Independent Prognostic Marker Research Articles

Multifaceted roles of IKZF1 gene, perspectives from bench to bedside.

The IKZF1 gene encodes a transcription factor that belongs to the family of zinc-finger DNA-binding proteins associated with chromatin remodeling. The protein product, IKAROS, had been proved to regulate lymphopoiesis. Subsequent mouse model studies have further confirmed its regulating role in lymphopoiesis as well as in hematopoiesis; besides, it associates with immune function, certain immune disorders like common variable immunodeficiency and dysgammaglobulinemia have been proved to be associated with germline IKZF1 mutations. Dysfunction of IKAROS also bears paramount significance in leukemic transformation and alterations of IKZF1 gene predicts a poor prognosis in hematological malignancies. As an independent prognostic marker, IKZF1 has been incorporated in the risk stratification of BCP-ALL and stratification-guided therapy has also been generated. In this review, we provide a concise and comprehensive overview on the multifaceted roles of IKZF1 gene.

Effect of Serum Ionic Magnesium on Neurological Outcome in Severe Traumatic Brain Injury Patients: A Prospective Study

Abstract Background Magnesium is considered to have important role in cytotoxic and reperfusion pathways, deficiency of which may lead to secondary brain injuries; thus, hypomagnesemia is thought to be detrimental in traumatic brain injury (TBI) patients. The aim of this study was to evaluate the relationship between serum ionic magnesium level and neurological outcome in severe TBI patients. Materials and Methods Eighty-four patients with severe TBI aged between 20 and 80 years admitted within 24 hours of injury included in our study. All patients were divided into two categories on the basis of initial serum magnesium levels as low serum magnesium level and normal serum magnesium level. Data was collected on the basis of age, gender, Glasgow Coma Scale (GCS) at the time of admission, and neurological outcome evaluation done on the basis of Glasgow Outcome Scale (GOS) at the end of 6 months. Results Among the total patients, 32 patients had low serum magnesium level (< 1.6 mg/dL) at the time of admission. About 87.5% patients with low serum magnesium level had poor neurological outcome as compared to 12.5% of patients (p < 0.001) had good neurological outcome evaluated on the basis of GOS. Logistic regression model identified low Mg level (odds ratio = 6.593, p = 0.002) and GCS score less than 5 (odds ratio = 3.099, p = 0.028) as independent predictors of TBI. Conclusion Hypomagnesemia seems to be an independent prognostic marker in severe TBI that can lead to poorer outcomes.

Absence of orthopaedia homeobox protein (OTP) expression is associated with disease spread and adverse outcome in pulmonary carcinoid tumour patients.

Pulmonary carcinoid (PC) tumours typically have a good prognosis, although metastases occur, and the disease may progress after a long period of time. Expression of orthopaedia homeobox protein (OTP) has been recognized as a possible independent prognostic marker in PCs. Immunohistochemical (IHC) OTP expression has been associated with better prognosis, but the staining has yet to be implemented in routine clinical diagnostics. In response to this, two new monoclonal OTP antibodies were recently developed.This retrospective study included 164 PC patients operated on at Helsinki University Hospital between 1990 and 2020. Tissue microarray slides, prepared from formalin-fixed and paraffin-embedded primary tumour samples, were stained with OTP IHC using one polyclonal and two novel monoclonal antibodies.Absence of OTP expression was associated with a shorter disease-specific survival (DSS) and disease progression (p < 0.001). Patients without OTP expression had a 5-year DSS of 73-79%, whereas 5-year DSS was 91-94% with OTP expression, depending on the primary antibody. In a univariable Cox regression model, absence of OTP expression was associated with adverse outcome along with atypical histological subtype, metastatic disease, Ki-67 proliferation index > 1%, and larger tumour size. In a multivariable Cox regression model, only absence of OTP expression and lymph node involvement at the time of diagnosis were associated with risk of worse prognosis. All three antibodies showed good concordance with each other.Our findings support the role of OTP as an independent prognostic marker in PCs and applicability of IHC staining in routine clinical use with novel monoclonal antibodies.

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

Mortality and COVID Infection: Predictors of Mortality 10 Months after Discharge.

The long-term survival of patients hospitalized with COVID-19 and the factors associated with poorer survival months after infection are not well understood. The aims of the present study were to analyze the overall mortality 10 months after admission. 762 patients with COVID-19 disease were included. Patients underwent a complete clinical evaluation, routine laboratory analysis and chest X-ray. Data collected included demographic and clinical data, such as vascular risk factors, tobacco or alcohol use, comorbidity, and institutionalization. Ten-month mortality was 25.6%: 108 deaths occurred in-hospital, while 87 patients died after discharge. In-hospital mortality was independently related to NT-proBNP values > 503.5 pg/mL [OR = 4.67 (2.38-9.20)], urea > 37 mg/dL [3.21 (1.86-7.31)] and age older than 71 years [OR = 1.93 (1.05-3.54)]. NT-proBNP values > 503.5 pg/mL [OR = 5.00 (3.06-8.19)], urea > 37 mg/dL [3.51 (1.97-6.27)], cognitive impairment [OR = 1.96 (1.30-2.95), cancer [OR = 2.23 (1.36-3.68), and leukocytes > 6330/mm3 [OR = 1.64 (1.08-2.50)], were independently associated with long-term mortality. the risk of death remains high even months after COVID-19 infection. Overall mortality of COVID-19 patients during 10 months after hospital discharge is nearly as high as that observed during hospital admission. Comorbidities such as cancer or cognitive impairment, organ dysfunction and inflammatory reaction are independent prognostic markers of long-term mortality.

Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. During the median follow-up period of 7.3months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42mg/L was a significant prognostic factor for OS (p = 0.001). The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Methylation of FAM110C is a synthetic lethal marker for ATR/CHK1 inhibitors in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. An epigenetic-based synthetic lethal strategy provides a novel opportunity for PDAC treatment. Finding more DNA damage repair (DDR)-related or cell fate-related molecules with aberrant epigenetic changes is becoming very important. Family with sequence similarity 110C (FAM110C) is a cell fate-related gene and its function in cancer remains unclear. Seven cell lines, 34 cases of intraductal papillary mucinous neoplasm (IPMN), 15 cases of mucinous cystic neoplasm (MCN) and 284 cases of PDAC samples were employed. Methylation-specific PCR, western blot, CRISPR knockout, immunoprecipitation and a xenograft mouse model were used in this study. FAM110C is methylated in 41.18% (14/34) of IPMN, 46.67% (7/15) of MCN and 72.89% (207/284) of PDAC, with a progression trend from IPMN/MCN to pancreatic cancer (P = 0.0001, P = 0.0389). FAM110C methylation is significantly associated with poor overall survival (OS) (P = 0.0065) and is an independent prognostic marker for poor OS (P = 0.0159). FAM110C inhibits PDAC cells growth both in vitro and in vivo, serving as a novel tumor suppressor. FAM110C activates ATM and NHEJ signaling pathways by interacting with HMGB1. Loss of FAM110C expression sensitizes PDAC cells to VE-822 (an ATR inhibitor) and MK-8776 (a CHK1 inhibitor). FAM110C methylation is a potential diagnostic and prognostic marker in PDAC, and its epigenetic silencing sensitizes PDAC cells to ATR/CHK1 inhibitors.

Establishment and validation of a prognostic scoring model based on disulfidptosis-related long non-coding RNAs in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD), a frequently occurring gastrointestinal tumour, is often detected late and has a poor prognosis. Long non-coding RNAs (lncRNAs) significantly affect tumour development. Recent studies have identified disulfidptosis as a previously unexplained form of cell death. Herein, we aimed to examine the predictive value of disulfidptosis-related lncRNA models for the clinical prognosis and immunotherapy of STAD. STAD-related transcriptomic data were obtained from The Cancer Genome Atlas (TCGA), whereas genes associated with disulfidptosis were identified from previously published papers. A risk prediction model for disulfidptosis-related lncRNAs was developed using the Cox regression and least absolute shrinkage selection algorithm methods. The accuracy of the model was confirmed using calibration curves, and the biological functions were analysed using Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA). Finally, the tumour mutation burden (TMB) and tumour immune dysfunction and exclusion (TIDE) algorithms were used to screen drugs that are sensitive to STAD. The risk prediction models were constructed using seven disulfidptosis-related lncRNAs. The validated results were consistent with the predicted ones, with significant survival differences. When combined with clinical data, the risk scores were used as independent prognostic markers. Based on the tumour mutation load, the high-risk patient group had a poorer survival rate as compared with the low-risk patient group. Further studies were conducted to understand the different groups' inconsistent responses to immune status; subsequently, relatively sensitive drugs were identified. Overall, seven markers of disulfidptosis-related lncRNAs associated with STAD were found to facilitate prognostic prediction, suggesting new ideas for immunotherapy and clinical applications.

Impact of serum iron levels on in-hospital mortality and clinical outcomes in patients with ST segment elevation myocardial infarction undergoing emergency percutaneous coronary intervention: a retrospective analysis.

Despite advances in percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI), in-hospital mortality remains a concern, highlighting the need for the identification of additional risk factors such as serum iron levels. This study aims to assess the relationship between serum iron levels and in-hospital mortality among patients with STEMI undergoing emergency PCI. A total of 685 patients diagnosed with STEMI, treated with emergency PCI between January 2020 and June 2023, were included in this retrospective observational study. Participants were categorized based on serum iron levels into a low serum iron group (Fe <7.8 μmol/L) and a control group (Fe ≥7.8 μmol/L). Clinical and biochemical variables were compared between the groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for in-hospital mortality. The low serum iron group demonstrated significantly higher in-hospital mortality rates (9.3 vs. 1.0%, P < 0.05) compared with the control group. Multivariate logistic regression revealed that a left ventricular ejection fraction less than 40% upon admission [odds ratio (OR), 8.01; 95% confidence interval (CI), 1.230-52.173; P = 0.029], the occurrence of no-reflow during PCI (OR, 7.13; 95% CI, 1.311-38.784; P = 0.023), and serum iron levels below 7.8 μmol/L (OR, 11.32; 95% CI, 2.345-54.640; P = 0.003) were independent risk factors for in-hospital mortality. Low serum iron levels are associated with increased in-hospital mortality in patients with STEMI undergoing emergency PCI. Serum iron levels may serve as an independent prognostic marker and could inform risk stratification and therapeutic targeting in this patient population.

Interleukin-1α as a Potential Prognostic Biomarker in Pancreatic Cancer.

We assessed the prognostic role of pro-inflammatory cytokines of the IL-1 superfamily in patients with pancreatic cancer. This retrospective study was performed using two independent cohorts of patients with pancreatic cancer: the International Cancer Genome Consortium (ICGC, N = 267) cohort and The Cancer Genome Atlas (TCGA, N = 178) cohort. Univariate Cox regressions were used to identify prognosis-related pro-inflammatory cytokines of the IL-1 superfamily. Cytokines associated with outcome were included in a multivariate Cox model with relevant clinicopathological variables to identify prognostic biomarkers. IL-1α was the only pro-inflammatory cytokine of the IL-1 superfamily that was significantly associated with prognosis in both cohorts. In the training cohort (ICGC), the decile of patients with the lowest IL1A expression had better overall survival (HR = 1.99 [1.01-3.93], p = 0.05) and better relapse-free survival (HR = 1.85 [1.02-3.34], p = 0.04) than the group with the highest IL1A expression. The validation cohort (TCGA) confirmed these results: the decile with the lowest IL1A expression had better overall survival (HR = 3.00 [1.14-7.90], p = 0.03) and a lower risk of progression (HR = 3.11 [1.24-7.80], p = 0.01). IL1A is an independent prognostic marker and could be considered a potential therapeutic target in pancreatic cancer patients.

PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer.

Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.

Automatic quantification of tumor-stroma ratio as a prognostic marker for pancreatic cancer.

This study aims to introduce an innovative multi-step pipeline for automatic tumor-stroma ratio (TSR) quantification as a potential prognostic marker for pancreatic cancer, addressing the limitations of existing staging systems and the lack of commonly used prognostic biomarkers. The proposed approach involves a deep-learning-based method for the automatic segmentation of tumor epithelial cells, tumor bulk, and stroma from whole-slide images (WSIs). Models were trained using five-fold cross-validation and evaluated on an independent external test set. TSR was computed based on the segmented components. Additionally, TSR's predictive value for six-month survival on the independent external dataset was assessed. Median Dice (inter-quartile range (IQR)) of 0.751(0.15) and 0.726(0.25) for tumor epithelium segmentation on internal and external test sets, respectively. Median Dice of 0.76(0.11) and 0.863(0.17) for tumor bulk segmentation on internal and external test sets, respectively. TSR was evaluated as an independent prognostic marker, demonstrating a cross-validation AUC of 0.61±0.12 for predicting six-month survival on the external dataset. Our pipeline for automatic TSR quantification offers promising potential as a prognostic marker for pancreatic cancer. The results underscore the feasibility of computational biomarker discovery in enhancing patient outcome prediction, thus contributing to personalized patient management.

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.

Serum IL-24 combined with CA125 as screening and prognostic biomarkers for NSCLC.

Noninvasive and effective methods for early screening of non-small cell lung cancer(NSCLC) still need to be developed. At present, a reasonable conclusion is that a combination of tumor markers is a superior predictor of screening. Cytokines, as important regulators of cancer development, have great potential for the screening and prognosis of NSCLC. This study screened novel biomarkers related to the early screening and prognosis of NSCLC. In the present study, the biological significance and immunoregulation of interleukin-24(IL-24) were analyzed based on The Cancer Genome Atlas data. Next, 150 serum samples from initially treated patients with NSCLC and 70 controls were collected, and we obtained pathological sections from 60 patients with NSCLC. The ELISA and immunohistochemistryresults showed the differential expression of IL-24 and carbohydrate antigen 125(CA125). The results show that IL-24 is an important tumor suppressor in NSCLCthat helps to improve the poor prognosis of these patients. A significantly negative correlation between IL-24 and CA125 levels was also found. Notably, serum IL-24 levels were significantly negatively correlated with the TNM stage of patients with NSCLC, consistent with an important role for tumor suppressors in NSCLC. The receiver operating characteristic curve analysis showed that a combination of IL-24 and CA125 was an effective panel for discriminating patients with NSCLC from HD, and individuals with other lung diseases. Serum IL-24 and CA125 levels were identified as independent prognostic markers for NSCLC. The IL-24 and CA125 panel exhibited good performance in the screening of NSCLC.

Can platelet distribution width lymphocyte ratio be a novel biomarker for predicting survival in metastatic renal cell cancer?

Renal cell carcinoma (RCC) constitutes 3% of all malignant tumors in the adult patient population (1). As in other cancer processes, inflammation affects each step of tumor formation, including initiation of tumorigenesis, tumor promotion, and metastatic progression in RCC (2,3). It is widely accepted that C-reactive protein, fibrinogen, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio, and platelet-lymphocyte ratio (PLR) are markers of inflammation in both inflammatory diseases and malignant disease processes (2,3). Furthermore, a relatively high NLR was reported to be associated with an unfavorable prognosis and reduced overall survival in urological cancers (4,5). Platelets can secrete active metabolites and proteins and take a significant role in various processes such as inflammation, sepsis, and tissue regeneration (5). In addition, it is known that they can release growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta, and vascular endothelial growth factor (VEGF), which may all induce tumor angiogenesis and growth (6). In line with these findings, Tsujino et al. reported that platelet count could be an independent prognostic marker of overall survival and recurrence-free survival for patients with localized RCC (7). Additionally, Wang et al. stated that a high PLR value indicated an unfavorable prognosis in all urological cancers (8). Although several studies investigated the significance of hematological indices such as NLR and PLR in localized or metastatic RCC (mRCC), none focused on the platelet distribution width-lymphocyte ratio (PDWLR) (7,9,10). Therefore, this study aimed to analyze the prognostic significance of these platelet parameters in patients with mRCC.

Lactylproteome analysis indicates histone H4K12 lactylation as a novel biomarker in triple-negative breast cancer.

The established link between posttranslational modifications of histone and non-histone lysine (K) residues in cell metabolism, and their role in cancer progression, is well-documented. However, the lactylation expression signature in triple-negative breast cancer (TNBC) remains underexplored. We conducted a comprehensive lactylproteome profiling of eight pairs of TNBC samples and their matched adjacent tissues. This was achieved through 4-Dimensional label-free quantitative proteomics combined with lactylation analysis (4D-LFQP-LA). The expression of identified lactylated proteins in TNBC was detected using immunoblotting and immunohistochemistry (IHC) with specific primary antibodies, and their clinicopathological and prognostic significance was evaluated. Our analysis identified 58 lactylation sites on 48 proteins, delineating the protein lactylation alteration signature in TNBC. Bioinformatic and functional analyses indicated that these lactylated proteins play crucial roles in regulating key biological processes in TNBC. Notably, lactylation of lysine at position 12 (H4K12lac) in the histone H4 domain was found to be upregulated in TNBC. Further investigations showed a high prevalence of H4K12lac upregulation in TNBC, with positive rates of 93.19% (137/147) and 92.93% (92/99) in TNBC tissue chip and validation cohorts, respectively. H4K12lac expression correlated positively with Ki-67 and inversely with overall survival (OS) in TNBC (HR [hazard ratio] =2.813, 95%CI [credibility interval]: 1.242-6.371, P=0.0164), suggesting its potential as an independent prognostic marker (HR=3.477, 95%CI: 1.324-9.130, P=0.011). Lactylation is a significant post-translational modification in TNBC proteins. H4K12lac emerges as a promising biomarker for TNBC, offering insights into the lactylation profiles of TNBC proteins and linking histone modifications to clinical implications in TNBC.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. Five hundred and ninety patients were included, with a median follow-up of 28months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Abstract PO3-14-04: Prognostic value of systemic inflammatory markers in neoadjuvant chemotherapy for breast triple negative cancer with pembrolizumab: development of a nomogram

Abstract Introduction: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), have shown promise as prognostic markers for various cancer types. Inflammation plays a crucial role in cancer development, progression, metastasis, and resistance to treatment. However, only a few preoperative biomarkers have been identified as independent prognostic markers. Systemic inflammatory markers offer a reliable and easily accessible approach for prognosis evaluation. Materials and Methods: This study evaluated two groups of patients who received neoadjuvant chemotherapy for triple-negative breast cancer outside of clinical trials. The first group underwent neoadjuvant chemotherapy in 2021 with the EC X4 and weekly paclitaxel regimen, whereas the second group received neoadjuvant chemotherapy in 2022 following the KEYNOTE-522 study protocol with pembrolizumab. A total of 44 patients were included, with 23 patients in the pembrolizumab group. The NLR was defined as the absolute blood neutrophil count divided by the absolute lymphocyte count, and the derived neutrophil/lymphocyte ratio (dNLR) was defined as the absolute neutrophil count divided by the derived lymphocyte count (absolute leukocyte count —neutrophil count). The PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. The LMR was defined as the absolute lymphocyte count divided by the absolute monocyte count. The association between systemic inflammatory markers (NLR, dNLR, PLR, and LMR) and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and two weeks before surgery. The χ2 test or Fisher’s exact test was used to analyze the correlation between the inflammatory indices and clinicopathologic parameters. Student’s t-test was used to compare different groups of continuous parametric data. Results: The pCR rates were 67% in the standard therapy group and 87% in the pembrolizumab group. There were no significant differences in other clinical characteristics between the two groups. The NLR, dNLR, PLR, and LMR at 6 months showed statistically significant differences compared to baseline levels. This difference was more evident in patients undergoing pembrolizumab therapy. ROC curves for the pembrolizumab group demonstrated an area under the curve (AUC) of 0.737, indicating a strong correlation between these systemic inflammatory markers and pCR. Based on these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusion: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with TNBC undergoing neoadjuvant chemotherapy. The significant differences observed in the pembrolizumab group and the high AUC of the ROC curves suggest the utility of these markers in predicting treatment response. The developed nomogram provides a practical tool for clinicians to estimate the probability of pCR based on NLR, dNLR, PLR, and LMR. Further research and validation are required to confirm the clinical utility of these markers in larger patient cohorts. Nomogram –insert figure image– ROC curve –insert figure image– Citation Format: Filippo Giovanardi, Giancarlo Bisagni, Elisa Gasparini, Alessandra Bologna, Roberto Di Cicilia, Gabriella Moretti, Claudia Degli Esposti, Carmine Pinto. Prognostic value of systemic inflammatory markers in neoadjuvant chemotherapy for breast triple negative cancer with pembrolizumab: development of a nomogram [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-14-04.

52: Sarcopenia as an independent prognostic marker in NSCLC patients with BMs treated with GKRS

52: Sarcopenia as an independent prognostic marker in NSCLC patients with BMs treated with GKRS

61: SII and NLR are independent prognostic markers of patients with NSCLC BM treated with GKRS

61: SII and NLR are independent prognostic markers of patients with NSCLC BM treated with GKRS