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Background: PD-1/PD-L1 inhibitors (PI) have shown promising results in both neoadjuvant and adjuvant therapies for resectable non-small cell lung cancer (NSCLC). However, substantial evidence from large-scale studies is still lacking for their use in the perioperative setting (neoadjuvant plus adjuvant). This meta-analysis aims to evaluate the integration of perioperative PI (PPI) with neoadjuvant chemotherapy for resectable NSCLC. Methods: To identify appropriate randomized controlled trials (RCTs), we thoroughly explored six different databases. The primary endpoint was survival, while the secondary measures included pathological responses and adverse events (AEs). Results: Six RCTs involving 2941 patients were included. The PPI group significantly improved overall survival (OS) (hazard ratio [HR]: 0.62 [0.51, 0.77]), event-free survival (EFS) (HR: 0.57 [0.51, 0.64]), pathological complete response (risk ratio [RR]: 5.81 [4.47, 7.57]), and major pathological response (RR: 2.60 [1.77, 3.82]). Benefits in EFS were seen across all subgroups. OS rates at 12–48 months and EFS rates at 6–48 months were higher in the PPI cohort. Furthermore, the advantages in OS and EFS increased with prolonged survival times. The PPI group also exhibited higher rates of surgery and R0 resections. However, the PPI group experienced more grade 3–5 AEs, serious AEs, and treatment discontinuations due to AEs. Conclusions: The integration of perioperative PI with neoadjuvant chemotherapy can significantly improve survival and pathological responses for resectable NSCLC. However, the increased incidence of grade 3–5 AEs must be carefully evaluated. [ABSTRACT FROM AUTHOR]

Lung transplantation (LTx) is a well-known treatment for end-stage lung disease. This study aimed to report the incidence of cancer after LTx and long-term outcome among lung transplant recipients with a pretransplant diagnosis of cancer. Patients who underwent LTx between 1990–2016 were included in the study. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer Registry and the Cause-of-Death registry. A total of 614 patients were followed for a median of 5.1 years. In all, 159 malignancies were diagnosed. The excess risk of cancer or standardized incidence ratio (SIR) following LTx was 5.6-fold compared to the general Swedish population. The most common malignancies were non-melanoma skin cancer (NMSC) (SIR 76.5 (95%CI 61.7–94.8); non-Hodgkin lymphoma (SIR 23.5, 95%CI 14.8–37.2); and lung cancer (SIR 8.89, 95%CI 5.67–13.9). There was no significant difference in overall survival between those with and without a history of cancer before LTx (p = 0.56). In total, 159 malignancies were identified after LTx, which was a 5.6-fold higher relative to the general population. A history of previous cancer yields similar survival in selected recipients, compared to those without cancer prior to LTx. [ABSTRACT FROM AUTHOR]

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Causeof-Death-Registry. A total of 664 patients were followed for a median of 7.7 years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx (p = 0.53). During a median follow-up of 7.7 years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx. [ABSTRACT FROM AUTHOR]

Background: Pancreatic Ductal Adenocarcinoma (PDAC) primarily affects older individuals with diminished physiological reserves. The Modified 5-Item Frailty Index (mFI-5) is a novel risk stratification tool proposed to predict postoperative morbidity and mortality. This study aimed to validate the mFI-5 for predicting surgical outcomes in patients undergoing pancreatoduodenectomy (PD) for PDAC. Methods: Our retrospective PDAC database included patients who underwent PD between 2014 and 2023. Patients were stratified by mFI-5 scores (0 best − 5 worst), which assess preoperative CHF, diabetes mellitus, history of COPD or pneumonia, functional health status, and hypertension requiring medication. Associations between mFI-5 scores and outcomes, including postoperative complications and mortality, were analyzed using logistic regression, Cox proportional hazards models, and Kaplan-Meier survival analysis. Results: Among 250 PDAC patients undergoing PD, 142 (56.8%) had mFI-5 scores ≤ 1, and 25 (10%) had scores ≥ 3. No patients had scores > 4. Higher mFI-5 scores correlated with older age (p < 0.001) and tobacco use (p = 0.036). Multivariate analysis identified age (RR 1.02, p = 0.038), ASA class (ASA III; RR 2.61, p < 0.001; ASA IV; RR 2.63, p = 0.026), and moderate alcohol consumption (RR 0.56, p = 0.038) as frailty predictors. An mFI-5 score > 2 independently associated with higher mortality (HR 2.08, p = 0.026). Median overall survival was significantly lower for patients with mFI-5 scores > 2 than for those with scores ≤ 2 (21.3 vs. 42.1 months, p = 0.022). Conclusions: The mFI-5 is a valuable tool for predicting postoperative morbidity and mortality in PDAC patients undergoing PD. Integrating frailty assessment into preoperative evaluations can enhance patient selection and surgical outcomes. Future research should focus on incorporating frailty assessments into surgical planning and patient management to improve outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion This study aimed to investigate exposure–response (ER) relationships in efficacy and safety for mirvetuximab soravtansine (MIRV) which is a first‐in‐class antibody–drug conjugate approved for the treatment of folate receptor‐α‐positive platinum‐resistant ovarian cancer.MIRV was characterized in 4 clinical studies. Exposure metrics for MIRV, its payload and a metabolite were derived from a population pharmacokinetic model. Efficacy was analysed in MIRV‐treated patients (n = 215) in a recent confirmatory, randomized, chemotherapy‐controlled MIRASOL trial and safety was evaluated in patients pooled across all 4 clinical studies (n = 757).In the MIRASOL trial (NCT04209855), MIRV demonstrated significant benefit over chemotherapy in progression‐free survival (PFS), objective response rate (ORR) and overall survival (OS). The most common adverse events (AEs) included ocular disorders, peripheral neuropathy and pneumonitis. For PFS, ORR and OS, the trough concentration of MIRV was the predictor consistently found in ER models for efficacy. In contrast, for ocular AEs (as well as the time to onset of ocular AEs) and peripheral neuropathy, the area under the concentration–time curve (AUC) of MIRV was identified as the exposure metric in ER models for safety. No exposure parameters were found to correlate with pneumonitis. Covariates in all models did not show clinically meaningful impact on efficacy or safety. Logistic regression models for ORR and ocular AEs based on AUC of MIRV were used to justify the clinical dose regimen approved for MIRV.The trough concentration of MIRV correlated with efficacy whereas the AUC of MIRV was associated with major AEs. The ER relationships supported the selected therapeutic dose regimen. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Limited information is available regarding the impact of sarcopenia on the prognosis of antiangiogenic therapy in individuals with advanced non‐small cell lung cancer (NSCLC). This study primarily sought to examine the prognostic significance of sarcopenia in individuals with advanced NSCLC undergoing antiangiogenic therapy.We retrospectively enrolled all patients who met the inclusion and exclusion criteria from 2019 to 2021 at Nantong University Hospital. Patients were grouped according to the presence or absence of sarcopenia. After propensity score matching (PSM), progression‐free survival (PFS), overall survival (OS), and adverse event rates were compared between the two groups. Factors associated with prognosis were screened using univariate and multivariate analyses.A total of 267 patients were included, with a total of 201 matched at baseline after PSM (77 in the sarcopenia group and 124 in the non‐sarcopenia group). The sarcopenia group had lower PFS (p = 0.043) and OS (p = 0.011) than the non‐sarcopenia group and a higher incidence of adverse events (p = 0.044). Multivariate analysis suggested that sarcopenia is an independent prognostic risk factor for OS in advanced NSCLC patients receiving antiangiogenic therapies (p = 0.009). Results of subgroup analyses showed some differences in the impact of sarcopenia on survival prognosis in populations with different characteristics.Patients with advanced NSCLC with comorbid sarcopenia exhibit a worse prognosis when treated with antiangiogenic therapy, and preventing and ameliorating sarcopenia may lead to better survival outcomes in patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

The article discusses enhancing systemic anti-cancer treatment (SACT) capacity by implementing subcutaneous atezolizumab for lung cancer treatment. Topics include the increasing demand for SACT in the United Kingdom, the benefits of subcutaneous over intravenous administration in reducing clinic time and improving patient comfort, and the need for wider adoption of subcutaneous immune checkpoint inhibitors to ease the burden on healthcare systems.

Background: Angiogenesis inhibitors targeting VEGF, or its receptors have consistently produced disappointing clinical outcomes in breast cancer. Therefore, there is an urgent need to explore alternative angiogenic pathways in breast cancer. This study aimed to describe the gene expression of pivotal pro-angiogenic genes in breast cancer and to further analyze the associations with the clinicopathologic tumor features, prognostic factors, and overall survival. Such findings would expand the understanding of the role of different angiogenic pathways in breast cancer pathogenesis and identify patients at risk of more aggressive disease who could be eligible for intense treatment regimens. Additionally, exploring angiogenic pathways helps identify new potential drug targets for breast cancer. Methods: The mRNA expression levels for eight pro-angiogenic genes [VEGFA, HGF, FGF1, FGF2, ANGPT1, ANGPT2, PDGFA, and PDGFB] were obtained from the METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) dataset available at cBioPortal public domain. Pertinent demographic and tumor information were retrieved. Results: VEGFA and ANGPT2 genes had the highest expression levels with average mRNA log intensities of 7.18±0.7 and 7.11±0.53, respectively. VEGFA expression was not correlated with the expression of other pro-angiogenic genes, the clinicopathologic tumor features, and the overall survival of patients. FGF1, ANGPT1, and PDGFA mRNA levels were negatively correlated with the age of patients at diagnosis. The expression of FGF1 and FGF2 correlated inversely with tumor size and the Nottingham Prognostic Index (p = 0.03 and p = 0.002, respectively). Expression of HGF was significantly associated with advanced tumor stage (p<0.05). Expression of ANGPT1 and ANGPT2 was associated with hormone receptor-negative status and the non-luminal subtypes. PDGFB expression was significantly higher in patients with high-grade disease and HER2-positive status. Patients with high expression status of ANGPT2 and PDGFB had significantly reduced overall survival compared to those with low expression levels of these genes (p = 0.004 and p = 0.0001, respectively). Conclusions: In this dataset of patients with breast cancer, the expression levels of 8 different pro-angiogenic genes revealed remarkable differences in terms of their association with clinicopathologic tumor characteristics and prognosis. The expression of ANGPTs and PDGFs was associated with adverse tumor features, worse prognosis, and reduced survival in patients. Targeting ANGPTs and PDGF pathways could provide new insights for effective anti-angiogenic drugs in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Tri-combination therapy based on hepatic arterial infusion chemotherapy (HAIC) of infusion fluorouracil, leucovorin, and oxaliplatin (FOLFOX-HAIC) plus immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the locally advanced hepatocellular carcinoma (HCC) patients have been proven effective. However, whether it was best for these HCC patients to start with the most potent therapeutic pattern was still under debate. This retrospective study evaluated the efficacy and safety of FOLFOX-HAIC combined with systemic therapies in the patterns of sequential and concurrent schedules. Methods: This real-world study included 117 unresectable HCC patients who initially received either FOLFOX-HAIC monotherapy (HAIC group, n = 44) or concurrent ICIs and TKIs (ConHAIC group, n = 73) from March 2020 and June 2022, during the period of FOLFOX-HAIC monotherapy in HAIC group, patients in the HAIC group (n = 30) experienced progressive disease (PD) would have their treatment pattern converted from the FOLFOX-HAIC monotherapy to the combination of FOLFOX-HAIC plus ICIs and TKIs sequentially (SeqHAIC group). The progression-free survival (PFS) and overall survival (OS), as primary outcomes, were compared between patients in the SeqHAIC and ConHAIC groups. Results: The median follow-up time of the SeqHAIC group was 24.92 months (95% CI, 12.74–37.09 months) and of the ConHAIC group was 17.87 months (95% CI, 16.85–18.89 months) and no significant difference was observed in both PFS (HR, 1.572; 95% CI, 0.848–2.916; p = 0.151) and OS (HR, 1.212; 95% CI, 0.574–2.561; p = 0.614) between the SeqHAIC and the ConHAIC groups. As for the tumor responses, there was no significant difference between the two groups regarding tumor responses, overall response rates (p = 0.658) and disease control rates (p = 0.641) were 50.0%, 45.2%, and 83.3%, 89.0% for the SeqHAIC and the ConHAIC groups, respectively. Conclusion: Our study revealed that sequential systemic ICIs and TKIs in combination with FOLFOX-HAIC provides similar long-term prognosis and better tolerability compared to concurrent therapy for locally advanced HCC patients. Prospective studies with a larger sample size and longer follow-up are required to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Lung cancer accounts for a significant proportion of cancer-related deaths in China, with the majority of the cases being classified as non-small cell lung cancer (NSCLC). The study aimed to investigate the expression of serum SNHG22 in patients with NSCLC, and its molecular mechanism and prognostic potential in NSCLC. Methods: Admitted 125 NSCLC patients were selected for the study, along with 125 healthy individuals in the same period. The levels of SNHG22 and miR-128-3p were quantified via RT-qPCR. Correlations between the SNHG22 level and the pathological characteristics of the NSCLC patients were investigated through the application of the chi-square test. The targeting relationship between SNHG22 and miR-128-3p was predicted by online database and confirmed by luciferase activity. The prognostic ability of SNHG22 in NSCLC was assessed by Kaplan-Meier curves and multivariate Cox analysis. Results: SNHG22 was upregulated in NSCLC and directly targeted miR-128-3p. The rate of overall survival is lower in patients with high-SNHG22 group compared to those with low-SNHG22 group. Silencing SNHG22 impaired the functionality of cells, which was restored by miR-128-3p inhibitor. SNHG22 stands as an independent predictor of poor prognosis in NSCLC patients. Conclusion: The overexpression of SNHG22 in NSCLC is related to lymph node metastasis, TNM stage and patient survival, which is expected to be a prognostic predictor of NSCLC patients. [ABSTRACT FROM AUTHOR]

Objectives: This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors. Methods: This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens. Results A total of 443 patients underwent rebiopsy, with 186 (42.0%) testing positive for the T790M mutation by the sixth rebiopsy. The final analysis included 143 eligible patients. Progression-free survival was not significantly different in terms of the methods (tissue: 13.3 months, 95% confidence interval [CI]: [9.4, 23.5] vs plasma: 11.1 months, 95% CI: [8.1, 19.4], p = 0.33) and numbers (one: 13.4 months, 95% CI: [9.4, 23.5] vs two or more: 11.0 months, 95% CI: [8.1, 14.8], p = 0.51) of repeated rebiopsies. Longer overall survival (OS) was found in patients in whom T790M was detected by tissue specimens rather than by plasma ctDNA (2-year OS rate: 81.7% for tissue vs 63.9% for plasma, p = 0.0038). Factors related to the lower numbers of rebiopsies included age and bone metastasis. Factor associated with T790M detection in tissue rather than in plasma was pleural metastasis, while advanced tumor stage was related to T790M confirmation in plasma rather than in tissue. Conclusions: Repeated rebiopsy for T790M detection in patients with NSCLC can increase the detection rate of the mutation. Detection of T790M by plasma ctDNA might be related to poor survival outcomes. [ABSTRACT FROM AUTHOR]

Background: To explore the association between radiation after surgery and the 5-year overall survival (OS) and 5-year cancer-specific survival (CSS) in patients with Wilms tumor. Methods: In this cohort study, 1564 participants were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The univariate and multivariable COX proportional risk model as well as competitive risk model were used to explore the covariates associated with 5-year OS and 5-year CSS of patients with Wilms tumor and the correlation between radiation after surgery and 5-year OS or 5-year CSS of patients with Wilms tumor, respectively. The Kaplan-Meier curves of participants were plotted. Results: The median follow-up was 126.00 (84.00, 178.00) months. Patients receiving surgery had higher 5-year survival probability than those not receiving surgery, while participants receiving radiation after surgery showed poor 5-year survival than those not. After adjusting for covariates including age and SEER stage, increased risk of 5-year overall mortality in patients with Wilms tumor [hazard ratio (HR) = 1.62, 95% confidence interval (CI): 1.10–2.41). After the adjustment for confounding factors including age, SEER stage and ethnicity, increased risk of 5-year cancer-specific mortality of patients with Wilms tumor was observed in those receiving radiation after surgery (HR = 1.77, 95%CI: 1.13–2.79). Conclusion: Radiation after surgery was associated with poor prognosis of patients with Wilms tumor, which indicated that the clinicians should assess whether the patient was suitable for using radiation after surgery. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectivesMaterials and methodsResultsConclusionImmune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs. However, predictors of irAEs remain unidentified.We evaluated the predictors of irAEs and compared the outcomes of ICIs with and without irAEs in patients with recurrent/metastatic head and neck cancers (R/M HNCs).We retrospectively analyzed 157 patients with R/M HNCs who were administered an anti-PD-1 antibody between September 2014 and December 2022. We examined whether various pretreatment factors were associated with irAEs. The overall survival (OS) and progression-free survival (PFS) in patients with and without irAEs were analyzed.Overall, 44 patients (28.0%) developed irAEs. The survival curve estimated for patients with and without irAEs showed a significant difference in PFS (p = 0.018), but not in OS (p = 0.208). Multivariate analysis revealed significant differences in relative eosinophil counts (p < 0.001), TP (p = 0.014), and NLR (p = 0.002), which may be independent predictors of irAEs.IrAEs may be associated with higher efficacy of ICIs and longer PFS. The relative eosinophil count may be predictors of irAEs and useful in routine medical practice. Using these biomarkers to predict irAEs will help predict ICI effects and manage irAEs. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Carcinoembryonic antigen (CEA) is one of the commonly used preoperative biomarkers for colorectal cancer (CRC), but no meta‐analysis has evaluated the findings of all recently published studies to determine whether its postoperative level can serve as a prognostic indicator.We conducted a systematic search for eligible literature from the PubMed, EMBASE, and Web of Science databases in October 2023. Studies that investigated the relationship between postoperative serum CEA levels and prognosis in CRC patients were included. Outcome indicators, including overall survival (OS), disease‐free survival (DFS), and progression‐free survival (PFS)/recurrence‐free survival (RFS), were analyzed using a fixed‐effects or random‐effects model. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values.This meta‐analysis included 20 eligible studies involving 10,114 CRC patients from the East Asian and Western countries. A comprehensive analysis revealed that elevated postoperative CEA levels were associated with low OS (HR: 2.92, 95% CI: 2.36–3.62, and p < 0.000), DFS (HR: 2.81, 95% CI: 2.01–3.94, and p < 0.000), and RFS/PFS (HR: 2.52, 95% CI: 1.75–3.62, p < 0.000). A subgroup analysis by region, analysis type, distant metastasis, HR obtain method, sample size, postoperative measurement date, and study design demonstrated that the negative correlation observed between high serum CEA levels after surgery and poor prognosis was not significantly different between the subgroups.When CEA levels are found to be elevated during postoperative follow‐up, more active intervention measures should be implemented to further improve the patient's survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a great clinical challenge because of its aggressiveness and poor prognosis. Zinc Finger Protein 64 (ZFP64), as a transcriptional factor, is responsible for the development and progression of cancers. This study aims to investigate whether ZFP64 regulates stem cell-like properties and tumorigenesis in BC by the glycolytic pathway. Results: It was demonstrated that ZFP64 was overexpressed in BC specimens compared to adjacent normal tissues, and patients with high ZFP64 expression had shorter overall survival and disease-free survival. The analysis of the association of ZFP64 expression with clinicopathological characteristics showed that high ZFP64 expression is closely associated with N stage, TNM stage, and progesterone receptor status. Knockdown of ZFP64 suppressed the viability and colony formation capacity of BC cells by CCK8 and colony formation assays. The subcutaneous xenograft models revealed that ZFP64 knockdown reduced the volume of formatted tumors, and decreased Ki67 expression in tumors. The opposite effects on cell proliferation and tumorigenesis were demonstrated by ZFP64 overexpression. Furthermore, we suggested that the stem cell-like properties of BC cells were inhibited by ZFP64 depletion, as evidenced by the decreased size and number of formatted mammospheres, the downregulated expressions of OCT4, Nanog, and SOX2 proteins, as well as the reduced proportion of CD44+/CD24− subpopulations. Mechanistically, glycolysis was revealed to mediate the effect of ZFP64 using mRNA-seq analysis. Results showed that ZFP64 knockdown blocked the glycolytic process, as indicated by decreasing glycolytic metabolites, inhibiting glucose consumption, and reducing lactate and ATP production. As a transcription factor, we identified that ZFP64 was directly bound to the promoters of glycolysis-related genes (ALDOC, ENO2, HK2, and SPAG4), and induced the transcription of these genes by ChIP and dual-luciferase reporter assays. Blocking the glycolytic pathway by the inhibition of glycolytic enzymes ENO2/HK2 suppressed the high proliferation and stem cell-like properties of BC cells induced by ZFP64 overexpression. Conclusions: These data support that ZFP64 promotes stem cell-like properties and tumorigenesis of BC by activating glycolysis in a transcriptional mechanism. [ABSTRACT FROM AUTHOR]

Purpose: This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results: This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p < 0.0001], and fewer overall complications [OR 0.62; 95% CI 0.45 to 0.86; p = 0.004], but a higher recurrence rate [OR 7.83; 95% CI 4.32 to 14.19; p < 0.00001]. There were no significant differences between the two groups in terms of operative time, minor complications (Clavien-Dindo Grade 1–2), major complications (Clavien-Dindo Grade 3–5), changes in renal function at 12 months post-operation, RFS (Recurrence-Free Survival), and OS (Overall Survival). Conclusion: The evidence provided by this meta-analysis indicates that the therapeutic effects of Cryoablation (CA) are similar to those of Robot-Assisted Partial Nephrectomy (RAPN) in terms of perioperative outcomes and renal function. However, the recurrence rate of tumors treated with CA is significantly higher. Systematic review registration: The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023465846). [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) patients beyond the Milan criteria (MC) who undergo liver resection have high recurrence rates and poor prognosis, and sometimes experience very early recurrence (VER) within six months after surgery. This study aimed to identify predictive factors, including the newly proposed C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, for VER after surgery for HCC beyond MC. Methods: We included patients who underwent initial liver resection for HCC beyond MC between 2000 and 2021. We defined VER as recurrence within six months after surgery and compared the clinicopathological factors and long-term prognosis between the VER and non-VER groups. Multivariate analysis identified risk factors for VER and evaluated the potential for prognostic stratification using these factors. Results: The overall survival (OS) and post-recurrence survival were significantly worse in the VER group compared to patients with recurrence in 7–12 months, over 12 months, and without recurrence (median survival time (MST) 1.16 vs. 5.14, 7.26, and undefined; and MST 0.81 vs. 4.34, and 5.48, respectively, P < 0.01). Alpha-fetoprotein (AFP) ≥ 200, non-simple nodule (SN) type on preoperative imaging, and CALLY index < 2.8 were independent prognostic factors (P < 0.01 for all). An increased risk factor count was correlated with poorer VER and OS rates, allowing for effective stratification. Conclusion: VER after hepatic resection for HCC beyond MC was associated with a significantly poorer prognosis. AFP, non-SN type on imaging, and CALLY index are valuable preoperative indicators. Patients with multiple risk factors have a worse prognosis and may be candidates for multimodal treatment. [ABSTRACT FROM AUTHOR]

To enhance the efficacy of radiotherapy (RT) in human papillomavirus (HPV)‐negative head and neck squamous cell carcinoma (HNSCC), we explored targeting ferroptosis, a regulated cell death process. We developed a gene signature associated with ferroptosis using Cox proportional hazard modeling in HPV‐negative HNSCC patients who underwent RT. This ferroptosis‐related gene signature (FRGS) was a significant predictor of overall survival and recurrence‐free survival in HPV‐negative HNSCC patients who received RT. Subtype B of the FRGS, characterized by decreased expression of ferroptosis inducers [nuclear receptor coactivator 4 (NCOA4) and natural resistance‐associated macrophage protein 2 homolog/divalent metal transporter 1 (NRAMP2/DMT1)] and increased expression of suppressors [phospholipid hydroperoxide glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1)], was associated with poorer prognosis, potentially indicating the inhibition of ferroptosis. Furthermore, our in vitro and in vivo studies demonstrated that treatment with statins, such as atorvastatin and simvastatin, induced ferroptosis and sensitized radioresistant HNSCC cells to irradiation, improving radiosensitivity and potentially enhancing the response to RT. Additionally, in xenograft models, the combination of statins and RT led to a significant reduction in tumor initiation. These findings provide valuable insights for enhancing treatment and improving prognosis in HPV‐negative HNSCC by targeting ferroptosis and utilizing statins to sensitize tumors to RT‐induced cell death. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions This study aims to develop a prognostic model that estimates the post‐operative risk of cancer‐specific mortality in patients with bladder cancer who underwent radical cystectomy (RC).We analyzed the data from patients with bladder cancer who had undergone radical cystectomy without receiving adjuvant chemotherapy across 36 institutions in the Japan Urological Oncology Group. The data were randomly split into training (N = 1348) and validation sets (N = 674) in a 2:1 ratio. Twenty‐five variables were analyzed, and a multivariable Cox regression model predicting cancer‐specific mortality was developed and validated. Prognostic scores were categorized into good and poor prognostic groups based on the upper tertile. The performance of the model was compared against the CheckMate 274 risk classification as a reference, which is used for determining the indication of adjuvant nivolumab therapy.The final model incorporated eight variables. In the validation set, it outperformed the CheckMate 274 risk classification with superior time‐dependent area under the curves (5‐year: 0.81 vs. 0.67) and was well‐calibrated. Furthermore, our model reclassified 27.8% of patients categorized as high‐risk by the CheckMate 274 risk classification into the good prognosis group.We developed and validated a prognostic model for patients with bladder cancer who underwent RC. This model will be beneficial in identifying patients with poor prognosis and those who are potential candidates for clinical trials of adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. Methods: Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. Results: A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18–0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16–0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08–0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021). Conclusions: High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC). Methods: The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS). Results: 133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012). Conclusions: Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence. [ABSTRACT FROM AUTHOR]

Objective: We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods: This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results: There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion: ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Identifying the drive genes and inhibiting their significant signals were persistently the main concepts in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear.A total of 120 OCSCC patients with corresponding pathologic specimens were collected in Taiwan. Whole‐exome sequencing was done and the prognostic impact of each gene was analyzed. TCGA database was used to validate.The incidences of caspase‐8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase‐8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) ([95% CI]: 3.83 [1.84–7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51 [1.00–2.29]). The 5‐year OSs of the patients with or without caspase‐8 mutation were 38.1% vs. 75.3% (p < 0.001) (HR [95% CI]: 3.264 [1.645–6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% (p = 0.048) (1.513 [1.001–2.288]) in the TCGA cohorts, respectively. Caspase‐8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. CASP8 R127* and R494*, defined as pathogenic mutations in ClinVar, were presented in both cohorts.Caspase‐8 mutation was the most significant genetic alteration impacting prognosis. [ABSTRACT FROM AUTHOR]

Portal vein tumor thrombosis (PVTT) is one of the common complications of HCC and represents a sign of poor prognosis. PVTT signifies advanced liver cancer, deteriorating liver function, and heightened susceptibility to intrahepatic dissemination, systemic metastasis, and complications related to portal hypertension. It is important to seek novel strategies for PVTT arising from HCC. Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. This study aimed to investigate the diagnostic value of the combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) in predicting the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan–Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI 0.697–0.888). Based on the DALP classification (three scores: 0–2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR] 5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention. [ABSTRACT FROM AUTHOR]

The systemic immune-inflammatory index (SII) has been identified as an independent prognostic factor for multiple diseases. However, the impact of SII on outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective study enrolled patients with ACLF treated with artificial liver support system. Restricted cubic spline (RCS) (knots at the 10th, 50th, and 90th percentiles) and Cox proportional hazards models were applied to investigate the relationship between SII and 90-day transplant-free survival and overall survival in patients with ACLF. A total of 258 patients with ACLF were included. The 90-day transplant-free survival rate and overall survival rate were 58.5% and 66.3%. The SII was 465.5 (277.3–804.4). Adjusted RCS models showed linear exposure–response relationship between SII and 90-day transplant-free survival (P for overall < 0.001, P for nonlinear = 0.154) and 90-day overall survival (P for overall < 0.001, P for nonlinear = 0.103), and adjusted Cox models confirmed the positive relationship. Compared with patients with SII < 480, patients with ≥ 480 had more serious condition, lower 90-day transplant-free survival rate (46.8% vs. 69.7%, adjusted HR (95% CI) for transplant or death: 2.13 (1.40–3.23), P < 0.001), and lower 90-day overall survival rate (56.3% vs. 75.8%; adjusted HR (95% CI) for death: 2.26 (1.42–3.61), P = 0.001). Stratified Cox models suggested no potential modifiers in the relationship between SII and 90-day transplant-free survival. Our findings suggested SII was positively associated with poor short-term prognosis of ACLF. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan–Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. Results: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan–Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). Conclusions: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS. [ABSTRACT FROM AUTHOR]

Purpose: This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results: This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p < 0.0001], and fewer overall complications [OR 0.62; 95% CI 0.45 to 0.86; p = 0.004], but a higher recurrence rate [OR 7.83; 95% CI 4.32 to 14.19; p < 0.00001]. There were no significant differences between the two groups in terms of operative time, minor complications (Clavien-Dindo Grade 1–2), major complications (Clavien-Dindo Grade 3–5), changes in renal function at 12 months post-operation, RFS (Recurrence-Free Survival), and OS (Overall Survival). Conclusion: The evidence provided by this meta-analysis indicates that the therapeutic effects of Cryoablation (CA) are similar to those of Robot-Assisted Partial Nephrectomy (RAPN) in terms of perioperative outcomes and renal function. However, the recurrence rate of tumors treated with CA is significantly higher. Systematic review registration: The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023465846). [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The purpose of this phase 1 trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel (PTX) for patients with gastric cancer metastatic to the peritoneum.A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel at weekly treatments for 3 weeks, followed by a 1‐week break, and then three additional treatments. The primary objective was to define the maximum tolerated dose. Secondary end points included safety, tolerability, and antitumor activity.A total of 25 patients were treated between January 2020 and April 2023. Five dose‐limiting toxicities were observed at 100 mg/m2. Treatment‐related grade 3–4 toxicity included leukopenia (32%) and neutropenia (32%). Seven patients required a schedule change to every other week treatments. The maximum tolerated dose for intraperitoneal PTX was 100 mg/m2. The peritoneum post‐intraperitoneal PTX demonstrated progression in five (20%), stable disease in five (20%), improvement in 10 (40%), and not evaluable in five (20%). Eight patients (32%) had resolution of their peritoneal disease and seven (28%) underwent attempted resection. The median overall survival (OS) from the diagnosis of metastatic disease was 18.8 months and from the date of treatment initiation was 10.8 months. One‐, 2‐, and 3‐year OS rates from the diagnosis of metastatic disease were 84%, 38%, and 25%, respectively.Paclitaxel may be safely used at intraperitoneal doses of 100 mg/m2. Neutropenia associated with weekly treatments was common. Peritoneal complete clinical response rates with multimodality therapy including PTX were promising. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment.We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses.Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage.Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment. [ABSTRACT FROM AUTHOR]

Summary Data on haematological features of telomere biology disorders (TBD) remain scarce. We describe haematological, extra‐haematological characteristics and prognosis of 127 genetically confirmed TBD patients diagnosed after the age of 15. Ninety‐three index cases and 34 affected relatives were included. At diagnosis of TBD, 76.3% of index cases had haematological features, half pulmonary features and a third liver features. At diagnosis, bone marrow failure (BMF) was present in 59 (46.5%), myelodysplastic syndrome (MDS) in 22 (17.3%) and acute myeloid leukaemia (AML) in 2 (1.6%) while 13 (10.2%) developed or worsened bone marrow involvement during follow‐up. At diagnosis, compared to MDS/AML patients, BMF patients were younger (median 23.1 years vs. 43.8, p = 0.007), and had a better outcome (4‐year overall survival 76.3% vs. 31.8%, p < 0.001). While frequencies and burden of cytogenetical and somatic mutations increased significantly in myeloid malignancies, some abnormalities were also observed in patients with normal blood counts and BMF, notably somatic spliceosome variants. Solid cancers developed in 8.7% patients, mainly human papillomavirus‐related cancers and hepatocellular carcinomas. TBD is a multiorgan progressive disease. While BMF is the main haematological disorder, high‐risk myeloid malignancies are common, and are, together with age, the only factors associated with a worse outcome. [ABSTRACT FROM AUTHOR]

Background: Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. Methods: In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c‐MET, VEGFR1, c‐KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti–PD‐L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression‐free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. Results: Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%–32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment‐related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35–5.68 months) and 5.98 months (95% CI, 3.71–8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%–83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%–89.10%) in patients with HCC. Conclusions: Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy‐refractory patients with advanced ESCC and HCC. This single‐arm, multicenter, open‐label, phase 1b cohort trial aimed to estimate the safety and efficacy of anti–PD‐L1 antibody TQB2450 and tyrosine kinase receptor inhibitor AL2846 combination therapy in patients with immunotherapy‐refractory advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC). The combination therapy exhibited a favorable safety profile in immunotherapy‐refractory patients with advanced ESCC and HCC. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high‐dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. Methods: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first‐line cisplatin‐based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression‐free survival and overall survival were analyzed using the Kaplan–Meier method. Medians with 95% confidence intervals were also calculated along with 2‐year probabilities. Results: The median age at HDCT was 30 years (range, 18–61 years). With a median follow‐up of 4.7 years (range, 1–14 years), the 2‐year progression‐free survival rate was 31% (95% confidence interval, 16%–47%), and the 2‐year overall survival rate was 35% (95% confidence interval, 19%–52%). At last follow‐up, nine patients (28%) remained without evidence of disease, including two platinum‐refractory patients and two patients who were receiving HDCT as third‐line therapy. There were three treatment‐related deaths. Conclusions: Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum‐refractory and third‐line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population. Patients who have relapsed primary mediastinal nonseminomatous germ cell tumors have poor outcomes with salvage chemotherapy. The authors report the results of high‐dose chemotherapy and peripheral blood stem cell transplantation, which permit more rapid succession to the subsequent cycle and potentially improved efficacy compared with historical regimens. [ABSTRACT FROM AUTHOR]

This study aims to develop and validate a nomogram for predicting overall survival (OS) in Asian patients with Esophageal Cancer (EC). Data from Asian EC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for initial variable selection, followed by multivariate Cox regression analysis to identify independent prognostic factors. A nomogram was subsequently constructed based on these factors. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves and calibration curves, while the clinical utility of the nomogram was assessed through decision curve analysis (DCA). The LASSO regression and multivariate Cox regression analysis identified age, sex, marital status, tumor size, M stage, surgery, and chemotherapy as independent prognostic factors. The ROC curve results demonstrated that the area under the curve (AUC) values for predicting 1-year, 3-year, and 5-year OS in the training cohort were 0.770, 0.756, and 0.783, respectively. In the validation cohort, the AUC values were 0.814, 0.763, and 0.771, respectively. Calibration curves indicated a high concordance between predicted and actual OS. The DCA demonstrated that the nomogram has significant clinical applicability. This nomogram provides reliable predictions and valuable guidance for personalized survival estimates and high-risk patient identification. [ABSTRACT FROM AUTHOR]

Background: Tumour, nodes, and metastases (TNM) staging has been deficient in prognosticating in patients suffering from non-small cell lung cancer (NSCLC). To supplement TNM staging, this systematic review and meta-analysis aimed to evaluate the prognostic value of the regulatory T cells (Treg). Methods: A keyword search was conducted in MEDLINE and EMBASE for full-text original human studies from any region published in English during the last 12 years. Eligible for inclusion were studies evaluating the prognostic value of the number of Treg cells in NSCLC except case studies, case series, systematic reviews, and meta-analyses. Two reviewers (one reviewer used an automation tool) independently screened the studies and assessed risk-of-bias using the Quality in Prognosis Studies (QUIPS) tool. Meta-analysis was done for studies reporting significant multivariate hazard ratio (HR). Results: Out of 809 retrievals, 24 studies were included in the final review. The low number of Treg cells was found significantly associated with improved overall survival (pooled log OR, 1.646; 95% CI, 1.349, 1.944; p (2-tailed) <.001; SE, 0.1217), improved recurrence-free survival (HR, 1.99; 95% CI, 1.15, 3.46; p =.01), improved progression-free survival (pooled log OR, 2.231; 95% CI, 0.424, 4.038; p (2-tailed).034; SE, 0.4200), and worse disease-free survival (pooled log OR, 0.992; 95% CI, 0.820, 1.163; p (2-tailed).009; SE, 0.0135), especially when identified by forkhead box P3 (FOXP3), in any stage or non-metastatic NSCLC. Conclusion: A low number of Treg cells indicated better survival, suggesting its potential use as a prognostic biomarker in NSCLC. Systematic review registration: The protocol of this review was prospectively registered on PROSPERO on August 28, 2021, and was assigned the registration number CRD42021270598. The protocol can be accessed from PROSPERO website. [ABSTRACT FROM AUTHOR]

Purpose: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended. Methods: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included. Results: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03–0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce. Conclusion: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies. [ABSTRACT FROM AUTHOR]

Background: Evaluating outcome reliability is critical in real-world evidence studies. Overall survival is a common outcome in these studies; however, its capture in real-world data (RWD) sources is often incomplete and supplemented with linked mortality information from external sources. Conflicting recommendations exist for censoring overall survival in real-world evidence studies. This simulation study aimed to understand the impact of different censoring methods on estimating median survival and log hazard ratios when external mortality information is partially captured. Methods: We used Monte Carlo simulation to emulate a non-randomized comparative effectiveness study of two treatments with RWD from electronic health records and linked external mortality data. We simulated the time to death, the time to last database activity, and the time to data cutoff. Death events after the last database activity were attributed to linked external mortality data and randomly set to missing to reflect the sensitivity of contemporary real-world data sources. Two censoring schemes were evaluated: (1) censoring at the last activity date and (2) censoring at the end of data availability (data cutoff) without an observed death. We assessed the performance of each method in estimating median survival and log hazard ratios using bias, coverage, variance, and rejection rate under varying amounts of incomplete mortality information and varying treatment effects, length of follow-up, and sample size. Results: When mortality information was fully captured, median survival estimates were unbiased when censoring at data cutoff and underestimated when censoring at the last activity. When linked mortality information was missing, censoring at the last activity date underestimated the median survival, while censoring at the data cutoff overestimated it. As missing linked mortality information increased, bias decreased when censoring at the last activity date and increased when censoring at data cutoff. Conclusions: Researchers should consider the completeness of linked external mortality information when choosing how to censor the analysis of overall survival using RWD. Substantial bias in median survival estimates can occur if an inappropriate censoring scheme is selected. We advocate for RWD providers to perform validation studies of their mortality data and publish their findings to inform methodological decisions better. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). β-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received β-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. Results: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0–6.6] and 9.8 months [95% CI: 7.2–12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. Conclusion: β-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Methods: From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups. Results: A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema. Conclusion: No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen. [ABSTRACT FROM AUTHOR]

Background: HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival. Materials and methods: The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA). Results: Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database. Conclusion: Overall, our study demonstrates that HPV-positive and HPV-negative cells' exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Overall Survival (OS) and Progression-Free Interval (PFI) as survival times have been collected in The Cancer Genome Atlas (TCGA). It is of biomedical interest to consider their dependence in pathway detection and survival prediction. We intend to develop novel methods for integrating PFI as condition based on parametric survival models for identifying pathways associated with OS and predicting OS. Results: Based on the framework of conditional probability, we developed a family of frailty-based parametric-models for this purpose, with exponential or Weibull distribution as baseline. We also considered two classes of existing methods with PFI as a covariate. We evaluated the performance of three approaches by analyzing RNA-seq expression data from TCGA for lung squamous cell carcinoma and lung adenocarcinoma (LUNG), brain lower grade glioma and glioblastoma multiforme (GBMLGG), as well as skin cutaneous melanoma (SKCM). Our focus was on fourteen general cancer-related pathways. The 10-fold cross-validation was employed for the evaluation of predictive accuracy. For LUNG, p53 signaling and cell cycle pathways were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. For GBMLGG, ten pathways (e.g., Wnt signaling, JAK-STAT signaling, ECM-receptor interaction, etc.) were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated better predictive performance compared to the approaches without the consideration of PFI. For SKCM, p53 signaling pathway was detected only by our Weibull-baseline-based model. And three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. Conclusions: Based on our study, it is necessary to incorporate PFI into the survival analysis of OS. Furthermore, PFI is a survival-type time, and improved results can be achieved by our conditional-probability-based approach. [ABSTRACT FROM AUTHOR]

Objective: To explore the high-risk factors affecting the prognosis of pT1 − 2N1M0 patients after mastectomy, establish a nomogram prediction model, and screen the radiotherapy benefit population. Method: The clinical data of 936 patients with pT1 − 2N1M0 who underwent mastectomy in the fourth hospital of Hebei Medical University from 2010 to 2016 were retrospectively analyzed. There were 583 patients received postmastectomy radiotherapy(PMRT), and 325 patients without PMRT. Group imbalances were mitigated using the propensity score matching (PSM) method, and the log-rank test was employed to compare overall survival (OS) and disease-free survival (DFS) between the cohorts. The efficacy of PMRT across various risk groups was evaluated using a nomogram model. Result: The median follow-up period was 98 months, Patients who received PMRT demonstrated significantly improved 5-year and 8-year OS and DFS compared to those who did not (P < 0.001). Multivariate analysis revealed that age, primary tumor site, positive lymph node, stage, and Ki-67 level independently influenced OS, while age, primary tumor site, and stage independently affected DFS. PMRT drastically enhanced OS in the high-risk group (P = 0.001), but did not confer benefits in the low-risk and intermediate risk groups (P = 0.057, P = 0.099). PMRT led to a significant improvement in disease-free survival (DFS) among patients in the intermediate and high-risk groups (P = 0.036, P = 0.001), whereas the low-risk group did not experience a significant benefit (P = 0.475). Conclusion: Age ≤ 40 years, tumor located in the inner quadrant or central area, T2 stage, 2–3 lymph nodes metastasis, and Ki67 > 30% were the high-risk factors affecting the prognosis of this cohort of patients. In OS nomogram, patients with a risk score of 149 or higher who received PMRT exhibited improved OS. Similarly, in DFS nomogram, patients with a risk score of 123 or higher who received PMRT demonstrated enhanced DFS. [ABSTRACT FROM AUTHOR]

Ovarian cancer's asymptomatic nature, high recurrence rate, and resistance to platinum‐based chemotherapy highlight the need to find and characterize new diagnostic and therapeutic targets. While prior studies have linked aberrant expression of fibroblast growth factor 8 (FGF8) to various cancer types, its precise role has remained elusive. Recently, we observed that FGF8 silencing reduces the cancer‐promoting properties of ovarian cancer cells, and thus, this study aimed to understand how FGF8 regulates the development of ovarian cancer. LC‐MS/MS‐based quantitative proteomics analysis identified 418 DEPs, and most of them were downregulated in FGF8‐silenced ovarian cancer cells. Many of these DEPs are associated with cancer progression and unfavorable prognosis. To decipher the biological significance of DEPs, bioinformatics analyses encompassing gene ontology, pathway analysis, protein‐protein interaction networks, and expression analysis of hub genes were carried out. Hub genes identified in the FGF8 protein network were upregulated in ovarian cancer compared to controls and were linked to poor prognosis. Subsequently, the expression of hub genes was correlated with patient survival and regulation of the tumor microenvironment. Conclusively, FGF8 and associated hub genes help in the progression of ovarian cancer, and their overexpression may lead to higher immune infiltration, poor prognosis, and poor survival. [ABSTRACT FROM AUTHOR]

Background: Our previous research showed that Porphyromonas gingivalis (P. gingivalis) infection can activate the inflammatory signaling pathway and promotes the malignancy development of esophageal squamous cell carcinoma (ESCC). However, the prognostic significance of inflammatory response-related genes (IRRGs) in P. gingivalis -infected ESCC requires further elucidation. Hence, our study constructed a prognostic signature based on P. gingivalis and IRRGs to forecast the survival of patients with ESCC, which may provide insight into new treatment options for ESCC patients. Methods: Differentially expressed genes (DEGs) were identified in P.gingivalis -infected and P.gingivalis -uninfected ESCC cell by RNA sequencing. A risk model was constructed and validated using the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database by using univariate Cox regression analysis, LASSO, and the multivariate Cox regression analysis. Kaplan-Meier analysis was carried out to compare the overall survival (OS) between high-risk and low-risk groups. Single-sample gene set enrichment analysis was used to analyze the immune cell infiltration. The Genomics of Drug Sensitivity in Cancer database was used to predict drug sensitivity. Results: There were 365 DEGs between the P.gingivalis -infected and P.gingivalis -uninfected groups. Four genes including DKK1, ESRRB, EREG, and RELN were identified to construct the prognostic risk model (P =.012, C-index = 0.73). In both the training and validation sets, patients had a considerably shorter OS in the high-risk group than those in the low-risk group (P <.05). A nomogram was established using the risk score, gender, and N stage which could effectively forecast the prognosis of patients (P =.016, C-index = 0.66). The high-risk group displayed lower immune infiltrating cells, such as activated dendritic cells, type 2 T helper cells, and neutrophils (P <.05). A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. Conclusion: We demonstrated the potential of a novel signature constructed from 4 P. gingivalis -related IRRGs for prognostic prediction in ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Tumour, nodes, and metastases (TNM) staging has been deficient in prognosticating in patients suffering from non-small cell lung cancer (NSCLC). To supplement TNM staging, this systematic review and meta-analysis aimed to evaluate the prognostic value of the regulatory T cells (Treg). Methods: A keyword search was conducted in MEDLINE and EMBASE for full-text original human studies from any region published in English during the last 12 years. Eligible for inclusion were studies evaluating the prognostic value of the number of Treg cells in NSCLC except case studies, case series, systematic reviews, and meta-analyses. Two reviewers (one reviewer used an automation tool) independently screened the studies and assessed risk-of-bias using the Quality in Prognosis Studies (QUIPS) tool. Meta-analysis was done for studies reporting significant multivariate hazard ratio (HR). Results: Out of 809 retrievals, 24 studies were included in the final review. The low number of Treg cells was found significantly associated with improved overall survival (pooled log OR, 1.646; 95% CI, 1.349, 1.944; p (2-tailed) <.001; SE, 0.1217), improved recurrence-free survival (HR, 1.99; 95% CI, 1.15, 3.46; p =.01), improved progression-free survival (pooled log OR, 2.231; 95% CI, 0.424, 4.038; p (2-tailed).034; SE, 0.4200), and worse disease-free survival (pooled log OR, 0.992; 95% CI, 0.820, 1.163; p (2-tailed).009; SE, 0.0135), especially when identified by forkhead box P3 (FOXP3), in any stage or non-metastatic NSCLC. Conclusion: A low number of Treg cells indicated better survival, suggesting its potential use as a prognostic biomarker in NSCLC. Systematic review registration: The protocol of this review was prospectively registered on PROSPERO on August 28, 2021, and was assigned the registration number CRD42021270598. The protocol can be accessed from PROSPERO website. [ABSTRACT FROM AUTHOR]

Objective: To compare therapeutic outcomes of predicted proliferative and nonproliferative hepatocellular carcinoma (HCC) after microwave ablation (MWA) using a previously developed imaging-based predictive model, the SMARS score. Methods: This multicenter retrospective study included consecutive 635 patients with unresectable HCC who underwent MWA between August 2013 and September 2020. Patients were stratified into predicted proliferative and nonproliferative phenotypes according to the SMARS score. Overall survival (OS) and recurrence-free survival (RFS) were compared between the predicted proliferative and nonproliferative HCCs before and after propensity score matching (PSM). OS and RFS were also compared between the two groups in subgroups of tumor size smaller than 30 mm and tumor size 30–50 mm. Results: The SMARS score classified 127 and 508 patients into predicted proliferative and nonproliferative HCCs, respectively. The predicted proliferative HCCs exhibited worse RFS but equivalent OS when compared with nonproliferative HCCs before (p < 0.001 for RFS; p = 0.166 for OS) and after (p < 0.001 for RFS; p = 0.456 for OS) matching. Regarding subgroups of tumor size smaller than 30 mm (p = 0.098) and tumor size 30–50 mm (p = 0.680), the OSs were similar between the two groups. However, predicted proliferative HCCs had worse RFS compared to nonproliferative HCCs in the subgroup of tumor size 30–50 mm (p < 0.001), while the RFS did not differ in the subgroup of tumor size smaller than 30 mm (p = 0.141). Conclusion: Predicted proliferative HCCs have worse RFS than nonproliferative ones after MWA, especially in tumor size larger than 30 mm. However, the phenotype of the tumor may not affect the OS. Critical relevance statement: Before performing microwave ablation for hepatocellular carcinoma, the tumor phenotype should be considered because it may affect the therapeutic outcome. Key Points: Proliferative hepatocellular carcinoma (HCC) may be identified using the SMARS score, an imaging-based predictive model. SMARS predicted proliferative HCCs have worse recurrence-free and equivalent overall survival compared to nonproliferative HCC after microwave ablation. Tumor phenotype should be considered before performing microwave ablation. [ABSTRACT FROM AUTHOR]

Plastic waste has recently become a major global environmental concern and one of the biggest challenges has been seeking for alternative management options. Several studies have revealed the potential of several coleopteran species to degrade plastics, and this is the first research paper on plastic-degradation potential by lesser mealworms from Africa. This study evaluated the whole mitogenomic profile of the lesser mealworm to further identify the insect. The ability of the mealworm to consume Polystyrene (PS) was also evaluated alongside its associated gut microbiota diversity. Our results showed a complete circular mitochondrial genome which clustered closely to the Alphitobius genus but also suggested that our insect might be a new subspecies which require further identification. During the PS feeding trials, overall survival rates of the larvae decreased when fed a sole PS diet while PS intake was observed to increase over a 30-day period. The predominant bacteria observed in larvae fed PS diets were Kluyvera, Lactococcus, Klebsiella, Enterobacter, and Enterococcus, while Stenotrophomonas dominated the control diet. These findings demonstrated that the newly identified lesser mealworm can survive on a PS diet and has a consortium of important bacteria strongly associated with PS degradation. This work provides a better understanding of bioremediation applications, paving the way for further research into the metabolic pathways of plastic-degrading microbes and bringing hope to solving plastic waste pollution while providing high-value insect protein towards a circular economy. [ABSTRACT FROM AUTHOR]

There is increasing awareness of radiotherapy's potential side effects, such as lymphopenia. Therefore, this study aimed to establish the association between WBRT and the development of lymphopenia in patients with brain metastases undergoing brain radiotherapy (RT), along with evaluating the corresponding clinical outcomes. Including 116 patients with brain metastases undergoing brain radiotherapy, the study collected the absolute lymphocyte counts (ALC) within 2 weeks before brain radiotherapy (pre-radiotherapy, pre-RT), as well as ones at 1 and 2 months after completing RT (post-RT). Univariate and multivariate analyses were performed to identify associations between radiation modality and post-RT ALC. The relationships between post-RT ALC and overall survival were evaluated with Kaplan–Meier analysis and a multivariate Cox regression model. The median ALC definitely decreased at 1 month post-RT, but at 2 months post-RT, gradually rose but not to the pre-RT ALC. The multivariate analysis identified WBRT and lower pre-RT ALC as independent risk factors associated with the decrease in post-RT ALC at 1 month. It also revealed more than 4 brain metastases, G3-4 lymphopenia at 1 month and lower post-RT ALC at 2 months exhibited significantly worse prognosis regardless of the radiation modality. However, there was indeed an independent correlation between radiation modality and the outcome of intracranial progression-free survival (PFS). To approach the feasibility and reasonableness of treatment, clinicians should carefully consider various factors to achieve long-term survival of patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes including safety and efficacy of drug-eluting bead trans-arterial chemo-embolization (DEB-TACE) in the treatment of locally advanced hepatocellular carcinoma (LA-HCC). Materials and methods: In this single-center, retrospective study, we evaluated 471 consecutive patients with LA-HCC who underwent DEB-TACE from 2015 to 2020. Efficacy of DEB-TACE was assessed based on the imaging response using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the biochemical response using alpha-fetoprotein (AFP) levels at 1-month follow-up. Adverse events, progression free survival (PFS), and overall survival were also examined. Results: HCC distribution was bilobar in 49% with largest lesion mean size of 4.3 cm ± 3.2, and a majority of patients (46.7%) were Barcelona Club Liver Cancer (BCLC) stage B. Complete radiologic response was achieved in 120 (25.5%) patients, comparable to a reported 28% rate for conventional TACE. Biochemically, 41 (8.7%) patients achieved complete response, and 113 (24%) had a partial response. A total of 59 (12.5%) patients were successfully bridged to liver transplantation. Major adverse events were observed in 3%, while 7.2% experienced post-embolization syndrome. Mean PFS was 6.7 months ± 6.6, and overall survival was 64%, 16.3%, 2.1% at 1, 3, and 5 years, respectively. Conclusion: Based on our real world experience at a single center, DEB-TACE remains the locoregional therapy of choice for LA-HCC due to its favorable safety and efficacy profile. [ABSTRACT FROM AUTHOR]

Background: The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability. Methods: This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP. Results: A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03). Conclusions: CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP. [ABSTRACT FROM AUTHOR]