Independent Predictor Of Progression-free Survival Research Articles

Computational pathology applied to clinical colorectal cancer cohorts identifies immune and endothelial cell spatial patterns predictive of outcome.

Colorectal cancer (CRC) is a histologically heterogeneous disease with variable clinical outcome. The role the tumour microenvironment (TME) plays in determining tumour progression is complex and not fully understood. To improve our understanding, it is critical that the TME is studied systematically within clinically annotated patient cohorts with long-term follow-up. Here we studied the TME in three clinical cohorts of metastatic CRC with diverse molecular subtype and treatment history. The MISSONI cohort included cases with microsatellite instability that received immunotherapy (n = 59, 24 months median follow-up). The BRAF cohort included BRAF V600E mutant microsatellite stable (MSS) cancers (n = 141, 24 months median follow-up). The VALENTINO cohort included RAS/RAF WT MSS cases who received chemotherapy and anti-EGFR therapy (n = 175, 32 months median follow-up). Using a Deep learning cell classifier, trained upon >38,000 pathologist annotations, to detect eight cell types within H&E-stained sections of CRC, we quantified the spatial tissue organisation and colocalisation of cell types across these cohorts. We found that the ratio of infiltrating endothelial cells to cancer cells, a possible marker of vascular invasion, was an independent predictor of progression-free survival (PFS) in the BRAF+MISSONI cohort (p = 0.033, HR = 1.44, CI = 1.029-2.01). In the VALENTINO cohort, this pattern was also an independent PFS predictor in TP53 mutant patients (p = 0.009, HR = 0.59, CI = 0.40-0.88). Tumour-infiltrating lymphocytes were an independent predictor of PFS in BRAF+MISSONI (p = 0.016, HR = 0.36, CI = 0.153-0.83). Elevated tumour-infiltrating macrophages were predictive of improved PFS in the MISSONI cohort (p = 0.031). We validated our cell classification using highly multiplexed immunofluorescence for 17 markers applied to the same sections that were analysed by the classifier (n = 26 cases). These findings uncovered important microenvironmental factors that underpin treatment response across and within CRC molecular subtypes, while providing an atlas of the distribution of 180 million cells in 375 clinically annotated CRC patients. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Enhanced Survival Outcomes with FOLFIRINOX in Initial Metastatic Pancreatic Cancer: Single-Center Study

Introduction. The aim of this article is to evaluate the efficacy and outcomes of FOLFIRINOX as a first-line treatment for initial metastatic pancreatic cancer patients at the Clinical Center University of Sarajevo. Methods. The research presents a retrospective analysis was conducted on 33 patients treated with FOLFIRINOX, between January 2021 and January 2023. Baseline characteristics, tumor markers (CEA, CA 19-9, CA 125), neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR) and initial metastatic site were evaluated using Cox regression analysis in order to identify predictive and prognostic factors for progression-free survival (PFS) and overall survival (OS). Results. The median age of patients was 64 (range 38-76). There were 18 males and 15 females. The median OS was 21.7 months (95% CI, 10.5-32.9) and the median PFS was 10.0 months (95% CI, 8.2-11.8). A statistically significant negative correlation was found between NLR and OS (r=-0.464, p=0.045). Patients with initial liver metastasis had a numerically worse median OS (16.3 months, 95% CI, 5.1-27.5), compared to those with non-liver metastasis (OS not reached, p=0.058). Tumor markers, NLR, NPR, and initial metastatic site were not independent predictors of PFS and OS. Conclusion. FOLFIRINOX demonstrates significant efficacy in treating metastatic pancreatic cancer in a real-world setting. Personalized approaches, including genetic profiling and microbiome analysis, along with AI integration, offer promising avenues to enhance treatment outcomes and quality of life for patients. Keywords: metastatic pancreatic cancer, enhanced outcomes, overall survival, progression-free survival.

Prognostic value of interim PET/CT in GCB and non-GCB DLBCL: comparison of the Deauville five-point scale and the ΔSUVmax method

BackgroundThis study aimed to identify the prognostic value of interim 18F-FDG PET/CT (I-PET) for germinal center B-cell-like (GCB) and non-GCB diffuse large B-cell lymphoma (DLBCL), respectively.MethodsBaseline 18F-FDG PET/CT (B-PET) and I-PET scans were performed in 112 patients with DLBCL. The prognostic value of I-PET using the Deauville five-point scale (D-5PS) criteria or percentage decrease in SUVmax (∆SUVmax) for GCB and non-GCB DLBCL were evaluated.ResultsA significant difference in progression-free survival (PFS) was found between GCB and non-GCB DLBCL patients (P < 0.05). Based on D-5PS criteria, I-PET was divided into positive (score > 3) and negative (score ≤ 3) subgroups. Results indicated that I-PET using D-5PS criteria was an independent predictor for PFS of GCB DLBCL (P < 0.05), but not for overall survival (OS) (P > 0.05). For non-GCB DLBCL, PFS and OS were significantly higher in I-PET negative group than I-PET positive group (P < 0.05). Receiver operating characteristic (ROC) curve analysis proved that I-PET using ΔSUVmax can also effectively predict PFS and OS of non-GCB DLBCL (P < 0.05), but not for GCB DLBCL (P > 0.05). Based on the optimal threshold found by ROC curve analysis, patients were dichotomized into ∆SUVmax high and low groups. Log-rank test and Cox regression demonstrated that the layered ∆SUVmax was predictive of PFS and OS in non-GCB DLBCL (P < 0.05).ConclusionsI-PET may have different prognostic values for GCB and non-GCB DLBCL. Thus, the pathology type of DLBCL may be considered while using I-PET as a prognostic tool in the future.

Association between quantitative CT body composition analysis and prognosis in cetuximab-based first-line treatment for advanced colorectal cancer patients

BackgroundThe objective of this study is to investigate the potential association between change in body composition before and after cetuximab-based therapy and the prognostic outcomes among individuals diagnosed with advanced colorectal cancer.MethodsA retrospective analysis was undertaken on a cohort of 81 patients diagnosed with RAS wild-type (WT) metastatic colorectal cancer (mCRC) who were treated with cetuximab-based first-line therapy. To assess relevant body composition parameters, quantitative computed tomography (QCT) scans were conducted both before and after cetuximab treatment. These parameters encompassed measurements of visceral fat area (VFA), subcutaneous fat area (SFA), total muscle area (TMA) at the third lumbar vertebra level (L3), and bone mineral density (BMD) at the first and second vertebrae levels (L1/2). The skeletal muscle index (SMI) was subsequently calculated, and changes in parameters (∆VFA, ∆SFA, ∆SMI, ∆BMD) were standardized.ResultsThe cut-off values for ∆VFA, ∆SFA, ∆SMI, and ∆BMD were 0.28%, -2.76%, -2.97%, and -7.98%, respectively. CEA, ∆VFA, ∆SMI, and ∆BMD were associated with poor outcomes of cetuximab-based first-line chemotherapy (P < 0.05). The risk of disease progression was higher when ∆VFA < 0.28%, ∆SFA < -2.76%, ∆SMI < -2.97%, and ∆BMD < -7.98%. Multivariate analysis indicated that CEA (HR: 0.396, 95% CI: 0.160–0.980, P = 0.045), ∆VFA (HR: 0.307, 95% CI: 0.145–0.651, P = 0.002), and∆SMI (HR: 0.725, 95% CI: 0.322–1.630, P = 0.001) have significant prognostic value for progression-free survival (PFS) in RAS WT mCRC patients treated with cetuximab-based first-line chemotherapy.ConclusionsCEA, ∆VFA, and ∆SMI are independent predictors for PFS in patients with advanced colorectal cancer. High levels of CEA, ∆VFA, and low levels of ∆SMI may indicate poorer outcomes. CEA, ∆VFA, and ∆SMI can be used to predict PFS in mCRC patients receiving cetuximab-based first-line chemotherapy.Trial registrationThis study was approved by the Ethics Committee of Anhui Provincial Cancer Hospital of Anhui Medical University (Batch No:2024-ZNY-02). All subjects signed an informed consent form.

Clinical characteristics and survival outcomes in patients with pulmonary sarcomatoid carcinoma: a multicenter retrospective study

Abstract Purpose The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain. Methods This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined. Results 46% PSC patients harbored KRAS mutation and 23% harbored EGFR mutation. Univariable analysis identified type and cTNM stage as significant predictor of PFS (type: HR 0.216; 95% CI 0.133–0.349; P &lt; 0.001, cTNM stage: HR 0.483; 95% CI 0.269–0.846; P = 0.014) and OS (type: HR 0.269; 95% CI 0.156–0.465; P &lt; 0.001, cTNM stage: HR 0.435; 95% CI 0.219–0.865; P = 0.018). Multivariable analysis confirmed sex, type and cTNM stage as independent predictors of PFS (sex: HR 2.026; 95%CI 1.027–3.996; P = 0.042; type: HR0.140; 95% CI 0.083–0.238; P &lt; 0.001, cTNM stage: HR0.305; 95% CI 0.165–0.564; P &lt; 0.001) and OS (type: HR0.231; 95% CI 0.132–0.404; P &lt; 0.001, cTNM stage: HR 0.394; 95% CI 0.194–0.797; P = 0.010). Significant differences in PFS (P &lt; 0.0001) and OS (P = 0.022) were observed between PSC and LUAD, and for PC compared with SCC (PFS: P = 0.00036, OS: P = 0.0053). Additionally, PSC patients treated with immunotherapy showed significantly better OS (P = 0.0019) compared with those treated without immunotherapy. Conclusions PSC exhibits high KRAS and EGFR mutation rates, and spindle cell carcinoma has a worse prognosis. Immunotherapy shows potential as a treatment for advanced PSC.

Preoperative CT-based morphological heterogeneity for predicting survival in patients with colorectal cancer liver metastases after surgical resection: a retrospective study

ObjectiveTo explore the value of preoperative CT-based morphological heterogeneity (MH) for predicting local tumor disease-free survival (LTDFS) and progression-free survival (PFS) in patients with colorectal cancer liver metastases (CRLM).MethodsThe latest CT data of 102 CRLM patients were retrospectively analyzed. The morphological score of each liver metastasis was obtained, and the morphological heterogeneity difference (MHD) was calculated. The receiver operating characteristic (ROC) curve was drawn, and the cutoff value was found. The Kaplan-Meier method was used to draw survival curves of patients with or without MH. The Cox regression analysis was used to build the model with MH and clinical characteristics for predicting PFS.ResultsIn 78 patients without MH, median PFS was 9.0 months (95% CI:6.5–11.5), while in 24 patients with MH, median PFS was 6.0 months (95% CI:4.0-8.1), indicating that MH significantly affected PFS (p = 0.001). MH affected PFS in both the chemotherapy group and the chemotherapy combined with targeted therapy group (p = 0.005, p = 0.043). MH, preoperative carcinoembryonic antigen (CEA) and chemotherapy after surgery were independent predictors for postoperative PFS in patients with CRLM.ConclusionPreoperative CT-based MH had good efficacy for predicting LTDFS and PFS of CRLM patients after surgical resection, regardless of preoperative treatment. MH is one of the independent predictors of PFS.

Prognostic value of inflammatory and nutritional indexes among patients with unresectable advanced gastric cancer receiving immune checkpoint inhibitors combined with chemotherapy-a retrospective study.

Recent studies have revealed that inflammatory factors and nutritional status of patients with advanced gastric cancer (AGC) are related to the efficacy of drug therapy and patient prognosis. This study seeks to evaluate the correlation between inflammatory markers, nutritional status, and clinical outcomes of immune checkpoint inhibitor (ICI)-based therapies among inoperable AGC patients. This retrospective study included 88 AGC patients who received ICIs combined with chemotherapy. Inflammatory and nutritional indicators from patients before and after two cycles of treatment were collected. Finally, the correlations between these indicators and the clinical response and survival of AGC patients with ICI treatment were examined. The results revealed that an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0, neutrophil count to lymphocyte count ratio (NLR) < 2.84, platelet count to lymphocyte count ratio (PLR) < 82.23, lymphocyte count to monocyte count ratio ≥ 2.35, the hemoglobin, albumin, lymphocyte and platelet score (HALP) ≥ 31.17, prognostic nutritional index (PNI) ≥ 46.53, albumin ≥ 41.65, the decreased HALP group and the decreased PNI group were significantly correlated with improved objective response rate. Additionally, an ECOG PS score of 0, NLR < 2.84 and the decreased HALP group was associated with a superior disease control rate. Meanwhile, an ECOG PS score of 0 (progression-free survival (PFS): P = 0.003; overall survival (OS): P = 0.001) and decreased PLR following treatment (PFS: P = 0.011; OS: P = 0.008) were significant independent predictors of PFS and OS. Lastly, a systemic immune inflammation index ≥ 814.8 was also a positive independent predictor of OS among AGC patients. Our study supports the potential of inflammatory and nutritional factors to serve as predictors of the efficacy and prognosis in patients undergoing ICI-based therapies for AGC. However, further investigations are necessary to validate these findings.

Skeletal Muscle Index Changes on Locoregional Treatment Application After FOLFIRINOX and Survival in Pancreatic Cancer.

Patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) require complex management strategies. This study evaluated the prognostic significance of the perichemotherapy skeletal muscle index (SMI) and carbohydrate antigen 19-9 (CA 19-9) in patients with BRPC or LAPC treated with FOLFIRINOX. We retrospectively evaluated 227 patients with BR or LAPC who received at least four cycles of chemotherapy between 2015 and 2020. We analysed chemotherapy response, changes in SMI (ΔSMI, %) on computed tomography (CT) and CA19-9 to determine their impact on progression-free survival (PFS) and overall survival (OS). After the early application of loco-regional treatments (LRT) within 3 months after completing four cycles of chemotherapy, the outcomes were compared between ΔSMI and CA19-9 subgroups. Among 227 patients (median age, 60 years; 124 [54.6%] male) with 97 BR and 130 LAPC, 50.7% showed partial response (PR) to chemotherapy, 44.5% showed stable disease and 4.8% showed progressive disease (PD). Post-chemotherapy CA19-9 levels were normalized in 41.0% of patients. The high and low ΔSMI groups (based on the gender-specific cut-off of -8.6% for males and -2.9% for females) comprised 114 (50.2%) and 113 (49.8%) patients, respectively. The high ΔSMI group had poorer survival rates than the low ΔSMI group in both PFS (HR = 1.32, p = 0.05) and OS (HR = 1.74, p = 0.001). Multivariable analysis showed that ΔSMI (high vs. low; PFS, HR = 1.39, p = 0.03; OS, HR = 1.82, p < 0.001) and post-chemotherapy response (PD vs. PR/SD; PFS, HR = 18.69, p < 0.001; OS, HR = 6.19, p < 0.001) were independently associated with both PFS and OS. Additionally, the post-chemotherapy CA19-9 (≥ 37 vs. < 37; HR = 1.48, p = 0.01) was an independent predictor for PFS. Early application of LRT after chemotherapy significantly improved PFS and OS in both ΔSMI groups (all p < 0.05). However, it was not beneficial in the group with high ΔSMI and post-chemotherapy CA19-9 ≥ 37 (PFS, p = 0.39 and OS, p = 0.33). Progressive sarcopenic deterioration after four cycles of chemotherapy was associated with poor survival outcomes in patients with BR or LAPC after FOLFIRINOX. We also investigated the optimal clinical setting for the early application LRTs using the ΔSMI and post-chemotherapy CA 19-9.

Predictive value of direct bilirubin and total bile acid in lung adenocarcinoma patients treated with EGFR-TKIs

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma.

Integrating 18F-FDG PET/CT radiomics and body composition for enhanced prognostic assessment in patients with esophageal cancer

BackgroundThis study aimed to develop a predictive model utilizing radiomics and body composition features derived from 18F-FDG PET/CT scans to forecast progression-free survival (PFS) and overall survival (OS) outcomes in patients with esophageal squamous cell carcinoma (ESCC).MethodsWe analyzed data from 91 patients who underwent baseline 18F-FDG PET/CT imaging. Radiomic features extracted from PET and CT images and subsequent radiomics scores (Rad-scores) were calculated. Body composition metrics were also quantified, including muscle and fat distribution at the L3 level from CT scans. Multiparametric survival models were constructed using Cox regression analysis, and their performance was assessed using the area under the time-dependent receiver operating characteristic (ROC) curve (AUC) and concordance index (C-index).ResultsMultivariate analysis identified Rad-scorePFS (P = 0.003), sarcopenia (P < 0.001), and visceral adipose tissue index (VATI) (P < 0.001) as independent predictors of PFS. For OS, Rad-scoreOS (P = 0.001), sarcopenia (P = 0.002), VATI (P = 0.037), stage (P = 0.042), and body mass index (BMI) (P = 0.008) were confirmed as independent prognostic factors. Integration of the Rad-score with clinical variables and body composition parameters enhanced predictive accuracy, yielding C-indices of 0.810 (95% CI: 0.737–0.884) for PFS and 0.806 (95% CI: 0.720–0.891) for OS.ConclusionsThis study underscored the potential of combining Rad-score with clinical and body composition data to refine prognostic assessment in ESCC patients.

Predictive Value of GINI and ALBI Grades in Esophageal Cancer Receiving Chemoradiotherapy.

Objectives: The principal objective of this study was to assess the predictive efficacy of the global immune-nutrition-inflammation index (GINI) and the albumin-bilirubin (ALBI) score among patients receiving chemoradiotherapy for esophageal cancer. Methods: A retrospective analysis was conducted on 46 patients who received definitive or neoadjuvant radiotherapy for esophageal cancer at our institution. Blood samples were collected from these patients prior to the initiation of radiotherapy to measure the biomarkers, including the C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), the global immune-nutrition-inflammation index (GINI), and the albumin-bilirubin (ALBI) grade. The predictive significance of these biomarkers for progression-free survival (PFS) and overall survival (OS) was evaluated using both univariate and multivariate Cox regression analyses. Results: The median follow-up time for this study was 19.5 months (range: 2.6-166.3 months). Univariate analysis revealed that the platelet count (p = 0.003) and monocyte count (p = 0.04) were significant predictors of PFS. In the multivariate analysis, only the platelet count (p = 0.005) remained an independent predictor of PFS. Univariate analysis demonstrated that the neutrophil count (p = 0.04), lymphocyte count (p = 0.01), NLR (p = 0.005), PLR (p = 0.004), CRP (p = 0.02), ALBI grade (p = 0.01), and GINI (p = 0.005) were significant predictors of OS. Multivariate analysis identified the GINI as a predictor of OS, approaching statistical significance (p = 0.08). Conclusion: The results of our study indicate that the pretreatment GINI and ALBI grades are significantly and independently associated with the OS rates in patients with esophageal cancer who are undergoing chemoradiotherapy.

Assessing the Value of 68Ga-FAPI PET/CT in Gastric Mucinous Adenocarcinoma or Signet Ring Cell Carcinoma.

Purpose To investigate the clinical impact and prognostic value of gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in gastric mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRCC). Materials and Methods Eighty-six participants with newly diagnosed or recurrent gastric MAC or SRCC were prospectively enrolled from April 2021 to October 2021 and underwent both fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT and 68Ga-FAPI PET/CT. The sensitivity, specificity, and accuracy of the two scans in primary and metastatic tumors were evaluated using the McNemar test. Changes of treatment strategies were recorded to compare the treatment management value of the two PET/CT scans. The maximum standardized uptake value (SUVmax) and peritoneal cancer index (PCI) were recorded for survival analysis. Progression-free survival (PFS) was defined as the time interval from the date of PET/CT scans to the date of disease progression. Results Eighty-six participants (median age, 62 years [IQR, 45-78 years]; 49 female) were evaluated. 68Ga-FAPI PET/CT showed higher diagnostic accuracy in detecting involved lymph nodes (87% [212 of 244] vs 71% [173 of 244], P < .001) and peritoneal metastases (96% [70 of 73] vs 55% [40 of 73], P < .001) than 18F-FDG PET/CT. Twenty-six participants (30% [26 of 86]) had treatment changes due to more accurate diagnosis with 68Ga-FAPI PET/CT. Additionally, the 68Ga-FAPI PCI was an independent predictor for PFS (hazard ratio, 6.9; 95% CI: 2.1, 23.1; P = .002). Conclusion 68Ga-FAPI PET/CT had higher accuracy in diagnosis of gastric MAC/SRCC compared with 18F-FDG PET/CT and demonstrated the potential to improve treatment strategies and predict prognosis. Keywords: PET/CT, Mucinous Adenocarcinoma, Signet Ring Cell Carcinoma, Oncology, Abdomen/GI, Molecular Imaging Supplemental material is available for this article. © RSNA, 2024.

5-Fluorouracil combined with CalliSphere drug-eluting beads or conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score weighting analysis

This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P < 0.001) and DCR (84.8% vs. 72.3%, P = 0.08). The ORR at 6 months (M6) was also higher in the 5-Fu-DEB-TACE group than in the 5-Fu-cTACE group (72.7% vs. 50.8%, P = 0.01). The median PFS after treatment with 5-Fu-DEB-TACE was longer than that after treatment with 5-Fu-cTACE (11 months vs. 6 months) (P = 0.004). Cox proportional hazards regression analysis indicated that 5-Fu-DEB-TACE (HR = 0.590, P = 0.044), Model for End-Stage Liver Disease (MELD) intermediate risk (HR = 2.470, P = 0.010), BCLC stage B (HR = 2.303, P = 0.036), BCLC stage C (HR = 3.354, P = 0.002) and ascitic fluid (HR = 2.004, P = 0.046) were independent predictors of PFS. No treatment-related deaths occurred in this study. The 5-Fu-DEB-TACE group had a greater incidence of abdominal pain (72.7% vs. 47.7%, P = 0.003). However, the incidence of postoperative elevated transaminase levels was higher in the 5-Fu-cTACE group (83.1% vs. 66.6%, P = 0.031). Subgroups analysis showed patients receiving 5-Fu-DEB-TACE have better PFS compared to those receiving 5-Fu-cTACE in the BCLC stage A group (P = 0.0093), BCLC stage B group (P = 0.0096), multifocal group (P = 0.0056), Child-Pugh stage A group (P<0.001), non- extrahepatic metastasis group (P = 0.022), non-vascular invasion group (P = 0.0093), and the group with a largest tumor diameter ≥ 5 cm (P = 0.0048). At M1, M3, and M6, patients with preserved liver function and in some cases of low tumor burden had higher Objective Response Rate (ORR) and Disease Control Rate (DCR) (P < 0.05). Compared with 5-Fu-cTACE, 5-Fu-DEB-TACE has superior therapeutic efficacy, prolongs PFS, and reduces hepatotoxicity. However, it is associated with an increased incidence of postoperative abdominal pain.

IRF4: A potential prognostic biomarker for immunotherapy in NSCLC

BackgroundImmunotherapy is revolutionizing the management of advanced non-small cell lung cancer (NSCLC). However, sustained responses are observed in only a minority of patients. Reliable biomarkers are required to identify potential beneficiaries. Interferon regulatory factor 4 (IRF4) plays a crucial role in immune regulation, suggesting its potential as a prognostic biomarker in NSCLC immunotherapy. This study aimed to investigate the predictive role of IRF4 expression in patients with NSCLC receiving immunotherapy. MethodsData from three NSCLC cohorts treated with immune checkpoint inhibitors were collected from the Gene Expression Omnibus (GEO) database. The prognostic significance of IRF4 was assessed across these cohorts, and gene set enrichment analysis (GSEA) was performed. IRF4-based nomograms were developed to predict the outcomes of immunotherapy. Correlations among IRF4 expression, immune cell infiltration, and immunotherapy prognosis were evaluated in our cohort. ResultsElevated IRF4 expression was associated with improved prognosis in patients with NSCLC undergoing immunotherapy, consistent with both GEO dataset and our cohort. IRF4 emerged as an independent predictor for progression-free survival (PFS) and overall survival (OS) in multivariable Cox regression analysis. GSEA analysis highlighted links between IRF4 expression and immune activation pathways such as Chemokine_Signaling_Pathway, Natural_Killer_Cell_Mediated_Cytotoxicity, B_Cell_Receptor_Signaling_Pathway, and T_Cell_Receptor_Signaling_Pathway. In our cohort, immunohistochemistry demonstrated correlations between IRF4 expression and the infiltration of CD8+ T cells, CD20+ B cells, and PD-L1 expression in the tumor microenvironment. ConclusionHigh IRF4 expression in baseline tumor tissue could serve as a favorable predictor of NSCLC immunotherapy outcomes, aiding in personalized treatment strategies.

Clinical value of SUVpeak-to-tumor centroid distance on FDG PET/CT for predicting neoadjuvant chemotherapy response in patients with breast cancer

BackgroundSince it has been found that the maximum metabolic activity of a cancer lesion shifts toward the lesion edge during cancer progression, normalized distances from the hot spot of radiotracer uptake to tumor centroid (NHOC) and tumor perimeter (NHOP) have been suggested as novel F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters that can reflect cancer aggressiveness. This study aimed to investigate whether NHOC and NHOP parameters could predict pathological response to neoadjuvant chemotherapy (NAC) and progression-free survival (PFS) in breast cancer patients.MethodsThis study retrospectively enrolled 135 female patients with breast cancer who underwent pretreatment FDG PET/CT and received NAC and subsequent surgical resection. From PET/CT images, normalized distances of maximum SUV and peak SUV-to-tumor centroid (NHOCmax and NHOCpeak) and -to-tumor perimeter (NHOPmax and NHOPpeak) were measured, in addition to conventional PET/CT parameters.ResultsOf 135 patients, 32 (23.7%) achieved pathological complete response (pCR), and 34 (25.2%) had events during follow-up. In the receiver operating characteristic (ROC) curve analysis, NHOCmax showed the highest area under the ROC curve value (0.710) for predicting pCR, followed by NHOCpeak (0.694). In the multivariate logistic regression analysis, NHOCmax, NHOCpeak, and NHOPmax were independent predictors for pCR (p < 0.05). In the multivariate survival analysis, NHOCpeak (p = 0.026) was an independent predictor for PFS along with metabolic tumor volume, with patients having higher NHOCpeak showing worse PFS.ConclusionNHOCpeak on pretreatment FDG PET/CT could be a potential imaging parameter for predicting NAC response and survival in patients with breast cancer.

Monitoring the Response of Cyclin-Dependent Kinase 4/6 Inhibitors with Mean Corpuscular Volume.

Currently, the combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy is a first-line treatment for hormone-receptor-positive and HER2-negative metastatic breast cancer. This study aimed to assess the impact of changes in Mean Corpuscular Volume (MCV) on predicting responses to treatment and survival in patients with hormone-receptor-positive, HER2-negative metastatic breast cancer receiving CDK4/6 inhibitors and endocrine therapy. Retrospectively, data on hemoglobin levels, MCV, B12, folate levels, and survival times were collected from 275 patients. Patients were categorized into two groups based on the degree of MCV change (delta MCV ≤ 10 vs. >10). Kaplan-Meier survival analysis was performed, with significance set at p < 0.05. The average age of the patients was 56.1 ± 12.1 years. In total, 72.7% received CDK4/6 inhibitors as first-line treatment, while 27.3% received them as second-line treatment. Before CDK4/6 inhibitor use, the median MCV level was 87.7 fL (IQR: 83-91), which increased to 98 fL (IQR: 92-103) after treatment (p < 0.001). ECOG performance score, CDK4/6 inhibitor treatment line, type of endocrine therapy, and MCV change were identified as independent predictors of progression-free survival in the Cox regression model. The median progression-free survival for the entire group was 28 months. Patients with MCV delta > 10 had a median progression-free survival of 33 months, compared to 23 months for those with MCV delta ≤ 10 (p = 0.029). There was no significant difference in median overall survival times between the two groups (p = 0.158). This study highlights that patients with MCV delta > 10 had longer median progression-free survival compared to those with MCV delta ≤ 10.

Real-World Survival Outcomes of First-Line Therapies in Patients with Metastatic Clear Cell Renal Cell Carcinoma: A Retrospective Analysis from Two Centres in Saudi Arabia.

Background: Metastatic renal cell carcinoma (mRCC) represents a challenging condition characterised by poor prognosis and limited response to chemoradiotherapy. In this retrospective study, we compared the survival outcomes of first-line ICI regimens versus single-agent TKIs in patients with mRCC from two centres in Saudi Arabia. Methods: This study included 84 patients diagnosed with clear cell mRCC between January 2016 and December 2023. Patients were grouped based on treatment regimens. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier curves and Cox proportional hazards regression. Results: The median first-line PFS was 9.7 months (95% CI: 5.3-14.1) for the overall cohort, with no significant difference between the single-agent tyrosine kinase inhibitor (TKI) group (9.4 months; 95% CI: 6.4-12.4), combination ICI group (9.0 months; 95% CI: 0.0-24.9), and single-agent ICI group (21.2 months; 95% CI: 2.6-39.8; p = 0.591). The median OS for the overall cohort was 42.0 months (95% CI: 14.9-69.2), with the single-agent TKI group having a median OS of 33.3 months (95% CI: 0.0-71.7), the combination ICI group, 42.0 months (95% CI: 0.06-84.0), and the single-agent ICI group, 23.0 months (95% CI: 19.2-26.7; p = 0.73). In comparison, the ICI-based combination therapy group exhibited a higher ORR of 41.0% (95% CI: 26.3-57.8%), while the single-agent ICI group had an ORR of 20.0% (95% CI: 3.5-55.8%). Cox regression identified liver metastasis as a significant independent predictor of PFS (HR = 1.8, p = 0.043), while a lower Karnofsky Performance Status was a significant independent predictor of OS (HR = 3.5, p < 0.001). Conclusions: In real-world practice from Saudi Arabia, first-line, single-agent ICI therapy offers promising anti-tumour activity and non-inferior survival outcomes compared to standard ICI-based combinations and single-agent TKIs.

Levels of serum lipids predict responses to PD-L1 inhibitors as first-line treatment in small cell lung cancer: an observational study

BackgroundImmunotherapy provides new hope to individuals with small cell lung cancer (SCLC). Predicting biomarkers for clinical effects is crucial for SCLC patients receiving programed death-ligand 1 (PD-L1) inhibitor treatment.AimThe aim of this study was to clarify the value of serum lipids as predictors of immune related adverse events (irAEs) and the anti-tumour effects in SCLC patients who received PD-L1 inhibitors as first-line treatment.MethodThis study included patients with SCLC who received at least one cycle of PD-L1inhibitors at Shanghai Pulmonary Hospital from August 2020 to December 2023. We collected the clinical data of the SCLC patients, including basic information and serum lipid levels, before immunotherapy.ResultsThe irAEs rate was 16.1% of 124 enrolled patients. In multivariate analysis, the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was an independent predictor of irAEs (p = 0.045). Tumour response analysis indicated that the objective response rate (ORR) was 43.4% and the disease control rate (DCR) was 79.5%. Seventy-seven patients experienced any progression-free survival (PFS) event. The median PFS was longer in the HDL-C-high group (10.03 months) than in the HDL-C-low group (6.67 months) (p = 0.043). In Cox regression analysis, the serum HDL-C level was an independent predictor of PFS (p = 0.002). For patients of the high TG/HDL-C ratio, the ORR significantly differed between patients who suffered from any irAEs and those who did not (p = 0.0139).ConclusionThis study found that serum lipid levels might predict the responses to anti-PD-L1 as first-line treatment for SCLC.

Peritumoral Adipose Tissue Features Derived from [18F]fluoro-2-deoxy-2-d-glucose Positron Emission Tomography/Computed Tomography as Predictors for Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

This study investigated whether the textural features of peritumoral adipose tissue (AT) on [18F]fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) can predict the pathological response to neoadjuvant chemotherapy (NAC) and progression-free survival (PFS) in breast cancer patients. We retrospectively enrolled 147 female breast cancer patients who underwent staging FDG PET/CT and completed NAC and underwent curative surgery. We extracted 10 first-order features, 6 gray-level co-occurrence matrix (GLCM) features, and 3 neighborhood gray-level difference matrix (NGLDM) features of peritumoral AT and evaluated the predictive value of those imaging features for pathological complete response (pCR) and PFS. The results of our study demonstrated that GLCM homogeneity showed the highest predictability for pCR among the peritumoral AT imaging features in the receiver operating characteristic curve analysis. In multivariate logistic regression analysis, the mean standardized uptake value (SUV), 50th percentile SUV, 75th percentile SUV, SUV histogram entropy, GLCM entropy, and GLCM homogeneity of the peritumoral AT were independent predictors for pCR. In multivariate survival analysis, SUV histogram entropy and GLCM correlation of peritumoral AT were independent predictors of PFS. Textural features of peritumoral AT on FDG PET/CT could be potential imaging biomarkers for predicting the response to NAC and disease progression in breast cancer patients.

Potential of Nutritional Markers as Predictors After Immunotherapy in Advanced Head and Neck Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Programmed death-ligand 1 (PD-L1) is clinically assessed before initiating ICIs; however, there are no established biomarkers for predicting the response to immunotherapy. In this study, inflammatory and nutritional parameters were examined to determine the therapeutic outcomes of ICIs for HNSCC. Sixty-five patients with metastatic or recurrent HNSCC who received programmed death-1 (PD-1) blockade were enrolled. Inflammatory and nutritional indices were correlated with patient outcomes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI). Patients aged <70 years were significantly associated with a high NLR, whereas those with a performance status of 2 or 3 were closely related to a high NLR, high SII, and low PNI. Although all patients achieved an objective response rate of 24.6% and a disease control rate of 36.9%, the NLR, PLR, SII, and PNI values were not significantly different between responders and non-responders. Univariate analysis showed that the NLR, PLR, SII, and PNI were significant predictors of progression-free survival (PFS) and overall survival (OS). Multivariate analysis identified PNI as an independent predictor of PFS and OS. PNI, as a nutritional marker, was identified as a significant predictor of outcomes following PD-1 blockade administration in patients with advanced HNSCC, compared to inflammatory markers, such as NLR, PLR, and SII.