Donna Niedzwiecki

Overview:

Primary interests include clinical trials design and the design and analysis of biomarker and imaging studies especially in the areas of GI cancer, lymphoma, melanoma, transplant and cancer immunotherapy.

Positions:

Professor of Biostatistics and Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1984

Yale University

Grants:

Planning a Duke Academic Public Private Partnership Program (AP4) Center

Administered By
Duke Cancer Institute
Awarded By
National Cancer Institute
Role
Biostatistician
Start Date
End Date

Role for TbetaRIII Shedding in the Tumor Microenvironment

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Graft Engineering and Immunotherapy After Unrelated Cord Blood Transplantation

Administered By
Pediatrics, Blood and Marrow Transplantation
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Dexasome Based Immunotherapy of Lung Cancer

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Statistician
Start Date
End Date

The Impact of Race, Ethnicity, and Socioeconomic Status on Listing for Liver Transplant after Referral

Administered By
Medicine, Gastroenterology
Awarded By
American Association for the Study of Liver Diseases
Role
Statistician
Start Date
End Date

Publications:

Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance).

PURPOSE: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic colorectal cancer. EXPERIMENTAL DESIGN: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic colorectal cancer participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. RESULTS: At study entry, 63% of patients were vitamin D deficient (<20 ng/mL) and 31% were vitamin D insufficient (20-<30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend = 0.0009 and 0.03, respectively). Compared with patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53-0.83) for OS and 0.81 (95% CI, 0.66-1.00) for PFS. The improved survival associated with higher 25(OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. CONCLUSIONS: In this large cohort of patients with advanced or metastatic colorectal cancer, higher plasma 25(OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in patients with colorectal cancer are warranted.
Authors
Yuan, C; Sato, K; Hollis, BW; Zhang, S; Niedzwiecki, D; Ou, F-S; Chang, I-W; O'Neil, BH; Innocenti, F; Lenz, H-J; Blanke, CD; Goldberg, RM; Venook, AP; Mayer, RJ; Fuchs, CS; Meyerhardt, JA; Ng, K
MLA Citation
Yuan, Chen, et al. “Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance)..” Clin Cancer Res, vol. 25, no. 24, Dec. 2019, pp. 7497–505. Pubmed, doi:10.1158/1078-0432.CCR-19-0877.
URI
https://scholars.duke.edu/individual/pub1412326
PMID
31548349
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
25
Published Date
Start Page
7497
End Page
7505
DOI
10.1158/1078-0432.CCR-19-0877

Assessment of Treatment With Sorafenib Plus Doxorubicin vs Sorafenib Alone in Patients With Advanced Hepatocellular Carcinoma: Phase 3 CALGB 80802 Randomized Clinical Trial.

Importance: Previous communication has reported significant improvement in overall survival (OS) when using doxorubicin plus sorafenib in the treatment of advanced hepatocellular cancer (HCC). Objective: To determine if doxorubicin added to sorafenib therapy improves OS, with stratification for locally advanced and metastatic disease. Design, Setting, and Participants: This unblinded randomized phase 3 clinical trial was led by Alliance in collaboration with Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Canadian Cancer Trials Group, and Southwest Oncology Group. It was launched in February 2010 and completed in May 2015; data were also analyzed during this time frame. Patients with histologically proven advanced HCC, no prior systemic therapy, Child-Pugh grade A score, Eastern Cooperative Oncology Group performance status of 0 to 2 (later amended to 0-1), and adequate hematologic, hepatic, renal, and cardiac function were eligible. The OS primary end point had a final analysis planned with 364 events observed among 480 total patients with 90% power to detect a 37% increase in median OS. Interventions or Exposures: Patients received either 60 mg/m2 of doxorubicin every 21 days plus 400 mg of sorafenib orally twice daily or the sorafenib alone, adjusted to half doses for patients with bilirubin levels of 1.3 to 3.0 mg/dL. Main Outcomes and Measures: The primary end point was OS, and progression-free survival (PFS) was a secondary end point. Results: Of 356 patients included in the study, the mean (SD) age was 62 (10.1) years, and 306 (86.0%) were men. Although it was planned to include 480 patients, the study was halted after accrual of 356 patients (180 patients treated with doxorubicin plus sorafenib and 176 with sorafenib alone) with a futility boundary crossed at a planned interim analysis. Median OS was 9.3 months (95% CI, 7.3-10.8 months) in the doxorubicin plus sorafenib arm and 9.4 months (95% CI, 7.3-12.9 months) in the sorafenib alone arm (hazard ratio, 1.05; 95% CI, 0.83-1.31). The median PFS was 4.0 months (95% CI, 3.4-4.9 months) in the doxorubicin plus sorafenib arm and 3.7 months (95% CI, 2.9-4.5 months) in the sorafenib alone arm (hazard ratio, 0.93; 95% CI, 0.75-1.16). Grade 3 or 4 neutropenia and thrombocytopenia adverse events occurred in 61 (36.8%) and 29 (17.5%) patients, respectively, being treated with doxorubicin plus sorafenib vs 1 (0.6%) and 4 (2.4%) patients treated with sorafenib. Conclusions and Relevance: This multigroup study of the addition of doxorubicin to sorafenib therapy did not show improvement of OS or PFS in patients with HCC. Trial Registration: ClinicalTrials.gov identifier: NCT01015833.
Authors
Abou-Alfa, GK; Shi, Q; Knox, JJ; Kaubisch, A; Niedzwiecki, D; Posey, J; Tan, BR; Kavan, P; Goel, R; Lammers, PE; Bekaii-Saab, TS; Tam, VC; Rajdev, L; Kelley, RK; El Dika, I; Zemla, T; Potaracke, RI; Balletti, J; El-Khoueiry, AB; Harding, JH; Suga, JM; Schwartz, LH; Goldberg, RM; Bertagnolli, MM; Meyerhardt, J; O'Reilly, EM; Venook, AP
MLA Citation
URI
https://scholars.duke.edu/individual/pub1409892
PMID
31486832
Source
pubmed
Published In
Jama Oncol
Published Date
DOI
10.1001/jamaoncol.2019.2792

Reply to S. Sorscher.

Authors
Innocenti, F; Ou, F-S; Qu, X; Zemla, T; Niedzwiecki, D; Tam, R; Mahajan, S; Goldberg, RM; Bertagnolli, MM; Blanke, CD; Sanoff, H; Atkins, J; Polite, B; Venook, AP; Lenz, H-J; Kabbarah, O
MLA Citation
Innocenti, Federico, et al. “Reply to S. Sorscher..” J Clin Oncol, vol. 37, no. 25, Sept. 2019, pp. 2291–93. Pubmed, doi:10.1200/JCO.19.01366.
URI
https://scholars.duke.edu/individual/pub1395772
PMID
31268798
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
37
Published Date
Start Page
2291
End Page
2293
DOI
10.1200/JCO.19.01366

Local Tumor Control and Patient Outcome Using Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: iRECIST as a Potential Substitute for Traditional Criteria.

OBJECTIVE. The purpose of this study was to investigate whether, compared with traditional criteria, the modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapeutics (iRECIST) improves prediction of local tumor control and survival in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS. Fifty-one HCC lesions (mean size, 3.1 cm) treated with SBRT in 41 patients (mean age, 67 years) were retrospectively included. Each patient underwent CT or MRI before SBRT and at least once after SBRT. Best overall response was categorized using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), iRECIST, World Health Organization (WHO) criteria, modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria. Lesions were then classified as local tumor control (i.e., stable disease, partial response, or complete response) or local treatment failure (i.e., progressive disease) by each tumor response criteria. Proportions of local tumor control were compared using the McNemar exact test. The 1-year overall survival was estimated using the Kaplan-Meier method. RESULTS. The median follow-up after SBRT was 21.0 months. The local tumor control rate was 94.1% (48/51) by iRECIST, 88.2% (45/51) by RECIST 1.1, 72.5% (37/51) by WHO criteria, 80.4% (41/51) by mRECIST, and 72.5% (37/51) by EASL criteria. The local tumor control rate was significantly higher according to iRECIST compared with WHO (p = 0.0010) and EASL (p = 0.0225) criteria. The 1-year survival rate for patients with local tumor control according to iRECIST (86.4%) was higher (although not statistically significant) compared with the 1-year survival rate for patients with local tumor control according to the other response criteria. CONCLUSION. iRECIST may provide more robust interpretation of HCC response after SBRT, yielding improved prediction of local tumor control and 1-year survival rates compared with traditional criteria.
Authors
Vernuccio, F; Godfrey, D; Meyer, M; Williamson, HV; Salama, JK; Niedzwiecki, D; Stephens, SJ; Ronald, J; Palta, M; Marin, D
MLA Citation
Vernuccio, Federica, et al. “Local Tumor Control and Patient Outcome Using Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: iRECIST as a Potential Substitute for Traditional Criteria..” Ajr Am J Roentgenol, vol. 213, no. 6, Dec. 2019, pp. 1232–39. Pubmed, doi:10.2214/AJR.18.20842.
URI
https://scholars.duke.edu/individual/pub1416636
PMID
31613663
Source
pubmed
Published In
Ajr. American Journal of Roentgenology
Volume
213
Published Date
Start Page
1232
End Page
1239
DOI
10.2214/AJR.18.20842

Disease-free survival as a surrogate for overall survival in neoadjuvant trials of gastroesophageal adenocarcinoma: Pooled analysis of individual patient data from randomised controlled trials.

INTRODUCTION: Disease-free survival (DFS) is increasingly being used as surrogate end-point for overall survival (OS) in cancer trials. So far, there has been no validation of the surrogacy of DFS for OS for neoadjuvant treatment of gastroesophageal adenocarcinoma. METHODS: The study uses individual patient data (IPD) from eight randomised controlled trials (RCTs) (n = 1126 patients) comparing neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. Correlation between OS time and DFS time was calculated to evaluate individual-level surrogacy. For each trial, survival curves using the Kaplan-Meier method were plotted and hazard ratios (HRs) on the treatment effects were calculated for OS and DFS separately. Those HRs were pooled in a random-effects meta-analysis. Observed HRs were compared with predicted HRs for OS using results from an error-in-variables linear regression model accounting for the uncertainty about the estimated effect. The strength of the association was quantified by the coefficient of determination to assess trial-level surrogacy. The surrogate threshold effect was calculated to determine the minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS. RESULTS: A strong correlation between OS time and DFS time was observed, indicating a high individual-level surrogacy. For all RCTs, estimated HRs for OS and DFS were highly similar. In the meta-analysis, the overall HR for OS was virtually identical to that for DFS. The estimated coefficient of determination r2 for the association between HRs for OS and DFS was 0.912 (95% confidence interval: 0.75-1.0), indicating a very good fit of the regression model and thus a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect based on the regression analysis was 0.79. DISCUSSION: Based on strong correlations between DFS and OS, as well as a strong correlation of the treatment effects of the two end-points in the error-in-variable regression, DFS seems an appropriate surrogate marker for OS in randomised trials of neoadjuvant chemotherapy or chemoradiotherapy for gastroesophageal adenocarcinoma.
Authors
Ronellenfitsch, U; Jensen, K; Seide, S; Kieser, M; Schwarzbach, M; Slanger, TE; Burmeister, B; Kelsen, D; Niedzwiecki, D; Piessen, G; Schuhmacher, C; Urba, S; van de Velde, C; Ychou, M; Hofheinz, R; Lorenzen, S
MLA Citation
URI
https://scholars.duke.edu/individual/pub1418226
PMID
31678767
Source
pubmed
Published In
Eur J Cancer
Volume
123
Published Date
Start Page
101
End Page
111
DOI
10.1016/j.ejca.2019.10.001