Poor Prognostic Factor In Patients Research Articles

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer

BackgroundHER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients. Materials and methodsUsing a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status. ResultsOne hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7). ConclusionsCo-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.

Preoperative decline in skeletal muscle strength of patients with cardiovascular disease affects postoperative pulmonary complication occurrence: a single-center retrospective study.

Dynapenia, defined as age-related skeletal muscle strength decline, has been reported as a poor prognostic factor in patients with cardiovascular disease. Decline in skeletal muscle strength (DS), the main symptom of dynapenia, may be an important clinical indicator in patients undergoing cardiac surgery. However, the relationship between DS and postoperative pulmonary complication occurrence is unclear. Herein, we investigated the relationship between preoperative DS and postoperative pulmonary complication occurrence in patients undergoing cardiac surgery. We enrolled 125 patients who underwent cardiac surgery. DS was determined by low grip strength and quadriceps isometric strength. The patients were divided into DS and non-DS groups. The relationship between the clinical characteristics and preoperative physical function was compared, and factors associated with postoperative pulmonary complication occurrence were investigated using multivariate logistic regression analysis. There were 42 (33.6%) patients in the DS group and 83 (66.4%) patients in the non-DS group. Compared with the non-DS group, the DS group was significantly older and had a higher body mass index and Japan SCORE (operative mortality rate and major complication rate). The DS group also had a lower estimated glomerular filtration rate and preoperative Barthel index than the non-DS group. Furthermore the DS group had a significantly higher incidence of postoperative pulmonary complications and length of intensive care unit stay, and their postoperative rehabilitation was prolonged compared to the non-DS group. Multivariate logistic regression analysis revealed that DS was a determinant of postoperative pulmonary complications (odds ratio 4.26, 95% confidence interval 1.63‒11.14). We showed that preoperative DS was an independent risk factor for postoperative pulmonary complications in patients undergoing cardiac surgery. Skeletal muscle strength before cardiac surgery may be an important clinical indicator for predicting the prognosis of patients from post-surgery to discharge and for planning postoperative rehabilitation programs.

Clinical study on the pattern of lower-level lymphatic metastasis in primary tongue squamous cell carcinoma.

To study and analyze the clinical patterns of lower-level lymph node (Ⅳ and Ⅴ) metastasis in primary tongue squamous cell carcinoma, and establish a reference for the decision-making of the lower-level neck dissection in tongue squamous cell carcinoma. A total of 203 patients with primary tongue squamous cell carcinoma were recruited. These patients underwent simultaneous/secondary comprehensive neck (level Ⅰ-Ⅴ) dissection in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2015. Their clinicopathological and follow-up data were obtained and analyzed to reveal the prognosis and risk factors of primary tongue squamous cell carcinoma with lower-level lymph node metastasis. Among the 203 patients, the metastasis rates of levels Ⅳ and Ⅴ are 14.78% and 4.93%, respectively. Level Ⅳ metastasis is more prevalent in males than females (P=0.04); non-smokers are more likely to have level Ⅴ metastasis than smokers (P=0.046). Lymph node status in levels Ⅲ and Ⅳ are significantly associated with the risk of metastasis in level Ⅴ (P=0.001). Patients with extracapsular invasion in level Ⅲ have a significantly increased risk of metastasis in levels Ⅳ (P=0.014) and Ⅴ (P=0.026). The 5-year survival rate of patients with lower lymph node (Ⅳ/Ⅴ) metastasis is only 14.70%, which is an independent poor prognostic factor for patients with primary tongue squamous cell carcinoma (P<0.000 1). Most primary tongue squamous cell carcinoma metastases occur in levels Ⅰ-Ⅲ. However, the rate of lower-level lymph node metastasis is rather low. For the cN0 and cN+ patients with levels Ⅰ-Ⅱ lymph node metastases without extracapsular invasion, the strategy for level Ⅴ management may be observation rather than dissection.

Poor prognostic factors in patients hospitalized for COVID-19

The clinical spectrum of COVID-19 varies from no or mild symptoms to pneumonia with fatal complications. The aim of the study was to find predictors of mortality and admission in the intensive care unit (ICU) in patients hospitalized for COVID-19. Retrospective study of a cohort of patients admitted for COVID-19 between March 2020 and February 2021. Demographic, clinical, radiological and laboratory variables were described at admission. Independent predictors of mortality and ICU admission were identified by means of backward stepwise logistic regression and described in terms of odds ratio (OR) and 95% confidence interval (95%CI). A total of 883 patients were included, 51.8% men with a mean age of 68; 1.8% readmissions. 17.6% of patients died (n=154). The independent predictors of mortality were age (OR=1.071; 95%CI: 1.046-1.095), percentage of oxygen saturation (SatO2) (OR=0.938; 95%CI: 0.903-0.974), diastolic blood pressure (DBP, OR= 0.972; 95%CI: 0.955-0.989), creatinine (OR=1.516; 95%CI: 1.088-2.113), INR (OR=1.199; 95%CI: 1.012-1.419) and sodium (OR=1.082; 95%CI: 1.037-1.128). Eight percent of patients were admitted to ICU; the independent predictors were: male sex (OR=2.079; 95%CI: 1.099-3.935), age (OR=0.960; 95%CI: 0.942-0.979), SatO2 (OR=0.925; 95%CI: 0.889-0.962), creatinine (OR=1.551; 95%CI: 1.118-2.152) and C-reactive protein (CRP, OR=1.003; 95%CI: 1.000-1.007). The identification of independent predictors of mortality (age, SatO2, DBP, creatinine, INR, sodium) and ICU admission (sex, age, SatO2, creatinine, and CRP) allowed for the stratification of patients to adapt clinical care protocols to these findings, thereby improving medical decisions.

Acute portal hypertension using portal vein ligation abrogates TRAIL expression of liver-resident NK cells.

The effects of acute portal hypertension (PHT), which is reported as poor prognostic factors in patients with hepatocellular carcinoma, are not well known on the liver immune system, including natural killer (NK) cells. The aim of this study, therefore, was to investigate how acute PHT influences the functions and characteristics of liver‐resident NK (lr‐NK) cells using an acute PHT mouse model. Acute PHT decreased the number of tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL+) lr‐NK cells by about 20% and attenuated cytotoxic activity against the Hepa1‐6 cell line by about 40%. Among various cytokine, only interleukin‐33 (IL‐33), which inhibits NK activity, significantly increased after portal vein ligation (PVL). Because lr‐NK cells highly expressed ST2/IL‐33R, IL‐33 co‐culture significantly suppressed TRAIL expression on lr‐NK cells by about 50%, and IL‐33 administration markedly decreased TRAIL expression and cytotoxic activity of lr‐NK cells. Furthermore, the TRAIL+ NK cells population was maintained by anti‐IL33 antibody or following portosystemic shunt procedure even after PVL. Finally, we demonstrated that IL‐33 decreased TRAIL expression in lr‐NK cells via AKT–forkhead box O (FoxO) and mitogen‐activated protein kinase (MAPK) signaling. Conclusion: This work demonstrates that PHT suppresses the TRAIL+ lr‐NK cell population and antitumor activities in the liver. Additionally, Akt‐FoxO and MAPK signaling pathways attenuate the TRAIL expression in lt‐NK cells via IL‐33 receptor in mice.

Post-PRRT scans: which scans to make and what to look for

AimThe aim of this study was to evaluate the clinical utility of SPECT/CT (imaging of uptake in tumor lesions and additional findings) and the additional value of planar imaging in order to simplify clinical imaging protocols and decrease patients burden.Materials and methodsOne hundred consecutive patients with metastatic neuroendocrine tumor (NET) treated with PRRT were included. Post-therapy imaging was performed 24 h after each PRRT cycle by both whole-body planar imaging and abdominal- and thoracic SPECT/CT. All images were evaluated for (1) the presence of new lesions, (2) discordant lesions between the two acquisitions (planar or SPECT), (3) location of lesions on SPECT (abdominal, thoracic, or both), and (4) additional findings on non-contrast enhanced CT imaging.ResultsIn total 368 PRRT cycles including post-therapy imaging were performed in 100 patients. 45 patients had abdominal disease only, whilst in 55 patients the disease was observed on both abdominal and thoracic SPECT. 16 patients had known bone lesions that were visible only on planar imaging as these were out of range of the SPECT/CT. During PRRT, one patient developed multiple new bone metastases after the second cycle of PRRT, which were visible on both planar and SPECT/CT images. In 11 patients additional findings were found on CT images, the most common and relevant being bowel obstruction, pleural effusion, and ascites. Patients who developed ascites during PRRT appeared to do extremely poor; a post-hoc analysis showed that overall survival was 13.2 months in patients that showed ascites during PRRT at any moment and 37.9 months in patients without ascites (p < 0.001).ConclusionFrom a clinical point of view, thoracoabdominal SPECT/CT imaging is the preferred method for post-PRRT imaging; planar imaging had no added value over SPECT/CT in this cohort. In patients with abdominal disease only on baseline imaging, SPECT/CT of the abdomen only might be sufficient for imaging during the PRRT course. All accompanying CT images should be reviewed for additional findings, especially ascites, which is suggested to be a poor prognostic factor in patients receiving PRRT.

TRIM24 Expression as an Independent Biomarker for Prognosis and Tumor Recurrence in HNSCC.

Background: Head and neck squamous cell carcinomas (HNSCCs) are among the most common cancers in humans worldwide and have a rather poor prognosis. TRIM24 has various intracellular functions and was identified in other cancer entities as a poor prognostic factor for patients. Methods: The expression of TRIM24 was evaluated by using immunohistochemistry. We used a large and representative cohort of 341 HNSCC patients. Data derived from immunohistochemistry evaluation was correlated with clinicopathological data from HNSCC patients. Results: The TRIM24 expression in HNSCC primary tumors is negatively correlated with the p16 status of the tumor tissues. Primary tumors of patients who developed a local recurrence were significantly more often positive for TRIM24. Kaplan–Meier analyses and Cox regression showed that patients with TRIM24 expressing tumors have significantly worse overall survival and progression-free survival and that TRIM24 expression is independent of other established risk factors. Conclusions: TRIM24 might be a new prognostic biomarker for the survival prognosis and early detection of local recurrences in HNSCC patients. It could be used for risk stratification of HNSCC patients and to identify those patients who are more prone to develop a local recurrence and therefore could profit from more frequent follow-up examinations.

Prognostic values of LDH and Hematological factors in Patients with Sudden Hearing Loss

Objective: In our study, we aimed to evaluate the relationship between Lactate Dehydrogenase and hematological parameters, neutrophil, Neutrophil lymphocyte ratio, platelet lymphocyte ratio, and mean platelet volume serum levels in patients with Sudden sensorineural hearing loss prognosis. Methods: 60 patients were hospitalized and treated for Sudden Hearing Loss at Dicle University Hospital Ear Nose Throat Clinic between May 2013 and April 2020, and 60 healthy individuals without any health problems were included in the study. Pretreatment peripheral blood was drawn from all subjects, followed by routine blood cell analysis. The absolute numbers of neutrophils, lymphocytes, and platelets in peripheral blood were obtained, and the Neutrophil lymphocyte ratio, platelet lymphocyte ratio, and mean platelet volume of each case were calculated. Results: A total of 120 participants, including 60 Sudden sensorineural hearing loss patients case group and 60 healthy individuals in the control group, were included in the study. The median age of the case group was 46.0 (29.0-55.0), and the control group was 48.0 (33.5-58.5), and no statistically significant difference was found between the groups in terms of age (p = 0.191). The median Lactate Dehydrogenase, Neutrophil, and Neutrophil lymphocyte ratio of the case group was significantly higher than the control group (p &lt;0.05). There was no significant difference between the groups in terms of thrombocyte, mean platelet volume, lymphocyte, platelet lymphocyte ratio, body mass index, and gender (p&gt; 0.05). Conclusion: We think that the increase in Lactate Dehydrogenase level may be a poor prognostic factor in patients with sudden hearing loss that does not improve. In addition, we believe that the increase in neutrophil count and Neutrophil lymphocyte ratio is quite significant but cannot be considered a poor prognostic factor.

Comparison of prognoses between cirrhotic and noncirrhotic patients with hepatocellular carcinoma and esophageal varices undergoing surgical resection

Esophageal varices (EV) is common and is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). However, the outcomes between cirrhotic and noncirrhotic HCC patients with EV is not well studied. The present study aimed to investigate the clinical manifestations and prognoses of HCC patients after surgical resection stratified by the cirrhosis status. A total of 111 patients with HCC and EV, who underwent surgical resection, were retrospectively enrolled between July 2003 and July 2019. The diagnosis of liver cirrhosis was established using the Ishak fibrosis score F5 or F6 in the nontumor part of liver specimens. Prognostic factors were analyzed using the Cox proportional hazards model. There were 85 (76.6%) and 26 (23.4%) patients with and without cirrhosis, respectively. Compared with those without cirrhosis, there were more females, less seropositive rate of hepatitis B surface antigen (HBsAg), more seropositive rate of antibody against to hepatitis C virus (HCV), less albumin-bilirubin (ALBI) grade 1, lower platelet count, and more had tumor burden within the Milan criteria in cirrhotic patients. Cirrhotic patients had a higher risk of posthepatectomy decompensation compared to noncirrhotic patients (hazard ratio 9.577, p = 0.017). No difference was observed in overall survival and recurrence-free survival between patients with or without cirrhosis. Compared with patients without cirrhosis, cirrhotic patients with HCC and EV are vulnerable to posthepatectomy decompensation. However, cirrhosis is not a poor prognostic factor of overall survival and recurrence for HCC patients after surgical resection.

Is hyperlipazemia a poor prognostic factor in patients with COVID-19 ?

Introduction: COVID-19 disease may pose a considerable health threat to healthy individuals and individuals with comorbidity. The SARS-CoV-2 virus affects the respiratory tract and may cause damage to the pancreas by binding to the ACE-2 receptor in the pancreas. In our study, we investigated the effects of hyperlipasemia on morbidity and mortality in patients diagnosed with COVID-19.&#x0D; Material and Method: In this study, 2350 patients diagnosed with COVID-19 between November 2020 and December 2020 were retrospectively reviewed. Other possible causes of hyperlipasemia were excluded. Hyperlipasemia secondary to COVID-19 was detected in 338 patients. These patients were divided into two groups based on their lipase elevation rates.&#x0D; Results: Hyperlipasemia was detected in 14.4% of the patients diagnosed with COVID-19, and severe hyperlipasemia (&gt;3x) was detected in 2.3%. The mean age of the patients was 64±13.8 (18-92), of which 59.5% (201) were male. In our study, 24 patients (1%) were diagnosed with acute pancreatitis. When compared according to lipase level, a significant difference was found between the groups regarding the history of HT, CCI score, development of ARF at follow-up, development of ARDS, need for ICU hospitalization, need for intubation, length of stay in ICU, and death rates. A weak correlation was found in the correlation analysis between hyperlipasemia and ARDS development and mortality.&#x0D; Conclusion: Elevated lipase levels were associated with poor prognosis and mortality in patients with COVID-19 infection.

NFE2L3 as a Novel Biomarker Associated With IL-2/STAT5/NLRP3 Signaling Pathway in Malignant Pleural Mesothelioma and Other Cancers.

Background: Malignant pleural mesothelioma (MPM) is a malignant tumor originating from pleural mesothelial cells and has a high mortality rate worldwide. With the advent of immunotherapy in MPM treatment, there is an urgent need to elucidate the immune-related mechanisms in this caner. Methods: Single-sample gene set enrichment analysis (ssGSEA) was used to score the immunocytes infiltration of data from different database sources. Identification of immunocyte-related genes was performed with weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, and correlation analysis. Pan-caner analysis was performed using “DiffExp” and “Correlation” modules in TIMER. Results: T-helper 2 (Th2) cell was found to be a poor prognostic factor for patients with MPM. Then a transcription factor, NFE2L3, was identified as a biomarker that showed a strong positive correlation with Th2 cell infiltration, and was highly expressed in MPM tissues and was related to the poor prognosis of these patients. At the same time, multiple NFE2L3 methylation sites were negatively correlated with Th2 cell infiltration, and patients with a high degree of methylation enjoy a better prognosis. Pan-caner analysis indicated that NFE2L3 might promote the differentiation of Th2 cells through the IL-2/STAT5/NLRP3 signaling pathway in MPM and many other cancers. Conclusion: We believe that NFE2L3 can serve as a potential biomarker related to the diagnosis and prognosis of patients with MPM, and speculate that NFE2L3 could promote Th2 cell differentiation via IL-2/STAT5/NLRP3 signaling pathway in MPM and many other cancers.

ZKSCAN5 Activates VEGFC Expression by Recruiting SETD7 to Promote the Lymphangiogenesis, Tumour Growth, and Metastasis of Breast Cancer.

The growth of lymphatic vessels (lymphangiogenesis) plays a pivotal role in breast cancer progression and metastasis and the immune response. Vascular endothelial growth factor C (VEGFC) has been demonstrated to accelerate cancer metastasis and modulate the immune system by enhancing lymphangiogenesis. However, it remains largely unclear how transcription factors physically regulate VEGFC expression by interacting with histone-modifying enzymes. Like many histone-modifying enzymes, SETD7 plays a key role in cell proliferation and inhibits tumour cell differentiation. In this study, we identified the role of the transcription factor zinc finger with KRAB and SCAN domains 5 (ZKSCAN5) in interacting with histone methyltransferase SETD7 and mediating VEGFC transcription and tumour lymphangiogenesis. ZKSCAN5 interacts with and recruits SETD7 to the VEGFC promoter. By regulating breast cancer-secreted VEGFC, ZKSCAN5 could induce the tube formation of lymph endothelial cells, which promotes tumour proliferation, migration, and metastasis. Clinically, the expression of ZKSCAN5 was frequently upregulated in patients with breast cancer and positively correlated with the expression of VEGFC and the number of lymphatic microvessels. ZKSCAN5 is a poor prognostic factor for patients with breast cancer. Our results characterise the role of ZKSCAN5 in regulating VEGFC transcription and predict ZKSCAN5 as a breast cancer therapeutic target.

Computed tomography based analyses of body mass composition in HER2 positive metastatic breast cancer patients undergoing first line treatment with pertuzumab and trastuzumab

Body composition parameters (BCp) have been associated with outcome in different tumor types. However, their prognostic value in patients with HER2-positive metastatic breast cancer (BC) receiving first line treatment with dual anti-HER2 antibody blockade is unknown. Preclinical evidences suggest that adipocytes adjacent to BC cells can influence response to anti-HER2 treatments. We retrospectively analyzed Computed Tomography (CT)-based BCp from 43 patients with HER2-positive metastatic BC who received first line pertuzumab/trastuzumab-based treatment between May 2009 and March 2020. The impact of baseline CT-based BCp on progression-free survival (PFS) was tested using Kaplan–Meier estimates and univariate and multivariate Cox regression models. We found a significantly worse PFS for patients with high baseline subcutaneous fat index (median 7.9 vs 16.1 months, p = 0.047, HR = 2.04, 95%CI 1–4.17) and for those with high total abdominal fat index (8.1 vs 18.8 months, p = 0.030, HR = 2.17, 95%CI 1.06–4.46). Patients with baseline sarcopenia did not show shorter PFS compared to those without sarcopenia (10.4 vs 9.2 months, p = 0.960, HR = 0.98, 95%CI 0.47–2.03). Total abdominal fat index remained a significant predictor of PFS at multivariate analysis. Our findings suggest that a high quantity of total abdominal fat tissue is a poor prognostic factor in patients receiving trastuzumab/pertuzumab-based first-line treatment for HER2-positive metastatic BC.

A Multi-Parametric Radiomics Nomogram for Preoperative Prediction of Microvascular Invasion Status in Intrahepatic Cholangiocarcinoma.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with increasing incidence in the last decades. Microvascular invasion (MVI) is a poor prognostic factor for patients with ICC, which correlates early recurrence and poor prognosis, and it can affect the selection of personalized therapeutic regime.PurposeThis study aimed to develop and validate a radiomics-based nomogram for predicting MVI in ICC patients preoperatively.MethodsA total of 163 pathologically confirmed ICC patients (training cohort: n = 130; validation cohort: n = 33) with postoperative Ga-DTPA-enhanced MR examination were enrolled, and a time-independent test cohort (n = 24) was collected for external validation. Univariate and multivariate analyses were used to determine the independent predictors of MVI status, which were then incorporated into the MVI prediction nomogram. Least absolute shrinkage and selection operator logistic regression was performed to select optimal features and construct radiomics models. The prediction performances of models were assessed by receiver operating characteristic (ROC) curve analysis. The performance of the MVI prediction nomogram was evaluated by its calibration, discrimination, and clinical utility.ResultsLarger tumor size (p = 0.003) and intrahepatic duct dilatation (p = 0.002) are independent predictors of MVI. The final radiomics model shows desirable and stable prediction performance in the training cohort (AUC = 0.950), validation cohort (AUC = 0.883), and test cohort (AUC = 0.812). The MVI prediction nomogram incorporates tumor size, intrahepatic duct dilatation, and the final radiomics model and achieves excellent predictive efficacy in training cohort (AUC = 0.953), validation cohort (AUC = 0.861), and test cohort (AUC = 0.819), fitting well in calibration curves (p > 0.05). Decision curve and clinical impact curve further confirm the clinical usefulness of the nomogram.ConclusionThe nomogram incorporating tumor size, intrahepatic duct dilatation, and the final radiomics model is a potential biomarker for preoperative prediction of the MVI status in ICC patients.

The Landscape of Actionable Genomic Alterations by Next-Generation Sequencing in Tumor Tissue Versus Circulating Tumor DNA in Chinese Patients With Non-Small Cell Lung Cancer.

BackgroundCirculating tumor DNA (ctDNA) sequence analysis shows great potential in the management of non-small cell lung cancer (NSCLC) and the prediction of drug sensitivity or resistance in many cancers. Here, we drew and compared the somatic mutational profile using ctDNA and tumor tissue sequence analysis in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), and assess its potential clinical value.MethodsIn this study, 221 tumor tissues and 174 plasma samples from NSCLC patients were analyzed by hybridization capture-based next-generation sequencing (NGS) panel including 95 cancer-associated genes. Tumor response assessments were applied to 137 patients with advanced-stage (III and IV) NSCLC who first received targeted agents.ResultsTwenty significantly mutated genes were identified such as TP53, EGFR, RB1, KRAS, PIK3CA, CD3EAP, CTNNB1, ERBB2, APC, BRAF, TERT, FBXW7, and HRAS. Among them, TP53 was the most frequently mutated gene and had a higher mutation probability in male (p = 0.00124) and smoking (p < 0.0001) patients. A total of 48.35% (191/395) of NSCLC patients possessed at least one actionable alteration according to the OncoKB database. Although the sensitivity of genomic profiling from ctDNA was lower than that from tumor tissue DNA, the mutational landscape of target genes from ctDNA is similar to that from tumor tissue DNA, which led to 61.22% (30/49) of mutational concordance in NSCLC. Additionally, the mutational concordance between tissue DNA and ctDNA in LUAD differs from that in LUSC, which is 63.83% versus 46.67%, indicating that NSCLC subtypes influence the specificity of mutation detection in plasma-derived ctDNA. Lastly, patients with EGFR and TP53 co-alterations showed similar responses to Gefitinib and Icotinib, and the co-occurring TP53 mutation was most likely to be a poor prognostic factor for patients receiving Gefitinib, indicating that the distributions and types of TP53 mutations may contribute to the efficacy and prognosis of molecular targeted therapy.ConclusionsAs a promising alternative for tumor genomic profiling, ctDNA analysis is more credible in LUAD than in LUSC. Genomic subtyping has strong potential in prognostication and therapeutic decision-making for NSCLC patients, which indicated the necessity for the utility of target NGS in guiding clinical management.

Prognostic significance of adipophilin expression in biopsy specimens of patients with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. The present authors recently demonstrated that expression of the lipid-related protein adipophilin (ADP) in operative specimens is a significant poor prognostic factor in patients with TNBC. Using biopsy specimens is important in making clinical decisions for patients with breast cancer; however, the prognostic significance of ADP expression in biopsy specimens from TNBC patients remains unclear. The present study determined the prognostic significance of ADP expression in biopsy specimens from TNBC patients and compared ADP-expression status between biopsy and operative specimens. The present study analyzed ADP-expression profiles in biopsy specimens from 102 patients with TNBC using immunohistochemical staining and determined relapse-free survival and risk factors associated with ADP expression in these specimens, as well as the concordance of ADP expression between biopsy and operative specimens. The results identified ADP expression in 35.3% of biopsy specimens from TNBC patients. The Ki-67 labelling index was significantly higher in ADP-positive patients (P<0.001). Univariate analysis revealed that ADP expression in biopsy specimens was significantly associated with poor relapse-free survival in patients not administered neoadjuvant chemotherapy or adjuvant chemotherapy (P=0.026). Furthermore, the concordance rate of ADP expression between biopsy and operative specimens was 73.1%, with a Cohen's kappa coefficient of 0.385 (P=0.003). These findings suggested that ADP expression in biopsy specimens might be a useful prognostic marker for patients with TNBC and could potentially provide important information regarding treatment strategies for these patients.

Abstract P2-02-03: Circulating tumor cells (CTCs), CTC heterogeneity and distinct morphological CTC subtypes predict worse survival in metastatic breast cancer (MBC)

Abstract Circulating tumor cells (CTCs), CTC heterogeneity and distinct morphological CTC subtypes predict worse survival in metastatic breast cancer (MBC)BackgroundThe presence of CTCs has been shown to be a poor prognostic factor in patients with MBC. Studies in prostate cancer have shown patients with distinct morphological subtypes of CTCs have worse outcomes than high CTC burden alone and could have treatment implications. In this study, we report a comprehensive analysis of CTC phenotypes in MBC and their impact on survival.MethodsA total of 148 blood samples from 90 patients with MBC whose disease was progressing on therapy were enrolled for CTC analysis. Blood was sent overnight to Epic Sciences, processed onto glass slides and biobanked. Replicate slides were stained with antibodies targeting the androgen receptor (AR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) in addition to cytokeratin, CD45, and DAPI. Total CTCs were quantified per sample from approximately 3 mL of blood. A threshold defining positive AR, ER, and HER2 protein expression was set using cultured cancer cell lines expressing the individual proteins. CTC morphology subtypes (heterogeneity [Scher et al Cancer Res 2017], small cell/neuroendocrine-like [SC/NE; Brown et al CCR 2021] and chromosomal instability [CIN+; Schonhoft et al Cancer Res 2020]) were quantified as previously described. High heterogeneity samples (Het+) were defined as having a Shannon Index (SI; a measure of morphologic diversity) of ≥1. CIN positivity was defined as having ≥0.7 CIN+ CTC/mL. Association with these CTC subtypes and survival were evaluated with a univariate COX proportional hazard model. ResultsOver 90% of samples and patients had CTCs (Table 1). The percentage of patients with the CTC subtypes evaluated are below. Table 1. Percentage of blood samples with CTCs and CTC subtypes in MBC patients, by MBC subtype The presence of CTCs was associated with worse survival, with a median survival of 15.3 months (mos) vs 24.0 mos with no CTCs (p=0.028). The presence of AR+ or HER2+ CTCs was not associated with survival. Analysis of ER is ongoing and will be presented. High morphologic heterogeneity or the presence of the SC/NE or CIN+ CTC subtypes, predicted for a worse survival outcome (Table 2). Table 2. Overall survival of patients with and without distinct CTC subtypes CTC morphological subtypes did not correlate with each other, except CTC heterogeneity by SI which correlated weakly with SC/NE and CIN+. HER2+ CTCs strongly correlated with a higher SI while AR+ CTCs did not. AR and HER2 expression did not associate with the CIN+ or SC/NE subtypes. ConclusionsDigital pathology analysis of CTCs identifies distinct CTC morphological subtypes that predict for worse prognosis in MBC patients. To our knowledge, this is the first report of SC/NE CTCs in MBC patients and that MBC patients with SC/NE and CIN+ CTCs have worse outcomes. Longitudinal characterization of CTC subtypes across the MBC continuum could potentially identify effective therapies against these more lethal cancers. Citation Format: Joyce A O'Shaughnessy, Maren K Levin, Esther San Roman Rodriguez, James Lu, Joshua T Jones, Amanda KL Anderson, Alisa Tubbs, Joseph D Schonhoft, Rick Wenstrup. Circulating tumor cells (CTCs), CTC heterogeneity and distinct morphological CTC subtypes predict worse survival in metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-02-03.

Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers

BackgroundDespite unprecedented benefit from immune checkpoint inhibitors (ICIs) in patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI-H) advanced gastrointestinal cancers, a relevant proportion of patients shows primary resistance or...

POS-828 RENAL FUNCTION RECOVERY IN MULTIPLE MYELOMA PATIENT POST AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE REPORT

Renal impairment is a common complication seen in patients with multiple myeloma (MM). Around 25 - 50% of patients with (MM) have renal insufficiency. Among those 2-5% required supportive hemodialysis. It has been linked also with poor survival, quality of life, and increase morbidity and mortality. Autologous hematopoietic stem cell transplantation (AHSCT) has been a standardized treatment for (MM) with good clinical response and a high remission rate. It is controversial whether renal impairment is considered a poor prognostic factor for patients undergoing (AHSCT) with (MM).

Clinical Analysis of Factors Affecting Hospital Mortality After Liver Transplant in Patients With High Model for End-Stage Liver Disease Score

This study was undertaken to identify poor prognostic factors in patients with high Model for End-Stage Liver Disease (MELD) scores. From September 2001 to December 2017, living donor liver transplant and deceased donor liver transplant were performed in 851 (84.4%) and 157 patients (15.6%), respectively, in our center. Eighty-one patients (8.0%) with MELD scores ≥ 35 were classified as patients with high MELD scores. The overall survival rates in patients with high MELD scores were significantly worse than those in patients with low MELD scores (P=.005). However, no significant difference in survival was found between the 2 groups when in-hospital mortality was excluded. In-hospital mortality occurred in 18 patients (22.2%), and the main cause of death was sepsis (n=14, 77.8%). On univariate analysis, the risk factors for in-hospital mortality were mean age (P=.028), mean MELD score (P=.045), intubation status (P < .001), culture positivity (P=.042), and encephalopathy grade 3 or 4 (P=.014). On multivariate analysis, age (P=.006), intubation status (P=.042), and culture positivity (P=.036) were significant. The main cause of in-hospital mortality was sepsis, and the risk factors for in-hospital mortality of patients with high MELD score were older age, preoperative intubation, and culture positivity. Special attention should be paid to the prevention and treatment of infection in the liver transplant of patient with high MELD scores.