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Background and Objectives: The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take into consideration its presence; however, emerging evidence about its potential harmful effect on patient survival outcomes suggests otherwise. In the present systematic review and meta-analysis, we sought to accumulate current evidence. Materials and Methods: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta function. A sensitivity analysis was carried out to evaluate the possibility of small-study effects and p-hacking. Trial sequential analysis was used to evaluate the adequacy of the sample size. The methodological quality of the included studies was assessed using the Newcastle–Ottawa scale. Results: Fifteen articles were finally included in the present systematic review that involved 19,255 women with early-stage endometrial cancer. The Newcastle–Ottawa scale indicated that the majority of included studies had a moderate risk of bias in their selection of participants, a moderate risk of bias in terms of the comparability of groups (positive peritoneal cytology vs. negative peritoneal cytology) and a low risk of bias concerning the assessment of the outcome. The results of the meta-analysis indicated that women with early-stage endometrial cancer and positive peritoneal cytology had significantly lower 5-year recurrence-free survival (RFS) (hazards ratio (HR) 0.26, 95% CI 0.09, 0.71). As a result of the decreased recurrence-free survival, patients with positive peritoneal cytology also exhibited reduced 5-year overall survival outcomes (HR 0.50, 95% CI 0.27, 0.92). The overall survival of the included patients was considerably higher among those that did not have positive peritoneal cytology (HR 12.76, 95% CI 2.78, 58.51). Conclusions: Positive peritoneal cytology seems to be a negative prognostic indicator of survival outcomes of patients with endometrial cancer. Considering the absence of data related to the molecular profile of patients, further research is needed to evaluate if this factor should be reinstituted in future staging systems. [ABSTRACT FROM AUTHOR]

Background and Objectives: Serum alpha-fetoprotein (AFP) is a recognized affordable oncological marker in patients with hepatocellular carcinoma (HCC). However, AFP's prognostic role has been assessed mainly after specific treatments, and no unanimously recognized cut-offs have been identified. The aim of this study is to investigate the prognostic role of different basal AFP cut-offs on survival and HCC course. Materials and Methods: In this single-center, retrospective study, all patients newly diagnosed with HCC between January 2009 and December 2021 were prospectively enrolled. Only patients suitable for curative HCC treatments were included in the analyses. Patients were stratified according to AFP cut-offs of 20, 200, 400, and 1000 ng/mL, which were correlated with survival outcomes and clinical parameters. Results: A total of 266 patients were analyzed, with a median follow-up time of 41.5 months. Median overall survival (OS) of all cohort was 43 months. At the multivariate Cox-regression analysis, AFP value ≥ 1000 ng/mL correlated with impaired OS (1-year OS: 67% vs. 88%, 5-year OS: 1% vs. 43%; p = 0.005); other risk factors were tumor dimension ≥ 5 cm (HR 1.73; p = 0.002), Child–Pugh class B–C (HR 1.72; p = 0.002), BCLC stage A (vs. 0) (HR 2.4; p = 0.011), and malignant portal vein thrombosis (HR 2.57; p = 0.007). AFP ≥ 1000 ng/mL was also associated with a reduced recurrence-free survival (HR 2.0; p = 0.038), while starting from AFP ≥ 20 ng/mL, a correlation with development of HCC metastases over time (HR 3.5; p = 0.002) was seen. AFP values ≥ 20 ng/mL significantly correlated with tumor size and higher histological grading; starting from AFP values ≥ 400 ng/mL, a significant correlation with Child–Pugh class B–C and female gender was also observed. Conclusions: Basal AFP correlates with relevant outcomes in patients with HCC. It could help identify patients at a higher risk of worse prognosis who might benefit from personalized surveillance and treatment programs. Prospective studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

This article examines disparities in melanoma presentation and overall survival among different Hispanic nationalities in the United States. The study found that Hispanic patients, particularly those of Mexican and South or Central American descent, were more likely to present with advanced melanoma and have worse outcomes compared to non-Hispanic White patients. Cuban and Mexican patients had the lowest 5-year overall survival rates. The study highlights the need for further research and targeted interventions to address these disparities, taking into account factors such as healthcare access, cultural practices, and skin types. [Extracted from the article]

Two recent studies reveal that the extent of fitness or anergy in tumor-associated memory B cells is vital to anti-tumor immune response, cancer patient survival, and response to immune therapy. The impact of these seminal findings demonstrates the untapped potential for using B cells to combat the lethality of cancer. [ABSTRACT FROM AUTHOR]

Objectives: Ovarian cancer (OC) can occur at different ages and is affected by a variety of factors. In order to evaluate the risk of cardiovascular mortality in patients with ovarian cancer, we included influencing factors including age, histological type, surgical method, chemotherapy, whether distant metastasis, race and developed a nomogram to evaluate the ability to predict occurrence. At present, we have not found any correlation studies on cardiovascular death events in patients with ovarian cancer. This study was designed to provide targeted measures for effective prevention of cardiovascular death in patients with ovarian cancer. Methods: Kaplan–Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of cardiovascular diseases on overall survival (OS) and ovarian cancer‐specific survival (OCSS). We compared multiple groups including clinical, demographic, therapeutic characteristics and histological types. Cox risk regression analysis, Kaplan–Meier survival curves, and propensity score matching were employed for analyzing the data. Results: A total of 88,653 ovarian cancer patients were collected, of which 2,282 (2.57%) patients died due to cardiovascular-related diseases. Age, chemotherapy and whether satisfactory cytoreduction surgery is still the most important factors affecting the prognosis of ovarian cancer patients, while different histological types, diagnosis time, and race also have a certain impact on the prognosis. The newly developed nomogram model showed excellent predictive performance, with a C-index of 0.759 (95%CI: 0.757–0.761) for the group. Elderly patients with ovarian cancer are still a high-risk group for cardiovascular death [HR: 21.07 (95%CI: 5.21–85.30), p < 0.001]. The calibration curve showed good agreement from predicted survival probabilities to actual observations. Conclusion: This study found that age, histology, surgery, race, chemotherapy, and tumor metastasis are independent prognostic factors for cardiovascular death in patients with ovarian cancer. The nomogram-based model can accurately predict the OS of ovarian cancer patients. It is expected to inform clinical decision-making and help develop targeted treatment strategies for this population. Highlights: • When patients with ovarian cancer are diagnosed, most are at an advanced stage and are diagnosed after menopause. • The nomogram is a powerful prediction model for the occurrence of CVM in elderly patients with ovarian cancer. • The model has good predictive ability and provides personalized treatment for the prevention of CVM in elderly OC patients. [ABSTRACT FROM AUTHOR]

Objective: To describe overall survival (OS) and disease-free survival (DFS) in a cohort of tongue cancer patients, together with the corresponding demographic, tumor and surgical characteristics. Methods: A retrospective study was made of 205 consecutive patients with primary tongue cancer subjected to surgery and adjuvant therapy according to the stage of the disease, in Hospital Clínico Universitario Virgen de la Arrixaca (HUVA) (Murcia, Spain) during the period 2000–2020. Survival was evaluated based on the Kaplan–Meier method, and the existence of significant differences between the different study variables was analyzed using the log-rank test. Cox regression analysis was performed for the identification of risk factors. Results: In relation to overall survival, 72.6% of the patients survived for a mean time of 14.43 years [standard error (SE) = 0.74; 95% CI: 12.98–15.87], with a cumulative survival rate of 49.8 ± 3%. Survival was reduced by the presence of tumor adjacent to resection margins [hazard ratio (HR) 2.20; 95% CI 1.09–4.43] (p = 0.028) and infiltrated resection margins (HR 3.86, 95% CI 1.56–9.57) (p = 0.004). Lymphadenectomy in turn increased survival (HR 0.15; 95% CI 0.06–0.42) (p < 0.001). In relation to disease-free survival, 55.3% of the patients suffered no relapse over a mean period of 9.91 years (SE = 0.66; 95% CI: 8.61–11.2), with a cumulative survival rate of 26.6% ± 8.4%. Conclusions: In tongue cancer patients, overall and specific survival were reduced in the presence of infiltrated resection margins. Lymphadenectomy in turn improved survival compared with patients in which this procedure was not carried out. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. Methods: This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan–Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. Results: A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan–Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. Conclusions: RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival. [ABSTRACT FROM AUTHOR]

Background: Pemetrexed (PEM) is the primary chemotherapy for non‐small cell lung cancer (NSCLC), showing potential for long‐term disease stability in certain cases. However, studies examining disease control with PEM therapy are lacking. This study aimed to pinpoint clinical traits in patients with NSCLC responding well to PEM therapy, predict factors influencing disease control, and suggest optimal treatment approaches. Methods: A retrospective analysis of patients with NSCLC treated with PEM was performed to compare patients who achieved disease control after treatment with those who did not. Results: Of 73 patients, 56 (76.7%) achieved disease control with PEM therapy. In the disease control group, a significantly higher proportion of patients exhibited good performance status (PS) and received PEM doses without reduction after the second cycle. Multivariate analysis identified bevacizumab (Bev) noncompliance, PEM dose reduction, and thyroid transcription factor‐1 (TTF‐1) negativity as significant independent risk factors for disease progression during PEM therapy. Additionally, overall survival was significantly longer in the disease control group (p < 0.001). Conclusions: Our findings indicated that maintaining the dose of PEM after the second treatment cycle in patients with NSCLC, along with concurrent use of Bev and the presence of TTF‐1 positivity, could enhance disease control rates and extend survival. [ABSTRACT FROM AUTHOR]

Background: The spleen plays an important role in systemic antitumor immune response, but whether spleen imaging features have predictive effect for prognosis and immune status was unknown. The aim of this study was to investigate computed tomography (CT)‐based spleen radiomics to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC) underwent definitive radiotherapy (dRT) and to try to find its association with systemic immunity. Methods: This retrospective study included 201 ESCC patients who received dRT. Patients were randomly divided into training (n = 142) and validation (n = 59) groups. The pre‐ and delta‐radiomic features were extracted from enhanced CT images. LASSO‐Cox regression was used to select the radiomics signatures most associated with progression‐free survival (PFS) and overall survival (OS). Independent prognostic factors were identified by univariate and multivariate Cox analyses. The ROC curve and C‐index were used to evaluate the predictive performance. Finally, the correlation between spleen radiomics and immune‐related hematological parameters was analyzed by spearman correlation analysis. Results: Independent prognostic factors involved TNM stage, treatment regimen, tumor location, pre‐ or delta‐Rad‐score. The AUC of the delta‐radiomics combined model was better than other models in the training and validation groups in predicting PFS (0.829 and 0.875, respectively) and OS (0.857 and 0.835, respectively). Furthermore, some spleen delta‐radiomic features are significantly correlated with delta‐ALC (absolute lymphocyte count) and delta‐NLR (neutrophil‐to‐lymphocyte ratio). Conclusions: Spleen radiomics is expected to be a useful noninvasive tool for predicting the prognosis and evaluating systemic immune status for ESCC patients underwent dRT. [ABSTRACT FROM AUTHOR]

Background: Although many studies have explored the correlation between quality of life and survival, none have reported this relationship for specific cancers assessed at distinct time points. This meta-analysis aimed to investigate the impact of pretreatment Global Quality of Life (QOL) and functioning QOL, including physical, social, role, emotional, and cognitive QOLs, on mortality risk in patients with lung cancer. Methods: A literature search was conducted across the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PubMed databases for articles published between their inception and December 2022. Subsequently, 11 studies were selected based on predefined eligibility criteria to investigate the relationship between pretreatment QOLs and mortality risk in patients with lung cancer. Results: Pretreatment global, physical, social, role, and emotional QOLs were significantly associated with mortality risk as follows: Global QOL (hazard ratio [HR] = 1.08 95% confidence interval [CI] = 1.03–1.13); Physical QOL (HR = 1.04 95% CI = 1.02–1.05); Social QOL (HR = 1.02 95% CI = 1.01–1.03; Role QOL (HR = 1.01 95% CI = 1.01–1.02); Emotional QOL (HR = 1.01 95% CI = 1.00–1.03). Conclusions: These findings underscore the importance of early QOL assessment after diagnosis as well as early provision of physical, social, and psychological support accommodating each patient's demands. Trial registration: The International Prospective Register of Systematic Reviews registration number CRD42023398206, Registered on February 20, 2023. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim was to develop a decision tree and a new prognostic tool to predict cancer-specific survival in patients with urothelial bladder cancer treated with radical cystectomy. Methods: A total of 11,834 patients with bladder cancer treated with radical cystectomy between 2004 and 2019 from the SEER database were randomly split into the derivation (n = 7889) and validation cohorts (n = 3945). Survival curves were estimated using conditional decision tree analysis. We used Multiple Imputation by Chained Equations for the treatment of missing values and the pec package to compare the predictive performance. We extracted data from our model following CHARMS and assessed the risk of bias and applicability with PROBAST. Results: A total of 4824 (41%) patients died during the follow-up period due to bladder cancer. A decision tree was made and 12 groups were obtained. Patients with a higher AJCC stage and older age have a worse prognosis. The risk groups were summarized into high, intermediate and low risk. The integrated Brier scores between 0 and 191 months for the bootstrap estimates of the prediction error are the lowest for our conditional survival tree (0.189). The model showed a low risk of bias and low concern about applicability. The results must be externally validated. Conclusions: Decision tree analysis is a useful tool with significant discrimination. With this tool, we were able to stratify patients into 12 subgroups and 3 risk groups with a low risk of bias and low concern about applicability. [ABSTRACT FROM AUTHOR]

Simple Summary: Adult-type astrocytomas usually present heterogeneous aspects under the microscope, reflecting their progression over time from grade 2 or 3 to grade 4, the highest possible grade. We identified a number of proteins and molecular pathways dysregulated in the high-grade areas of astrocytomas, which are involved in tumor evolution that could be targeted to avoid or detain glioma progression to higher grades. We identified HMGB2 as a potential biomarker of glioma evolution and predictive of response to treatment in more than 300 adult-type gliomas, using molecular profiling and immunohistochemistry, which are highly accessible for most pathology laboratories. HMGB2 expression increased even before histological markers of evolution appeared in grades 2 and 3 astrocytomas, and it was associated with poor survival. In glioblastomas, high HMGB2 expression identified tumors with better response to the standard treatment and could be used as additional inclusion/exclusion criterion to enroll patients in future clinical trials of new treatments. Although grading is defined by the highest histological grade observed in a glioma, most high-grade gliomas retain areas with histology reminiscent of their low-grade counterparts. We sought to achieve the following: (i) identify proteins and molecular pathways involved in glioma evolution; and (ii) validate the high mobility group protein B2 (HMGB2) as a key player in tumor progression and as a prognostic/predictive biomarker for diffuse astrocytomas. We performed liquid chromatography tandem mass spectrometry (LC-MS/MS) in multiple areas of adult-type astrocytomas and validated our finding in multiplatform-omics studies and high-throughput IHC analysis. LC-MS/MSdetected proteomic signatures characterizing glioma evolution towards higher grades associated with, but not completely dependent, on IDH status. Spatial heterogeneity of diffuse astrocytomas was associated with dysregulation of specific molecular pathways, and HMGB2 was identified as a putative driver of tumor progression, and an early marker of worse overall survival in grades 2 and 3 diffuse gliomas, at least in part regulated by DNA methylation. In grade 4 astrocytomas, HMGB2 expression was strongly associated with proliferative activity and microvascular proliferation. Grounded in proteomic findings, our results showed that HMGB2 expression assessed by IHC detected early signs of tumor progression in grades 2 and 3 astrocytomas, as well as identified GBMs that had a better response to the standard chemoradiation with temozolomide. [ABSTRACT FROM AUTHOR]

Simple Summary: The two major histological subtypes of breast cancer are ductal and lobular cancers. Histology impacts the biological behavior of breast cancer, so it is imperative to study its influence on the overall survival of breast cancer patients. The existing literature reports conflicting conclusions regarding the impact that histology might have on survival, so we aimed to study a large sample of patient data obtained from the National Cancer Database to determine if histology and several other clinical factors have an impact on the survival of early-stage breast cancer patients who have T1–T2 tumors, are clinically node-negative and have no metastatic activity. These results may help clinicians better understand the behaviors of different subtypes of breast cancer and will help them take a more tailored approach to breast cancer treatment. Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1–T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan–Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77–0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) ranks as among the top two commonly diagnosed cancers in women worldwide. Triple-negative breast cancer (TNBC) is recognized globally as the most lethal subtype of BC, with patients often building resistance to conventional chemotherapy treatments. This study assesses the relationship between taxane-based chemotherapy resistance in BC and the oncoprotein epithelial membrane protein 2 (EMP2), with an emphasis on the aggressive TNBC group. Analyses of preclinical models and human tissue samples reveal that EMP2 may not only be used to predict patient response to taxanes but also serve as a therapeutic target for resistant disease. Our findings demonstrate a correlation between elevated EMP2 expression post-chemotherapy and reduced survival outcomes and reveal that targeting EMP2 in conjunction with chemotherapy yields a synergistic reduction in TNBC tumor volume. Thus, results shed light on a novel biomarker for guiding the personalized, targeted treatment of intractable and recurrent TNBC. Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: In cancer, including head and neck cancer (HNC), certain key players in the body's inflammatory process, such as the interleukin (IL)-6 and IL-1 systems, are associated with outcomes. We studied some of these key players in a subgroup of HNC patients. From one blood sample measured at diagnosis, we determined high levels of molecules from members of the IL-6 and IL-1 families with their associated soluble cytokine receptors. High values indicated a lower survival rate. This prediction was to some extent better than the standard clinical predictors used. The results highlight potential new targets for immune treatment development. Additionally, these findings could contribute to the refinement of cancer treatment strategies, particularly in the context of emerging immune therapies. Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (−) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(−) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Regional lymph node recurrence after radical surgery for non‐small cell lung cancer (NSCLC) is an oligo‐recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular‐targeted therapy. Methods: We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022. Results: A total of 53 patients were included in this study. The median time between surgery and detection of recurrence was 1.21 years. Radiotherapy (RT) alone and chemoradiotherapy (CRT) were performed in 38 and six patients, respectively. Driver gene alterations were detected in eight patients (EGFR: 6, ROS1:1, and BRAF: 1) and programmed death‐ligand 1 (PD‐L1) expression was examined in 22 patients after 2016. Median progression‐free survival (PFS) and overall survival (OS) after lymph node recurrences were 1.32 and 4.34 years, respectively. Multiple lymph node recurrence was an independent prognostic factor for PFS, whereas driver gene alteration was the only prognostic factor for OS. There was no significant difference in the OS between patients stratified according to the initial treatment modality for lymph node recurrence. Conclusion: Our results suggest that the number of tumor recurrences may correlate with PFS, while detection of driver gene alterations could guide decision‐making for the appropriate molecular‐targeted therapy to achieve longer OS. [ABSTRACT FROM AUTHOR]

Background: Prognostic prediction for surgical treatment of gastric cancer remains valuable in clinical practice. This study aimed to develop survival models for postoperative gastric cancer patients. Methods: Eleven thousand seventy-five patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and 122 patients from the Chinese database were used for external validation. The training cohort was created to create three separate models, including Cox regression, RSF, and DeepSurv, using data from the SEER database split into training and test cohorts with a 7:3 ratio. Test cohort was used to evaluate model performance using cindex, Brier scores, calibration, and the area under the curve (AUC). The new risk stratification based on the best model will be compared with the AJCC stage on the test and Chinese cohorts using decision curve analysis (DCA), the net reclassification index (NRI), and integrated discrimination improvement (IDI). Results: It was discovered that the DeepSurv model predicted postoperative gastric cancer patients' overall survival (OS) with a c-index of 0.787; the area under the curve reached 0.781, 0.798, 0.868 at 1-, 3- and 5- years, respectively; the Brier score was below 0.25 at different time points; showing an advantage over the Cox and RSF models. The results are also validated in the China cohort. The calibration plots demonstrated good agreement between the DeepSurv model's forecast and actual results. The NRI values (test cohort: 0.399, 0.288, 0.267 for 1-, 3- and 5-year OS prediction; China cohort:0.399, 0.288 for 1- and 3-year OS prediction) and IDI (test cohort: 0.188, 0.169, 0.157 for 1-, 3- and 5-year OS prediction; China cohort: 0.189, 0.169 for 1- and 3-year OS prediction) indicated that the risk score stratification performed significantly better than the AJCC staging alone (P < 0.05). DCA showed that the risk score stratification was clinically useful and had better discriminative ability than the AJCC staging. Finally, an interactive native web-based prediction tool was constructed for the survival prediction of patients with postoperative gastric cancer. Conclusion: In this study, a high-performance prediction model for the postoperative prognosis of gastric cancer was developed using DeepSurv, which offers essential benefits for risk stratification and prognosis prediction for each patient. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients. Methods: A retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan–Meier method. Results: The cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 – 13.3 months] vs. 3.7 months [95%CI 3.4 – 4.0 months]). Conclusion: Systemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population. [ABSTRACT FROM AUTHOR]

Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed. [ABSTRACT FROM AUTHOR]

Background: Human Papillomavirus-associated oropharyngeal cancer (HPV-OPC) incidence is increasing among men in the United States. Poor dental health has previously been associated with risk of head and neck cancers, oral HPV infection, and persistence but it is not understood whether dental health is associated with outcomes. We sought to determine the association of dental health with progression free survival and overall mortality among men with an HPV-OPC. Methods: A cross sectional study of men diagnosed with HPV-OPC between 2014–2020 at Moffitt Cancer Center in Tampa, FL was conducted. Dental records were abstracted for assessment of dental fitness prior to cancer treatment. Five dental factors including number of teeth lost, pocket depth, gingival score, loss of attachment, and bone loss were individually examined. Risk factor and outcome data were collected from a patient risk questionnaire and medical record. Using item response theory, an overall dental fitness score from five dental factors was developed in which missing data were multiply imputed. Cox proportional hazards model was used to assess whether dental factors were associated with progression-free survival or overall mortality. Results: Among 206 HPV-OPC cases, median follow-up was 3.4 years (IQR: 2.4–4.4) during which 40 cases involved progression or mortality and 25 deaths occurred. Overall dentition was significantly associated with progression free survival (p = 0.04) and with overall survival (p = 0.03) though findings were not significant after adjustment for age at diagnosis, stage, and smoking history (p = 0.146 and p = 0.120, respectively). A pocket depth of 7 mm or more was associated with overall survival (HR: 5.21; 95% CI: 1.43—19.11) and this remained significant after adjustment for confounding (aHR: 4.14; 95% CI: 1.72—16.26). Conclusions: Among men diagnosed with an HPV-associated OPC in the US, worse dental health was associated with reduced progression free survival and overall survival, but not after adjustment for confounders. Further studies are needed to examine whether dental health is associated with other prognostic factors and subsequent treatment-related outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Radiotherapy (RT) plays an indispensable role in postoperative breast cancer treatment. This study aimed to assess the feasibility of preoperative RT for stage III breast cancer by comparing preoperative RT with postoperative RT in terms of overall survival (OS). Methods: Based on the information in the Surveillance, Epidemiology, and End Results database from 2000 to 2018, patients with stage III breast cancer who had undergone radical surgery and RT were divided into two groups: a preoperative RT group and a postoperative RT group. OS was calculated using Kaplan-Meier analysis. The Cox proportional hazards model was used to evaluate independent factors associated with OS. Propensity score matching (PSM) was used to balance stratification factors. Results: In total, 9,605 patients were enrolled, of whom 9,456 received postoperative RT and 149 received preoperative RT. After a median follow-up of 72 months, postoperative RT was found to be superior to preoperative RT in terms of OS (p < 0.000). Compared to the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (OS: hazard ratio [HR] = 1.653, 95% confidence interval [CI]: 1.288–2.123, p < 0.000) and multivariate analyses (OS: HR = 1.409, 95% CI: 1.096–1.810, p = 0.007). After PSM, the OS of the postoperative RT group was superior to the OS in the preoperative RT group (p = 0.041). Compared with the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (HR = 1.312, 95% CI: 1.010–1.704, p = 0.042) and multivariate analyses (HR = 1.466, 95% CI: 1.127–1.906, p = 0.004). Conclusion: Preoperative RT does not improve OS in patients with stage III breast cancer and has a worse prognosis. Preoperative RT has not changed the existing treatment paradigm in the current therapeutic context for patients with stage III breast cancer. [ABSTRACT FROM AUTHOR]

Objective To report the incidence of indeterminate pulmonary nodules (IPN) and the rate of progression of IPNs to metastasis in patients with primary bone cancers. We also aimed to evaluate clinical or radiological parameters that may identify IPNs more likely to progress to metastatic disease and their effect on overall or event-free survival in patients with primary bone sarcoma. Methods A systematic search of the electronic databases Medline, Embase, and Cochrane Library was undertaken for eligible articles on IPNs in patients with primary bone sarcomas, published in the English language from inception of the databases to 2023. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was utilized to evaluate risk of bias in included studies. Results Six studies, involving 1667 patients, were included in this systematic review. Pooled quantitative analysis found the rate of incidence of IPN to be 18.1% (302 out of 1667) and the rate of progression to metastasis to be 45.0% (136 out of 302). Nodule size (more than 5 mm diameter), number (more than or equal to 4), distribution (bilaterally distributed), incomplete calcification, and lobulated margins were associated with an increased likelihood of IPNs progressing to metastasis, however, their impact on overall or event-free survival remains unclear. Conclusion The risk of IPNs progressing to metastasis in patients with primary bone sarcoma is non-negligible. Large IPNs have a high risk to be an actual metastasis. We suggest that IPNs in these patients be followed up for a minimum of 2 years with CT imaging at 3, 6, and 12 month intervals, particularly for nodules measuring >5 mm in average diameter. Advances in knowledge This is the first systematic review on IPNs in patients with primary bone sarcomas only and proposes viable management strategies for such patients. [ABSTRACT FROM AUTHOR]

Objective: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. Data source: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. Data summary: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. Conclusion: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups. [ABSTRACT FROM AUTHOR]

Background: Molecular classification, tumor diameter, Ki67 expression, and brachytherapy administration still act as the most potent potential predictors of breast cancer recurrence and overall survival. Methods: Over the period of 23 months, we included in the study 92 invasive breast cancer (IBrC) patients initially diagnosed at the Clinical Ward of Breast Cancer and Reconstructive Surgery, Oncology Center in Bydgoszcz, Poland. The probability of disease-free survival (DFS) and overall survival (OS) in relation to potential prognostic factors for the patients were determined using a Kaplan–Meier analysis, and univariate and multivariate Cox regression analyses evaluated the predictive factors of IBrC patients. The investigation of the potential prognostic model's accuracy was analyzed using the ROC curve. Results: Patients with tumor size < 2 cm, Ki67 expression < 20%, luminal-A molecular subtype, and extra-dose brachytherapy boost administration displayed the most favorable prognosis according to breast cancer disease-free survival and overall survival. The estimated 5 year probability of DFS and OS rates in women with tumor diameter < 2 cm were 89% and 90%, respectively. In tumor diameter > 2 cm, the estimated 5 year probability of DFS was 73% and OS was 76%. Interestingly, the tumor diameter of 1.6 cm with a specificity of 60.5% and a sensitivity of 75% occurred as the best threshold point to differentiate patients with cancer recurrence from those without cancer progression. Conclusions: Our study provides essential information on the clinicopathological profile and future outcomes of early stage IBrC patients. Furthermore, the tumor diameter cut-off value of 1.6 cm discriminating between disease recurrence and those without disease progression patients represents an innovative direction for further research. [ABSTRACT FROM AUTHOR]

OBJECTIVE We investigated the outcomes of radiotherapy (RT) combined with systemic chemotherapy (CHT) including carboplatin and paclitaxel in patients with locally advanced non-small-cell lung cancer. METHODS This retrospective study included 105 patients. Treatment involved concurrent carboplatin and paclitaxel with RT administered weekly followed by two cycles of consolidation carboplatin and paclitaxel administered triweekly. RESULTS Comorbid disease was present in 46 (48.6%) patients. At least four cycles of CHT in the concurrent phase and both cycles of CHT in the consolidation phase were able to be administered to 92.3% and 45.4% of patients, respectively. The most common type of toxicity in the entire treatment protocol was hematological toxicity (34.8%). The objective response rate was 71.4%. Overall, recurrence was found in 71 (67.6%) patients. The most common type of recurrence was distant metastasis, which occurred in 47 (66.2%) patients. The median progression-free survival was 14 months. The 1, 2, and 3-year progression-free survival rates were 59%, 30%, and 26%, respectively. The median overall survival was 27 months. The 1, 2, and 3-year overall survival rates were 81%, 57%, and 34%, respectively. CONCLUSION The survival outcomes in this study closely match those reported in the literature. This is notable because our study included a higher proportion of patients with additional health conditions and fewer concurrent CHT cycles during RT compared to randomized studies. These findings prompt us to consider what the ideal number of concurrent CHT cycles should be when using modern involved-field RT techniques after accurate disease staging. [ABSTRACT FROM AUTHOR]

BACKGROUND: FAM170B-AS1 is usually expressed low in all organs except for testicular tissues. No study was performed to explore its role in breast cancer (BC). Contradictory results were reported about hsa-miR-1202 and hsa-miR-146a-5p in BC. OBJECTIVE: The present study aimed to explore the involvement of FAM170B-AS1 in BC using bioinformatics predictive tools, followed by a practical validation besides exploring the impact of hsa-miR-1202 and hsa-miR-146a-5p in BC. METHODS: This study enrolled 96 female patients with BC, 30 patients with benign breast diseases (BBD), and 25 control subjects. The expressions of circulating FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p were quantified using qRT-PCR. These ncRNAs' associations, predictive, and diagnostic roles in BC were statistically tested. The underlying miRNA/mRNA targets of FAM170B-AS1 in BC were bioinformatically predicted followed by confirmation based on the GEPIA and TCGA databases. RESULTS: The expression of FAM170B-AS1 was upregulated in sera of BC patients and hsa-miR-1202 was upregulated in sera of BBD and BC patients while that of hsa-miR-146a-5p was downregulated in BC. These FAM170B-AS1 was significantly associated with BC when compared to BBD. FAM170B-AS1 and hsa-miR-1202 were statistically associated with the BC's stage, grade, and LN metastasis. FAM170B-AS1 and hsa-miR-146a-5p gave the highest specificity and sensitivity for BC. KRAS and EGFR were predicted to be targeted by FAM170B-AS1 through interaction with hsa-miR-143-3p and hsa-miR-7-5p, respectively. Based on the TCGA database, cancer patients having mutations in FAM170B show good overall survival. CONCLUSIONS: The present study reported that for the first time, FAM170B-AS1 may be a potential risk factor, predictive, and diagnostic marker for BC. In addition, FAM170B-AS1 might be involved in BC by interacting with hsa-miR-143-3p/KRAS and hsa-miR-7-5p/EGFR through enhancement or repression that may present a new therapeutic option for BC. [ABSTRACT FROM AUTHOR]

Background: The evidence on the role of retroperitoneal lymphadenectomy is limited to less common histology subtypes of epithelial advanced ovarian cancer. Methods: This retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results Program from January 1, 2010, to December 31, 2019. Patients with stage III–IV epithelial ovarian cancer were included and divided into two groups based on whether they received retroperitoneal lymphadenectomy. The primary outcomes are overall survival (OS) and cause‐specific survival (CSS). Results: Among the 10 184 included patients, 5472 patients underwent debulking surgery with retroperitoneal lymphadenectomy, while 4712 patients only underwent debulking surgery. No differences were found in the baseline information between the two groups after propensity score matching. Retroperitoneal lymphadenectomy during debulking surgery was associated with improved 5‐year OS (43.41% vs. 37.49%, p < 0.001) and 5‐year CSS (46.43% vs. 41.79%, p < 0.001). Subgroup analysis further validate the retroperitoneal lymphadenectomy increased the 5‐year OS and CSS in patients with high‐grade serous cancer. Although the results were not validated in the less common ovarian cancer (including endometrial cancer, mucinous cancer, low‐grade serous cancer, and clear cell cancer), the tendency showed patients with the above four subtypes may benefit from the lymphadenectomy which is restricted for small sample size after propensity score matching. Conclusions: This study revealed that retroperitoneal lymphadenectomy could further improve the survival outcome during debulking surgery in patients with advanced epithelial ovarian cancer. The conclusion was affected by the histology subtypes of ovarian cancer and further studies are needed to validate the conclusion in less common ovarian cancer. [ABSTRACT FROM AUTHOR]

Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the TTN mutant group showed shorter progression-free survival (p < 0.001) and overall survival (p < 0.001) than TTN wild-type group. Additionally, we discovered that the number of TTN mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (p < 0.05). And the number of TTN mutations per sample in POLE mutant group was greater than in the POLE wild-type group (p < 0.0001). In conclusion, TTN mutation may serve as a biomarker for EEC prognosis. TTN mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique. [ABSTRACT FROM AUTHOR]

The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P =.005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P =.65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P <.001). Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach. [ABSTRACT FROM AUTHOR]

With the prevalence of malignant melanoma increasing gradually and the progressive westernization of the Asian lifestyle, it is important to analyze and follow up on the characteristics of malignant melanoma at regular intervals. We identified the characteristics of malignant melanoma by analyzing consecutive patients from a single medical center. We also examined the trend of malignant melanoma and prognostic factors in Asian patients. We investigated 200 consecutive patients with malignant melanoma in a single medical center between 2000 and 2022. Each patient's sex and age, tumor stage, site of the primary lesion, histological subtype, Breslow thickness, Clark level, and period of survival were collected from the historical medical records of the patients and analyzed. Survival analyses were performed using the Kaplan–Meier method to investigate the prognostic factors. The ratio of man-to-woman was 1:1.53; the most common site of the primary tumor was the lower extremity (60%), and acral lentiginous melanoma was the most common histological subtype (61%). Malignant melanoma commonly occurs in the lower extremities, primarily in the form of the lentiginous subtype. In situ melanomas are most prevalent regarding Breslow thickness, while Clark Level 4 is the most common type of malignant melanoma. Sex and Breslow thickness were significantly associated with the survival rate. However, others were not significant prognostic indicators for survival in this cohort. This study confirmed that the epidemiology of malignant melanoma in Asian patients was maintained without significant change. We also confirmed several significant prognostic indicators for survival. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) of patients who underwent interval cytoreductive surgery after 3–4 cycles or 6 cycles of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer patients. Methods: Out of 219 patients with advanced epithelial ovarian cancer, 123 patients received 3–4 cycles and 96 patients received 6 cycles of platinum-based NACT. Afterward, laparotomy was performed for interval cytoreductive surgery. Results: No statistically significant difference was found for DFS and OS of the patients who received 3–4 cycles and those who received 6 cycles of NACT (HR: 1.047, 95.0% CI [0.779–1.407]; p: 0.746 for DFS, and HR: 1.181, 95.0% CI [0.818–1.707]; p: 0.368 for OS). Evaluating 123 patients who received 3–4 cycles of NACT, 87 patients (70.7%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS compared to 36 patients (29.3%) with any residual tumor (HR: 1.830, 95.0% CI [1.194–2.806]; p: 0.003 for DFS, and HR: 1.946, 95.0% CI [1.166–3.250]; p: 0.009 for OS). 96 patients who received 6 courses of NACT were evaluated; 63 patients (65.6%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS than 33 patients (34.4%) with any residual tumor (HR: 1.716, 9 5.0% CI [1.092–2.697]; p: 0.010 for DFS, and HR: 1.921, 95.0% CI [1.125–3.282]; p: 0.013 for OS). Conclusion: In patients with advanced ovarian cancer, there is no significant difference in DFS and OS between 3 and 4 cycles or 6 cycles of NACT. The most important factor determining survival is whether macroscopic residual tumor tissue remains after interval cytoreductive surgery following NACT. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of textbook outcome (TO) on long‐term survival in oral cancer surgery. Subjects and Methods: In total, 386 patients with tumor resection, neck dissection (ND), and reconstruction between 2011 and 2020 were included. TO was defined as negative margin; adequate ND; no 3‐day emergency room revisit; no 30‐day readmission; and length of stay ≤22 days. Multivariate Cox regression was used to evaluate the impact of TO and 5‐year overall survival (OS). Results: The TO rate was 35%. Younger age, subsite in buccal area, Charlson Comorbidity Index Score of 0, higher body mass index, higher hemoglobin, higher albumin, and unilateral ND were associated with TO. 5‐year OS was 70.5% in overall TO patients and 49.0% in non‐TO patients (HR, 0.47; 95% CI, 0.31–0.70; p < 0.001). Non‐TO was associated with an increased mortality rate (aHR, 1.73; 95% CI, 1.14–2.63) after adjusting other factors and the result remained robust with inverse probability of treatment weighting analysis. The impact of TO on OS was more significant in age <60, advanced stage, and diagnosis year before 2018. Conclusion: Not achieving TO in oral cancer surgery was associated with worse long‐term outcome. TO could be used as a proxy for surgical quality improvement. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. Materials and Methods: This retrospective study enrolled 144 AdCC patients. RNA‐sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over‐expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate‐resistant acid phosphatase staining and resorption assays. Results: RNA‐sequencing analysis showed that genes down‐regulated in Notch‐mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1‐wild‐type AdCCs showed SPARC over‐expression, whereas 30 out of 34 (88.2%) Notch1‐mutant tumours showed low SPARC expression. SPARC over‐expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over‐expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. Conclusions: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target. [ABSTRACT FROM AUTHOR]

Simple Summary: The proximity to tumor cells is pivotal to the anti-tumor functions of CD8+ T cells, but the mechanism underlying the regulation of CD8+ T cell spatial distribution remains elusive. Here, we utilize the cellular neighborhood algorithm to identify the spatial architectures that regulate the localization and inter-cellular communication of CD8+ T cells in human pancreatic ductal adenocarcinoma. The presence of CD8+ T cells, CD4+ T cells, and other lymphocytes in the same cellular neighborhoods were identified as one type of spatial architecture that restricted the proximity of CD8+ T cells to tumor cells and heralded a poor prognosis. In such architecture, CD8+ T cells tended to aggregate around themselves and CD4+ T cells instead of approaching tumor cells. In this study, we identified a spatial architecture for the regulation of CD8+ T cells and deciphered a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner. The anti-tumor function of CD8+ T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+ T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+ T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+ T and CD4+ T cell-enriched neighborhoods enriched the majority of CD8+ T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+ T cells in this spatial architecture were significantly closer to themselves and the CD4+ T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+ T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide, with liver resection being the most effective for curative intent. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and TAC score are intricately connected with the postoperative evolution of cirrhosis. The primary objective of our study is to evaluate the predictive value of key parameters for surgical patients. The proposed predictors can better presume treatment outcomes in HCC and potentially allow an improvement in therapeutic strategy. Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child–Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C–P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C–P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004). [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is the third-most-diagnosed cancer in males and in females, and about 20% of patients diagnosed with CRC present metastatic disease; pulmonary metastasectomy in CRC patients therefore represents a frequent scenario to be managed by thoracic surgeons. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9–12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: Dexamethasone is frequently administered in brain tumor patients for symptomatic relief. However, an increasing number of publications suggests that dexamethasone may lead to worse outcome in patients with glioblastoma. Our study reviews all the published evidence and aggregates the available data in a meta-analysis. We found that dexamethasone indeed significantly reduces overall and progression-free survival in glioblastoma patients, even when accounting for clinical status. Given the potential detrimental association of dexamethasone use on overall survival, its administration to glioblastoma patients should be approached with caution. Objective: Glioblastomas are the most common primary central nervous system (CNS) tumors. Although modern management strategies have modestly improved overall survival, the prognosis remains dismal, with treatment side effects often impinging on the clinical course. Glioblastomas cause neurological dysfunction by infiltrating CNS tissue and via perifocal oedema formation. The administration of steroids such as dexamethasone is thought to alleviate symptoms by reducing oedema. However, despite its widespread use, the evidence for the administration of dexamethasone is limited and conflicting. Therefore, we aimed to review the current evidence concerning the use and outcomes of dexamethasone in patients with glioblastoma. Methods: We performed a systematic review and meta-analysis according to the PRISMA-P guidelines. We performed a restricted search using the keywords "Dexamethasone" and "Glioblastoma" on PubMed, Web of Science, Cochrane Library, and Academic Search Premier. We included studies reporting on overall survival (OS) and progression-free survival (PFS) in glioblastoma patients receiving higher or lower dexamethasone doses. The risk of bias was assessed using ROBINS-I. We performed a meta-analysis using a random effects model for OS and PFS. Results: Twenty-two retrospective studies were included. Higher doses of dexamethasone were associated with poorer OS (hazard ratio 1.62, confidence interval 1.40–1.88) and PFS (1.49, 1.23–1.81). OS remained worse even when studies corrected for clinical status (1.52, 1.38–1.67). Conclusion: Despite the widespread use of dexamethasone in glioblastoma patients, its use is correlated with worse long-term outcomes. Consequently, Dexamethasone administration should be restricted to selected symptomatic patients. Future prospective studies are crucial to confirm these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the efficacy of combining radiofrequency ablation (RFA) with stenting versus stenting alone in treating inoperable cholangiocarcinoma. Through a systematic review and meta-analysis of randomized controlled trials, it assessed the impact of the treatment on overall survival and stent patency. Although the results show no significant difference in overall survival between the groups, there was a trend toward improved survival in the subgroup treated with RFA plus plastic stents. Stent patency was significantly better in the RFA group. Adverse events were not different between the groups. These findings suggest that RFA may offer benefits in palliative care for these patients, warranting further research to explore the potential cumulative effects of RFA. Endoluminal biliary radiofrequency ablation (RFA) has been proposed as a palliative treatment for patients with malignant biliary obstruction (MBO) in order to improve stent patency and survival. However, the existing data on patients with inoperable extrahepatic cholangiocarcinoma (eCCA) are conflicting. We performed a meta-analysis of randomized trials comparing RFA plus stenting versus stenting alone in patients with inoperable eCCA. We searched for trials published in the PubMed/MEDLINE, Scopus, and Cochrane databases up to November 2023. Data extraction was conducted from published studies, and a quality assessment was carried out in accordance with the guidelines recommended by the Cochrane Collaboration. Hazard ratios (HRs) with 95% CI were estimated from the trials. The primary endpoints of interest were overall survival and stent patency. Out of 275 results, 5 randomized trials and 370 patients were included. While overall survival was not different between the groups (HR 0.62; 95% CI 0.36–1.07; p = 0.09; I2 = 80%;), the subgroup analysis of studies employing plastic stents showed a trend toward better survival in the RFA-treated group (HR 0.42; 95% CI 0.22–0.80; p = 0.009; I2 = 72%). Stent patency was improved in patients receiving RFA (HR 0.64; 95% CI 0.45–0.90; p = 0.01; I2 = 23%). Adverse events were not different between the groups (OR 1.21; 95% CI 0.69–2.12; p = 0.50; I2 = 0%). Despite the promising results, high heterogeneity and potential biases in the included studies suggest the need for further high-quality randomized trials to explore the potential cumulative effects of RFA on CCA treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from the adrenal medulla or extra-adrenal sympathetic or parasympathetic ganglia. They have the potential to secrete catecholamines, leading to e.g., hypertension. The only curative treatment modality is radical surgery. In disseminated diseases, limited data are available to guide proper medical treatment. Peptide receptor radionuclide therapy (PRRT) represents a rather novel treatment modality for these tumours. In the present nation-wide study, including all patients (n = 28) treated with PPRT in Denmark, we show a median overall survival of 72 and a median progression-free survival of 30 months with low toxicity. In conclusion, PRRT seems to represent an effective treatment option. The sequence of PRRT in treatment algorithms for pheochromocytomas and paragangliomas remains to be clarified. Introduction: Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. Method: In this study, we report retrospective data on median overall survival (OS) and median progression-free survival (PFS) for all Danish patients treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate or 90Y-Dotatate over the past 15 years. One standard treatment of PRRT consisted of 4 consecutive cycles with 8–14-week intervals. Results: We included 28 patients; 10 were diagnosed with pheochromocytoma and 18 with paraganglioma. Median age at first PRRT was 47 (IQR 15–76) years. The median follow-up time was 31 (IQR 17–37) months. Eight patients died during follow-up. Median OS was 72 months, and 5-year survival was 65% with no difference between pheochromocytoma and paraganglioma. Patients with germline mutations had better survival than patients without mutations (p = 0.041). Median PFS after the first cycle of PRRT was 30 months. For patients who previously received systemic treatment, the median PFS was 19 months, compared with 32 months for patients with no previous systemic treatment (p = 0.083). Conclusions: The median OS of around 6 years and median PFS of around 2.5 years found in this study are comparable to those reported in previous studies employing PRRT. Based on historical data, the efficacy of PRRT may be superior to 131I-MIBG therapy, and targeted therapy with sunitinib and PRRT might therefore be considered as first-line treatment in this patient group. [ABSTRACT FROM AUTHOR]

Simple Summary: The effects of immune checkpoint inhibitor (ICI) therapy on 40 melanoma patients who developed immune-related hypophysitis were examined in this study. These patients were compared to 40 matched ones who did not develop hypophysitis. The onset of hypophysitis varied depending on the type of ICI used. Symptoms commonly included fatigue, headaches, and digestive problems. Patients with hypophysitis had low T4 hormone levels regardless of ICI type. However, low T3 and TSH hormone levels were only observed in patients who developed hypophysitis from ipilimumab. A rapid drop in blood sodium levels was also noted at the time of hypophysitis diagnosis. Additionally, the number of eosinophils and lymphocytes in the blood increased consistently in hypophysitis patients. Early diagnosis of hypophysitis is important because of its potential complications. Monitoring patients for specific symptoms and blood value changes could aid in early detection, allowing for prompt intervention and management. Background: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is critical. Methods: We retrospectively analyzed 40 melanoma patients who developed hypophysitis during ICI treatment with either ipilimumab and/or anti-PD1 therapy and compared them to 40 control patients who did not develop hypophysitis during the ICI treatment, matched for age, gender, type of immunotherapy, and stage. Clinical data and blood values such as LDH, CRP, TSH, T3, T4, and absolute immune cell counts were retrieved from the medical records. Patient characteristics, laboratory values, progression-free survival, and overall survival were compared between the two groups. Results: Patients with ir-hypophysitis had a median age of 59 years, and most of them were male. Clinically, frequent symptoms were fatigue, headache, dizziness, and gastrointestinal symptoms such as nausea or abdominal pain. The onset of ir-hypophysitis differed much between ipilimumab- (median 8 weeks) and anti-PD1 (median 40 weeks)-induced hypophysitis (p < 0.001). At baseline, besides a slightly increased CRP level (p = 0.06), no differences were observed in patients who later developed hypophysitis compared to the control. After treatment started, hypophysitis patients showed a constant and significant decline in T4 levels from the start of therapy until diagnosis (p < 0.05), independent of the ICI treatment regime. However, a decline in T3 and TSH was only noted in patients with ipilimumab-induced ir-hypophysitis. Furthermore, serum sodium levels declined rapidly at the diagnosis of hypophysitis (p < 0.001). In addition, there was a constant increase in the absolute counts of eosinophils and lymphocytes from baseline in hypophysitis patients (p < 0.05). Conclusion: Ir-hypophysitis reveals different clinical pictures and onset times depending on the ICI regime used. Whereas a drop in T4 levels was indicative of developing hypophysitis independent of the ICI regime, TSH levels only declined in patients under ipilimumab-based ICI regimes. To best monitor our patients, it is important to recognize these differences. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma is the deadliest form of skin cancer and its incidence and mortality may vary by demographic factors, such as sex, age, race, and socioeconomic status. Few studies, however, have characterized disparities in survival improvement across these demographic groups in melanoma. In the present study, the authors highlight disparities in melanoma survival improvement, both in diagnosed melanoma and carcinoma in situ. While melanoma survival has improved overall, some patient subgroups have experienced a lower improvement in survival from 2004 to 2018. Background: Melanoma is the deadliest form of skin cancer and its incidence and mortality vary by sex, age, race, and socioeconomic status. Relatively few studies, however, have characterized disparities in survival improvement across these demographic groups in melanoma. Methods: Survival data from the Surveillance, Epidemiology, and End Results (SEER) database were obtained from 2004 to 2018. The compiled data were analyzed for cancer-specific survival (CSS) to produce multivariable Cox regressions that estimate sex-based survival disparities across patient demographic groups. Additionally, time-to-progression and survival analyses were conducted for a cohort of patients with carcinoma-in situ (CIS) that developed into melanoma. Results: In both female and male patients, melanoma diagnosis in more recent years (2014–2018 versus 2004–2008) was associated with an improved CSS, with females demonstrating an HR of 0.55 (95% CI: 0.49–0.60) and males demonstrating an HR of 0.49 (0.46–0.53). The trend remained consistent upon analyzing the effects of both sex and race on survival improvement for White and Hispanic males and females, but the results were not significant for Black and Asian patients. Joint sex and age analysis demonstrated significant reductions in HR across all age groups for female and male patients with a diagnosis in more recent years. Analysis of lesions progressing from CIS to melanoma (high-risk CIS) demonstrated an increased OR for males over females (OR: 1.70; 95% CI: 1.55–1.85), while survival analysis demonstrated no difference between sexes in the HR. Finally, for male patients, high-risk CIS demonstrated worse CSS compared to female patients with high-risk CIS (OR: 1.43; 95% CI: 1.15–1.79). Conclusion: Overall, melanoma survival has improved in recent years, though some patient subgroups have experienced a lower improvement in survival from 2004 to 2018. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is the most aggressive brain cancer in adults and there is great interest in accurate stratification of people based on their survival after surgery. These proposed stratification methods are inconsistent regarding the importance of tumour size. For 279 patients diagnosed with GBM in our institute, we calculated the diameter and volume of their tumours using their MRI scan prior to surgery and used statistical modelling to investigate (1) if tumour size was important in stratifying survival in these patients and (2) why other proposed models may or may not have shown the importance of tumour size. Our results showed that tumour diameter and volume were important for predicting the outcome of patients after we considered the extent of the surgery and that diameter was also important when all other clinical factors such as age, gender, genetic changes, and post-operative cancer treatment were taken into account. Published models inconsistently associate glioblastoma size with overall survival (OS). This study aimed to investigate the prognostic effect of tumour size in a large cohort of patients diagnosed with GBM and interrogate how sample size and non-linear transformations may impact on the likelihood of finding a prognostic effect. In total, 279 patients with a IDH-wildtype unifocal WHO grade 4 GBM between 2014 and 2020 from a retrospective cohort were included. Uni-/multivariable association between core volume, whole volume (CV and WV), and diameter with OS was assessed with (1) Cox proportional hazard models +/− log transformation and (2) resampling with 1,000,000 repetitions and varying sample size to identify the percentage of models, which showed a significant effect of tumour size. Models adjusted for operation type and a diameter model adjusted for all clinical variables remained significant (p = 0.03). Multivariable resampling increased the significant effects (p < 0.05) of all size variables as sample size increased. Log transformation also had a large effect on the chances of a prognostic effect of WV. For models adjusted for operation type, 19.5% of WV vs. 26.3% log-WV (n = 50) and 69.9% WV and 89.9% log-WV (n = 279) were significant. In this large well-curated cohort, multivariable modelling and resampling suggest tumour volume is prognostic at larger sample sizes and with log transformation for WV. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, hepatocellular carcinoma (HCC) is one of the most prevalent oncological diagnoses worldwide. Despite intensive research into its pathogenesis and clinical course, numerous issues remain unresolved. In the presented meta-analysis and systematic review, we investigate the potential of blood platelet levels in patients with HCC for prognostic assessment. Blood platelets may play a significant role as an easily measurable laboratory parameter in assessing the prognosis of patients with HCC. Background: Platelets (PLT) have a role in the pathogenesis, progression, and prognosis of hepatocellular carcinoma (HCC) and could represent a readily measurable laboratory parameter to enhance the comprehensive evaluation of HCC patients. Methods: The PubMed, Web of Science, and Scopus databases were searched with a focus on survival as well as patient and tumor-specific characteristics in correlation to reported PLT counts. Survival outcomes were analyzed with both common-effect and random-effects models. The hazard ratio (HR) and its 95% confidence interval (CI) from analyzed trials were incorporated. Studies that did not provide survival data but focused on platelet count correlation with HCC characteristics were reviewed. Results: In total, 26 studies, including a total of 9403 patients, met our criteria. The results showed that thrombocytopenia in HCC patients was associated with poor overall survival (common-effect HR = 1.15, 95% CI: 1.06–1.25; random-effect HR = 1.30, 95% CI: 1.05–1.63). Moreover, three studies reveal significant correlations between PLT indices and tumor characteristics such as size, foci number, and etiology of HCC development. Conclusion: Our meta-analysis confirmed that PLT count could act as a prognostic marker in HCC, especially with a PLT count cut off <100 × 103/mm3. Further prospective studies focusing on the role of PLT in clearly defined subgroups are necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial carcinoma is the most frequently diagnosed gynecologic cancer in the United States. It used to be known as a disease of only postmenopausal women. Currently, pre-menopausal women are being diagnosed with endometrial cancer at a higher rate; however, this condition is primarily a disease of post-menopausal women. Hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection followed by adjuvant therapy have been the standard treatment of endometrial carcinoma. Management of advanced endometrial carcinoma has become more advanced and individualized. The introduction of minimally invasive surgery, immunotherapy, and neoadjuvant chemotherapy as treatment approaches has resulted in improved short- to long-term outcomes. The results of this study indicate that, despite an increase in the number of individuals with advanced endometrial carcinoma, the overall survival rate has improved significantly, probably due to advancements in treatment options and patient care. Endometrial cancer has continued to see a rising incidence in the US over the years. The main aim of this study was to assess current trends in patients' characteristics and outcomes of treatment for endometrial carcinoma over 16 years. A dataset from the National Cancer Database (NCDB) for patients diagnosed with endometrial carcinoma from 2005 to 2020 was used in this retrospective, case series study. The main outcomes and measures of interest included tumor characteristics, hospitalization, treatments, mortality, and overall survival. Then, 569,817 patients who were diagnosed with endometrial carcinoma were included in this study. The mean (SD) age at diagnosis was 62.7 (11.6) years, but 66,184 patients (11.6%) were younger than 50 years, indicating that more patients are getting diagnosed at younger ages. Of the patients studied, 37,079 (6.3%) were Hispanic, 52,801 (9.3%) were non-Hispanic Black, 432,058 (75.8%) were non-Hispanic White, and 48,879 (8.6%) were other non-Hispanic. Patients in the 4th period from 2017 to 2020 were diagnosed more with stage IV (7.1% vs. 5.2% vs. 5.4% vs. 5.9%; p < 0.001) disease compared with those in the other three periods. More patients with severe comorbidities (Charlson Comorbidity Index score of three) were seen in period 4 compared to the first three periods (3.9% vs. ≤1.9%). Systemic chemotherapy use (14.1% vs. 17.7% vs. 20.4% vs. 21.1%; p < 0.001) and immunotherapy (0.01% vs. 0.01% vs. 0.2% vs. 1.1%; p < 0.001) significantly increased from period 1 to 4. The use of laparotomy decreased significantly from 42.1% in period 2 to 16.7% in period 4, while robotic surgery usage significantly increased from 41.5% in period 2 to 64.3% in period 4. The 30-day and 90-day mortality decreased from 0.6% in period 1 to 0.2% in period 4 and 1.4% in period 1 to 0.6% in period 4, respectively. Over the period studied, we found increased use of immunotherapy, chemotherapy, and minimally invasive surgery for the management of endometrial cancer. Overall, the time interval from cancer diagnosis to final surgery increased by about 6 days. The improvements observed in the outcomes examined can probably be associated with the treatment trends observed. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to pinpoint immune-related genes that show heightened activity in cancerous tissue and explore their correlation with cell infiltration in the tumor microenvironment using bioinformatics analysis. By examining gene expression from both stomach cancer and adjacent healthy tissues, we aimed to uncover their significance in cancer development and their impact on the body's immune response. We identified several genes, including FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN, which appear to be associated with poorer outcomes for stomach cancer patients. These genes also demonstrate connections to specific immune cells within cancerous tissue. Understanding the role of these genes in the immune response to cancer could facilitate the development of novel treatments and enhance prognostic capabilities for individuals with stomach cancer. Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Results: Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Conclusion: Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of robot-assisted radical cystectomy (RARC) is increasing, although its definitive superiority over open radical cystectomy (ORC) has not been proven. Randomized controlled trials (RCTs) have demonstrated RARC's superiority regarding perioperative and functional outcomes but not in terms of oncologic and survival outcomes. Composite outcomes, such as the trifecta and pentafecta, have been proposed to evaluate the quality of the surgery. The aim of our retrospective study was to assess the superiority of RARC over ORC using the PROMETRIC group's trifecta and pentafecta criteria in a propensity score-matched analysis to reduce biases. No differences were found in the success rates of trifecta and pentafecta. The overall survival was comparable between the two cohorts. We confirmed the superiority of RARC in significantly reducing the estimated blood loss and perioperative transfusion rates. Background: This study aimed to evaluate the surgical and oncological outcomes of robot-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) using trifecta and pentafecta parameters. Methods: The clinical data of 41 patients who underwent RARC between 2018 and 2022 were prospectively collected and retrospectively compared to those of 330 patients undergoing ORC using 1:1 propensity score matching. Trifecta was defined as simultaneous negative surgical margins (SMs), a lymph node (LN) yield ≥ 16, and the absence of major complications (Clavien–Dindo grade III–V) within 90 days postoperatively. Pentafecta additionally included a 12-month recurrence-free rate and a time between the transurethral resection of a bladder tumor (TURBT) and radical cystectomy (RC) ≤ 3 months. The continuous variables were compared using the Mann–Whitney U test, and the categorical variables were analyzed using the chi-squared test. Results: No statistically significant differences in trifecta and pentafecta success rates were observed between the RARC and ORC cohorts after propensity score matching. However, the RARC group exhibited significantly reduced blood loss (RARC: 317 mL vs. ORC: 525 mL, p = 0.01). Conclusions: RARC offers distinct advantages over ORC in terms of reduced blood loss, while trifecta and pentafecta success rates do not differ significantly between the two surgical approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: According to the literature, 35–71% of multiple myeloma patients have nutritional disorders. In the development of cachexia and malnutrition, the inflammatory process, accompanied by an increase in the level of proinflammatory cytokines, plays a key role. Interleukin-1β is a cytokine that plays an important role in the mechanisms responsible for muscle and adipose tissue breakdown during malnutrition and cachexia. This study aimed to investigate the association of IL1B gene polymorphism and interleukin-1β plasma concentration with the occurrence of nutritional disorders and survival in patients with multiple myeloma. The presence of the CC genotype of the IL1B gene was associated with a higher plasma concentration of interleukin-1β, a higher risk of cachexia, and poor prognosis. Determination of IL1B polymorphism may be a useful predictive marker of the risk of cachexia and prognostic factor in multiple myeloma patients. Background: Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35–71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. Methods: In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Results: Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Conclusions: Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis, a critical aspect of oncologic diseases, is intricately governed by genetic factors. This article delves into the role of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation, investigating its implications in human cervical cancer. We analyzed five RRP1B polymorphisms in 172 cervical cancer patients to understand their associations with disease characteristics and survival. Certain variations were linked to decreased tumor size, reduced metastasis risk, and improved overall survival, suggesting their potential as markers for predicting prognosis in cervical cancer. Metastasis is a key determinant of cancer progression, influenced significantly by genetic mechanisms. RRP1B, primarily a nucleolar protein, emerges as a suppressor of metastasis, forming alliances with various cellular components and modulating gene expression. This study investigates the involvement of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation in cervical cancer. Through a comprehensive analysis of 172 cervical cancer patients, we evaluated five RRP1B single nucleotide polymorphisms (SNPs) (rs2838342, rs7276633, rs2051407, rs9306160, and rs762400) for their associations with clinicopathological features and survival outcomes. Significant associations were observed between specific genetic variants and clinicopathological parameters. Notably, the A allele of rs2838342 was associated with reduced odds of advanced tumor size, worse prognosis, and, preliminarily, distant metastasis, while the T allele of rs7276633 correlated with a decreased risk of higher tumor size and worse prognosis. Additionally, the C allele of rs2051407 demonstrated protective effects against larger tumors, metastasis, and adverse prognosis. The rs9306160 C allele exhibited a protective effect against metastasis. The rs762400 G allele was significant for reduced tumor size and metastasis risk. Furthermore, the rs2838342 A allele, rs7276633 T allele, rs2051407 C allele, and rs762400 G allele were associated with improved overall survival, demonstrating their potential significance in predicting prognoses in cervical cancer. Linkage disequilibrium and haplotypes analysis enabled us to evaluate the collective effect of the analyzed SNPs, which was in line with the results of allelic models. Our findings underscore the clinical relevance of RRP1B SNPs as prognostic markers in cervical cancer, shedding light on the intricate interplay between genetic factors and disease-progression dynamics. This research provides critical insights for future investigations and underscores the importance of incorporating RRP1B SNP detection into prognostic-assessment tools for accurate prediction of disease outcomes in cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with oncogene-addicted lung cancers that have developed resistance to oral targeted therapy have limited treatment options. Several studies have shown conflicting results in this setting, but those using Bevacizumab and Paclitaxel in combination with immunotherapy (ABCP) have consistently shown activity. Spread to the brain is common, but it is not known how many patients with brain metastases are amenable to chemo-immunotherapy, and its effect in this patient group has not been reported to date. We present here our retrospective real-life experience in patients treated with ABCP. Our results in 34 patients underlined that spread to the brain occurred in 19 patients (56%), 17 of them without previous brain radiotherapy. In these 19 patients, chemo-immunotherapy triggered frequent and quick responses inside and outside the brain and showed similar outcomes to those shown in patients with smoking-related lung cancer and previously untreated brain metastases. Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32–77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4–21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Intrathecal Drug Delivery Systems (IDDS) are underused in the management of cancer-related pain despite evidence of both efficacy and survival benefit. There is currently limited evidence to indicate which patients might benefit most from IDDS. Aim: The aim of the study was to describe the baseline characteristics and survival outcomes of patients who accepted IDDS, patients who declined IDDS and patients who wished to go ahead with IDDS but whose condition deteriorated before they could do so. Design/participants: The survival data for 75 consecutive patients who had been offered intrathecal drug delivery were examined as part of a retrospective cohort study. Survival data was compared between three groups: those who accepted intrathecal drug delivery and went on to receive it (n = 41), those who accepted it but whose condition deteriorated before it commenced (n = 17) and those who declined this treatment modality (n = 17). Results: Patients who received IDDS survived significantly longer after assessment compared to those who declined IDDS (hazard ratio (HR) for the IDDS group relative to the declined group 0.29 (95% CI 0.16 to 0.53), and 0.23 (95% CI 0.12 to 0.44) after adjustment for gender and baseline functional status. In patients who accepted IDDS but who were unable to commence treatment, survival after assessment was not significantly different from those who declined the IDDS (HR for the deteriorated group relative to the declined group 1.28 (95% CI 0.65 to 2.53), and 0.80 (95% CI 0.65 to 2.53) after adjustment for gender and baseline functional status). Conclusion: In this retrospective analysis, an improvement in survival may be associated with patients who accept ongoing pain management with an implanted intrathecal drug delivery system compared to those patients who either declined intrathecal drug delivery or deteriorated before it could be commenced. [ABSTRACT FROM AUTHOR]