Independent Prognostic Marker In Patients Research Articles

Bone mineral density as a prognostic marker in patients with biliary tract cancer undergoing surgery

BackgroundBiliary tract cancer (BTC) is one of the most aggressive malignancies and surgery represents the only curative treatment approach. However, even in patients with complete tumor resection 5-year survival rates are below 30%. So far, prognostic markers to assess the outcome of these patients are lacking. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients receiving surgery for BTC.methods76 BTC patients undergoing tumor resection in our clinic (Duesseldorf cohort) as well as an external validation cohort of 34 BTC patients (Cologne cohort) were included. BMD was analyzed at the first lumbar vertebra, using routine CT scans which has been proven comparable to DXA.ResultsMedian overall survival (OS) of the Duesseldorf cohort after surgery was 527 days, one- and five-year survival probabilities were 62 and 18%. Patients with BMD above 156.5 HU had significantly improved OS (1435 days vs. 459 days; p = 0.002). The prognostic value for BMD was confirmed using Cox-regression analysis, as well as an external validation cohort. In subgroup analysis the prognostic effect of BMD was only present in female patients, suggesting sex specific differences.ConclusionBMD is a valuable, easily accessible and independent prognostic marker in patients receiving liver surgery for BTC.

Neutrophil-to-lymphocyte ratio at the end of treatment with CDK4/6 inhibitors is an independent prognostic factor for ER-positive HER2-negative advanced breast cancer.

The aim of this study was to elucidate the clinical significance of peripheral blood biomarkers, including absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR), at the end of treatment (EOT) with CDK4/6 inhibitors abemaciclib and palbociclib in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer. We included 67 patients treated with fulvestrant plus abemaciclib or palbociclib. Overall survival (OS) since the EOT with CDK/4/6 inhibitors was compared in relation to the levels of ALC and NLR. The cut-off values of ALC and NLR were set at 1000/μL and 3, respectively. Patients with a high ALC at EOT showed significantly longer OS than those with a low ALC (p = 0.0358). Moreover, patients with a low NLR at EOT showed significantly longer OS than those with a high NLR at EOT (p = 0.0044). Looking at the changes of ALC and NLR between baseline and the EOT, patients with a high ALC both at baseline and at the EOT showed significantly longer OS than others (p = 0.0201). Similarly, patients with a low NLR both at baseline and at the EOT showed significantly longer OS after EOT than others (p = 0.0136). Multivariable analysis revealed that the NLR at EOT (low vs. high) and changes in NLR (low at baseline to low at EOT vs. others) were significant and independent prognostic factors for OS after EOT (p = 0.0337, p = 0.0039, respectively). NLR at EOT with CDK4/6 inhibitors is a significant and independent prognostic marker for patients with ER-positive HER2-negative advanced breast cancer.

628. GUSTAVE ROUSSY IMMUNE SCORE IS A PROGNOSTIC MARKER IN PATIENTS WITH ESOPHAGEAL CANCER AFTER NEOADJUVANT THERAPY: A MULTICENTER RETROSPECTIVE STUDY

Abstract Background GRIm-Score (Gustave Roussy Immune Score), a novel nutritional and inflammatory-based prognostic score, is an unfavorable prognostic factor in patients with esophageal carcinoma (EC). However, the prognostic importance of GRIm-Scores after neoadjuvant chemo-radiotherapy in these patients remains unclear. Methods A retrospective study including 432 EC patients undergoing surgical resection was performed. The GRIm-Score was calculated by lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), and albumin (ALB). The over survival (OS) and disease-free survival (DFS) were analyzed for the current study with Cox regression analyses, Kaplan-Meier methods, and propensity score matching (PSM). Results There were 374 (86.6%) men and 58 (13.4%) women with a mean age of 62.1 ± 7.7 years (range: 39-80 years). After PSM, cohorts consisted of 55 patients in the high GRIm-Score group and 55 in the low GRIm-Score group. Patient with a high GRIm-Score had poor OS (Cohort: p = 0.001; PSM: p = 0.007) and DFS (Cohort: p = 0.001; PSM: p = 0.008). The GRIm-Score, instead of NLR, LDH, or ALB in multivariate analyses, was an independent prognostic factor for OS (p = 0.019) before PSM. However, after PSM, it was a powerful independent prognostic factor for both OS (p = 0.028) and DFS (p = 0.039). Subgroup analyses showed that GRIm-Score could identify cases with worse OS or DFS among pT3-4 patients, indicating the complementary role of GRIm-Score in the decision-making of adjuvant therapy. Conclusion The GRIm-Score was an independent prognostic marker in patients with EC undergoing surgical resection after neoadjuvant therapy. Our study is also the first to discuss the prognostic value of GRIm-Score in patients with EC after neoadjuvant treatment.

Frailty and Cardiovascular Health.

The incidence of frailty and cardiovascular disease (CVD) increases as the population ages. There is a bidirectional relationship between frailty and CVD, and both conditions share several risk factors and underlying biological mechanisms. Frailty has been established as an independent prognostic marker in patients with CVD. Moreover, its presence significantly influences both primary and secondary prevention strategies for adults with CVD while also posing a barrier to the inclusion of these patients in pivotal clinical trials and advanced cardiac interventions. This review discusses the current knowledge base on the relationship between frailty and CVD, how managing CVD risk factors can modify frailty, the influence of frailty on CVD management, and future directions for frailty detection and modification in patients with CVD.

Prognostic value of exercise longitudinal right ventricular free wall strain in patients with sickle cell disease.

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2years. The cohort consisted of 87 patients (mean age was 31 ± 11years, 66% females). All patients had normal resting TRV < 2.8m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stressTRV andSPAP, but lower resting and peak stressTAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stresscardiac output when compared to patients with peak stressRVFWS ≥ 20% (p < 0.05). Patients with baseline peak stressRVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7min at baseline vs. 5.5 ± 2.8min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stressRVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up.

The role of preoperative FPR and FAR in prognostic evaluation of stages II and III radical colorectal cancer: A single-center retrospective study.

The inflammatory and nutritional states of body are 2 important causes associated with the initiation and progression of colorectal cancer (CRC). The aim of this study is to investigate the prognostic evaluation value of preoperative fibrinogen-to-prealbumin ratio (FPR) and preoperative fibrinogen-to-albumin ratio (FAR) in CRC. The clinical data of 350 stages II and III patients with CRC who received radical resection were retrospectively analyzed. All patients were followed up for 5 years to observe the overall survival and disease-free survival of 5 years and analyze the relationship between preoperative FPR and FAR and prognosis of all enrolled patients. In addition, we analyzed the diagnostic and application value of combined biomarkers. This study showed high-level preoperative FPR and FAR were significantly associated with poor overall survival and disease-free survival of stages II and III patients with CRC. The elevated preoperative FPR and FAR level was significantly related to age, tumor differentiation level, TNM stage, vascular infiltration, carcinoembryonic antigen, carbohydrate antigen199, etc. The combination of FPR, FAR, neutrophil-to-lymphocyte ratio, and carbohydrate antigen199 had the maximum area under curve (AUC = 0.856, 95% CI: 0.814-0.897, Sen = 78.20%, Spe = 82.49%, P < .05) under the receiver-operating characteristics curve. The preoperative FPR and FAR have important prognostic value and they can be used as independent prognostic marker for patients with stages II and III CRC undergoing radical resection. Moreover, the combination of biomarkers could further enhance the diagnostic and prognostic efficacy of CRC.

Prognostic Utility of Left Atrial Strain From MRI Feature Tracking in Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome (p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

Abstract 3466: Prognostic implications of lymph node micrometastasis in patients with gastric cancer

Abstract Purpose: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of patients with LNMM GC.Methods: A total of 624 patients with pathologically lymph node metastasis negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Results: Patients with lymph node tumors of diameter &amp;lt; 1500 μm (LNMM) had significantly better prognosis than those with tumors of diameter ≥ 1500 μm (p = 0.012; log-rank test). Cox’s proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for overall survival of patients with pN1 GC. There was no significant difference in overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). Conclusions: LNMM is associated with favorable prognosis and could be an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered as one of the factors preventing adjuvant chemotherapy. Citation Format: Atsushi Yamamoto, Hirotaka Okamoto. Prognostic implications of lymph node micrometastasis in patients with gastric cancer [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 3466.

Abstract 3420: Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters

Abstract The androgen receptor (AR) serves as a pivotal transcription factor in prostate cancer (PCa) development. Its transcriptional activity is linked to the number of glutamines in the N-terminal domain. While current screening for PCa and prognostic biomarkers include serum prostate-specific antigen (PSA) levels and histopathological characteristics (specifically, ISUP grade and margin involvement), the heterogeneity of these tumors underscores the need for additional markers to enhance clinical management. Thus, this study aimed at characterizing an Argentinian PCa patient cohort based on the CAG polymorphism (CAG)n in AR and establish associations between genotypes and clinical-pathological characteristics to refine disease prognosis. We designed a hospital-based case-case study for PCa patients to determine the association between AR polymorphisms and PCa biochemical relapse after radical prostatectomy (RP). We retrospectively recruited 112 patients histologically diagnosed with PCa at the Hospital de Clínicas José de San Martín, Buenos Aires, Argentina. All patients underwent RP as their primary therapeutic strategy. All patients were, by definition, Hispanics, predominantly of Caucasian ancestry and, at a lesser extent, Amerindian or African. Written informed consent and institutional review board approval were acquired. Blood samples were collected post-RP for genomic DNA extraction using the CTAB method. (CAG)n in AR was genotyped by fluorescent PCR followed by capillary electrophoresis, and correlations between genotypes and clinical-pathological variables were analyzed using R. Results categorized patients into three subgroups based on the length of the CAG tandem repeat in AR: long (&amp;gt;23 repeats, n=29), medium (20-23 repeats, n=44), and short (&amp;lt;20 repeats, n=38). No associations were found between the length of the polymorphism and age of diagnosis, pre-RP PSA serum values, ISUP grade, and margin involvement. However, patients with family cancer history had a higher frequency of the intermediate-length allele (p=0.02). Moreover, among patients with pre-RP PSA &amp;lt;10 ng/ml and intermediate-length allele had 2.72-fold risk of biochemical recurrence (BCR) (HR=2.72, 95%CI=1.05-7.03, p=0.039). Furthermore, multivariable BCR analysis including the ISUP grade and margin involvement as co-variates showed that the (CAG)n in AR was independent of these histopathological parameters (HRadj=3.37, 95%IC=1.24-9.10, padj=0.017). Altogether, the AR polymorphism is associated with family history of cancer. Consequently, determining the number of CAG repetitions in AR through a blood sample could serve as an independent prognostic marker in patients with PSA &amp;lt;10 ng/ml prior to PR, independent of the histopathological features. Citation Format: Gastón Mario Pascual, Agustina Sabater, Juan Bizzotto, Rocio Seniuk, Pablo Sanchis, Carlos M. Roggero, Carlos Scorticati, Osvaldo Mazza, Elba Vazquez, Ayelen Toro, Geraldine Gueron, Javier Cotignola. Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters [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 3420.

CCDC71L as a novel prognostic marker and immunotherapy target via lipid metabolism in head and neck squamous cell carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most widespread cancer globally with high rate and poor prognosis. Coiled-coil domain containing 71 like (CCDC71L) exerts an important role in cellular lipid metabolic process. However, its function in HNSCC remains unclear. To this end, we examined the CCDC71L implications for prognosis and tumor microenvironment in HNSCC. Materials and methodsFirst, CCDC71L expression was explored through The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Gene Expression Omnibus (GEO) databases. The clinicpathological information were obtained from the dataset of TCGA. The Kaplan–Meier Plotter databases and Cox model were performed for the determination of prognostic values of CCDC71L, including the overall survival (OS), progress free interval (PFI), recurrence-free survival (RFS) and disease specific survival (DSS). Then, the potential mechanism of CCDC71L in HNSCC development was elucidated by means of Gene set enrichment analysis (GSEA) and Metascape databases. Furthermore, the relevance of CCDC71L to immune cells infiltration and immune checkpoints was assessed. The correlations among CCDC71L expression, mutational landscape and genome heterogeneity [mutant-allele tumor heterogeneity (MATH) and tumor purity] were detected by the data in TCGA. ResultsCCDC71L expression was significantly upregulated in HNSCC, and positively associated with age, gender and N stage. Higher CCDC71L expression resulted in poor OS, RFS, DSS and PFI. Multivariate Cox regression analysis showed CCDC71L would be an independent prognostic marker in patients with HNSCC. Moreover, CCDC71L and the level of macrophage and neutrophil cells infiltration were significantly correlated in HNSCC. High expression of CCDC71L was related to immune checkpoint genes, oncogene mutations and genome heterogeneity markers. ConclusionThese results implied that CCDC71L plays vital roles in HNSCC progression, which could be used as a underlying biomarker for the diagnosis and prognosis of HNSCC. Meanwhile, CCDC71L participates in immune regulation, which has a potential value for the immunotherapy of HNSCC patients.

Baseline metastatic growth rate is an independent prognostic marker in patients with advanced BRAF V600 mutated melanoma receiving targeted therapy

BackgroundTargeted therapy (TT) of BRAF V600 mutated unresectable melanoma with inhibitors of the MAPK pathway achieves response rates of up to 76%, but most patients develop secondary resistance. Albeit TT is strikingly efficacious during the first days of treatment, even in advanced cases, long-term survival is highly unlikely, especially in patients with unfavorable baseline characteristics like elevated lactate dehydrogenase (LDH). In patients treated with anti-PD-1 immune checkpoint inhibitors, elevated baseline metastatic growth rate (MGR) was the most important prognostic factor. Here, we aimed at investigating the prognostic impact of MGR in patients with unresectable melanoma receiving TT. MethodsClinical records of 242 patients with at least one measurable target lesion (TL) receiving TT at seven skin cancer centers were reviewed. Baseline MGR was determined measuring the largest TL at baseline and at one earlier timepoint. ResultsOverall survival (OS) and progression-free survival (PFS) were significantly impaired in patients with an MGR > 3.9 mm/month (median OS: 11.4 vs. 35.5 months, P < 0.0001; median PFS: 4.8 vs. 9.2 months, P < 0.0001). Multivariable analysis of OS and PFS revealed that the prognostic impact of elevated MGR was independent of LDH, presence of brain and liver metastases, tumor burden, and line of treatment. The prognostic significance of elevated MGR was highest in patients with normal LDH. ConclusionsBaseline MGR is an important independent prognostic marker for OS and PFS in melanoma patients treated with TT. Its implementation in clinical routine is easy and could facilitate the prognostic stratification.

248. SYSTEMIC INFLAMMATORY MARKERS AS PROGNOSTIC FACTORS IN ESOPHAGEAL CANCER: A MEXICAN PERSPECTIVE

Abstract Background Esophageal cancer (EC) represents the eighth most commonly diagnosed cancer, and sixth cause of cancer-related deaths worldwide. Several studies have demonstrated an association between systemic inflammation, anti-cancer immunity, and poor oncological outcomes in patients with EC. Biomarkers including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) may reflect the balance between pro-cancer inflammation and anti-cancer immune response and have prognostic implications in Mexican esophageal cancer patients. Methods A retrospective review of a prospectively collected database of all EC patients from 2011–2022 was performed. Baseline pre-treatment NLR, LMR and PLR was collected. The date of last follow-up or death was ascertained from medical records. ROC curves were used to calculate cut-off values for NLR and PLR, while the median-value was used for LMR. Serum albumin of &amp;lt;3.5 g/dL was considered malnutrition. Kaplan–Meier (univariate) and Cox regression (multivariate) were performed to evaluate survival against prognostic factors. Results 498 patients were included during the study period, 80.1% men and 19.9% women, median age 60 (±12.2) years old. Adenocarcinoma (49.8%) was the most common histological subtype, followed by squamous cell carcinoma (31.7%). Clinical stage included: I (3%), IIA-B (11.8%), III (37.6%), IVA (2.6%), and IVB (44.2%). Neoadjuvant chemoradiotherapy was the predominant initial therapy (50.4%), followed by chemotherapy (41.7%). ROC curves revealed the following cut-off value: 2.92 for NLR, 174 for IPL, and 3.5 for LMR. In the univariate analysis, four prognostic factors were significant for overall survival (NLR, PLR, LMR, albumin) (Table 1), while in the multivariate analysis only NLR and albumin remained independent factors for survival (Table 2). Conclusion In our population, low NLR and high albumin can be considered independent prognostic markers in patients with esophageal cancer. These common pretreatment biomarkers can serve to identify patients with good prognostic factors, contributing to an improved consent process and therapeutic decision making. Further research should focus on more accurate cut-off values for survival prognostication.

FDG PET/CT Prognostic Markers in Patients with Advanced Melanoma Treated with Ipilimumab and Nivolumab.

Background Despite improved response to combined ipilimumab and nivolumab (hereafter, IpiNivo) treatment for advanced melanoma, many patients exhibit primary or acquired resistance. This, combined with high risk of immune-related adverse events, makes identifying markers predictive of outcomes desirable. Purpose To investigate the prognostic value of fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT parameters at baseline and as part of response monitoring in patients with advanced melanoma undergoing IpiNivo treatment. Materials and Methods This was a single-center retrospective study of adult patients with melanoma who received IpiNivo. Baseline FDG PET/CT parameters that included metabolic tumor volume (MTV), tumor stage, mutation status, Eastern Cooperative Oncology Group performance score, lactate dehydrogenase level, and treatment line were correlated with overall survival in univariable and multivariable Cox regression analyses. Treatment response as determined with FDG PET/CT was correlated with overall survival. Results In total, 122 patients (median age, 61 years [IQR, 51-69 years]; 89 men) were included; 78% (95 of 122) had an Eastern Cooperative Oncology Group score of 0, 52% (45 of 86) had an elevated lactate dehydrogenase level, 39% (48 of 122) had a metastatic stage of M1c and 45% (55 of 122) M1d, 45% (55 of 122) had BRAF V600E/K mutation, and the median MTV was 42 mL. Patients with a higher than median MTV at baseline FDG PET/CT had a lower 12-month survival rate compared with those with a lower than median MTV (43% [95% CI: 32, 58] vs 66% [95% CI: 55, 79], P < .001). In multivariable analysis, higher versus lower than median MTV, Eastern Cooperative Oncology Group performance scores of 1-2 versus 0, and subsequent versus first-line IpiNivo treatment were independently associated with overall survival (hazard ratio [HR]: 1.68 [95% CI: 1.02, 2.78], P = .04; 3.1 [95% CI: 1.8, 5.4], P < .001; and 11.2 [95% CI: 3.4, 37.1], P = .002, respectively). The 12-month overall survival rate was lower in patients with progressive disease than in those without progression (35% [95% CI: 24, 51] vs 90% [95% CI: 83, 99]; HR, 7.3 [95% CI: 3.9, 13.3]; P < .001). Conclusion Baseline fluorine 18 fluorodeoxyglucose PET/CT metabolic tumor volume was an independent prognostic marker in patients with advanced melanoma who received ipilimumab and nivolumab treatment. © RSNA, 2023 Supplemental material is available for this article.

Evaluation of Dynamic Variation in Red Cell Distribution Width as a Septic Marker in Comparison with Procalcitonin Levels and Clinical Scores in Patients with Sepsis or Septic Shock: A Prospective Observational Study

BACKGROUND: Sepsis is a dysregulated host response to infection resulting in potentially life-threatening organ dysfunction. Elevation in red cell distribution width (RDW), a simple routinely done investigation, could be a prognostic marker in these patients. AIM: We performed this prospective observational study to assess role of dynamic variation of RDW in predicting 30-day mortality in patients with sepsis or septic shock presenting and getting admitted in intensive care unit (ICU) in Fayoum, Egypt. METHODS: Between January 2019 and January 2021, 150 patients with sepsis or septic shock at admission were prospectively evaluated for association between RDW value on admission, on day 4, on day 7, and 30-day mortality. To find out factors associated independently with 30-day mortality, we applied multivariate logistic regression analysis and used the analysis to develop nanogram for prediction of mortality on admission. RESULTS: Among 150 patients, 89 (59.3%) were male. Mean age of the patients was 59.6 ± 12.28 years. Regarding RDW on admission (RDW-0), the mean was 14.1 ± 1.9 while on day 4 (RDW-4), the mean was 14.5 ± 1.97, and on day 7 (RDW-7), the mean was 14.4 ± 2.03. Seventy-four (49.3%) patients died during the period of 30 days follow-up. Multiple logistic regression models for the parameters associated with the mortality outcome at admission were done, for age, higher age was associated with higher probability of mortality, OR = 1.07 (95% CI: 1.02, 1.13). Male sex was associated with lower probability of mortality as compared to females, OR = 0.02 (95% CI: 0.06, 0.80). Higher acute physiologic assessment and chronic health evaluation (APACHE) II score, RDW value, and procalcitonin level, all were associated with higher mortality probability. For APACHE II score, higher level was associated with higher odds of mortality, OR = 1.16. For RDW value on admission, higher value was associated with higher odds of mortality, OR = 1.66. For procalcitonin level at admission, higher level was associated with higher odds of mortality, OR = 1.54. Odds for mortality for those who showed any increase in RDW in day 4 as compared to day 0 are higher as compared to those who showed a decrease or no change in RDW, OR = 2.8, p-value = 0.007. CONCLUSIONS: We found that an increase in RDW value on admission and on day 4 is significantly associated with mortality. And that, an increase in RDW value from day 0 to day 4 is also significantly associated with mortality Therefore, a combination of baseline RDW value and an increase in serial RDW values can be a promising independent prognostic marker in patients with sepsis or septic shock.

PD1+CD8+ Cells Are an Independent Prognostic Marker in Patients with Head and Neck Cancer.

Head and neck squamous cell carcinomas (HNSCCs) belong to a group of diverse tumors, which can be induced by infection with human papillomavirus (HPV) or tobacco and alcohol consumption. The viral etiology of HNSCC relates to better clinical outcomes reflecting a different immune system response. Here, we retrospectively analyzed 97 tissue samples from oral and oropharyngeal carcinomas associated and non-associated with HPV infection using multispectral fluorescent immunohistochemistry. To evaluate the immune cell infiltration in tumor and stroma compartments, we designed four panels of four to five antibodies. We detected more T lymphocytes in the stroma, compared to the tumor parenchyma. In HPV positive (HPV+) in comparison to HPV negative (HPV-) tumors, higher counts of CD3+CD4+, CD3+CD8+, PD1+CD4+, PD1+CD8+ T cells, and ICOS- Treg cells were detected while more ICOS+ Treg cells and CTLA4+CD4+ T cells were observed in HPV- than in HPV+ tumors. The results of the univariate and multivariate analyses confirmed the predominant impact of HPV status on prognosis. More importantly, the number of CD8+PD-1+ T cells was identified as an independent factor, influencing the overall and/or disease-specific survival of patients with oral cavity or oropharyngeal carcinomas.

PROGNOSTIC VALUE OF EXERCISE RIGHT VENTRICULAR FREE WALL STRAIN IN PATIENTS WITH SICKLE CELL DISEASE

PROGNOSTIC VALUE OF EXERCISE RIGHT VENTRICULAR FREE WALL STRAIN IN PATIENTS WITH SICKLE CELL DISEASE

Serine protease inhibitor Kazal type 1 (SPINK1) promotes proliferation, migration, invasion and radiation resistance in rectal cancer patients receiving concurrent chemoradiotherapy: a potential target for precision medicine

Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.

Prognostic Impact of Serum CRP Level in Head and Neck Squamous Cell Carcinoma.

ObjectiveThis study evaluated the association of pretreatment serum C-reactive protein (CRP) level with prognosis in patients with head and neck squamous cell carcinoma (HNSCC).MethodsWithin a single-center retrospective study, HNSCC patients receiving treatment between 2014 and 2016 were analyzed regarding the prognostic value of CRP serum levels. X-Tile software was used to determine the optimal cutoff value of serum CRP level. The log-rank test and Kaplan–Meier method were used to assess the effects of CRP level on prognosis in patients with HNSCC. Univariate and multivariate analyses (enter method) using a Cox proportional hazards model were utilized to identify prognostic indicators of progression-free survival (PFS) as the primary outcome and overall survival (OS) as the secondary outcome.ResultsA total of 221 patients with HNSCC were assessed for eligibility, and 208 cases were included in the analysis. The HNSCC patients in the low-group (CRP ≤11.3 mg/L) showed better survival than those in the high-group (CRP > 11.3 mg/L). The univariate and multivariate analyses showed that N1-3 stage and a high serum CRP level (>11.3 mg/L) were unfavorable prognostic factors for PFS and OS in patients with HNSCC.ConclusionSerum CRP level is an independent prognostic marker for patients with HNSCC. CRP level could be regarded as a novel prognostic factor for HNSCC patients.

Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI.

Background and Objectives: Functional capacity (FC) assessed via cardiopulmonary exercise testing (CPET) is a novel, independent prognostic marker for patients with coronary artery disease (CAD). Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are two readily available predictors of systemic inflammation and cardiovascular event risk, which could be used as cost-effective predictors of poor FC. The purpose of this study was to evaluate the utility of NLR and PLR in predicting poor FC in patients with CAD and recent elective percutaneous coronary intervention (PCI). Materials and Methods: Our cross-sectional retrospective analysis included 80 patients with stable CAD and recent elective PCI (mean age 55.51 ± 11.83 years, 71.3% male) who were referred to a cardiovascular rehabilitation center from January 2020 to June 2021. All patients underwent clinical examination, cardiopulmonary exercise testing on a cycle ergometer, transthoracic echocardiography and standard blood analysis. Results: Patients were classified according to percent predicted oxygen uptake (% VO2 max) in two groups—poor FC (≤70%, n = 35) and preserved FC (>70%, n = 45). There was no significant difference between groups regarding age, gender ratio, presence of associated comorbidities, left ventricular ejection fraction and NLR. PLR was higher in patients with poor FC (169.8 ± 59.3 vs. 137.4 ± 35.9, p = 0.003). A PLR cut-off point of 139 had 74% sensitivity and 60% specificity in predicting poor FC. After multivariate analysis, PLR remained a significant predictor of poor functional status. Conclusions: Although CPET is the gold standard test for assessing FC prior to cardiovascular rehabilitation, its availability remains limited. PLR, a cheap and simple test, could predict poor FC in patients with stable CAD and recent elective PCI and help prioritize referral for cardiovascular rehabilitation in high-risk patients.

Abstract 6124: Interleukin-1β and exosomal M6PR secreted by serglycin-overexpressing esophageal cancer cells instigate fibroblasts and endothelial cells to promote esophageal cancer progression

Abstract Non-tumor cells can be recruited and educated by cancer cells to facilitate cancer progression. Previously, we found that serum serglycin (SRGN), a secretory proteoglycan, was an independent prognostic marker for patients with esophageal squamous cell carcinoma (ESCC), and that the autocrine pro-invasive effect of SRGN on ESCC cells was mediated by midkine (MDK). Here, we investigated the effects of cancer cell-derived SRGN on human esophageal fibroblasts (HEF) and human umbilical vein endothelial cells (HUVECs). We found that conditioned medium from SRGN-overexpressing ESCC cells (SRGN-CM) promoted the migration and proliferation of HEF. After SRGN-CM treatment, HEF showed increased expression of fibroblast activation protein alpha (FAP), hepatocyte growth factor (HGF) and amphiregulin, and could enhance tumor growth in vivo. In addition, exosomes derived from SRGN-overexpressing ESCC cells (SRGN-Exo) enhanced the tube formation ability of HUVECs. We found that the effects of SRGN-CM on activation, migration and proliferation of HEF were mediated by MDK. To elucidate the mechanisms by which SRGN upregulates HGF and amphiregulin, and promotes endothelial tube formation, cytokine array and mass spectrometry were performed to analyze differentially expressed proteins in SRGN-CM and SRGN-Exo respectively. The results showed upregulated secretion of interleukin (IL)-1β, IL-18 and tumor necrosis factor-α in SRGN-CM, as well as enriched cation-dependent mannose-6-phosphate receptor (M6PR), integrin alpha-5, teneurin-2 and neurogenic locus notch homolog protein 2 in SRGN-Exo, which were validated by Western blot. These effects were dependent on the glycosaminoglycan chains on SRGN. Our data also showed that the enhanced secretion of IL-1β promoted the expression of HGF in HEF by activating extracellular signal-regulated kinase/activating protein-1. Treatment with SU11274, a c-Met (the receptor of HGF) inhibitor, attenuated the proliferation of ESCC cells co-cultured with HEF, which further indicates that IL-1β-induced HGF from HEF plays a significant role in the tumor microenvironment. In addition, the upregulated exosomal M6PR was found to mediate the enhancing effect of SRGN-Exo on endothelial tube formation ability. Notably, the expression level of M6PR in serum samples of patients with ESCC was positively correlated with that of SRGN and with poor survival. Taken together, SRGN overexpression in ESCC cells created a tumor-promoting microenvironment by altering the ESCC cell secretome including exosomes to exert influence on HEF and HUVECs. [This study was supported by Research Grants Council of the Hong Kong SAR, China, GRF Project No. 17100819] Citation Format: Dongdong Yan, Di Cui, Yun Zhu, Cecilia Ka Wing Chan, Chung Hang Jonathan Choi, Tengfei Liu, Sai Wah Tsao, Stephanie Ma, Annie Lai-Man Cheung. Interleukin-1β and exosomal M6PR secreted by serglycin-overexpressing esophageal cancer cells instigate fibroblasts and endothelial cells to promote esophageal cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6124.