scholarly journals Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma

2020 ◽  
Vol 11 ◽  
Author(s):  
Yong Cui ◽  
Wei Zeng ◽  
Haihui Jiang ◽  
Xiaohui Ren ◽  
Song Lin ◽  
...  

Objective: To explore the prognostic significance of metabolic parameters in postoperative peritumoral edema zone (PEZ) of patients with glioblastoma (GBM) based on proton magnetic resonance spectroscopy (MRS).Methods: The postoperative MRS data of 67 patients with GBM from Beijing Tiantan Hospital were retrospectively reviewed. Metabolite ratios including Cho/NAA, Cho/Cr, and NAA/Cr in both postoperative PEZ and contralateral normal brain region were recorded. Log-rank analysis and Cox regression model were used to identify parameters correlated with progression-free survival (PFS) and overall survival (OS).Results: Compared with the contralateral normal brain region, postoperative PEZ showed a lower ratio of NAA/Cr (1.20 ± 0.42 vs. 1.81 ± 0.48, P < 0.001), and higher ratios of Cho/Cr and Cho/NAA (1.36 ± 0.44 vs. 1.02 ± 0.27, P < 0.001 and 1.32 ± 0.59 vs. 0.57 ± 0.14, P < 0.001). Both the ratios of Cho/NAA and NAA/Cr were identified as prognostic factors in univariate analysis (P < 0.05), while only Cho/NAA ≥ 1.31 was further confirmed as an independent risk factor for early recurrence in the Cox regression model (P < 0.01). According to the factors of MGMT promoter unmethylation, without radiotherapy and Cho/NAA ≥ 1.31, a prognostic scoring scale for GBM was established, which could divide patients into low-risk, moderate-risk, and high-risk groups. There was a significant difference of survival rate between the three groups (P < 0.001).Conclusions: Higher Cho/NAA ratio in the postoperative PEZ of GBM predicts earlier recurrence and is associated with poor prognosis. The prognostic scoring scale based on clinical, molecular and metabolic parameters of patients with GBM can help doctors to make more precise prediction of survival time and to adjust therapeutic regimens.

2019 ◽  
Author(s):  
Zhimin Zhang ◽  
Ge Wang ◽  
Feng Jin ◽  
Jijun Zheng ◽  
He Xiao ◽  
...  

Abstract Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG) , who were treated with CCRT within 5 years.The paired serum was collected before and after treatment and biomarkers were discovered by TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. We used the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results: Using fold change≥2.0 or ≤0.5 and p≤0.05 as cutoff levels, we identified 1 up-regulated and 9 down-regulated miRNAs, 1 up-regulated and 6 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After significantly down-regulated miRNAs from EG versus CG were removed, only 9 different miRNAs were significantly reduced. In the serum samples of 48 NPC patients, there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT. We calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR=3.149, 95%CI:1.018-9.115, p=0.034), whereas combining the former two is independent for OS (HR=5.146, 95%CI:1.674-15.817, p=004). Conclusions: For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs such as miRNA-29a, miRNA-125b and miRNA-26b etc, play an important role in predicting prognosis factors for PFS and OS, which will contribute to the strategic direction of future research.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 649-649 ◽  
Author(s):  
Azusa Komori ◽  
Satoshi Otsu ◽  
Mototsugu Shimokawa ◽  
Taiga Otsuka ◽  
Futa Koga ◽  
...  

649 Background: Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have limited treatment options. Moreover, it is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine+ nab-PTX (GnP) or FOLFIRINOX. Methods: This analysis was performed as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with unresectable pancreatic cancer (NAPOLEON study) conducted by 14 centers in Japan. From December 2013 to March 2017, 255 patients with advanced or recurrent pancreatic cancer received GnP or FOLFIRINOX as 1st-line CTx. Excluding censored cases in first-line treatment, 156 and 77 patientsreceived 2nd-line CTx and best supportive care (BSC), respectively. Variables at the refractory or intolerant to the 1st-line treatment were used to investigate correlation with prognosis by Cox regression model. Then, we made scoring system using the prognostic factors to reveal the benefit of 2nd-line CTx. Results: Median post-progression survivals (PPSs) were 5.2 months in 2nd-line CTx group and 2.7 months in BSC group, respectively (hazard ratio [HR]; 0.42, 95% confidence interval [CI]; 0.31-0.57, p<0.01). According to the Cox regression model, serum Alb level of less than 3.5 g/dL (HR; 1.98, 95% CI; 1.33–2.96, p<0.01) and CA19-9 level of greater than 1,000 U/mL (HR; 1.87, 95% CI; 1.25–2.80, p<0.01) were independent predictive factors. The scoring system for PPS was designed using these factors, which was obtained by summing up serum Alb (≥ and < 3.5 g/dL allocated to scores 0 and 1) and CA19-9 (< and ≥ 1,000 U/mL allocated to scores 0 and 1) at disease progression in patients with 2nd-line CTx group. Patients with score 0 and 1 displayed significantly favorable PPSs in comparison with BSC group; however, there was no significant difference in PPS between patients with score 2 and BSC group (Table). Conclusions: Survival benefit of 2nd-line CTx was observed in patients with the score 0 and 1, but not in the score 2. [Table: see text]


2019 ◽  
Author(s):  
Zhimin Zhang ◽  
jiangbiao Huang ◽  
Ge Wang ◽  
Feng Jin ◽  
Jijun Zheng ◽  
...  

Abstract Background: Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods: This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years.The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results: Using fold change≥2.0 or ≤0.5 and p≤0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR=3.149, 95%CI:1.018-9.115, p=0.034), whereas combining the former two is independent for OS (HR=5.146, 95%CI:1.674-15.817, p=0.04). Conclusions : For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19013-e19013
Author(s):  
M. Cobo ◽  
J. Martinez ◽  
A. Montesa ◽  
S. Gil-Calle ◽  
E. Villar-Chamorro ◽  
...  

e19013 Background: phase II trial-efficacy & toxicity of sequential erlotinib in advanced NSCLC after platinum-based CT Methods: Pts with adv NSCLC, PS 0/1, adequate renal, hepatic and bone marrow function, no PD after CT. Treatment: erlotinib 150 mg/day starting 3–4 weeks after CT until progression. Safety was evaluated monthly and tumor evaluation bimonthly. Results: 47 pts enrrolled:42(89%)stageIV & 5(11%)wet IIIB, all valid for response & toxicity. Median age 62 y(r:39 -77): 39(83%) males and 8(17%) females. Histology: adenocarcinoma 8(61.7%), bronquioloalveolar 3(6.4%), large cell 3(6.4%), squamous12(25.5%). PS 0: 23(49%), PS 1:24(51%). 38(81.9%) completed 6 cycles of CT. Response: CR: 1(2.1%), PR: 2(51.1%), EE: 22 (46%). Sequential erlotinib improved RR in 6 (12.8%), 23 (48.9) prolonged stabilization, 18 (38.3%) had progression. Median TTP and OS were 9.4 m (95% CI, 4.96–13–84), and 19.23 m (95% CI, 8.82–29.64). No significant differences in TTP according to age, sex, PS, histology or previous response to CT, but yes depending on RR to erlotinib: PR: 31.5 m (95% CI 15.37–47.63), EE: 12.8 m (95% CI, 10.58–15.03), PD: 6.3 m (95% CI, 5.36–7.3), p < 0.001; and moreover depending on smoking status: Never: 21.67 m(95% CI, 5.39–37.94), previous smoker > 5 years: 14.03 m(95% CI, 10.77–17.30), previous smoker 1 year: 7.77 m(95% CI, 7.62–7.91), current smoker: 5.9 m(95% CI, 5.12–6.34), p <0.001. In Cox-regression model, smoking status ( p< 0.001), and response to erlotinib (p=0.002) were associated with a significant difference in TTP. Similar results in OS, although in Cox-regression model only never smoker or > 5 years previous smoker pts had a significant better survival. Toxicity: The most frequent was skin rash, grade (g) 1 in 11(23.4%), g 2: 16(34%) and g 3: 3(6.4%). Only 1 p had diarrea g 3, and no other side effects were observed. We found a significant benefit in p with g 2–3 skin toxicity respect g 0–1, in both TTP( p= 0.0003) and OS (p= 0.0014). Conclusions: Erlotinib-maintenance therapy after platinum-based CT had promising results. Pts with the best benefit were those with response to erlotinib, in never or past (> 5 years) smokers and with g 2–3 skin toxicity. No significant financial relationships to disclose.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S448-S449
Author(s):  
Jongtak Jung ◽  
Pyoeng Gyun Choe ◽  
Chang Kyung Kang ◽  
Kyung Ho Song ◽  
Wan Beom Park ◽  
...  

Abstract Background Acinetobacter baumannii is one of the major pathogens of hospital-acquired infection recently and hospital outbreaks have been reported worldwide. On September 2017, New intensive care unit(ICU) with only single rooms, remodeling from old ICU with multibed bay rooms, was opened in an acute-care tertiary hospital in Seoul, Korea. We investigated the effect of room privatization in the ICU on the acquisition of carbapenem-resistant Acinetobacter baumannii(CRAB). Methods We retrospectively reviewed medical records of patients who admitted to the medical ICU in a tertiary care university-affiliated 1,800-bed hospital from 1 January 2015 to 1 January 2019. Patients admitted to the medical ICU before the remodeling of the ICU were designated as the control group, and those who admitted to the medical ICU after the remodeling were designated as the intervention group. Then we compared the acquisition rate of CRAB between the control and intervention groups. Patients colonized with CRAB or patients with CRAB identified in screening tests were excluded from the study population. The multivariable Cox regression model was performed using variables with p-values of less than 0.1 in the univariate analysis. Results A total of 1,105 cases admitted to the ICU during the study period were analyzed. CRAB was isolated from 110 cases in the control group(n=687), and 16 cases in the intervention group(n=418). In univariate analysis, room privatization, prior exposure to antibiotics (carbapenem, vancomycin, fluoroquinolone), mechanical ventilation, central venous catheter, tracheostomy, the presence of feeding tube(Levin tube or percutaneous gastrostomy) and the length of ICU stay were significant risk factors for the acquisition of CRAB (p&lt; 0.05). In the multivariable Cox regression model, the presence of feeding tube(Hazard ratio(HR) 4.815, 95% Confidence interval(CI) 1.94-11.96, p=0.001) and room privatization(HR 0.024, 95% CI 0.127-0.396, p=0.000) were independent risk factors. Table 1. Univariate analysis of Carbapenem-resistant Acinetobacter baumannii Table 2. Multivariable Cox regression model of the acquisition of Carbapenem-resistant Acinetobacter baumannii Conclusion In the present study, room privatization of the ICU was correlated with the reduction of CRAB acquisition independently. Remodeling of the ICU to the single room would be an efficient strategy for preventing the spreading of multidrug-resistant organisms and hospital-acquired infection. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ilari Kuitunen ◽  
Ville T. Ponkilainen ◽  
Mikko M. Uimonen ◽  
Antti Eskelinen ◽  
Aleksi Reito

Abstract Background Survival analysis and effect of covariates on survival time is a central research interest. Cox proportional hazards regression remains as a gold standard in the survival analysis. The Cox model relies on the assumption of proportional hazards (PH) across different covariates. PH assumptions should be assessed and handled if violated. Our aim was to investigate the reporting of the Cox regression model details and testing of the PH assumption in survival analysis in total joint arthroplasty (TJA) studies. Methods We conducted a review in the PubMed database on 28th August 2019. A total of 1154 studies were identified. The abstracts of these studies were screened for words “cox and “hazard*” and if either was found the abstract was read. The abstract had to fulfill the following criteria to be included in the full-text phase: topic was knee or hip TJA surgery; survival analysis was used, and hazard ratio reported. If all the presented criteria were met, the full-text version of the article was then read. The full-text was included if Cox method was used to analyze TJA survival. After accessing the full-texts 318 articles were included in final analysis. Results The PH assumption was mentioned in 114 of the included studies (36%). KM analysis was used in 281 (88%) studies and the KM curves were presented graphically in 243 of these (87%). In 110 (45%) studies, the KM survival curves crossed in at least one of the presented figures. The most common way to test the PH assumption was to inspect the log-minus-log plots (n = 59). The time-axis division method was the most used corrected model (n = 30) in cox analysis. Of the 318 included studies only 63 (20%) met the following criteria: PH assumption mentioned, PH assumption tested, testing method of the PH assumption named, the result of the testing mentioned, and the Cox regression model corrected, if required. Conclusions Reporting and testing of the PH assumption and dealing with non-proportionality in hip and knee TJA studies was limited. More awareness and education regarding the assumptions behind the used statistical models among researchers, reviewers and editors are needed to improve the quality of TJA research. This could be achieved by better collaboration with methodologists and statisticians and introducing more specific reporting guidelines for TJA studies. Neglecting obvious non-proportionality undermines the overall research efforts since causes of non-proportionality, such as possible underlying pathomechanisms, are not considered and discussed.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 674.1-674
Author(s):  
C. C. Mok ◽  
C. S. Sin ◽  
K. C. Hau ◽  
T. H. Kwan

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared


1998 ◽  
Vol 19 (3) ◽  
pp. S78-S79
Author(s):  
Charles Oprian ◽  
Kwan Hur ◽  
William Henderson ◽  
Bharat Thakkar ◽  
Frederick Masoudi ◽  
...  

2019 ◽  
Vol 29 (5) ◽  
pp. 1447-1465 ◽  
Author(s):  
DE McGregor ◽  
J Palarea-Albaladejo ◽  
PM Dall ◽  
K Hron ◽  
SFM Chastin

Survival analysis is commonly conducted in medical and public health research to assess the association of an exposure or intervention with a hard end outcome such as mortality. The Cox (proportional hazards) regression model is probably the most popular statistical tool used in this context. However, when the exposure includes compositional covariables (that is, variables representing a relative makeup such as a nutritional or physical activity behaviour composition), some basic assumptions of the Cox regression model and associated significance tests are violated. Compositional variables involve an intrinsic interplay between one another which precludes results and conclusions based on considering them in isolation as is ordinarily done. In this work, we introduce a formulation of the Cox regression model in terms of log-ratio coordinates which suitably deals with the constraints of compositional covariates, facilitates the use of common statistical inference methods, and allows for scientifically meaningful interpretations. We illustrate its practical application to a public health problem: the estimation of the mortality hazard associated with the composition of daily activity behaviour (physical activity, sitting time and sleep) using data from the U.S. National Health and Nutrition Examination Survey (NHANES).


2020 ◽  
Vol 39 (10) ◽  
pp. 1558-1572
Author(s):  
Euloge C. Kenne Pagui ◽  
Enrico A. Colosimo

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