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Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan–Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis. [ABSTRACT FROM AUTHOR]

Background: Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated. Methods: Cytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan–Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals. Results: CCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality. Conclusion: Circulating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy. [ABSTRACT FROM AUTHOR]

Objectives: Pretreatment biomarkers are needed to identify patients with non‐small‐cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real‐world cohort of NSCLC patients who received ICIs. Materials and Methods: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced‐stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil‐to‐lymphocyte ratio, C‐reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low‐ and high‐risk groups were defined using literature‐based cut‐offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. Results: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low‐risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36–4.06) than CAR alone (aHR 2.22, 95% CI 1.79–2.76) or PNI alone (aHR 2.09, 95% CI 1.66–2.61). Conclusion: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment. [ABSTRACT FROM AUTHOR]

Background: Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods: We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results: Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions: Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is a pivotal treatment for lymphoma patients. The BeEAM regimen (Bendamustine, Etoposide, Cytarabine, Melphalan) traditionally relies on cryopreservation, whereas the CEM regimen (Carboplatin, Etoposide, Melphalan) has been optimized for short-duration administration without the need for cryopreservation. This study rigorously compares the clinical and safety profiles of the BeEAM and CEM regimens. Methods: A controlled, randomized clinical trial was conducted with 58 lymphoma patients undergoing ASCT at the International Medical Center (IMC) in Cairo, Egypt. Patients were randomly assigned to either the BeEAM (n = 29) or CEM (n = 29) regimen, with an 18-month follow-up period. Clinical and safety outcomes were meticulously compared, focusing on time to engraftment for neutrophils and platelets, side effects, length of hospitalization, transplant-related mortality (TRM), and survival rates. Results: The findings demonstrate a significant advantage for the CEM regimen. Neutrophil recovery was markedly faster in the CEM group, averaging 8.5 days compared to 14.5 days in the BeEAM group (p < 0.0001). Platelet recovery was similarly expedited, with 11 days in the CEM group versus 23 days in the BeEAM group (p < 0.0001). Hospitalization duration was substantially shorter for CEM patients, averaging 18.5 days compared to 30 days for those on BeEAM (p < 0.0001). Furthermore, overall survival (OS) was significantly higher in the CEM group at 96.55% (95% CI: 84.91–99.44%) compared to 79.31% (95% CI: 63.11–89.75%) in the BeEAM group (p = 0.049). Progression-free survival (PFS) was also notably superior in the CEM group, at 86.21% (95% CI: 86.14–86.28%) versus 62.07% (95% CI: 61.94–62.20%) in the BeEAM group (p = 0.036). Conclusion: The CEM regimen might demonstrate superiority over the BeEAM regimen, with faster neutrophil and platelet recovery, reduced hospitalization time, and significantly improved overall and progression-free survival rates. Future studies with longer duration and larger sample sizes are warranted. Trial registration: This study is registered on ClinicalTrials.gov under the registration number NCT05813132 (https://clinicaltrials.gov/ct2/show/NCT05813132). (The first submitted registration date: is March 16, 2023). [ABSTRACT FROM AUTHOR]

Background: Invasive micropapillary carcinoma (IMPC) was first proposed as an entity by Fisher et al. In the 2003 World Health Organization (WHO) guidelines for histologic classification of the breast tumors. IMPC was recognized as a distinct, rare histological subtype of breast cancer. IMPC is emerging as a surgical and oncological challenge due to its tendency to manifest as a palpable mass, larger in size and higher in grade than IDC with more rate of lymphovascular invasion (LVI) and lymph node (LN) involvement, which changes the surgical and adjuvant management plans to more aggressive, with comparative prognosis still being a point of ongoing debate. Aim of the study : In this study, we compared the clinicopathological characteristics, survival and surgical management of breast cancer patients having invasive micropapillary carcinoma pathological subtype in comparison to those having invasive duct carcinoma. Method: This is a comparative study on female patients presented to Baheya center for early detection and treatment of breast cancer, in the period from 2015 to 2022 diagnosed with breast cancer of IMPC subtype in one group compared with another group of invasive duct carcinoma. we analyzed 138 cases of IMPC and 500 cases of IDC. Results: The incidence of LVI in the IMPC group was 88.3% in comparison to 47.0% in the IDC group (p < 0.001). IMPC had a higher incidence of lymph node involvement than the IDC group (68.8% and 56% respectively). IMPC had a lower rate of breast conserving surgery (26% vs.37.8%) compared with IDC. The survival analysis indicated that IMPC patients had no significant difference in overall survival compared with IDC patients and no differences were noted in locoregional recurrence rate and distant metastasis rate comparing IMPCs with IDCs. Conclusion: The results from our PSM analysis suggested that there was no statistically significant difference in prognosis between IMPC and IDC patients after matching them with similar clinical characteristics. However, IMPC was found to be more aggressive, had larger tumor size, greater lymph node metastasis rate and an advanced tumor stage. [ABSTRACT FROM AUTHOR]

Introduction: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. Study design: Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE Objectives: To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. Methods: Settings and participants: It is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. Variables: Full details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methods: The data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. Results: The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC), the most prevalent form of oral cancer, poses significant challenges to the medical community due to its high recurrence rate and low survival rate. Mitochondrial Damage-Related Genes (MDGs) have been closely associated with the occurrence, metastasis, and progression of OSCC. Consequently, we constructed a prognostic model for OSCC based on MDGs and identified potential mitochondrial damage-related biomarkers. Gene expression profiles and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Differential analysis was conducted to identify MDGs associated with OSCC. COX analysis was employed to screen seven prognosis-related MDGs and build a prognostic prediction model for OSCC. Cases were categorized into low-risk or high-risk groups based on the optimal risk score threshold. Kaplan-Meier (KM) analysis revealed significant survival differences (P < 0.05). Additionally, the area under the ROC curve (AUC) for patient survival at 1 year, 3 years, and 5 years were 0.687, 0.704, and 0.70, respectively, indicating a high long-term predictive accuracy of the prognostic model. To enhance predictive accuracy, age, gender, risk score, and TN staging were incorporated into a nomogram and verified using calibration curves. Risk scoring based on MDGs was identified as a potential independent prognostic biomarker. Furthermore, BID and SLC25A20 were identified as two potential independent mitochondrial damage-related prognostic biomarkers, offering new therapeutic targets for OSCC. [ABSTRACT FROM AUTHOR]

Mucinous adenocarcinoma (MAC) is a distinct subtype of colorectal cancer. Previous studies have confirmed the poor prognosis of rectal or left-sided colon MAC, while the prognosis and response to chemotherapy in proximal colon MAC remains controversial. The aim of this study was to investigate the clinicopathological characteristics, prognosis, response to chemotherapy, and risk prediction factors of proximal colon MAC. Patients with proximal colon MAC and non-mucinous adenocarcinoma (NMAC) were retrospectively analyzed in this study. The analyzed variables included gender, age, smoking, drinking, chemotherapy, metastasis, pathological stage, and tumor size. Overall survival (OS) was the primary outcome. Kaplan–Meier analysis was used to assess the impact of mucinous subtype and chemotherapy on OS. We conducted univariate and multivariate Cox regression analyses to determine prognosis factors for proximal colon MAC and NMAC. A total of 284 cases of proximal colon MAC and 1384 cases of NMAC were included in the study. Compared to NMAC, proximal colon MAC was diagnosed at a younger age. The proportion of synchronous and metachronous metastasis was also higher, as well as the pathological stage and tumor size. Proximal colon MAC had a worse prognosis than NMAC, especially in stage 3. Moreover, the prognosis of proximal colon NMAC improved after chemotherapy, while MAC showed no improvement in prognosis after chemotherapy. Advanced age, N1 and N2 stage were independent prognostic factors for adverse outcomes in MAC. For proximal colon adenocarcinoma, the independent predictors of adverse outcomes included mucinous subtype, order age, N1 and N2 stages, and pathological stage 4. Proximal colon MAC had a worse prognosis compared to NMAC. Chemotherapy did not improve the prognosis of proximal colon mucinous adenocarcinoma. [ABSTRACT FROM AUTHOR]

To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals. [ABSTRACT FROM AUTHOR]

Background: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated. Methods: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients. Results: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects. Conclusions: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC. [ABSTRACT FROM AUTHOR]

Background: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). Methods: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. Results: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). Conclusions: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients. Methods: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0. Results: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45–2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42–2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup. Conclusions: TBS may be an efficient prognostic index in HCC patients. [ABSTRACT FROM AUTHOR]

The Gasdermin E gene (GSDME) plays roles in deafness and cancers. However, the roles and mechanisms in cancers are complex, and the same gene exhibits different mechanisms and actions in different types of cancers. Online databases, such as GEPIA2, cBioPortal, and DNMIVD, were used to comprehensively analyze GSDME profiles, DNA methylations, mutations, diagnosis, and prognosis in patients with tumor tissues and matched healthy tissues. Western blotting and RT-PCR were used to monitor the regulation of GSDME by Cordycepin (CD) in cancer cell lines. We revealed that GSDME expression is significantly upregulated in eight cancers (ACC, DLBC, GBM, HNSC, LGG, PAAD, SKCM, and THYM) and significantly downregulated in seven cancers (COAD, KICH, LAML, OV, READ, UCES, and UCS). The overall survival was longer only in ACC, but shorter in four cancers, including COAD, KIRC, LIHC, and STAD, when GSDME was highly expressed in cancers compared with the corresponding normal tissues. Moreover, the high expression of GSDME was negatively correlated with the poor prognosis of ACC, while the low expression of GSDME was negatively correlated with the poor prognosis of COAD, suggesting that GSDME might serve as a good prognostic factor in these two cancer types. Accordingly, results indicated that the DNA methylations of those 7 CpG sites constitute a potentially effective signature to distinguish different tumors from adjacent healthy tissues. Gene mutations for GSDME were frequently observed in a variety of tumors, with UCES having the highest frequency. Moreover, CD treatment inhibited GSDME expression in different cancer cell lines, while overexpression of GSDME promoted cell migration and invasion. Thus, we have systematically and successfully clarified the GSDME expression profiles, diagnostic values, and prognostic values in pan-cancers. Targeting GSDME with CD implies therapeutic significance and a mechanism for antitumor roles in some types of cancers via increasing the sensitivity of chemotherapy. Altogether, our study may provide a strategy and biomarker for clinical diagnosis, prognostics, and treatment of cancers by targeting GSDME. [ABSTRACT FROM AUTHOR]

Introduction: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. Methods: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan–Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. Results: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P =.007), DFS (HR 1.129, P =.015), LRFS (HR 1.211, P =.002), and DMFS (HR 1.131, P =.057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. Conclusions: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify the risk factors that influence metastasis and prognosis in patients with nodular melanoma (NM), as well as to develop and validate a prognostic model using artificial intelligence (AI) algorithms. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 4,727 patients with NM based on the inclusion/exclusion criteria. Their clinicopathological characteristics were retrospectively reviewed, and logistic regression analysis was utilized to identify risk factors for metastasis. This was followed by employing Multilayer Perceptron (MLP), Adaptive Boosting (AB), Bagging (BAG), logistic regression (LR), Gradient Boosting Machine (GBM), and eXtreme Gradient Boosting (XGB) algorithms to develop metastasis models. The performance of the six models was evaluated and compared, leading to the selection and visualization of the optimal model. Through integrating the prognostic factors of Cox regression analysis with the optimal models, the prognostic prediction model was constructed, validated, and assessed. Results: Logistic regression analyses identified that marital status, gender, primary site, surgery, radiation, chemotherapy, system management, and N stage were all independent risk factors for NM metastasis. MLP emerged as the optimal model among the six models (AUC = 0.932, F1 = 0.855, Accuracy = 0.856, Sensitivity = 0.878), and the corresponding network calculator (https://shimunana-nm-distant-m-nm-m-distant-8z8k54.streamlit.app/) was developed. The following were examined as independent prognostic factors: MLP, age, marital status, sequence number, laterality, surgery, radiation, chemotherapy, system management, T stage, and N stage. System management and surgery emerged as protective factors (HR < 1). To predict 1-, 3-, and 5-year overall survival (OS), a nomogram was created. The validation results demonstrated that the model exhibited good discrimination and consistency, as well as high clinical usefulness. Conclusion: The developed prediction model more effectively reflects the prognosis of patients with NM and differentiates between the risk level of patients, serving as a useful supplement to the classical American Joint Committee on Cancer (AJCC) staging system and offering a reference for clinically stratified individualized treatment and prognosis prediction. Furthermore, the model enables clinicians to quantify the risk of metastasis in NM patients, assess patient survival, and administer precise treatments. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. Methods: The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. Results: In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. Conclusion: Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC), one of the most fatal urologic tumors, accounts for approximately 3% of all adult cancers and exhibits a high metastatic index at diagnosis and a high rate of relapse. Radical or partial nephrectomy is a curative option for nonmetastatic RCCs. Targeted therapy has been shown to improve the survival of patients with metastatic RCCs. However, the underlying cellular and molecular events associated with RCC pathogenesis are not well known. Methods: To investigate the clinical role of the transcription factor activator protein (AP)-2α in RCC, methylated CpG island recovery assays and microarray analysis were employed. COBRA and RT‒qPCR assays were performed to assess AP-2α expression in RCC. Results: A negative correlation was noted between AP-2α mRNA expression levels and methylation status. Multivariate analyses showed that AP-2α mRNA was a major risk factor not only for overall and disease-free survival in RCC but also for disease-free survival in clear cell RCC. Conclusions: Our results indicated that AP-2α expression was deregulated in RCC and associated with overall patient survival and disease-free survival. Such findings suggest that AP-2α might play an important role in the pathogenesis of RCC. [ABSTRACT FROM AUTHOR]

Summary Background Methods Results Conclusions The benefits of HCV eradication on distinct recurrence patterns and long‐term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long‐term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR).We retrospectively enrolled 274 patients receiving RFA for HCV‐related HCC, including 73 and 88 patients treated with interferon‐based (IFN) and direct‐acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation.SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB‐4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB‐4 score after SVR, rather than the baseline FIB‐4, predicted distant recurrence.HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV‐related HCC. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation. Results: A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03–3.19). Conclusions: Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Recent advancements in anti-CD38 monoclonal antibody therapies, such as daratumumab and isatuximab, have significantly improved MM patient survival. However, the lack of predictive factors of response to these therapies remains a challenge. Notably, anti-CD38 antibodies can interfere with laboratory tests, complicating response assessment. We conducted a retrospective study to evaluate the association between the appearance of positive IgGk (therapeutic antibody) on immunofixation/immunosubtraction (IF) and clinical parameters in 87 non-IgGk MM patients treated with anti-CD38 therapy. Positive IgGk IF was observed in 42 patients after a median of three treatment courses. Patients with positive IgGk IF had higher rates of complete/very good partial responses (p = 0.03) and improved progression-free survival (median not reached vs. 21.83 months, p < 0.01). High BMI (p = 0.03), higher hemoglobin (p = 0.02), lower CRP (p = 0.04), and lower monoclonal protein levels (p = 0.03) were associated with positive IgGk IF. Our findings suggest that monitoring therapeutic antibody appearance on IF may predict and optimize anti-CD38 therapy in MM. Potential explanations include the impact of patient factors (e.g. BMI) on drug pharmacokinetics, the relationship between antibody levels and immune response, and the influence of tumor biology. Further research is needed to elucidate the underlying mechanisms and clinical utility of this biomarker. Nonetheless, our results highlight the importance of considering therapeutic antibody detection when interpreting laboratory tests and managing MM patients receiving anti-CD38 therapies. [ABSTRACT FROM AUTHOR]

The role of neoadjuvant chemotherapy and its benefits in patients with triple-negative breast cancer (TNBC) and small tumors are unclear. This study aims to compare survival differences between clinical T1 TNBC receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Data for patients with clinical T1 TNBC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized according to whether they received chemotherapy before or after surgery. Propensity Score Matching (PSM) was used to minimize the influence of confounding factors. OS and BCSS were compared between the two treatment sequences using Kaplan–Meier and univariate and multivariable Cox proportional hazards regression analyses. The study included 6249 women with T1 TNBC. In multivariate analysis, compared with that in the AC group, the hazard ratio for death in the NAC group was 1.54 (95% confidence interval 1.26–1.89, p < 0.001). NAC offers no additional benefits in any age group or T, N subgroups. Our findings suggest that NAC does not provide additional benefit to patients with clinical T1 TNBC, even in the presence of lymph node metastasis, or T1c. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 to 2021 and received systemic chemotherapy. Descriptive clinical statistics were performed, including staging, front-line chemotherapy, multimodal therapy usage, response rates, and survival analyses. Results: 49 ARMS patients who received upfront chemotherapy were identified. Locoregional treatments included radiotherapy (RT) alone (29%, n = 14), surgery alone (10%, n = 5), or both (45%, n = 22). Median overall survival (OS) for the entire cohort was 3.6 years, and the overall response rate to systemic therapy was 89%. No chemotherapy regimen showed OS benefit, specifically analyzing the pediatric-based vincristine, actinomycin-D, cyclophosphamide (VAC) or adult-based vincristine, doxorubicin, ifosfamide (VDI) regimens, even when controlled for other clinical risk factors. Conclusion: In this single-center contemporary series, adult ARMS patient outcomes remain poor. There was no statistically significant OS difference in patients who did or did not receive adult or pediatric based ARMS regimens, although a high overall response rate to chemotherapy was seen across the entire cohort. Based on these observations, further randomized prospective studies are necessary to delineate which frontline chemotherapy regimen is most beneficial in this rare adult cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). Methods: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. Results: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. Conclusion: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, is overexpressed in various cancers and facilitates immune evasion by inhibiting T-cell activation. GDFATHER-TRIAL's phase 2a results demonstrated promising outcomes when combining the GDF-15 neutralizing antibody visugromab (CTL002) with nivolumab, enhancing the response to immunotherapy. This study evaluated the prognostic significance of GDF-15 expression in non-small cell lung cancer (NSCLC) tumor tissues in terms of immunotherapy response. Methods: This retrospective study included 50 patients with metastatic NSCLC treated with nivolumab at Gazi University Hospital between January 2021 and July 2023. GDF-15 expression was evaluated using immunochemistry staining and categorized based on the intensity of cytoplasmic or membranous staining. Samples were divided into a low expression group (scores 0 and 1) and a high expression group (scores 2 and 3). The primary outcomes were progression-free survival (PFS) and overall survival (OS), which were analyzed using Kaplan‒Meier and Cox proportional hazards models. Objective response rates were assessed in secondary outcomes. Results: Of the 50 patients, 43 were men (86%), with a median age of 63.9 years. Half of the patients exhibited low GDF-15 expression. High GDF-15 expression correlated with shorter PFS and OS. The median PFS was 7.8 months for the low-expression group versus 4.4 months for the high-expression group (HR, 0.41; 95% CI, 0.20–0.83; p = 0.013). The median OS was 18.1 months for the low-expression group compared to 11.8 months for the high-expression group (HR, 0.36; 95% CI, 0.16–0.78; p = 0.007). The objective response rate was significantly greater in the low GDF-15 group (52%) than in the high GDF-15 group (24%) (p = 0.040). Conclusion: Elevated GDF-15 expression in NSCLC tumor tissues is associated with poorer response to nivolumab, suggesting that GDF-15 is a potential prognostic biomarker for immunotherapy efficacy. These findings warrant further validation through prospective studies to optimize treatment strategies for NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC. Methods: We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024. Results: Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively. Conclusion: ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population. [ABSTRACT FROM AUTHOR]

Objectives: High‐grade gliomas (HGGs) are highly malignant, aggressive, and have a high incidence and mortality rate. The aim of this study was to investigate survival outcomes and prognostic factors in patients with HGGs. Methods: In this retrospective study, a total of 159 patients with histologically confirmed HGGs were included. The recruitment period was from January 2011 to December 2019. We evaluated patient demographic data, tumor characteristics, treatment methods, immunocytochemistry results, overall survival (OS) time, and progression‐free survival (PFS) time using Kaplan–<>Meier survival analysis with log‐rank testing. Additionally, we employed Cox regression analysis to identify independent factors associated with survival outcomes. Results: Kaplan–Meier survival analysis revealed that the 1‐, 2‐, and 5‐years OS rates were 81.8%, 50.3%, and 12.6%, respectively. Similarly, the 1‐, 2‐, and 5‐years PFS rates were 50.9%, 22.4%, and 3.1%, respectively. The median OS duration was 35.0 months. The univariate analysis indicated that postoperative pathological classification, grade, and age were significantly associated with patient outcomes (p < 0.01). Among the patients, 147 received concurrent chemoradiotherapy, while 12 did not. The immunohistochemical markers of ki‐67, MGMT, IDH1R132H, and p53 demonstrated statistically significant differences in their prognostic impact (p = 0.001, p = 0.020, p = 0.003, and p = 0.021, respectively). In conclusion, we found that grades, age, pathological classification, ki‐67, MGMT, and IDH1R132H expression were statistically significantly associated with PFS (p < 0.01, p = 0.004, p = 0.003, p = 0.001, p = 0.036, and p = 0.028). Additionally, immunohistochemical expressions of TRIB3 and AURKA were significantly higher in patients with shorter survival (p = 0.015 and p = 0.023). Conclusions: Tumor grade and the use of concurrent chemoradiotherapy after surgery were independent prognostic factors that significantly influenced patient survival. Additionally, tumor grade and MGMT expression were found to be independent factors affecting progression‐free survival (PFS). Notably, the expression of TRIB3 and AURKA was higher in patients with poor survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Hypoxia is often involved in tumor microenvironment, and the hypoxia‐induced signaling pathways play a key role in aggressive cancer phenotypes, including angiogenesis, immune evasion, and therapy resistance. However, it is unknown what role genetic variants in the hypoxia‐related genes play in survival of patients with non‐small cell lung cancer (NSCLC). Methods: We evaluated the associations between 16,092 single‐nucleotide polymorphisms (SNPs) in 182 hypoxia‐related genes and survival outcomes of NSCLC patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were used as the discovery dataset, and the Harvard Lung Cancer Susceptibility (HLCS) Study served as the replication dataset. We also performed additional linkage disequilibrium analysis and a stepwise multivariable Cox proportional hazards regression analysis in the PLCO dataset. Results: An independent SNP, ERRFI1 rs28624 A > C, was identified with an adjusted hazards ratio (HR) of 1.31 (95% CI = 1.14–1.51, p = 0.0001) for overall survival (OS). In further analyses, unfavorable genotypes AC and CC, compared with the AA genotype, were associated a worse OS (HR = 1.20, 95% CI = 1.03–1.39, p = 0.014) and disease‐specific survival (HR = 1.21, 95% CI = 1.04–1.42, p = 0.016). Further expression quantitative trait loci analysis indicated that ERRFI1 rs28624C genotypes were significantly associated with higher ERRFI1 mRNA expression levels in the whole blood. Additional analysis showed that high ERRFI1 mRNA expression levels were associated with a worse OS in patients with lung adenocarcinoma. Conclusion: Our findings suggest that genetic variants in the hypoxia‐related gene ERRFI1 may modulate NSCLC survival, potentially through their effect on the gene expression. [ABSTRACT FROM AUTHOR]

Background: Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). Results: The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%–89.09% in training group, and 82.16%–88.74% in test group) and discriminatory power (AUC: 0.806–0.894 in training group, and 0.808–0.882 in test group) in both training and testing datasets. An interactive web‐based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma%5fsurvival%5fprediction/) was developed, simplifying the survival prediction process for clinicians. Conclusions: This study successfully employed RPA to develop a user‐friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision‐making. Future prospective studies are recommended to validate these findings and further refine the predictive model. [ABSTRACT FROM AUTHOR]

Mediation analysis is a useful tool to study the mechanism of how a treatment exerts effects on the outcome. Classical mediation analysis requires a sequential ignorability assumption to rule out cross-world reliance of the potential outcome of interest on the counterfactual mediator in order to identify the natural direct and indirect effects. In recent years, the separable effects framework has adopted dismissible treatment components to identify the separable direct and indirect effects. In this article, we compare the sequential ignorability and dismissible treatment components for longitudinal outcomes and time-to-event outcomes with time-varying confounding and random censoring. We argue that the dismissible treatment components assumption has advantages in interpretation and identification over sequential ignorability, whereas these two conditions lead to identical estimators for the direct and indirect effects. As an illustration, we study the effect of transplant modalities on overall survival mediated by leukemia relapse in patients undergoing allogeneic stem cell transplantation. We find that Haplo-SCT reduces the risk of overall mortality through reducing the risk of relapse, and Haplo-SCT can serve as an alternative to MSDT in allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

This 10-year retrospective cohort study at a single-center clinic in Germany aimed to analyze the outcomes of endometrial cancer patients and explore the impact of lymphovascular invasion (LV) on patient outcomes and disease-free survival (DFS). Identifying correlations among demographic data, tumor characteristics, treatment modalities, and survival outcomes could enhance patient management and improve survival rates. The study encompassed patients diagnosed and treated for endometrial cancer from January 2010 to December 2020. Clinical and pathological data were extracted from medical records for 311 patients, focusing on variables such as age, histological type, tumor grade, type of surgical treatment, and adjuvant therapies. Survival analysis was conducted using the Kaplan–Meier method and multivariate Cox proportional hazard models to identify factors independently associated with survival. The study demonstrated that lymphovascular invasion significantly impacted survival outcomes on Kaplan–Meier analysis (log-rank p-value = 0.0058). Patients with LV showed a marked decrease in DFS compared to those without LV invasion, with a median DFS of 3.2 years and a hazard ratio of 2.18 (95% CI: 1.56–3.04, p < 0.001). Furthermore, high-grade tumors and p53 positivity were strongly associated with reduced DFS, with hazard ratios of 1.93 (p = 0.001) and 2.11 (p < 0.001), respectively. Patients with distant metastasis exhibited the most significant decline in survival, with a hazard ratio of 5.56 (95% CI: 2.45–10.18, p < 0.001). Despite comprehensive surgical and adjuvant therapies, these high-risk factors dictated poorer outcomes. The presence of lymphovascular invasion, high-grade tumors, and genetic markers like MSI and p53 are pivotal in predicting the course of endometrial cancer. This study underscores the necessity for aggressive management strategies in patients exhibiting these high-risk features to potentially improve prognosis and survival outcomes. The findings advocate for enhanced therapeutic strategies tailored to the biological behavior of the tumor, thereby aiming to elevate the overall survival rates for women diagnosed with endometrial cancer. [ABSTRACT FROM AUTHOR]

Programmed cell death-1 (PD1) inhibitors, a form of immune checkpoint inhibitor, are efficacious for metastatic melanoma but are associated with cutaneous adverse reactions (CARs). Studies in Europe and North America showed that CARs are associated with an increased overall survival. However, studies from Asia showed mixed results. There is a paucity of data regarding the efficacy of PD1 inhibitors and the effect of CARs on overall survival from Southeast Asia. A retrospective study of patients in the National Cancer Centre Singapore who were diagnosed with melanoma between 2015 and 2020 was conducted. Patients were included in the study if they had stage IV melanoma (advanced melanoma). Sixty-two patients were included in the study. The median age was 62.5 years and acral melanoma was the commonest subtype. Forty-three patients received PD1 inhibitors. Comparing patients who did not receive PD1 inhibitors to patients who received PD1 inhibitors, the former had a median overall survival of 6 months (95% CI: 5.07, 6.93), whereas the latter had a median overall survival of 21 months (95% CI: 13.33, 28.67; p < 0.001) (Hazard ratio 0.32; 95% CI: 0.16, 0.63; p = 0.001). Amongst patients who received PD1 inhibitors, patients who developed CARs had a greater median overall survival of 33 months (95% CI: 17.27, 48.73) compared to 15 months (95% CI: 9.20, 20.80; p = 0.013) for patients who did not (HR 0.29; 95% CI: 0.098, 0.834; p = 0.022). This study provides insight into the outcomes of metastatic melanoma in Singapore, and adds to the body of evidence supporting the use of PD1 inhibitors in Asians. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of metastatic lung cancer has been largely modified with targeted therapies and immunotherapies. Whether this survival benefit for subgroups of patients is beneficial to all patients treated for lung cancer has never been explored. The Institut Curie is an anti-cancer center in Paris, France, treating patients with lung cancer. Since the 2000s, Institut Curie has implemented dematerialized medical records, allowing for a large overview of the survival of patients with lung cancer according to treatment evolution. We found that the survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC (non-small cell lung cancer) but not in SCLC (small cell lung cancer). SCLC remains a disease with poor prognosis for which novel therapies are needed. Over the past 20 years, several innovative therapies have been implemented in the treatment of lung cancer that have had reported survival benefits in clinical trials. Whether these improvements translate into the clinic setting has not been studied yet. We retrospectively analyzed all patients consecutively treated at Institute Curie for metastatic lung cancer. Diagnosis date was used to define three periods, based on the approvals of novel treatment strategies in the first-line setting, including targeted therapies in 2010 and immunotherapy in 2018. Endpoints included Overall survival (OS), survival rate of 2 years and 5 years, and a conditional survival rate of 2 years (if still alive at 6 months from treatment initiation). A total of 673 patients were identified for Period 1—2000 to 2009, 752 for Period 2—2010 to 2017, and 768 for Period 3—2018 to 2020. Median OS in the whole cohort was 11.1, 15.5, and 16.2 months, respectively. Median OS for patients with NSCLC or SCLC was 11.2, 17.2, and 18.2 months, or 10.9, 11.7, and 11.2 months, respectively. The two-year conditional survival was more favorable for NSCLC than SCLC patients. Outcomes were statistically higher for women as compared to men in all periods and all subgroups. Survival of patients with metastatic lung cancer has improved over the past 20 years, mostly in NSCLC, along with the implementation of novel treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: A model predicting responders to corticosteroid switch during abiraterone therapy in patients with metastatic castration-resistant prostate cancer is warranted. The model using logistic regression was developed in a cohort of 67 and validated in another cohort of 42 patients. The use of this model is easy and all needed parameters are available from routine laboratory and history of patients. The overall accuracy was 92%. Multivariate analysis revealed that responsiveness was a marker of longer treatment duration and overall survival. For non-responders a new systemic treatment was indicated. Background: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients' history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. Results: The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85–0.96). After a median follow-up of 27.9 (26.3–84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1–6.5) and 11.1 (8.5–12.9) months and the median overall survival (OS) was 23.2 (15.6–25.8) and 33.5 (26.1–38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. Conclusions: A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the involvement of the immune system in oral and lung squamous cell carcinoma. Given the increasing recognition of the immune system's significance in cancer, the study analyzes key components of both tumor macroenvironment and microenvironment. In detail, the focus is on systemic inflammation markers, such as Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR). Additionally, this study investigates Tumor-Infiltrating Lymphocytes (TILs) and CD8+ cells in the tumor microenvironment. We aimed to better understand the impact of these prognostic factors on overall survival (OS) and disease-free survival (DSF) in order to enhance cancer risk stratification and guide therapeutic decisions. Background: The interplay between cancer cells and the immune system is crucial in cancer progression and treatment. In this regard, the tumor immune microenvironment and macroenvironment, marked by systemic inflammation markers and TILs, could be considered key prognostic factors in tumors, including oral and lung squamous cell carcinoma. Methods: We conducted a retrospective clinical study on patients with Oral Squamous Cell Carcinoma (OSCC) and Lung Squamous Cell Carcinoma (LUSCC), examining stages, comorbidities, treatments, and outcomes. We evaluated the prognostic significance of pre-surgical systemic inflammation markers and tumor microenvironment composition. Results: Associations were found between systemic inflammation markers—NLR, MLR, and PLR—and tumor microenvironment factors, such as TILs and CD8+ cell prevalence—elevated inflammation markers correlated with advanced stages. Specifically, NLR was prognostic in OSCC, whereas PLR was prognostic in LUSCC. Using a cutoff value, we divided our tumor samples into two prognostic groups. Moreover, TILs levels >15% of tumor stroma correlated with prolonged overall survival in both OSCC and LUSCC, while increased CD8+ expression was linked to extended disease-free survival in LUSCC. Discussion: Systemic inflammation markers and TILs can be valuable prognostic factors of survival, highlighting the immune response's role in OSCC and LUSCC. Despite limited clinical integration of the presented cohorts due to a lack of standardization, we concluded that analyzing tumor immune profiles may offer novel prognostic insights. Conclusions: Future integration into cancer classification could improve risk stratification and treatment guidance. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to assess the 3-year time to relapse (TTR) and overall survival (OS) of melanoma, including acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or the combination of dabrafenib and trametinib. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). This study suggests that both acral and mucosal types in the adjuvant setting are less effective than non-acral cutaneous melanoma at the 3-year TTR. Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib. Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib. Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05). Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is an aggressive form of brain cancer characterized by its poor prognosis due to its resistance and recurrence capabilities. Liquid biopsies have been increasingly utilized when studying GBM as they provide extensive amounts of data at multiple time points without the invasiveness of tissue samples. We used a large-scale proteomic panel from the serum of GBM patients collected before chemoradiation therapy (CRT) to study the connections of CD133, a protein recognized as involved in GBM resistance. We used a novel machine learning process to identify 24 proteins associated with CD133 and 12-month survival, successfully grouping patients into risk groups based on protein profiles. Our results identify a potentially harmful protein profile while revealing important serum associations of CD133. These identified proteins are possible prognostic indicators and treatment entry points with heightened value because they can be frequently traced and monitored. Glioma is the most prevalent type of primary central nervous system cancer, while glioblastoma (GBM) is its most aggressive variant, with a median survival of only 15 months when treated with maximal surgical resection followed by chemoradiation therapy (CRT). CD133 is a potentially significant GBM biomarker. However, current clinical biomarker studies rely on invasive tissue samples. These make prolonged data acquisition impossible, resulting in increased interest in the use of liquid biopsies. Our study, analyzed 7289 serum proteins from 109 patients with pathology-proven GBM obtained prior to CRT using the aptamer-based SOMAScan® proteomic assay technology. We developed a novel methodology that identified 24 proteins linked to both serum CD133 and 12-month overall survival (OS) through a multi-step machine learning (ML) analysis. These identified proteins were subsequently subjected to survival and clustering evaluations, categorizing patients into five risk groups that accurately predicted 12-month OS based on their protein profiles. Most of these proteins are involved in brain function, neural development, and/or cancer biology signaling, highlighting their significance and potential predictive value. Identifying these proteins provides a valuable foundation for future serum investigations as validation of clinically applicable GBM biomarkers can unlock immense potential for diagnostics and treatment monitoring. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored how genetic changes influence treatment effectiveness and survival in patients with advanced pancreatic cancer. By examining tumors from 142 patients, researchers identified specific genetic mutations that can predict how well a patient responds to chemotherapy. Findings showed that mutations in certain genetic pathways are associated with longer survival and better treatment outcomes. This research highlights the importance of tailoring cancer treatment based on individual genetic profiles, potentially leading to more personalized and effective therapies for pancreatic cancer patients. (1) Background: Pancreatic ductal adenocarcinoma (PDAC) has low survival rates despite treatment advancements. Aim: This study aims to show how molecular profiling could possibly guide personalized treatment strategies, which may help improve survival outcomes in patients with PDAC. (2) Materials and Methods: A retrospective analysis of 142 PDAC patients from a single academic center was conducted. Patients underwent chemotherapy and next-generation sequencing for molecular profiling. Key oncogenic pathways were identified using the Reactome pathway database. Survival analysis was performed using Kaplan–Meier curves and Cox Proportional Hazards Regression. (3) Results: Patients mainly received FOLFIRINOX (n = 62) or gemcitabine nab-paclitaxel (n = 62) as initial chemotherapy. The median OS was 13.6 months. Longer median OS was noted in patients with NOTCH (15 vs. 12.3 months, p = 0.007) and KIT pathway mutations (21.3 vs. 12.12 months, p = 0.04). Combinatorial pathway analysis indicated potential synergistic effects on survival. In the PFS, PI3K pathway (6.6 vs. 5.7 months, p = 0.03) and KIT pathway (10.3 vs. 6.2 months, p = 0.03) mutations correlated with improved PFS within the gemcitabine nab-paclitaxel subgroup. (4) Conclusions: Molecular profiling could play a role in PDAC for predicting outcomes and responses to therapies like FOLFIRINOX and gemcitabine nab-paclitaxel. Integrating genomic data into clinical decision-making can benefit PDAC treatment, though further validation is needed to fully utilize precision oncology in PDAC management. [ABSTRACT FROM AUTHOR]

Simple Summary: Aquaporins (AQPs) have emerged as potential predictors of response to cancer therapy and as targets for increasing sensitivity to treatment. However, systemic therapeutic inhibition using pan-AQP or AQP-specific inhibitors has not been characterized for efficacy in treating breast cancer or as a component of combination treatment. We evaluated AQP inhibition using established AQP inhibitors in cytotoxicity and pharmacologic assays. This study identified AQPs as a targetable vulnerability in breast cancer. AQP inhibitors can increase therapeutic efficacy, both as single agents and in a combination therapy strategy, in treating breast cancer progression and metastasis. These results provide significant insights that support the future development of improved AQP inhibitors. AQPs contribute to breast cancer progression and metastasis. We previously found that genetic inhibition of Aqp7 reduces primary tumor burden and metastasis in breast cancer. In this study, we utilized two AQP inhibitors, Auphen and Z433927330, to evaluate the efficacy of therapeutic inhibition of AQPs in breast cancer treatment. The inhibitors were evaluated in breast cancer for both cytotoxicity and metabolic stability assays across both murine and human breast cancer cell lines. Both AQP inhibitors also affected the expression of other AQP transcripts and proteins, which demonstrates compensatory regulation between AQP family members. As a single agent, Auphen treatment in vivo extended overall survival but did not impact primary or metastatic tumor burden. However, Auphen treatment made cells more responsive to chemotherapy (doxorubicin) or endocrine treatment (tamoxifen, fulvestrant). In fact, treatment with Tamoxifen reduced overall AQP7 protein expression. RNA-seq of breast cancer cells treated with Auphen identified mitochondrial metabolism genes as impacted by Auphen and may contribute to reducing mammary tumor progression, lung metastasis, and increased therapeutic efficacy of endocrine therapy in breast cancer. Interestingly, we found that Auphen and tamoxifen cooperate to reduce breast cancer cell viability, which suggests that Auphen treatment makes the cells more susceptible to Tamoxifen. Together, this study highlights AQPs as therapeutic vulnerabilities of breast cancer metastasis that are promising and should be exploited. However, the pharmacologic results suggest additional chemical refinements and optimization of AQP inhibition are needed to make these AQP inhibitors appropriate to use for therapeutic benefit in overcoming endocrine therapy resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma has a low 5-year survival rate due to delayed diagnosis, rapid growth, tumor complexity, and difficulties in surgical resection. Treatments involving new targeted chemotherapeutic options are required due to challenges such as drug resistance, low efficacy, severe toxicity, high metastatic potential, and clinical trial failures. This study demonstrates the preclinical efficacy and potential of the novel combination of abemaciclib and panobinostat in multiple pancreatic cancer cell lines. Our results depict that a novel combination of these agents aids in synergistic effects, causing cell death in pancreatic cancer cells. The current 5-year survival rate of pancreatic cancer is about 12%, making it one of the deadliest malignancies. The rapid metastasis, acquired drug resistance, and poor patient prognosis necessitate better therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC). Multiple studies show that combining chemotherapeutics for solid tumors has been successful. Targeting two distinct emerging hallmarks, such as non-mutational epigenetic changes by panobinostat (Pan) and delayed cell cycle progression by abemaciclib (Abe), inhibits pancreatic cancer growth. HDAC and CDK4/6 inhibitors are effective but are prone to drug resistance and failure as single agents. Therefore, we hypothesized that combining Abe and Pan could synergistically and lethally affect PDAC survival and proliferation. Multiple cell-based assays, enzymatic activity experiments, and flow cytometry experiments were performed to determine the effects of Abe, Pan, and their combination on PDAC cells and human dermal fibroblasts. Western blotting was used to determine the expression of cell cycle, epigenetic, and apoptosis markers. The Abe-Pan combination exhibited excellent efficacy and produced synergistic effects, altering the expression of cell cycle proteins and epigenetic markers. Pan, alone and in combination with Abe, caused apoptosis in pancreatic cancer cells. Abe-Pan co-treatment showed relative safety in normal human dermal fibroblasts. Our novel combination treatment of Abe and Pan shows synergistic effects on PDAC cells. The combination induces apoptosis, shows relative safety, and merits further investigation due to its therapeutic potential in the treatment of PDAC. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma, as well as the survival benefits from induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (5-FU). The dNLR is an independent negative predictive factor for the disease. Patients with cTNM stage III disease and a low dNLR may benefit from induction chemotherapy. Background: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). Methods: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan–Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. Results: A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018–1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000–1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002–1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010–1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. Conclusions: The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC. [ABSTRACT FROM AUTHOR]

Simple Summary: Response to treatment and prognosis after 223Ra treatment varies among patients. Using a combination of clinical, biochemical, and radiomic data from bone scintigraphy and 18F-Fluorocholine PET/CT obtained from our prospective ChoPET-Rad study, we identified predictive and prognostic variables. The goal was to create a nomogram able to predict therapeutic failure and overall survival, aiding in the selection of more suitable candidates for this treatment. Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events, and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from the Castilla-La Mancha Spanish region were prospectively included in the ChoPET-Rad multicenter study from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using the Kaplan–Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS were 4 and 14 months (mo), respectively. The variables that showed independent and significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p = 0.022) and the characteristics of BM on the CT portion of PET/CT (p = 0.017). In the case of OS, the significant variables were therapeutic failure (p = 0.038), the number of lines received after 223Ra (p < 0.001), average SUVmax (p = 0.002), bone marrow infiltration in FCH PET/CT (p = 0.006), and interim FCH PET/CT response (p = 0.048). Final nomograms included these variables, showing good discrimination among the 100 patients included in our study. In the study of skeletal events, only OS showed a significant association in the multivariate analysis, resulting in an inconsistent nomogram design. Conclusions: FCH PET/CT appears to be a good tool for evaluating patients eligible for treatment with 223Ra, as well as for their follow-up. Thus, findings derived from it, such as the morphological characteristics of BM in the CT, bone marrow infiltration, or the response to 223Ra in the interim study, have proven to be solid and useful variables in the creation of nomograms for predicting therapeutic failure and OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with stage IIB and IIC melanoma are considered to have high-risk localized disease and, in some cases, demonstrate worse recurrence-free and overall survival than patients with stage IIIA and even IIIB disease. The mainstay of treatment for patients with high-risk clinical stage II melanoma is surgical resection of the primary tumor and sentinel lymph node biopsy (SLNB), which confers accurate pathologic staging and prognostication for further treatment decisions. Building on the success of adjuvant therapy for stage III melanoma, the KEYNOTE-716 and CheckMate 76K trials found improved recurrence-free survival for patients with high-risk stage II melanoma with adjuvant pembrolizumab and nivolumab, respectively, after complete resection with SLNB. Given these findings, the National Comprehensive Cancer Network now recommends discussing adjuvant pembrolizumab or nivolumab with patients with high-risk stage IIB/C melanoma, weighing the risks of recurrence against the risks of treatment-related adverse events when making the decision regarding adjuvant therapy. Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Tertiary lymphoid structures (TLS) arise in non-lymphoid tissues due to inflammation or cancer and play a key role in adaptive immune responses. In this study, we analyzed the TLS maturity in 78 patients with pathological T4 colorectal cancer (CRC). Mature TLS, identified by organized T (CD3+) and B (CD20+) lymphocytes with Ki-67-positive B cells, have been linked to microsatellite instability and improved cancer-specific and post-recurrence survival. High tumor Ki-67 expression correlated with poorer outcomes. The absence of mature TLS independently predicted poor survival. Tumors with mature TLS showed a higher infiltration of CD3+ T cells, FOXP3+ T cells, and CD86+ immune cells, including M1-like macrophages. Focusing on the Ki-67 expression pattern, the simultaneous evaluation of TLS maturity and tumor proliferation potency is suggested to be a potential prognostic indicator in CRC. Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is discussed. We evaluated the impact of cALND omission on survival in breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 BC, the non-SN involvement rate was 13.2%. With a median follow-up of 66.46 months, multivariate analysis showed that cALND omission was significantly associated with overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly impacted by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative patients, DFS, OS, RFS, and MFS were also significantly affected (HR: 2.358, 3.317, 2.538, 2.756). For 161 patients ≤ 50 years with ER-positive/Her2-negative BC, OS and BCSS were notably associated with cALND omission (HR: 103.47 and 50.874). These findings suggest a negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is debated due to potential under-treatment, with non-sentinel node (NSN) involvement detected in 7% to 18% of patients. This study evaluated the survival impact of cALND omission in a cohort of breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 early BC patients (391 pN1mi, 163 ITC), the NSN involvement rate was 13.2% (49/371). With a median follow-up of 66.46 months, multivariate analysis revealed significant associations between cALND omission and overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly affected by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative BC, DFS, OS, recurrence-free survival (RFS), and MFS were significantly associated with cALND omission (DFS HR: 2.358, p = 0.043; OS HR: 3.317; RFS HR: 2.538; MFS HR: 2.756). For 161 patients aged ≤50 years with ER-positive/Her2-negative cancer, OS and breast cancer-specific survival (BCSS) were notably impacted by cALND omission (OS HR: 103.47, p = 0.004; BCSS HR: 50.874, p = 0.035). These findings suggest a potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Further randomized trials are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a promising and recently approved treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to analyze which laboratory and PET imaging parameters are able to predict biochemical response and overall survival with this treatment. Two quantitative imaging biomarkers were identified that allow prediction of RLT outcome, further improving the pre-therapeutic characterization of mCRPC patients undergoing PSMA-RLT. The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [68Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [177Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUVmax), the mean standardized uptake value of all tumor lesions (SUVmean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann–Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUVmean of all lesions was significantly different between responders and non-responders (SUVmean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUVmean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of metastatic melanoma is rising, making it imperative to identify patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker, using segmentations from 146 baseline and 146 first follow-up CT scans, to predict best overall response, progression-free survival, and overall survival across various immunotherapies. We volumetrically segmented the total tumour load, excluding cerebral metastases. This study also examined whether reducing the number of segmented metastases per patient affects predictive accuracy. The findings suggest that delta radiomics could enhance the prediction of best overall response, progression-free survival, and overall survival in metastatic melanoma patients undergoing first-line immunotherapy. Although volumetric whole tumour load segmentation is complex, it may provide predictive benefits. Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the endpoints best overall response (BOR), progression-free survival (PFS), and overall survival (OS), encompassing various immunotherapies. Additionally, this study investigated whether reducing the number of segmented metastases per patient affects predictive capacity. Methods: The total tumour load, excluding cerebral metastases, from 146 baseline and 146 first follow-up CTs of melanoma patients treated with first-line immunotherapy was volumetrically segmented. Twenty-one random forest models were trained and compared for the endpoints BOR; PFS at 6, 9, and 12 months; and OS at 6, 9, and 12 months, using as input either only clinical parameters, whole-tumour-load delta radiomics plus clinical parameters, or delta radiomics from the largest ten metastases plus clinical parameters. Results: The whole-tumour-load delta radiomics model performed best for BOR (AUC 0.81); PFS at 6, 9, and 12 months (AUC 0.82, 0.80, and 0.77); and OS at 6 months (AUC 0.74). The model using delta radiomics from the largest ten metastases performed best for OS at 9 and 12 months (AUC 0.71 and 0.75). Although the radiomic models were numerically superior to the clinical model, statistical significance was not reached. Conclusions: The findings indicate that delta radiomics may offer additional value for predicting BOR, PFS, and OS in metastatic melanoma patients undergoing first-line immunotherapy. Despite its complexity, volumetric whole-tumour-load segmentation could be advantageous. [ABSTRACT FROM AUTHOR]

Simple Summary: We retrospectively evaluated the clinical outcomes and prognostic factors of 127 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from the initiation of ARSI were assessed. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS varied among patients treated with enzalutamide, abiraterone acetate, apalutamide, and darolutamide (27.0, 20.0, 10.0, and 14.0 months, respectively; p = 0.33). Multivariate analysis indicated that a baseline PSA level of ≥3.67 ng/mL (p = 0.002) was significantly associated with poorer OS prognosis. ARSI demonstrated favorable efficacy in nmCRPC patients, with no significant differences in clinical outcomes among different types of ARSI. High baseline PSA of ARSI was found to have a significantly poor prognosis associated with OS. We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen–progression-free survival (PSA–PFS) from ARSI initiation were assessed using the Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA–PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥ 3.67 ng/mL at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS. [ABSTRACT FROM AUTHOR]

Simple Summary: The adrenal glands represent a frequent localization area for metastases of various primary tumors. The standard of care for treating adrenal metastases is currently surgical resection, but radiotherapy is becoming a feasible and well-tolerated treatment alternative. However, the literature shows contradictory results regarding the optimal local treatment for adrenal metastases. This study analyzed oncological outcomes (local control, progression free survival, and overall survival) and complication rates after stereotactic body radiotherapy or surgical resection of adrenal metastases to further asses the benefits of stereotactic body radiotherapy. To our knowledge, this analysis is the first direct comparison of stereotactic body radiotherapy and adrenalectomy for adrenal metastases. Background: This single-center retrospective study aimed to evaluate the efficacy and toxicity profiles of stereotactic body radiotherapy (SBRT) and surgical resection in patients with adrenal metastases originating from solid tumors. Methods/Materials: Patients with advanced tumor conditions or comorbidities typically received SBRT, whereas those considered physically fit underwent standard surgical treatment. Endpoints included local control (LC), progression free survival (PFS), overall survival (OS), and complication rates (CR). Results: 41 patients with 48 adrenal metastases were included, with 27 (65.9%) patients receiving SBRT and 14 (34.1%) patients undergoing adrenalectomy. One- and two-year LC values were 100% for both periods after adrenalectomy, and 70.0% and 52.5% after SBRT (p = 0.001). PFS showed values of 40.2% and 32.1% at one and two years after adrenalectomy and of 10.6% for both periods after SBRT (p = 0.223). OS was 83.3% both one and two years after surgery and 67.0% and 40.2% after SBRT (p = 0.031). There was no statistically significant difference between the two groups regarding acute complications (p = 0.123). Conclusion: Despite potential confounders, adrenalectomy exhibited statistically significant superior LC and OS compared to SBRT in managing adrenal metastases, while both treatment methods displayed acceptable toxicity profiles. However, patient selection bias must be taken into account when directly comparing the two therapy modalities. Nevertheless, the study provides new and important results for the scientific and medical communities regarding oncological outcomes after SBRT or surgical resection of adrenal metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: Early-stage hepatocellular carcinoma (HCC) is notorious for its high recurrence rate even after curative treatment. Several studies have suggested the association between diabetes mellitus (DM) and the risk of HCC. However, current evidence regarding the impact of glycemic burden on the outcomes of HCC is still limited. The present study provides an important insight into the relationship between glycemic burden and outcomes of early-stage HCC. Lower glycemic burden was an independent factor associated with better overall survival as well as lower recurrence in early-stage HCC. Moreover, there was a dose–response relationship between recurrence/overall survival and glycemic burden. Good glycemic control should be considered as a significant part of HCC management. Early-stage hepatocellular carcinoma (HCC) is still difficult to cure for its high recurrence rate. This study aimed to examine whether glycemic burden management could be one way to improve outcomes of early-stage HCC. A total of 137 very early or early-stage HCC patients who underwent resection or ablation at Samsung Medical Center and had glycemic burden assessment were analyzed. Glycemic burden was assessed using hemoglobin A1c (HbA1c) level. Outcomes were recurrence and overall survival. Risks of recurrence and overall survival were compared according to glycemic burden using a cut-off point of 6.5% or two cut-off points of 6.0% and 7.5%. Overall, 51 (37.2%) patients experienced HCC recurrence. The adjusted hazard ratio (aHR) for recurrence comparing patients with HbA1c > 6.5% to those with HbA1c ≤ 6.5% was 2.66 (95% CI: 1.26–5.78). The risk of recurrence increased in a dose-dependent manner by glycemic burden; aHR for 6.0 < HbA1c ≤ 7.5%: 2.00 (95% CI: 0.78–5.55); aHR for HbA1c > 7.5%: 6.05 (95% CI: 2.31–17.5). Mortality was observed in 16 (11.7%) patients. The risk of mortality was higher for HbA1c > 6.5% than for HbA1c ≤ 6.5% (aHR: 2.33; 95% CI: 1.10–5.08). There was also a dose–response relationship between overall survival and glycemic burden. Glycemic burden assessed using HbA1c level was significantly associated with outcomes of early-stage HCC patients. Good glycemic control could be a therapeutic goal to improve clinical outcomes in these populations. [ABSTRACT FROM AUTHOR]