority over TMN staging in predicting overall survival.

A hypoxia-targeting and hypoxia-responsive nano-probe for tumor detection and early diagnosis.

Accurate imaging of tumor hypoxia in vivo is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine N-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.

Treatment initiation and completion among head and neck squamous cell carcinoma patients in Tanzania.

Few studies characterizing clinical outcomes of head and neck cancer (HNC) patients in sub-Saharan Africa report the proportion of patients who initiate and complete treatment, information integral to contextualizing survival outcomes. This retrospective cohort study describes HNC patients who presented to Muhimbili National Hospital and Ocean Road Cancer Institute in 2018, the highest-volume oncology tertiary referral centers in Tanzania. Logistic regression was applied to assess predictors of treatment initiation and completion. Among the 176 head and neck squamous cell carcinoma (HNSCC) patients, 34% (59) had no treatment documented, 34%(59) had documentation of treatment initiation but not completion, and 33%(58) had documentation of treatment completion based on the modalities started. Univariate logistic regression showed that late-stage disease was associated with increased odds of initiating treatment (OR 8.24, 95% CI 2.05-33.11, p = 0.003) and trends toward completing treatment (OR 7.41, 95% CI 0.90-60.99, p = 0.063). At last visit, 36.9%(65) were alive with a median follow up of 5.6 months (IQR 1.64-12.5 months). A large proportion of HNC patients who presented to MNH and ORCI did not initiate or complete treatment. These metrics are critical to contextualize care outcomes of HNC patients in resource-constrained health systems and develop interventions.

Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy.

we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT). 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA. 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS>10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new "outlier" variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations. ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.