Association of germ-line single nucleotide polymorphisms (SNPs) with pathologic response to neoadjuvant cisplatin-based chemotherapy in patients with resectable non-small cell lung cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7558-7558
Author(s):  
Jamie E. Chaft ◽  
Sohela Shah ◽  
Esther N. Drill ◽  
Camelia S. Sima ◽  
Vijai Joseph ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Association Studies ◽  
Predictive Biomarkers ◽  
Pathologic Response ◽  
North American Population ◽  
Candidate Snps ◽  
Genome Wide Association Studies ◽  
Lung Cancers ◽  
Study Results ◽  
Response To Neoadjuvant Chemotherapy

7558 Background: Pathologic response to neoadjuvant chemotherapy correlates with survival in resected lung cancers. Predictive biomarkers of response are needed. Tumor-specific biomarkers have been hindered by reproducibility and specimen adequacy. Genome-wide association studies (most in SE Asia) have identified candidate SNPs that correlate with clinical outcomes after cisplatin-based chemotherapy. We evaluated whether these candidate SNPs are predictive of pathologic response to neoadjuvant chemotherapy in a US population. Methods: We aimed to correlate SNPs with near complete PR (ncPR) to neoadjuvant cisplatin + docetaxel in patients with resectable lung cancers. ncPR was defined as 90% necrosis, inflammation and fibrosis across serial 1cm sections of the resected tumor. Germline DNA was extracted and 50 candidate SNPs were genotyped by Sequenom Mass ARRAY iPLEX. SNPs were analyzed for correlation with ncPR using recessive (aa vs AA/aA) , dominant (AA vs aa/aA) and log-additive (linear increase in risk with each additional allele) genetic models. In this exploratory dataset, a p-value <0.1 was considered worthy of further study. Results: 60 patients were treated and had sufficient DNA for analysis. Nine patients had a ncPR. 7 of 50 SNPs (table) correlated with pathologic response in one of the three models. Conclusions: Of the candidate SNPs identified from the literature, 7 showed a promising correlation to ncPR to neoadjuvant chemotherapy. This expands upon the experience evaluating SNPs and chemotherapy sensitivity into a North American population. Study of these 7 SNPs is ongoing in our current multimodality trial as a validation cohort. This study was funded by the Lung Cancer Research Foundation. [Table: see text]

Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients

The Breast ◽  
2018 ◽  
Vol 39 ◽  
pp. 19-23 ◽  
Author(s):  
Annina Baumgartner ◽  
Christoph Tausch ◽  
Stefanie Hosch ◽  
Bärbel Papassotiropoulos ◽  
Zsuzsanna Varga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathologic Response ◽  
Breast Cancer Patients ◽  
Response To Neoadjuvant Chemotherapy

scholarly journals Single-plant GWAS coupled with bulk segregant analysis allows rapid identification and corroboration of plant-height candidate SNPs

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Abiskar Gyawali ◽  
Vivek Shrestha ◽  
Katherine E. Guill ◽  
Sherry Flint-Garcia ◽  
Timothy M. Beissinger
Keyword(s):  
Plant Height ◽  
Bulk Segregant Analysis ◽  
Association Studies ◽  
Significant Snps ◽  
Rapid Identification ◽  
Candidate Snps ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Plant ◽  
Crop Species

Abstract Background Genome wide association studies (GWAS) are a powerful tool for identifying quantitative trait loci (QTL) and causal single nucleotide polymorphisms (SNPs)/genes associated with various important traits in crop species. Typically, GWAS in crops are performed using a panel of inbred lines, where multiple replicates of the same inbred are measured and the average phenotype is taken as the response variable. Here we describe and evaluate single plant GWAS (sp-GWAS) for performing a GWAS on individual plants, which does not require an association panel of inbreds. Instead sp-GWAS relies on the phenotypes and genotypes from individual plants sampled from a randomly mating population. Importantly, we demonstrate how sp-GWAS can be efficiently combined with a bulk segregant analysis (BSA) experiment to rapidly corroborate evidence for significant SNPs. Results In this study we used the Shoepeg maize landrace, collected as an open pollinating variety from a farm in Southern Missouri in the 1960’s, to evaluate whether sp-GWAS coupled with BSA can efficiently and powerfully used to detect significant association of SNPs for plant height (PH). Plant were grown in 8 locations across two years and in total 768 individuals were genotyped and phenotyped for sp-GWAS. A total of 306 k polymorphic markers in 768 individuals evaluated via association analysis detected 25 significant SNPs (P ≤ 0.00001) for PH. The results from our single-plant GWAS were further validated by bulk segregant analysis (BSA) for PH. BSA sequencing was performed on the same population by selecting tall and short plants as separate bulks. This approach identified 37 genomic regions for plant height. Of the 25 significant SNPs from GWAS, the three most significant SNPs co-localize with regions identified by BSA. Conclusion Overall, this study demonstrates that sp-GWAS coupled with BSA can be a useful tool for detecting significant SNPs and identifying candidate genes. This result is particularly useful for species/populations where association panels are not readily available.

The predictive role of metabolic tumor volume on no response to neoadjuvant chemotherapy in patients with breast cancer

2020 ◽  
Vol 26 (6) ◽  
pp. 1415-1420
Author(s):  
Serdar Arici ◽  
Sevda S Karyagar ◽  
Savas Karyagar ◽  
Caglayan Geredeli ◽  
Ruhper Cekin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Volume ◽  
Growth Factor Receptor ◽  
Metabolic Tumor Volume ◽  
Pathologic Response ◽  
Pathological Response ◽  
Number Of Patients ◽  
Study Results ◽  
Response Group

Introduction To evaluate the predictive significance of pretreatment metabolic tumor volume on pathologic response in patients who received neoadjuvant chemotherapy for breast cancer. Methods Seventy patients who received neoadjuvant chemotherapy between 2013 and 2017 years were enrolled in the study. Pathologic responses and 18-fluorodeoxyglucose positron emission tomography/computed tomography metabolic dates of patients were obtained from archive files. Results Forty-six (65.7%) patients were in stage II and 24 (34.3%) patients were in stage III; 25 (35.7%) patients were human epidermal growth factor receptor 2 positive, 46 (65.7%) patients were estrogen receptor-positive, 26 (37.1%) patients were progesterone receptor-positive. According to the Miller-Payne grading system, 24 (34.3%) patients constituted 100% pathological response; patients with 91–99% pathological response were 12 (17.1%), the number of patients with non-pathologic response was 6 (8.6%). Median metabolic tumor volume was 7.3 cm3 (7.1 ± 3.5), 8.8 (11.4 ± 9.4), 7.7 (8.3 ± 4.6) and 22 cm3 (19.8 ± 11.0) in patients with stages IIA, IIB, IIIA, and IIIB, respectively ( p = 0.032). In Miller-Payne grading, the median metabolic tumor volume value was higher in patients with no pathologic response group than 100% response group ( p = 0.003). The cut-off metabolic tumor volume value determining no pathologic response was calculated as higher than 13.62 cm3 (sensitivity 83.3% and specificity 82.8%). Conclusions Our study results suggest that higher pretreatment metabolic tumor volume values are predictive on no pathologic response in patients treated with neoadjuvant chemotherapy for breast cancer.

Response to neoadjuvant chemotherapy and impact on survival for resected gastric cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 122-122
Author(s):  
Erin Greenleaf ◽  
Christopher S Hollenbeak ◽  
Joyce Wong
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Disease Progression ◽  
Median Time ◽  
Pathologic Response ◽  
Early Stage Disease ◽  
Stage Disease ◽  
The Impact ◽  
Response To Neoadjuvant Chemotherapy

122 Background: This study assesses the survival impact of perioperative chemotherapy, with further analysis of pathologic response to neoadjuvant chemotherapy (NAC), in patients undergoing gastrectomy for gastric cancer (GC) in a large US sample. Methods: Using the 2003-2012 ACS National Cancer Database, 16,128 patients underwent gastrectomy for cancer. Treatment groups were categorized as: NAC, adjuvant chemotherapy, and surgery only. Patients receiving NAC were further categorized as: down-staged, no response, and disease progression. Univariate and multivariate analyses were performed to estimate the impact of treatment on overall survival. Results: Of patients undergoing gastrectomy, 36.6% received NAC, 19.5% received adjuvant chemotherapy, and 43.9% underwent surgery only. Median time of survival was longer in patients with more advanced disease who underwent either NAC or adjuvant chemotherapy versus surgery alone (see Table). In multivariate analysis, patients who received NAC had 20% lower hazard of death than surgery only patients (HR = 0.80, p < 0.0001). Within the NAC cohort (N = 5,909), 47.7% were down-staged, 36.5% had no response, and 15.7% demonstrated disease progression. Having a pathologic response to NAC was associated with having private insurance (OR = 1.22, p < 0.0001), higher socioeconomic status (OR = 1.21, p = 0.003), treatment in the central US (p < 0.0001, both), and undergoing proximal gastrectomy (OR = 1.59, p < 0.0001). Among patients who received NAC, median time of survival was longer if NAC down-staged patients to stages 0 or 1, with no survival difference in advanced stage disease. Conclusions: Neoadjuvant chemotherapy elicits a survival benefit in patients with advanced GC. Pathologic response is achieved in nearly half of patients undergoing NAC and is associated with improved survival, although only when down-staging to early stage disease. [Table: see text] [Table: see text]

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