Prognostic Factor For Poor Survival Research Articles

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.

Patterns of care and survival in patients with multifocal glioblastoma: A Danish cohort study

Abstract Background This Danish cohort study aims to (1) compare patterns of care (POC) and survival of patients with multifocal glioblastoma (mGBM) to those with unifocal glioblastoma (uGBM), and (2) explore the association of patient-related factors with treatment assignment and prognosis, respectively, in the subgroup of mGBM patients. Methods Data on all adults with newly diagnosed, pathology-confirmed GBM between 2015 and 2019 were extracted from the Danish Neuro-Oncology Registry. To compare POC and survival of mGBM to uGBM, we applied multivariable logistic and Cox regression analysis, respectively. To analyze the association of patient-related factors with treatment assignment and prognosis, we established multivariable logistic and Cox regression models, respectively. Results In this cohort of 1343 patients, 231 had mGBM. Of those, 42% underwent tumor resection and 41% were assigned to long-course chemoradiotherapy. Compared to uGBM, mGBM patients less often underwent a partial (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2–0.6), near-total (OR 0.1, 95% CI 0.07–0.2), and complete resection (OR 0.1, 95% CI 0.07–0.2) versus biopsy. mGBM patients were furthermore less often assigned to long-course chemoradiotherapy (OR 0.6, 95% CI 0.4–0.97). Median overall survival was 7.0 (95% CI 5.7–8.3) months for mGBM patients, and multifocality was an independent poor prognostic factor for survival (hazard ratio 1.3, 95% CI 1.1–1.5). In mGBM patients, initial performance, O[6]-methylguanine-DNA methyltransferase promotor methylation status, and extent of resection were significantly associated with survival. Conclusions Patients with mGBM were treated with an overall less intensive approach. Multifocality was a poor prognostic factor for survival with a moderate effect. Prognostic factors for patients with mGBM were identified.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review.

Gastric cancer is the third most common cause of cancer related death worldwide. Surgery with or without chemotherapy is the most common approach with curative intent; however, the prognosis is poor as mortality rates remain high. Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy. The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed. The aim of this systematic review was to assess the role of the prognostic nutritional index (PNI) in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent. To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma. A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival (OS) of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value. The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review. The patients were divided into high- and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study. The 5-year OS of patients in the low-PNI groups ranged between 39% and 70.6%, while in the high-PNI groups, it ranged between 54.9% and 95.8%. In most of the included studies, patients with high preoperative PNI showed statistically significant better OS than the low PNI groups. In multivariate analyses, low PNI was repeatedly recognised as an independent prognostic factor for poor survival. According to the present study, low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

Motor dysfunction as a primary symptom predicts poor outcome: multicenter study of glioma symptoms.

The objectives of this study were to investigate the prognostic value of primary symptoms and leading symptoms in adult patients with diffuse infiltrating glioma and to provide a clinical perspective for evaluating survival. This study included a retrospective cohort from two tertiary university hospitals (n = 604, 2006-2013, Tampere University Hospital and Turku University Hospital) and a prospective cohort (n = 156, 2014-2018, Tampere University Hospital). Preoperative symptoms were divided into primary and leading symptoms. Results were validated with the newer WHO 2021 classification criteria. The most common primary symptoms were epileptic seizure (30.8% retrospective, 28.2% prospective), cognitive disorder (13.2% retrospective, 16.0% prospective), headache (8.6% retrospective, 12.8% prospective), and motor paresis (7.0% retrospective, 7.1% prospective). Symptoms that predicted better survival were epileptic seizure and visual or other sense-affecting symptom in the retrospective cohort and epileptic seizure and headache in the prospective cohort. Predictors of poor survival were cognitive disorder, motor dysfunction, sensory symptom, tumor hemorrhage, speech disorder and dizziness in the retrospective cohort and cognitive disorder, motor dysfunction, sensory symptom, and dizziness in the prospective cohort. Motor dysfunction served as an independent predictor of survival in a multivariate model (OR = 1.636). Primary and leading symptoms in diffuse gliomas are associated with prognoses in retrospective and prospective settings. Motor paresis was an independent prognostic factor for poor survival in multivariate analysis for grade 2-4 diffuse gliomas, especially in glioblastomas.

Comparison of post-hepatectomy long-term survival outcome between non-colorectal non-neuroendocrine and colorectal liver metastases: A population-based propensity-score matching analysis

BackgroundHepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. MethodsFrom 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n ​= ​133) or CLM (n ​= ​831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. ResultsThere were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 ​% vs 1.5 ​%) and morbidity (19.5 ​% vs 20.3 ​%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 ​% vs 39.8 ​%) and recurrence-free (25.1 ​% vs 23.4 ​%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. ConclusionHepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.

[Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma].

To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Only FLT3-ITD Mutation Did Not Have a Deleterious Effect on Acute Myeloid Leukemia Patients with NPM1 Mutation, but Concomitant with DNMT3A Mutation or a＜3log Reduction of MRD2 Predicted Poor Survival

Background Co-occurring mutations were observed in NPM1-mutated acute myeloid leukemia (AML) frequently, and the measurable residual disease (MRD) for NPM1 is effective for the prognosis of NPM1-mutated AML. However, the combined effects of co-occurring gene mutation at the baseline and MRD on survival are unclear. We investigated the impact of gene mutation status and NPM1 MRD on predictive value of AML patients with NPM1 mutation. Methord A single-center, retrospective cohort study was carried out in patients diagnosed as AML with NPM1 mutation in Peking University Peoples'hospital. Patients were treated by an anthracycline and cytarabine-based or homoharringtonine and cytarabine-based induction chemotherapy regimen and followed by high dose cytarabine as consolidation therapy. Patients who had the indications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) underwent allo-HSCT. A small part of patients with FLT3-ITD mutation received FLT3 inhibitor. Targeted next-generation sequencing (NGS) were analyzed at diagnosis, and quantitative NPM1 mutation (A, B, and D type) were detected at diagnosis and each end of chemotherapy cycle. As MRD for NPM1 rare type (NPM1 RT) was not available, MRD, relapse free survival (RFS) or overall survival (OS) analysis were conducted in patients received chemotherapy only (NGS chemo), excluding harboring NPM1 RT. Results A total of 234 patients, with NGS results, diagnosed as NPM1-mutated AML were included. 68.4% (160/234) patients including 17 patients with NPM1 RT received chemotherapy only, and NGS chemo patients were 143. After chemotherapy, 31.6% (74/234) patients underwent allo-HSCT. 1.7% (4/234) patients died of infection or hemorrhage during induction therapy. 15.8% (37/234) patients received FLT3 inhibitor，and 92.2% (212/230) patients achieved complete remission rate (CR) or incomplete hematologic recovery (CRi). During median follow-up time of 24.9 [interquartile range (IQR) 11.6-47.8] months, 40.6% (95/234) patients died. Median transcription of NPM1 at diagnosis was 31.13 (IQR 17.23-56.91)%, and would take a median time of 4.1 (IQR 2.6-5.6) months to converted to negativity.Reduction of MRD at the end of second cycle of consolidation (MRD2) ≥3log associated with higher RFS (3-year RFS rate 66.3% vs. 11.1%, p＜0.001) and OS (3-year OS rate 78.4% vs. 32.4%, p＜0.001) than reduction＜3log, and consistent negativity of MRD also predicted higher RFS (3-year RFS rate, 98.1% vs. 42.3%, p＜0.001) and OS (3-year OS rate, 100% vs. 67.7%, p＜0.001) than those whose MRD turned from negativity to positivity. 9 genes were mutated in＞10% in 234 patients, and DNMT3A and FLT3-ITD were the most prevalence (Figure 1). Univariate analysis showed FLT3-ITD, DNMT3A and reduction of MRD2＜3log were associated with poorer RFS and OS in 143 NGS chemo patients. But In multivariate analysis, only DNMT3A mutation [RFS, hazard ratio (HR)=1.9, p =0.023; OS, HR=2.1, p =0.032] and reduction of MRD2 ≥3log（RFS, HR=0.1; OS, HR =1.9, both p＜0.001）were independent prognostic factors for survival. Four subgroups were divided by different status of DNMT3A and FLT3-ITD, that were both FLT3-ITD and DNMT3A negative, FLT3-ITD positive and DNMT3A negative, FLT3-ITD negative and DNMT3A positive, and both FLT3-ITD and DNMT3A positive. The concurrence of FLT3-ITD and DNMT3A was associated with lowest RFS and OS (3-year RFS rate 29.2%, p＜0.001; 3-year OS rate 53.5%, p＜0.001). However, patients with only FLT3-ITD mutation did not contribute to poor survival compared with patients without FLT3-ITD mutation (3-year RFS rate 71.4% vs. 74.4%, p＜0.843; 3-year OS rate 74.5% vs.75.8%, p = 0.759). Three risk group were re-stratified by the gene mutation and gene reduction of MRD2 (Figure2), and the RFS and OS of the poor risk group, defined by patients with ＜3log reduction of MRD2, or with both FLT3-ITD and DNMT3A mutation, could be improved by allo-HSCT(3-year RFS rate, 56.4% vs. 29.2%, p = 0.015; 3-year OS rate, 72.0% vs. 31.6%, p = 0.001). Conclusion In AML patients with NPM1 mutation, the deleterious effect of FLT3-ITD could be pronounced in patients concomitant with DNMT3A mutation. A＜3log reduction of MRD2 was also another independent poor prognostic factor for survival, which could be improved by allo-HSCT. Meanwhile, the conversion of MRD for NPM1 from negative to positive might be a poor prognostic factor, but it requires to be validated by multivariate analysis.

Prognostic significance of mediastinal standardized uptake value on positron emission tomography/computed tomography in patients with left upper lobe non-small cell lung cancer: Is invasive staging of aortopulmonary window lymph nodes necessary?

Background: This study aims to investigate whether the invasive staging of aortopulmonary window lymph nodes could be omitted in the presence of a suspected isolated metastasis in the aortopulmonary window lymph node on positron emission tomography/computed tomography. Methods: Between January 2010 and January 2016, a total of 67 patients (54 males, 13 females; mean age: 59.9±8.7 years; range, 44 to 76 years) with metastatic left upper lobe tumors to aortopulmonary window lymph nodes were retrospectively analyzed. According to positron emission tomography/computed tomography findings in clinical staging, the patients were classified as positive (+) (n=33) and negative (-) (n=34) groups. Results: There was a statistically significant difference between the two groups in terms of sex distribution, lymph node diameter on computed tomography, maximum standardized uptake value of aortopulmonary window lymph nodes, and tumor diameter (p&lt;0.001 for all). A trend toward significance was found to be in pT status, LN #6 metastases, and pathological stage between the two groups (p=0.067). The five-year overall survival rate for all patients was 42.4% and there was no significant difference between the groups (p=0.896). The maximum standardized uptake value of the aortopulmonary window lymph nodes was a poor prognostic factor for survival (area under the curve=0.533, 95% confidence interval: 0.407-0.675, p=0.648). Conclusion: Invasive staging of aortopulmonary window lymph nodes can be omitted in patients with isolated suspected metastasis to aortopulmonary window lymph nodes in non-small cell lung cancer of the left upper lobe.

Association Between Fat Depletion and Prognosis of Amyotrophic Lateral Sclerosis: CT-Based Body Composition Analysis.

The purpose of this study was to present the results of our investigation of the prognostic value of adipopenia and sarcopenia in patients with amyotrophic lateral sclerosis (ALS). Consecutive patients with ALS with abdominal computed tomography (CT) were retrospectively identified at a single tertiary hospital between January 2010 and July 2021. Deep learning-based volumetric CT body composition analysis software was used to obtain abdominal waist fat volume, fat attenuation, and skeletal muscle area at the L3 level, then normalized to the fat volume index (FVI) and skeletal muscle index (SMI). Adipopenia and sarcopenia were defined as the sex-specific lowest quartile and SMI reference values, respectively. The associations of CT-derived body composition parameters with clinical variables, such as body mass index (BMI) and creatinine, were evaluated by Pearson correlation analyses, and associations with survival were assessed using the multivariable Cox regression analysis. Eighty subjects (40 men, 65.5 ± 9.4 years of age) were investigated (median interval between disease onset and CT examination = 25 months). The mean BMI at the CT examination was 20.3 ± 4.3 kg/m2 . The BMI showed a positive correlation with both FVI (R = 0.70, p < 0.001) and SMI (R = 0.63, p < 0.001), and the serum creatinine level was associated with SMI (R = 0.68, p < 0.001). After adjusting for sex, age, King's stage, BMI, creatinine, progression rate, and sarcopenia, adipopenia was associated with shorter survival (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 1.01, 35.0, p = 0.049). In a subgroup analysis for subjects with nutritional failure (stage 4a), the HR of adipopenia was 15.1 (95% CI = 2.45, 93.4, p = 0.003). Deep learning-based CT-derived adipopenia in patients with ALS is an independent poor prognostic factor for survival. ANN NEUROL 2023;94:1116-1125.

Expression of Vascular Endothelial Growth Factor-A (VEGF-A) in Adenocarcinoma and Squamous Cell Cervical Cancer and Its Impact on Disease Progression: Single Institution Experience.

Background and Objectives: The aim of this retrospective study was to determine the difference in VEGF-A expression in adenocarcinoma and squamous cell cervical cancer and to show the influence of VEGF-A expression on clinical, pathological, and therapeutic prognostic factors on the outcome of treatment and the survival of patients. Materials and Methods: The study included patients with cervical cancer who were treated in the period from 1 January 2010 to 31 December 2021 at the Clinic for Gynecology and Obstetrics, University Hospital Centre, Osijek. The researchers conducted a retrospective analysis of data from patients' medical history, along with the pathohistological findings and oncologist findings. The study included 66 patients with cervical cancer (divided into two subgroups of 33 with adenocarcinoma or squamous cell cervical cancer). Diagnosis was based on the pathohistological status and FIGO staging. VEGF-A expression was significantly higher in adenocarcinoma. Subjects with a higher expression of VEGF-A had a significantly higher rate of disease progression and a higher possibility for lethal outcome. Results: Statistically significant prognostic factors in bivariate analysis in predicting a negative treatment outcome were: older age, greater depth of stromal invasion, FIGO IIB stage, chemotherapy, and positive lymph nodes. In the multivariate analysis, age and positive lymph nodes were shown to be significant predictors for a negative treatment outcome. Conclusions: VEGF-A has shown to be statistically more expressed in adenocarcinoma, which correlates with disease progression, but not statistically significant in multivariate regression analysis as an independent prognostic factor for poor survival of the subjects.

[Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era].

To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival. The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis. There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）. The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

Association of somatic mutations and histologic subtype/grade on prognosis and PD-L1 expression in mesothelioma.

8507 Background: Mesothelioma includes epithelioid, sarcomatoid, and biphasic histologic subtypes, and the epithelioid subtype is histologically graded based on mitotic count and nuclear atypia. Correlation between the most common somatic mutations ( BAP1, NF2, TP53, CDKN2A), and overall survival is poorly understood. High PD-L1 expression is a poor prognostic factor for survival and may be a predictor of response to immunotherapy. Few studies have evaluated the relationships between these factors. Methods: We performed a retrospective study in 217 patients with pleural, peritoneal and bicavitary mesothelioma as part of an IRB-approved biobanking protocol. Histologic subtype, grade of epithelioid mesothelioma, tumor stage, and overall survival time were determined. Next-generation DNA sequencing (NGS) was used to identify the prevalence of somatic mutations. PD-L1 immunohistochemistry was obtained on 184 samples and quantified as percentage of tumor cells. Histologic subtype, nuclear grade, clinical stage, PD-L1 expression, survival time, and the prevalence of each mutation were compared using chi-squared, Kruskal-Wallis, or Cox proportional hazard tests. All p-values were determined in R version 4.2.0 using a two-sided alpha error of 0.05 to mark statistical significance. Results: The most frequent somatic mutations were found in BAP1 (99/217, 45.6%), CDKN2A (47/217, 21.7%), TP53 (37/217, 17.1%), and NF2 (31/217, 14.3%). Patients with CDKN2A-mutated mesothelioma experienced shorter survival (p=0.032). TP53 mutations were associated with higher nuclear grade (p=0.015), higher mitotic count (p=0.013), and greater nuclear atypia (p=0.015). TP53 mutations were more prevalent in pleural than peritoneal mesothelioma (p=0.016) and in tumors without lymph node metastasis (p=0.05). As expected, patients with epithelioid mesothelioma had superior overall survival (p=0.02) and their tumors had lower PD-L1 expression (p=0.007) than either sarcomatoid or biphasic mesotheliomas. Neither PD-L1 expression nor mutations in BAP1, NF2, CDKN2A, or TERT were associated with nuclear grade, atypia, or mitotic count. No association was found between BAP1 or NF2 mutations and tumor stage, lymph node metastasis, or PD-L1 expression. Conclusions: To our knowledge, this is the first study of this scale to correlate PD-L1 expression, somatic mutation data, histologic features, and survival in mesothelioma patients. The most significant findings were that patients with CDKN2A mutations had shorter survival and TP53 mutations, which were more prevalent in pleural mesotheliomas, were associated with higher nuclear grade, higher mitotic count, and greater nuclear atypia. An ongoing analysis evaluates the contribution of germline mutations, which occurred in a significant proportion (15.7%) of this mesothelioma patient cohort.

Liver Segment Disposition of Hepatocellular Carcinoma Predicts Microvascular Invasion.

Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survival after tumor resection. This study evaluated the relation between MVI and HCC within various anatomical Couinaud's segments of the liver. A multicenter retrospective review of HCC records was conducted from 2012 to 2017. HCC cases were identified using ICD-9 and 10 codes 155, C22.0, and C22.8. HCC patients who underwent liver transplants were included in this study. Liver segment of the location of HCC was obtained from radiographic records, and MVI information was obtained from pathology reports. Segmental distributions of HCC in MVI versus non-MVI groups were compared using Wilcoxon rank sum tests. p value was set at <0.05. We analyzed 120 HCC patients who underwent liver transplantation. The mean age of our cohort was 57 years, and the most common etiology of liver disease was hepatitis C at 58.3%. The median HCC size was 3.1 cm, and MVI was present in 23.3% of the explanted specimens. MVI was 2 to 3 times significantly higher in patients with HCC affecting segments 2 and 3 and segments 4b and 5 (p = 0.01). Moreover, median survival was significantly lower in patients with MVI versus those without MVI (50 vs. 137 months, p < 0.05). MVI was significantly higher in HCC tumors located in liver segments 2 and 3 and 4b and 5, and survival was lower in patients with MVI compared with those without.

Treatment outcomes of mucosal melanoma of the head and neck: Analysis of 190 cases from a single institution.

To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution. From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis. With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p = .015). The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival.

Small RNA sequencing identified miR-3180 as a potential prognostic biomarker for Chinese hepatocellular carcinoma patients.

MicroRNAs (miRNAs) and their target genes are aberrantly expressed in many cancers and are linked to carcinogenesis and metastasis, especially among hepatocellular carcinoma (HCC) patients. This study sought to identify new biomarkers related to HCC prognosis using small RNA sequencing from the tumor and matched normal adjacent tissue of 32 patients with HCC. Eight miRNAs were downregulated and 61 were upregulated more than twofold. Of these, five miRNAs, hsa-miR-3180, hsa-miR-5589-5p, hsa-miR-490-5p, hsa-miR-137, and hsa-miR-378i, were significantly associated with 5-year overall survival (OS) rates. Differential upregulation of hsa-miR-3180 and downregulation of hsa-miR-378i in tumor samples supported the finding that low and high concentrations of hsa-miR-3180 (p = 0.029) and hsa-miR-378i (p = 0.047), respectively, were associated with higher 5-year OS. Cox regression analyses indicated that hsa-miR-3180 (HR = 0.08; p = 0.013) and hsa-miR-378i (HR = 18.34; p = 0.045) were independent prognostic factors of poor survival. However, high hsa-miR-3180 expression obtained larger AUCs for OS and progression-free survival (PFS) and had better nomogram prediction than hsa-miR-378i. These findings indicate that hsa-miR-3180 may be associated with HCC progression and could serve as a potential biomarker for this disease.

Analysis of systemic inflammatory and coagulation biomarkers in advanced cervical cancer: Prognostic and predictive significance.

Peripheral systemic inflammatory, nutritional, and coagulation biomarkers have prognostic and predictive value in various malignancies. We evaluated the prognostic and predictive roles of systemic inflammatory, nutritional, and coagulation biomarkers in the circulating blood of patients with advanced cervical cancer. A retrospective study of 795 patients with cervical cancer who received concurrent chemoradiation therapy was performed. Overall survival was evaluated by the Kaplan-Meier estimator. Univariate and multivariate Cox regression models were used to determine prognostic factors associated with overall survival. The median follow-up time was 76 months. In the univariate analysis, overall survival showed positive prognostic value in patients with a platelet-to-lymphocyte ratio (PLR) <164.29 (P = 0.010), and a plasma fibrinogen (FIB) level <4 g/L(P = 0.012). In the multivariate analysis, the PLR (P = 0.036), and FIB level (P = 0.047) maintained their significance for overall survival. Therefore, the PLR and FIB levels are independent prognostic factors in patients with advanced cervical cancer. Systemic inflammatory and coagulation biomarkers could help to understand survival differences in the clinical treatment of advanced cervical cancer. The PLR and FIB levels are independent prognostic factors of poor survival in patients with advanced cervical cancer.

The factors affecting mortality in intensive care unit of a burns center.

To determine the characteristics of patients, mortality-affecting factors and mortality rate in follow-up burn-injured patients in an intensive care setting at a burns treatment centre. The retrospective study was conducted between May and November 2014 at Kocaeli Derince Training and Research Hospital Burn Treatment Centre, Kocaeli, Turkey, and comprised data from January 2008 to January 2013 of in-patients who had been treated at the intensive care unit. The therapy outcomes and the follow-up processes were evaluated. Data was analysed using SPSS 17. Of the 381 patients, 105(27.6%) were females and 276(72.4%) were males. The overall mean age was 28.4±21.1 years. There were 52(13.6%) mortalities, while 329(86.4%) survived. The mean total body surface area was 18.3±12.9% in those who survived compared to 52±24.3% in those who died (p<0.000). The highest rate of death was observed in those aged >66 years (p<0.000). The impact of flame burns on mortality was statistically significant (p<0.05). The impact of inhalation burns, suicide, abuse, operational requirements and systemic disease on mortality was statistically significant (p<0.05). Older age, higher total body surface area, flame burns, presence of inhalation burn, third degree burn, suicide attempt, presence of systemic disease, duration of prolonged mechanical ventilation and operation requirements were found to be poor prognostic factors for survival in burn patients.

Cytologically proven leptomeningeal carcinomatosis in gastric cancer patients: Experience in a tertiary referral center

AbstractLeptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. The reported incidence may be underestimated because of the non‐specific clinical presentation and the suboptimal accuracy of the confirmation tests. Despite advances in multidisciplinary care, the prognosis for patients with LMC remains poor. Gastric cancer (GC) ranking 9th in incidence among all kinds of malignancies in Taiwan. We aimed to review our experience with LMC in GC patients at a tertiary referral center to analyze the clinical features and survival outcomes. All patients with a malignant diagnosis of cerebrospinal fluid (CSF) cytology at the National Taiwan University Hospital were reviewed from January 2002 to December 2018. The survival analysis was calculated by the Kaplan‐Meier method. Univariate and multivariate Cox proportional hazards regression analysis were used to identify factors associated with survival. We identified 18 patients with a diagnosis of GC‐related LMC. LMC occurred in approximately 0.45% of GC patients during this period. Nine (50%) were male, and the median age was 58.5 years old. The most frequent neurological symptom of these patients was altered mental status (72.2%), followed by headache (44.4%) and nausea/vomiting (44.4%). Intracranial hypertension was noted in 87.5% with the mean opening pressure to be 385.3 mmCSF. Intrathecal (IT) chemotherapy was administered to nine patients, principally with methotrexate alone (55.6%). Fourteen patients received CSF drainage by ventriculo‐peritoneal shunt or external ventricular drainage via Ommaya reservoir for relieving intracranial hypertension. In the univariate Cox proportional hazards regression analysis, the poor ECOG performance status (&gt;2), absence of other metastases, and absence of CSF drainage were all prognostic factors of poor survival. In conclusion, LMC was a rare manifestation of GC and was associated with an extremely poor survival when the performance status was poor at presentation. CSF drainage may have some impact on the survival duration in selected cases with LMC.

Abstract P4-03-37: The characteristics of male breast cancer by molecular subtypes: a population-based study

Abstract Background: To explore the characteristics of molecular subtype in male breast cancer. Methods: A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. Results: A total of 1597 cases were enrolled, including 1373 cases with HR+/HER2- (86%), 182 cases with HR+/HER+ (11.4%), 13 cases with HR-/HER2+ (0.8%) and 29 cases with Triple Negative (1.8%), respectively. There were significant differences in distributions in age, race, grade, tumor size and AJCC stage between the molecular subtypes. The molecular subtypes differed significantly in 5 years overall survival and 5 years cause specific survival, establishing the following sequence with HER2-/HR+ &amp;gt; HER2+/HR+ &amp;gt; HER2+/HR- &amp;gt; Triple negative. According to Cox regression, age&amp;gt;65y, ER negative, PR negative, TN subtype, advanced AJCC stage, larger tumor size, stage T3 and M1 were independent prognostic factors for poorer survival. Conclusion: The prognosis of male breast cancer varied by molecular subtypes. Age, ER and PR, status, stage as well as tumor size were independent prognostic factors. Citation Format: Min Wang, Deyue Liu, Li Zhu. The characteristics of male breast cancer by molecular subtypes: a population-based study [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 P4-03-37.