Survival Of Patients Research Articles

Dissecting the Single-Cell Diversity and Heterogeneity Underlying Cervical Precancerous Lesions and Cancer Tissues.

The underlying cellular diversity and heterogeneity from cervix precancerous lesions to cervical squamous cell carcinoma (CSCC) is investigated. Four single-cell datasets including normal tissues, normal adjacent tissues, precancerous lesions, and cervical tumors were integrated to perform disease stage analysis. Single-cell compositional data analysis (scCODA) was utilized to reveal the compositional changes of each cell type. Differentially expressed genes (DEGs) among cell types were annotated using BioCarta. An assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis was performed to correlate epigenetic alterations with gene expression profiles. Lastly, a logistic regression model was used to assess the similarity between the original and new cohort data (HRA001742). After global annotation, seven distinct cell types were categorized. Eight consensus-upregulated DEGs were identified in B cells among different disease statuses, which could be utilized to predict the overall survival of CSCC patients. Inferred copy number variation (CNV) analysis of epithelial cells guided disease progression classification. Trajectory and ATAC-seq integration analysis identified 95 key transcription factors (TF) and one immunohistochemistry (IHC) testified key-node TF (YY1) involved in epithelial cells from CSCC initiation to progression. The consistency of epithelial cell subpopulation markers was revealed with single-cell sequencing, bulk sequencing, and RT-qPCR detection. KRT8 and KRT15, markers of Epi6, showed progressively higher expression with disease progression as revealed by IHC detection. The logistic regression model testified the robustness of the resemblance of clusters among the various datasets utilized in this study. Valuable insights into CSCC cellular diversity and heterogeneity provide a foundation for future targeted therapy.

Extended 73-month survival in an elderly patient with BRAF V600E-mutated lung adenocarcinoma: A case report.

BRAF is a mediator that activates the mitogen-activated protein kinase pathway. A mutation in BRAF can cause abnormal pathway activation, leading to cell proliferation. In a Phase II study, the combination therapy of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib was found to be effective in non-small cell lung cancer (NSCLC) patients with the BRAF mutation. However, this study has limited efficacy and safety data for elderly patients. We present a case of a patient who started treatment at 87 years old and showed a good prognosis, remaining alive 73 months from the start of treatment with no significant adverse events. The patient also maintained a partial response (PR) according to RECIST 1.1 at the last follow-up. This case suggests that the dabrafenib and trametinib combination therapy is safe and effective for elderly NSCLC patients with the BRAF mutation.

Positive Lymph Node Ratio as a new prognostic score in Geriatric patients with operated gastric cancer

ObjectiveThe pivotal prognostic determinant for recurrence and survival in surgically treated gastric cancer (GC) patients remains the lymph node status. Despite the adoption of D2 lymph node dissection as the standard approach in recent years, its association with increased morbidity in elderly patients raises concerns. This study aims to explore the prognostic significance of the Positive Lymph Node Ratio (PLNR) score in the context of recurrence and survival among elderly patients with surgically treated GC. Material and methodA retrospective review of files about surgically treated patients with GC was conducted. The prognostic impact of the PLNR score on overall survival (OS) was assessed through Receiver Operating Characteristic (ROC) analysis. ResultsThe cut-off value for the PLNR, determined through ROC analysis, was identified as 0.138. This value serves as a crucial threshold, as it distinguishes patients with a higher risk of poor outcomes. Patients with a PLNR score of 0.138 or below exhibited a median OS of 111 months, whereas those with a PLNR score above 0.138 had a significantly lower median OS of 22 months (p = 0.004). ConclusionOur findings revealed that the PLNR emerged as an independent predictor of survival and recurrence in patients undergoing GC resection.However, it's important to note that while valuable, the PLNR system has limitations. It does not encompass the T stage, a key factor in cancer staging. Therefore, it cannot be a direct substitute for the comprehensive information TNM staging provides. It should be used as a supplementary tool in predicting prognosis, particularly in elderly patients unsuitable for standard lymph node dissection.

Patient and care team experiences with an EHR-integrated symptom management program (eSyM) in routine oncology practice.

324 Background: Clinical trials have shown that collecting electronic patient-reported outcomes (ePROs) improves quality of life and survival in cancer patients. To bolster integration of ePROs into routine care, the SIMPRO Research Consortium developed an electronic symptom management (eSyM) program, deployed it at six cancer centers, and conducted a hybrid effectiveness-implementation study. eSyM, an ePRO toolkit integrated into the Epic EHR, enables patients to report and care teams to triage symptoms in real-time. To assess eSyM, we conducted structured qualitative interviews with patients and clinic staff, including doctors, nurses, advanced practice providers, and administrative staff. We sought to understand eSyM from the patient and staff perspectives. Methods: Using an iterative process, we developed semi-structured interview guides to query the experiences and perceptions of patients and staff exposed to eSyM. Questions were informed by the Consolidated Framework for Implementation Research. One year after eSyM was launched, sites identified and referred participants for interviews or focus groups. Participants must have either used eSyM to submit symptoms (patients) or had access to eSyM at their institution (staff). Patients provided written consent; a consent waiver was obtained for staff. Interviews were recorded and transcribed, and a common analytic codebook was developed. Transcripts were dual or triple-coded and underwent thematic analysis to identify key contexts and concepts within and across patient and staff groups. Results: From 9/28/20 to 4/14/23, 50 staff participated in individual interviews and 29 participated in focus groups (79 total). From 9/14/23 to 3/14/24, 14 patient interviews were conducted. Transcripts revealed that staff and patients held similar beliefs regarding eSyM compatibility, communication, and prioritization. 93% (13/14) of patients and 72% (57/79) of staff believed eSyM was easy to use and improved communication. Both cohorts (66% staff, 36% patients) noted that competing demands often needed to be prioritized over responding to symptom concerns. Discordance emerged in the domains of receptivity and technology; patients were more receptive and capable of using eSyM than staff perceived. Both groups believed eSyM was helpful but perceived that deeper engagement from patients and staff was necessary for sustainability. Conclusions: Most interviewees reported that eSyM added value and was easy to navigate. Competing clinical demands, however, frequently deprioritized use of eSyM. Staff tended to underestimate patients’ receptivity to use eSyM and were more likely to cite competing demands as a barrier to their own use of eSyM. Sites looking to adopt eSyM, or similar ePRO programs, will benefit from understanding the facilitators that need to be incorporated and the barriers that need to be surmounted to optimize success. Clinical trial information: NCT03850912 .

Upregulation of LY6K induced by FTO-mediated demethylation promotes the tumorigenesis and metastasis of oral squamous cell carcinoma via CAV-1-mediated ERK1/2 signaling activation.

Lymphocyte antigen 6 complex locus K (LY6K) has been demonstrated to play a significant role in cancers and identified as a therapeutic biomarker for head and neck squamous cell carcinoma. However, the role of LY6K in oral squamous cell carcinoma (OSCC) has not been explored. The current study discovered that LY6K was aberrantly upregulated in OSCC cell lines and tissues and that high LY6K expression significantly correlated with poorer survival of OSCC patients. Through stable knockdown of LY6K, we found that the growth, colony formation, migration, and invasion of OSCC cells were substantially suppressed. In addition, tumor growth and lung metastasis in vivo were effectively inhibited by LY6K depletion. Mechanically, LY6K binds with CAV-1 and activates CAV-1-mediated MAPK/ERK signaling to exert its oncogenic effects on OSCC. In addition, LY6K expression in OSCC was discovered to be regulated by FTO-mediated RNA N6-methyladenosine (m6A) modification in an IGF2BP1-dependent manner. Generally, LY6K expression was upregulated by FTO-mediated demethylation in OSCC, which promoted the tumorigenesis and metastasis of OSCC via activating the CAV-1-mediated ERK1/2 signaling pathway.

Integrative microbiomics, proteomics and lipidomics studies unraveled the preventive mechanism of Shouhui Tongbian Capsules on cerebral ischemic stroke injury

Ethnopharmacological relevanceCerebral ischemic stroke (CIS) is one of the most important factors leading to death and disability, which seriously threaten the survival and health of patients. The intentional flora and its derived metabolites are demonstrated to play vital roles in the physiology and onset of CIS. Shouhui Tongbian Capsules (SHTB), a Traditional Chinese Medicine, could regulate gut microbiota and metabolites. Study has found that SHTB has protective effect on CIS, but the mechanism is still unclear. Aim of studyThis study was designed to evaluate the preventive effects and the mechanism of SHTB on CIS injury. Materials and methodsThe rats were pretreated with SHTB for 5 days, then the middle cerebral artery occlusion/reperfusion (MCAO/R) was established. Neurological deficit score, TTC staining, brain water content, H&E and Nissl staining were preformed to evaluate the preventive effects of SHTB on CIS. The Occludin and ZO-1 were analyzed to evaluate the blood-brain barrier (BBB). 16S rDNA sequencing and LC-ESI-MS/MS-based metabolomics profiling were performed to analyze the gut microbiota composition and short chain fatty acids (SCFAs) profile in gut. Serum lipopolysaccharide specific IgA antibody (LPS-SIgA) and diamine oxidase (DAO), as well as colon Claudin 5 and ZO-1 were analyzed to evaluate the intestinal barrier. Proteomics was used to evaluated the proteins profile in brain. Lipidomics were used to evaluate the brain SCFAs as well as medium and long chain fatty acids (MCFAs and LCFAs). Malondialdehyde (MDA), Total Superoxide dismutase (T-SOD), Glutathione (GSH), Glutathione peroxidase (GSH-Px), Catalase (CAT) and reactive oxygen species (ROS) were assayed to evaluate the oxidative stress in brain. Western blot was performed to evaluate the expression of PPARγ, Nrf2, SLC3A2, SCL7A11, GPX4, ACSL4 and LOX. ResultsSHTB prevented rats from MCAO/R injury, which was confirmed by lower cerebral infarct rate, brain water content, neurological deficit score and nissl body loss, and improved brain pathology. Meanwhile, SHTB upregulated the expression of ZO-1 and Occludin to maintain the integrity of BBB. 16S rDNA sequencing and LC-ESI-MS/MS-based targeted metabolomics found that SHTB increased the abundance of gut microbiota, regulated the numbers of intestinal bacteria to increase the production of Acetic acid, Propionic acid, and Butyric acid, as well as decrease the production of Valeric acid and Hexanoic acid in the gut. Meanwhile, SHTB improved the intestinal barrier by upregulating the protein levels of Claudin 5 and ZO-1, which was confirmed by low concentrations of LPS-SIgA and DAO in serum. Multi omics and spearman correlation analysis indicated that SHTB regulated the abundance of Escherichia-Shigella and Lactobacillus to increase Acetic acid, Propionic acid, and Butyric acid to induce the expression of PPARγ, thereby regulating fatty acid metabolism and degradation, improving lipid metabolism disorders, downregulating lipid oxidative stress, inhibiting ferroptosis, and alleviating brain injury. ConclusionThis study confirmed that SHTB improved the disturbance of fatty acid metabolism in brain tissue by regulating gut microbiota and the production of fecal SCFAs to inhibit ferroptosis caused by lipid oxidative stress and prevent CIS injury, which provided a potential candidate drug for the prevention of CIS.

Stereotactic body radiotherapy with a focal boost to the intraprostatic tumor for intermediate and high risk prostate cancer: 5-year efficacy and toxicity in the hypo-FLAME trial

BackgroundThe addition of an integrated focal boost to the intraprostatic lesion is associated with improved biochemical disease-free survival (bDFS) in patients with intermediate- and high-risk prostate cancer (PCa) in conventionally fractionated radiotherapy. Furthermore, whole gland stereotactic body radiotherapy (SBRT) demonstrated to be non-inferior to conventional radiotherapy for low- and intermediate-risk PCa. To investigate the combination of ultra-hypofractionated prostate SBRT with iso-toxic focal boosting for intermediate- and high-risk PCa, we performed the hypo-FLAME trial. MethodsPatients with intermediate- or high-risk PCa were enrolled in the phase II hypo-FLAME trial. All patients were treated with 35 Gy in 5 weekly fractions to the whole prostate gland with an iso-toxic integrated boost up to 50 Gy to the multiparametric MRI-defined tumor(s). If the dose constraints to the normal tissues would be exceeded, these were prioritised over the focal boost dose. The current analysis reports on the 5-year bDFS, late toxicity and health-related quality of life (HRQoL). ResultsBetween 2016 and 2018, 100 men were treated with a median follow-up of 61 months. The estimated 5-year bDFS (95 % CI) was 93 % (86 % to 97 %). At 5 years, the prevalence of grade 2 + genitourinary and gastrointestinal toxicity was 12 % and 4 %, respectively. ConclusionUltra-hypofractionated focal boost SBRT is associated with encouraging biochemical control rates up to 5-year follow-up in patients with intermediate- and high-risk PCa. Furthermore, prostate SBRT with iso-toxic focal boosting is associated with acceptable late genitourinary and gastrointestinal toxicity rates.

Preoperative Serum Glycan Levels Reflect Progression of Patients With Hepatocellular Carcinoma.

Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge. A study dynamically comparing levels of fifteen lectin-specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan-Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression-free survival (PFS) of the HCC patients. HCC patients presented significantly higher levels of the lectin-specific glycans in preoperative serum than disease-free individuals (p < 0.001 - p = 0.029), except ConA. The glycans in preoperative sera were significantly related to tumor size, pTNM, metastasis, BCLC stage, portal hypertension (PHT), and platelet count (PLT), respectively (p < 0.05). Multivariate logistic analyses indicated that tumor size and pTNM independently impact on glycan-specific lectins either LTL, UEA-I, VVL, NPL, WGA, PNA, MAL-I, SNA, or PHA-L (p = 0.003 - p = 0.044); BCLC stage and PLT were independent factors influencing the serum glycans recognizable DSA (p = 0.024) and SNA (p = 0.050), respectively. Surgical excision of tumor mass significantly reduced glycan levels in sera. Tumor differentiation, albumin, and ABO type significantly revealed independent influence on glycan-specific lectins, such as RCA-I (p = 0.024), VVL (p = 0.024), and Con A (p = 0.026) in the postoperative serum. HCC patients with high levels of VVL-binding glycans significantly benefited from a longer OS time (p = 0.016, HR: 0.460, 95% CI: 0.237-0.892) and a better PFS time (p = 0.004; HR: 0.435, 95% CI: 0.237-0.799), respectively. Serum glycans could reflect surgical outcomes in at-risk patients and become valuable biomarkers in evaluating the progression of HCC patients.

The prognosis of patients with locally advanced cervical cancer undergoing surgical versus non-surgical treatment: A retrospective cohort study based on SEER database and a single-center data.

The aim of this study was to investigate the impact of surgical treatment on the survival prognosis of patients with locally advanced cervical cancer (LACC) and to identify factors that may influence the efficacy of surgery. Data from the SEER database (2000-2020) and a hospital (2013-2023) were collected for this investigation. Utilizing multivariable Cox regression analysis, Kaplan-Meier survival analysis, and log-rank tests, we assessed the effects of surgical intervention on overall survival (OS) and disease-specific survival (DSS) in LACC patients. Our results revealed that in the SEER database, the surgical group exhibited significantly better OS and DSS compared to the non-surgical group. Particularly noteworthy was the significantly higher survival rate in the surgical group for patients with tumor diameters less than 6 cm. Furthermore, both OS and DSS were improved in the surgical group regardless of whether the cancer was squamous cell carcinoma or adenocarcinoma. Additionally, patients who underwent surgery combined with radiotherapy had notably better OS and DSS compared to those who received chemoradiotherapy alone. Similarly, our hospital data showed that the surgical group demonstrated significantly better OS than the non-surgical group, especially for patients with tumors smaller than 6 cm in diameter. These findings suggest that surgery combined with radiotherapy may offer more favorable outcomes than chemoradiotherapy alone, particularly for LACC patients with smaller tumors.

Decoding the immune microenvironment: unveiling CD8 + T cell-related biomarkers and developing a prognostic signature for personalized glioma treatment

BackgroundGliomas are aggressive brain tumors with poor prognosis. Understanding the tumor immune microenvironment (TIME) in gliomas is essential for developing effective immunotherapies. This study aimed to identify TIME-related biomarkers in glioma using bioinformatic analysis of RNA-seq data.MethodsIn this study, we employed weighted gene co-expression network analysis (WGCNA) on bulk RNA-seq data to identify TIME-related genes. To identify prognostic genes, we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Based on these genes, we constructed a prognostic signature and delineated risk groups. To validate the prognostic signature, external validation was conducted.ResultsCD8 + T cell infiltration was strongly correlated with glioma patient prognosis. We identified 115 CD8 + T cell-related genes through integrative analysis of bulk-seq data. CDCA5, KIF11, and KIF4A were found to be significant immune-related genes (IRGs) associated with overall survival in glioma patients and served as independent prognostic factors. We developed a prognostic nomogram that incorporated these genes, age, gender, and grade, providing a reliable tool for clinicians to predict patient survival probabilities. The nomogram’s predictions were supported by calibration plots, further validating its accuracy.ConclusionIn conclusion, our study identifies CD8 + T cell infiltration as a strong predictor of glioma patient outcomes and highlights the prognostic value of genes. The developed prognostic nomogram, incorporating these genes along with clinical factors, provides a reliable tool for predicting patient survival probabilities and has important implications for personalized treatment decisions in glioma.

Patient- and Areal-Level Risk Factors Associated With Lung Cancer Mortality in Victoria, Australia: A Bayesian Spatial Survival Analysis.

In Australia, lung cancer is the leading cause of cancer-related deaths. In Victoria, the mortality risk is assumed to vary across Local Government Areas (LGAs) due to variations in socioeconomic advantage, remoteness, and healthcare accessibility. Thus, we applied Bayesian spatial survival models to examine the geographic variation in lung cancer survival in Victoria. Data on lung cancer cases were extracted from the Victorian Lung Cancer Registry (VLCR). To account for spatial dependence and risk factors of survival in lung cancer patients, we employed a Bayesian spatial survival model. Conditional Autoregressive (CAR) prior was assigned to model the spatial dependence. Deviance Information Criterion (DIC), Watanabe Akaike Information Criterion (WAIC), and Log Pseudo Marginal Likelihood (LPML) were used for model comparison. In the final best-fitted model, the Adjusted Hazard Ratio (AHR) with the 95% Credible Interval (CrI) was reported. The outcome variable was the survival status of lung cancer patients, defined as whether they survived or died during the follow-up period (death was our interest). Our study revealed substantial variations in lung cancer mortality in Victoria. Poor Eastern Cooperative Oncology Group (ECOG) performance status, diagnosed at a regional hospital, Small Cell Lung Cancer (SCLC), advanced age, and advanced clinical stage were associated with a higher risk of mortality, whereas being female, presented at Multidisciplinary Team (MDT) meeting, and diagnosed at a metropolitan private hospital were significantly associated with a lower risk of mortality. Identifying geographical disparities in lung cancer survival may help shape healthcare policy to implement more targeted and effective lung cancer care services.

Impact of uniportal thoracoscopic segmentectomy on long-term survival in elderly patients with stage I non-small cell lung cancer.

Impact of uniportal thoracoscopic segmentectomy on long-term survival in elderly patients with stage I non-small cell lung cancer.

Single-cell sequencing analysis reveals the dynamic tumour ecosystems of primary and metastatic lymph nodes in nasopharyngeal carcinoma.

Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment and the cellular communications of lymph node metastasized tumours determine the tumour progression and therapeutic effect, but the ecosystems about the lymph node metastasis (LNM) for NPC patients remain poorly characterized. Here, we integrated the transcriptomes of 47,618 single cells from eight samples related to NPC LNM. The dynamic immune ecosystems and immunosuppressive microenvironment including T cells, myeloid cells and B cells were observed in the lymph node metastatic samples compared with primary tumours. Additionally, the heterogeneity of epithelial cells was also revealed, and several clusters with expression programs that were associated with the progression-free survival of NPC patients were identified. Additionally, our data revealed the complex intercellular communications from primary to lymph node metastasis. The rewiring of CCL signalling which plays an important role in tumour metastasis was further identified. Altogether, we systematically characterized the ecosystem of NPC primary and lymph node metastasized tumours, which may shed light on the development of a therapeutic strategy to improve clinical outcomes of NPC patients with lymph node metastasis.

The changing influence of neighborhood socioeconomic status on long-term survival in diffuse large B-cell lymphoma patients: A German metropolitan case-control study spanning over three decades.

The changing influence of neighborhood socioeconomic status on long-term survival in diffuse large B-cell lymphoma patients: A German metropolitan case-control study spanning over three decades.

Association of various RAS codon mutations and prognostic outcomes of patients with colorectal liver metastases after hepatectomy.

The prognostic and predictive value of RAS mutations in patients with colorectal liver metastases (CRLM) who have undergone hepatectomy holds substantial importance. The present study aimed to investigate the impact of different RAS codon mutations on long-term survival in CRLM patients. A retrospective analysis was conducted on clinicopathological data from 399 CRLM patients with RAS mutations who underwent hepatectomy between January 2000 and December 2020. The RAS mutation gene status was assessed in KRAS codons (G12, G13, Q61, and A146) and NRAS codons (G12, G13, and Q61). Survival curves were generated using the Kaplan-Meier plotter and compared using the log-rank test. Univariate and multivariate analyses were performed to analyze the clinicopathological data. In the entire cohort, patients with KRAS G12 mutations exhibited the most favorable prognosis (p = 0.018). Comparatively, patients harboring KRAS Q61 mutations experienced poorer overall survival (OS) with a median of 15 months versus 33 months (p = 0.011) when compared to those with KRAS G12 mutations. Moreover, patients with NRAS Q61 mutations also showed decreased OS with a median of 26 months versus 33 months (p = 0.020) in comparison to KRAS G12 mutation patients. The results of multivariate analysis showed that both KRAS Q61 mutation (HR 2.130; 95% CI 1.088-4.168; p = 0.027) and NRAS Q61 mutation (HR 2.877; 95% CI 1.398-5.922; p = 0.004) were independent influencing factors of OS. Based on all identified risk factors, patients with RAS mutation were divided into high-risk and low-risk groups. Notably, in the high-risk group, the incorporation of postoperative chemotherapy was associated with longer OS, while it did not improve the survival of patients in the low-risk group. KRAS Q61 and NRAS Q61 mutations are promising predictors for OS in CRLM patients after hepatectomy. Postoperative chemotherapy may significantly benefit CRLM patients with RAS mutations, particularly those identified as high-risk.

Development of a predictive model for patients with bone metastases referred to palliative radiotherapy: Secondary analysis of a multicenter study (the PRAIS trial).

The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short-, intermediate-, and long-term overall survival (OS) for patients in this clinical setting. This study constitutes a sub-analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer-induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC). Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non-bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL-8], chloride levels, C-reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL-8 included both in the PMs for short- and long-term OS. The AUC values for ROC curves for 3-week, 24-week, and 52-week OS were 0.901, 0.767, and 0.806, respectively. We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases.

Which pretreatment immunonutritional index best predicts overall survival in elderly patients with locally advanced gastric cancer treated with perioperative FLOT therapy?

Which pretreatment immunonutritional index best predicts overall survival in elderly patients with locally advanced gastric cancer treated with perioperative FLOT therapy?

Bulk integrated single-cell-spatial transcriptomics reveals the impact of preoperative chemotherapy on cancer-associated fibroblasts and tumor cells in colorectal cancer, and construction of related predictive models using machine learning

BackgroundPreoperative chemotherapy (PC) is an important component of Colorectal cancer (CRC) treatment, but its effects on the biological functions of fibroblasts and epithelial cells in CRC are unclear. MethodsThis study utilized bulk, single-cell, and spatial transcriptomic sequencing data from 22 independent cohorts of CRC. Through bioinformatics analysis and in vitro experiments, the research investigated the impact of PC on fibroblast and epithelial cells in CRC. Subpopulations associated with PC and CRC prognosis were identified, and a predictive model was constructed using machine learning. ResultsPC significantly attenuated the pathways related to tumor progression in fibroblasts and epithelial cells. NOTCH3 + Fibroblast (NOTCH3 + Fib), TNNT1 + Epithelial (TNNT1 + Epi), and HSPA1A + Epithelial (HSPA1A + Epi) subpopulations were identified in the adjacent spatial region and were associated with poor prognosis in CRC. PC effectively diminished the presence of these subpopulations, concurrently inhibiting pathway activity and intercellular crosstalk. A risk signature model, named the Preoperative Chemotherapy Risk Signature Model (PCRSM), was constructed using machine learning. PCRSM emerged as an independent prognostic indicator for CRC, impacting both overall survival (OS) and recurrence-free survival (RFS), surpassing the performance of 89 previously published CRC risk signatures. Additionally, patients with a high PCRSM risk score showed sensitivity to fluorouracil-based adjuvant chemotherapy (FOLFOX) but resistance to single chemotherapy drugs (such as Bevacizumab and Oxaliplatin). Furthermore, this study predicted that patients with high PCRSM were resistant to anti-PD1therapy. ConclusionIn conclusion, this study identified three cell subpopulations (NOTCH3 + Fib, TNNT1 + Epi, and HSPA1A + Epi) associated with PC, which can be targeted to improve the prognosis of CRC patients. The PCRSM model shows promise in enhancing the survival and treatment of CRC patients.

Survival analysis of the metastatic cohort of Italian Association of Medical Oncology (AIOM) GARIBALDI survey

This analysis from the GARIBALDI study was aimed to address the role of center self-declared expertise, type and commitment on the overall survival (OS) of patients with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC).Treatment-naïve patients ≥18-year with pathological diagnosis of mPDAC were enrolled. OS was defined as the time from chemotherapy start to death from any cause. The impact of clinical-demographic and centers characteristics on OS was evaluated using Cox models.Between July 2017 and October 2019, 473 patients enrolled in 43 centers were eligible for this analysis. Median age was 69.3 (first-third quartile 61.2–74.5); 46.1 % females; 90.8 % ECOG PS 0–1; 67.4 % had liver metastases; median CA19.9700.5 UI/mL (first-third quartile 77.5-6629.5). For 37.1 % of patients chemotherapy started <4 weeks from diagnosis; 69.9 % of patients received nab-paclitaxel + gemcitabine; 16.9 % gemcitabine alone; 7.6 % FOLFIRINOX. The median follow-up was 51.8 months and 428 patients died. No statistically significant role of the type of institution was observed. Additionally, no statistically significant role of neither the self-declared expertise nor the accrual rate was observed.The GARIBALDI study suggests that the self-declared center expertise and the academic brand are not associated to OS in patients with mPDAC, while center commitment warrants further exploration.

Caveolin-1 expression is a predictor of survival and recurrence patterns in resected pancreatic ductal adenocarcinoma

Background/objectiveCaveolin-1 (Cav1) expressed in cancer cells (cCav1) or cancer-associated fibroblasts (fCav1) exerts either pro- or anti-tumorigenic effects depending on the cancer type or stage of cancer. We aimed to clarify the impact of cCav1 or fCav1 on survival, recurrence patterns, and efficacy of neoadjuvant chemotherapy (NAC) in resected pancreatic ductal adenocarcinoma (PDAC). MethodsTissue microarrays were constructed including 615 patients who underwent curative resection for PDAC. Cav1 expression was evaluated by immunohistochemistry. Patients were divided into two groups based on Cav1 expression in cancer cells (cCav1high vs. cCav1low) or cancer-associated fibroblasts (fCav1high vs. fCav1low). ResultsAmong all 615 patients, 40.7% were cCav1high and 72.7% were fCav1high. cCav1high was associated with worse overall survival (OS) (p = 0.001) and recurrence-free survival (RFS) (p = 0.001) than cCav1low, and was an independent prognostic factor in multivariate analysis of OS and RFS (OS: p = 0.001, hazard ratio [HR] 1.361; RFS: p = 0.001, HR 1.348). Among 596 patients with resectable/borderline resectable PDAC, cCav1high patients with NAC showed better OS than those without, while there was no significant difference between cCav1low patients with NAC and those without. cCav1high was associated with early recurrence (< 6 months) and liver metastasis after resection. Multivariate analysis revealed cCav1high as an independent predictor of liver metastasis. ConclusionscCav1high correlated with worse survival, early recurrence, and liver metastasis after resection for PDAC, while NAC improved survival in cCav1high patients. The Evaluation of cCav1 status could provide additional information contributing to the personalized management of PDAC.