Significant Predictors Of Poor Survival Research Articles

Abstract 1756: Characterizing the mutational spectrum of metastatic mucinous adenocarcinoma of the appendix

Abstract Background: Appendiceal cancer (AC) is an orphan malignancy with only 1-2 cases per 100,000 people in the US. The genomic composition of metastatic, mucinous AC is yet to be resolved at the whole exome level and few groups have assessed the clinical actionability of target genes. Here we performed whole-exome sequencing (WES) on AC specimens to 1) elucidate the mutational spectrum of AC, 2) identify recurrent mutations at frequencies unique to AC or in common with colorectal cancer (CRC), and 3) uncover recurrent AC mutations that are associated with patient survival outcomes. Methodology: Twenty-four FFPE samples, one from each of 24 AC patients treated at our institution with cytoreductive surgery (CRS) followed by heated intraperitoneal chemotherapy (HIPEC), were collected from our tumor bank with IRB approval. DNA from tumor and corresponding normal tissue (PBMCs) was extracted, assessed for integrity and quantity, then analyzed by WES using the Illumina NextSeq 6000 platform. The resulting data were processed using both GATK and DRAGEN pipelines. The frequencies of recurrent mutations in AC were compared with those of CRC from cBioPortal and statistically compared by Fisher’s Exact Test. Logrank test was performed to estimate survival associations based off mutation status. Mutational signatures derived from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were cross-compared to our cohort to identify previously unknown mutational processes in AC. Results: The most frequent mutations were found in MUC6 (63%), KRAS (58%), HLA-B (54%), PABPC1 (50%), and MUC5AC (50%). Distinct from a 534-patient CRC cohort, AC had lower rates of alteration in APC (4% vs 73% CRC, p<0.001) and TP53 (21% vs. 62%, p<0.001), with higher rates of alteration in HLA-B (54% vs 3%, p<0.001), GNAS (38% vs 5%, p<0.001), and ABCA1 (29% vs 7%, p=0.001). Notably, ABCA1 mutation frequency was higher in mucinous CRC (n=56) when compared to non-mucinous CRC (n=478, 20% vs 7%; p<0.001), suggesting that ABCA1 may be uniquely altered in bowel cancers of mucinous phenotype. Alterations in Rho-A were a statistically significant predictor of poor survival in both AC (p<0.001) and CRC (p=0.05). PCAWG analysis showed that the predominant mutational signature in AC most resembles SBS5, suggesting that the mutational etiology of AC may be linked to age and/or smoking status. Discussion: Here we present the largest whole-exome sequencing analysis of AC analyzed to date and identify previously undescribed recurrently mutated genes unique to AC as compared to CRC. We demonstrate novel associations between altered genes and patient survival, which opens discussion regarding the clinical utility of molecular markers in AC for assisting treatment decision making. Citation Format: Daniel J. Gironda, Ming Leung, Guangxu Jin, Liang Liu, Konstantinos I. Votanopoulos, Edward A. Levine, Lance D. Miller. Characterizing the mutational spectrum of metastatic mucinous adenocarcinoma of the appendix [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1756.

Identification of CDT1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches.

Lung cancer has the highest cancer-related mortality worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC). Chromatin licensing and DNA replication factor 1 (CDT1), a key regulator of cell cycle control and replication in eukaryotic cells, has been implicated in various cancer-related processes. Given its significant role in cancer, the focus on CDT1 in this study is justified as it holds promise as a potential biomarker or therapeutic target for cancer treatment. However, its prognostic value in lung adenocarcinoma (LUAD) remains unclear. Bioinformatics analysis was conducted using data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to predict biological processes and signaling pathways, respectively. The LinkedOmics database was employed to identify differentially expressed genes (DEGs) associated with CDT1. Nomograms and Kaplan-Meier plots were generated to assess the survival rates of patients with lung adenocarcinoma (LUAD). To determine the RNA and protein expression levels of CDT1 in LUAD and adjacent normal tissues, quantitative polymerase chain reaction (qPCR) and immunohistochemistry techniques were employed, respectively. CDT1 was upregulated in the vast majority of cancer tissues, based on pan-cancer analysis in TCGA and GEO datasets, as to lung cancer, the level of CDT1 expression was much higher in LUAD tissue than in healthy lung tissue. Our clinical data supported these findings. In our study, we used a specific cutoff value to dichotomize the patient samples into high and low CDT1 expression groups. The Kaplan-Meier survival curve revealed poor survival rates in CDT1 high expression group than the low expression group. To determine if CDT1 expression was an independent risk factor in LUAD patients, univariate and multivariate Cox regression analyses were performed. The result showed that CDT1 was a potential novel prognosis factor for LUAD patients, whose prognosis was poorer when CDT1 expression was higher. Based on functional enrichment analysis, highly expressed DEGs of CDT1-high patients were predicted to be involved in the cell cycle. According to our analysis of immune infiltration, CDT1 exhibited a strong correlation with specific immune cell subsets and was found to be a significant predictor of poor survival in patients with LUAD. Our research found that CDT1 was upregulated in LUAD and that high CDT1 expression predicted poor prognosis. We comprehensively and systematically analyzed the expression level in the datasets as well as in our own clinical samples, we also evaluated the prognostic and diagnostic value of CDT1, and finally, the potential mechanisms of CDT1 in the progression of LUAD. These results suggested that CDT1 may be a prognostic marker and therapeutic target for LUAD.

The Prognostic Utility of the Metastatic Lymph Node Ratio and the Number of Regional Lymph Nodes Removed from Patients with Small Bowel Adenocarcinomas.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is characterized by diagnosis at an advanced stage, low rate of operability and poor survival. Therefore, there is a need for a biomarker in NSCLC patients to predict the likely outcome and to accurately stratify the patients in terms of the most appropriate treatment modality. To evaluate prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in NSCLC. A total of 124 NSCLC patients (mean ± standard deviation age: 60.7 ± 9.3 years, 94.4% were males) were included in this retrospective study. Data were retrieved from the hospital records. The association of NLR and PLR with clinicopathological factors and overall survival was analyzed. One-year, 2-year and 5-year survival rates were 59.2%, 32.0%, and 16.2%, respectively. Median duration of survival was shorter in patient groups with elevated NLR and PLR. Five-year survival rate was quite lower in patient groups with elevated NLR and PLR. Hazard rate (HR) for mortality was 1.76 (95% confidence interval [CI]: 1.19-2.61, P = .005) for NLR ≥ 3 over NLR < 3. HR was 1.64 (95%CI: 1.11-2.42, P = .013) for PLR ≥ 150 over PLR < 150. Cox-regression analysis revealed that, when adjusted for other independent predictors of survival, NLR and PLR still remain significant predictors of poorer survival. Our findings indicate that elevated pretreatment NLR and PLR are associated with advanced disease and poor survival in NSCLC patients, NLR and PLR values are correlated with each other.

Retrospective study of combined pelvic organ resection in the treatment of primary and recurrent pelvic malignant tumors.

e15635 Background: For locally advanced or recurrent pelvic malignancies, combined pelvic organ resection has been used to treat rectal, bladder, gynecological and other related malignancies. As an interdisciplinary and high-risk operation, the perioperative safety and future information are often very limited. We retrospectively analyzed the efficacy of PE surgery in our institution. Methods: In this retrospective study, 59 patients with pelvic malignant tumors received PE surgery from July 2015 to July 2021. They were divided into two groups according to the location of the disease: rectal tumor group (n = 40) and cervical cancer group (n = 19). The baseline data, gene detection reports, pathological reports, perioperative conditions and prognosis were analyzed. The two groups were compared by independent sample t-test; Comparison between groups χ2 test, the survival curve was drawn by Kaplan-Meier method and compared by log rank test. Results: Among these 59 patients treated with PE, the rectal tumor group and the cervical cancer group did not differ significantly in terms of demographics, operative time, hospital stay, intraoperative blood loss, and rates of use of preoperative and intraoperative radiotherapy. Compared with the two groups, the overall incidence of postoperative complications was 37% in the group with rectal tumours and 26% in the group with perineal wound infection being the most common, cervical cancer 46% and urinary tract infection being the most common. Comparing the postoperative survival OS between patients in the rectal tumor group and those in the cervical cancer group, the former was better, with 5-year overall survival rates of 37% in the rectal tumor group and 28% in the cervical cancer group. Within the group of rectal tumours, however, there are differences in survival between patients with primary (LARC) and recurrent (lrrc) rectal tumours; Patients with LARC have shown a significant survival benefit postoperatively, with 5-year overall survival rates of 40% for patients with LARC and 27% for patients with lrrc. OS was significantly better in patients with well differentiated tumors, N0 stage, and high microsatellite instability (MSI). On the basis of univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI, and no chemotherapy received perioperatively were significant predictors of poor survival (P &lt; 0.05). Conclusions: PE is currently an effective treatment for pelvic malignancies with aggressive radical resection of lesions, which can effectively improve their cure rate, improve quality of life, and careful patient selection can optimize outcomes.

Combination of Sarcopenia and Hypoalbuminemia Is a Poor Prognostic Factor in Surgically Treated Nonmetastatic Renal Cell Carcinoma.

The purpose of this study is to observe how preoperative sarcopenia and hypoalbuminemia affect the oncological outcome of nonmetastatic renal cell carcinoma (RCC) after partial or radical nephrectomy. This study retrospectively analyzes 288 Japanese patients with nonmetastatic RCC who underwent radical treatment at Kanazawa University Hospital between October 2007 and December 2018. Relationships between sarcopenia as indicated by the psoas muscle mass index and hypoalbuminemia (albumin ≤ 3.5 g/dL) with overall survival (OS) and metastasis-free survival (MFS) were determined. The study found that 110 (38.2%) of the 288 patients were sarcopenic and 29 (10.1%) had hypoalbuminemia. The combination of sarcopenia and hypoalbuminemia was associated with a shorter OS and MFS (p for trend = 0.0007 and <0.0001, respectively), according to Kaplan-Meier curves. The concurrent presence of sarcopenia and hypoalbuminemia were found to be significant and independent predictors of poor MFS (hazard ratio (HR), 2.96; 95% confidence interval (95% CI), 1.05-8.39; p = 0.041) and poor OS (HR, 6.87; 95% CI, 1.75-26.94; p = 0.006), respectively. In Japanese patients with surgically treated nonmetastatic RCC, combined preoperative sarcopenia and hypoalbuminemia was a significant predictor of poor survival.

ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer.

There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients' clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. 193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

Identification of Prominent Genes between 3D Glioblastoma Models and Clinical Samples via GEO/TCGA/CGGA Data Analysis.

A paradigm shift in preclinical evaluations of new anticancer GBM drugs should occur in favour of 3D cultures. This study leveraged the vast genomic data banks to investigate the suitability of 3D cultures as cell-based models for GBM. We hypothesised that correlating genes that are highly upregulated in 3D GBM models will have an impact in GBM patients, which will support 3D cultures as more reliable preclinical models for GBM. Using clinical samples of brain tissue from healthy individuals and GBM patients from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases, several genes related to pathways such as epithelial-to-mesenchymal transition (EMT)-related genes (CD44, TWIST1, SNAI1, CDH2, FN1, VIM), angiogenesis/migration-related genes (MMP1, MMP2, MMP9, VEGFA), hypoxia-related genes (HIF1A, PLAT), stemness-related genes (SOX2, PROM1, NES, FOS), and genes involved in the Wnt signalling pathway (DKK1, FZD7) were found to be upregulated in brain samples from GBM patients, and the expression of these genes were also enhanced in 3D GBM cells. Additionally, EMT-related genes were upregulated in GBM archetypes (wild-type IDH1R132 ) that historically have poorer treatment responses, with said genes being significant predictors of poorer survival in the TCGA cohort. These findings reinforced the hypothesis that 3D GBM cultures can be used as reliable models to study increased epithelial-to-mesenchymal transitions in clinical GBM samples.

Historical redlining and breast cancer treatment and survival among older women in the United States.

Breast cancer (BC) is the most common cancer among US women, and institutional racism is a critical cause of health disparities. We investigated impacts of historical redlining on BC treatment receipt and survival in the United States. Home Owners' Loan Corporation (HOLC) boundaries were used to measure historical redlining. Eligible women in the 2010-2017 Surveillance, Epidemiology, and End Results-Medicare BC cohort were assigned a HOLC grade. The independent variable was a dichotomized HOLC grade: A and B (nonredlined) and C and D (redlined). Outcomes of receipt of various cancer treatments, all-cause mortality (ACM), and BC-specific mortality (BCSM) were analyzed using logistic or Cox models. Indirect effects by comorbidity were examined. Among 18 119 women, 65.7% resided in historically redlined areas (HRAs), and 32.6% were deceased at a median follow-up of 58 months. A larger proportion of deceased women resided in HRAs (34.5% vs 30.0%). Of all deceased women, 41.6% died of BC; a larger proportion resided in HRAs (43.4% vs 37.8%). Historical redlining is a statistically significant predictor of poorer survival after BC diagnosis (hazard ratio = 1.09, 95% confidence interval [CI] = 1.03 to 1.15 for ACM, and hazard ratio = 1.26, 95% CI = 1.13 to 1.41 for BCSM). Indirect effects via comorbidity were identified. Historical redlining was associated with a lower likelihood of receiving surgery (odds ratio = 0.74, 95% CI = 0.66 to 0.83, and a higher likelihood of receiving palliative care odds ratio = 1.41, 95% CI = 1.04 to 1.91). Historical redlining is associated with differential treatment receipt and poorer survival for ACM and BCSM. Relevant stakeholders should consider historical contexts when designing and implementing equity-focused interventions to reduce BC disparities. Clinicians should advocate for healthier neighborhoods while providing care.

Circulating Glypican-4 Is a Predictor of 24-Month Overall Survival in Metastatic Breast Cancer

Introduction: Endocrine treatment combined with CDK4/6 inhibitors is the preferred treatment strategy in patients presenting with ER-positive/HER2-negative breast cancer, but the clinical course remains highly variable among individual patients. There is an unmet need for prognostic or predictive biomarkers in this important group of patients. Recently, we have identified circulating glypican-4 (GPC4) as a new biomarker of inferior outcomes in patients with metastatic colorectal cancer. The impact of plasma GPC4 levels on the survival of breast cancer patients is unknown and has been addressed in the present study. Methods: Our study included 47 patients with ER-positive/HER2-negative metastatic breast cancer prior to treatment with CDK4/6 inhibitors combined with endocrine therapy. The endpoint was overall survival (OS) at 24 months. GPC4 levels were measured in plasma using an enzyme-linked immunosorbent assay. Results: Increased circulating GPC4 levels were significantly linked to advanced age, postmenopausal state, visceral metastases, and invasive lobular carcinoma. During the 2-year observational follow-up period, 25.5% of patients died. The area under the receiver operating characteristic curve (ROC-AUC) analysis revealed an AUC of 0.713 [0.555–0.871]; p = 0.029 for OS; and an optimal cutoff value of GPC4 for predicting OS of 4.77 ng/mL. No patient showing GPC4 values below this cutoff died during the observational period. Cox regression analysis showed a hazard ratio of 2.14 [95% confidence interval: 1.24–3.67]; p = 0.006 for one standard deviation change of plasma GPC4. Conclusions: Our study suggests circulating GPC4 as a significant predictor of poor survival in metastatic breast cancer patients.

Survival and characteristics of older adults receiving home-based medical care: A nationwide analysis in Taiwan.

In Taiwan, the National Health Insurance Administration initiated the integrated home-based medical care (iHBMC) program in 2016 to improve accessibility to health care for homebound patients. This study aimed to describe the characteristics of older people receiving iHBMC services in Taiwan as well as the relationship between patient characteristics and survival. All older adults registered in the iHBMC application dataset were enrolled between March 1, 2016, and December 31, 2018. Data on social determinants of health (income level, residential area), functional status, consciousness status, nasogastric tube or urinary catheter placement, and major diseases were retrieved from the database. Data on the frequency of multidisciplinary team members' visits were collected. The survival rate was investigated using the Kaplan-Meier method. A Cox proportional hazards univariate regression was conducted to analyze factors influencing survival rates. A total of 41,079 patients aged ≥65 years were enrolled in iHBMC services. The results showed that the one-year survival rates were 72.1%, 67.4%, and 14.7% in the home-based primary care (HBPC), home-based primary care plus (HBPC-Plus), and home-based palliative care (HBPalC), respectively. Nearly two-thirds of the HBPC-Plus patients underwent nasogastric tube placement. The Cox proportional hazards univariate regression analysis showed that a low urbanization level, a low income level, a low functional status, and an impaired consciousness status were significant predictors of poor survival after adjustment for confounding variables. Older adults receiving iHBMC services had a high mortality rate. The high rate of feeding tube use indicated that education and support for both clinical practitioners and family caregivers regarding careful hand feeding are warranted. There was a relationship between low income levels and poor survival in rural areas. Further research on whether social care could impact prognosis should be considered.

Clinicopathologic Review of Metastatic Breast Cancer to the Gynecologic Tract.

Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis.

Handgrip strength: A simple and effective tool to predict mortality after liver transplantation.

Malnutrition is a widely prevalent yet unrecognized problem of patients with end-stage liver disease (ESLD) awaiting liver transplant (LT). The aim of this study was to ascertain pre-LT nutritional status of adult Asian Indian patients with ESLD including functional deficit (frailty) and determine predictor/s of poor post-LT outcome (futility). A prospective, longitudinal, single-center study which enrolled adults listed for LT between October 2014 and April 2018. Consecutive patients who consented, met the inclusion criteria, and underwent LT were included. The demographic data, nutritional, functional and dietary assessments from evaluation till 1-year-post-LT were documented. Data was analyzed using SPSS-25.0. One hundred and fifty two patients, aged 50.6±8.3 years, predominantly men (82.9%), underwent LT (predominantly deceased donor LT (DDLT) 78.3%). One hundred and thirty five patients (88.8%) were discharged alive after LT. The presence of pre-LT hepatorenal syndrome (HRS), baseline handgrip strength (HGS) <20kg and SGA rated malnutrition, 1st-pre-LT follow-up HGS (<20kg), non-achievers of ≥80% targeted energy and protein intake were associated with increasing 1-year-post-LT mortality rate (p<0.05). A cut-off of 18.15kg HGS was found to predict 1-year-post-LT survival, with optimal sensitivity (77.4); specificity (43.5), and an area under a receiver operating curve (ROC) of 0.676 (p=0.008), with a 95% CI [0.545-0.806]. Step-wise binary logistic regression indicated that non-achievers of ≥80% targeted protein at 1st-pre-LT follow-up and baseline HGS (<18.15kg) are two independent factors that predict 1-year-post-LT survival with an odds ratio of 13.168 and 7.041, respectively. A cut-off of 18.15kg baseline HGS before LT was found to be a significant predictor of poor survival in Asian Indian patients with ESLD. It was also instrumental in identifying patients at risk and helping to target intensive nutritional intervention therapy. Patients in whom ≥80% pre-LT nutritional goal was successfully achieved during the waiting period had an improved 1-year-post-LT survival.

HL-048 Clinicopathological, Immunohistochemical Characteristics, and Outcomes of Hodgkin Lymphoma Patients in Erbil City, Iraq

Hodgkin lymphoma (HL) has unique epidemiological features with diverse pathologies and exhibits considerable clinicopathological variations in different parts of the world. In this study, we aimed to assess the clinicopathological features, immunohistochemistry, and outcomes of HL patients treated in Erbil, northern Iraq. This was a retrospective study conducted in Nanakaly Hospital for Blood Diseases and Oncology in Erbil, Iraq. A total of 125 patients diagnosed between January 2012 and December 2016 were assessed for their clinical characteristics, histopathology, immunophenotype, and outcome. The median age was 28 years (range: 18-71 years); 55% were male and 41% had Stage II HL. The most common histological type was nodular sclerosis (51.2%) followed by mixed cellularity (43.2%). CD30 was positive in nearly all cases of classical HL. CD15 and CD20 were positive in 98.7% and 75% of patients with the nodular lymphocyte predominant subtype, respectively. Most of the patients received adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and the 5-year overall survival in our study is 70%. Advanced stage (IV), high lactate dehydrogenase levels, low hemoglobin, and splenomegaly are significant predictors of poor survival. Our patients exhibited outcomes that were lower than those reported in developed countries.

Important CT Findings for Prediction of Incomplete (R1 or R2) Resection and Poor Survival of Perihilar Cholangiocarcinoma after Curative-Intent Surgery

Purpose: To evaluate CT findings to predict incomplete (R1 or R2) resection and poor survival in patients with perihilar cholangiocarcinoma using pre-operative CT.Materials and Methods: From 2006 to 2012, a total of 139 patients with perihilar cholangiocarcinoma who underwent pre-operative multiphase CT and subsequent curative-intent surgery were included. After two radiologists independently reviewed CT findings including the likelihood of bile duct (BD) involvement from intrapancreatic common bile duct (CBD) to bilateral second-order branches and peritumoral fat stranding using a 5-point scale, vessel involvement (no, abutment, encasement), and LN involvement, imaging findings were finalized by a consensus of two radiologists. When the likelihood scale of 4 or more on preoperative CT was regarded as BD involvement, the diagnostic ability of CT was analyzed by the receiver operating curve using histopathologic results as a reference standard. Residual tumor categorized into no residual tumor (R0) and residual tumor (R+; R1 or R2). Predictive factors of R+ resection on pre-operative CT were analyzed by logistic regression. Cox proportional hazard model was used to determine the prognostic factor for overall survival by using pre-operative CT findings and laboratory results.Results: Seventy-one patients were R0 and sixty-eight patients were R+ resection. For resectability evaluation, mid-CBD involvement (score ≥ 4) in pre-operative CT was significant factor for R+ resection in multivariable analysis (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) with substantial interobserver agreement. In multivariable Cox regression, intrapancreatic CBD involvement (score ≥ 4, hazard ratio [HR] = 1.81, &lt;i&gt;P&lt;/i&gt; &lt; 0.01) as well as elevated total bilirubin (HR = 1.53, &lt;i&gt;P&lt;/i&gt; = 0.04) and CA 19-9 level (HR = 1.75, &lt;i&gt;P&lt;/i&gt; &lt; 0.01) were significant predictors for poor survival. Diagnostic ability to predict mid-CBD and intrapancreatic CBD involvement on pre-operative CT were 0.71 and 0.72 (AUC values).Conclusions: Distal longitudinal extent of perihilar cancer on pre-operative CT is a significant factor for margin positive resection and poor survival on curative-intent surgery.

Metabolic Biomarkers Assessed with PET/CT Predict Sex-Specific Longitudinal Outcomes in Patients with Diffuse Large B-Cell Lymphoma.

Simple SummaryThere is a sex disparity in lymphoma where males have higher incidence and mortality compared to females. Sex differences in metabolism may be a significant factor underlying this phenomenon where visceral obesity, a known biomarker for poor outcomes in multiple pathophysiological states, is higher in males compared to females. Here, we report that visceral fat, although higher in males with diffuse large B-cell lymphoma (DLBCL), selectively predicted worse outcomes in females. Moreover, females that selectively gained visceral fat during chemotherapy did worse, and combining the change in visceral fat over the course of chemotherapy and tumor glucose uptake measured by FDG-PET at end of treatment identified a subgroup of females with extremely poor outcomes.In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion.

Overall and cancer specific survival following radical or adjuvant (chemo)radiotherapy in a retrospective cohort of elderly patients with endometrial cancer

To report the overall survival and cancer specific survival outcomes of elderly women aged ≥70 years who received radical or adjuvant (chemo)radiotherapy for endometrial cancer, we conducted a retrospective review of 93 patients from the West of Scotland Cancer Network (WoSCAN) who received pelvic (+/− para-aortic) radiotherapy over a 5-year period (January 2011 to December 2015, inclusive). Association of treatment type and other variables with overall survival (OS) and cancer specific survival (CSS) were analysed using log rank tests and Cox proportional hazards models. Median age of the study population was 74 years (range 70–90 years); over 50% of patients were aged ≥75 years, and over 25% were ≥80 years. The majority of patients had endometrioid endometrial cancer (75.3%), and 24.7% had a high-risk histological subtype. Stage distribution was as follows: I/II (40.9%); III/IV (41.9%); recurrent disease (17.2%). Radiotherapy was predominantly delivered in the adjuvant setting (61.3%); intent was primary (22.6%) or salvage (16.1%) in the remaining patients. Chemotherapy was administered to almost 50% of the cohort, mainly in conjunction with adjuvant radiotherapy. After median follow up of 96 months, 5-year OS and CSS were 50.5%and CSS 59.3% for the entire series, 57.9% and 62.8% in the adjuvant group, 23.8% and 35.7% in the primary group, and 60.0% and 80.0% in the salvage group, respectively. Age ≥80 years and primary radiotherapy were statistically significant predictors of poorer survival, adjusting for pathology, stage and grade (hazard ratio (HR) 2.06, 95%Confidence Interval (CI) (1.11–3.80), p = 0.021; and HR 2.42 (CI 1.28–4.57), p = 0.006 respectively). In summary, poorer OS was associated with use of (chemo)radiotherapy as primary treatment of endometrial cancer and/or in women aged ≥80 years, suggesting that careful risk/benefit analysis is required in these two groups.

Serum Lactate Dehydrogenase is a Predictive Biomarker in Oropharyngeal Cancer Patients Undergoing Radiotherapy

<h3>Purpose/Objective(s)</h3> The present study aimed to evaluate prognostic factors, particularly with respect to their role in establishing distinct prognostic subsets of human papillomavirus (HPV)-positive and -negative oropharyngeal cancer (OPC). <h3>Materials/Methods</h3> This study retrospectively evaluated 101 patients with OPC who underwent radiotherapy (RT) alone or chemoradiotherapy (CRT) at our institution between August 2008 and December 2018. Whole neck RT (44.0-50.0 Gy/22-25 fractions) was delivered by intensity-modulated RT (IMRT), followed by boost IMRT to high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Seventy patients (69.3%) received concurrent chemotherapy. Clinical factors which were potentially associated with prognosis were analyzed. Receiver-operating characteristic curve analysis was adopted to determine the most appropriate cut-off points of hematological biomarkers including the serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/ albumin ratio (CRP/Alb). <h3>Results</h3> The median follow-up period of the surviving patients was 68 (range; 8-164) months. The 5-year overall survival rate were 69.8%. Univariate analyses revealed that poor survival was associated with gender of male, smoking≥30 pack years, Eastern Cooperative Oncology Group performance status≥1, tumor-node-metastasis (TNM) stage of III-IV (8th edition), HPV-negative, LDH≥202, CRP/Alb≥0.15, LMR < 2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack years (<i>P</i> < 0.01), LDH ≥202 (<i>P</i> = 0.02). Patients were divided into two groups according to HPV status as HPV-positive and negative OPC and potential prognostic factors were assessed in univariate analyses. In HPV-positive OPC patients, poor survival was significantly associated with smoking ≥30 pack years (<i>P</i> = 0.03), LDH ≥202 (<i>P</i> = 0.04), and LMR < 2.90 (<i>P</i> < 0.01). In HPV-negative OPC patients, gender of male (<i>P</i> < 0.01), smoking ≥30 pack years (<i>P</i> < 0.01), LDH ≥202 (<i>P</i> < 0.01), and CRP/Alb ≥0.15 (<i>P</i> = 0.01) were significant predictors of poor survival. <h3>Conclusion</h3> The present study revealed that high LDH levels predicted poor survival after definitive radiotherapy in both HPV-positive and HPV-negative OPC patients. High LDH levels were stronger poor prognostic factor than HPV status and TNM stage in this study.

Long-Term Outcomes of Cervical Cancer Patients With Complete Metabolic Response After Definitive Chemoradiotherapy

The utility of metabolic positron-emission tomography (PET) parameters in patients with cervical cancer who had complete metabolic response (CMR) after chemoradiotherapy (ChRT) is unclear. We investigated the importance of metabolic parameters measured with 18F-FDG-PET/CT for predicting progression-free survival (PFS) and overall survival (OS).The clinical data of 152 patients with biopsy-proven cervical cancer treated with definitive ChRT at our institution between November 2006 and August 2012 were retrospectively evaluated. The clinical data and PET parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 122 patients having CMR in post-treatment 18F-FDG-PET/CT delivered a median of 3.9 months after ChRT completion were analyzed. The PET parameters were measured for primary tumors (p) and metastatic lymph nodes (ln) separately.With a median follow-up of 8.4 years, 55 patients (45%) presented with disease a median of 19.7 months after ChRT. The cut-off values determined with receiver operating curve analysis for survival were 15.8, 48.7 cm³, 552.3, 8.7, 7.0 cm³, and 24.6 and for disease recurrence were 19.9, 49.8 cm³, 597.4, 9.1, 7.3 cm³, and 25.2 for SUVp, MTVp, TLGp, SUVln, MTVln, and TLGln, respectively. All metabolic PET parameters were significant prognostic factors for OS and PFS in univariate analysis. FIGO stage was predictive of both OS and PFS, while pelvic and/or para-aortic lymph node metastasis were predictive of OS only. In multivariate analysis, FIGO stage ≥IIB [HR = 2.53 (95% CI, 1.02-7.34), P = 0.04], MTVp ≥49.8 cm³ [HR = 4.13 (95% CI, 2.51-6.78), P < 0.001] and TLGp ≥597.4 [HR = 2.21 (95% CI, 1.06-4.61), P = 0.03] were predictive of worse OS. Advanced stage [HR = 4.11 (95% CI, 0.98-7.22) P = 0.05], presence of lymph node metastasis [HR = 1.48 (1.09-2.39), P = 0.04], higher TLGp [HR = 2.31 (95% CI, 1.14-4.68), P = 0.02] and larger MTVln [HR = 2.24 (1.05-4.74), P = 0.04] were significant factors for poor PFS rates.Advanced stage and higher TLGp values were significant predictors for poor survival and higher progression rates. Additional prognostic factors for worse OS were larger MTVp and lymph node metastasis and for disease progression, MTVln. We also found that most disease recurrences presented as distant metastasis, which suggests a need for effective systemic treatment.C. Onal: None. O. Guler: None. M. Reyhan: None. A. Yapar: None.

Prognostic Implication of Diagnostic Confidence Level in Patients with Fibrotic Hypersensitivity Pneumonitis

Background: Hypersensitivity pneumonitis (HP) has various clinical courses and outcomes, but the prognostic factors are not well-defined. Vasakova et al. [Am J Respir Crit Care Med. 2017 Sep;196(6):680–9] have proposed a diagnostic algorithm that categorized suspected patients according to the level of confidence in the diagnosis. This study aimed to investigate whether the confidence level of clinical diagnosis has prognostic implication in patients with fibrotic HP. Methods: This study included 101 biopsy-proven fibrotic HP patients diagnosed between 2002 and 2017. The patients were retrospectively classified into confident, probable, possible, and unlikely chronic HP, according to the confidence level in the diagnostic criteria/algorithm. The survival and forced vital capacity (FVC) changes were compared between the groups. Risk factors for mortality were analysed using a Cox proportional hazard model. Results: The median follow-up duration was 67.6 months. The mean age was 60.4 years, and percentages of women were 60.4%. When classified based on the diagnostic criteria/algorithm, possible HP was the most common (51.5%), followed by probable (26.7%), confident (9.9%), and unlikely HP (6.9%). Distinctive survival curves were found according to the diagnostic confidence level, showing the worst outcome in unlikely chronic HP (median survival, 30.2 months). In a multivariable Cox analysis, unlikely HP was a significant predictor of poor survival (hazard ratio, 4.652; 95% confidence interval, 1.231–17.586; p = 0.023), after adjustment for age, body mass index, FVC, and diffusing capacity. Conclusions: The diagnostic confidence level may predict clinical outcomes in patients with HP. Unlikely HP was shown to have a significantly poorer survival than other diagnostic confidence levels.