Independent Survival Research Articles

Lymph node ratio as a survival predictor for head and neck squamous cell carcinoma with multiple adverse pathological features.

The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features. In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled. The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016). For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR.

Determinants of overall survival (OS) of elderly patients with multiple myeloma: A National Cancer Database (NCDB) analysis of years 2004-2017.

e20035 Background: The survival of older adults with multiple myeloma (MM) continues to improve due to advancements in therapy but there is limited real-world data around the outcome of elderly (≥ 75 years old) MM patients. These patients are at risk due to comorbidities, frailty and potential for reduced tolerance to treatment. In this IRB approved retrospective analysis, the NCDB was used to evaluate the 30-day mortality and the determinants of overall survival (OS) of elderly MM patients who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 54,766 patients ≥ 75 years old diagnosed and treated for MM from 2004 to 2017. Multivariable cox regression analysis with backward elimination was utilized to identify the independent survival factors, using significance level of p < 0.05. Kaplan-Meier survival curves were produced, and SAS version 9.4 was used to analyze the data. Results: Overall median survival time was 23 months; while survival rates of 1, 3, and 5-year were 61.9%, 38.0%, and 23.6%, respectively. Multivariable cox regression analysis with backward elimination method revealed that there were 10 significant independent survival factors including age, sex, race, ethnicity, education level, Charlson-Deyo score, facility type, median income, year of diagnosis, and treatment-regimen. Male patients were more likely to die compared to female patients (HR = 1.08, p < 0.0001). Black patients were predicted to have less death events compared to White patients (HR = 0.90, p < 0.0001). In addition to that, patients of Hispanic ethnicity were more likely to die compared to non-Hispanic patients (HR = 1.16, p < 0.0001). Subjects who were treated in non-academic facilities were more likely to suffer death compared to the ones who received care in academic centers (HR = 1.15, p < 0.0001). Patients with median income < $38,000 (HR = 1.10, p < 0.0001), $38,000-$47,999 (HR = 1.06, p = 0.0011) and $48,000-$62,999 (HR = 1.04, p = 0.0031) were more likely to die compared to patients with higher median income ≥ $63,000. The hematopoietic stem cell transplantation utilization rate was 0.1%. The 30-day mortality rate was 8%. Detailed analysis will be presented. Conclusions: This large real-world analysis of elderly MM patients shows that White and Hispanic patients have inferior OS compared to Blacks and non-Hispanics. Patients with lower economic status and those treated at a non-academic facility also had inferior survival compared to those with higher income and with access to care at an academic facility. The 30-day mortality is strikingly high (8%) in the elderly. The unacceptably high mortality could be improved by facilitating access to high quality care and prompt use of novel agents. Prospective studies are needed to identify and address determinants of disparity in MM care in elderly patients.

Racial disparities in the treatment of unresectable, stage III non-small cell lung cancer: An analysis of the National Cancer Database.

e20560 Background: The standard of care (SOC) for treatment of unresectable, stage III non-small cell lung carcinoma (NSCLC) utilizes both chemotherapy and radiation therapy. Historically, concurrent chemo-radiation therapy (CCRT) has been associated with improved survival outcomes compared to sequential chemotherapy and radiation therapy (SCRT). Using data extracted from the National Cancer Database (NCDB). Our primary objective was to assess if a particular race cohort received less than the standard of care treatment (CCRT) and any impact on survival outcomes in unresectable, stage III NSCLC. Methods: From the complete dataset years of 2010-2016 of the NCDB, we extracted patients diagnosed with stage III NSCLC according to the AJCC 7th edition. Patients were classified according to the treatments received and include CCRT, SCRT, radiotherapy alone (RT), chemotherapy alone (CT) and no treatment. Chi-square test was performed to evaluate the baseline sociodemographic and clinico-pathologic categorical characteristics between the different treatment arms. Multivariable Cox regression analysis was utilized to identify the independent survival factors. In addition, Kaplan-Meier survival curves for different treatments in White and Black patients were evaluated. Multinominal logistic regression analysis was utilized to establish association of different treatment modalities with race. SAS version 9.4 was used to analyze the data. Results: There was 52,677 patient who met inclusion criteria. Multinominal logistic regression revealed that Black patients were 21% more likely to receive CT alone than standard CCRT compared to White patients (p < 0.0001, OR 1.21 and CI 1.10-1.32). In addition, Black patients were 27% more likely to receive RT alone than standard CCRT compared to White patients (OR = 1.27 and CI 1.13-1.42 and p < 0.0001). There was no statistically significant difference between the use of CCRT vs. SCRT among White and Black patients. Based on Kaplan-Meier survival curves, CCRT and SCRT were found to have superior median overall survival (mOS) in both Black patients (23 month for CCRT and 19 month for SCRT) and White patients (19 month for both) compared to other treatment modalities (P < 0.001). Multivariable Cox regression analysis method revealed that there were several significant independent survival factors, such as age, Charlson-Deyo Score (CDS), histologic grade, insurance status, stage, and race. Conclusions: The use of either CCRT or SCRT was associated with improved overall survival in both Black and White patients with unresectable, stage III NSCLC compared to other treatment modalities. Interestingly, Black patients appear to benefit more from CCRT than SCRT compared to White patients. However, Black patients were less likely to receive standard CCRT and more likely to receive less effective RT or CT alone compared to White patients.

Survival outcomes, clinical features and treatment patterns of solitary plasmacytoma in the United States: A National Cancer Database (NCDB) analysis of years 2004-2017.

e20060 Background: Due to its rarity, comprehensive studies on plasmacytoma are limited. There are two main subtypes: solitary bone plasmacytoma (P-Bone) and extramedullary plasmacytoma (P-EM). In this IRB approved retrospective analysis, the NCDB was used to evaluate the clinical features and factors affecting the overall survival of patients with plasmacytoma who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 6,579 patients with plasmacytoma from 2004 to 2017, after excluding multiple myeloma patients. N = 4,816 patients had P-Bone & N = 1,763 patients had P-EM. Descriptive statistics were used and multivariable cox regression analysis was utilized to identify the independent survival factors, using significance level of p < 0.05. Kaplan-Meier curves were produced. SPSS was used to analyze the data. Results: P-Bone represented 73.2% of cases. Overall median survival time was 105 and 147 months for P-Bone and P-EM respectively; 56 and 149 months for < 37 Gy and ≥ 37 Gy radiation dose respectively; 66, 112, 107 and 132 months for no treatment, surgery alone, radiation therapy alone and combination therapy (surgery + radiation) respectively. Multivariable cox regression revealed that there were 10 significant independent survival factors including age, ethnicity, facility type, insurance status, median income, education level, Charlson-Deyo score, year of diagnosis, plasmacytoma site and treatment pattern. Patients with P-EM were less likely to die compared to P-Bone (HR = 0.734, p < 0.001). Hispanic patients were less likely to die compared to non-Hispanics (HR = 0.66, p < 0.001). In addition to that, patients with private insurance were less likely to suffer death compared to patients with no insurance (HR = 0.71, p = 0.01). Subjects who were treated in academic facilities were less likely to die compared to the ones who received care in non-academic centers (HR = 0.86, p < 0.001). Moreover, patients with median income ≥ $63,000 were less likely to die compared to patients with median income < $38,000 (HR = 0.85, p = 0.04). Subjects with higher level of education (no high school diploma in < 7%) were less likely to suffer death compared to subjects with lower level of education (no high school diploma in ≥ 21%) (HR = 0.82, p = 0.018). Patients who were treated with radiation alone (HR = 0.54, p < 0.001), surgery alone (HR = 0.57, p < 0.001), and combination therapy (HR = 0.43, p < 0.001) were less likely to die compared to patients who did not receive any treatment. Detailed analysis will be presented. Conclusions: In this largest real-world plasmacytoma cohort ever reported, we found that patients with P-Bone and those with lower socio-economic status had worse outcomes. In addition use of combination therapy and the use of a higher radiation dose ≥ 37 Gy were associated with better outcomes.

Determinants of overall survival of young adults with multiple myeloma: A National Cancer Database (NCDB) analysis of years 2004-2017.

8052 Background: There is paucity of real-world data on the outcomes of younger patients with multiple myeloma (MM). In this IRB approved retrospective analysis, the NCDB was used to evaluate the determinants of overall survival (OS) of young adults ≤ 50 years with MM who were treated at commission on cancer (CoC) accredited facilities across the USA. Methods: Using the NCDB, we identified N = 16,792 patients ≤ 50 years old diagnosed and treated for MM from 2004 to 2017. Multivariable cox regression analysis with backward elimination was utilized to identify the independent survival factors, using significance level of p < 0.05. Kaplan-Meier survival curves were generated and SAS version 9.4 was used to analyze the data. Results: Overall median survival time was 119 months; while survival rates of 1, 3, and 5-year were 90.6%, 78.0%, and 67.8%, respectively. Multivariable cox regression analysis with backward elimination method revealed that there were 13 significant independent survival factors: age, sex, race, ethnicity, Charlson-Deyo score, insurance status, facility type, median income, education level, distance to facility, year of diagnosis, hematopoietic stem-cell transplantation (HSCT), and treatment-regimen. Male patients were more likely to die compared to female patients (HR = 1.22, p < 0.0001). Black patients were predicted to have less death events compared to White patients (HR = 0.91, p = 0.004). In addition to that, Hispanic patients were more likely to die compared to non-Hispanics (HR = 1.2, p = 0.0006). Subjects who were treated in non-academic facilities were more likely to die compared to the ones who received care in academic centers (HR = 1.2, p < 0.0001). Moreover, patients with Medicare (HR = 1.65, p < 0.0001), Medicaid (HR = 1.49, p < 0.0001), and no insurance (HR = 1.63, p < 0.0001) had higher chance of death compared to those with private insurance. Patients with lower income < $38,000 were more likely to die compared to income ≥ $63,000 (HR = 1.19, p = 0.0007). Only 6.8% of patients underwent HSCT and 93.2% did not. Patients undergoing HSCT had worse OS compared to those treated without HSCT (HR = 0.36, p < 0.0001). Detailed analysis will be presented. Conclusions: In this large cohort of real-world data analysis of very young MM patients, we found that White and Hispanic patients age ≤ 50 years had significantly inferior survival compared to Black and non-Hispanic patients. Patients with lower income, lower education level, non-private insurance, and those without access to academic centers for MM care had worse survival outcomes. The findings can be useful for designing prospective studies addressing disparity and equitable access to MM care. Despite being a pivotal part of MM therapy, HSCT utilization in the real-world setting is minimal. The barriers to HSCT utilization and the reason why it is inferior to no-HSCT in real-world setting need to be identified and addressed.

Preoperative neurocognitive function as an independent survival prognostic marker in primary glioblastoma.

Aim of the present study is to investigate whether preoperative neurocognitive status is prognostically associated with overall survival (OS) in newly diagnosed glioblastoma (GBM) patients. Ninety patients with dominant-hemisphere IDH-wild-type GBM were assessed by Mini Mental Status Exam (MMSE), Trail Making Test (TMT) A and B parts, and Control Word Association Test (COWAT) phonemic and semantic subtests. Demographics, Karnofsky Performance Scale, tumor parameters, type of surgery, and adjuvant therapy data were available for patients. According to Cox proportional hazards model the neurocognitive variables of TMT B (P < .01), COWAT semantic subset (P < .05), and the MMSE (P < .01) were found significantly associated with survival prediction. From all other factors, only tumor volume and operation type (debulking vs biopsy) showed a statistical association (P < .05) with survival prediction. Kaplan Meier Long rank test showed statistical significance (P < .01) between unimpaired and impaired groups for TMT B, with median survival for the unimpaired group 26 months and 10 months for the impaired group, for COWAT semantic (P < .01) with median survival 23 months and 12 months, respectively and for MMSE (P < .01) with medial survival 19 and 12 months respectively. Our study demonstrates that neurocognitive status at baseline-prior to treatment-is an independent prognostic factor for OS in wild-type GBM patients, adding another prognostic tool to assist physicians in selecting the best treatment plan.

Prognostic analysis and clinical characteristics of osteosarcoma and Ewing sarcoma of the rib, sternum, and clavicle: a SEER-based study

Osteosarcoma and Ewing sarcoma of the rib, sternum, and clavicle are rare tumor entities, and their clinical features and treatment outcomes have been rarely reported. The present study was performed to evaluate their survival and confirm independent survival predictors. Data on patients with osteosarcoma or Ewing sarcoma of the rib, sternum, and clavicle from 1973 to 2016 were retrospectively extracted from the database. Univariate and multivariate Cox regression analyses were used to determine the independent risk factors. Kaplan-Meier survival curves were applied to examine the prognostic difference between the groups. In total, 475 patients with osteosarcoma or Ewing sarcoma of the rib, sternum, and clavicle were eligible for this study, including 173 (36.4%) with osteosarcoma and 302 (63.6%) with Ewing sarcoma. The 5-year overall survival and cancer-specific survival rates of all patients were 53.6% and 60.8%, respectively. Six independent variables were identified, including age at diagnosis, sex, histological grade, metastatic status, tumor type, and surgery. Surgical resection is a reliable treatment for osteosarcoma and Ewing sarcoma of the rib, sternum, and clavicle. Further research is needed to reconfirm the role of chemotherapy and radiotherapy in survival of these patients.

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

The defense response is a type of self-protective response of the body that protects it from damage by pathogenic factors. Although these reactions make important contributions to the occurrence and development of tumors, the role they play in osteosarcoma (OS), particularly in the immune microenvironment, remains unpredictable. This study included the clinical information and transcriptomic data of 84 osteosarcoma samples and the microarray data of 12 mesenchymal stem cell samples and 84 osteosarcoma samples. We obtained 129 differentially expressed genes related to the defense response (DRGs) by taking the intersection of differentially expressed genes with genes involved in the defense response pathway, and prognostic genes were screened using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression and multivariate Cox regression were then used to establish a DRG prognostic signature (DGPS) via the stepwise method. DGPS performance was examined using independent prognostic analysis, survival curves, and receiver operating characteristic (ROC) curves. In addition, the molecular and immune mechanisms of adverse prognosis in high-risk populations identified by DGPS were elucidated. The results were well verified by experiments. BNIP3, PTGIS, and ZYX were identified as the most important DRGs for OS progression (hazard ratios of 2.044, 1.485, and 0.189, respectively). DGPS demonstrated outstanding performance in the prediction of OS prognosis (area under the curve (AUC) values of 0.842 and 0.787 in the training and test sets, respectively, adj-p < 0.05 in the survival curve). DGPS also performed better than a recent clinical prognostic approach with an AUC value of only 0.674 [metastasis], which was certified in the subsequent experimental results. These three genes regulate several key biological processes, including immune receptor activity and T cell activation, and they also reduce the infiltration of some immune cells, such as B cells, CD8+ T cells, and macrophages. Encouragingly, we found that DGPS was associated with sensitivity to chemotherapeutic drugs including JNK Inhibitor VIII, TGX221, MP470, and SB52334. Finally, we verified the effect of BNIP3 on apoptosis, proliferation, and migration of osteosarcoma cells through experiments. This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

Prognostic and Immunological Significance of the Molecular Subtypes and Risk Signatures Based on Cuproptosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a challenging medical problem. Cuproptosis is a novel form of cell death that plays a crucial role in tumorigenesis, angiogenesis, and metastasis. However, it remains unclear whether cuproptosis-related genes (CRGs) influence the outcomes and immune microenvironment of HCC patients. From The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we obtained the mRNA expression file and related clinical information of HCC patients. We selected 19 CRGs as candidate genes for this study according to previous literature. We performed a differential expression analysis of the 19 CRGs between malignant and precancerous tissue. Based on the 19 CRGs, we enrolled cluster analysis to identify cuproptosis-related subtypes of HCC patients. A prognostic risk signature was created utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. We employed independent and stratification survival analyses to investigate the predictive value of this model. The functional enrichment features, mutation signatures, immune profile, and response to immunotherapy of HCC patients were also investigated according to the two molecular subtypes and the prognostic signature. We found that 17 CRGs significantly differed in HCC versus normal samples. Cluster analysis showed two distinct molecular subtypes of cuproptosis. Cluster 1 is preferentially related to poor prognosis, high activity of immune response signaling, high mutant frequency of TP53, and distinct immune cell infiltration versus cluster 2. Through univariate and LASSO Cox regression analyses, we created a cuproptosis-related prognostic risk signature containing LIPT1, DLAT, MTF1, GLS, and CDKN2A. High-risk HCC patients were shown to have a worse prognosis. The risk signature was proved to be an independent predictor of prognosis in both the TCGA and ICGC datasets, according to multivariate analysis. The signature also performed well in different stratification of clinical features. The immune cells, which included regulatory T cells (Treg), B cells, macrophages, mast cells, NK cells, and aDCs, as well as immune functions containing cytolytic activity, MHC class I, and type II IFN response, were remarkably distinct between the high-risk and low-risk groups. The tumor immune dysfunction and exclusion (TIDE) score suggested that high-risk patients had a higher response rate to immune checkpoint inhibitors than low-risk patients. This research discovered the potential prognostic and immunological significance of cuproptosis in HCC, improved the understanding of cuproptosis, and may deliver new directions for developing more efficacious therapeutic techniques for HCC patients.

FBXW7 loss of function promotes esophageal squamous cell carcinoma progression via elevating MAP4 and ERK phosphorylation

BackgroundIncreasing evidence suggests that FBXW7 has a high frequency of mutations in esophageal squamous cell carcinoma (ESCC). However, the function of FBXW7, especially the mutations, is not clear. This study was designed to investigate the functional significance of FBXW7 loss of function and underlying mechanism in ESCC.MethodsImmunofluorescence was applied to clarify the localization and main isoform of FBXW7 in ESCC cells. Sanger sequencing were performed to explore mutations of FBXW7 in ESCC tissues. Proliferation, colony, invasion and migration assays were performed to examine the functional roles of FBXW7 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, GST-pulldown, LC–MS/MS and co-immunoprecipitation assay were used to explore the molecular mechanism underlying the actions of FBXW7 functional inactivation in ESCC cells. Immunohistochemical staining were used to explore the expression of FBXW7 and MAP4 in ESCC tissues.ResultsThe main FBXW7 isoform in ESCC cells was the β transcript in the cytoplasm. Functional inactivation of FBXW7 led to activation of the MAPK signaling pathway and upregulation of the downstream MMP3 and VEGFA, which enhanced tumor proliferation cell invasion and migration. Among the five mutation forms screened, S327X (X means truncated mutation) had an effect similar to the FBXW7 deficiency and led to the inactivation of FBXW7 in ESCC cells. Three other point mutations, S382F, D400N and R425C, attenuated but did not eliminate FBXW7 function. The other truncating mutation, S598X, which was located outside of the WD40 domain, revealed a tiny attenuation of FBXW7 in ESCC cells. Notably, MAP4 was identified as a potential target of FBXW7. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system. Immunohistochemical staining indicated that FBXW7 loss of function was associated with tumor stage and shorter survival of patients with ESCC. Univariate and multivariate Cox proportional hazards regression analyses showed that high FBXW7 and low MAP4 was an independent prognostic indicator and prospective longer survival. Moreover, a combination regimen that included MK-8353 to inhibit the phosphorylation of ERK and bevacizumab to inhibit VEGFA produced potent inhibitory effects on the growth of FBXW7 inactivation xenograft tumors in vivo.ConclusionsThis study provided evidence that FBXW7 loss of function promoted ESCC via MAP4 overexpression and ERK phosphorylation, and this novel FBXW7/MAP4/ERK axis may be an efficient target for ESCC treatment.

Risk Factors for Cytomegalovirus Infection and Its Impact on Survival after Living Donor Liver Transplantation in South Korea: A Nested Case-Control Study.

Cytomegalovirus (CMV), a common pathogen, causes infectious complications and affects long-term survival after transplantation. Studies examining living donor liver transplantation (LDLT) are limited. This study analyzed the risk factors for CMV infection and its impact on the survival of LDLT patients. A nested case-control design retrospectively analyzed data from 952 patients who underwent LDLT from 2005-2021. The incidence of CMV infection for the study cohort was 15.2% at 3 months for LDLT patients managed preemptively. Patients with CMV infections were matched with those without the infection at corresponding time points (index postoperative day) in a 1:2 ratio. Graft survival was significantly lower in the CMV infection group than in the control group. CMV infection was an independent risk factor for graft survival in the matched cohort (HR 1.93, p = 0.012). Independent risk factors for CMV infection were female sex (HR 2.4, p = 0.003), pretransplant MELD (HR 1.06, p = 0.004), pretransplant in-hospital stay (HR 1.83, p = 0.030), ABO incompatibility (HR 2.10, p = 0.009), donor macrovesicular steatosis ≥10% (HR 2.01, p = 0.030), and re-operation before index POD (HR 2.51, p = 0.035). CMV infection is an independent survival risk factor, and its risk factors should be included in the surveillance and treatment of CMV infections after LDLT.

Prognostic Value of Radiomics Analysis of Skeletal Muscle After Radical Irradiation of Esophageal Cancer.

Sarcopenia is an independent survival predictor in several tumor types. Computed tomography (CT) is the standard measurement for body composition assessment. Radiomics analysis of CT images allows for the precise evaluation of skeletal muscles. This study aimed to construct a prognostic survival model for patients with esophageal cancer who underwent radical irradiation using skeletal muscle radiomics. We retrospectively identified patients with esophageal cancer who underwent radical irradiation at our institution between April 2008 and December 2017. Skeletal muscle radiomics were extracted from an axial pretreatment CT at the third lumbar vertebral level. The prediction model was constructed using machine learning coupled with the least absolute shrinkage and selection operator (LASSO). The predictive nomogram model comprised clinical factors with radiomic features. Three prediction models were created: clinical, radiomics, and combined. Ninety-eight patients with 98 esophageal cancers were enrolled in this study. The median observation period was 57.5 months (range=1-98 months). Thirty-five radiomics features were selected by LASSO analysis, and a prediction model was constructed using training and validation data. The average of the accuracy, specificity, sensitivity, and area under the concentration-time curve for predicting survival in esophageal cancer in the combined model were 75%, 92%, and 0.86, respectively. The C-indices of the clinical, radiomics, and combined models were 0.76, 0.80, and 0.88, respectively. A prediction model with skeletal muscle radiomics and clinical data might help determine survival outcomes in patients with esophageal cancer treated with radical radiotherapy.

Comparison of Four Albumin-Based Liver Reserve Models (ALBI/EZ-ALBI/PALBI/PAL) against MELD for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

(1) Background: The severity of liver functional reserve plays an important role in the management of hepatocellular carcinoma (HCC). Noninvasive models such as the model for end-stage liver disease (MELD), albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade, platelet-albumin-bilirubin (PALBI) and platelet-albumin (PAL) are used to evaluate liver dysfunction. We aimed to compare the prognostic performance of these four albumin-based models against MELD in HCC patients undergoing transarterial chemoembolization (TACE). (2) Methods: A total of 1038 treatment naïve HCC patients who received TACE as the primary treatment were enrolled. A multivariate Cox model was used to determine independent survival predictors. (3) Results: Multivariate analysis revealed that higher serum creatinine and α-fetoprotein level, vascular invasion, large tumor size, ALBI grades 2-3, EZ-ALBI grades 2-3, PALBI grades 2-3, PAL grades 2-3, but not the MELD score, were independent predictors associated with decreased survival in different Cox models. Among these models, the PALBI grade had the highest homogeneity and lowest corrected Akaike information criteria value, followed by EZ-ALBI, PAL, ALBI and, lastly, MELD. (4) Conclusions: All four albumin-based liver reserve models are better prognostic tools than MELD score in HCC patients undergoing TACE. Of these, the PALBI score is the best model to evaluate the liver reserve and should be considered a surrogate marker in these patients.

Abstract P6-04-15: AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas

Abstract Introduction Tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs) in breast carcinomas are prognostic for survival and predictive of certain therapy responses. The presence of TLSs and TILs are identified by manual pathological examination; however, this method often lacks reproducibility, limiting its use in routine clinical practice. Here, we demonstrate that morphological evaluation of whole slide images (WSIs) using an artificial intelligence (AI)-based analytic workflow comprised of convolutional neural network (CNN) deep learning models that accurately and reproducibly characterizes TILs, measured as the lymphocyte immune-infiltrated area (LIIA), and TLSs in the tumor microenvironment (TME) of breast carcinomas. Methods We collected a cohort of 445 TCGA breast cancer H&amp;E WSIs, including clinical and sequencing data, and divided this cohort into luminal invasive lobular carcinoma (ILC) (n = 192), HER2-enriched (n = 110), and basal-like (n = 143) molecular subtypes. After 55 samples were excluded due to artifacts or incomplete clinical annotation, a total of 390 samples were analyzed. A combination of CNN-based deep learning models was used to detect and classify the tumor area, TLSs present in the TME, TLS density (number of TLS per mm2 of tumor), and lymphocyte-rich regions. The LIIA was calculated as the area of the stromal and TIL components of the TME. Validation was performed by manually annotating 10 random WSIs from the dataset. Spatial model predictions of the tumor and TLSs were combined to identify TLS locations. Each model’s predictions were verified by univariate (Kaplan-Meier) and multivariate (Cox regression) survival analyses, and the log-rank test was used to calculate overall survival. Additionally, the relationship between TLSs and LIIAs with CD274 expression (PD-L1) and a high tumor mutational burden (TMB &amp;gt; 10) was analyzed. Statistical analyses included Spearman’s rank correlation and Mann-Whitney tests. Results TLS were detected in 53% (n = 207) of the samples, with a mean density of 26.02 TLS/mm2 (Q3 = 5.53 TLS/mm2). TLS density was higher in basal-like subtype samples compared to luminal and HER2-enriched subtypes. While LIIA and TMB-high samples exhibited a significant relationship (p = 0.00001), no significant association was found between TME and TLS quantities or density. PD-L1 gene expression exhibited weak to moderate correlations with predicted LIIA in basal-like (r = 0.38, p = 0.00001) and HER2-enriched subtypes (r = 0.38, p = 0.0001). The luminal subtype had no significant correlation between PD-L1 expression and predicted LIIA. As a result, LIIA and TLS were characterized as positive prognostic factors for the basal-like subtype. After adjusting for age, stage, and grade, the LIIA and TLS density were found to be significant independent positive prognostic overall survival factors for the basal-like subtype (LIIA HR: 0.02, p = 0.003; TLS-high group HR: 0.09, p = 0.002). For the HER2-enriched subtype, TLS density was also a significant predictor (HR: 0.05, p = 0.035), while LIIA was not a statistically significant prognostic factor (HR: 0.0002, p = 0.08). Associations were not observed between the TLSs and LIIA between the ILC subtypes and survival outcomes. The same result was observed for univariate analyses. Conclusion The developed analytic pipeline accurately identified the presence of LIIA and TLS on H&amp;E slides, demonstrating the potential of CNN for automated characterization of the breast cancer TME. AI-based TLS and LIIA quantification can be a robust tool for pathology processes, offering additional information to help in clinical decision-making. This approach can be used to detect features of immune morphology biomarkers in other cancer types. Citation Format: Vladimir Kushnarev, Daniil Dymov, Nadezhda Lukashevich, Lev Popyvanov, Anna Belozerova, Diana Shamsutdinova, Aida Akaeva, Yury Popov, Svetlana Khorkova, Ivan Valiev, Anastasia Zotova, Jessica H. Brown, Anna Love, Alexander Bagaev, Ekaterina Postovalova, Nathan Fowler. AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-15.

Survival Status and Predictors of Mortality Among Women with Uterine Rupture at Public Hospitals of Eastern Ethiopia. Semi-Parametric Survival Analysis.

Uterine rupture is the most dangerous complication of labor and contributes to high maternal mortality. Despite efforts to improve basic and comprehensive emergency obstetric treatment, women continue to suffer from disastrous maternal outcomes. This study aimed to assess the survival status and predictors of mortality among women with uterine rupture at public hospitals in the Harari Region, Eastern Ethiopia. We conducted a retrospective cohort study among women with uterine rupture in public hospitals in Eastern Ethiopia. All women with uterine rupture were followed for 11 years retrospectively. Statistical analysis was conducted with STATA version 14.2. Kaplan-Meier curves together with a Log rank test were used to estimate the survival time and show the presence of differences among groups. Cox Proportion Hazard (CPH) model was used to determine the association between independent variables and survival status. There were 57,006 deliveries in the study period. We found that 10.5% (95% CI: 6.8-15.7) of women with uterine rupture have died. The median recovery and death time for women with uterine rupture were 8 and 3 days with interquartile range (IQR) of 7-11 days and 2-5 days, respectively. Antenatal care follow-up (AHR: 4.2, 95% CI: 1.8-9.79), education status (AHR: 0.11; 95% CI: 0.02-0.85), visiting health center (AHR: 4.89; 95% CI: 1.05-22.88), and admission time (AHR: 4.4; 95% CI: 1.89-10.18) were the predictors of survival status of women with uterine rupture. One out of ten study participants died due to uterine rupture. Factors including not having ANC follow-up, visiting health centers for treatment, and being admitted during the night time were predictors. Thus, a great emphasis has to be given to the prevention of uterine rupture and the linkage within health institutions has to be smooth to improve the survival of patients with uterine rupture with the help of different professionals, health institutions, health bureaus, and policymakers.

The inflammatory-nutritional score and nomogram for R0 resected head and neck soft tissue sarcoma.

To explore the predictive value of inflammatory-nutritional score (INS) and a nomogram for survivals in head and neck soft tissue sarcoma (HNSTS) patients with negative resection margins (R0). Clinical characteristics and hematological features of 315 HNSTS patients underwent R0 surgery were analyzed. The 5-year overall survival (OS) rate, 3-year recurrence-free survival rate and disease-free survival (DFS) rate were 77.3%, 61.0% and 55.4%, respectively. High INS was associated with a deep tumor location (p < 0.001), high tumor grade (p < 0.001), and advanced AJCC stage (p < 0.001). The low-risk group (INS 0) exhibited a higher 5-year OS rate and 3-year DFS rate than others (87.6% vs. 81.3% vs. 53.3%, p < 0.001; 62.2% vs. 56.9% vs. 37.9%, p=0.007). The INS (p=0.023), tumor depth (p < 0.001), pT classification (p=0.022), pN classification (p < 0.001) and tumor grade (p < 0.001) were independent survival predictors. Moreover, a novel nomogram for predicting OS was generated and assessed by the concordance index, exhibiting a better performance than the p7TNMG classification alone (p < 0.001). For R0 resected HNSTS patients, the oncological outcomes can be predicted using the INS system and a specific nomogram.

Age independent survival benefit for patients with small hepatocellular carcinoma undergoing percutaneous cryoablation: A propensity scores matching study.

Hepatocellular carcinoma (HCC) is the major cause of malignancy-related deaths worldwide, and its incidence is likely to increase in the future as life expectancy increases. Therefore, the management of elderly patients with HCC has become a global issue. Aim of this study was to assess whether elderly patients with small HCC could obtain survival benefit from cryoablation (CRYO) in a real-world. From July 2007 to June 2013, 185 patients with small HCC who underwent curative-intent percutaneous CRYO. All patients were divided into three groups according to age distribution. Overall survival (OS) and tumor-free survival (TFS) were compared between among of groups before and after the 1:1 propensity score matching, respectively. Univariate and multivariate Cox analyses were performed to determine the potential relationships between variables and prognostic outcomes. One hundred and eighty-five patients (144 men, 41 women) received CRYO for small HCC, including 59 patients with age <50 years, 105 patients with age between 50 and 65 years, and 21 patients with age >65 years. The three age groups showed significant differences in the terms of underlying chronic liver disease and the number of patients with minor postoperative complications. After propensity score matching, the younger and elderly groups showed significant differences in mean OS (P=0.008) and tumor progression (P=0.050). However, no significant differences were shown in mean progression-free survival (PFS) (P=0.303). The Cox multivariate analysis showed that the Child-Pugh grade (HR=3.1, P<0.001), albumin (HR=0.85, P=0.004) and total of bilirubin (HR=1, P=0.024) were the independent prognostic factor for mean OS. Our propensity-score-matched study suggested that elderly patients with small HCC can achieve acceptable prognostic outcomes with PFS similar to those of younger patients with small HCC after treatment with CRYO, while Child-Pugh grade, bilirubin and serum albumin levels were associated with the prognosis of small HCCs.

Implant–Prosthetic Rehabilitation of Maxillary Lateral Incisor Agenesis with Narrow Diameter Implants and Metal–Ceramic vs. All-Ceramic Single Crowns: A 16-Year Prospective Clinical Study

The main objectives of the present prospective clinical study were to evaluate the marginal bone resorption and the peri-implant soft tissue conditions around narrow diameter implants, as well as the clinical performances of metal–ceramic and all-ceramic single crowns in the implant–prosthetic treatment of maxillary lateral incisors agenesis. Seventy-two patients affected by monolateral or bilateral agenesis of the maxillary lateral incisors were included in the study, and a total of 105 narrow diameter implants were inserted. The final single crowns were fabricated 4 months after the surgical procedures by means of either titanium abutments with Auro-Galvan Crowns (AGC) veneered with feldspathic ceramics or zirconia abutments with all-ceramic (alumina or zirconia) crowns layered with dedicated veneering ceramics. Both marginal bone resorption and soft tissue quality were evaluated after a maximum period of 16 years. Two independent survival curves for patients wearing AGC or all-ceramic crowns were calculated by means of Kaplan–Meier analysis, and a log-rank test was performed in order to compare these curves (p &lt; 0.05). After 16 years of clinical function, a mean marginal bone resorption of 1.2 ± 0.61 mm and good response of peri-implant soft tissues were observed. Descriptive statistics resulted in 80% and 87.1% cumulative success rates for patients provided with AGC prostheses onto titanium abutments and all-ceramic crowns on-to zirconia abutments, respectively. The cumulative survival rate calculated for AGC group was 93.3%, whereas all-ceramic group showed a cumulative survival rate of 95.7%. No statistically significant differences were found with the log-rank tests. The overall success and survival rates calculated were 85% and 95% for all the restorations, respectively. Mucositis, abutment unscrewing, loss of retention, chipping, core fracture, and esthetic failure were the major complications reported. The implant–prosthetic approach can be considered an effective and viable solution to treat cases of maxillary lateral incisor agenesis in the long term.

Elucidating Analytic Bias Due to Informative Cohort Entry in Cancer Clinico-genomic Datasets.

Oncologists often order genomic testing to inform treatment for worsening cancer. The resulting correlation between genomic testing timing and prognosis, or "informative entry," can bias observational clinico-genomic research. The efficacy of existing approaches to this problem in clinico-genomic cohorts is poorly understood. We simulated clinico-genomic cohorts followed from an index date to death. Subgroups in each cohort who underwent genomic testing before death were "observed." We varied data generation parameters under four scenarios: (i) independent testing and survival times; (ii) correlated testing and survival times for all patients; (iii) correlated testing and survival times for a subset of patients; and (iv) testing and mortality exclusively following progression events. We examined the behavior of conditional Kendall tau (Tc) statistics, Cox entry time coefficients, and biases in overall survival (OS) estimation and biomarker inference across scenarios. Scenario #1 yielded null Tc and Cox entry time coefficients and unbiased OS inference. Scenario #2 yielded positive Tc, negative Cox entry time coefficients, underestimated OS, and biomarker associations biased toward the null. Scenario #3 yielded negative Tc, positive Cox entry time coefficients, and underestimated OS, but biomarker estimates were less biased. Scenario #4 yielded null Tc and Cox entry time coefficients, underestimated OS, and biased biomarker estimates. Transformation and copula modeling did not provide unbiased results. Approaches to informative clinico-genomic cohort entry, including Tc and Cox entry time statistics, are sensitive to heterogeneity in genotyping and survival time distributions. Novel methods are needed for unbiased inference using observational clinico-genomic data.

Effects of wound infection on prognosis after laparoscopic abdominoperineal resection of rectal cancer.

In two facilities in Chongqing, this research sought to retrospectively evaluate the effects of perineal wound infection on survival after laparoscopic abdominoperineal resection (LAPR) of rectal cancer. To obtain clinical information on patients who underwent LAPR between January 2013 and December 2021, we performed a multicenter cohort study. A total of 473 patients were enrolled: 314 in the non-infection group and 159 in the group with perineal infection. The general data, perioperative conditions, and tumor outcomes between groups were analyzed. The infection rates, recurrence rates, and survival rates of the two centers were compared. The age, height, weight, body mass index (BMI), preoperative complications, preoperative treatment, and intraoperative conditions of patients in the LAPR infection group were not statistically different from those in the non-infection group. The percentage of men, typical postoperative hospital stay, length of initial postoperative therapy, and recurrence and metastasis rates were all considerably higher in the infection group than those in the non-infection group. Wound infection was an independent factor affecting tumor recurrence and metastasis after LAPR as well as an independent factor shortening patient survival time according to multivariate analysis. The incidence of wound infection, the rate of recurrence, and the rate of mortality did not vary significantly across sites. Wound infection after LAPR increases the mean postoperative hospital stay, prolongs the time to first postoperative treatment, and decreases the disease-free survival (DFS) and overall survival (OS). Therefore, decreasing the rate of LAPR wound infection is expected to shorten the postoperative hospital stay and prolong the patient DFS and OS. Patients with postoperative infection may require intensive adjuvant therapy.