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Objectives: This study aimed to quantitatively evaluate the efficacy and safety of first-line systemic therapies for treating advanced hepatocellular carcinoma (aHCC). Methods: The study included clinical trials of first-line systemic therapies for aHCC since the approval of sorafenib in 2007. Hazard function models were used to describe changes in overall survival (OS) and progression-free survival (PFS) over time. Monte Carlo simulation was used to compare OS and PFS for different treatments, including sorafenib, antiangiogenic therapies (AATs) (except sorafenib), immune checkpoint inhibitor (ICI) monotherapy, AAT + targeted therapy, AAT + chemotherapy, AAT + ICIs, and ICIs + ICIs. Furthermore, the objective response rate (ORR) and incidence of grade ≥ 3 adverse events were analyzed. Results: Fifty studies comprising 12,918 participants were included. AAT + ICIs demonstrated a significant benefit in median OS (mOS), median PFS (mPFS), and ORR (20.5 [95% CI 17.5–24] months, 7.5 [95% CI 6.5–8.8] months, and 24% [95% CI 17%–30%], respectively). ICIs + ICIs and ICI monotherapy ranked second and third, respectively with an mOS of 20 (95% CI 18.5–21.5) months and 14.5 (95% CI 13.5–16) months, respectively. The OS, PFS, and ORR of patients treated with AAT, AAT + targeted therapy, and AAT + chemotherapy were similar to those of patients treated with sorafenib. A higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage C had a shorter OS. OS was associated with publication year, and PFS was associated with the proportion of patients with BCLC stage C. The incidence of grade ≥ 3 adverse events in the ICIs and ICIs + ICIs treatment groups was low. Conclusions: The study results provide valuable information from which to base rational clinical drug use and serves as a reliable external control for evaluating new treatments for aHCC. [ABSTRACT FROM AUTHOR]

Background: Upper urinary tract urothelial carcinoma (UTUC) is an aggressive malignant tumor, with surgical intervention as the primary treatment. This study evaluates the prognostic effects of laparoscopic radical nephroureterectomy (LNU), open radical nephroureterectomy (ONU), robot-assisted laparoscopic radical nephroureterectomy (Robotic LNU), and hand-assisted laparoscopic radical nephroureterectomy (Hand LNU) in the treatment of UTUC through a network meta-analysis. Methods: A systematic search of the PubMed, EMBASE, Cochrane, and Web of Science databases was conducted for randomized controlled trials meeting the criteria from database inception until April 2024. Bayesian network meta-analysis was performed to compare the effects of each surgical method on overall survival (OS), cancer-specific survival (CSS), and overall recurrence rate (ORE). Results: Seventeen randomized controlled trials were included in this network meta-analysis. The results indicated that LNU significantly improved CSS compared to ONU [HR = 0.81, 95%CI= (0.7, 0.93)], while there were no significant differences between Hand LNU and Robotic LNU compared to ONU. Among minimally invasive surgeries, Hand LNU significantly shortened CSS compared to LNU [HR = 1.49, 95%CI=(1.1, 2.03)]. Regarding ORE, no significant differences were found between LNU, Hand LNU, and Robotic LNU compared to ONU, although LNU had a higher recurrence rate than Robotic LNU [HR = 1.705, 95%CI=(1.007, 3.001)]. For OS, both LNU [HR = 0.84, 95%CI=(0.75, 0.94)] and Robotic LNU [HR = 0.81, 95%CI=(0.68, 0.96)] were significantly better than ONU, whereas Hand LNU significantly shortened OS compared to LNU and Robotic LNU. There were no significant differences in progression-free survival (PFS) between LNU and ONU. The cumulative efficacy ranking indicated that Robotic LNU ranked highest for ORE and OS, while LNU ranked first for CSS. Conclusion: Robotic LNU demonstrates advantages in prolonging OS and reducing recurrence rates, while LNU excels in improving CSS. Although Hand LNU shows suboptimal effects in some comparisons, it remains valuable, and surgical choices should be based on individualized needs. [ABSTRACT FROM AUTHOR]

Objective: This study aims to elucidate the relationship between postoperative monocyte count and gastric cancer prognosis. We introduce a standardized monocyte ratio (MMR) to predict postoperative survival rates in gastric cancer patients effectively. Methods: A test cohort was created to develop and evaluate the pre- and postoperative MMR as a mortality predictor in gastric cancer patients. We used Kaplan-Meier survival analysis, complemented by univariate and multivariate analyses. The predictive utility of MMR was assessed via time-dependent ROC curves and decision-curve analysis. Results: The sample distributions in both cohorts were similar. The MMR showed high predictive value and significant clinical benefits in 1, 3, and 5-year overall survival (OS) assessments. These findings enhance understanding of prognosis and aid in developing more precise treatment plans. Conclusions: MMR is confirmed as an independent factor in predicting overall survival in gastric cancer patients, proving to be a reliable and cost-effective prognostic indicator. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is a common comorbidity in patients with head and neck cancer (HNC), significantly impacting survival rates. The Geriatric Nutritional Risk Index (GNRI) and the Controlling Nutritional Status (CONUT) score are tools used to assess the nutritional status, yet their prognostic value in HNC remains to be fully established. Methods: We performed a systematic review and meta-analysis, adhering to PRISMA guidelines, to evaluate the prognostic significance of GNRI and CONUT on survival outcomes in patients with HNC. Relevant studies up to March 2024 were identified through comprehensive searches of PubMed, EMBASE, and Cochrane CENTRAL databases. The quality of each included study was assessed using the Newcastle-Ottawa Scale. Results: Seventeen studies were included, encompassing a total of 3,816 patients with HNC. Our findings reveal that a lower GNRI is consistently associated with poor overall survival (OS, adjusted hazard ratio [aHR]: 3.9, 95% confidence interval [CI]: 2.47–6.14) and progression-free survival (PFS, aHR: 1.76, 95% CI: 1.41–2.21), demonstrating its utility as a prognostic indicator. However, CONUT scores revealed no significant differences in OS (aHR: 1.65, 95% CI: 0.94–2.91) or PFS (aHR: 1.43, 95% CI: 0.68–3.02). Conclusion: GNRI appears to be a reliable prognostic tool for predicting poorer survival outcomes in HNC patients, underscoring the importance of nutritional assessments in this population. Further research is needed to clarify the prognostic value of the CONUT score, which exhibited less consistent results. [ABSTRACT FROM AUTHOR]

Ferroptosis, a form of regulated cell death, is characterized by iron‐dependent lipid peroxidation. It is recognized increasingly for its pivotal role in both cancer development and the response to cancer treatments. We assessed associations between 370,027 single‐nucleotide polymorphisms (SNPs) within 467 ferroptosis‐related genes and survival of non‐small cell lung cancer (NSCLC) patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial served as our discovery dataset, while the Harvard Lung Cancer Susceptibility Study used as our validation dataset. For SNPs that remained statistically significantly associated with overall survival (OS) in both datasets, we employed a multivariable stepwise Cox proportional hazards regression model with the PLCO dataset. Ultimately, two independent SNPs, PARK7 rs225120 C>T and DDR2 rs881127 T>C, were identified with adjusted hazard ratios of 1.32 (95% confidence interval = 1.15–1.52, p =.0001) and 1.34 (95% confidence interval = 1.09–1.64, p =.006) for OS, respectively. We aggregated these two SNPs into a genetic score reflecting the number of unfavorable genotypes (NUG) in further multivariable analysis, revealing a noteworthy association between increased NUG and diminished OS (ptrend =.001). Additionally, an expression quantitative trait loci analysis indicated that PARK7 rs225120T genotypes were significantly associated with higher PARK7 mRNA expression levels in both whole blood and normal lung tissue. Conversely, DDR2 rs881127C genotypes were significantly associated with lower DDR2 mRNA expression levels in normal lung tissue. Our findings suggest that genetic variants in the ferroptosis‐related genes PARK7 and DDR2 are associated with NSCLC survival, potentially through their influence on gene expression levels. [ABSTRACT FROM AUTHOR]

Background: The prognostic role of the fibrosis-4 (FIB-4) index relative to intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study sought to characterize the impact of the FIB-4 index and tumor burden score (TBS) on recurrence and overall survival (OS). Methods: ICC patients undergoing hepatectomy (2000–2020) were identified using a multi-institutional database. Patients were categorized as low (low TBS/low FIB-4 index), intermediate (low TBS/high FIB-4 index or high TBS/low FIB-4 index), and high (high TBS/high FIB-4 index). Results: Among 1168 patients in different TBS and FIB-4 index cohorts, 3-year recurrence varied considerably. For instance, among the patients with low TBS, individuals with a high FIB-4 index had a greater risk of recurrence than patients with a low FIB-4 index (59.9 vs. 47.7%; P = 0.01). Among patients with a high TBS, individuals with a high versus a low FIB-4 index had a higher incidence of recurrence (76.8 vs. 69.0%; P = 0.04). A similar pattern was observed among patients with both a low FIB-4 index (low [47.7%] vs. high [69.0%] TBS) and a high FIB-4 index (low [59.9%] vs. high [76.8%] TBS; both P < 0.001). Patients with a high [27.5%] versus a low [48.8%] TBS; P < 0.001) and patients with a high [34.2%] versus a low [43.5%] FIB-4 index; P = 0.01) had a worse OS. The multivariable analysis demonstrated an increasing risk of recurrence in the intermediate-index (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.20–2.16; P = 0.001) and high-index (HR, 2.13; 95% CI 1.45–3.13; P < 0.001) groups versus the low-index group. Conclusions: Both tumor-related and non-tumorous characteristics should be used to predict risk of recurrence and survival more accurately among patients with ICC following hepatic resection. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer worldwide and immune checkpoint inhibitors have shown favorable therapeutic effects in recurrent or metastatic or locally advanced head and neck squamous cell carcinoma (R/M/LA HNSCC). However, the effects of immunotherapy in HNSCC are still inconsistent because of complicating factors. This meta-analysis tries to provide a more precise assessment of the efficacy and safety of this integrated approach in HNSCC. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs). A total of 8 out of 2445 articles were analyzed, including 5067 HNSCC patients, including 823 and 4244 patients with LA HNSCC and R/M HNSCC. Results: The combined data revealed that immunotherapy has an apparent difference in OS (HR 0.86 95% CI 0.77-0.98) compared with standard of care (Soc, like fluoropyrimidine, methotrexate, docetaxel, or cetuximab) but was equal with the other treatment in PFS (HR 1.08, 95% CI 0.85-1.37). Furthermore, the occurrence of grade 3 or higher adverse events related to the drugs was lower than systematic therapy (OR 0.35, 95% CI 0.17-0.73). Conclusions: The study has provided compelling evidence that immunotherapy is a significant benefit in OS for HNSCC patients, either R/M HNSCC or LA HNSCC, immunochemotherapy may benefit more for these patients, but double-agent immunotherapy showed no more benefit for R/M HNSCC patients. Systematic Review Registration: https://www.crd.york.ac.uk/ , identifier CRD42023471570. [ABSTRACT FROM AUTHOR]

Background: Metabolic reprogramming is increasingly recognized as a crucial factor influencing the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). Despite this, the potential association of specific metabolic characteristics and PDAC remains ambiguous due to the variability introduced by individual patient differences. In this study, we aimed to find out metabolic pathways that may be associated with the overall survival (OS) of PDAC patients. Methods: We utilized Mendelian randomization (MR) to assess the associations between 1400 metabolites and metabolite ratios and PDAC. We performed functional annotation and pathway enrichment analysis on both significant metabolites and the shared proteins corresponding to the significant metabolite ratios. Additionally, we analyzed peripheral blood metabolites from 32 PDAC patients to correlate metabolites with clinicopathological features and OS. Functional enrichment analysis was also conducted on the significant metabolites. Results: Our MR analysis revealed 55 metabolites/metabolite ratios associated with PDAC. Among the top 20 enriched metabolic pathways involving proteins related to significant metabolite ratios, seven were associated with amino acid metabolism, three with carbohydrate metabolism, and two with lipid metabolism. Serum metabolomics of PDAC patients highlighted significant upregulation in pathways related to primary bile acid biosynthesis, as well as taurine and hypotaurine metabolism, which correlated negatively with OS. Conversely, pathways involved in arginine biosynthesis, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis were notably downregulated and positively associated with OS. Both upregulated and downregulated differential metabolites were notably enriched in the pyrimidine metabolism pathway, which was linked to poorer OS. These associations were corroborated by MR analysis. Conclusion: The study provides valuable insights into the metabolic characteristics associated with PDAC, offering a reference point for improving diagnosis and treatment for PDAC. [ABSTRACT FROM AUTHOR]

Melanoma poses significant challenges due to its resistance to conventional therapies and increasing incidence rates. Stage III melanoma, characterised by regional lymph node involvement, has a high risk of recurrence despite surgical resection. Adjuvant immunotherapy, particularly using the PD-1 inhibitors pembrolizumab and nivolumab, has shown promising results in improving recurrence-free survival (RFS) and overall survival (OS) in Stage III melanoma patients. This retrospective analysis examined the effects of adjuvant pembrolizumab or nivolumab on patients with Stage III melanoma treated in a tertiary oncology centre. Of the 110 patients, 95 received pembrolizumab and 15 received nivolumab. The pembrolizumab completion rate was 62.1%, with 31.2% discontinuing due to disease progression or adverse effects. The nivolumab completion rate was lower at 40%, with 60% discontinuing due to toxicity or disease progression. Grade 3 or higher toxicities were observed in 17% of pembrolizumab and 53.3% of nivolumab patients. Disease progression occurred in 27.4% of pembrolizumab and 26.7% of nivolumab patients. Pembrolizumab showed a 12-month RFS of 78.9% and 24-month RFS of 77.6%, with an OS of 97.9% at 12 months. Nivolumab exhibited a 12-month RFS of 86.7% and 24-month RFS of 80%. RFS rates varied by disease stage and mutation status. Adjuvant pembrolizumab and nivolumab both demonstrate efficacy in improving RFS and OS in Stage III melanoma patients. Pembrolizumab has higher completion rates and fewer toxicities compared to nivolumab. Further studies are warranted to explore long-term outcomes and optimise treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer, which is resistant to platinum-based chemotherapy, has limited therapeutic options, and there is uncertainty over the role of surgery to remove all visible tumour cells (cytoreductive surgery), and its survival benefits. We performed a systematic review to evaluate the oncological benefit of this surgery in patients with platinum-resistant ovarian cancer and the associated surgical morbidity and mortality. Although evidence is limited, surgery appears to prolong survival in these patients, particularly with isolated recurrences and where there has been a full resection of all visible tumour. However, surgery is associated with substantial risks and limited benefits when all visible tumours cannot be removed. There is a need for prospective clinical trials in these patients. Background/Objective: Platinum-resistant ovarian cancer (PROC) has limited therapeutic options, and the role of cytoreductive surgery (CRS) in improving survival outcomes remains uncertain. We performed a systematic review to evaluate the oncological benefit of CRS on PROC patients and the associated surgical morbidity and mortality. Methods: We followed a prospective protocol according to PRISMA guidelines. We searched PubMed, Medline, and Embase till October 2024. We used a "Population Intervention Comparator Outcomes (PICO)" framework. Our population included women with epithelial PROC who underwent CRS with/without chemotherapy. Our outcomes included overall survival (OS), progression-free-survival (PFS), post-operative morbidity and mortality and Quality of Life. Results: Our search yielded 6590 citations; six studies (N = 155 patients) were included. There is limited evidence available on the role of CRS in PROC, with notable variation in reported outcomes and outcomes' measures; therefore, we were unable to perform quantitative synthesis. CRS demonstrated survival benefits in well-selected PROC patients, particularly those with limited, isolated recurrences, low tumour burden, and good performance status. Complete resection (R0) was associated with significantly longer OS/PFS compared to those who had suboptimal surgeries (R1/R2). Conclusions: CRS seems to extend survival in carefully selected PROC patients, especially those with limited disease spread and favourable surgical profiles. Nevertheless, CRS carries substantial surgical risks, and its benefits appear contingent upon achieving R0. Further prospective trials with standardised patient selection criteria are needed to define CRS's role in PROC. At present, CRS in PROC should be considered within a multidisciplinary approach in specialised gynaecological oncology centres, with the careful assessment of patient-specific risk factors and potential for R0 resection. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) play crucial roles in the treatment of various cancers and improve overall survival (OS) and progression-free survival (PFS). However, resistance is a major problem that limits the prognosis of ICI-based therapy. Determining inflammatory markers may ameliorate the benefits of ICI-based therapies. Peripheral blood cells and biochemical markers are big candidates as inflammatory markers. Therefore, this study aimed to evaluate and compare the prognostic value of blood-based inflammatory markers in ICI-based therapy. Background: Although immune checkpoint inhibitors (ICIs) have significantly improved cancer treatment, a substantial proportion of patients do not benefit from these therapies, revealing the crucial need to identify reliable biomarkers. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune inflammation value (PIV), systemic inflammation response index (SIRI), lactate dehydrogenase (LDH), and C-reactive protein (CRP), may provide insights into treatment outcomes. Objectives: This study aimed to evaluate the prognostic value of multiple inflammatory markers in patients with cancer receiving ICI-based therapies. Methods: A retrospective analysis was performed on 226 patients treated with ICI-based therapies at a single center between 2012 and 2023. The inflammatory markers NLR, PIV, SII, SIRI, LDH, CRP, and albumin were assessed. Cut-off values were determined using maximally selected rank statistics, and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method and Cox regression analysis. Results: High NLR, PIV, SII, SIRI, LDH, and CRP, as well as low albumin levels, were associated with worse OS and PFS (p < 0.001). In the multivariate analysis, high CRP, LDH, NLR, PIV, and SII independently predicted worse OS. Conclusions: Our findings confirm the prognostic utility of several inflammatory biomarkers in patients with cancer receiving ICIs, highlighting their potential for treatment stratification. Further studies are necessary to standardize cut-off values and validate these findings across broader, more diverse populations. [ABSTRACT FROM AUTHOR]

Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression‐free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real‐world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18‐months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real‐world study recapitulate results from clinical trials including meta‐analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer (BC) is a heterogeneous disease, traditionally classified by hormone receptor and HER2 (human epidermal growth factor receptor 2) status. HER2-low, characterized by low HER2 expression without gene amplification, recently gained attention. While new therapies are promising, its clinical significance remains unclear. We analysed 241,510 BC patients diagnosed between 2000 and 2020 in Germany using data from the German Cancer Registry Group. HER2 status was determined using immunohistochemistry and fluorescence in situ hybridization results, and patients were classified as HER2-positive, HER2-low or HER2-zero. Clinical features, chemosensitivity and long-term outcomes - metastasis-free survival (MFS), recurrence-free survival (RFS), and overall survival (OS) - were analysed using Cox models. HER2-low comprised 42% of female and 47% of male patients, predominantly hormone receptor positive. Metastatic patterns in HER2-low and HER2-zero were similar but differed from HER2-positive, which showed more liver metastasis and multiple metastatic sites. HER2-positive showed worse MFS, RFS, and OS than HER2-zero and HER2-low subtypes. Pathological complete response (pCR) rates after neoadjuvant chemotherapy were highest in HER2-positive. HER2-low has higher hormone receptor positivity, distinguishing it from HER2-zero. While metastatic behaviour, treatment and long-term response in HER2-low were comparable to HER2-zero, the hormone receptor status seems to play a critical role in these outcomes.

Abstract The liver stands out as one of the most frequent sites for distant metastasis in breast cancer cases. However, effective risk stratification tools for patients with breast cancer liver metastases (BCLM) are still lacking. We identified BCLM patients from the SEER database spanning from 2010 to 2016. After meticulously filtering out cases with incomplete data, a total of 3179 patients were enrolled and randomly divided into training and validation cohorts at a ratio of 2:1. Leveraging comprehensive patient data, we constructed a nomogram through rigorous evaluation of a Cox regression model. Validation of the nomogram was conducted using a range of statistical measures, including the concordance index (C-index), calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA). Both univariable and multivariable analyses revealed significant associations between OS and CSS in BCLM patients and 14 variables, including age, race, and tumor stage, among others. Utilizing these pertinent variables, we formulated nomograms for OS and CSS prediction. Subsequent validation involved rigorous assessment using time-dependent ROC curves, decision curve analysis, C-index evaluations, and calibration curves. Our web-based dynamic nomogram represents a valuable tool for efficiently analyzing the clinical profiles of BCLM patients, thereby aiding in informed clinical decision-making processes.

The liver stands out as one of the most frequent sites for distant metastasis in breast cancer cases. However, effective risk stratification tools for patients with breast cancer liver metastases (BCLM) are still lacking. We identified BCLM patients from the SEER database spanning from 2010 to 2016. After meticulously filtering out cases with incomplete data, a total of 3179 patients were enrolled and randomly divided into training and validation cohorts at a ratio of 2:1. Leveraging comprehensive patient data, we constructed a nomogram through rigorous evaluation of a Cox regression model. Validation of the nomogram was conducted using a range of statistical measures, including the concordance index (C-index), calibration curves, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA). Both univariable and multivariable analyses revealed significant associations between OS and CSS in BCLM patients and 14 variables, including age, race, and tumor stage, among others. Utilizing these pertinent variables, we formulated nomograms for OS and CSS prediction. Subsequent validation involved rigorous assessment using time-dependent ROC curves, decision curve analysis, C-index evaluations, and calibration curves. Our web-based dynamic nomogram represents a valuable tool for efficiently analyzing the clinical profiles of BCLM patients, thereby aiding in informed clinical decision-making processes. [ABSTRACT FROM AUTHOR]

Purpose: Stage III colorectal cancer (CRC) is typically treated with surgery; however, it has a high recurrence rate and inconsistent benefits from postoperative chemotherapy. Inflammatory markers like the neutrophil-to-lymphocyte ratio (NLR) have shown prognostic value in various cancers. However, the prognostic significance of NLR measured before and after CRC surgery is not clear. This study aims to clarify the prognostic value of the combination of pre- and post-surgery NLR in stage III CRC patients. Methods: Patients with stage III CRC treated between 2001 and 2022 were retrospectively analyzed using data from the Chang Gung Medical Research Database. Patients were categorized into 4 groups based on their pre- and post-operative NLR levels. Kaplan–Meier survival analysis and Cox proportional hazard models were used to assess the associations between NLR levels and overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). Results: Data from 2,742 patients, median age of 62 years and 54% male, were analyzed. After adjustment, patients in Group IV, with high NLR values both before and after surgery, had greater risks of worse DFS (adjusted hazard ratio [aHR] = 1.30, 95% confidence interval [CI]: 1.13–1.50), OS (aHR = 1.36, 95% CI: 1.14–1.63), and CSS (aHR = 1.27, 95% CI: 1.04–1.55) compared to Group I. Conclusions: High NLR levels before and after surgery is a strong predictor of poor outcomes in stage III CRC patients. The findings suggest that monitoring NLR at both time points can be a valuable prognostic tool, guiding postoperative care and treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Retroperitoneal liposarcomas(RPL) are rare malignant tumors, accounting for approximately 15% of soft tissue sarcomas and 0.07–0.2% of all cancers. The annual incidence is 0.5 to 1 per 100,000 individuals. Surgical resection is the only curative option, but recurrence rates are high, and the role of neoadjuvant radiotherapy(NRT) remains uncertain. This study aimed to assess the impact of preoperative NRT on overall survival(OS) and recurrence-free survival(RFS) in RPL patients undergoing compartmental resection, while identifying prognostic factors. A retrospective monocentric review of 94 patients with confirmed RPL treated between 2008 and 2022 was conducted. Forty-six patients received NRT, while 48 underwent surgery alone. Data on preoperative, intraoperative, and postoperative variables, including complications, recurrence, and survival, were analyzed. Kaplan-Meier analysis evaluated OS and RFS, and multivariate Cox regression identified independent prognostic factors. With a median follow-up of 46.5 months, OS did not significantly differ between the NRT and surgery-only groups (HR = 0.8; 95% CI [0.4–1.54], p = 0.48). However, RFS was significantly improved in the NRT group (HR = 0.41; 95% CI [0.21–0.83], p = 0.001), particularly in patients with dedifferentiated RPL (HR = 0.38; 95% CI [0.18–0.83], p = 0.015). Tumor rupture (HR = 5.5; p < 0.001) was a strong risk factor for recurrence, while NRT was a protective factor (HR = 0.3; p = 0.002). NRT did not improve OS but significantly enhanced RFS, particularly in dedifferentiated RPL cases. These results warrant further prospective studies to better define NRT's role in RPL management. [ABSTRACT FROM AUTHOR]

Objective: We aimed to develop and validate a nomogram based on MRI radiomics to predict overall survival (OS) for patients with de novo oligometastatic prostate cancer (PCa). Methods: A total of 165 patients with de novo oligometastatic PCa were included in the study (training cohort, n = 115; validating cohort, n = 50). Among them, MRI scans were conducted and T2‐weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences were collected for radiomics features along with their clinicopathological features. Radiological features were extracted from T2WI and ADC sequences for prostate tumors. Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) combined with 10‐fold cross‐validation were used to select the optimal features on each sequence. Then, a weighted radiomics score (Rad‐score) was generated and independent risk factors were obtained from univariate and multivariate Cox regressions to build the nomogram. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration, and decision curve analysis (DCA). Results: Eastern Cooperative Oncology Group (ECOG) score, absolute neutrophil count (ANC) and Rad‐score were included in the nomogram as independent risk factors for OS in de novo oligometastatic PCa patients. We found that the areas under the curves (AUCs) in the training cohort were 0.734, 0.851, and 0.773 for predicting OS at 1, 2, and 3 years, respectively. In the validating cohort, the AUCs were 0.703, 0.799, and 0.833 for predicting OS at 1, 2, and 3 years, respectively. Furthermore, the clinical relevance of the predictive nomogram was confirmed through the analysis of DCA and calibration curve analysis. Conclusion: The MRI‐based nomogram incorporating Rad‐score and clinical data was developed to guide the OS assessment of oligometastatic PCa. This helps in understanding the prognosis and improves the shared decision‐making process. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a prevalent form of head and neck cancer, particularly in specific regions with a higher incidence. The optimal treatment strategy for locally advanced NPC (stage III and IVA, LA-NPC) involves various combinations of induction chemotherapy (IC), concurrent chemoradiotherapy (CCRT), and adjuvant chemotherapy (AC), each with distinct advantages. This one institutional study aims to retrospectively analysis the efficacy and clinical outcomes of IC with CCRT (IC+CCRT), CCRT with AC (CCRT+AC), and the comprehensive approach of IC followed by CCRT and subsequently AC (IC+CCRT+AC) in the management of LA-NPC. Materials and methods: A total of 352 LA-NPC patients were included: 173 accepted IC+CCRT, 60 received CCRT+AC, and 119 underwent IC+CCRT+AC. The primary endpoints including overall survival (OS) and progression-free survival (PFS), were assessed using the Kaplan-Meier method and log-rank test. Results: The median follow-up was 61.2 months (1-216 months). There was no significant difference in 5-year OS and PFS between IC group and no IC group, extending the observation time to 90 months, the OS and PFS were significantly better in IC group than no IC group (OS: 76% vs. 70%,P<0.05; PFS: 76% vs. 71%, P<0.05). Patients with 1, 2, or 3 cycles of IC had higher 5-year OS and PFS than those with more than 3 cycles (1-4 cycles IC OS: 89% vs. 87% vs. 88% vs. 79%, P<0.05; 1-4 cycles IC PFS: 87% vs. 85% vs. 85% vs. 70%, P<0.05). NP regimen demonstrated higher OS and PFS than TP, PF, and TPF regimens (OS: 95% vs. 82% vs. 85% vs. 71%, P<0.05; PFS: 93% vs. 83% vs. 81% vs. 80%, P<0.05). The 5-year OS and PFS were significantly better in AC group than no AC group (OS: 82% vs. 72%, P<0.05; PFS: 81% vs. 69%, P<0.05). In the AC group, there was no differential effect of chemotherapy cycles and chemotherapy regimens on patients' OS and PFS. In the ThNh group, patients receiving IC+CCRT+AC had higher OS and PFS compared to those receiving IC+CCRT, with no significant difference in the rest (OS: 85% VS 66% P<0.05; PFS: 78% VS 62%, P<0.05). Conclusion: CCRT combined with IC or AC could benefit LA-NPC patients. The IC+CCRT +AC regimen was most beneficial for NPC patients with later T and N stages. [ABSTRACT FROM AUTHOR]

To investigate the prognostic factors of recurrent meningioma patients who underwent reoperation, so as to make relevant recommendations for the treatment. A retrospective analysis was performed on 73 patients with recurrent meningioma. Patients' clinical data were obtained from their medical records. Progression-free Survival (PFS) was defined as the interval from the date of surgery to the date of tumor recurrence, or to the date of the last imaging review. Overall survival (OS) was defined as the time from the date of surgery to death from any cause, or to the date of the last follow-up. The multivariate COX regression showed that dural attachment length (HR = 1.238, 95%CI1.011–1.516, P = 0.039) and WHO grade (HR = 2.184, 95%CI1.135–4.203, P = 0.019) were independent risk factors for tumor progression. The factors associated with survival in multivariate regression analysis were preoperative Karnofsky Performance Scale (KPS) (HR = 0.951, 95%CI0.923–0.979, P = 0.001), dural attachment length (HR = 1.520, 95%CI1.124–2.057, P = 0.007) and WHO grade (HR = 4.829, 95%CI1.891–12.331, P = 0.001). The dural attachment length (OR = 1.843, 95%CI1.236–2.748, P = 0.003) was the only risk factor associated with postoperative pulmonary infection. No correlation was observed between Simpson's grade and either PFS or OS. The dural attachment length is closely related to the prognosis of recurrent meningioma, which should be given importance during the perioperative assessment. [ABSTRACT FROM AUTHOR]

Objective To investigate the influencing factors of immune-related thyroid dysfunction (irTD) treated with programmed death-1(PD-1)/programmed death ligand-1(PD-L1) inhibitors and their impact on overall survival (OS) of cancer. Methods We enrolled 211 cancer patients treated with PD-1/PD-L1 inhibitors. Clinical differences between irTD groups were compared, and subgroup analysis was performed. Multifactor Logistic regression analysis was used to identify influencing factors of irTD, while survival analysis was used to explore the relationship between the occurrence of irTD and OS, and the log-rank test was used for comparison between groups. The multi-model COX regression analysis was used to evaluate the impact of irTD on OS. Results The incidence rate of irTD was 26. 1％, with 13. 3％, 10. 0％and 2. 8％, respectively for grade 1, grade 2, and grades 3-4, and the median time of occurrence was at week 9(IQR:5-25 weeks). Significant differences were observed between the irTD and non-irTD groups in terms of gender, smoking history, targeted therapy history, and baseline thyroid antibody status (P＜0. 05). In irTD patients, thyroglobulin antibody (TGAb) levels began to increase from week 3, remained above the baseline from week 6 to week 30, and then gradually declined to the baseline level after week 30. The change in thyroid microsomal antibody (TMAb) levels was less pronounced than that of TGAb. Subgroup analysis showed that patients with hyperthyroidism were younger at the time of initial immunotherapy than those with hypothyroidism (P＜0. 05) and had lower baseline TSH levels (P＜0. 05). Multifactor Logistic regression analysis revealed that patients with positive baseline thyroid antibodies had a 4. 595-fold higher risk of developing irTD compared to those with negative antibodies (95％CI:2. 286-9. 239, P＜0. 001). Survival analysis revealed that patients with irTD had a longer OS and the multi-model COX regression analysis revealed that after adjusting for factors such as age, gender, chemotherapy, tumor type and tumor metastasis status, patients with irTD had a significantly longer OS (HR=0. 228, 95％CI:0. 079-0. 656, P=0. 006). Conclusion The severity of irTD was predominantly grades 1-2, with grades 3-4 being rare. Positive baseline thyroid antibodies were an independent risk factor for the development of irTD. Patients who develop irTD have a longer OS, which may be due to their stronger immune response. [ABSTRACT FROM AUTHOR]

Background: Serum neuron-specific enolase (NSE) had been associated with survival of several cancers. However, its prognostic significance for colorectal cancer (CRC) has not been effectively discussed. We aimed to investigate the relationship between baseline serum NSE and the overall survival (OS) of colorectal adenocarcinoma (CRAD) patients. Methods: A retrospective study had been conducted by including 564 histopathology confirmed CRAD patients between January 2013 and December 2018 from Yunnan Provincial Cancer hospital, China. Cox proportional hazards model was used to estimate the crude and adjusted associations between serum NSE measured at diagnosis and the OS of the patients. Restricted cubic spline (RCS) was further applied to delineate dose-response trend of the NSE-OS association. Results: After controlling for possible confounding factors, baseline serum NSE was significantly associated with OS in CRAD: when dichotomizing by the median, patients with higher baseline serum NSE (NSE >= 12.93 ng/mL) were observed a worse prognosis (hazard ratio, HR: 1.82, 95% CI [1.30–2.55], p < 0.01). Stratified analysis by tumor stage revealed a stronger NSE-OS association in advanced CRAD patients. RCS disclosed a prominent dose-response relationship in NSE-OS association for all CRAD patients: along with the increase of baseline serum NSE, the adjusted HR of CRAD patients increased gradually. This dose-response trend is also evident in advanced stage CRAD patients, but not in early stage CRAD patients. Conclusions: Serum NSE measured at diagnosis might be a useful prognostic indicator for CRAD, especially for advanced stage patients. [ABSTRACT FROM AUTHOR]

Background: Head and neck carcinosarcoma (HNCS) is a rare and highly aggressive malignancy with limited research, resulting in an incomplete understanding of disease progression and a lack of reliable prognostic tools. This study aimed to retrospectively analyze the clinical characteristics and outcomes of HNCS patients using data from the Surveillance, Epidemiology, and End Results (SEER) database and to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS). Methods: Patients diagnosed with HNCS from 1975 to 2020 were identified in the SEER database. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic indicators, with the optimal model selected using the minimal Akaike Information Criterion (AIC). The identified prognostic factors were incorporated into nomograms to predict OS and CSS. Model performance was assessed using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Survival curves were generated using Kaplan–Meier analysis and compared via the log-rank test. Results: A total of 152 HNCS patients were included, with 108 assigned to the training cohort and 44 to the validation cohort in a 7:3 ratio. Prognostic factors including age, primary tumor site, marital status, radiotherapy, chemotherapy, tumor size, pathological grade, and tumor stage were incorporated into the nomogram models. The models demonstrated strong predictive performance, with C-index values for OS and CSS of 0.757 and 0.779 in the training group, and 0.777 and 0.776 in the validation group, respectively. AUC values for predicting 3-, 5-, and 10-year OS were 0.662, 0.713, and 0.761, and for CSS the values were 0.726, 0.703, and 0.693. Kaplan–Meier analysis indicated significantly improved survival for patients with lower risk scores. The 3-, 5-, and 10-year OS rates for the entire cohort were 54.1%, 45.6%, and 35.1%, respectively, and the CSS rates were 62.9%, 57.5%, and 52.2%, respectively. Conclusions: This study provides validated nomograms for predicting OS and CSS in HNCS patients, offering a reliable tool to support clinical decision-making for this challenging malignancy. These nomograms enhance the ability to predict patient prognosis and personalize treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has indicated possible efficacy benefit of platinum‐based chemotherapy as neoadjuvant treatment for invasive ductal carcinoma triple‐negative breast cancer (TNBC). However, it has not been endorsed by current guidelines due to highly controversial results. Materials and Methods: Present study aims to investigate predictive and prognostic roles concerning single nucleotide polymorphisms (SNPs) in XRCC1 and BRCA1, BRCA2 genes for early stage TNBC patients that received platinum‐based neoadjuvant treatment. We prospectively enrolled women with stage IIB‐IIIB TNBC that had progressed on neoadjuvant taxane and anthracycline‐based chemotherapy at Xinjiang Medical University Affiliated Cancer Hospital. Tumor response and pathological complete response (pCR) rate were assessed. Invasive disease‐free survival (iDFS) and overall survival (OS) were analyzed. Patients' blood samples were subject to Sanger sequencing to genotype XRCC1 Arg194Trp and Arg399Gln, BRCA1 s1799949, and BRCA2 rs206115. Univariate and multivariate logistic regressions were employed to investigate associations between SNPs and clinical characteristics with treatment response and pCR. A total of 45 patients were enrolled. Results: The cohort showcased ORR of 44.4%, pCR of 28.9%, median iDFS of 22 months, and a 3‐year OS of 73.3%. The A/G and G/G genotypes of BRCA1 rs1799949, and the T/T genotype of BRCA2 rs206115 were associated with higher responsive rate. Histologic grade of III and Ki67 expression > 65% were associated with low responsive rate. Moreover, the A/G genotype of BRCA1 rs1799949 and T/T genotype of BRCA2 rs206115 correlated to high pCR. The histologic III and T4 stage correlated to inferior iDFS. Carrier of BRCA1 rs1799949 G/G had the most favorable OS, carriers of A/A showed the poorest OS, and those with A/G genotype showed an intermediate OS. Conclusions: Platinum‐based chemotherapy might serve as a therapeutic option for TNBC patients who were resistant to anthracycline‐ and taxane‐based neoadjuvant therapy. Our study identified several genetic and clinical features that might function as prognostic and predictive markers. [ABSTRACT FROM AUTHOR]

Background: Abnormal mitochondrial pyruvate carrier 1 (MPC1) expression plays a key role in tumor metabolic reprogramming and progression. Understanding its significance in non-small cell lung cancer (NSCLC) is crucial for identifying therapeutic targets. Methods: TIMER 2.0 was utilized to assess the expression of MPC1 in both normal and cancer tissues in pan-cancer. Overall survival (OS) differences between high and low MPC1 expression were analyzed in NSCLC using the Cancer Genome Atlas (TCGA) datasets. We also examined the expression of MPC1 in NSCLC cell lines using western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). In addition, the tissue samples and clinical information of 80 patients with NSCLC from our hospital were collected. Immunohistochemistry (IHC) was used to assess MPC1 expression, and OS was evaluated using Kaplan-Meier curves and the log-rank test. Univariate and multivariate Cox regression analyses were conducted to evaluate the prognostic values of the clinical characteristics and MPC1expression. Results: Analysis of public databases suggested that MPC1 was downregulated in NSCLC compared to that in normal lung tissue and predicted poor prognosis. In addition, the expression of MPC1 in NSCLC cell lines was lower than that in human bronchial epithelial (HBE) cells at both protein and mRNA levels. Further clinical analysis suggested that MPC1 expression was correlated with age, tumor T stage, and TNM stage. Kaplan-Meier analysis revealed that NSCLC patients with high MPC1 expression had a better prognosis, particularly in lung adenocarcinoma (LUAD), whereas no survival benefit was observed in lung squamous cell carcinoma (LUSC). Univariate and multivariate analyses suggested that MPC1 was an independent prognostic factor for patients with NSCLC. Conclusions: MPC1 is poorly expressed in NSCLC, particularly in LUAD, which predicts a poor prognosis and may serve as an independent prognostic factor. Further studies on MPC1 may reveal new targets for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aims to elucidate the relationship between postoperative monocyte count and gastric cancer prognosis. We introduce a standardized monocyte ratio (MMR) to predict postoperative survival rates in gastric cancer patients effectively.MethodsA test cohort was created to develop and evaluate the pre- and postoperative MMR as a mortality predictor in gastric cancer patients. We used Kaplan-Meier survival analysis, complemented by univariate and multivariate analyses. The predictive utility of MMR was assessed via time-dependent ROC curves and decision-curve analysis.ResultsThe sample distributions in both cohorts were similar. The MMR showed high predictive value and significant clinical benefits in 1, 3, and 5-year overall survival (OS) assessments. These findings enhance understanding of prognosis and aid in developing more precise treatment plans.ConclusionsMMR is confirmed as an independent factor in predicting overall survival in gastric cancer patients, proving to be a reliable and cost-effective prognostic indicator.

Cutaneous immune-related adverse events (cirAEs) may be associated with tumoral response and survival in patients using immune checkpoint inhibitors, but this relationship remains unclear because previous reports on the topic have various limitations. The purpose of this study was to examine the association of cirAEs with overall survival and progression-free survival in patients starting immune checkpoint inhibitors. A prospective observational study was conducted in a Spanish tertiary care hospital, including participants between March 2020 and May 2022. The statistical analysis involved the Kaplan–Meier method, log-rank test, and multivariable Cox proportional hazards regression models. At total of 189 patients were included, of whom 82 (43.4%) presented cirAEs. Most participants (56.6%) were diagnosed with non-small cell lung cancer (NSCLC). Mortality and progression rates were lower in patients with vs without cirAEs (p

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer worldwide and immune checkpoint inhibitors have shown favorable therapeutic effects in recurrent or metastatic or locally advanced head and neck squamous cell carcinoma (R/M/LA HNSCC). However, the effects of immunotherapy in HNSCC are still inconsistent because of complicating factors. This meta-analysis tries to provide a more precise assessment of the efficacy and safety of this integrated approach in HNSCC.MethodsWe conducted a systematic review and meta-analysis of randomized clinical trials according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs). A total of 8 out of 2445 articles were analyzed, including 5067 HNSCC patients, including 823 and 4244 patients with LA HNSCC and R/M HNSCC.ResultsThe combined data revealed that immunotherapy has an apparent difference in OS (HR 0.86 95% CI 0.77-0.98) compared with standard of care (Soc, like fluoropyrimidine, methotrexate, docetaxel, or cetuximab) but was equal with the other treatment in PFS (HR 1.08, 95% CI 0.85-1.37). Furthermore, the occurrence of grade 3 or higher adverse events related to the drugs was lower than systematic therapy (OR 0.35, 95% CI 0.17-0.73).ConclusionsThe study has provided compelling evidence that immunotherapy is a significant benefit in OS for HNSCC patients, either R/M HNSCC or LA HNSCC, immunochemotherapy may benefit more for these patients, but double-agent immunotherapy showed no more benefit for R/M HNSCC patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier CRD42023471570.

Abstract Background This study aimed to construct a novel nomogram based on the number of positive lymph nodes to predict the overall survival of patients with pancreatic head cancer after radical surgery. Materials and methods 2271 and 973 patients in the SEER Database were included in the development set and validation set, respectively. The primary clinical endpoint was OS (overall survival). Univariate and multivariate Cox regression analyses were used to screen independent risk factors of OS, and then independent risk factors were used to construct a novel nomogram. The C-index, calibration curves, and decision analysis curves were used to evaluate the predictive power of the nomogram in the development and validation sets. Results After multivariate Cox regression analysis, the independent risk factors for OS included age, tumor extent, chemotherapy, tumor size, LN (lymph nodes) examined, and LN positive. A nomogram was constructed by using independent risk factors for OS. The C-index of the nomogram for OS was 0.652 [(95% confidence interval (CI): 0.639–0.666)] and 0.661 (95%CI: 0.641–0.680) in the development and validation sets, respectively. The calibration curves and decision analysis curves proved that the nomogram had good predictive ability. Conclusions The nomogram based on the number of positive LN can effectively predict the overall survival of patients with pancreatic head cancer after surgery.

Abstract Background Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed. Methods A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan–Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments. Results FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times. Conclusions FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients.

Purpose: Radiotherapy (RT) plays an important role in the treatment of hepatocellular carcinoma (HCC). To screen patients who benefit most from RT, a nomogram for survival prediction of RT based on a large sample of patients with HCC was created and validated. Methods: A total of 2,252 cases collected from the Surveillance, Epidemiology, and End Results (SEER) database were separated into a training or an internal validation cohort in a 7:3 ratio (n = 1,565:650). An external validation cohort of cases from our institute was obtained (n = 403). LASSO regression and Cox analyses were adopted to develop a nomogram for survival prediction. The decision curve analysis (DCA), calibration curve, and time-dependent receiver operating characteristic curves (TROCs) demonstrated the reliability of the predictive model. Results: For patients with HCC who received RT, the analyses revealed that the independent survival prediction factors were T stage {T2 vs. T1, hazard ratio (HR) =1.452 [95% CI, 1.195–1.765], p < 0.001; T3 vs. T1, HR = 1.469 [95% CI, 1.168– 1.846], p < 0.001; T4 vs. T1, HR = 1.291 [95% CI, 0.951–1.754], p = 0.101}, N stage (HR = 1.555 [95% CI, 1.338–1.805], p < 0.001), M stage (HR = 3.007 [95% CI, 2.645–3.418], p < 0.001), max tumor size (>2 and ≤5 vs. ≤2 cm, HR = 1.273 [95% CI, 0.992–1.633], p = 0.057; >5 and ≤10 vs. ≤2 cm, HR = 1.625 [95% CI, 1.246– 2.118], p < 0.001; >10 vs. ≤2 cm, HR = 1.784 [95% CI, 1.335–2.385], p < 0.001), major vascular invasion (MVI) (HR = 1.454 [95% CI, 1.028–2.057], p = 0.034), alpha fetoprotein (AFP) (HR = 1.573 [95% CI, 1.315–1.882], p < 0.001), and chemotherapy (HR = 0.511 [95% CI, 0.454–0.576], p < 0.001). A nomogram constructed with these prognostic factors demonstrated outstanding predictive accuracy. The area under the curve (AUC) in the training cohort for predicting overall survival (OS) at 6, 12, 18, and 24 months was 0.824 (95% CI, 0.803–0.846), 0.824 (95% CI, 0.802–0.845), 0.816 (95% CI, 0.792–0.840), and 0.820 (95% CI, 0.794–0.846), respectively. The AUCs were similar in the other two cohorts. The DCA and calibration curve demonstrated the reliability of the predictive model. Conclusion: For patients who have been treated with RT, a nomogram constructed with T stage, N stage, M stage, tumor size, MVI, AFP, and chemotherapy has good survival prediction ability. [ABSTRACT FROM AUTHOR]

Background: Family with sequence similarity 109, member B (FAM109B) is involved in endocytic transport and affects genetic variation in brain methylation. It is one of the important genes related to immune cell-associated diseases. In the tumor immune system, methylation can regulate tumor immunity and influence the maturation and functional response of immune cells. Whether FAM109B is involved in tumor progression and its correlation with the tumor immune microenvironment has not yet been disclosed. Methods: A comprehensive pan-cancer analysis of FAM109B expression, prognosis, immunity, and TMB was conducted. The expression, clinical features, and prognostic value of FAM109B in low-grade gliomas (LGG) were evaluated using TCGA, CGGA, and Gravendeel databases. The expression of FAM109B was validated by qRT-PCR, immunohistochemistry (IHC), and Western blotting (WB). The relationship between FAM109B and methylation, Copy Number Variation (CNV), prognosis, immune checkpoints (ICs), and common chemotherapy drug sensitivity in LGG was explored through Cox regression, Kaplan–Meier curves, and Spearman correlation analysis. FAM109B levels and their distribution were studied using the TIMER database and single-cell analysis. The potential role of FAM109B in gliomas was further investigated through in vitro and in vivo experiments. Results: FAM109B was significantly elevated in various tumor types and was associated with poor prognosis. Its expression was related to aggressive progression and poor prognosis in low-grade glioma patients, serving as an independent prognostic marker for LGG. Glioma grade was negatively correlated with FAM109B DNA promoter methylation. Immune infiltration and single-cell analysis showed significant expression of FAM109B in tumor-associated macrophages (TAMs). The expression of FAM109B was closely related to gene mutations, immune checkpoints (ICs), and chemotherapy drugs in LGG. In vitro studies showed increased FAM109B expression in LGG, closely related to cell proliferation. In vivo studies showed that mice in the sh-FAM109B group had slower tumor growth, slower weight loss, and longer survival times. Conclusions: FAM109B, as a novel prognostic biomarker for low-grade gliomas, exhibits specific overexpression in TAMs and may be a potential therapeutic target for LGG patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to construct a novel nomogram based on the number of positive lymph nodes to predict the overall survival of patients with pancreatic head cancer after radical surgery. Materials and methods: 2271 and 973 patients in the SEER Database were included in the development set and validation set, respectively. The primary clinical endpoint was OS (overall survival). Univariate and multivariate Cox regression analyses were used to screen independent risk factors of OS, and then independent risk factors were used to construct a novel nomogram. The C-index, calibration curves, and decision analysis curves were used to evaluate the predictive power of the nomogram in the development and validation sets. Results: After multivariate Cox regression analysis, the independent risk factors for OS included age, tumor extent, chemotherapy, tumor size, LN (lymph nodes) examined, and LN positive. A nomogram was constructed by using independent risk factors for OS. The C-index of the nomogram for OS was 0.652 [(95% confidence interval (CI): 0.639–0.666)] and 0.661 (95%CI: 0.641–0.680) in the development and validation sets, respectively. The calibration curves and decision analysis curves proved that the nomogram had good predictive ability. Conclusions: The nomogram based on the number of positive LN can effectively predict the overall survival of patients with pancreatic head cancer after surgery. [ABSTRACT FROM AUTHOR]

Background: Small renal masses (SRMs) have been shown to have low malignant potential. Active surveillance (AS), typically characterized by regular follow-up and delayed nephrectomy if necessary, is recommended as an option for frail patients with SRMs. Nevertheless, the impact of tumor size on survival in T1a RCC patients undergoing delayed nephrectomy for SRMs remains unclear. Methods: Patients diagnosed with non-metastatic T1a RCC who underwent nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database and divided into immediate (< 6 months) and delayed nephrectomy (≥ 6 months) groups based on the duration from diagnosis to nephrectomy. After propensity score matching (PSM), overall survival (OS) and cancer-specific survival (CSS) were estimated by K-M curves and compared with log-rank test. Results: A total of 27,502 patients were enrolled, of whom 26,915 (97.9%) received immediate nephrectomy and 587 (2.1%) received delayed nephrectomy. After PSM, 1174 patients who underwent immediate nephrectomy and 587 patients who underwent delayed nephrectomy were included. With a median delay of 7 months, delayed nephrectomy resulted in non-inferior OS for RCC tumors sized 0.1–2.0 cm (HR = 1.12, p = 0.636). However, for RCC tumors sized 2.1–3.0 cm (HR = 1.60, p = 0.008) and 3.1–4.0 cm (HR = 1.89, p < 0.001), delayed nephrectomy showed inferior OS compared to immediate nephrectomy. Delayed nephrectomy did not result in significantly worse CSS than immediate nephrectomy in all tumor size subgroups (all p > 0.05), however this may be due to sample size limiting statistical power. Conclusion: Based on the SEER database, we found that with a median delay of 7 months, 2 cm may be an appropriate cut-off point of delayed nephrectomy for patients diagnosed with non-metastatic T1a RCC. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10−3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan–Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804–6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC. [ABSTRACT FROM AUTHOR]

Background: Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. Methods: This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan–Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). Results: We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27–0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001). Conclusion: The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival. [ABSTRACT FROM AUTHOR]

Objective: Robotic surgery or thoracoscopic surgery are both options for minimally invasive lobectomy. While the two strategies are said to have comparable short-term results, it is unknown whether the strategy is more successful against cancer. This study's goal is to examine variations in the long-term patient endurance rates for robotic and thoracoscopic lobectomies. Methods: Non-Small Cell Lung Cancer (NSCLC) sufferers who had a roboticassisted (n=42) and thoracoscopic lobectomy (n=387), were analyzed using chance matching. The several groups were identical in every way, including the illnesses they experienced, the treatments they received and the qualities they shared. We analyzed the rates of Cancer Specific Mortality (CSM) and Overall Survival (OS) in the two distinct cohorts. Results: The median follow-up time after surgical treatment was 35 months, and the middle age at operation was 72 (65-91). The OS and CSM of the robotic aided and thoracoscopic groups were identical. Conclusions: The greater tendency research shows that, in comparison to patients who received Thoracoscopic Lobectomy (TL), both OS and CSM were similar for those who received robotic-assisted lobectomy compared to those who did not. There is no significant distinction between the two minimally invasive techniques in terms of oncologic outcomes. These results suggest that more study, such as a randomized control experiment or its differences or further important data analysis, is needed to corroborate these outcomes. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) patients with compensated cirrhosis typically face a high prevalence and unfavorable prognosis. However, there is currently a deficiency in prediction models to anticipate the prognosis of these patients. Therefore, our study included the Gammaglutamyl transpeptidase-to-platelet ratio (GPR) in analysis and aimed to develop a nomogram for HCC patients with compensated cirrhosis after local ablation. Methods: Enrolling 669 patients who underwent local ablation at Beijing You'an Hospital during the period from January 1, 2014, to December 31, 2022, this study focused on individuals with compensated cirrhotic HCC. In a ratio of 7:3, patients were allocated to the training cohort (n=468) and the validation cohort (n=201). Lasso-Cox regression was employed to identify independent prognostic factors for overall survival (OS). Subsequently, a nomogram was constructed using these factors and was validated through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: GPR, age, and hemoglobin were identified by Lasso-Cox regression as independent prognostic factors of the nomogram. The area under the ROC curves (AUCs) for 3-, 5-, and 8-year OS (0.701, 0.755, and 0.768 for the training cohort; 0.684, 0.707, and 0.778 for the validation cohort), and C-indices (0.695 for training cohort; 0.679 for validation cohort) exhibited the excellent predictive ability of the nomogram. Calibration curves and DCA curves indicated favorable calibration performance and clinical utility. Patients were further stratified into two risk groups according to the median nomogram score. There existed an obvious distinction between the two groups both in the training cohort and validation cohort. Conclusion: In summary, this research established and validated a novel nomogram to predict OS, which had good predictive power for HCC patients with compensated cirrhosis after local ablation. [ABSTRACT FROM AUTHOR]

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the LassoCOX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications. [ABSTRACT FROM AUTHOR]

Background: The purpose of this work was to investigate the prognostic significance of Ki67 in acral melanoma (AM). Patients and Methods: Ki67 values in primary lesions (pKi67) of 481 patients with primary non-metastatic AM (primary cohort) from three tertiary hospitals and in recurrent lesions (rKi67) of 97 patients (recurrent cohort) were recorded. The associations of p/rKi67 with clinicopathological features and prognosis were analyzed. Results: In the primary cohort, high pKi67 group tended to have more ulceration, pT4, lymph node metastasis (LNM), nodal macrometastases, and recurrence (all P < 0.05). Logistic regression analysis revealed that pKi67 was significantly associated with pT4 and LNM (P = 0.004 and 0.027, respectively). Furthermore, both 5-year overall survival (OS) and recurrence-free survival (RFS) rates in high pKi67 group were significantly worse than those in moderate and low pKi67 groups (OS 47.8% versus 55.7 versus 76.8%, P = 0.002; RFS: 27.1 versus 42.8 versus 61.8%, P < 0.001). Similarly, in the recurrent cohort, the 5-year survival after recurrence (SAR) rates in high rKi67 group was significantly worse than those in moderate and low rKi67 groups (31.7 versus 47.4 versus 75%; P = 0.026). Stratified analysis also indicated a significant survival difference among pKi67 groups within various subgroups. Most importantly, multivariate Cox analysis demonstrated that pKi67 could be independently associated with OS and RFS, as well as rKi67 for SAR (all P < 0.05). Conclusions: A high Ki67 value was significantly associated with adverse pathological and prognostic features in both primary and recurrent AM cohorts. Ki67 should be routinely evaluated to guide risk stratification and prognostic prediction. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi‐omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs‐associated machine learning model (MOCM) based on eight MOCs‐specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability. [ABSTRACT FROM AUTHOR]

BackgroundNasopharyngeal carcinoma (NPC) is a prevalent form of head and neck cancer, particularly in specific regions with a higher incidence. The optimal treatment strategy for locally advanced NPC (stage III and IVA, LA-NPC) involves various combinations of induction chemotherapy (IC), concurrent chemoradiotherapy (CCRT), and adjuvant chemotherapy (AC), each with distinct advantages. This one institutional study aims to retrospectively analysis the efficacy and clinical outcomes of IC with CCRT (IC+CCRT), CCRT with AC (CCRT+AC), and the comprehensive approach of IC followed by CCRT and subsequently AC (IC+CCRT+AC) in the management of LA-NPC.Materials and methodsA total of 352 LA-NPC patients were included: 173 accepted IC+CCRT, 60 received CCRT+AC, and 119 underwent IC+CCRT+AC. The primary endpoints including overall survival (OS) and progression-free survival (PFS), were assessed using the Kaplan-Meier method and log-rank test.ResultsThe median follow-up was 61.2 months (1-216 months). There was no significant difference in 5-year OS and PFS between IC group and no IC group, extending the observation time to 90 months, the OS and PFS were significantly better in IC group than no IC group (OS: 76% vs. 70%,P

Background Serum neuron-specific enolase (NSE) had been associated with survival of several cancers. However, its prognostic significance for colorectal cancer (CRC) has not been effectively discussed. We aimed to investigate the relationship between baseline serum NSE and the overall survival (OS) of colorectal adenocarcinoma (CRAD) patients. Methods A retrospective study had been conducted by including 564 histopathology confirmed CRAD patients between January 2013 and December 2018 from Yunnan Provincial Cancer hospital, China. Cox proportional hazards model was used to estimate the crude and adjusted associations between serum NSE measured at diagnosis and the OS of the patients. Restricted cubic spline (RCS) was further applied to delineate dose-response trend of the NSE-OS association. Results After controlling for possible confounding factors, baseline serum NSE was significantly associated with OS in CRAD: when dichotomizing by the median, patients with higher baseline serum NSE (NSE >= 12.93 ng/mL) were observed a worse prognosis (hazard ratio, HR: 1.82, 95% CI [1.30–2.55], p < 0.01). Stratified analysis by tumor stage revealed a stronger NSE-OS association in advanced CRAD patients. RCS disclosed a prominent dose-response relationship in NSE-OS association for all CRAD patients: along with the increase of baseline serum NSE, the adjusted HR of CRAD patients increased gradually. This dose-response trend is also evident in advanced stage CRAD patients, but not in early stage CRAD patients. Conclusions Serum NSE measured at diagnosis might be a useful prognostic indicator for CRAD, especially for advanced stage patients.

Background: Autoimmune disorders (ADs) are prevalent among patients with myelodysplastic syndrome (MDS), yet their impact on MDS outcomes, including overall survival (OS), mortality, and transformation to acute myeloid leukemia (AML), is not well defined. Methods: We conducted a systematic review of articles published up to April 2024, sourced from PubMed, Web of Science, Embase, and Google Scholar, focusing on the influence of ADs on survival and AML transformation rates in MDS patients. The methodological quality of each study was assessed using the Newcastle Ottawa Scale. Results: From 8 studies that met the inclusion criteria, ADs were present in 17.5% (3074/17,481) of MDS patients. Data analysis indicated mortality rates ranging from 15.3% to 67% in MDS patients with ADs and 12% to 69% in those without. The rate of AML transformation varied from 0% to 23% in patients with ADs compared to 4% to 30% in those without. Conclusions: The influence of ADs on survival and AML transformation in MDS patients appears variable. This systematic review highlights the need for further large-scale prospective studies to clarify the relationship between ADs and MDS outcomes.

Abstract Purpose Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages. Methods Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan–Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics. Results 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18–45, 46–55, 56–65, and 65–80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18–45 years: OS P = 0.019, BCSS P = 0.016; age group of 46–55 years: OS P