scholarly journals MPC-04 MOLECULAR FEATURES AND CLINICAL OUTCOMES OF ELDERLY GLIOBLASTOMA PATIENTS: ANALYSES OF KANSAI NETWORK AND TCGA COHORTS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii22-ii23
Author(s):  
Junya Fukai ◽  
Hideyuki Arita ◽  
Toru Umehara ◽  
Ema Yoshioka ◽  
Tomoko Shofuda ◽  
...  

Abstract INTRODUCTION Aging is a negative prognostic factor in glioblastoma (GB) and the genetic background in clinical outcome of elderly GB could exist. This study investigates the difference of elderly patients from younger ones regarding molecular characteristics as well as clinical outcomes in IDH-wildtype GB. METHODS We collected adult cases diagnosed with IDH-wildtype GB and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network) (212 cases) and The Cancer Genome Atlas (TCGA) project (359 cases). Clinical and pathological characteristics were analyzed retrospectively and compared between elderly cases (≥70 years) and younger ones (≤50 years). Molecular analysis included copy number alterations (CNAs) of eight genes (EGFR, PDGFRA, PTEN, CDKN2A, CDK4, MDM2, TP53, NFKBIA). RESULTS Included in the study were 92 (≥70 years)/33 (≤50 years) cases of Kansai Network and 88 (≥70 years)/69 (≤50 years) cases of TCGA. Median overall survival was 12.8 (≥70 years)/ 21.0 (≤50 years) months in Kansai Network cohort and 8.8 (≥70 years)/ 21.09 (≤50 years) months in TCGA cohort. MGMT promoter was methylated in 50 (54.3%) (≥70 years)/14 (42.4%) (≤50 years) tumors in Kansai Network and 34 (48.6%) (≥70 years)/16 (36.4%) (≤50 years) tumors in TCGA. TERT promoter was mutated in 51 (55.4%) (≥70 years)/13 (39.4%) (≤50 years) tumors in Kansai Network and unknown in TCGA. Significant difference of CNA profiles between ≥70 years and ≤50 years was as follows: PTEN del, 43 (46.7%)/8 (24.2%); CDK4 amp, 17 (18.5%)/1 (3.0%) in Kansai Network and CDKN2A del, 69 (78.4%)/ 42 (60.9%) in TCGA. CONCLUSION Elderly patients have several potential factors for poor prognosis and different molecular profiles might explain the survival differences among generations.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
S. Mehta ◽  
D. Rice ◽  
A. McIntyre ◽  
H. Getty ◽  
M. Speechley ◽  
...  

Objective.The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability.Methods.Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership.Results.In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p<0.05). Significant difference in disability was seen between the subgroups.Conclusions.The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.


2021 ◽  
Vol 10 (9) ◽  
pp. 1802
Author(s):  
Grzegorz Meder ◽  
Paweł Żuchowski ◽  
Wojciech Skura ◽  
Violetta Palacz-Duda ◽  
Milena Świtońska ◽  
...  

Endovascular treatment is a rapidly evolving technique; therefore, there is a constant need to evaluate this method and its modifications. This paper discusses a single-center experience and the results of switching from the stent retriever only (SO) mechanical thrombectomy (MT) to the combined approach (CA), with a stent retriever and aspiration catheters. Methods: The study involved a retrospective analysis of 70 patients undergoing MT with the use of either SO or CA. The primary endpoint was the frequency of perfect reperfusion defined as grade 3 of the modified Thrombolysis in Cerebral Infarction scale (mTICI) after the first pass. The secondary endpoints were the procedure success, defined as mTICI grades 2b-3; time of the procedure; clinical outcome, measured by 90 days’ modified Rankin Scale (mRS) score; Δ NIHSS, defined as the difference between National Institutes of Health Stroke Scale (NIHSS) score at patients’ admission and discharge; and the total number of device passes. Results: Out of the 70 patients included, 33 were treated with SO and 37 with CA. In both groups, a total number of 42 patients received intravenous recombined tissue plasminogen activator (iv-rTPA: 20 patients (60.6%) in the SO group and 22 patients (59.5%) in the CA group (p = 1.000). There was a significant difference between the groups regarding first-pass success rate, with 46% in the CA group and 18% in the SO group, (OR 3.83, 95% CI 1.28 to 11.44, p = 0.016). Complete procedure success tended to be more frequent in the CA group than in the SO group—94.6% vs. 84.8% (OR 3.13, 95% CI 0.56 to 17.34, p = 0.193)—and CA tended to require a lower number of passes than SO (mean 1.76 vs. 2.09 passes per procedure, p = 0.114), yet these differences did not reach statistical significance. Mean duration of the procedure was significantly shorter in the CA group than in the SO group (49 min vs. 64 min, p = 0.017). There was a significant difference in clinical outcomes, with higher Δ NIHSS (9.3 in the CA group vs. 6.7 in the SO group, p = 0.025) after the procedure and 90-day mRS (median 2 in the CA group vs. 4 in the SO group, p = 0.031). Conclusions: Combining stent retrievers with aspiration catheters may offer a beneficial effect on angiographic results and clinical outcomes in stroke patients undergoing endovascular treatment.


2018 ◽  
Vol 12 (2) ◽  
pp. 285-293 ◽  
Author(s):  
Seungman Ha ◽  
Youngho Hong ◽  
Seungcheol Lee

<sec><title>Study Design</title><p>Case-control study.</p></sec><sec><title>Purpose</title><p>In this study, we aimed to investigate clinical outcomes and morphological features in elderly patients with lumbar spinal stenosis (LSS) who were treated by minimally invasive surgery (MIS) unilateral laminectomy for bilateral decompression (ULBD) using a tubular retractor.</p></sec><sec><title>Overview of Literature</title><p>Numerous methods using imaging have been attempted to describe the severity of spinal stenosis. But the relationship between clinical symptoms and radiological features remains debatable.</p></sec><sec><title>Objective</title><p>In this study, we aimed to investigate clinical outcomes and morphological features in elderly patients with LSS who were treated by MIS-ULBD.</p></sec><sec><title>Methods</title><p>We methodically assessed 85 consecutive patients aged &gt;65 years who were treated for LSS. The patients were retrospectively analyzed in two age groups: 66–75 years (group 1) and &gt;75 years (group 2). Clinical outcomes were assessed using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and the modified MacNab criteria. Outcome parameters were compared between the groups at the 1-year follow-up. Core radiologic parameters for central and lateral stenosis were analyzed and clinical findings of the groups were compared.</p></sec><sec><title>Results</title><p>At the 1-year follow-up, patients in both groups 1 and 2 demonstrated significant improvement in their VAS and ODI scores. All clinical outcomes, except postoperative ODI, were not significantly difference between the groups. In addition, no significant difference was noted in the preoperative radiological parameters between the groups. There was no statistically significant correlation between radiological parameters and clinical symptoms or their outcomes. Moreover, no differences were noted in perioperative adverse events and in the need for repeat surgery at follow-ups between the groups.</p></sec><sec><title>Conclusions</title><p>MIS-ULBD by tubular approach is a safe and effective treatment option for elderly patients with LSS. Clinical outcomes in patients with LSS and aged &gt;75 years were comparable with those in patients with LSS and aged 66–75 years. Moreover, we did not find any correlation between radiological parameters and clinical outcomes in either of the two patient groups.</p></sec>


2020 ◽  
Author(s):  
Wanjin Qin ◽  
Peng Yang ◽  
Nanning Lv ◽  
Kaiwen Chen ◽  
Huilin Yang ◽  
...  

Abstract Background The aim of this study was to evaluate the different clinical outcomes after removing or retaining syndesmotic screws, and the difference in clinical outcomes after retaining broken or loose syndesmotic screws was also evaluated. Methods A systematic literature search was performed using PubMed, Web of Science, EMBASE and the Cochrane Central Register of Controlled Trials. In this meta-analysis, we conducted online searches using the search terms “syndesmotic diastasis”, “syndesmotic injury”, “syndesmotic screw”, “syndesmotic fixation”, and “tibiofibular syndesmosis”. The analysis was performed on individual patient data from all the studies that met the selection criteria. Clinical outcomes were expressed as standard mean differences for continuous outcomes with 95% confidence intervals. Heterogeneity was assessed using the Chi 2 test and the I 2 statistic. Results There were 2 randomized controlled trials (RCTs) and 6 observational articles included in this analysis. In the comparison between retained and removed screws and the comparison between broken or loose and removed screws, no significant difference was found in terms of visual analogue scale (VAS), Olerud-Molander Ankle Score (OMAS) and American Orthopaedic Foot and Ankle Society (AOFAS) ankle/hindfoot score. Broken or loose screws were associated with better AOFAS scores compared with removed or intact screws, and no significant difference was found in terms of VAS and OMAS scores. Conclusions According to our analysis, there was no significant difference in clinical outcomes between removed and retained screws. Broken or loose screws were not associated with bad functional outcomes and may even lead to better function compared with removed or retained screws.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Wang ◽  
Maode Wang ◽  
Haitao Jiang ◽  
Tuo Wang ◽  
Rong Da

Abstract Background The effects of BRAFnon-V600E and BRAFV600E on the outcomes and the molecular characteristics of adult glioma patients are unknown and need to be explored, although BRAFV600E has been extensively studied in pediatric glioma. Methods Co-occurring mutations and copy number alterations of associated genes in the MAPK and p53 pathways were investigated using data from The Cancer Genome Atlas (TCGA) public database retrieved by cBioPortal. The prognosis of available adult glioma cohorts with BRAFV600E and BRAFnon-V600E mutations were also investigated. Results Ninety patients with BRAFV600E or BRAFnon-V600E were enrolled in this study, and data from 52 nonredundant patients were investigated. Glioblastoma multiform was the most common cancer type, with BRAFnon-V600E and BRAFV600E. TP53 (56.00% vs. 7.41%), IDH1/2 (36.00% vs. 3.70%), and ATRX (32.00% vs. 7.41%) exhibited more mutations in BRAFnon-V600E than in BRAFV600E, and TP53 was an independent risk factor (56.00% vs. 7.41%). Both BRAFnon-V600E and BRAFV600E frequently overlapped with CDKN2A/2B homozygous deletions (HDs), but there was no significant difference. Survival analysis showed no difference between the BRAFnon-V600E and BRAFV600E cohorts, even after excluding the survival benefit of IDH1/2 mutations and considering the BRAFnon-V600E mutations in the glycine-rich loop (G-loop) and in the activation segment. The estimated mean survival of patients with BRAFnon-V600E & IDH1/2WT with mutations in the G-loop groups was the shortest. Conclusions BRAFnon-V600E exhibited a stronger association with IDH1/2 mutations than BRAFV600E, but no survival advantage was found.


2021 ◽  
pp. 1-4
Author(s):  
Takahiro Kaki ◽  
◽  
Yoshiaki Minakata ◽  
Yoichi Nakanishi ◽  
Seigo Sasaki ◽  
...  

Background: Although there have been some reports about adverse drug reactions (ADRs) in pulmonary tuberculosis treatment, there are few detailed data and the effect of age among elderly patients on ADRs and the period of medication discontinuation due to ADRs is unknown. Purpose: We evaluated the difference in the incidence of ADRs necessitating discontinuation or a change of medication (dADR) among the different age groups and the period of discontinuation in elderly patients undergoing pulmonary tuberculosis treatment. Subjects and Methods: We conducted a retrospective medical record survey of patients who started anti-tuberculosis medication at our hospital from April 1st, 2018 to March 31st, 2020. Results: A total of 120 patients were recruited. There was no significant difference in the incidence of dADR among the different age groups every 10 years in patients ≥50 years of age (p=0.78). The median period of discontinuation was approximately 4 weeks for fever (29.5 days), approximately 3 weeks for rash (18.5 days), approximately 2 weeks for gastrointestinal disorders (16 days), and hepatocellular liver injury (15.5 days), and approximately 1 week for cholestatic liver injury (8 days) and eosinophilia (7 days). Conclusion: The incidence of dADR was not different among the age groups when patients of ≥50 years of age were compared by age. The median times of onset were 1–3 weeks after the start of treatment. The median periods of discontinuation were 1–4 weeks, and the period of discontinuation due to allergic reactions tended to be the longest


2018 ◽  
Vol 1 (2) ◽  
pp. 48
Author(s):  
Wei Zhao ◽  
Chongbin Gao ◽  
Li Cui ◽  
Fengqun Wang

Purpose: to explore the effect of dexmedetomidine hydrochloride on early cognitive function in postoperative elderly patients. Methods: during December 2015 to November 2016, 80 elderly patients who received surgical treatment in our hospital were selected as research object. Result: patients were randomly divided into two groups (control group and research group). On the basis of routine anesthetic induction, patients in research group took dexmedetomidine, in comparison, patients in control group took an equal dose of sodium chloride solution. The goal was to evaluate the anesthetic effect of those two methods. One hour before surgery, there was no significant difference in the MMSE score between the two groups (P>0.05). In research group, the MMSE scores at postoperative 1d and 3d were (23.8 ± 2.4) and (27.1 ± 2.0) respectively. In control group, the MMSE scores at postoperative 1d and 3d were (20.5 ± 3.2) and (24.6 ± 3.4) respectively. The difference was statistically significant (P<0.05). There was no significant difference in anesthesia time, awake time and extubation time between those two groups (P>0.05). Conclusion: using dexmedetomidine in elderly patients after surgery can protect early cognitive function and improve the prognosis.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3513-3513
Author(s):  
Scott Kopetz ◽  
Danielle A. Murphy ◽  
Jie Pu ◽  
Fortunato Ciardiello ◽  
Jayesh Desai ◽  
...  

3513 Background: Encorafenib + binimetinib + cetuximab (enco/bini/cetux; triplet) and enco + cetux (doublet) regimens improved overall survival and objective response rate vs standard of care in pts with previously treated BRAF V600E-mutant mCRC in the randomized phase 3 BEACON study. To identify molecular correlates of clinical outcome, we performed molecular profiling in tumors from pts in the study. Methods: Baseline tumor samples were retrospectively analyzed by whole-exome sequencing (WES) and whole transcriptome sequencing (WTS) using ImmunoID NeXT (Personalis, Menlo Park, CA, USA). BRAF-mutant (BM) and consensus molecular subtypes (CMS) were determined using published classifiers. Pathway activities were evaluated with gene set variation analysis. Objective tumor response was evaluated according to each subtype. Additional association and interaction analyses between molecular features and clinical outcomes by treatments are ongoing and will be presented. Results: Baseline tumor samples were analyzed by WES and/or WTS from 527 of 665 (79.2%) randomized pts. The biomarker analyses set is representative of the total pt population and had similar clinical outcomes. Of the 460 pts analyzed by WTS (165/224 [73.7%] in the triplet arm, 146/220 [66.4%] in the doublet arm, and 149/221 [67.4%] in the control arm), 84.6% were classified as either CMS1 (n = 225) or CMS4 (n = 164). The proportion of pts classified as BM1 was 32.2% (n = 148) and the majority (84.5%) of these were CMS4, whereas many of those classified as BM2 (67.8%, n = 312) were CMS1 (64.7%). In the BM1 and CMS4 tumors, expression of inflammatory response and epithelial mesenchymal transition genes were elevated, and expression of cell cycle genes was reduced. The response rate in pts with CMS4 and/or BM1 tumors was higher in the triplet arm (CMS4: 33.3% [95% CI: 21.7–46.7]; BM1: 33.3% [95% CI: 21.4–47.1]) compared with the doublet arm (CMS4: 19.2% [95% CI: 9.6–32.5]; BM1: 14.9% [95% CI: 6.2–28.3]). Conclusions: Molecular characteristics and biological properties observed in BRAF V600E-mutant mCRC suggest that a subset of pts with specific molecular features may derive greater clinical benefit from triplet than doublet therapy. Additionally, these findings support the utility of gaining further understanding of the biological landscape in BRAF-mutant mCRC to enable potential hypotheses for pt selection to improve clinical outcome in future studies. Clinical trial information: NCT02928224.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Youliang Ren ◽  
Junsong Yang ◽  
Chien-Min Chen ◽  
Kaixuan Liu ◽  
Xiang-Fu Wang ◽  
...  

Objective. To compare the difference in clinical and radiographic outcomes between anterior transcorporeal and transdiscal percutaneous endoscopic cervical discectomy (ATc-PECD/ATd-PECD) approaches for treating patients with cervical intervertebral disc herniation (CIVDH). Method. We selected 77 patients with single-segment CIVDH and received ATc-PECD or ATd-PECD in the Second Affiliated Hospital of Chongqing Medical University between March 1, 2010, and July 1, 2015. 35 patients suffered from ATc-PECD, and there were 42 patients in the ATd-PECD group. Obtaining the data of 1, 3, 6, 12, and 24 months postoperatively, the VAS for neck and arm pain and the modified MacNab criteria were used to evaluate the clinical outcomes, comparing radiographic outcomes and complications of these two groups. Results. We found that the mean operative time was significantly longer in the ATc-PECD group (P<0.05). At the 2-year follow-up, the mean VAS score for neck and arm pain was significantly decreased in both two groups. There was no significant difference in the VAS score for arm pain and neck pain between the two groups at the 2-year follow-up (P=0.783 and P=0.785, respectively). For the ATc-PECD group, the difference in the height of IVS or vertebral body was significant between the preoperative and postoperative groups (P<0.05, respectively). For the ATd-PECD group, there was only a significant decrease in the height of the IVS (P<0.05); the decrease in the surgical vertebral body was not significant between the preoperative and postoperative groups (P>0.05). Conclusion. In the 2-year follow-up, there is no significant difference in the clinical outcomes between the 2 approaches. While the longer time was consumed in the ATc-PECD group, the lower rate of disc collapse and recurrence is notable. Additionally, when the center diameter of tunnel was limited to 6 mm, the bony defect can be healed without the occurrence of the collapse of the superior endplate, and ATc-PECD may be preferable in the endoscopic treatment of CIVDH.


2019 ◽  
Vol 07 (03) ◽  
pp. E355-E360 ◽  
Author(s):  
Toshiro Iizuka ◽  
Daisuke Kikuchi ◽  
Shu Hoteya

Abstract Background and study aims Endoscopic submucosal dissection (ESD) is increasingly being used to treat superficial esophageal cancer in the elderly. However, data on clinical outcomes in this age group are limited. The aim of this study was to evaluate the safety and efficacy of ESD in treatment of superficial esophageal cancer and its effect on long-term outcome in the elderly. Patients and methods In total, 664 consecutive patients with a histological diagnosis of squamous cell carcinoma or high-grade intraepithelial neoplasia who underwent ESD between April 2008 and March 2016 at our institution were enrolled. Clinical outcomes and prognostic factors were compared retrospectively between those aged 75 years or older (n = 162) and those aged younger than 75 years (n = 502). Results There was no significant difference in post-ESD bleeding (0 vs. 0.8 %, P = 0.27) and perforation rates (1.8 vs. 1.2 %, P = 0.47) between the two age groups; however, stricture rate was higher in younger patients than in elderly patients (20.8 % vs 11 %; P = 0.036). There was no significant difference in the rate of locoregional recurrence between the two groups. Overall survival was significantly different between the two groups, but cause-specific survival was similar. Conclusion These findings confirm the efficacy of ESD for superficial esophageal cancer in selected elderly patients (75 years or older) who were fit for the treatment because they can achieve similar long-term survival to younger patients.


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