scholarly journals Methylation-To-Expression Feature Models of Breast Cancer Accurately Predict Overall Survival, Distant-Recurrence Free Survival, And Pathologic Complete Response in Multiple Cohorts

2017 ◽  
Author(s):  
Jeffrey A. Thompson ◽  
Brock C. Christensen ◽  
Carmen J. Marsit
Keyword(s):  
Overall Survival ◽  
Conflicts Of Interest ◽  
External Validation ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Distant Recurrence ◽  
Prognostic Models ◽  
Recurrence Free Survival ◽  
Validation Data ◽  
Free Survival

AbstractBackground:Approaches that capitalize on the benefits of multi-omic data integration in invasive breast carcinoma to define prognostic biomarkers for precision medicine have been slow to emerge. In this work, we examined the efficacy of our methylation-to-expression feature model (M2EFM) approach to combining molecular and clinical predictors as part of a single analysis to create prognostic risk scores for overall survival, distant metastasis, and chemosensitivity.Methods:Gene expression and DNA methylation values as well as clinical variables were integrated via M2EFM to build prognostic models of overall survival using 1028 breast tumor samples and further applied to external validation cohorts of 61 and 327 samples. Data-integrated prognostic models of distant recurrence-free survival and pathologic complete response were built using 306 samples and validated on 182 samples of external validation data. Additionally, we compared the discrimination and calibration of M2EFM models to other approaches.Results:Despite different populations and assays, M2EFM models validated with good accuracy (C-index or AUC ≥ .7) for all outcomes in all validation data. M2EFM models had the most consistent performance overall and superior calibration, suggesting a greater likelihood of clinical utility. Finally, we demonstrated that M2EFM identifies functionally relevant genes, which could be useful in translating an M2EFM biomarker to the clinic.Conclusion:M2EFM uses multiple levels of genomic data to infer disrupted regulatory patterns, thus providing a gene signature that connects loss of regulatory control with cancer prognosis.Funding:The analyses described in this report were supported by NIH grants R01ES022222, P30CA138292, P30ES019776, and R01DE022772.Conflicts of Interest:The authors declare no potential conflicts of interest.

External validation of preoperative AST/ALT (De-Ritis) ratio as a prognostic indicator in localized and metastatic renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 589-589
Author(s):  
Dattatraya H Patil ◽  
Rishi Robert Sekar ◽  
Jeff Pearl ◽  
Yoram Baum ◽  
Mehrdad Alemozaffar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
External Validation ◽  
Prognostic Indicator ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Metastatic Rcc

589 Background: Recently, the De-Ritis ratio, defined as the ratio of preoperative aspartate aminotransferase (AST) to alanine aminotransferase (ALT), was shown to be an independent predictor of overall and recurrence-free survival in a European cohort with localized renal cell carcinoma (RCC). In this study, we perform an external validation of the De-Ritis ratio as a prognostic indicator in a distinct cohort of patients with localized and metastatic RCC. Methods: Patients that underwent nephrectomy for localized and metastatic RCC between 2001 and 2014 with available laboratory values within one week of surgery were queried from the Emory Nephrectomy Database. De-Ritis ratio of 1.2 was used to divide subjects into high and low subgroups. Using clinical follow-up data, prognostic value of the De-Ritis ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. Results: In a cohort of 451 patients, an elevated De-Ritis ratio (AST/ALT ≥ 1.2) was associated with significantly decreased overall survival (log-rank, p=0.0023) and recurrence-free survival (Log-rank, p=0.0395). On multivariate analysis, De-Ritis ratio was shown to be an independent and significant predictor of overall survival (HR=0.52, p=0.002) and recurrence-free survival (HR=0.47, p=0.014) as seen in Table. Conclusions: Elevated De-Ritis ratio (AST/ALT ≥ 1.2) is an independent and significant predictor of overall and recurrence-free survival and is capable of differentiating high-risk disease in patients with localized and metastatic RCC. These findings are consistent with a previous study investigating the prognostic value of the De-Ritis ratio in a European cohort, and further validates its prognostic ability in a geographically distinct cohort including patients who presented with metastatic disease [Table: see text]

scholarly journals CDK9 Expression Shows Role as a Potential Prognostic Biomarker in Breast Cancer Patients Who Fail to Achieve Pathologic Complete Response after Neoadjuvant Chemotherapy

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ashley J. Schlafstein ◽  
Allison E. Withers ◽  
Soumon Rudra ◽  
Diana Danelia ◽  
Jeffrey M. Switchenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Recurrence Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Risk Of Death

Failure to achieve pathologic complete response is associated with poor prognosis in breast cancer patients following neoadjuvant chemotherapy (NACT). However, prognostic biomarkers for clinical outcome are unclear in this patient population. Cyclin-dependent kinase 9 (CDK9) is often dysregulated in breast cancer, and its deficiency results in genomic instability. We reviewed the records of 84 breast cancer patients from Emory University’s Winship Cancer Institute who had undergone surgical resection after NACT and had tissue available for tissue microarray analysis (TMA). Data recorded included disease presentation, treatment, pathologic response, overall survival (OS), locoregional recurrence free survival (LRRFS), distant-failure free survival (DFFS), recurrence-free survival (RFS), and event-free survival (EFS). Immunohistochemistry was performed on patient samples to determine CDK9 expression levels after NACT. Protein expression was linked with clinical data to determine significance. In a Cox proportional hazards model, using a time-dependent covariate to evaluate the risk of death between groups beyond 3 years, high CDK9 expression was significantly associated with an increase in OS (HR: 0.26, 95% CI: 0.07-0.98, p=0.046). However, Kaplan-Meier curves for OS, LRRFS, DFFS, RFS, and EFS did not reach statistical significance. The results of this study indicate that CDK9 may have a potential role as a prognostic biomarker in patients with breast cancer following NACT. However, further validation studies with increased sample sizes are needed to help elucidate the prognostic role for CDK9 in the management of these patients.

scholarly journals Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

2012 ◽  
Vol 30 (26) ◽  
pp. 3242-3249 ◽  
Author(s):  
Laura J. Esserman ◽  
Donald A. Berry ◽  
Angela DeMichele ◽  
Lisa Carey ◽  
Sarah E. Davis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Biology ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
High Risk Group ◽  
Hazard Ratio ◽  
Recurrence Free Survival ◽  
Her2 Positive ◽  
Free Survival

PurposeNeoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.Patients and MethodsEligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.ResultsIn 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.ConclusionIn this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

Adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma: Retrospective cohort analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4641-4641
Author(s):  
Mouhammed Amir Habra ◽  
Shamim Ejaz ◽  
Lei Feng ◽  
Prajnan Das ◽  
Ferhat Deniz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Local Recurrence ◽  
Adrenocortical Carcinoma ◽  
Adjuvant Radiotherapy ◽  
Distant Recurrence ◽  
Hazard Ratio ◽  
Control Group ◽  
Recurrence Free Survival ◽  
Free Survival

4641 Background: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and mortality rates. The role of adjuvant radiotherapy (RT) to improve outcome remains unclear. Considering the rarity of ACC, we conducted a historical cohort study to ascertain the effect of adjuvant RT on overall survival and recurrence rates. Methods: Patients were selected from the MD Anderson Cancer Center (MDACC) ACC registry (1998- 2011) who had primary tumor resection with no evidence of distant metastasis at the time of initial diagnosis and a minimum follow-up of 6-months. The adjuvant RT group included patients who received adjuvant RT within 3 months of diagnosis. Control group included patients who did not receive RT and matched based on resection margin status and stage at diagnosis. Results: There were no significant differences between the adjuvant RT group (n=15) and comparison group (n =45) in gender distribution, age, tumor size, functional status, and use of adjuvant mitotane therapy. On multivariate Cox proportional hazard model for overall survival, the adjuvant RT group had hazard ratio of 1.981(95% confidence interval [CI] 0.894-4.391, p=0.0922) compared to the control group. The differences in median time to local recurrence, distant recurrence and of recurrence free survival were not significant between the two groups. In subgroup analysis including only the patients whose initial treatments were from outside of MDACC, RT group (n=15) had hazard ratio of overall survival of 1.604 (95% CI 0.712- 3.613, p=0.2543) compared to group without adjuvant RT (n= 32). Median times to local recurrence, distant recurrence, or of recurrence free survival were also not significantly different between the two groups. Conclusions: To our knowledge, this is the largest single institution report about adjuvant RT use in ACC. In our study, RT did not appear to cause a significant difference in overall survival, recurrence rate, or time to recurrence. However, it is still possible that patients offered adjuvant RT and control groups may have been inherently different. Hence, a prospective study is needed to clarify the role of adjuvant RT in patients with resectable ACC.

The utility of PET-CT after preoperative chemoradiation in predicting treatment outcomes in locally advanced esophageal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 182-182
Author(s):  
Gary Lewis ◽  
Bin S. Teh ◽  
Shraddha Dalwadi ◽  
Stephen Chiang ◽  
Edward Brian Butler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Preoperative Chemoradiation ◽  
Survival Outcomes ◽  
Free Survival ◽  
Pet Ct ◽  
Pre Treatment ◽  
Disease Free

182 Background: In the treatment of gastroesophageal junction (GEJ) cancer, trimodality treatment with preoperative chemoradiation followed by surgery is the standard of care. However, predicting patient survival outcomes remains difficult. One possible means of predicting outcomes is comparing pre-treatment PET-CT with post-treatment PET-CT to see if a favorable response on imaging correlates with survival outcomes. Methods: We conducted a retrospective chart review of locally advanced GEJ cancer patients who underwent preoperative chemoradiotherapy followed by esophagectomy with negative margins. All patients underwent two PET-CT scans (before and after preoperative chemoradiation). We compared PET-CT imaging results and pathology results with survival outcomes. Values such as pre-treatment max SUV, post-treatment max SUV, change in max SUV, percent residual max SUV, complete response on PET-CT, and pathologic complete response were analyzed for potential impacts on recurrence rates and survival outcomes. Results: Forty patients had sufficient data to be included in our study. The median follow-up was 22.5 months. The majority of patients were male (82.5%), Caucasian (84.2%) and had adenocarcinoma histology (97.5%). Altogether, 75% of patients had stage III disease and 67.5% had locoregional nodal involvement. The majority (90%) of patients received some form of taxane and platinum based chemotherapy. Pre-treatment max SUV, post-treatment max SUV, change in max SUV, percent residual max SUV, and complete response on PET-CT were not associated with local recurrence, regional recurrence, disease-free survival, or overall survival. Pathologic complete response was associated with a decrease in the rate of distant metastasis ( P= 0.021) but not disease-free survival ( P= 0.411) or overall survival ( P= 0.878). Conclusions: Response on PET-CT after preoperative chemoradiation is not a predictive factor for recurrence, disease-free survival, or overall survival. Pathologic complete response predicted for a decrease in the rate of distant metastasis but not disease-free survival or overall survival.

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