scholarly journals Radiomic assessment as a method for predicting tumor mutation burden (TMB) of bladder cancer patients: a feasibility study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Tang ◽  
Wen-lei Qian ◽  
Wei-feng Yan ◽  
Tong Pang ◽  
You-ling Gong ◽  
...  

Abstract Background Tumor mutation burden (TMB) is an emerging prognostic biomarker of immunotherapy for bladder cancer (BLCA). We aim at investigating radiomic features’ value in predicting the TMB status of BLCA patients. Methods Totally, 75 patients with BLCA were enrolled. Radiomic features extracted from the volume of interest of preoperative pelvic contrast-enhanced computed tomography (CECT) were obtained for each case. Unsupervised hierarchical clustering analysis was performed based on radiomic features. Sequential univariate Logistic regression, the least absolute shrinkage and selection operator (LASSO) regression and the backward stepwise regression were used to develop a TMB-predicting model using radiomic features. Results The unsupervised clustering analysis divided the total cohort into two groups, i.e., group A (32.0%) and B (68.0%). Patients in group A had a significantly larger proportion of having high TMB against those in group B (66.7% vs. 41.2%, p = 0.039), indicating the intrinsic ability of radiomic features in TMB-predicting. In univariate analysis, 27 radiomic features could predict TMB. Based on six radiomic features selected by logistic and LASSO regression, a TMB-predicting model was built and visualized by nomogram. The area under the ROC curve of the model reached 0.853. Besides, the calibration curve and the decision curve also revealed the good performance of the model. Conclusions Our work firstly proved the feasibility of using radiomics to predict TMB for patients with BLCA. The predictive model based on radiomic features from pelvic CECT has a promising ability to predict TMB. Future study with a larger cohort is needed to verify our findings.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16528-e16528
Author(s):  
Liping Li ◽  
Mengmei Yang ◽  
Mengli Huang

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yuto Takenaka ◽  
Satoru Kishi ◽  
Kyosuke Nishio ◽  
Kazunobu Masaki ◽  
Toyohiro Hashiba ◽  
...  

Abstract Background and Aims The aim of this study was to investigate the prognostic impact of intradialytic hypotension (IDH). Method This study comprised 237 hemodialysis patients (158 males, 64±13 years old, dialysis vintage:110±88 months) in a community-based dialysis center. IDH was recorded in 12 consecutive hemodialysis sessions from February to April in 2014. The patients were divided into 2 groups: Group A, patients with IDH, and Group B, those without IDH, and all-cause mortality rates for 4 years were examined. IDH was defined as a rapid symptomatic fall of systolic blood pressure by at least 30 mmHg or that required medical intervention. Logistic regression was used to investigate the association between IDH and mortality. Results IDH was observed in 123 patients (52 %). The frequency of IDH was 3.8±3.1 times during 12 hemodialysis sessions in Group A. Mortality rates from all causes of death were significantly higher in Group A than in Group B (40 % and 17 % at 4 years, respectively, p < 0.05). Univariate analysis showed that IDH, age, female, dry weight, ultrafiltration rate (UFR), serum albumin level, and serum hemoglobin level were significantly associated with all-cause mortality. In multivariate analysis, IDH, age, UFR, and serum hemoglobin level were independent risk factors for all-cause mortality (Table). Conclusion In our population, IDH was associated with a poor prognosis at 4 years.


2019 ◽  
Vol 8 (5) ◽  
pp. 634 ◽  
Author(s):  
Hiroki Nishikawa ◽  
Hirayuki Enomoto ◽  
Kazunori Yoh ◽  
Yoshinori Iwata ◽  
Yoshiyuki Sakai ◽  
...  

Association between sarcopenia, as evaluated by grip strength (GS) and skeletal muscle mass (SMM), and depression, as evaluated by Beck Depression Inventory-2nd edition (BDI-II) in chronic liver diseases (CLDs, n = 414, average age = 61.5 years), was investigated. Study subjects were classified into four groups: Group A (n = 60), lower GS and lower SMM (sarcopenia); group B (n = 44), lower GS and higher SMM; group C (n = 100), higher GS and lower SMM; group D (n = 210), higher GS and higher SMM. Factors associated with BDI-II score ≥11 were examined. BDI-II score 0–10 (normal) was found in 284 (68.6%), 11–16 (minimal) in 76 (18.4%), 17–20 (mild) in 24 (5.8%), 21–30 (moderate) in 15 (3.6%), and ≥31 (severe) in 15 (3.6%). The average ± standard deviation BDI-II score in liver cirrhosis (LC) patients (10.2 ± 9.6, n = 152) was significantly higher than that in non-LC patients (7.4 ± 7.2, n = 262) (p = 0.0058). Univariate analysis identified three factors to be significantly associated with BDI-I score ≥11: Our classification (groups of A, B, C, and D) (p = 0.0259), serum albumin (p = 0.0445), and the presence of LC (p = 0.0157). Multivariate analysis revealed that only group A (p = 0.0074, group D as a reference) was significant. In conclusion, sarcopenia can be an independent predictor for depression in CLDs.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3563-3563
Author(s):  
Jee Hyun Kong ◽  
Hyun Ae Jung ◽  
Hee Kyung Ahn ◽  
Silvia Park ◽  
Hee-Jin Kim ◽  
...  

Abstract Abstract 3563 The distinctive features of the World Health organization (WHO) classification compared to French-America-British Co-operative group (FAB) classification of acute myeloid leukemia is the new morphological entity “AML with multilineage dysplasia (MLD)”, and now this subgroup has been renamed as 'AML with myelodysplasia-related change (MRC)”. It generally accepted that dysplasia was most frequently noted in older individual, is often associated with an unfavorable cytogenetic profiles and unfavourable response to therapy. However it is still controversial. Therefore, we evaluated the impact of MRC on overall survival (OS) and leukemia free survival (LFS) in acute myeloid leukemia patients. A total of 644 adult AML patients diagnosed at Samsung Medical Center (SMC) between Sep.1994 and Oct. 2010 were enrolled. We reviewed their medical histories, clinical parameters, hemogram data, bone marrow aspirate and cytogenetic studies, and reclassified them into AML with of MRC and without MRC groups. Of 664 patients, 543 patients were received induction chemotherapy, among them, 84 patients demonstrated MRC and 451 patients did not. Median age was 50 (15–88) years old, and 57.1% of patients were male. Median follow up period was 77.3 [0–191] months. AML without MRC group had more favorable cytogenetic risk, higher WBC counts and LDH levels than those with MRC. However, other variable such as age, sex, hemoglobin level, absolute neutrophil, and peripheral blast count, induction chemotherapy regimen, hematopoietic stem cell transplantation, CR1 (complete response after induction chemotherapy), CRp (complete recovery of platelet), and relapse rate were not different between two groups. Since FLT3-ITD and NPM1 tests were introduced into laboratory work after 2005, results of these tests were available only in 158 and 75 patients respectively, and these were not different between two groups. In univariate analysis, advanced age (>65 years) predicted worse LFS (median LFS [95% C.I.]; ° Â65 years vs >65 years; 9.3[7.2–11.4] vs 5.9[4.6–7.2] months, p =0.014). In terms of OS, young age (p=0.000), female (p=0.000), favorable cytogenetic risk (p=0.000), CR1 (p=0.000), CRp (p=0.000), absence of relapse (p=0.000), and HSCT (p=0.000) showed a higher probability of longer OS (Table 1). The presence of MRC, FLT3-ITD, and NPM1 did not affect OS (Table 1).Table 1.Summary of univariate analysis for overall survival.Median OS (months) [95% C.I.] or mean OS ± SD (months)pAge°Â65 years47.9 [17.1 – 78.6]0.000>65 years13.1 [5.9 – 20.4]SexMale23.2 [16.5 – 30.0]0.000¢Female112.2 [ – ]Cytogenetic risk¢Favorable107.0±7.40.000Intermediate28.0 [19.0 – 36.9]Unfavorable10.8 [7.8 – 13.7]Unknown17.5 [6.8 – 28.1]MRCAbsence35.9 [6.6 – 65.2]0.081Presence19.0 [6.9 – 31.0]CR1¢Yes112.2 [–]0.000No3.6 [1.1 – 6.1]CRp¢Yes70.9±4.40.000No54.8 [18.5 – 91.1]RelapseYes21.5 [17.2 – 25.9]0.000No17.5 [–]HSCT¢Auto86.2±5.60.000¢Allo83.8±6.5Not done17.5 [10.8 – 24.1]FLT3-ITDPositive8.2 [0–26.1]0.595Negative29.5 [20.9–38]NPM1¢Positive104.1±11.00.978¢Negative78.9±15.0¢“median survival not reached Next, we analyzed MRC effect in each variable to OS. The presence MRC did not affect OS of each group which divided according to the age (Figure 1. A and B), sex, cytogenetic risk groups (Figure 1. C and D), relapse, CR1, HSCT, and FLT3-ITD, though AML with MRC group had tendancy to have poor survival rate in intermediate cytogenetic risk group (Figure 1. C). However in patients who did not acheived CRp or showed NPM1, the presence of MRC correlated with shorter OS.Figure 1.Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).Figure 1. Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D). In this study, patients with MRC did not show inferior outcomes than those without MRC. Therefore it is not necessary to decide different treatment strategy according to the presence of MRC Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 260-260
Author(s):  
T. Tsushima ◽  
N. Boku ◽  
Y. Honma ◽  
H. Takahashi ◽  
S. Ueda ◽  
...  

260 Background: No standard care has been established for advanced small-bowel adenocarcinoma (SBA). The aim of this study is to explore a most promising chemotherapy regimen for advanced SBA. Methods: All data were collected from medical records of patients with advanced or recurrent SBA who received chemotherapy between April 1999 and March 2009 at 41 hospitals in Japan. Selection criteria were as follows: 1) histologically proven SBA, excluding ampullary carcinoma, 2) no previous chemotherapy or radiotherapy, 3) ECOG PS 0-2, 4) adequate bone marrow, hepatic and renal functions, 5) no concomitant malignancy. Patients were divided into the five groups by regimens: group A, fluoropyrimidine alone; group B, fluoropyrimidine + cisplatin; group C, fluoropyrimidine + oxaliplatin; group D, fluoropyrimidine + irinotecan; group E, others. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Results: Demographics of selected 132 patients were: median age (range), 59 (23-78) years; male/female, 87/45; location of primary tumor, duodenum/jejunum/ileum/unknown, 80/32/17/3; advanced/recurrent disease, 91/41. The numbers of the patients in group A, B, C, D and E were 60, 17, 22, 11 and 22, and objective response rates (ORR) in the patients with target lesions were 20% (9/46), 38% (5/13), 42% (8/19), 25% (2/8), 21% (4/19), respectively. Median PFS and OS were 6.0 and 14.0 months for the whole population, and those in each group are shown in the Table.In comparison with fluoropyrimidine alone (A), oxaliplatin-combined regimens (C) associated with better PFS (HR=0.53 [0.31-0.93], p=0.03) and OS (HR=0.64 [0.33-1.25], p=0.19), while cisplatin-combined regimens (B) did not (HR=1.54 [0.88-2.68], p=0.13 for PFS and HR=1.67 [0.94-2.97], p=0.08 for OS) by univariate analysis. Conclusions: It is suggested that oxaliplatin-combined regimens might be the most promising regimen for advanced SBA. [Table: see text] No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15149-e15149
Author(s):  
Sara Marinelli ◽  
Alessandro Granito ◽  
Eleonora Terzi ◽  
Simona Leoni ◽  
Fabio Piscaglia ◽  
...  

e15149 Background: Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). Little is known about clinical-laboratoristic parameters predicting treatment benefit. Methods: Between 2008-2012, 94 consecutiveclinically compensatedcirrhoticpatients [M/F=85/9, median age 69-years (38-88)] with advanced HCC (BCLC-C, n=57) and those with an intermediate HCC (BCLC-B, n=37) who failed to respond or not eligible to locoregional therapies, received sorafenib. Clinical-laboratoristic data were reviewed. RECIST criteria were used to assess objective benefit. Toxicities were classified using NCIC Toxicity Criteria v-3.0 and treatment managed according to drug label. Results: The median treatment duration (TD) was 3.9 months (range 0.1-48). The median survival was 9.2 months (range 0.4-45). On the basis of TD we identified two groups of patients with a significant different overall survival (OS): group A (TD>6.6 months, median-TD 11.4, 33 patients) and group B (TD<6.6 months, median-TD 2.3, 61 patients). Median OS in group A and B was 20.6 and 6.6 months, respectively (p<0.001). CPT score, BCLC stage and neoplastic portal vein thrombosis were similar in the two groups. On univariate analysis, group A showed an higher rate of ECOG-PS 0 (75% vs 50%, p=0.034), lower basal serum levels of alfa fetoprotein (best cut-off: AFP<19 ng/dl, p=0.006). Fatigue and nausea were more frequent in group B (67.2% vs 43.8%, p=0.044; 19.3% vs 3.2%, p=0.05, respectively). ECOG-PS 0, AFP serum levels and nausea were significantly associated with a longer OS (p=0.003; p=0.006; p=0.008, respectively, log-rank test). On multivariate analysis, basal AFP levels (>19 ng/ml) remained predictor of shortened OS (p=0.028, OR=4). Conclusions: Development of nausea and fatigue on sorafenib is associated with poorer OS. AFP basal levels <19 ng/ml indipendently predict a better survival. Clinical-laboratoristic parameters may be useful to identify patients more likely to benefit from sorafenib.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 523-523
Author(s):  
Marshall Strother ◽  
Alexander Kutikov ◽  
Bianca Lewis ◽  
Mengying Deng ◽  
Elizabeth A. Handorf ◽  
...  

523 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by cystectomy is the standard of care for muscle-invasive urothelial bladder cancer (MIBC). 15-35% of MIBC patients present with ureteral obstruction. Poor renal function increases cisplatin toxicity. It is unknown whether patients with ureteral obstruction which has been relieved (whether by nephrostomy tube or nephroureteral stent) have the same risk of toxicity as patients without ureteral obstruction. Methods: We retrospectively reviewed an institutional database of all patients undergoing NAC for MIBC with either dose dense MVAC (ddMVAC) or gemcitabine and cisplatin (GC) from January 2004 through May 2017. Patients without ureteral obstruction prior to initiation of NAC (Group A) were compared to those who had ureteral obstruction which was relieved prior to undergoing NAC (Group B). Continuous variables were compared using the Wilcoxon rank-sum test and categorical variables were compared using Fisher’s exact test. The primary outcome was premature discontinuation of NAC, which was defined as failure to complete all planned cycles. Logistic regression was used to test for differences between the groups in this outcome adjusting for age, ECOG performance status, and baseline glomerular filtration rate (GFR). Results: 160 patients in Group A and 59 patients in Group B were identified. Baseline age, Charlson Comorbidity Index, race, smoking status, and ECOG performance status were similar. Patients in Group B had lower GFR (99.2% vs 78.8% p <0.001) and were more likely to be female (21.9% vs 27.3% p <0.025) and to receive ddMVAC (65.0% vs. 83.1% p =0.012). There was no significant difference between groups in rates of premature NAC discontinuation (15.8% vs 22.0% p = 0.284) or grade ≥3 adverse events (23.4% vs 30.5% p = 0.285). Adjusted analysis showed no significant difference between the groups in frequency of premature NAC discontinuation (OR 1.96, 95% CI 0.84-4.57 p=0.12). Conclusions: We detected no difference in frequency of premature discontinuation of NAC in patients with relieved malignant ureteral obstruction relative to patients without obstruction. NAC for MIBC is likely safe in this population.


2011 ◽  
Vol 5 ◽  
pp. CMC.S7170 ◽  
Author(s):  
Feridoun Sabzi ◽  
Abdol Hamid Zokaei ◽  
Abdol Rasoul Moloudi

Background Atrial fibrillation (AF) is a frequent and serious complication of coronary artery bypass graft (CABG) surgery. Methods: We undertook a retrospective review of the records of patients undergoing CABG at Imam Ali Hospital between February 1, 2003 and February 1, 2006. The patients were divided in two groups, ie, Group A (AF) and Group B (no AF). The association between the occurrence of AF following CABG and other variables was compared with respect to continuous or categorical variables by t-test and χ2-test. Results Multivariate logistic regression analysis of potentially predictive factors in univariate analysis showed that opium use, type of operation, and crossclamp time were predictors of AF following CABG. Conclusion This study identifies some new predictors of postoperative AF, control of which could lead to a lower incidence of AF and reduced morbidity, mortality, and resource utilization for patients undergoing cardiac surgery.


Vascular ◽  
2013 ◽  
Vol 22 (2) ◽  
pp. 98-104 ◽  
Author(s):  
Nikolaos Tsilimparis ◽  
Joseph J Ricotta ◽  
Anand Dayama ◽  
James G Reeves ◽  
Sebastian Perez ◽  
...  

The aim of the study was to investigate the effect of recent chemotherapy (Chx) on outcome of aorto-iliac aneurysm (AAA) repair. The 2005–2010 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify vascular patients undergoing AAA repair within 30 days after Chx. Seventy-one patients underwent AAA repair within 30 days of receiving Chx, group A (71 ± 8.4 years, 77.5% males) and 20,024 patients underwent AAA repair without prior Chx, group B (73 ± 9 years, 79.2% males). The two groups did not significantly differ with respect to open or endovascular repair (open repair A: 32%, B: 35%, P = 0.66). However, patients in group A presented more often as emergent cases (A: 27%, B: 12%, P = 0.001). Multivariable regression analysis for emergent cases after adjustment for relevant confounders also demonstrated that patients with recent Chx present more often as emergency ( P = 0.001, odds ratio [OR]: 2.4). Thirty-day non-surgical complications were more common in group A (A: 25%, B: 16.5%, P = 0.046) while surgical complications were equivalent (A: 15.5%, B: 12.3%, P = 0.414). Risk of death was significantly higher in group A in univariate analysis (A: 13%, B: 5%, P = 0.005, OR: 2.6). Patients who receive Chx within 30 days prior to AAA repair present more frequently as emergencies leading to higher mortality. The reason for this cannot be sufficiently explained by the current database but patient selection for elective repair or the effect of Chx on the natural course of AAA may play a role.


2021 ◽  
Vol 28 (06) ◽  
pp. 854-860
Author(s):  
Khalid Hussain ◽  
Muhammad Asif ◽  
Farooq Malik ◽  
Munazza Yasmeen ◽  
Maria Tariq ◽  
...  

Objective: To compare the recurrence rate of superficial transitional cell carcinoma of urinary bladder using intravesical BCG and Mitomycin-C. Study Design: Randomized Controlled Trial. Setting: Urology Department, Teaching DHQ Hospital, Gujranwala. Period: November 2018, to Sep, 2019. Material & Methods: Was carried out on total 270 patients, admitted with suspicion of urothelial tumors. They were grouped in Group A and B, comprising 135 in each group. Group A received BCG and Group B received Mtiomycin-C intravesically following TUR-BT. Results: Out of 270 patients male to female ratio was 3:1. Age range of patients was between 30 to 70 years with mean of 50.0± 13.1 and 552.3 ± 12.9 years in Group A and B respectively. Recurrence was noted in 05.38% and 15.38% patients in Group A and B respectively. Regarding side effects pyrexia was associated with BCG in 27.40% patients which were self-limited in 26.66% cases however required anti-tuberculosis therapy for six months in 0.74%. Whereas only 06.67% patients receiving Mitomycin had pyrexia. Dysuria occurred in 74% and frequency in 68% patients who received BCG. Whereas Dysuria occurred in 20% and frequency in 36.29% patients who received Mitomycin-C. However genital skin rash was more common (08.14%) in Mitomycin group than BCG. Conclusion: Keeping in mind less recurrence rate and bearable toxicity, it is concluded that BCG is superior to Mitomycin. This study suggests long term follow up is required to establish recurrence in the management of superficial bladder cancer.


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