Strong Independent Prognostic Factor Research Articles

Prognostic impact of immunophenotypic variation in subcapsular sinus endothelium of sentinel lymph nodes in invasive breast carcinoma

Introduction Several studies demonstrated the de novo-formation of lymphatic vessels in tumor-draining lymph nodes (LN), partly preceding lymphatic metastases. This “lymphovascular niche” supposedly facilitates survival of metastatic tumor cells. This study aims at evaluating the previously observed immunophenotypic variations of subcapsular endothelial cells (SEC) in a larger cohort by software-assisted image analysis. Methods Suitable cases with sentinel-LN (SLN) of invasive breast cancer were identified in the Institute of Pathology, corresponding data was extracted. LN of 231 patients were stained for HE, D2-40, CD31 and Prox1. QuPath software was used for assessing the immunohistochemical stained area of endothelial cells of the subcapsular sinus. The Cutoff Finder web application was used for identification of the best cutoff for continuous parameters according to overall survival (OS). Collected data was statistically evaluated for available data. Results A larger area of CD31-positive SEC was significantly associated with worse OS (p=0.001), as was a higher proportion of D2-40-stained subcapsular sinus (p=0.045). Larger area of D2-40-/CD31-/Prox1-positive SEC and higher proportion of D2-40 stained subcapsular sinus were independent marker for worse OS in multivariate analysis in the whole cohort, for D2-40- and CD31-positive SECs as well as higher proportion of D2-40-stained sinus including nodal-negative status, respectively. Conclusion QuPath-assisted evaluation of immunophenotypic variation in subcapsular sinus endothelium in SLN essentially confirmed and extended our previous findings. Larger positive area of D2-40 and CD31-positive SECs emerged as a strong independent negative prognostic factor, even before evident nodal metastasis. The potential function of alterations in D2-40-/CD31-expression in SECs has yet to be elucidated.

The Effect of Systemic Inflammation and Clinicopathologic Features on Survival in Malignant Pleural Mesothelioma: A Multicenter Analysis.

Background and Objectives: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with a poor prognosis. Identifying reliable prognostic factors is crucial for risk stratification and optimizing treatment strategies. This study aimed to evaluate the impact of clinicopathologic factors and systemic inflammatory markers on survival outcomes in patients with MPM. Materials and Methods: This retrospective, multicenter study included 217 patients diagnosed with MPM between January 2009 and March 2024. Data on age, gender, histology, disease stage, treatment modalities, and inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) were collected. Survival outcomes were analyzed using Kaplan-Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: CAR was identified as an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Patients with CAR < 0.98 had significantly longer OS (87.0 months vs. 14.0 months, p < 0.001) and PFS (17.61 months vs. 8.96 months, p = 0.010). While NLR was significant in univariate analysis (OS: 25.0 months for NLR < 2.58 vs. 21.0 months for NLR ≥ 2.58, p = 0.040), it did not retain significance in the multivariate model (p = 0.180). Epithelioid histology and early-stage disease were strongly associated with improved survival outcomes (OS: 32.0 vs. 11.0 months for epithelioid vs. non-epithelioid histology, p < 0.001; 32.0 vs. 12.0 months for early-stage vs. metastatic disease, p < 0.001). Conclusions: CAR is a strong independent prognostic factor in MPM, reflecting systemic inflammation and nutritional status. Epithelioid histology and early-stage disease are associated with significantly longer survival, underscoring the critical role of early detection in improving patient outcomes.

Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma

AbstractAimThe relationship between sarcopenia, tumor‐infiltrating lymphocytes (TILs), and long‐term survival in patients with hepatocellular carcinoma (HCC) has not been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC.MethodsWe included 351 patients with HCC following liver resection. Sarcopenia was defined based on the skeletal muscle index using computed tomography. Tumor‐infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liver resection specimens.ResultsSarcopenia patients had a significantly lower lymphocyte count (p = 0.003), prognostic nutritional index (p = 0.017), and CD4+ and CD8+ T cell counts (p = 0.008 and p = 0.006, respectively). The overall survival (OS) and recurrence‐free survival (RFS) rates of sarcopenia patients were significantly lower than non‐sarcopenia patients (both p &lt; 0.001). Multivariate analysis revealed that sarcopenia and low CD8 levels were strong independent poor prognostic factors for OS and RFS (both p &lt; 0.001). Regardless of sarcopenia, patients with high CD8 levels had significantly better OS and RFS rates and increased expression of perforin and granzyme B. Particularly, sarcopenia patients with high CD8 levels had much better OS and RFS than those with low CD8 levels and were even comparable to non‐sarcopenia patients with high CD8 levels.ConclusionsSarcopenia and low CD8 levels are strong independent poor prognostic factors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levels had favorable survival and activated local immunity, suggesting that tumor‐infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.

Predictors of occult metastases in potentially Resectable pancreatic ductal adenocarcinoma

BackgroundPatients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) sometimes show unexpected liver, peritoneal, and para-aortic lymph node metastases intraoperatively. Despite radical pancreatectomy, a nonnegligible number of patients relapse within 6 months after surgery. The aim of this study was to identify the preoperative predictors of occult metastases (OM), defined as intraoperative distant metastases or within 6 months after pancreatectomy. Materials and methodsThis study included patients with R and BR PDAC who underwent curative-intent pancreatectomy or staging laparoscopy between 2006 and 2021. Multivariate logistic regression and Cox hazard analyses were performed to identify the preoperative predictors of OM and to assess the impact of these factors on prognosis after pancreatectomy. ResultsOf the 279 patients, OM was observed intraoperatively in 47 and postoperatively in 34. In the OM group, there were no differences in prognosis between patients who had intraoperative metastases and recurrence within 6 months (median survival time [MST], 18.1 vs. 12.9 months), and between patients who underwent pancreatectomy and those who did not (MST, 13.9 vs. 18.1 months). Preoperative tumor size ≥22 mm (odds ratio [OR], 2.03; 95 % confidence interval [CI], 1.16–3.53; p = 0.013) and preoperative CA19–9 level ≥ 118.8 U/mL (OR, 2.64; 95 % CI, 1.22–5.73; p = 0.014) were significant predictors of OM. Additionally, positive OM predictors were strong independent prognostic factors for overall survival after pancreatectomy (hazard ratio, 2.47; 95 % CI, 1.54–3.98; p < 0.001). ConclusionMultidisciplinary treatment strategies should be considered for patients with predictors of OM to avoid inappropriate surgical interventions.

OTHR-13. A RETROSPECTIVE ANALYSIS OF A CLINICO-PATHOLOGICAL DATA ON CHILDHOOD AND ADOLESCENT MENINGIOMA- A SINGLE CENTRE EXPERIENCE

Abstract BACKGROUND Meningiomas in young patients remain poorly understood in terms of their origin, outcomes, and best treatment approaches. Current knowledge is limited to small studies and applying adult data, making dedicated research crucial for better understanding and management of these tumours. METHOD We reviewed meningioma cases (1990-2023) from our database, analysing demographics, tumour details, treatment, and outcomes. Neuroimaging and records confirmed tumour location and resection extent. Pathology was reviewed for alignment with WHO 2016 classification. RESULTS At GOSH, 60 patients with meningioma were treated over 33 years. Ages ranged from infants (142 days) to young adults (21 years) of which 51.7% were males. The commonest tumour location was at the skull base (31.6%), followed by the convexity (23.3%). Notably, 6.6% were previously exposed to therapeutic irradiation, and 20% were diagnosed with neurofibromatosis type 2 (NF-2) while 3 others had suspected mosaic NF-2. Among 55 cases with slides available for histopathology review, 26 (46.42%) were WHO grade-I, while 25 (44.64%) WHO grade-II and 4 (7%) WHO grade-III which had a 50% fatality rate. Complete surgical removal offered the best outcome, with only 3 out of 29 patients (10%) experiencing relapse as compared to 11 out of 17 (64.7%) in those who underwent incomplete resection alone. However, radiotherapy after incomplete surgery showed promise, with all 8 patients remaining relapse-free. Unfortunately, the single patient with a very aggressive tumour type (rhabdoid histology) progressed even after complete removal and irradiation. CONCLUSION In children and teens with meningioma, extent of initial surgical resection is considered the strongest independent prognostic factor, but radiotherapy after incomplete removal can improve relapse-free survival. Careful monitoring is crucial for those with partial resections, high-grade tumours, or NF2. Molecular data may bring light in the future on how the unique characteristics of paediatric meningiomas impact clinical status, management approach and survival.

Nutritional status as independent prognostic factor of outcome and mortality until five years after hip fracture: a comprehensive prospective study

SummaryWe determined the prognostic value of nutritional status for outcome after hip fracture. Nutritional status was a strong independent prognostic factor for clinical outcome and 5-year mortality. Physical function showed incomplete recovery. Elderly care should focus on prevention already before hip fracture.PurposeTo determine the prognostic value of nutritional status in hip fracture patients for multiple clinical and functional outcomes over 6 months, and for new fractures and survival over 5 years post-fracture.MethodsWe included 152 well-characterized subjects (age 55+ years) with a hip fracture from a previously published randomized controlled trial. Nutritional status was appraised using the Mini Nutritional Assessment (MNA). Multivariable linear, logistic and Cox regression models were fitted, adjusted for age, sex, ASA score, group and additional prognostic covariates identified in backward regression models.ResultsAt baseline, impaired nutritional status was significantly associated with physical disability, depression, impaired cognition and lower quality of life. Prospective analyses showed that impaired baseline nutritional status was an independent prognostic factor for postoperative complications (OR 2.00, 95%CI 1.01–3.98, p = 0.047), discharge location from hospital (home vs. rehabilitation clinic, OR 0.41, 95%CI 0.18–0.98, p = 0.044), hospital readmission (OR 4.59, 95%CI 1.70–12.4, p = 0.003) and total length of hospital stay (HR of being discharged: 0.63, 96%CI 0.44–0.89, p = 0.008), as well as for 5-year mortality (HR 3.94, 95%CI 1.53–10.2, p = 0.005), but not for risk of new fractures (5y-HR 0.87, 95%CI 0.34–2.24, p = 0.769). Curves of physical disability over time showed that the three nutritional status categories followed almost parallel trajectories from baseline until 6 months after hip fracture, without complete recovery and even with further deterioration in malnourished subjects from 3 to 6 months post-fracture.ConclusionAs baselline nutritional status is a strong independent prognostic factor for clinical outcome after hip fracture, affecting even five-year survival, elderly health care should focus on prevention and identification of at-risk individuals already before hip fracture.

High immune cell infiltration predicts improved survival in cholangiocarcinoma.

Antitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis. CD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells. Low ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup. Identifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy.

The therapeutic effect and targets of herba Sarcandrae on breast cancer and the construction of a prognostic signature consisting of inflammation-related genes

BackgroundThe prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. MethodsThe active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The “drug-active compound-potential target” network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. ResultsForty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. ConclusionsHerba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

The emerging role of cell-free DNA as a molecular marker for duodenal adenocarcinoma.

Duodenal adenocarcinoma is rare and its prognostic factors remain controversial. In our study, the role of cell-free deoxyribonucleic acid (cfDNA) as prognostic factor in duodenal adenocarcinoma was evaluated. From June 2003 to July 2021, plasma samples were collected from 41 patients with duodenal adenocarcinoma. Plasma cfDNA was assessed in combination with clinicopathological and biochemical characteristics. Univariate and multivariate analyses were conducted to identify independent prognostic factors for overall survival with a Cox proportional hazards regression model. The 1- and 5-year survival rates of the patients with high plasma cfDNA level (>9288 copies/mL) group were 58.7% and 17.6%, respectively, which were much lower than patients with low cfDNA level (≤9288 copies/mL), with 95.2% and 64.6%. In univariate analysis, high cfDNA level, lymph node involvement, lymphovascular invasion, and tumor stage were associated with decreased survival. When subjected to multivariate analysis, only high cfDNA level showed significance in influencing the overall survival of duodenal cancer. cfDNA analysis is simple and noninvasive. High cfDNA level is a strong independent prognostic factor for decreased overall survival and it should be integrated into clinical care.

HPV-Related Oropharyngeal Cancer in Southern Thailand: Proportion Trend and Survival Outcome.

Persistent high-risk human papillomavirus (HPV) infection is one of the major etiologies of oropharyngeal squamous cell carcinoma (OPSCC). This study aimed to determine the proportion, temporal trend, and prognostic significance of HPV-related OPSCC in Thai patients. The study included patients with OPSCC who were treated at Songklanagarind Hospital (Songkhla, Southern Thailand) from 2009 to 2020. HPV status was screened by p16 expression using immunohistochemistry and confirmed by real-time polymerase chain reaction. Cox regression was used to determine prognostic significance. The overall proportion of HPV+ OPSCC was 15.3% (95% confidence interval [CI]: 12.1-18.5) with a slightly increased proportion from 10.6% in 2009-2010 to 16.5% (2019-2020) (P for trend = 0.166). Among the HPV+ cases, HPV16 was detected in 65.3%, HPV18 in 34.7%, and other high-risk HPV types in 24%. Patients with P16+ or HPV+ OPSCC had significantly better overall survival (hazard ratio [HR]: 0.63, 95% CI: 0.45-0.90 and HR: 0.63, 95% CI: 0.45-0.88, respectively). Thai patients in the southern region have a low proportion of HPV-related OPSCC with an increasing trend. Both P16 expression and HPV DNA status are strong independent prognostic factors of OPSCC.

Serum ferritin level is an effective prognostic factor for lung cancer immunotherapy

ABSTRACT Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X2 = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X2 = 6.475, P = .011). However, the “integrated factor”, which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy.

The prognostic value of bone marrow retention index and bone marrow-to-liver ratio of baseline 18F-FDGPET/CT in diffuse large B-cell lymphoma.

To determine prognostic value of bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) measured on baseline dual-phase 18F-FDG PET/CT in a series of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated homogeneously with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. This prospective study enrolled 135 patients with newly diagnosed DLBCL. All patients underwent dual-phase 18F-FDGPET/CT. The following PET parameters were calculated for both tumor and bone marrow: maximum standardized uptake value (SUVmax) at both time points (SUVmax early and SUVmax delayed), SUVmax increment (SUVinc), RI, and BLR. Patients were treated with R-CHOP regimen and response at end of treatment was assessed. The final analysis included 98 patients with complete remission. At a median follow-up of 22months, 57 patients showed no relapse, 74 survived, and 24 died. The 2-year relapse-free survival (RFS) values for patients with higher and lower RI-bm were 20% and 65.1%, respectively (p < 0.001), and for patients with higher and lower BLR were 30.2% and 69.6%, respectively (p < 0.001). The 2-year overall survival (OS) values for patients with higher and lower RI-bm were 60% and 76.3%, respectively (p = 0.023), and for patients with higher and lower BLR were 57.3% and 78.6%, respectively (p = 0.035). Univariate analysis revealed that RI-bm and BLR were independent significant prognostic factors for both RFS and OS (hazard ratio [HR] = 4.02, p < 0.001, and HR = 3.23, p < 0.001, respectively) and (HR = 2.83, p = 0.030 and HR = 2.38, p = 0.041, respectively). Baseline RI-bm and BLR were strong independent prognostic factors in DLBCL patients. Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) could represent suitable and noninvasive positron emission tomography/computed tomography (PET/CT) parameters for predicting pretreatment risk in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. • Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) are powerful prognostic variables in diffuse large B-cell lymphoma (DLBCL) patients. • High BLR and RI-bm are significantly associated with poor overall survival (OS) and relapse-free survival (RFS). • RI-bm and BLR represent suitable and noninvasive risk indicators in DLBCL patients.

Diabetes Mellitus Is a Strong Independent Negative Prognostic Factor in Patients with Brain Metastases Treated with Radiotherapy.

Brain metastases (BM) cause relevant morbidity and mortality in cancer patients. The presence of cerebrovascular diseases can alter the tumor microenvironment, cellular proliferation and treatment resistance. However, it is largely unknown if the presence of distinct cerebrovascular risk factors may alter the prognosis of patients with BM. Patients admitted for the radiotherapy of BM at a large tertiary cancer center were included. Patient and survival data, including cerebrovascular risk factors (diabetes mellitus (DM), smoking, arterial hypertension, peripheral arterial occlusive disease, hypercholesterolemia and smoking) were recorded. 203 patients were included. Patients with DM (n = 39) had significantly shorter overall survival (OS) (HR 1.75 (1.20-2.56), p = 0.003, log-rank). Other vascular comorbidities were not associated with differences in OS. DM remained prognostically significant in the multivariate Cox regression including established prognostic factors (HR 1.92 (1.20-3.06), p = 0.006). Furthermore, subgroup analyses revealed a prognostic role of DM in patients with non-small cell lung cancer, both in univariate (HR 1.68 (0.97-2.93), p = 0.066) and multivariate analysis (HR 2.73 (1.33-5.63), p = 0.006), and a trend in melanoma patients. DM is associated with reduced survival in patients with BM. Further research is necessary to better understand the molecular mechanisms and therapeutic implications of this important interaction.

YTHDF3as a prognostic predictive biomarker of thyroid cancer and its correlation with immune infiltration

PurposeThyroid cancer (TC) is one of the most common endocrine malignancies, and its morbidity continues to rise. N6-methyladenosine (m6A) RNA methylation, an epigenetic modification, is an important regulator of gene expression in TC. Therefore, it’s worth finding the characteristics and predictive value of the m6A RNA methylation regulators in thyroid cancer (TC).MethodRNA-seq data of TC was downloaded from the Cancer Genome Atlas (TCGA) database to screen out the differential expressed regulators. The absolute contraction selection operator (Lasso) Cox regression was used to construct the risk model of m6A methylation regulators. The predictive value of the risk scoring model was evaluated by Kaplan Meier (K-M) analysis and receiver operating characteristic (ROC) curves. The underlying mechanism of m6A methylation regulators in TC was predicted by gene set enrichment analysis (GSEA). Further validation was performed by using immunohistochemistry (IHC) and q-PCR. The correlation between risk-related gene and immune infiltration was evaluated by Tumour Immune Estimation Resource (TIMER).ResultsIGF2BP2, YTHDF1 and YTHDF3 were screened out as strong independent prognostic factors of TC. Then a risk score model was established to further screen the predictors. Finally, according to the results of overall survival (OS) and clinical characteristics of TC, YTHDF3 was screened out as a potential predictor. Meanwhile, IHC and qPCR confirmed that YTHDF3 was expressed differential in TC. The expression of YTHDF3 was positively associated with the infiltration level of CD4+ T cells and macrophages. It was strongly correlated with a variety of immune markers in TC.ConclusionWe confirmed that YTHDF3 can be used as a potential prognostic biomarker of TC. It not only plays a decisive role in the initiation and development of TC, but also provides a new perspective for understanding the modification of m6A RNA in TC.

Clinical applications of measurable residual disease monitoring by multi-parametric flow cytometry and next-generation sequencing in B-cell precursor acute lymphoblastic leukemia.

121 Background: Minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The most frequently used methods for MRD monitoring include multi-parametric flow cytometry (MFC) and next-generation sequencing (NGS)-based IGH/IGK gene rearrangement. Both methods have been described to reach a low sensitivity threshold and be broadly applicable to most patients with BCP-ALL, although the clinical MRD cut-off of the two methods has not been fully defined. In this study, we compared MFC-MRD and NGS-MRD and established their clinical cut-off in BCP-ALL. Methods: Bone marrow aspirates with less than 5% blasts were obtained from 117 treated BCP-ALL patients. MFC-MRD assessment was performed using DuraClone RE ALB tubes (Beckman Coulter, Marseille, France) modified by adding 5 additional antibodies. In total, up to 1×105 cells were acquired using DxFLEX flow cytometer (Beckman Coulter), and all acquired data were analyzed using the Kaluza software v2.1. NGS-MRD was performed using the LymphoTrack IGH and IGK assay panels (InVivoScribe, San Diego, CA). We amplified 240 ng of high-quality DNA with a single multiplex master mix containing primers, and the library DNA was denatured and loaded onto a Miseq reagent kit v2. The FASTQ files were analyzed using the LymphoTrack MRD software v2.0.2. MRD evaluated using both of MFC and NGS in each sample, and the virtual sensitivity of both methods was 10-5. For 84 patients available, we analyzed the relapse-free survival (RFS) and overall survival (OS) rate for each MRD status and established a clinical cutoff. Results: We found a high correlation between methods (r=0.640) and a concordance rate of 81.2% for detecting MRD at 0.01% level. An MRD value of 0.01% proved to be a significant threshold value for 1-year RFS and OS. There was a difference in prognosis in both RFS and OS, but statistical significance was found only in RFS (MFC-MRD: 93.4±3.2% for MRD &lt;0.01% vs. 37.5±27.3% for MRD ≥0.01%, P=0.007; NGS-MRD: 93.7±3.6% for MRD &lt;0.01% vs. 68.8±14.2% for MRD ≥0.01%, P=0.016). In a Kaplan-Meier estimate of RFS at a threshold of 0.01%, patients who were negative for MRD by MFC and positive by NGS (n=12) had an intermediate prognosis between patients who were negative by both MFC and NGS (n=55) and patients who were positive by both MFC and NGS (n=11) (98.14±3.2%, 83.34±10.8%, 40.94±29.5%, respectively, P=0.017). Conclusions: An MRD threshold of 0.01% for both MFC and NGS is reasonable for clinical identification of poor-risk patients. NGS-MRD detection improves risk stratification for BCP-ALL.

The Prognostic Impact of Log Odds of Positive Lymph Nodes on Survival of Patients With Early-stage Non-small Cell Lung Cancer: A Population Study Based on the Seer Database and a Chinese Cohort

Objective The purpose of this study was to investigate the prognostic value of log odds of positive lymph nodes (LODDS) in patients with early-stage non-small cell lung cancer (NSCLC). Methods Four hundred and eighty-seven NSCLC patients with pT2N0M0 who underwent radical resection from June 1999 to September 2009 at Sun Yat-Sen University Cancer Center and 8,702 patients from the Surveillance, Epidemiology, and End Results (SEER) were reviewed. According to the X-tile analysis, the patients were classified into two groups based on their log odds ratio [≤ –1.40 (group LODDS1) and &gt; –1.40 (group LODDS2)]. Cox univariate and multivariate analyses were used to identify the prognostic factors for survival. Result Patients were divided into two groups according to the value of LODDS: ≤ – 1.40 (group LODDS1) and &gt; – 1.40 (group LODDS2). For the development cohort, the 5-year CSS rate for patients was 79.6% and 69.3% in the group LODDS1 and LODDS2, respectively ( P = .009). For the validation cohort, the 5-year CSS rate was 85.4% for patients in group LODDS1, compared with 82.5% for those in group LODDS2 ( P = .006). In multivariate analysis, LODDS was associated with CSS significantly [hazard ratio (HR), 1.487; 95% confidence intervals (CI), 1.126–1.963] in the development cohort. The HR value of LODDS for CSS was 1.260 (95% CI,1.107–1.434) in the validation cohort. Conclusion LODDS was a strong independent prognostic factor for early-stage NSCLC.

Weight Loss and Disease Progression in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis (P2-8.009)

<h3>Objective:</h3> We studied the association of changes in body mass index (BMI) with disease progression among amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) Multicenter Cohort Study of Oxidative Stress (COSMOS) study participants, prospectively followed up to 24 months. <h3>Background:</h3> Weight loss is a poor prognostic factor in ALS. However, less is known about weight change in PLS. <h3>Design/Methods:</h3> Participants had a confirmed diagnosis of ALS or PLS and completed baseline and at least one follow-up visit. The rate of BMI change (ΔBMI) and total revised ALS functional rating scale change (ΔALSFRS-r) were calculated between baseline and the first follow-up. Correlation between ΔBMI and ΔALSFRS-r were assessed using Pearson correlation among ALS and PLS participants separately. The demographics and proportion of participants with swallowing dysfunction at baseline and significant weight loss were compared between ALS and PLS groups using chi-square test. Cox proportional hazard models examined the association between significant weight loss (ΔBMI&lt;−1kg/m2/year) and survival in ALS, adjusted for other prognostic factors. <h3>Results:</h3> 279 ALS and 37 PLS participants were included. Mean age of ALS and PLS were both 60 years and 61% male. At baseline, swallowing dysfunction was more frequent in the PLS (78% vs 48%, p&lt;0.001) while significant weight loss was more frequent in the ALS (53% vs 19%, p&lt;0.001). ΔBMI and ΔALSFRS-r correlated significantly in ALS (r=0.3, p&lt;0.0001) but not in PLS (r= −0.21, p=0.2). Significant weight loss was associated with increased risk of death (hazard ratio 2.08, p&lt;0.0001) in ALS after adjusting for age, disease-duration, bulbar-onset, diagnostic-certainty, riluzole-intake, forced vital capacity, baseline BMI, baseline ALSFRS-r and ΔALSFRS-r. <h3>Conclusions:</h3> In ALS, significant weight loss is a strong independent prognostic factor for survival and rate of BMI change correlates with faster functional decline. In contrast, significant weight loss is infrequent in PLS despite a high prevalence of swallowing dysfunction. <b>Disclosure:</b> Dr. Lee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Lee has received personal compensation in the range of $0-$499 for serving as a Consultant for Amylyx. Dr. Lee has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron. The institution of Dr. Lee has received research support from Myasthenia Gravis Foundation of America. The institution of Dr. Lee has received research support from CReATe consortium/American Brain Foundation. Dr. Mitsumoto has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Pam Factor-Litvak has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ICF. Pam Factor-Litvak has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Publishing. The institution of Pam Factor-Litvak has received research support from NIH. Prof. Nieves has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Bone Health and Osteoporosis Foundation. The institution of Prof. Nieves has received research support from Radius Pharmaceuticals. Prof. Nieves has received personal compensation in the range of $0-$499 for serving as a DSMB member with NIH.

Evaluating the Correlation of Mortality and Biochemical Parameters in Community-acquired and Hospital-acquired Pneumonia

Objective: The associations of inflammation and immunity of host lead to higher mortality in both community-acquired and hospital-acquired pneumonia patients. Therefore, several inflammatory and immunological biomarkers are essential for diagnosis, prognosis, and survival. Among these inflammatory markers, such as older age, and higher blood urea nitrogen, creatinine, procalcitonin and C-reactive protein, and lower albumin levels have been shown to have strong correlations with worse outcomes and high mortality, especially in community-acquired pneumonia patients. In this study, we investigated the correlation between several biochemical markers, which are mostly involved in inflammation, and mortality in not only community-acquired but also hospital-acquired pneumonia patients. Material and Methods: This was a retrospective study of hospitalized community-acquired and hospital-acquired pneumonia patients in a third degree university hospital. In their initial blood tests (also used for diagnosis), blood urea nitrogen, creatinine, procalcitonin, C-reactive protein and albumin levels, and white blood cell, lymphocyte, neutrophil, platelet and erythrocyte counts, red blood cell distribution width and hemoglobin levels were measured. The outcome variable was mortality at 30 days. Statistical analysis included univariate comparisons of continuous variables between deceased and survivor groups, subject to mortality analysis and logistic regression in both community-acquired and hospital-acquired pneumonia patients. Results: 272 hospitalized community-acquired and 80 hospital-acquired pneumonia patients were included. Patients who died during follow-up had older age and higher levels of procalcitonin, blood urea nitrogen, creatinine, and red blood cell distribution width in community-acquired pneumonia group. Remarkably, logistic regression analysis showed a significant relationship between creatinine and mortality, regardless of age, severity of community-acquired pneumonia and comorbidities. Creatinine is a strong independent prognostic factor, subject to mortality in community-acquired pneumonia group. Conclusions: Older age, higher procalcitonin, blood urea nitrogen, creatinine and red blood cell distribution width levels are significant biomarkers for prediction of higher mortality in hospitalized community-acquired pneumonia patients.

Necrosis as a strong independent prognostic factor required in the implementation of pathological reporting for pancreatic adenocarcinoma resection specimens

IntroductionPancreatic ductal adenocarcinoma (PDAC) is a major public health issue with an incidence/mortality ratio reaching 98 %. Only 15–20 % of patients with PDAC can undergo surgery. Following PDAC surgical resection, 80 % of patients will experience local or metastatic recurrence of this disease. pTNM staging is the gold standard for risk stratification but is not sufficient to recapitulate the prognosis. Several prognostic factors are known to impact survival after surgery when uncovered during pathological examination. However, necrosis has been poorly studied in pancreatic adenocarcinoma. Materials & methodsWe retrieved clinical data and reviewed all tumor slides from patients who had a pancreatic surgery between January 2004 and December 2017, in the Hospices Civils de Lyon, to assess the presence of histopathological prognosis factors associated with poor prognosis. Results514 patients with complete clinico-pathological description were included. Necrosis was found in 231 PDAC (44.9 %) and had an important impact on overall survival with a double risk of death when present in tumor samples (HR: 1.871, 95 % CI [1.523; 2.299], p < 0.001). When integrated in the multivariate model, necrosis is the only morphological aggressive feature to retain high statistical significance associated with the TNM staging but independently of it. This effect is independent of the preoperative treatment. ConclusionsDespites improvement in treatment of PDAC, mortality rates remain relatively stable amongst the last years. There is a desperate need to better stratify patients. Here, we report the strong and prognostic impact of necrosis in surgical PDAC samples and encourage pathologists to report its presence in the future.

Occurrence and prognostic significance of different histology relative to urinary tract tumors: A SEER population-based study.

485 Background: To evaluate the prevalence and prognostic value of variant histology in urinary tract tumors according to primary location and metastatic status. Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2015) databases, patients with urinary tract tumors were identified. Propensity Score Matching was used to balance the clinicopathologic features between different histologies. Kaplan-Meier plots were used to compare the cancer specific survival (CSS) and overall survival (OS) of different histologies. The cox regression analysis were also applied. Results: Of all 93,200 eligible patients with urinary tract tumors, 87,323 (93.7%) harbored bladder cancer (3,685 in M1 stage). Among them, urothelial tumors (UC) accounted for 96.67%, followed by squamous neoplasm (SCC), urachal carcinoma (Urachal), adenocarcinoma (Adeno), neuroendocrine tumors (NE) and tumor of Müllerian type (Müllerian). A total of 5877 (6.35%) harbored upper urinary tract tumors (950 in M1 stage). Among them, UC accounted for 96.39%, followed by SCC, Urachal, Müllerian, NE, Adeno. In patients with localized diseases, those with non-urothelial tumors had significantly worse prognosis in overall urinary tract tumors based on OS and CSS (P&lt;0.001). In terms of specific histology in bladder cancer (BC), patients with UC had most favorable prognosis, followed by Adeno, Urachal and Müllerian, while those with SCC and NE were associated with the worst survival outcomes. In patients with upper urinary tract tumors (UUTT), those with Müllerian had the best survival outcomes, followed by UC, while those with NE, Adeno, SCC, and Urachal had relatively worse prognosis. In M1 stage, although there was a statistical difference in OS and CSS between all patients with urothelial and non-urothelial tumors (P&lt;0.001), the 5-year survival rate (3.74%, 2.50%) and 5-year CSM (4.93%, 3.28%) were similar. In metastatic BC, there was no difference in OS among all histology. However, in terms of CSS, significant differences were still observed in patients with different histologies. In metastatic UUTT, no difference in survival was found among different histologies. After PSM, the similar results were observed in BC, while there is no statistical difference of survival among different histologies in UUTT, no matter the M stage. Cox analyses revealed that primary location, histology type, surgery, chemotherapy and M stage were the common and strong independent prognostic factors in both BC and UUTT. Conclusions: In urinary tract tumors, the incidence of different histology types between BC and UUTT is roughly similar. Overall, patient with variant histology have a worse prognosis than those with urothelial carcinoma. However, differences in survival among the histology types vary by primary location and metastatic status, especially the metastatic status.