World Journal of Oncology最新文献

Background: While the prognosis for patients with human epidermal growth factor receptor 2 (HER2)-positive pT1a-bN0M0 breast cancer is generally favorable, the optimal approach to personalize adjuvant treatment for T1a tumors remains unclear, which prompted an impetus to conduct a systematic review and meta-analysis for the latter group.

Methods: We examined the literature for studies that provided relevant data about HER2-positive T1a patients. Patient and disease characteristics, therapy details, and survival outcomes were extracted.

Results: Thirteen studies with 2,089 patients were eligible; four were prospective and nine were retrospective. In the studies where patients did not receive chemotherapy or anti-HER2 therapy, the prognosis was generally favorable, with disease-free survival (DFS) and overall survival of approximately 92% to 99%. Studies comparing treated versus untreated patients showed a survival benefit that varied between 2% and 15%, favoring adjuvant therapy without reaching statistical significance. In the only included randomized trial where all patients received adjuvant paclitaxel and trastuzumab, 10% demonstrated 5-year invasive DFS events. A meta-analysis of four studies showed a nonsignificant survival advantage trend among treated patients. There was inconsistency about the prognostic role of the co-existing hormone receptor status.

Conclusion: Patients with HER2-positive T1aN0 have a favorable prognosis; the benefit of adjuvant chemotherapy plus anti-HER2 varied and showed no convincing statistically significant benefit. The decision to offer adjuvant therapy should balance the expected benefits and risks. Prospective trials that include this population should be able to identify who should receive adjuvant therapy and determine the magnitude of benefit.

Background: One of the most common cancers is bladder cancer, characterized by a high mortality rate and a high incidence of recurrence. An identified susceptibility factor for bladder cancer is the presence of single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) genes, specifically -2578C>A and -7C>T polymorphisms.

Methods: This pilot study was conducted to uncover the association between the SNP VEGF -2578C>A and -7C>T in bladder cancer. A total of 20 patients were tested, consisting of both 10 controls and patients with bladder cancer, for the SNP of VEGF -2578C>A and -7C>T through polymerase chain reaction (PCR).

Results: This study showed a significant association between the VEGF -2578C>A polymorphism (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.03 - 2.01) and an increased risk of bladder cancer, especially in individuals with the A allele. However, the results for the -7C>T polymorphism in relation to bladder cancer risk showed a non-significant association in this study population. We did not detect a significant association between the VEGF -2578C>A (OR 0.93 (0.39 - 2.01)) and -7C>T (OR 0.74 (0.32 - 1.57)) polymorphisms and bladder cancer severity, as indicated by stages.

Conclusion: This pilot study suggests that VEGF -2578C>A has a connection between polymorphism and bladder cancer susceptibility. Further large-scale studies need to be done to validate these findings and elucidate the underlying mechanisms linking VEGF polymorphisms to bladder cancer pathogenesis.

Background: Delays in cancer treatment initiation can significantly impact survival outcomes, but the magnitude of this effect varies by cancer type, stage, and patient demographics. This study examined the association between time-to-treatment initiation (TTI) and all-cause mortality across multiple common cancers, evaluating differential impacts and sociodemographic disparities.

Methods: A retrospective cohort analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database, including 991,771 adults diagnosed with breast, lung, prostate, or colorectal cancers between 2015 and 2020. TTI intervals were divided into four categories: 0 - 1, 2 - 5, 6 - 9, and ≥ 10 months. Cox proportional hazards models, adjusted for demographic, socioeconomic, cancer-specific, and treatment factors, assessed the impact of TTI on all-cause mortality, accounting for time-varying covariates.

Results: Overall, 63.9% of patients initiated treatment within 1 month. Unadjusted analyses revealed paradoxically lower mortality with longer TTI intervals (26.1% for 0 - 1 month vs. 11.4% for ≥ 10 months). After adjusting for time-varying effects, longer TTI significantly correlated with higher mortality risks (hazard ratio (HR): 1.02 for 2 - 5 months, 1.08 for 6 - 9 months, 1.23 for ≥ 10 months; P < 0.001 each), compared to treatment within 1 month. Older age (HR: 1.06), male gender (HR: 1.08), unmarried status (HR: 1.06), and non-Hispanic Black race (HR: 1.03) were independently associated with increased mortality. Lung cancer patients had significantly higher mortality than breast, prostate, and colorectal cancers (all P < 0.001). Treatment differences emerged, with reduced chemotherapy (40.2% to 10.0%) and surgical interventions (70.6% to 48.8%) at longer intervals.

Conclusion: Our analysis showed that increased TTI is independently associated with significantly higher all-cause mortality across major cancers, emphasizing the urgency of timely treatment initiation. Sociodemographic disparities in TTI and outcomes highlight systemic barriers disproportionately affecting vulnerable populations, necessitating targeted interventions to improve equitable cancer care and survival outcomes.

Background: Immune checkpoint inhibitors (ICIs) which target programmed cell death-1 (PD-1) receptor or its ligand (PD-L1) are used extensively in non-small cell lung cancer (NSCLC). In this article, we compared the relative efficacy of PD-1 inhibitors and PD-L1 inhibitors in PD-L1-negative advanced NSCLC.

Methods: We searched MEDLINE (host: PubMed, Scopus, and Google Scholar) for randomized trials for advanced NSCLC in which ICIs (anti-PD-1 or anti-PD-L1) were used where outcome data were reported based on PD-L1 testing, including the subset of PD-L1-negative patients. We extracted hazard ratios (HRs) and related 95% confidence intervals (CIs) and/or P values for progression-free survival (PFS) and overall survival (OS) for the PD-L1-negative subgroup of each included trial. We then pooled data using a random effects meta-analysis and compared anti-PD-1 to anti-PD-L1 inhibitors. Variations in effect size were examined using subgroup analyses.

Results: Twenty-three trials were included in the meta-analysis. PD-L1 testing was performed in all participants. A total of 4,548 PD-L1-negative patients were included in the analysis, representing 33% of all participants in the included clinical trials. Overall, the addition of anti-PD-1 was associated with better OS in PD-L1-negative advanced NSCLC patients (HR: 0.75, 95% CI: 0.67 - 0.83, P < 0.01), while the addition of anti-PD-L1 inhibitors showed no improvement in OS (HR: 0.90, 95% CI: 0.78 - 1.05, P = 0.18). Compared to anti-PD-L1 agents, anti-PD-1 resulted in better OS in PD-L1-negative patients (HR: 0.83, 95% CI: 0.67 - 0.99, P = 0.01). The differential benefit of anti-PD-1 over anti-PD-L1 was of larger magnitude when checkpoint inhibitors were used in the first-line setting (pairwise comparison HR: 0.79, 95% CI: 0.66 - 0.93, P = 0.01), while there was no difference for later lines of therapy (pairwise comparison 1.13; 95% CI: 0.82 - 1.55, P = 0.45). These differences in OS were not observed when pooling PFS data.

Conclusions: Compared to checkpoint inhibitors targeting PD-L1, those targeting PD-1 are associated with better OS in PD-L1-negative advanced NSCLC, a finding influenced by trials performed in the first-line sitting. These data should be validated using real-world studies.

Background: This study aimed to develop functional nomograms to predict overall survival (OS) and cancer-specific survival (CSS) of small cell carcinoma of ovary (SCCO).

Methods: SSCO case data were recruited retrospectively from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed to predict the probabilities of OS and CSS in SCCO patients based on independent predictors. The predictive performance of nomogram was evaluated with the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA).

Results: The independent risk factors affecting the prognosis of SCCO patients were older age, lower income, surgery, chemotherapy, radiation, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, and number of primary tumors. The C-index for the OS nomogram was 0.78 (95% confidence interval (CI): 0.75 - 0.82), and AUCs for 1-, 3-, and 5-year OS were 0.861, 0.807, and 0.821, respectively. The C-index for the CSS nomogram was 0.79 (95% CI: 0.76 - 0.83), and AUCs for 1-, 3-, and 5-year OS were 0.873, 0.841, and 0.864, respectively. The calibration curves indicated reasonable agreement between the observed and predicted probabilities of the OS and CSS nomograms, which indicated a good degree of confidence. According to the C-index, ROC, and DCA, the prognostic nomograms of OS and CSS showed better prediction accuracy and clinical application value for SCCO than the FIGO staging system.

Conclusions: We constructed original nomograms that provided useful prediction of OS and CSS for patients with SCCO. These models could facilitate the postoperative personalized assessment and the identification of treatment strategy.

Background: The heterogenous expression of human epidermal growth factor receptor (HER) family members may contribute to poor response to current therapies with HER inhibitors in cancer. This study aimed to explore the co-expression and prognostic significance of HER family members with epidermal growth factor receptor variant III (EGFRvIII), cluster of differentiation 44 (CD44), cluster of differentiation 109 (CD109), and claudin 18.2 (CLDN18.2) in patients with stomach cancer.

Methods: The relative expression and prognostic significance of these biomarkers at different cut-off values were determined in 78 patients with stomach adenocarcinoma by immunohistochemistry.

Results: Of the 78 cases, positive tumor staining was present for wild-type EGFR (13%), HER2 (82%), HER3 (9%), HER4 (33%), EGFRvIII (33%), CD44 (41%), CD109 (60%), and CLDN18.2 (40%). Furthermore, the expression of HER2 was accompanied with the co-expression of EGFR (9%), HER3 (8%), HER4 (27%), EGFRvIII (28%), CD44 (33%), CD109 (49%), and CLDN18.2 (32%). Interestingly, at the cut-off value ≥ 5% of tumor cells with positive staining, the co-expressions of HER2/EGFRvIII, EGFRvIII/CD44, and HER2/EGFRvIII/CD44 were associated with poor overall survival. Moreover, CLDN18.2 immunostaining of intensity of 3+, membranous expression of CD109, the co-expression of CD109/CLDN18.2 and CD109/EGFRvIII/CD44 were also associated with poorer overall survival and a higher risk of poor overall survival. All these remained as independent prognostic factors for survival in multivariate analysis.

Conclusion: This study provides first comprehensive analysis of the novel biomarker combinations that are significantly associated with overall survival. Co-expression of HER2 with EGFRvIII, CD44, and CD109, plus membranous CD109 and high-intensity CLDN18.2, independently predicted poor survival in stomach adenocarcinoma, highlighting their potential as prognostic biomarkers. These biomarker combinations may represent potential therapeutic targets for novel combination therapies, and future studies should investigate their predictive value for the response to therapy.

Background: Because partial nephrectomy (PN) may remove malignant tissue while maintaining kidney function, it is currently the gold standard for nephrectomy. However, the blood arteries that supply the kidney are clamped at the start of the procedure. The most common method for evaluating surgical margins during PN is intraoperative frozen section (FS) evaluation. Its long duration and high false-negative rate question its reliability and efficacy. This encouraged us to search for a much quicker and easier method.

Methods: The infrared (IR) imaging approach uses the differences in optical density between tumor and healthy tissue to create the sharp contrast in the IR images. The cancerous kidneys were examined after a radical nephrectomy. Following the removal of the cancerous tissue and some of the surrounding healthy tissue, the samples were examined using the IR method. For the IR analysis, we created specific software. Following that, tissue samples taken from both healthy and malignant areas were subjected to a histomorphological analysis.

Results: Experiments showed that malignant tissue appeared as areas of high blackness in the IR picture, while healthy tissue appeared as areas of high illumination. Our software highlighted the areas of the IR image that were associated with the healthy and malignant portions, computed their average brightness, and calculated the ratio of the average illumination (RAI) of the malignant area to that of the healthy area. RAI is an interval of numbers obtained as a result of dividing the average brightness of all dark areas in all examined samples by all light areas of all examined samples. The 95% probability interval for RAIs taking place, which ranged from 0.25 to 0.41, was calculated. The location of the malignancy was then identified by a histomorphological examination. The compliance between histomorphological results and the outcomes of IR examination was confirmed in all cases.

Conclusions: The IR imaging technique offers significant promise for improving the accuracy and efficiency of margin assessment during kidney cancer surgeries. The IR imaging technique can provide immediate feedback on the tumor boundaries, which could potentially reduce the duration of warm ischemia during surgery. Subsequent investigations should be focused on verifying the technology in further clinical trials and investigating its integration into the surgical process, which could result in its acceptance as a standard instrument for intraoperative decision-making in kidney cancer operations.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver carcinoma that is composed of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Given its low incidence, there is no standardized treatment protocol or systemic regimens. With the development of immune checkpoint inhibitors (ICIs), one of the immunotherapies that modulate the immune system by restoring antitumor immune response, studies have shown promising results for the use of ICI as systemic therapy for advanced solid tumors, including liver cancers. Moreover, prospective clinical studies displayed favorable outcomes of the use of ICIs in HCC and biliary tract cancers. Here, we review the recent evidence in application and comparison of ICIs for HCC, CCA, and cHCC-CCA as well as the future direction of systemic therapy for cHCC-CCA.

Background: Carbohydrate antigen 19-9 (CA19-9) is widely used to assess treatment response and monitor recurrence alongside imaging. However, the criteria for determining resectability after completion of neoadjuvant therapy (NAT) remain poorly defined. Therefore, this study aimed to investigate the indications for surgical resection as a prognostic factor following NAT with gemcitabine and S-1 (NATGS).

Methods: In this retrospective cohort study, we examined patients who underwent curative pancreatic resection following NATGS at our institution between April 2018 and December 2023. After excluding six patients who did not undergo pancreatectomy, the remaining 50 patients were included in the study. Univariate and multivariate analyses were conducted to identify factors potentially associated with survival after NATGS.

Results: Post-NATGS CA19-9 levels (< 100 U/mL) were identified as a significant prognostic factor for disease-free survival (DFS) in both univariate and multivariate analyses (hazard ratio (HR) = 11.72251, P < 0.001). For overall survival (OS), both CA19-9 levels (< 100 U/mL) and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels (< 150 U/mL) were significant prognostic factors in univariate and multivariate analyses (CA19-9: HR = 17.88, P = 0.002; DUPAN-2: HR = 2.667, P = 0.03). The median DFS was 24.1 months in the low CA19-9 group compared with the 7.1 months in the high CA19-9 group (P = 0.002). The median OS in the low CA19-9 group was not reached, whereas it was 14.7 months in the high CA19-9 group (P = 0.001).

Conclusions: The CA19-9 cut-off value is clinically significant for patients undergoing NATGS regimens. Patients with pre-operative CA19-9 levels ≥ 100 U/mL may benefit from extended GS treatment or a switch to a more potent regimen rather than proceeding directly to surgical resection.

Background: In Jordan, lung cancer ranks as the second most common tumor, and there is an urgent need to explore the genetic landscape of lung cancer. This study aimed to identify the actionable mutations in lung cancer samples in Jordanians by targeted next-generation sequencing (NGS) and to investigate the correlations with clinical and pathological parameters.

Methods: Totally, 121samples were prepared for NGS by DNA extractions from formalin-fixed paraffin-embedded (FFPE) blocks, followed by library preparation using the AmpliSeq Colon and Lung panel, which covers mutational hot spot regions for 22 cancer genes.

Results: Amongst 121 patients, 88% of those treated for non-small lung carcinoma were successfully analyzed; 35 (29%) carried one mutation or more in actionable genes (KRAS, EGFR, ALK, BRAF, and MET). There are no significant differences between actionable mutation carriers and non-carriers concerning histological tumor type, tumor stage, metastasis, smoking habits, and gender. However, the analysis of survival probabilities revealed lower survival times for females compared to males, as well as for those patients who had metastasis events, smoking, or relapse after treatment.

Conclusions: The type and rates of mutations detected for lung tumors in Jordan are relatively similar to those found in other populations previously studied, although some differences exist. However, lung tumors in Jordan require new customized treatment prescriptions based on prior genetic studies, as part of the hoped-for trend toward precision medicine.