scholarly journals RADI-09. Clinical factors associated with death after radiotherapy for brain metastases

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii19-iii19
Author(s):  
Divya Natesan ◽  
David Carpenter ◽  
William Giles ◽  
Taofik Oyekunle ◽  
Donna Niedzwiecki ◽  
...  

Abstract Introduction It can be challenging to accurately identify patients with brain metastases who have very poor prognosis and are unlikely to benefit from radiation (RT). We characterized factors of patients who died within 30 days of receiving RT for brain metastases. Methods Patients who received whole brain RT (WBRT) or stereotactic radiosurgery (SRS) for brain metastases between 1/1/2017–9/30/2020 at a single institution were identified. Patient, tumor, treatment, and death variables were collected. Characteristics between those who did and did not die within 30 days were compared using the Wilcoxon Rank-Sum or Chi-Square test. Survival was estimated with Kaplan-Meier method. Results 636 patients received WBRT (n=117) or SRS (n=519). Median age was 61. Median survival was 6 months (95% CI 5–7 months). 75 (12%) died within 30 days of RT. Patients who died within 30 days had worse median KPS (50 vs 80, p<0.001). A higher proportion who died within 30 days had innumerable intracranial metastases (45% vs 11%, p<0.001), leptomeningeal disease (16% vs 5%, p<0.001), and higher burden of neurologic symptoms at presentation (seizures (12% vs 4%, p=0.003); cranial neuropathies (32% vs 9%, p<0.001); motor/sensory deficits (51% vs 29%, p<0.001); altered mentation (60% vs 26%, p<0.001); headaches (48% vs 30%, p<0.001); steroid use (68% vs 48%, p<0.001)). Patients who died within 30 days had progressive extracranial disease (intrathoracic: 87% vs 50%; spinal: 57% vs 18%; liver/adrenal: 60% vs 24%), p<0.001. More patients who died within 30 days received inpatient RT (39% vs 4%, <0.001) and did not complete RT (24% vs 1%, p<0.001). Discussion Patients who died within 30 days of RT had worse KPS, intracranial/extracranial disease burden, and neurologic symptoms. Future analyses will assess whether these factors can inform a prognostic model to identify patients with poor prognosis who may be appropriate for supportive care alone.

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yue Zhong ◽  
Zhenjie Zhuang ◽  
PeiJu Mo ◽  
Qi Shang ◽  
Mandi Lin ◽  
...  

Background. Myelin and lymphocyte, T cell differentiation protein 2 (MAL2) is highly expressed in various cancers and associated with the development and prognosis of cancer. However, the relationship between MAL2 and breast cancer requires further investigation. This study aimed to explore the prognostic significance of MAL2 in breast cancer. Methods. MAL2 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas (TCGA) database and verified by quantitative real-time polymerase chain reaction (RT-qPCR). The chi-square test or Fisher’s exact test was used to explore the association between clinical characteristics and MAL2 expression. The prognostic value of MAL2 in breast cancer was assessed by the Kaplan–Meier method and Cox regression analysis. Gene set enrichment analysis (GSEA) was performed to identify the biological pathways correlated with MAL2 expression in breast cancer. Besides, a single-sample GSEA (ssGSEA) was used to assess the relationship between the level of immune infiltration and MAL2 in breast cancer. Results. Both bioinformatics and RT-qPCR results showed that MAL2 was expressed at high levels in breast cancer tissues compared with the adjacent tissues. The chi-square test or Fisher’s exact test indicated that MAL2 expression was related to stage, M classification, and vital status. Kaplan–Meier curves implicated that high MAL2 expression was significantly associated with the poor prognosis. Cox regression models showed that high MAL2 expression could be an independent risk factor for breast cancer. GSEA showed that 14 signaling pathways were enriched in the high-MAL2-expression group. Besides, the MAL2 expression level negatively correlated with infiltrating levels of eosinophils and plasmacytoid dendritic cells in breast cancer. Conclusion. Overexpression of MAL2 correlates with poor prognosis and lower immune infiltrating levels of eosinophils and plasmacytoid dendritic cells in breast cancer and may become a biomarker for breast cancer prognosis.


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Junjie Hang ◽  
Steven Yuk-Fai Lau ◽  
Ruohan Yin ◽  
Lina Zhu ◽  
Siyuan Zhou ◽  
...  

Abstract Compelling evidence suggests that phosphoprotein phosphatases (PPPs) are involved in a large spectrum of physiological and pathological processes, but little is known about their roles in pancreatic cancer. We investigated the expression level, prognostic value, and potential function of PPPs with data from Oncomine, GEPIA, THPA, and TCGA databases and an independent cohort of patients with pancreatic cancer. Among all the PPP catalytic subunits (PPPcs), the transcription levels of PPP1CA, PPP1CB, PPP3CA, PPP3CB, and PPP4C were higher in pancreatic cancer than in normal pancreas (P<0.01, fold change > 2). Kaplan–Meier analysis showed that high transcription levels of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, and PPP4C correlated with poorer survival. In contrast, patients with high levels of PPP3CB, PPP3CC, PPP5C, PPP6C, and PPEF2 had much better prognoses. Data from THPA and patients with pancreatic cancer enrolled in our hospital also confirmed the prognostic value of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, PPP3CB, and PPP6C at the protein level. In addition, the Pearson Chi-square test showed that PPP3CB level was significantly correlated with T and N stages. GO and KEGG analyses showed that the genes and pathways related to the pathogenesis and progression of pancreatic cancer were greatly affected by alterations in PPPcs. Results of the present study suggest that PPP1CA, PPP1CB, PPP2CA, PPP2CB, and PPP3CA have deleterious effects but PPP3CB, PPP5C, and PPP6C have beneficial effects on pancreatic cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoling Xu ◽  
Na Li ◽  
Ding Wang ◽  
Wei Chen ◽  
Yun Fan

BackgroundInvasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma. At present, people have no idea whether IMA patients can benefit from immunotherapy and target therapy; thus there is an urgent need to clarify the immune microenvironment and genetic characteristics of this cohort.MethodsA total of 31 IMA patients matched with 27 non-mucinous adenocarcinoma (non-IMA) patients were enrolled in this study, and clinical data was collected. The expression of PD-L1, CD8+ tumor-infiltrating lymphocytes (TILs) and ALK was determined by immunohistochemistry. Polymerase Chain Reaction was used to determine the mutations of EGFR. The Chi-square test, Kaplan–Meier method and Cox proportional hazard regression model were used to explore the correlations between these clinicopathological variables, survival and identify risk factors.ResultsOf the patients with IMA 9.7% (3/31) revealed positive PD-L1 expression and 35.5% (11/31) showed CD8+ TIL infiltration, which were markedly lower than that of non-IMA group [PD-L1: 48.1% (13/27); CD8: 81.5% (22/27)]. Moreover, five (16.1%) patients in IMA group and 10 (37.0%) patients in non-IMA group had EGFR mutations, and nine (29.0%) patients in IMA group and zero (0.0%) patient in non-IMA group had ALK rearrangements. Additionally, we observed that IMA patients with CD8+ TIL infiltration had a worse prognosis than CD8-negative group (P = 0.024). Multivariate analyses showed that CD8 was an independent prognostic factor for patient’s survival (HR = 5.60, 95% CI: 1.35–23.22, P = 0.017).ConclusionPatients with IMA have down-regulated expression of PD-L1 and less CD8+ TIL infiltration in tumor microenvironment. Besides, a lower frequency of EGFR mutations was detected in patients with IMA than non-IMA patients while a higher rate of ALK rearrangements was found. Our results provide important reference for therapy of lung IMA.


2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.


2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.


2019 ◽  
Vol 130 (6) ◽  
pp. 1877-1888
Author(s):  
Mark G. Bigder ◽  
Sandeep Krishnan ◽  
E. Francis Cook ◽  
Anthony M. Kaufmann

OBJECTIVEPatients with multiple sclerosis (MS)–associated trigeminal neuralgia (TN) have higher recurrence and retreatment rates than non-MS patients. The optimal management strategy and role for microsurgical rhizotomy (MSR) for MS-TN remains to be determined. The aim of this study was to report time to treatment failure (TTF) and pain scores following MSR compared to percutaneous and Gamma Knife procedures.METHODSTime to treatment failure was analyzed after MSR (n = 14) versus prior procedures (n = 53) among MS-TN patients. Kaplan-Meier curves and log-rank test were utilized to compare TTF after MSR versus prior procedures using the same cohort of patients as their own control group. Subsequent analysis compared TTF after MSR to TTF after 93 other procedures among a second cohort of 18 MS-TN patients not undergoing MSR. BNI pain scores were compared between MSR and other procedures among the MS-TN cohort using a chi-square test.RESULTSTTF was significantly longer after MSR than after other procedures in the MSR cohort (median TTF 79 vs 10 months, respectively, p < 0.0001). Similarly, TTF was longer after MSR than after prior procedures in the non-MSR cohort (median TTF 79 vs 13 months, respectively, p < 0.001). MSR resulted in a higher proportion of excellent pain scores when compared to other procedures in the non-MSR cohort (77% vs 29%, p < 0.001). Probability of treatment survival was higher after MSR than after other procedures at all time points (3, 6, 12, 24, 36, and 48 months). There were no deaths or major complications after MSR.CONCLUSIONSTTF was significantly longer following MSR compared to prior procedures in MS-TN patients. Additionally, a higher proportion of patients achieved excellent BNI pain scores after MSR.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Margherita Ratti ◽  
Nicola Valeri ◽  
Jens Claus Hahne ◽  
Andrea Lampis ◽  
Michele Ghidini ◽  
...  

e15566 Background: Identification of prognostic biomarkers for gastric cancer (GC) patient selection is compelling to improve survival outcomes. Microsatellite instability (MSI) is related with a positive prognostic effect in GC, whereas perioperative chemotherapy resulted detrimental in this subgroup. In metastatic GC, immunotherapy with anti-PD1/PD-L1 drugs has shown promising results. Nevertheless, in early stages, data on the relation between MSI, clinic-pathological features, PD-L1 expression and overall survival (OS) remains sparse, especially in Western population. In our study, the prognostic role of MSI, clinic-pathological features and PD-L1 expression in a cohort of Italian GC patients was examined. Methods: CP data of 148 consecutive stage I-III GC pts resected in Cremona Institute between 2010 and 2014 (mostly chemo and/or radio-naive) were collected. MSI analysis was performed on tissue samples for all cases by polymerase chain reaction. PDL-1 expression, evaluated by immunohistochemistry, was assessed in MSI group. Differences between subgroups were evaluated with Chi-square test; Kaplan-Meier method and Long Rank test were used to calculate OS. Results: Female sex (p=0.012), earlier TNM stages (p=0.011) and limited nodal involvement (p=0.29) significantly correlated with MSI status. MSI is significantly associated with better prognosis, exhibiting an advantage of 28.6 months in OS compared with microsatellite stable subgroup (p<0.001). Most MSI patients expressed PD-L1. MSI patients without PD-L1 expression showed higher percentage of clinical features correlated with better prognosis compared with PD-L1 expressing MSI patients and MSS subgroup. Conclusions: MSI is an independent prognostic biomarker in GC and identifies a subset of patients with better OS and specific clinic-pathological features, including high percentage of PD-L1 expression. MSI could represent a promising biomarker to select patients for chemotherapy versus immunotherapy in non-metastatic disease.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 555-555
Author(s):  
Samantha Ann Armstrong ◽  
Bhavana Pendurthi Singh ◽  
Monika Kulasekaran ◽  
Petra Prins ◽  
Aiwu Ruth He

555 Background: Despite advances in understanding the molecular pathways of HCC, therapeutic options are limited and patient survival is dismal. IO is a promising HCC treatment. There are currently no indicators to identify which patients (pts) will have a prolonged response. Methods: In this single-institutional retrospective analysis, pts received one of five IO containing regimens with nivolumab, pembrolizumab, atezolizumab plus bevacizumab, durvalumab or cemiplimab until disease progression (PD) or unacceptable toxicity. Relevant factors including: stage, viral etiology, vascular invasion (VI), tumor thrombus (TT), multifocal disease, toxicity grade, steroid use for IO mediated toxicities and derived Neutrophil-to Lymphocyte ratio (dNLR), were correlated to clinical outcome: progression free survival (PFS), overall survival (OS), response rate (RR), using Pearson’s chi-square test or student's t-test . Responses were assessed using RECIST v 1.1 criteria for stable disease (SD), partial response (PR) and PD were correlated with best response and PFS. OS was calculated by the Kaplan-Meier method. Results: Cohort demographics (n = 76) were: 72% male; 38% African American, 30% Caucasian and 16% Asian; 29% of pts had HBV, 41% had HCV, 1% had both HBV/HCV and 13% had no viral etiology (n = 64). The majority of pts were stage III (43%) or IV (38%). At the start of IO, 32% had VI, 32% had TT and 80% had multifocal or metastatic disease. 65% of pts experienced IO toxicity, with 24.3% at grade 3 or higher, and 34% requiring steroids. Best response to IO was SD in 65.7% of pts, PR in 25.7% and PD in 8.6%. Median OS was 13m (95% CI 7.9-18.1) from the start of IO and median PFS (n = 65) was 14m (95% CI 6.8-21.2). Median OS and PFS were significantly improved in pts with PR compared to PD (45 vs 8m, p < 0.0005, PFS 15 vs 3m p = 0.007). Both OS and PFS showed benefits for SD of ≥2 months compared to those with PD (11 vs 8m, p < .0005, PFS 5 vs 3m p = .007). VI, TT, stage, viral etiology, toxicity grade or dNLR did not correlate with OS, PFS and RR, however need of steroid treatment trended toward worse outcome. Conclusions: PR and SD are independent predictors for prolonged PFS and OS in HCC pts receiving IO therapy. Absence of steroid use for toxicity trended toward improved IO response.


2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  

Abstract Background: Previous studies have demonstrated that microRNAs (miRNAs) played a crucial role in various diseases, including cancers. The aim of the study was to evaluate the clinical significance of miR-124 in patients with cholangiocarcinoma (CCA).Methods: The expression pattern of miR-124 was detected in CCA tissues using quantitative reserve transcription polymerase chain reaction (qRT-PCR). The correlation of miR-124 expression with clinicopathological features and overall survival of patients were explored using chi-square test, Kaplan-Meier methods and Cox regression analyses.Results: The miR-124 expression level was strong down-regulated in CCA tissues compared with normal para-cancerous tissues (P<0.001). Moreover, aberrant miR-124 expression was significantly associated with differentiation (P=0.045) and lymph node metastasis (P=0.040). In addition, Kaplan-Meier method and log-rank test revealed that patients with low miR-124 expression has a poorer overall survival compared with those with high miR-124 expression (P=0.002). Furthermore, multivariate analysis confirmed that miR-124 expression (P=0.006; HR=2.006; 95%CI: 1.224-3.289) was an independent prognostic indicator in CCA.Conclusions: Collectively, our results defined miR-124 expression plays important roles in CCA patients. MiR-124 expression might used as a valuable prognostic biomarker for patients with CCA.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12506
Author(s):  
Yue Zhong ◽  
Zhenjie Zhuang ◽  
Peiju Mo ◽  
Mandi Lin ◽  
Jiaqian Gong ◽  
...  

Background Spindle and kinetochore associated complex subunit 3 (SKA3) plays an important role in tumorigenesis and the progression of various tumors. But the relationship between SKA3 and early breast cancer remains unclear. The study aimed to explore the prognostic significance of SKA3 in breast cancer. Methods In the study, SKA3 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas database (TCGA). Then, we presented validation results for RT-qPCR (quantitative reverse transcription PCR) and ELISA (enzyme-linked immunosorbent assay). The relationship between clinical characteristics and SKA3 expression was assessed by Chi-square test and Fisher’s exact test. Kaplan–Meier method and Cox regression analysis were conducted to evaluate the prognostic value of SKA3. Gene set enrichment analysis (GSEA) was performed to screen biological pathways using the TCGA dataset. Besides, single sample gene set enrichment analysis (ssGSEA) was utilized to identify immune infiltration cells about SKA3. Results SKA3 mRNA was expressed at high levels in breast cancer tissues compared with normal tissues. Chi-square test and Fisher’s exact test showed SKA3 expression was related to age, tumor (T) classification, node (N) classification, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race. RT-qPCR results showed that SKA3 expression was overexpressed in ER, PR status, and molecular subtype in Chinese people. Kaplan–Meier curves implicated that high SKA3 expression was related to a poor prognosis in female early breast cancer patients. Cox regression models showed that high SKA3 expression could be used as an independent risk factor for female early breast cancer. Four signaling pathways were enriched in the high SKA3 expression group, including mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early. Besides, the SKA3 expression level was associate with infiltrating levels of activated CD4 T cells and eosinophils in breast cancer. Conclusion High SKA3 expression correlates with poor prognosis and immune infiltrates in breast cancer. SKA3 may become a biomarker for the prognosis of breast cancer.


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