scholarly journals Commercially Available Gene Expression Assays as Predictive Tools for Adjuvant Radiotherapy? A Critical Review

Breast Care ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. 118-127 ◽  
Author(s):  
David Krug ◽  
René Baumann ◽  
Wilfried Budach ◽  
Marciana Nona Duma ◽  
Jürgen Dunst ◽  
...  
Keyword(s):  
Gene Expression ◽  
Decision Making ◽  
Predictive Value ◽  
Adjuvant Radiotherapy ◽  
Clinical Indication ◽  
Adjuvant Radiation ◽  
Recurrence Rates ◽  
Hormone Receptor Positive ◽  
Prospective Trials

Background: Gene expression assays are increasingly used for decision-making regarding adjuvant chemotherapy in patients with hormone receptor-positive, HER2-negative breast cancer. There are some clinical situations in which there is also a need for better prognostic and predictive markers to better estimate the amount of benefit from adjuvant radiotherapy. The rising availability of gene expression analyses prompts the question whether their results can also be used to guide clinical decisions regarding adjuvant radiation. Summary: Multiple studies suggest a correlation between results from gene expression assays and locoregional recurrence rates. Only few publications addressed the predictive value of results from gene expression analysis for the role of adjuvant radiotherapy in different settings. Key Messages: To date, the available evidence on the possible predictive value of gene expression assays for radiotherapy does not support their inclusion into the decision-making process for adjuvant radiation. This is due to methodological weaknesses and limitations regarding patient selection, the nonrandomized design of all studies in terms of radiotherapy use, and limited availability of tissue from prospective trials. Thus, utilization of the present knowledge for clinical indication of radiotherapy should be very cautious.

scholarly journals Outcomes following myxopapillary ependymoma resection: the importance of capsule integrity

2015 ◽  
Vol 39 (2) ◽  
pp. E8 ◽  
Author(s):  
Mohammed Abdulaziz ◽  
Grant W. Mallory ◽  
Mohamad Bydon ◽  
Rafael De la Garza Ramos ◽  
Jason A. Ellis ◽  
...  
Keyword(s):  
Recurrence Rate ◽  
Adjuvant Radiotherapy ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Myxopapillary Ependymoma ◽  
Adjuvant Radiation ◽  
Recurrence Rates ◽  
En Bloc

OBJECT While extent of resection has been shown to correlate with outcomes after myxopapillary ependymoma (MPE) resection, the effect of capsular violation has not been well studied. The role of adjuvant radiation also remains controversial. In this paper the authors' goals were to evaluate outcomes following resection of MPE based on intraoperative capsular violation and to explore the role of adjuvant radiotherapy in cases of capsular violation. METHODS A retrospective review of patients undergoing resection of MPE at 2 academic institutions between 1990 and 2013 was performed. Cases with dissemination at presentation, less than 12 months of follow-up, or incomplete records were excluded. Extent of resection was defined as en bloc if all visible tumor was removed without capsular violation, gross-total resection (GTR) if all visible tumor was removed, but with capsular violation, and subtotal resection (STR) if a known residual was left at the time of surgery. Postoperative MR images were reviewed to confirm the extent of resection. Primary outcomes were progression-free survival (PFS) and overall recurrence rates. The effects of extent of resection, capsular violation, and adjuvant radiotherapy on recurrence rates and PFS were analyzed using Kaplan-Meier statistics. Associations between recurrence and preoperative variables were evaluated using Fisher exact methods and t-tests where appropriate. RESULTS Of the 107 patients reviewed, 58 patients (53% were male) met inclusion criteria. The mean age at surgery was 40.8 years (range 7–68 years). The median follow-up was 51.5 months (range 12–243 months). Extent of resection was defined as en bloc in 46.5% (n = 27), GTR in 34.5% (n = 20), and STR in 18.9% (n = 11). No recurrences were noted in the en bloc group, compared with 15% (n = 3) and 45% (n = 5) in the GTR and STR groups. En bloc resection was achieved most frequently in tumors involving the conus. Twelve patients (20%) underwent adjuvant radiotherapy following either STR or GTR. The overall recurrence rate was 13.8% (n = 8), and the 5-year PFS was 81%. Capsular violation was associated with a higher recurrence rate (p = 0.005). Adjuvant radiotherapy showed a nonsignificant trend of lower recurrence rates (16.7% vs 31.6%, p = 0.43) and longer PFS at 5 years (83.3% vs 49.9%, p = 0.16) in cases of capsular violation. CONCLUSIONS A strong correlation between capsular violation and recurrence was found following removal of MPE and should be assessed when defining extent of resection in future studies. Although the use of adjuvant radiotherapy in cases of capsular violation showed a trend toward improved PFS, further investigation is needed to establish its role as salvage therapy also appears to be effective at halting disease progression.

scholarly journals The Role of VEGFA, COX2, HUR and CUGBP2 in Predicting the Response to Neoadjuvant Therapy in Rectal Cancer Patients

Medicina ◽  
2020 ◽  
Vol 56 (4) ◽  
pp. 192
Author(s):  
Henrikas Pauzas ◽  
Ugne Gyvyte ◽  
Tadas Latkauskas ◽  
Laura Kairevice ◽  
Paulius Lizdenis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Predictive Value ◽  
Post Treatment ◽  
Treatment Changes ◽  
Pre Treatment ◽  
Cox2 Expression ◽  
Vegfa Gene

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.

Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation

2002 ◽  
Vol 12 (3) ◽  
pp. 237-249 ◽  
Author(s):  
K Look
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Adjuvant Radiotherapy ◽  
Survival Benefit ◽  
Older Patients ◽  
Endometrial Adenocarcinoma ◽  
Stage I ◽  
Surgical Staging ◽  
Adjuvant Radiation

Abstract.Look K. Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation.The objective was to review the English-language literature regarding the utility of adjuvant radiation therapy following surgery for endometrial adenocarcinoma. An OVID software (Ovid Technologies, Inc., New York, NY) search of Medline articles from 1975 to 2001 was conducted using the keywords “endometrial neoplasm,”“surgery,” and “radiation therapy.” The papers were assessed with regard to (a) extent of surgical staging (b) type of adjuvant radiotherapy utilized: external vs. brachytherapy vs. combination therapy; and (c) whether the patients were treated as part of prospective trial or reported as a descriptive series reflecting an institution's practice pattern. Survival rates are excellent for patients with early stage disease treated in either paradigm of extended-surgical staging with more restricted use of the adjuvant therapy or simple hysterectomy bilateral salpingoophorectomy with more frequent use of adjvuant radiotherapy. All three prospecctive-randomized trials (PRCT) have shown an improvement in local control but no overall survival benefit for the entire accrued group. All three PRCTs have shown a higher risk of disease recurrence in older patients or those with grade 3 histology or deep invasion. Each suggests there may be a survival benefit for the subset of patients with such high-risk features, but at present there is no prospective data that demonstrates adjuvant radiotherapy will improve the overall survival for the highest-risk subset of older patients with high-grade deeply invasive disease.

scholarly journals Radiotherapy of Ductal Carcinoma In Situ

Breast Care ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. 259-264 ◽  
Author(s):  
David Krug ◽  
Rainer Souchon
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Multidisciplinary Treatment ◽  
Breast Conserving Surgery ◽  
Adjuvant Radiation ◽  
Recurrence Rates ◽  
The Past

Ductal carcinoma in situ (DCIS) is a heterogeneous disease in both its biology and clinical course. In the past, recurrence rates after breast-conserving surgery have been as high as 30% after 10 years. The introduction of mammography screening and advances in imaging have led to an increase in the detection of DCIS. The focus of this review is on the role of radiotherapy in the multidisciplinary treatment, including current developments in hypofractionation and boost delivery, and attempts to define low-risk subsets of DCIS for which the need for adjuvant radiation is repeatedly questioned.

scholarly journals MicroRNAs in AKI and Kidney Transplantation

2019 ◽  
Vol 14 (3) ◽  
pp. 454-468 ◽  
Author(s):  
Kristien J. Ledeganck ◽  
Els M. Gielis ◽  
Daniel Abramowicz ◽  
Peter Stenvinkel ◽  
Paul G. Shiels ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Transplantation ◽  
Kidney Disease ◽  
Disease Prevention ◽  
Clinical Evidence ◽  
Prospective Trials ◽  
Epigenetic Regulators ◽  
Novel Targets ◽  
Posttranscriptional Level

MicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation.

scholarly journals Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis

2019 ◽  
Vol 46 (6) ◽  
pp. E3 ◽  
Author(s):  
Abhinav K. Reddy ◽  
James S. Ryoo ◽  
Steven Denyer ◽  
Laura S. McGuire ◽  
Ankit I. Mehta
Keyword(s):  
Adjuvant Radiotherapy ◽  
Survival Benefit ◽  
Atypical Meningioma ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Total Resection ◽  
Cause Specific Survival ◽  
End Results

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Surgery versus surgery with adjuvant radiotherapy for T4 colon cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 673-673 ◽  
Author(s):  
Nikhil Sebastian ◽  
Eric David Miller ◽  
Dayssy Alexandra Diaz Pardo
Keyword(s):  
Colon Cancer ◽  
Adjuvant Radiotherapy ◽  
Cox Regression ◽  
Locally Advanced ◽  
Adjuvant Radiation ◽  
Disease Specific Survival ◽  
T4 Colon Cancer ◽  
National Databases ◽  
Disease Specific

673 Background: There is no randomized prospective evidence to clarify the role of adjuvant radiotherapy in localized colon cancer. Despite this, national consensus guidelines recommend that adjuvant radiotherapy be considered for patients with T4 disease. Given the lack of prospective data, the aim of this study was to evaluate the role of adjuvant radiation therapy (RT) in colon cancer using two large national databases to help to guide treatment decisions. Methods: We evaluated the association of receipt of adjuvant RT with overall survival (OS), using the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER), as well as with disease-specific survival (DSS) using SEER. We analyzed cohorts of patients with histologically confirmed locally advanced T4 adenocarcinoma of the colon, who underwent oncologic surgery with or without adjuvant radiation and had at least 5 years of follow up. For the NCDB cohort, we restricted RT patients to those who received a dose of 45-60 Gy and those who received treatment within 3 months after surgery. We used nearest-neighbor propensity score matching on the basis of age, race, sex, year of diagnosis, grade, N-stage, receipt of chemotherapy, anatomical subsite, margin status, and comorbidity score. To validate our findings, using SEER, we used propensity matching using the same covariates (except comorbidity). Results: After matching of the NCDB cohort, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=1.08; 95% CI 0.89 - 1.30; p=0.448). Using SEER, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=0.9; 95% CI 0.50 - 1.63; p=0.731) or DSS (HR=0.84; 0.54 – 1.33; p=0.46). Conclusions: In summary, after comprehensively adjusting for covariates using two independent national databases, we found no statistically significant association of adjuvant RT with overall- or disease-specific survival for T4 colon cancer. These findings are limited by the retrospective nature of the data and should be tested in a prospective fashion.

Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Cognitive Processes ◽  
Evolutionary History ◽  
Behavioral Responses ◽  
History Of ◽  
Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

Role of small nuclear RNAs in eukaryotic gene expression

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Stability ◽  
Splice Sites ◽  
Branch Site ◽  
Small Nuclear Rnas ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

The Role of Shared Decision-Making in Audiologic Rehabilitation

2014 ◽  
Vol 21 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Helen Pryce ◽  
Amanda Hall
Keyword(s):  
Decision Making ◽  
Shared Decision Making ◽  
Behavior Changes ◽  
Shared Decision ◽  
Patient Centered ◽  
Treatment Information ◽  
Centered Care ◽  
Potential Risks ◽  
Audiologic Rehabilitation

Shared decision-making (SDM), a component of patient-centered care, is the process in which the clinician and patient both participate in decision-making about treatment; information is shared between the parties and both agree with the decision. Shared decision-making is appropriate for health care conditions in which there is more than one evidence-based treatment or management option that have different benefits and risks. The patient's involvement ensures that the decisions regarding treatment are sensitive to the patient's values and preferences. Audiologic rehabilitation requires substantial behavior changes on the part of patients and includes benefits to their communication as well as compromises and potential risks. This article identifies the importance of shared decision-making in audiologic rehabilitation and the changes required to implement it effectively.

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