What prognostic factors have impacted the efficacy of immune checkpoint inhibitors in patients with recurrent or metastatic oral cancer?

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely adapted for recurrent or metastatic head and neck cancer (RM-HNC), and various studies on its prognostic factors have been reported. We aimed to elucidate the prognostic factors of ICI treatment for RM oral cancer (RM-OC) in a retrospective study. METHODS: We retrospectively reviewed patients with RM-OC treated with ICIs (nivolumab and pembrolizumab) at our department from May 2017 to February 2023. The objective response rate (ORR) for ICI treatment and the relationship between several potential prognostic factors, progression-free survival (PFS), and overall survival (OS) were analyzed statistically. RESULTS: The investigation enrolled 31 patients, 16 with nivolumab and 15 with pembrolizumab. There were no significant differences in the ORR or disease control rate between the nivolumab and pembrolizumab groups (p = 0.4578 and 0.2524). In multivariate analysis, the prognostic nutritional index (PNI) and C-reactive protein to albumin ratio (CAR) exhibited statistical correlations with PFS, whereas the use of antibiotics and proton pump inhibitors (PPIs), neutrophil to lymphocyte ratio (NLR), and PNI demonstrated statistical associations with OS. CONCLUSION: Our findings imply that the use of antibiotics and PPIs, which can modify the gut microbiota, may also serve as a prognostic determinant for ICI treatment in RM-OC, consistent with previous studies. Additionally, PNI may be essential in affecting the survival rates of both PFS and OS and could be an exceedingly valuable inflammatory biomarker for RM-OC.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

GNL3L exhibits pro-tumor activities via NF-κB pathway as a poor prognostic factor in acute myeloid leukemia.

Acute myeloid leukemia (AML) is the leukemia with the worst prognosis, and current knowledge of AML pathogenesis and available therapies for AML remain limited. 40% of AML patients exhibit elevated nuclear factor kappa B (NF-κB) activity, which provides a compelling rationale for targeting the NF-κB pathway in AML. Guanine nucleotide-binding protein-like 3-like protein (GNL3L) is a recently identified pro-oncogene that promotes NF-κB activation in a variety of malignancies. For the first time, we comprehensively examined GNL3L expression in AML, reporting GNL3L as a poor prognostic factor in three independent AML cohorts. GNL3L enhanced RELA activity, activated NF-κB, promoted AML cell proliferation, resisted apoptosis, and encouraged cytarabine resistance in AML. In conclusion, these data suggest a role for GNL3L in the malignant process of AML and as a promising therapeutic target.

ECT2 promotes the occurrence and is a prognostic biomarker of head and neck squamous cell carcinoma.

Background: Epithelial Cell Transforming Sequence 2 (ECT2) has been implicated in various tumorigenic processes, including proliferation, migration, and invasion. However, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Methods: This study integrates transcriptomic and single-cell RNA sequencing (scRNA-seq) data to explore the potential role of ECT2 in HNSCC. Differential expression analysis, cell-based assays (including CCK-8 for proliferation, transwell for migration, invasion assays, and flow cytometry for apoptosis and cell cycle analysis), and enrichment analysis were employed to investigate ECT2 expression levels and its regulatory effects on cellular phenotypes. Additionally, Mendelian randomization analysis was utilized to identify genes causally related to HNSCC using publicly available Genome-Wide Association Study (GWAS) data. Results: ECT2 is highly expressed in HNSCC samples and its downregulation inhibits proliferation, migration, invasion, induces apoptosis, and affects the cell cycle transition in HSC-3 cells. Furthermore, differential analysis revealed significant differences in the immune microenvironment and drug sensitivity between high and low ECT2 expression groups. The pathways enriched in different groups include CCR and its related chemokines, as well as HLA in antigen presentation and immune response. There are also significant differences in the sensitivity to drugs such as bortezomib and dasatinib between the two groups. Prognostic models constructed from prognosis-related genes showed significant differences in prognosis between high and low-risk groups. Integration of scRNA-seq data identified Monocyte clusters as high-scoring cell clusters based on genes interacting with ECT2.Mendelian randomization analysis identified three genes (LGALS2, SLC11A1, and TKT) causally related to HNSCC within this cell cluster. Conclusion: The findings suggest that ECT2 overexpression is associated with the survival rate of HNSCC, indicating its potential as a prognostic biomarker for this malignancy.

Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

BACKGROUND: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. PATIENTS AND METHODS: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. RESULTS: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. CONCLUSION: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

Survival outcomes according to the tumor location and prognostic factor in metastatic rectal cancer: a multicenter retrospective cohort study.

Background & aims: Prognostic factors of metastatic rectal cancer are not well known. We aim to determine prognostic factors affecting survival for metastatic rectal cancer patients and also to investigate the effect of tumor localization on overall survival. Methods: Metastatic rectal cancer patients who received treatment in 5 different centers between 2012 and 2022 were included. Prognostic factors for survival were evaluated using univariate and multivariate analysis. The statistical methods included Pearson's chi-square test, Fisher exact test, Log-rank test, and Cox regression model. Results: A total of 283 patients with metastatic rectal cancer were included in the study. The median OS was not significantly different among the three groups (upper rectum 30.1 months, middle rectum 28.3 months, and low rectum cancer 24.8 months; log-rank p = 0.25). In univariate analysis, Grade 3, ECOG performance status 2, the presence of multiple metastatic sites, the presence of KRAS mutation, the presence of liver metastases, the presence of nonregional lymph node metastases, and the presence of bone metastases were significant predictors of poor survival. In multivariate analysis, Grade 3, ECOG performance status 2, and the presence of multiple metastatic sites were determined as indicators of worse prognosis. Conclusion: Our findings, primary tumor location did not affect survival in metastatic rectal cancer. The most important factors affecting survival were multiple metastatic sites, tumor grade, and ECOG performance status.

Tumor budding - a potential biomarker in low grade salivary gland carcinomas?

Background: Low-grade salivary gland carcinoma is regularly treated with surgical therapy of the salivary gland without elective neck dissection in T1/2 carcinomas, either alone or with adjuvant radiation therapy. However, occult metastasis and locoregional recurrence influence therapy and outcome. Tumor budding is an emerging prognostic pathological factor in many carcinomas, but has not yet been adequately considered in salivary gland carcinomas. Methods: We conducted a retrospective single-center study of 64 patients diagnosed with low-grade carcinoma of the major salivary glands treated between 2003 and 2017. Pathological risk factors and TNM classification were thoroughly assessed for each case. All hematoxylin and eosin (HE)-stained histological specimens underwent careful examination, and tumor budding was identified following the guidelines set forth by the International Tumor Budding Consensus Conference in 2016. Results: Tumor budding was not statistically significant concerning 5-year survival rate (5-YSR) (p=0.969) and mean overall survival (log-rank p=0.315). Whereas 5-year disease-free survival rate (5-YDFSR) was 87% in the low tumor budding group and 61.1% in the intermediate and high tumor budding group (p=0.021). Mean disease-free survival accounted for 100.2 months (CI: 88.6;111.9) in the low budding score group and 58.7 months (CI: 42.8;74.6) in the other group (log-rank p=0.032). Notably, pT1/2 showed significantly lower tumor buds than pT3/4 stages (2.43 tumor buds/0.785 mm2 vs. 4.19 tumor buds/0.785 mm2, p=0.034). Similar findings were noted comparing nodal-positive and nodal-negative patients, as well as patients with and without lymphovascular invasion and perineural invasion (each p<0.05). Conclusions: Tumor budding might be used as an additional prognostic factor for recurrence in low-grade salivary gland carcinoma, seemingly associated with a higher nodal metastasis rate and advanced tumor stages and a worse 5-YDFSR. Consequently, the evaluation of tumor budding in resection specimens of low-grade salivary gland tumor may prove valuable in decision-making for neck dissection and follow-up strategy.

Clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 seed implantation for the treatment of superficial soft tissue metastasis: a 12-year retrospective analysis.

BACKGROUND: Superficial soft tissue metastasis (S-STM) of malignant tumors is uncommon and often brings great pain to patients. However, current treatment options are limited. The purpose of this study was to explore the clinical efficacy and prognostic factors of CT-guided radioactive iodine-125 (125I) seed implantation (RISI) for the treatment of S-STM. METHODS: We retrospectively evaluated 132 patients with S-STM who received RISI between June 2010 and July 2022. Local tumor progression-free survival (ltPFS), tumor response, pain control and complication were analyzed. The independent factors affecting ltPFS were screened out using a layered Cox proportional hazards model. RESULTS: The median follow-up time was 8.3 months (interquartile range [IQR], 4.5-15.3 months). The objective response rate (ORR) was 81.8%. The median ltPFS was 9.1 (95% CI: 6.6, 11.6) months. The Cox proportional hazard regression model revealed that the independent factors influencing ltPFS included KPS score, primary tumor, metastases, boundary, density and postoperative D90 (All P < 0.05). After RISI, the rate of pain relief was 92.3%. 66 (84.6%) patients reported pain marked relief, and 6 (7.7%) experienced pain moderate relief. No severe adverse events associated with RISI were observed during follow-up. CONCLUSIONS: CT-guided RISI was associated with high local control and pain relief without severe adverse events and should be considered as a reliable palliative treatment modality for S-STM. TRIAL REGISTRATION: Trial registration Retrospectively registered.

Prognostic Factors Associated with Breast Cancer-Specific Survival from 1995 to 2022: A Systematic Review and Meta-Analysis of 1,386,663 Cases from 30 Countries.

Breast cancer is the fifth-ranked cancer globally. Despite early diagnosis and advances in treatment, breast cancer mortality is increasing. This meta-analysis aims to examine all possible prognostic factors that improve/deteriorate breast cancer-specific survival. MEDLINE, PubMed, ScienceDirect, Ovid, and Google Scholar were systematically searched until September 16, 2023. The retrieved studies from 1995 to 2022 accumulated 1,386,663 cases from 30 countries. A total of 13 out of 22 prognostic factors were significantly associated with breast cancer-specific survival. A random-effects model provided a pooled estimate of the top five poorest prognostic factors, including Stage 4 (HR = 12.12; 95% CI: 5.70, 25.76), followed by Stage 3 (HR = 3.42, 95% CI: 2.51, 4.67), a comorbidity index ≥ 3 (HR = 3.29; 95% CI: 4.52, 7.35), the poor differentiation of cancer cell histology (HR = 2.43; 95% CI: 1.79, 3.30), and undifferentiated cancer cell histology (HR = 2.24; 95% CI: 1.66, 3.01). Other survival-reducing factors include positive nodes, age, race, HER2-receptor positivity, and overweight/obesity. The top five best prognostic factors include different types of mastectomies and breast-conserving therapies (HR = 0.56; 95% CI: 0.44, 0.70), medullary histology (HR = 0.62; 95% CI: 0.53, 0.72), higher education (HR = 0.72; 95% CI: 0.68, 0.77), and a positive estrogen receptor status (HR = 0.78; 95% CI: 0.65, 0.94). Heterogeneity was observed in most studies. Data from developing countries are still scarce.

C-reactive Protein Is a Prognostic Factor for Survival in Metastatic Upper Tract Urothelial Carcinoma Patients Receiving Pembrolizumab.

BACKGROUND/AIM: The number of available treatment options for urothelial carcinoma has increased recently. Upper tract urothelial carcinoma (UTUC) is relatively rare compared with bladder cancer. There are few reports on the efficacy of immune checkpoint inhibitors (ICIs) for metastatic UTUC, and ICIs may occasionally show less efficacy and cause severe side effects. Therefore, it is important to predict the treatment response and change the treatment strategy as appropriate. We investigated the prognostic factors for treatment response in patients with metastatic UTUC treated with pembrolizumab at our hospital. PATIENTS AND METHODS: Patients who received pembrolizumab for UTUC between January 2018 and June 2023 were analyzed. Patients who presented with bladder cancer complications at initial diagnosis were excluded. The primary endpoints assessed were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted using laboratory values obtained before and after pembrolizumab administration. The relationship between cancer and inflammation is important. Therefore, we analyzed this relationship using prognostic factors for urothelial carcinoma as previously reported. Specifically, pretreatment C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and NLR/albumin values were examined. RESULTS: Forty-seven patients were analyzed. The median PFS was 66 days (24-107 days), and the median OS was 164 days (13-314 days). A CRP level <1 before the first cycle was a useful factor in the multivariate analysis for both OS and PFS [OS: p=0.004, hazard ratio (HR)=3.244, 95% confidence interval (CI)=1.464-7.104; PFS: p=0.003, HR=2.998, 95%CI=1.444-6.225]. CONCLUSION: CRP level is a prognostic factor for pembrolizumab treatment response in patients with UTUC.

Predicting prognosis in colorectal cancer patients with curative resection using albumin, lymphocyte count and RAS mutations.

Colorectal cancer (CRC) poses a significant global health challenge, demanding reliable prognostic tools to guide treatment decisions. This study introduces a novel prognostic scoring system, the albumin-total lymphocyte count-RAS index (ALRI), integrating serum albumin, lymphocyte count, and RAS gene mutations. A cohort of 445 stage I-III CRC patients undergoing curative resection was analyzed, revealing ALRI's association with clinicopathological factors, including age, tumor location, and invasion depth. The ALRI demonstrated superior prognostic value, with a cutoff value of 2 distinguishing high and low-risk groups. The high-ALRI group exhibited elevated rates of recurrence. Univariate and multivariate analyses identified ALRI as an independent predictor for both 5 year recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier curves illustrated significant differences in RFS and OS between high and low-ALRI groups, emphasizing ALRI's potential as a prognostic marker. Importantly, ALRI outperformed existing nutritional indices, such as controlling nutritional status and neutrophil-to-lymphocyte ratio, in predicting overall survival. The study underscores the comprehensive insight provided by ALRI, combining inflammatory, nutritional, and genetic information for robust prognostication in CRC patients. This user-friendly tool demonstrates promise for preoperative prognosis and personalized treatment strategies, emphasizing the crucial role of inflammation and nutrition in CRC outcomes.

A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel.

The lack of non-invasive methods for detection of early metastasis is a crucial reason for the poor prognosis of lung cancer (LC) liver metastasis (LM) patients. In this study, the goal was to identify circulating biomarkers based on a biomarker model for the early diagnosis and monitoring of patients with LCLM. An 8-gene panel identified in our previous study was validated in CTC, cfRNA and exosomes isolated from primary lung cancer with & without metastasis. Further multivariate analysis including PCA & ROC was performed to determine the sensitivity and specificity of the biomarker panel. Model validation cohort (n = 79) was used to verify the stability of the constructed predictive model. Further, clinic-pathological factors, survival analysis and immune infiltration correlations were also performed. In comparison to our previous tissue data, exosomes demonstrated a good discriminative value with an AUC of 0.7247, specificity (72.48%) and sensitivity (96.87%) for the 8-gene panel. Further individual gene patterns led us to a 5- gene panel that showed an AUC of 0.9488 (p = < 0.001) and 0.9924 (p = < 0.001) respectively for tissue and exosomes. Additionally, on validating the model in a larger cohort a risk score was obtained (RS > 0.2) for prediction of liver metastasis with an accuracy of 95%. Survival analysis and immune filtration markers suggested that four exosomal markers were independently associated with poor overall survival. We report a novel blood-based exosomal biomarker panel for early diagnosis, monitoring of therapeutic response, and prognostic evaluation of patients with LCLM.

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study.

Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.

CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas.

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.

Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.

BACKGROUND: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). OBJECTIVE: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA. METHODS: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites. RESULTS: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037). CONCLUSION: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.

Predictors of outcome following an epidural steroid injection for disc-related sciatica: a Delphi consensus study.

PURPOSE: Trial data shows modest reductions in leg pain, disability and surgery avoidance following epidural steroid injections (ESI) for severe sciatica. Despite their common use, there is no clear evidence about which patients are more likely to benefit from ESI. The aim of this study was to generate consensus on potential predictors of outcome following ESI for disc-related sciatica. METHODS: A list of potential predictors of outcome was generated during a consensus meeting of seven experts. The items were subsequently presented in a two round on-line Delphi study to generate consensus among experts on which items are potential predictors of outcome. Consensus was defined as 70% agreement among participants. RESULTS: Sixty-one items were generated during the consensus meeting. Of ninety experts invited to participate in the on-line Delphi study, 44 (48%) and 33 (73%) took part in rounds one and two respectively. Twenty-eight additional items suggested by participants in round one were included in round two. Overall, 14 items reached consensus reflecting domains of health, medication use, pain intensity, psychosocial factors, imaging findings and type of injection. CONCLUSION: Based on expert consensus, items that can be routinely collected in clinical practice were identified as potential predictors of outcomes following ESI.

Maintenance chemotherapy for esophageal squamous cell carcinoma after standard concurrent chemoradiotherapy: a national propensity score matching cohort study.

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive cancer, and its standard treatment is concurrent chemoradiotherapy (CCRT). Maintenance chemotherapy is often used to help prevent cancer recurrence, but its efficacy for patients with ESCC receiving CCRT remains unclear. We conducted a large head-to-head propensity score matching cohort study to estimate the effects of maintenance chemotherapy on overall survival and cancer-specific survival in patients with ESCC receiving standard CCRT. After propensity score matching (PSM), we recruited 2724 patients with ESCC (2177 in the maintenance chemotherapy group and 547 in the non-maintenance chemotherapy group). The adjusted hazard ratios (95% confidence intervals) of all-cause mortality and cancer-specific mortality for the maintenance chemotherapy group were 1.15 (1.06-1.26, P = 0.0014) and 1.08 (0.88-1.29, P = 0.1320), respectively, compared with the non-maintenance chemotherapy group. We also found that older age, relatively lower body mass index (BMI), higher American Joint Committee on Cancer clinical stage, and poor response to CCRT as measured using the Response Evaluation Criteria in Solid Tumors were poor independent predictors of all-cause mortality and cancer-specific mortality. Our findings indicated that maintenance chemotherapy may not improve the survival of patients with ESCC who have received CCRT. Additionally, we identified several key prognostic factors for patients with ESCC receiving CCRT, including relatively low BMI and poor response to CCRT. Further research is needed to understand the benefits and risks of maintenance chemotherapy in similar patient populations in order to identify new therapies that could improve treatment responses.

HALP score as a novel prognostic factor for patients with myelodysplastic syndromes.

Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients' median age was 68 (19-84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34-49.88) months by the Kaplan-Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS.

Artificial intelligence to unlock real-world evidence in clinical oncology: A primer on recent advances.

PURPOSE: Real world evidence is crucial to understanding the diffusion of new oncologic therapies, monitoring cancer outcomes, and detecting unexpected toxicities. In practice, real world evidence is challenging to collect rapidly and comprehensively, often requiring expensive and time-consuming manual case-finding and annotation of clinical text. In this Review, we summarise recent developments in the use of artificial intelligence to collect and analyze real world evidence in oncology. METHODS: We performed a narrative review of the major current trends and recent literature in artificial intelligence applications in oncology. RESULTS: Artificial intelligence (AI) approaches are increasingly used to efficiently phenotype patients and tumors at large scale. These tools also may provide novel biological insights and improve risk prediction through multimodal integration of radiographic, pathological, and genomic datasets. Custom language processing pipelines and large language models hold great promise for clinical prediction and phenotyping. CONCLUSIONS: Despite rapid advances, continued progress in computation, generalizability, interpretability, and reliability as well as prospective validation are needed to integrate AI approaches into routine clinical care and real-time monitoring of novel therapies.

Toll-like receptor (TLR) 4 is a potent prognostic factor in prostate cancer associated with proliferation and invasion.

Prostate cancer is one of the most common malignancies in men, and there is a need to explore novel biomarkers or therapeutic targets. Toll-like receptor 4 (TLR4) is expressed not only in antigen-presenting cells but also types of human malignancies, contributing to disease progression, although its clinical significance or functional role in prostate cancer remains unclear. Therefore, we immunolocalized TLR4 in 117 prostate cancer tissues to address its clinicopathological significance. Additionally, we performed in vitro assays to examine the effects of TLR4 on proliferation and migration of prostate cancer cell lines (LNCaP, DU-145 and PC-3). TLR4 immunoreactivity was predominantly detected in the cytoplasm of prostate cancer cells, and it was positively associated with proliferation and invasion abilities, as well as Gleason score. Subsequent in vitro experiments revealed that the inhibition of TLR4 by Sparstolonin B (SsnB) significantly suppressed the proliferation and migration of LNCaP, DU-145 and PC-3 cells. Therefore, we concluded that TLR4 was a potent prognostic factor associated with proliferation and invasion, and it might serve as a therapeutic target in prostate cancer.