Clinicopathological Variables Research Articles

Multicenter analysis of the efficacy of early cholecystectomy and preoperative cholecystostomy for severe acute cholecystitis: a retrospective study of data from the multi-institutional database of the Hiroshima Surgical Study Group of Clinical Oncology

BackgroundSevere acute cholecystitis (AC) is a challenging disease because it comprises coexisting systemic infections that lead to vital organ dysfunction. This study evaluated the optimal surgical timing and efficacy of preoperative percutaneous cholecystostomy (PC) for patients with severe AC.MethodsData of 142 patients who underwent cholecystectomy for severe AC between 2011 and 2021 were retrospectively collected from the multi-institutional database of the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into the early cholecystectomy (EC) group (within 72 h of symptom onset) and delayed cholecystectomy (DC) group. They were also subdivided into the upfront cholecystectomy group and preoperative PC before cholecystectomy group. The diagnosis and severity of AC were graded according to the Tokyo Guidelines 2018. Clinicopathological variables and outcomes were compared.ResultsNo significant differences in age, body mass index, American Society of Anesthesiologists (ASA) classification, and Charlson comorbidity index between the EC and DC groups were observed. Preoperative drainage was more commonly performed for the DC group than for the EC group. Local severe AC features were more commonly detected in the DC group than in the EC group. The postoperative outcomes of the EC and DC groups were comparable. Compared to the PC before cholecystectomy group, the upfront cholecystectomy group included more patients with ASA physical status ≥ 3 and more patients who used oral warfarin. Warfarin usage and cardiovascular dysfunction rates of the PC after cholecystectomy group were higher than those of the upfront cholecystectomy group. PC was associated with significantly less intraoperative bleeding and shorter hospital stays.ConclusionsPatients who can tolerate general anesthesia are good candidates for EC. Patients who use warfarin and those with cardiovascular dysfunction are considered to be at high risk for postoperative complications; therefore, to prevent AC recurrence during the waiting period, PC before cholecystectomy during the same admission is more appropriate than upfront cholecystectomy for these patients.

MRI-based radiomics for stratifying recurrence risk of early-onset rectal cancer: a multicenter study

Early-onset rectal cancer (EORC) is characterized by a unique disease process with different clinicopathological features compared with late-onset rectal cancer (LORC). Research on the risk of recurrence in EORC patients, however, is limited. We aim to develop a predictive model to accurately predict EORC recurrence risk. Rectal cancer patients who underwent radical surgery and T2-weighted imaging and diffusion-weighted imaging magnetic resonance imaging (MRI) were retrospectively enrolled from three medical institutions from November 2012 to November 2018. Differences in clinicopathological characteristics between EORC and LORC were compared. Five prediction models for disease-free survival were constructed based on clinicopathological variables and five radiomic features from pretreatment MRI of the EORC. A fixed cut-off value calculated in the training set was used to stratify EORC patients into high-risk and low-risk groups of post-operative recurrence. Model performance was evaluated by concordance index (C-index) and receiver operating characteristic curve. A total of 264 EORC patients (median age, 43 years, 163 males) and 778 LORC patients (median age, 62 years, 520 males) were enrolled. Pretreatment positive carcinoembryonic antigen [hazard ratio (HR)= 2.84, P= 0.006], pathological positive lymph node status (pN positive) [HR= 2.86, P= 0.011] and MRI-based radiomics score [HR= 2.72, P < 0.001] are independent risk factors for disease-free survival in EORC patients. The EORC-ClinPathRadiom model, constructed by integrating the clinicopathological characteristics and MRI-based radiomics features of EORC, showed C-index of 0.82, 0.82, and 0.81 in the training, internal, and external test sets, respectively. This model effectively stratified EORC patients into high risk and low risk of recurrence (HRs for the training, internal, and external test sets were 8.96, 6.81, and 7.46, respectively). The EORC-ClinPathRadiom model can effectively predict and stratify the risk of post-operative recurrence in EORC patients.

TNBC-DX genomic test in early-stage triple-negative breast cancer treated with neoadjuvant taxane-based therapy

BackgroundIdentification of biomarkers to optimize treatment strategies for early-stage triple-negative breast cancer (TNBC) is crucial. This study presents the development and validation of TNBC-DX, a novel test aimed at predicting both short- and long-term outcomes in early-stage TNBC. MethodsInformation from 1,259 patients with early-stage TNBC (SCAN-B, CALGB-40603, and BrighTNess) were used to establish the TNBC-DX scores. Independent validation of TNBC-DX was carried out in 3 studies: i) WSG-ADAPT-TN, ii) MMJ-CAR-2014-01, and iii) NeoPACT, including 527 patients with stage I-III TNBC undergoing neoadjuvant chemotherapy. In WSG-ADAPT-TN, patients were randomized to receive nab-paclitaxel plus gemcitabine or carboplatin. In MMJ-CAR-2014-01, patients received carboplatin plus docetaxel. In NeoPACT, patients received carboplatin plus docetaxel and pembrolizumab. The objective of this study was to evaluate the association between TNBC-DX and efficacy outcomes (pCR, distant disease-free survival [DDFS] or event-free survival [EFS], and overall survival [OS]) in the validation cohorts. ResultsTNBC-DX test was created incorporating 10-gene core immune gene module, 4-gene tumor cell proliferation signature, tumor size, and nodal staging. In the 2 independent validation cohorts without pembrolizumab, the TNBC-DX pCR score was significantly associated with pCR after adjustment for clinicopathological variables and treatment regimen (odds ratio per 10-units increment=1.34, 95% CI 1.20-1.52, p<0.001). pCR rates for the TNBC-DX pCR-high, -medium, and -low categories were 56.3%, 53.6%, and 22.5% respectively (odds ratio for pCR-high vs pCR-low=3.48 [95% CI 1.72-7.15], p<0.001). Additionally, the TNBC-DX risk score was significantly associated with DDFS (hazard ratio [HR] high-risk vs low-risk=0.24, 95% CI 0.15-0.41, p<0.001) and OS (HR=0.19, 95% CI 0.11-0.35, p<0.001). In the validation cohort with pembrolizumab, the TNBC-DX scores were significantly associated with pCR, EFS, and OS. ConclusionsTNBC-DX predicts pCR to neoadjuvant taxane-carboplatin in stage I-III TNBC and helps to forecast the patient´s long-term survival in the absence of neoadjuvant anthracycline/cyclophosphamide, and independent of pembrolizumab use.

HIPEC for metastatic gastric cancer: Moving the needle towards 3-year survival

IntroductionPrior work has established hyperthermic intraperitoneal chemotherapy (HIPEC) administration as a safe treatment option for select patients with gastric adenocarcinoma and carcinomatosis. However, identifying patients who will maximally benefit from HIPEC remains unclear. This study assessed a single-institution experience with HIPEC for metastatic gastric cancer to identify variables associated with improved survival. MethodsA database of patients treated for metastatic gastric adenocarcinoma at MD Anderson Cancer Center from 2013 to 2022 was queried for patients undergoing HIPEC as part of their treatment regimen. Patients were stratified by overall survival (OS)≥36 months or <36 months and assessed along demographic and clinicopathologic variables to identify factors associated with OS ≥ 36 months. ResultsAmong 104 patients, 1,2, and 3-year OS from diagnosis was 89 %,44 %, and 18 %. Patients with OS ≥ 36 months were more likely to have moderately differentiated tumors, positive cytology only (i.e. no visible carcinomatosis), and lower peritoneal cancer index (PCI) than those with OS < 36 months (p = 0.002, p = 0.01, p = 0.001,respectively). Groups did not otherwise differ with respect to demographic parameters or treatment or pathologic details. Among patients who underwent gastrectomy, those with OS < 36 months had higher pathologic T and N category (p = 0.003 and p = 0.02, respectively). Postoperative mortality was zero in both groups among patients undergoing gastrectomy. ConclusionsHIPEC may provide more durable survival benefit among patients with metastatic gastric cancer with moderately differentiated disease, low PCI, and positive cytology alone. Additionally, among patients who undergo gastrectomy, higher final pathologic T and N category are associated with worse survival. Trials are needed to compare 3-year OS rates in patients treated with HIPEC versus systemic therapy alone.

Exploring the Potential of Enhanced Prognostic Performance of NCCN-IPI in Diffuse Large B-Cell Lymphoma by Integrating Tumor Microenvironment Markers: Stromal FOXC1 and Tumor pERK1/2 Expression.

FOXC1 and ERK1-2 are proteins implicated in aggressive biological behavior of various malignancies including lymphomas. We investigate the additive prognostic value of stromal FOXC1 expression and tumor phosphorylated ERK1-2 (pERK1-2) expression to the established National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), in 92 diffuse large B-cell lymphoma (DLBCL) cases. Multidimensional analysis using statistics and machine learning (ML) models assessed prognostic value of established clinicopathologic variables with stromal FOXC1 and tumor pERK1-2 expressions. Both high FOXC1 stroma group and high pERK1-2 tumor group were significantly associated with shorter progression-free survival (PFS) and overall survival (OS) compared with low group (p = 0.015, 0.034 and p = 0.025, 0.025 each respectively). In multivariable analysis, high FOXC1 stromal expression was an independent prognostic factor of OS (p = 0.037). The addition of stromal FOXC1 and tumor pERK1-2 to the NCCN-IPI score significantly improved prediction of time to death compared with NCCN-IPI score alone (Harrell's C-index = 0.801 vs. 0.764; p = 0.030). ML models reconfirmed the addition of stromal FOXC1 expression and tumor pERK1-2 to NCCN-IPI score had the highest C-index (0.952) among combinations. Stromal FOXC1 and tumor pERK1-2 were determinants of DLBCL prognosis, whose addition significantly improved prognostic performance of the NCCN-IPI.

The Evaluation of Gastric Cancer Lymphovascular Invasion Using CT Volume Perfusion.

The best treatment option for patients with resectable gastric cancer is radical gastric cancer surgery. However, the postoperative overall survival rate is low. Lymphovascular invasion (LVI) is a risk factor for cancer recurrence and a stand-alone predictor of a poor post-operative prognosis for gastric cancer (GC) patients. Current evaluation of tumor LVI performed on histological specimens, which can only be assessed after surgery, is also limited by intra-tumoural heterogeneity via biopsy. This study explored the value of CT volume perfusion in assessing tumors' lymphovascular invasion of gastric cancer. 59 gastric cancer patients confirmed by pathology who underwent both computed tomography (CT) volume perfusion examinations and gastrectomy surgery were prospectively included. Tumour lymphovascular invasion (LVI, positive or negative) was evaluated. The relationship between clinicopathological variables associated with LVI and CT perfusion parameters was analyzed by univariate analysis, followed by multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. The LVI-positive and LVI-negative groups differed significantly in terms of time to start (TTS), mean transit time (MTT), Tmax, and flow extraction product (FEP). Both FEP (odds ratio (OR), 1.048; 95% confidence interval (CI): 1.005-1.092) and MTT (OR, 0.549; 95% CI: 0.351-0.858) have the potential to be employed as independent predictors of LVI (both p < 0.05). There were different correlations between LVI, lower MTT and greater FEP. The specificity of MTT (87.88%) was higher than that of FEP (72.73%), while the sensitivity of MTT (53.85%) was lower than that of FEP (57.69%). Compared to MTT and FEP alone, the combination demonstrated a comparatively higher area under the curve (AUC) (0.797) and sensitivity (84.62%). CT volume perfusion helps evaluate LVI in gastric cancer before surgery. MTT and FEP are independent predictors for LVI, and the combination variation has better diagnostic performance. Clinical Trial Register: Jiangmen Central Hospital, https://www.chictr.org.cn/showproj.html?proj=24375, ChiCTR1800014455.

Prognostic utility of the modified albumin-bilirubin score among patients undergoing curative-intent surgery for gallbladder cancer

BackgroundGallbladder cancer (GBC) has been associated with high rates of recurrence and dismal prognosis even after curative-intent resection. The prognostic utility of the modified albumin-bilirubin (mALBI) score among individuals undergoing curative-intent resection for GBC has not been determined. MethodsPatients who underwent radical resection for GBC between 2000 and 2022 were identified from an international, multi-institutional database. Preoperative albumin and bilirubin levels were used to calculate the mALBI score. The relationship among mALBI score, overall survival (OS), and recurrence-free survival (RFS) was examined. ResultsAmong 269 patients who underwent radical resection for GBC, 161 (59.9%) had mALBI grade 1, 48 (17.8%) had grade 2a, 47 (17.5%) had grade 2b, and 13 (4.8%) had mALBI grade 3. After surgery, compared with patients with a low mALBI grade (grade 1/2a), individuals with a high mALBI grade (grade 2b/3) had worse 5-year OS (54.4% vs 19.2%, respectively; P < .001) and RFS (42.0% vs 17.8%, respectively; P < .001). On multivariable analysis, after controlling for relevant clinicopathologic variables, individuals with a high mALBI score remained independently associated with higher risks of death and recurrence (OS: hazard ratio [HR], 2.38 [95% CI, 1.50–3.79]; RFS: HR, 2.12 [95% CI 1.41–3.20]) versus patients with a low mALBI score after curative-intent resection for GBC. Of note, mALBI score was associated with incrementally worse survival within T2, T3, and N+ categories, whereas classic American Joint Committee on Cancer subclassifications failed to distinguish patients with long-term survival. ConclusionThe mALBI score presents a simple, objective measure of hepatic functional reserve and may be a useful prognostic tool for patients undergoing curative-intent resection for GBC.

Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.

Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8+ T cells include less differentiated stem-like exhausted T (Texstem) cells and terminally exhausted T (Texterm) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort. Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Texstem and Texterm CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire. Higher frequency of Texstem was associated with significantly increased OS [median 9.9 vs. 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Texterm was not associated with OS. These findings were validated in the mesothelioma cohort (high vs. low Texstem, median OS 32.1 vs. 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Texstem cells also contained 'bystander' virus-specific T cells. This study demonstrates that PE CD8 Texstem cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.

Expression of Axl Receptor Tyrosine Kinase and Its Association With Ki-67 Proliferation Marker, BCL-2 Anti-apoptotic Protein, Hormone Receptor Status, and HER2/Neu Status in Breast Cancer Among Women From Duhok, Iraq.

Background Breast cancer (BC) is the most prevalent cancer among women worldwide, contributing to high mortality rates, especially in Iraqi women. Detecting the disease before metastasis may increase survival chances for many patients, but that is not the case for most of them. Thus the search for new prognostic biomarkers or testing the relevance of existing ones could contribute to therapeutic decisions complementing the traditional methods, including TNM (tumor, node, and metastasis) staging, tumor grade, and other clinicopathological features in addition to the use of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). The Axl receptor is frequently associated with invasion, migration, poor prognosis, and angiogenesis. Furthermore, its association with chemotherapyand targeted therapy resistance makes itan ideal biomarker for therapeutic targeting. Methodology This study involved 50 malignant cases with 25 benign fibroadenoma and non-neoplastic cases represented by inflammatory conditions, collected with their corresponding data from the central lab in Duhok Governorate, Iraq. Expression of Kiel 67 (Ki-67) proliferation marker and B-cell lymphoma 2 (BCL-2) anti-apoptotic protein was measured using immunohistochemistry (IHC) to estimate tumor growth and apoptosis. Gene expression of the Axl receptor was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Cases with high Ki-67 accounted for 68% and low Ki-67 cases were 32% across the graded groups and were significantly associated with tumor grade, PR, and HER2. BCL-2-negativecases accounted for 62% and BCL-2-positive cases were 38%. It was revealed that BCL-2 had a strong correlation with age, especially inthose under 50 years.As for the Axl gene expression, the average fold change in expression in the high-grade (H.) group was 1.74 times higher than in the control group, while in the low/intermediate (L.) group, it was 3.74 times higher. Additionally, when comparing these results with other variables, no significant associations were observed. Conclusion Axl receptor was not associated with all of the clinicopathological variables, the expression values were high in malignant tumors in comparison with the benign tumors, and it was found that Axl receptor expression was associated with low/intermediate grade, which is considered a favorable prognostic factor. Although Axl receptor expression was previously linked with proliferation and invasiveness in BC, its association with the Ki-67 proliferation marker and BCL-2 anti-apoptotic protein was not observed.

Increased neutrophil counts are associated with poor overall survival in patients with colorectal cancer: a five-year retrospective analysis.

Colorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC. A total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured. The non-survival group had increased levels of white blood cells, neutrophils (both p<0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05]. This study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools.

Biomarker Profiling of Upper Tract Urothelial Carcinoma Only and with Synchronous or Metachronous Bladder Cancer.

Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes. A retrospective cohort of UTUC was divided into UTUC-only (n = 71) and UTUC + UBC (n = 43). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERTp, FGFR3, RAS, and TP53 status. Kaplan-Meier and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients. No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508-8.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513-3.190, p = 0.597). This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.

Abstract C094: Differential expression analysis with transcriptome data in FFPE samples from Colombian patients with colorectal cancer

Abstract Introduction: Colorectal cancer (CRC) is a significant public health issue in Colombia, It occupies third place in incidence and ranking as the fifth leading cause of cancer-related deaths. Understanding the sociodemographic, clinicopathological, and molecular characteristics of CRC patients is crucial for prognosis, effective management, and treatment. Several molecular alterations and clinicopathological variables have been associated with the prognosis of the disease in different populations; However, we do not know if there are differentially expressed genes specific to Colombian population that are associated with CRC prognosis. Objective: Perform differential expression analysis using RNA-seq data obtained from formalin-fixed paraffin-embedded (FFPE) tissue samples from Colombian patients with CRC. Methodology: For this preliminary analysis were included 5 patients diagnosed with CRC between 2010-2014 at Instituto Nacional de Cancerologia from Colombia. From each patient, formalin-fixed and paraffin-embedded (FFPE) samples of tumor tissue and non-tumor tissue from the surgical remnant were obtained. Extracted RNA was used to perform whole-genome RNA sequencing (RNA-seq) at a depth of 100X. Bioinformatic analysis was performed using Fastqc, Cutadapt, Ribodetector, and STAR on a Linux server. The DESeq2 package in RStudio was used to perform the differential expression analysis between tumor samples vs. non-tumorous. A significant differential expression was considered using an FDR-adjusted p ≤0.05 and a log fold change of 2. Results and discussion: A list of 18 differentially expressed genes was obtained which 5 underexpressed stand out: B3GNT6 (LFC:-10.66; padj=0.0093), ITLN1 (LFC:-6.23; padj=0.0231), NR3C2 (LFC:-3.34; padj=0.0231), NLGN1 (LFC:- 0.46; padj=0.0301), CEACAM7 (LFC:-5.91; padj= 0.0301); and one overexpressed gene: RPL9 (LFC:5.44; padj=0.0267). These genes have been previously characterized and associated with the progression and prognosis of this disease in other populations. Conclusions: 6 differentially expressed genes were found using RNA-seq in FFPE samples. These genes have been associated with CRC progression and prognosis in previous studies, but have not been evaluated in the Colombian population. From this perspective, we propose to continue with the analysis by increasing the number of samples and evaluating their association with the different clinicopathological variables and their impact on the prognosis of the disease. Citation Format: Wendy J. Montero Ovalle, Silvia J Serrano Gómez, Diego F Ballen Lozano. Differential expression analysis with transcriptome data in FFPE samples from Colombian patients with colorectal cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C094.

Abstract B013: Host phenotype profiling predicts progression to resection in neoadjuvant pancreatic cancer

Abstract Introduction Neoadjuvant chemotherapy offers a modest survival benefit in pancreatic cancer. Current methods for assessing response to chemotherapy are limited to CA19-9 and post- treatment imaging. However, these methods are not without caveats and focus heavily on tumour biology and staging the tumour, without consideration of host biology or staging the host. We sought to explore the relationship between host biology and outcomes in neoadjuvantly- treated pancreatic cancer, and determine the utility of host phenotype profiling as a tool for predicting chemotherapy response and subsequent progression to resection. Methods Host phenotype profiling was performed by measuring body composition (BC) pre- and post- neoadjuvant chemotherapy in a large international pancreatic cancer cohort (n = 301). Patients with resectable or borderline resectable disease were included if they received chemotherapy with neoadjuvant intent. BC was determined with contrast-enhanced CT scans by measuring single-slice L3 cross-sectional area. Results There were significant differences in BC change from baseline to post-treatment between resected (n = 174) and non-resected patients (n = 127). Patients who did not progress to resection exhibited greater loss in all BC compartments vs those who progressed to resection (muscle area -3.4 vs -0.7, visceral fat -10.1 vs -2.1, subcutaneous fat -12.0 vs -1.4, all p &amp;lt; 0.001, median percentage change per 100 days). We used these values to define a adverse and favourable host phenotypes, which significantly correlated with progression to resection (58.8% adverse phenotype, 74.3% favourable phenotype, p &amp;lt; 0.001). The independence of this effect was confirmed in a logistic regression model with well-established clinico-pathological variables including CA19-19 rise (adverse phenotype OR of non-resection 4.57, 95% CI 1.55-13.48, p = 0.006). Conclusion Host phenotype profiling represents a useful addition to an otherwise limited toolbox of methods for assessing treatment response and selecting for surgery in neoadjuvant pancreatic cancer. Clinicians will be familiar with the subjective “gut feeling” of identifying patients in the clinic who are unlikely to be candidates for surgery, and we demonstrate an objective measurement of this. Early identification of patients on an adverse trajectory may highlight those who would benefit from early intervention such as prehabilitation, salvage change of chemotherapy regimen, or nutritional optimization to switch the phenotype from adverse to favourable and reverse adverse host biology. Citation Format: Adam Bryce, Stephan Dreyer, Ross Dolan, Fieke Froeling, Dario Solinas, Alice Cattelani, Antonio Pea, David Chang. Host phenotype profiling predicts progression to resection in neoadjuvant pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B013.

B7H3 Immune Checkpoint Overexpression Is Associated with Decreased Complete Response Rates to Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

Rectal cancer accounts for approximately one-third of colorectal cancers, with over 340,000 deaths globally in 2022. Despite advancements in treatment, the five-year overall survival for locally advanced rectal cancer (LARC) remains at 74%, with significant morbidity. B7H3 (CD276), an immune checkpoint protein, plays a role in tumor progression and resistance to therapy, and correlates with poor prognosis in various cancers, including colorectal cancer. This study aims to evaluate the expression of B7H3 in LARC and its impact on overall complete response (oCR) rates to neoadjuvant therapy. A retrospective study was conducted on 60 patients with LARC who received neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision (TME). B7H3 expression was assessed using immunohistochemistry on surgical specimens. Expression levels were categorized as high or low based on a composite score, and their association with oCR rates was analyzed. High B7H3 expression was observed in 60% of patients, with 73.5% showing expression in more than 50% of tumor cells. Patients who achieved oCR had significantly lower B7H3 expression compared to those with residual disease (p < 0.001). No nuclear expression of B7H3 was detected. No significant correlation was found between B7H3 expression and other clinicopathological variables, except for a higher likelihood of non-restorative surgery in patients with elevated B7H3 levels (p = 0.049). Mucinous adenocarcinoma had high expression of B7H3. Elevated B7H3 expression is associated with reduced oCR rates in LARC, highlighting its potential role as a prognostic biomarker. Further studies with larger cohorts are warranted to validate these findings and explore B7H3-targeted therapies as a treatment strategy for LARC.

Liver-First Resection in Patients With Synchronous Colorectal Liver Metastases Is Associated with Inferior Recurrence-Free Survival: Reconsidering the Importance of the Primary Cancer.

Synchronous colorectal liver metastases may be managed with primary-first, simultaneous, or liver-first resection. Relative oncologic outcomes based upon treatment sequencing are understudied. This study aimed to assess oncologic survival outcomes in patients with synchronous colorectal liver metastases managed with each of the three treatment strategies, with respect to early or delayed removal of the primary tumor. Retrospective analysis of prospectively maintained database, with 1:1 propensity-matching of relevant clinicopathologic variables comparing liver-first to primary-first/simultaneous approaches. Single-institution, tertiary cancer center. Patients undergoing curative-intent hepatectomy for synchronous colorectal liver metastases from 2003-2019. Overall and recurrence-free survival. Of 151 patients, 23% (n = 35) had liver-first and 77% (n = 116; primary-first = 93 and simultaneous = 23) had primary-first/simultaneous approaches. Median follow-up was 45 months. Recurrence-free survival was worse for liver-first versus primary-first/simultaneous groups (median 12 versus 16 months, p = 0.02), driven by three-year extrahepatic recurrence-free survival of 19%, 58%, and 50% for liver-first, primary-first, and simultaneous groups, respectively. Three-year overall survival was not significantly different at 86%, 79%, and 86%, respectively. Oncologic outcomes did not significantly differ between primary-first and simultaneous groups (all p > 0.4). Matching yielded 34 clinicopathologically similar patients per group (liver-first = 34, primary-first = 28/simultaneous = 6). The liver-first approach was associated with shorter recurrence-free survival (median 12 versus 23 months, p = 0.004), driven by extrahepatic recurrence-free survival (3-year: 20% versus 55%, p = 0.04). Overall survival was not significantly different at 3-years (79% versus 80%, p = 0.95) or 5-years (59% versus 59%, p > 0.99). This study has a retrospective design and limited sample size. A liver-first approach is associated with worse recurrence free-survival compared to primary-first or simultaneous resection, driven by extrahepatic recurrence. Prospective study of whether oncologic risk is associated with leaving the primary in situ is needed. Multidisciplinary treatment sequencing and enhanced postoperative surveillance for patients receiving liver-first resection is recommended. See Video Abstract.

Poor Survival of Patients With Very Small But Locally Advanced (T4) Oropharyngeal Cancer.

Objective : The size of T4 tumor could vary in oropharyngeal squamous cell carcinoma (OPSCC). Using the Surveillance, Epidemiology, and End Results (SEER) database, this study aimed to investigate the role of tumor size in the prognosis of patients with T4 OPSCC. Study Design: Retrospective cross-sectional. Setting: SEER-Medicare-linked database. Methods: This study enrolled 1153 patients diagnosed with T4 OPSCC from the SEER registry between 2010 and 2016. The primary study variables were tumor size, human papillomavirus (HPV) infection, and disease-specific survival (DSS). Primary tumor size and clinicopathological variables according to HPV status were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression. Results: The 5-year DSS of patients with HPV-negative T4 OPSCC tumors ≤1 cm was worse than that of patients with tumors >1 cm (P < .001). The results were consistent even after propensity score matching (P = .002). Tumors ≤1 cm had a hazard ratio (HR) as high as that of distant metastasis (HR 2.8 vs HR 2.6, P = .006). A decreased DSS of ≤ 1 cm tumors was observed in HPV-negative T4 OPSCC, but not in HPV-positive T4 OPSCC (P < .001 vs P = .96). Conclusion: A tumor diameter ≤1 cm was associated with poor prognosis in patients with HPV-negative T4 OPSCC. Tumor diameter ≤1 cm could be a predictive factor for poor outcomes in HPV-negative T4 OPSCC.

Immunohistochemical Expression of Cyclooxygenase-2 in endometrioid carcinoma

Background and objectives: Cyclooxygenase-2 functions as an enzyme which synthesize prostaglandins from Arachidonic acid Cyclooxygenase -2 is one of the important factors in maintaining the endometrium during menstrual cycle. The Aim of this study was to assess expression of Cyclooxygenase-2 in endometrioid carcinoma by immunohistochemistry to explore association between Cyclooxygenase-2 expression and a certain number of clinicopathologic variables. Methods: A retrospective study was carried out for seventy-eight blocks that were preseved in formalin and embedded in paraffin of endometrioid carcinoma were obtained and randomly selected from a private laboratory in Erbil city during October 2020 to October 2022. COX-2 rabbit monoclonal antibody was used to satin slides obtained from endometrioid carcinoma blocks and the expression was scored by multiplying the number of stained cells by the intensity of staining. Results: Cyclooxygenase-2 expressed in 15.4% of cases of study cases. It is down-expressed in high grade endometrioid carcinoma while over-expressed in cases with myometrial invasion ?50%. Regarding other clinicopathological parameters like, lymphovascular invasion, tumor stage and lymphnode status, Cyclooxygenase-2 showing down-expression, there is no existence of notable link between the expression of Cyclooxygenase-2 and clinicopathological parameters, including: Age(p=0.197), Tumor grade(p=0.069), Myometrial invasion(p=0.261), Lympho vascular invasion(p=0.516), Lymph node status(p=1000) and Tumor stage(p=0.872). Conclusion: Cyclooxygenase-2 is expressed in a limited number of endometrioid carcinoma and there is lack of significant association between Cyclooxygenase-2 expression and clinicopathological parameters

Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach.

The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from 10 cases each of GBC and inflammatory lesions, with technical duplicates.Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan-Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real time-polymerase chain reaction (RT-PCR). Out of 5,714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables.Prognostic factors such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival. Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.

Hyperprogressive disease in patients with advanced cancer treated with immune checkpoint inhibitors.

Hyperprogressive disease (HPD) is a new phenomenon developing in the era of immune checkpoint inhibitor (ICI) therapy. HPD is characterized by an unexpected and fast progression in tumor volume and poor survival. There is no standardized definition for HPD and clinicopathological variables associated with HPD are unclear. Herein, we assessed incidence, treatment outcomes and factors predictive of HPD in patients treated with ICIs. We retrospectively analyzed patients with advanced cancer treated with ICI at one academic center between 2014 and 2021. We used the Lo Russo's adopted criteria combined with clinical and radiologic parameters for the definition of HPD. All patients who underwent their first tumor evaluation according to RECIST1.1 were included. Of 155 patients, 147 were eligible for analysis. The median age was 61 and 83% were male. The cancer types were; lung 67.3%, bladder 12.9%, gastric 9.5%, 5, colon 5.4% and renal cell carcinoma 4.8%. 59.9% of patients were treatment-naive and others had one or more lines of chemotherapy. 19 (12.9%) patients had HPD. In patients who had HPD, progression-free survival (PFS) was significantly shorter (1.5 vs 9.8months, (HR 9.56; 95% CI (5.51-16.57), p < 0.001). The median overall survival (OS) was also shorter for HPD patients than non-HPD (3.0 vs 23.1months, respectively, HR 12.03, 95% CI (6.64-21.81), p < 0.001). Gastric cancer, larger sum of target lesion diameters at baseline, liver metastases, higher LDH level and higher neutrophil-lymphocyte ratio (NLR) were significantly associated with HPD. Our findings demonstrated that HPD was a rapid phenomenon with significantly poor survival rates. Several clinicopathological factors and tumor characteristics might indicate HPD.

The prevalence and risk factors associated with zinc deficiency after pancreatic surgery.

To clarify the prevalence, risk factors, and clinical implications associated with zinc deficiency in patients undergoing pancreatic surgery. The serum zinc levels were measured in 329 patients post-pancreatic surgery between January and April 2021. The postoperative serum zinc levels and clinicopathological variables were retrospectively analyzed. The median serum zinc level was 73µg/dL (33-218). Zinc deficiency (zinc level < 60µg/dL) was observed in 52 patients (16%). A total of 329 patients were classified into zinc-deficient (n = 52) and non-deficient (zinc ≥ 60µg/dL, n = 277) groups. A univariate analysis revealed significant differences in sex, postoperative body mass index, serum albumin, total cholesterol, creatinine, aspartate aminotransferase (AST), HbA1c levels, diabetes, surgical procedures, and operative blood loss. According to a multivariate analysis, male sex [odds ratio (OR) 3.70; 95% confidence interval (CI) 1.67-8.20; p = 0.001], postoperative serum albumin levels < 3.9g/dL (OR 6.39; 95% CI 3.30-12.37; p < 0.001), postoperative serum AST ≥ 51 U/L (OR, 4.6; 95% CI 0.07-0.29; p < 0.001), and total pancreatectomy (OR 3.68; 95% CI 1.37-9.85; p = 0.009) were found to be independent predictors of zinc deficiency after pancreatic surgery. Zinc deficiency frequently occurs in patients undergoing pancreatic surgery. Lower postoperative zinc levels could be linked to sex, the serum albumin and AST levels, and surgery type.