Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis.

BACKGROUND: Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. METHODS: Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. RESULTS: Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. CONCLUSIONS: Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics.

Univariable and multivariable Mendelian randomization study identified the key role of gut microbiota in immunotherapeutic toxicity.

BACKGROUND: In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse events (irAEs). However, the exact roles of gut microbiota and the causal associations are yet to be clarified. METHODS: To investigate this, we first conducted a univariable bi-directional two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) for gut microbiota were retrieved from the MiBioGen consortium (18,340 participants). GWAS summary data for irAEs were gathered from an ICIs-treated cohort with 1,751 cancer patients. Various MR analysis methods, including inverse variance weighted (IVW), MR PRESSO, maximum likelihood (ML), weighted median, weighted mode, and cML-MA-BIC, were used. Furthermore, multivariable MR (MVMR) analysis was performed to account for possible influencing instrumental variables. RESULTS: Our analysis identified fourteen gut bacterial taxa that were causally associated with irAEs. Notably, Lachnospiraceae was strongly associated with an increased risk of both high-grade and all-grade irAEs, even after accounting for the effect of BMI in the MVMR analysis. Akkermansia, Verrucomicrobiaceae, and Anaerostipes were found to exert protective roles in high-grade irAEs. However, Ruminiclostridium6, Coprococcus3, Collinsella, and Eubacterium (fissicatena group) were associated with a higher risk of developing high-grade irAEs. RuminococcaceaeUCG004, and DefluviitaleaceaeUCG011 were protective against all-grade irAEs, whereas Porphyromonadaceae, Roseburia, Eubacterium (brachy group), and Peptococcus were associated with an increased risk of all-grade irAEs. CONCLUSIONS: Our analysis highlights a strong causal association between Lachnospiraceae and irAEs, along with some other gut microbial taxa. These findings provide potential modifiable targets for managing irAEs and warrant further investigation.

Tyrosine kinase inhibitors for radioiodine refractory differentiated thyroid cancer: A systematic review and meta-analysis.

BACKGROUND: The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs) in radioiodine refractory differentiated thyroid cancer (RAIR-DTC). However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC. METHODS: This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT) of RAIR-DTC patients treated with the TKI system. Outcomes, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were reported. RESULTS: Seven studies involving 1310 patients with RAIR-DTC was conducted to compare the PFS and OS of various TKI monotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR] 0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR 0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC, although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTC patients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment. CONCLUSIONS: The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC. This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.

The association between aspirin use and immune-related adverse events in specific cancer patients receiving ICIs therapy: analysis of the FAERS database.

Background: The promise of immune checkpoint inhibitors (ICIs) therapy in cancer treatment is tempered by the occurrence of immune-related adverse events (irAEs). Many patients undergoing ICIs also take aspirin, but the association between aspirin and irAEs is not well understood. Methods: This study analyzed adverse reaction data associated with the use of ICIs in the US Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database, from the approval date of each drug until 1 October 2022. Multivariate logistic regression was employed to assess the association of aspirin use with irAEs in patients receiving ICIs. Results: The results indicated that aspirin use was associated with an increased risk of irAEs in a pan-cancer analysis, with a more pronounced association in specific cancer types such as lung cancer, mesothelioma, and pancreatic cancer. However, in lymphoma, aspirin use was associated with a reduced risk of irAEs. Furthermore, aspirin use was associated with an increased risk of certain irAEs, such as anemia, colitis, myocarditis, myositis, pancreatitis, pericarditis, and pneumonia, while it was associated with a reduced risk of rash, Stevens-Johnson syndrome, and thyroiditis. Conclusion: This study has unveiled an association between aspirin use and irAEs in cancer patients receiving ICIs therapy, emphasizing the need for individualized consideration of patients' medication history when devising cancer treatment plans to enhance efficacy and reduce risks.

Liquid‒liquid phase separation: roles and implications in future cancer treatment.

Liquid‒liquid phase separation (LLPS) is a phenomenon driven by weak interactions between biomolecules, such as proteins and nucleic acids, that leads to the formation of distinct liquid-like condensates. Through LLPS, membraneless condensates are formed, selectively concentrating specific proteins while excluding other molecules to maintain normal cellular functions. Emerging evidence shows that cancer-related mutations cause aberrant condensate assembly, resulting in disrupted signal transduction, impaired DNA repair, and abnormal chromatin organization and eventually contributing to tumorigenesis. The objective of this review is to summarize recent advancements in understanding the potential implications of LLPS in the contexts of cancer progression and therapeutic interventions. By interfering with LLPS, it may be possible to restore normal cellular processes and inhibit tumor progression. The underlying mechanisms and potential drug targets associated with LLPS in cancer are discussed, shedding light on promising opportunities for novel therapeutic interventions.

Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study.

Background: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. Methods: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. Results: In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. Conclusion: This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.

Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study.

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear. Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated. Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results. Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention.

Prevalence and Prognostic Significance of Malnutrition in Patients with Brain Metastasis.

BACKGROUND: Malnutrition is a severe but modifiable risk factor for cancers. However, the relationship between malnutrition and the survival of patients with brain metastases has not been fully revealed. We aimed to evaluate the prevalence of malnutrition and assess its prognostic value on patients with brain metastases. METHODS: We retrospectively recruited 2,633 patients with brain metastases between January 2014 and September 2020. Three malnutrition scores were used to evaluate patients' malnutrition status at their first admission, including controlling nutritional status, the nutritional risk index, and the prognostic nutritional index. The association between malnutrition and overall survival (OS) was estimated. RESULTS: The three malnutrition scores were associated with each other and with body mass index (BMI). Malnutrition assessed by any of the three scores was significantly associated with poor OS. All three malnutrition scores were better indicators than BMI, and adding malnutrition scores to the Graded Prognostic Assessment (GPA) scoring system could significantly improve the accuracy of prognosis prediction. CONCLUSIONS: Malnutrition monitoring using any of the three malnutrition scores on patients' first admission could be a better survival indicator for patients with brain metastases compared with BMI alone. IMPACT: Malnutrition is a more significant indicator of survival stratification compared with BMI. Adding malnutrition to the GPA score system achieves better survival prediction.

Function of stem cells in radiation-induced damage.

PURPOSE: The aim of this review is to discuss previous studies on the function of stem cells in radiation-induced damage, and the factors affecting these processes, in the hope of improving our understanding of the different stem cells and the communication networks surrounding them. This is essential for the development of effective stem cell-based therapies to regenerate or replace normal tissues damaged by radiation. CONCLUSION: In salivary glands, senescence-associated cytokines and inflammation-associated cells have a greater effect on stem cells. In the intestinal glands, Paneth cells strongly affect stem cell-mediated tissue regeneration after radiation treatment. In the pancreas, ß-cells as well as protein C receptor positive (Procr) cells are expected to be key cells in the treatment of diabetes. In the bone marrow, a variety of cytokines such as CXC-chemokine ligand 12 (CXCL12) and stem cell factor (SCF), contribute to the functional recovery of hematopoietic stem cells after irradiation.

Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk.

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K-Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infection-induced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions.

Association of smoking with the survival of patients with brain metastasis of lung cancer.

Background: Smoking is associated with increased mortality in patients with cancer. However, there are limited data on the impact of smoking on the survival of patients with brain metastases. Therefore, this study aimed to evaluate whether smoking was associated with survival and whether smoking cessation was beneficial to these patients. Methods: This study used lung cancer with a brain metastasis cohort of the West China Hospital of Sichuan University from 2013 to 2021. Patients were stratified according to smoking history; the distribution, clinical characteristics, and survival data of each group were estimated. Kaplan-Meier analysis and risk analysis were performed for the survival endpoint. Results: Of the 2,647 patients included in the analysis, the median age was 57.8 years, and 55.4% were men. Among them, 67.1% had no smoking history, 18.9% still smoked, and 14% reported quitting smoking. Compared with never smokers, current smokers [HR, 1.51 (95% CI, 1.35-1.69), p < 0.01] and former smokers [HR, 1.32 (95% CI, 1.16-1.49), p<0.01] had an increased risk of death. However, quitting smoking was not associated with improved survival [HR, 0.90 (95% CI, 0.77-1.04), p = 0.16]. The overall survival increased with the increase of smoking cessation years. Conclusions: In lung cancer patients with brain metastases, smoking was associated with an increased risk of death, but quitting smoking was not associated with improved survival.

Association between nut consumption and cancer risk: a meta-analysis.

This study aims to conduct a meta-analysis and dose-response analysis of the relationship between nut intake and cancer risk and mortality. Electronic databases were searched. A meta-analysis was conducted to calculate the pooled effect sizes (ESs) with the corresponding 95% CIs, and a dose-response analysis was performed. A random-effects model was used in the statistical analysis. Two independent reviewers completed the full-text screening, data extraction, and quality assessment. We included 17 articles in the present meta-analysis. Total nuts intake was revealed to be significantly associated with reduced cancer risk (ES: 0.9; 95% CI: 0.86-0.95; P < 0.001) and cancer mortality (ES: 0.88; 95% CI: 0.85-0.92, P < 0.001), especially lung cancer risk (ES: 0.86; 95% CI: 0.81-0.91, P < 0.001) and gastric cancer risk (ES: 0.79; 95% CI: 0.68-0.91, P = 0.001). Moreover, a 10 g/d increment of tree nuts consumption was associated with a 20% cancer mortality reduction (ES: 0.80; 95% CI: 0.71-0.89; P < 0.0001). Nuts intake is significantly associated with the reduction of cancer risk and mortality. Especially, nuts intake is significantly associated with reduced lung cancer risk and gastric cancer risk. Noticeably, a 10 g/d increase in tree nuts intake is related to a 20% reduction in overall cancer mortality.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

Association between Statin Use and Survival in Cancer Patients with Brain Metastasis: Retrospective Analysis from the Chinese Population.

Brain metastasis predicts a worse clinical outcome in cancer patients. Emerging observational evidence suggests that statin use has a protective role in overall cancer prevention. Whether statin use could also be a supplementary treatment for advanced-stage cancers remains under researched and controversial. Data for cancer patients with brain metastasis were selected from the linked electronic medical care records of the West China Hospital between October 2010 and July 2019. Fisher's exact chi-square test was used to compare the differences between cohorts. Multivariate Cox analysis was conducted to adjust the potential confounders in evaluating the role of statin use in the overall survival (OS) of cancer patients with brain metastasis. There were 4510 brain metastatic patients included in this retrospective study. The overall statin use rate in our patients was 5.28% (219 cases/4510 cases). Compared with the non-statin use cohort, patients who received statin therapy showed a decreased Karnofsky performance score (KPS, p < 0.001) and lower high-density lipoprotein (HDL, p = 0.020) but higher body mass index (BMI, p = 0.002) and triglyceride (TG, p < 0.001) at admission. There was no association between statin use and the OS of the cancer patients with brain metastasis (Hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.73−1.07, p = 0.213) during the univariate analysis. However, after adjusting for baseline patient characteristics, metabolism indicators, and cancer-specific factors, statin use was shown to have a significant protective role, aiding the survival of the cancer patients with brain metastasis (adjustHR = 0.82, 95%CI: 0.69−0.99, p = 0.034). Our results highlight that statin use shows significant survival benefits in cancer patients with brain metastasis. However, future research is needed to validate our findings.

Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis.

PURPOSE: Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes. METHODS: Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7-12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS. RESULTS: From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group. CONCLUSION: Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin D deficiency is related to increased cancer risk and deaths. However, whether vitamin D supplementation reduces cancer mortality remains unclear, and several randomized controlled trials yield inconsistent results. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception until 28 June 2022, for randomized controlled trials investigating vitamin D supplementation. Pooled relative risks (RRs) and their 95% confidence intervals (CIs) were estimated. Trials with vitamin D supplementation combined with calcium supplementation versus placebo alone and recruiting participants with cancer at baseline were excluded in the present study. RESULTS: This study included 12 trials with a total of 72,669 participants. Vitamin D supplementation did not reduce overall cancer mortality (RR 0.96, 95% CI 0.80-1.16). However, vitamin D supplementation was associated with a reduction in lung cancer mortality (RR 0.63, 95% CI 0.45-0.90). CONCLUSIONS: Vitamin D supplementation could not reduce cancer mortality in this highly purified meta-analysis. Further RCTs that evaluate the association between vitamin D supplementation and total cancer mortality are still needed.

Treatment plan comparison of volumetric-modulated arc therapy to intensity-modulated radiotherapy in lung stereotactic body radiotherapy using either 6- or 10-MV photon energies.

PURPOSE: The aim of this study was to dosimetrically compare volumetric-modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) techniques using either 6- or 10-MV photon beam energies in lung stereotactic body radiation therapy (SBRT) plans. METHODS: Thirty patients with primary or metastatic lung tumors eligible for SBRT were randomly selected. VMAT and IMRT treatment plans using either 6- or 10-MV photon energies were generated through automatic SBRT planning software in the RayStation treatment planning system. RESULTS: For planning target volume, there was no difference in D95% for all plans, whereas D2% and D50% were significantly increased by 5.22%-5.98% and 2.47%-2.59%, respectively, using VMAT6/10-MV plans compared to IMRT6/10-MV plans. When comparing the Dmax of organs at risk (OARs), VMAT6/10-MV was 18.32%-47.95% lower than IMRT6/10-MV for almost all OARs. VMAT6/10-MV obviously decreased Dmean , V5Gy , V10Gy , and V20Gy of whole lung by 9.68%-20.92% than IMRT6/10-MV . Similar results were found when comparing VMAT6-MV with IMRT10-MV or VMAT10-MV with IMRT6-MV . The differences in the D2% , heterogeneity index, and conformity index between 6- and 10-MV plans are not statistically significant. Plans using 6-MV performed 4.68%-8.91% lower levels of Dmax of spinal cord, esophagus, great vessels, and trachea and proximal bronchial tree than those using 10-MV plans. Similarly, Dmean , V5Gy , V10Gy , and V20Gy of whole lung were also reduced by 2.79%-5.25% using 6-MV. For dose fall-off analysis, the D2cm and R50% of VMAT6/10-MV were lower than those of IMRT6/10-MV . Dose fall-off curve based on 10 rings was steeper for VMAT plans than IMRT plans regardless of the energy used. CONCLUSIONS: For lung SBRT plans, VMAT-based plans significantly reduced OARs dose and steepened dose fall-off curves compared to IMRT-based plans. A 6-MV energy level was a better choice than 10-MV for lung SBRT. In addition, the dose differences between different techniques were more obvious than those between different energy levels.

Lactate dehydrogenase as promising marker for prognosis of brain metastasis.

BACKGROUND: Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM. METHODS: The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients. RESULTS: The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P < 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660). CONCLUSIONS: Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Association of Underweight and Weight Loss With Poor Prognosis and Poor Therapy Effectiveness in Brain Metastases: A Retrospective Study.

Background: The prognostic role of body mass index (BMI) in patients with brain metastases is controversial. We aim to investigate the impact of BMI on prognosis and anti-cancer therapy effectiveness in brain metastases. Methods: Patients diagnosed with brain metastases between Oct 2010 and July 2019 were followed for mortality through April 2021. The prognostic role of BMI on overall survival was assessed by a restricted cubic spline (RCS) using a flexible model to visualize the relationship between the BMI values and hazard ratios of all-cause mortality, followed by a cox regression model. The disparity of survival outcomes in patients receiving anti-cancer therapies or those did not was evaluated according to the classification of BMI. Results: A total of 2,466 patients were included in the analysis, including 241 in the underweight (BMI < 18.5 kg/m2) group, 1,503 in the normal weight group (BMI 18.5-23.9 kg/m2), and 722 in the overweight (BMI ≥ 24 kg/m2) group. Relative to the normal weight group, underweight patients were associated with poor prognosis (adjusted HR 1.25, 95% CI 1.07-1.46, p = 0.005). However, those in the overweight group showed similar overall survival when compared to the normal-weight group. Patients with weight loss were associated with a higher risk of mortality compared with patients without significant weight loss. In underweight patients, there was an insignificant difference in survival outcomes whether they received anti-cancer therapies or not. Conclusion: Underweight and significant weight loss were associated with poor prognosis in brain metastases. Meanwhile, anti-cancer therapies did not significantly improve overall survival in patients with underweight. These findings suggest that improving nutrition to maintain body weight is critical for patients with brain metastases.

The Development and Validation of a Nomogram Incorporating Clinical, Pathological, and Therapeutic Features to Predict Overall Survival in Patients With Penile Cancer: A SEER-Based Study.

Objective: This study aimed to investigate the prognostic factors of penile cancer and establish a comprehensive predictive model for clinical application. Methods: A total of 581 patients from the Surveillance, Epidemiology, and End Results (SEER) program (2000-2018) were used to develop the prognostic model. The multivariate Cox proportional hazards regression was performed to identify independent prognostic factors to develop the nomogram. The performance of this model was validated internally by a cohort with 143 patients from the SEER database and validated externally by a cohort with 70 patients from the West China Hospital, Sichuan University (2010-2020). Results: Age, marital status, size of the primary lesion, primary tumor (T), regional lymph nodes status, distant metastasis (M), and the surgery of regional lymph node (LND) were the independent prognostic factors for overall survival (OS) and were incorporated in the prognostic model. The prognostic nomogram showed a good risk stratification ability for OS in the development cohort, internal validation cohort, and external validation cohort. Conclusion: This study incorporates the clinical, pathological, and therapeutic features comprehensively to develop a novel and clinically effective prognostic model for patients with penile cancer.