Clinicopathological analysis of KRAS mutation in an Irish population.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 467-467
Author(s):  
M. Teo ◽  
S. O'Reilly ◽  
E. Moylan ◽  
D. G. Power

467 Background: Clinical trials have shown that tumor KRAS status predicts response to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). We sought to compare distribution of wild-type and mutated KRAS in an Irish population and identify clinicopathologic correlates. Methods: From our prospectively maintained database we retrospectively identified patients with mCRC and documented KRAS status between Jan 2007 to June 2010. Medical notes were examined for patient demographics and disease characteristics. Variables were extracted and compared using unpaired t test and chi2 test. Results: 52 patients were identified, 29 (55.8%) with mutated (mt) and 23 (44.2%) with wild type (wt) KRAS from tumor tissue. Males accounted for 61.5% (n=31). Median age at diagnosis of metastatic disease for the KRASmt group was 66.4 years (range 56.7-82.1) and for the KRAS wt group was 64.2 years (40.1-76.8), p= 0.08. 21 (72.4%) of the KRASmt group and 16 (69.6%) of the KRASwt group had metastatic disease at presentation (p=0.81). For patients who presented initially with localised disease, time to development of metastases was 22.5mo (range 14-37.6) for the KRASmt group and 16.7mo (3.2-123.7) for the KRASwt (p=0.30). 21 (72.4%) of KRASmt and 17 (74.1%) of KRASwt tumors had left-sided primary (p = 0.84) with equal numbers of primary tumor resection in both groups. There was no statistical difference in TN-stage or the presence of liver metastases. Numbers of patients with KRASmt tumors with one, two and three or more different sites of metastases was 22 (75.9%), 5 (17.2%), and 2 (6.9%), and in KRASwt tumors there was no significant difference: 18 (78.3%), 4 (17.4%), and 1 (4.3%), respectively (p = 0.93). Median CEA at diagnosis for both groups were 19.7 μg/l (range 1.2-5958) and 6.1 (1.3-696.9; p = 0.11). Conclusions: We found that the ratio of KRASmt to KRASwt tumours in an Irish population is comparable to that in large international trials. Our analysis revealed no association between KRAS status and clinicopathologic variables. The inclusion of BRAF status, not readily available in our institution, may help define poor prognosis tumors. At present there is no validated molecular biomarker that is superior to standard clinicopathologic variables. No significant financial relationships to disclose.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 664-664
Author(s):  
Michael Schacht ◽  
Douglas M. Coldwell ◽  
Vivek Sharma

664 Background: Radioembolization with either Yttrium-90 labeled resin or glass microspheres is an FDA approved treatment for hepatic metastases from primary colorectal cancer. Y-90 therapy is used almost exclusively in unresectable liver metastases. However, radioembolization is only an optional part of the treatment process along with first-line, second-line, and salvage chemotherapy. KRAS is a known proto-onco gene that has typically been studied as a negative prognostic factor in the chemotherapeutic treatment of metastatic colorectal cancer (mCRC). KRAS is a known marker for resistance to anti-EGFR antibodies and generally have a poorer prognosis. The aim of this study is to begin to shed light on the impact of KRAS status on the outcome of patients undergoing radioembolization for the treatment of unresectable liver predominant metastatic CRC, regardless of their chemotherapy regimens. Methods: This is a retrospective analysis of 18 subjects treated with radioembolization for liver predominant metastatic CRC. KRAS status and treatment outcomes were followed for each patient up to the study close date of 9/15/13. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the 18 subjects included in the study, 5 were found to have KRAS mutant oncogene. The remaining 13 were found to have the KRAS wildtype. Overall, those subjects with KRAS mutant were found to have a statistically significant difference in median time to progression of intrahepatic metastatic disease burden when compared to KRAS wildtype even when liver-directed therapy was utilized (2.0 vs. 6.4 months). Differences in median time to progression of extrahepatic metastatic disease burden and overall survival were not found to be statistically significant at this time. Conclusions: KRAS mutant patients are exceedingly difficult to treat due to both intrahepatic and extrahepatic disease recurrence/progression.


2018 ◽  
Vol 80 (04) ◽  
pp. 364-370
Author(s):  
David M. Rosenberg ◽  
Brett W. Geever ◽  
Akash S. Patel ◽  
Anisse N. Chaker ◽  
Abhiraj D. Bhimani ◽  
...  

Objectives Neoplasms involving the pineal gland are rare. When they do occur, tumor resection is anatomically challenging and is traditionally addressed by either a supratentorial or an infratentorial approach. To date, no large, multicenter studies have been performed that systematically analyze outcomes comparing these two approaches. This study aimed to evaluate outcomes for patients undergoing pineal neoplasm resection, comparing supratentorial and infratentorial approaches. Design Retrospective database review. Setting Multi-institutional database. Participants From 2005 to 2016, 60 patients were identified, with 13 undergoing a supratentorial approach and 47 undergoing an infratentorial approach. Main Outcome Measures Patient demographics, comorbidities, and 30-day postoperative outcomes were investigated using the American College of Surgeons National Surgical Quality Improvement Program database. Demographics, readmission, reoperation, and complication rates were analyzed and compared with previous studies. Results Patient demographics were similar between these two groups. The overall complication rates for the supratentorial and infratentorial approaches were 30.8 and 17%, respectively, and the difference was not statistically significant. The most common medical complications encountered were respiratory and hematological. Conclusion As the first multi-institutional database analysis of approaches to the pineal gland, this study provides an analysis of patient demographics, comorbidities, and postoperative complications. After controlling for preoperative risk factors and demographic characteristics, no statistically significant differences in postoperative outcomes were found between infratentorial and supratentorial approaches. The mean readmission, reoperation, and complication rates were found to be 2.1, 8.3, and 20%, respectively. The lack of significant difference between approaches suggests that clinical decision-making should depend upon anatomical considerations and physician preference, although the complications illustrated here may provide some preoperative guidance.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ke Wang ◽  
Yeming Li ◽  
Haiyang Cheng ◽  
Shenjie Li ◽  
Wei Xiang ◽  
...  

Abstract Background The aim of this study was to investigate the relationship between tumor biology and values of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), permeability surface (PS) of tumor in patients with glioma. Methods Forty-six patients with glioma were involved in the study. Histopathologic and molecular pathology diagnoses were obtained by tumor resection, and all patients accepted perfusion computed tomography (PCT) before operation. Regions of interests were placed manually at tumor and contralateral normal-appearing thalamus. The parameters of tumor were divided by those of contralateral normal-appearing thalamus to normalize at tumor (relative [r] CBV, rCBF, rMTT, rTTP, rPS). The relationships of the parameters, world health organization (WHO) grade, molecular pathological findings were analysed. Results The rCBV, rMTT and rPS of patients are positively related to the pathological classification (P < 0.05). The values of rCBV and rPS in IDH mutated patients were lower than those IDH wild-type. The values of rCBF in patients with MGMT methylation were lower than those MGMT unmethylation (P < 0.05). The MVD of TERT wild-type group was lower than TERT mutated group (P < 0.05). The values of rCBV were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). The progression free survival (PFS) and overall survival (OS) were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). Conclusions Our study introduces and supports the changes of glioma flow perfusion may be closely related to its biological characteristics.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S430-S431
Author(s):  
I Chu ◽  
R Little ◽  
M Sparrow ◽  
M Ward

Abstract Background Data on outcomes following de-intensification of anti-TNF therapy in inflammatory bowel disease (IBD) are limited and concerns about relapse limit the willingness to de-escalate. This study aimed to evaluate rates of successful de-escalation at 12 months and to determine factors that may predict success. Methods Single-centre retrospective study of IBD patients on dose-intensified infliximab (IFX) or adalimumab (ADA) for secondary loss of response. De-escalation was considered in patients achieving sustained biomarker normalisation. Patients were followed for 12 months post-de-escalation and classified as ‘successes’ if remaining on reduced dose anti-TNF or ‘failures’ if requiring re-escalation, steroids, surgery or enrolment into a clinical trial. Patient demographics, disease characteristics, biomarkers (faecal calprotectin (FCP), C-reactive protein (CRP), albumin), anti-TNF drug levels and thiopurine metabolites were collected. Results Of 24 patients (20 CD, 4 UC), 18 received IFX and 6 received ADA. Patients on IFX were de-escalated to 5 mg/kg 8-weekly (89%) or 10 mg/kg 6-weekly (11%), while patients on ADA were de-escalated to 40 mg fortnightly (83%) or 40 mg weekly (17%). Fifteen out of 24 (63%) patients were successes 12 months post-de-escalation. Of the 9 failures, median time to failure was 6 months (IQR 4.6–9.9) – 6/9 failures required re-escalation of anti-TNF therapy and 3/9 entered a clinical trial. Re-escalation successfully recaptured response in 6/6 (100%) patients after a median of 1.4 years follow-up (IQR 1.1–2.3). Albumin at de-escalation was higher in the success group compared with failures (38 g/l vs. 36 g/l, p = 0.025). There was no significant difference in CRP, FCP, anti-TNF drug level or 6-TGN level between the two groups. There was no difference in IFX levels between successes and failures at the time of de-escalation (5.5 vs. 7.5, p = 0.524) as well as 6 months (3.1 vs. 5.1, p = 0.628) and 12 months (3.2 vs. 6.1, p = 0.457) post de-escalation. There were insufficient data for ADA drug level comparison post-de-escalation. Conclusion Nearly two-thirds of patients remained on reduced anti-TNF dosing at 12 months post-de-escalation. All patients who failed de-escalation were recaptured after dose re-escalation. Other than albumin, no baseline predictors for the success or failure of de-escalation could be identified, although cohort size is small, follow-up was short and the majority of patients achieved sustained biomarker normalisation prior to de-escalation. De-escalation may be considered in patients on intensified anti-TNF therapy in sustained deep remission.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 239-239
Author(s):  
Meaghan Dendy Case ◽  
Anish Ghodadra ◽  
Paula M. Novelli ◽  
Vincent Wu ◽  
Suvranu Ganguli ◽  
...  

239 Background: Assessment of the clinical outcome and prognostic factors of patients receiving Y90 radioembolization to treat colorectal liver metastases. Methods: Multi-institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, systemic therapy regimens, tumor characteristics, laboratory values and overall survival were analyzed between patients with differing histopathologic and genomic status. Genomic profiling was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 445 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 430 patients were available who had documented KRAS mutation status. Average age at diagnosis was found to be 58.4 years for all patients (57.6% male, 42.4% female). Decreased survival post Y90 treatment was shown in those patients with mutant KRAS. The median survival in patients with mutated KRAS was 5.7 months, as compared to 8.0 months in those patients with wild-type KRAS (p< 0.0001). Patient demographics including age, gender and race were not shown to be significant in overall survival post-Y90 treatment (p-values >0.05). The average number of systemic chemotherapy treatments prior to Y90 was 2.15 and was similar between KRAS groups (mutant vs wild type.) KRAS status persisted as a significant predictor of survival on multivariate analysis (p< 0.0001; HR 2.1 CI: 1.54-2.85). Conclusions: KRAS status is shown as a significant prognostic factor in patients with colorectal liver metastases receiving Y90 radioembolization.


2020 ◽  
Vol 132 (4) ◽  
pp. 1033-1042 ◽  
Author(s):  
Nico Sollmann ◽  
Alessia Fratini ◽  
Haosu Zhang ◽  
Claus Zimmer ◽  
Bernhard Meyer ◽  
...  

OBJECTIVENavigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.METHODSFifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).RESULTSA significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.CONCLUSIONSnTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.


2015 ◽  
Vol 16 (12) ◽  
pp. 1300-1311 ◽  
Author(s):  
Daniel Kantor ◽  
Sunil Panchal ◽  
Vikram Patel ◽  
Iwona Bucior ◽  
Richard Rauck

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P&lt;0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P&lt;0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 11 (15) ◽  
pp. 7118
Author(s):  
Ermina Hadzic ◽  
Garth Blackler ◽  
Holly Dupuis ◽  
Stephen James Renaud ◽  
Christopher Thomas Appleton ◽  
...  

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 197-199
Author(s):  
M Patterson ◽  
M Gozdzik ◽  
J Peña-Sánchez ◽  
S Fowler

Abstract Background Appropriate management of inflammatory bowel disease (IBD) often requires multiple specialist appointments per year. Living in rural locations may pose a barrier to regular specialist care. Saskatchewan (SK) has a large rural population. Prior to COVID-19, telehealth (TH) in SK was not routinely used for either patient assessment or follow up. Furthermore, TH was exclusively between hospitals and specific TH sites without direct contact using patient’s personal phones. Aims The objective of this study was to assess the differences in demographics, disease characteristics, outcomes, and health care utilization between patients from rural SK with IBD who used TH and those who did not. Methods A retrospective chart review was completed on all rural patients (postal code S0*) with IBD in SK who were followed at the Multidisciplinary IBD Clinic in Saskatoon between January 2018 and February 2020. Patients were classified as using TH if they had ever used it. Information on demographics, disease characteristics, and access to IBD-related health care in the year prior to their last IBD clinic visit or endoscopy was collected. Data was not collected for clinic visits after March 1, 2020 as all outpatient care became remote secondary to the COVID-19 pandemic. Mean, standard deviations, median and interquartile ranges (IQR) were reported. Mann-Witney U and Chi-Square tests were used to determine differences between the groups. Results In total, 288 rural SK IBD patients were included, 30 (10.4%) used TH and 258 (89.6%) did not. Patient demographics were not significantly different between the two groups; although, there was a statistically significant difference in the proportion of ulcerative colitis patients (17% TH vs. 38% non-TH, p=0.02). The percentage of patients with clinical remission was 87% for TH patients and 74% for non-TH patients (p=0.13). There were no significant differences in health care utilization patterns and biochemical markers of disease, including c-reactive protein (CRP) and fecal calprotectin (FCP) (p&gt;0.05). Conclusions Prior to the pandemic, a small percentage of patients with IBD in rural SK ever used TH. A small proportion of UC patients used TH. No significant differences in disease characteristics, outcomes, or health care utilization were identified. Further study is warranted to identify barriers to use of this technology to tailor care to this patient group and improve access to care, especially now as the COVID-19 pandemic has drastically changed the use of virtual care. Funding Agencies None


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