Susan Halabi

Overview:

Design and analysis of clinical trials, statistical analysis of biomarker and high dimensional data, development and validation of prognostic and predictive models.

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. 1994

University of Texas Health Sciences Center at Houston

Grants:

Prognostic Models of Clinical Outcomes In Men With Castration Resistant Prostate Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Surrogate Endpoints of Overall Survival in Men with Metastatic Hormone Sensitive Prostate Cancer

Administered By
Biostatistics & Bioinformatics
Role
Principal Investigator
Start Date
End Date

Precision Medicine in Platinum-treated Lethal Bladder Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
Memorial Sloan Kettering Cancer Center
Role
Principal Investigator
Start Date
End Date

Serum Androgens and Survival in CRPC

Administered By
Duke Cancer Institute
Awarded By
University of California, San Francisco
Role
Principal Investigator
Start Date
End Date

Admin Suppl to Study Mechanisms of Ca Sensitivity and Resistance... CALGB 90203

Administered By
Duke Cancer Institute
Awarded By
Brigham and Women's Hospital
Role
Principal Investigator
Start Date
End Date

Publications:

Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).

BACKGROUND: Multiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS. METHODS: Data from 1050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors. RESULTS: Median baseline values for T, A, and, DHEA were 1.0, 13.5, and 8.1 ng/dL respectively while 6 week levels were 0.64, 7.0, and 6.8 ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI = 1.01-1.03, p = 0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ≥50% decline in PSA with an odds ratio of 0.93 (95% CI = 0.85-0.98, p-value = 0.039). CONCLUSIONS: Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.
Authors
Ryan, CJ; Dutta, S; Kelly, WK; Russell, C; Small, EJ; Morris, MJ; Taplin, M-E; Halabi, S; From The Alliance for Clinical Trials in Oncology Genitourinary Committee,
MLA Citation
Ryan, Charles J., et al. “Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC)..” Prostate Cancer Prostatic Dis, May 2019. Pubmed, doi:10.1038/s41391-019-0152-3.
URI
https://scholars.duke.edu/individual/pub1383880
PMID
31053766
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-019-0152-3

Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To update guideline recommendations on the role of bone-modifying agents in multiple myeloma. Methods An update panel conducted a targeted systematic literature review by searching PubMed and the Cochrane Library for randomized controlled trials, systematic reviews, meta-analyses, clinical practice guidelines, and observational studies. Results Thirty-five relevant studies were identified, and updated evidence supports the current recommendations. Recommendations For patients with active symptomatic multiple myeloma that requires systemic therapy with or without evidence of lytic destruction of bone or compression fracture of the spine from osteopenia on plain radiograph(s) or other imaging studies, intravenous administration of pamidronate 90 mg over at least 2 hours or zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks is recommended. Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative. Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting. The update panel recommends that clinicians consider reducing the initial pamidronate dose in patients with preexisting renal impairment. Zoledronic acid has not been studied in patients with severe renal impairment and is not recommended in this setting. The update panel suggests that bone-modifying treatment continue for up to 2 years. Less frequent dosing has been evaluated and should be considered in patients with responsive or stable disease. Continuous use is at the discretion of the treating physician and the risk of ongoing skeletal morbidity. Retreatment should be initiated at the time of disease relapse. The update panel discusses measures regarding osteonecrosis of the jaw. Additional information is available at www.asco.org/hematologic-malignancies-guidelines and www.asco.org/guidelineswiki .
Authors
Anderson, K; Ismaila, N; Flynn, PJ; Halabi, S; Jagannath, S; Ogaily, MS; Omel, J; Raje, N; Roodman, GD; Yee, GC; Kyle, RA
MLA Citation
Anderson, Kenneth, et al. “Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update..” J Clin Oncol, vol. 36, no. 8, Mar. 2018, pp. 812–18. Pubmed, doi:10.1200/JCO.2017.76.6402.
URI
https://scholars.duke.edu/individual/pub1296173
PMID
29341831
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
36
Published Date
Start Page
812
End Page
818
DOI
10.1200/JCO.2017.76.6402

Association of on-treatment plasma HGF levels with overall survival (OS) in patients (pts) with advanced renal cell carcinoma (RCC) treated with interferon alpha (INF) +/- bevacizumab (BEV): Results from CALGB 90206 (Alliance).

Authors
George, DJ; Halabi, S; Starr, MD; Hurwitz, H; Brady, JC; Barak, I; Morris, MJ; Rini, BI; Small, EJ; Kim, W; Taplin, M-E; Nixon, AB
MLA Citation
George, Daniel J., et al. “Association of on-treatment plasma HGF levels with overall survival (OS) in patients (pts) with advanced renal cell carcinoma (RCC) treated with interferon alpha (INF) +/- bevacizumab (BEV): Results from CALGB 90206 (Alliance)..” Journal of Clinical Oncology, vol. 35, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. 4522–4522. Crossref, doi:10.1200/jco.2017.35.15_suppl.4522.
URI
https://scholars.duke.edu/individual/pub1386299
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
35
Published Date
Start Page
4522
End Page
4522
DOI
10.1200/jco.2017.35.15_suppl.4522

Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.

BACKGROUND: Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery. METHODS: Men with localized PC treated with radical prostatectomy at the Durham VA Medical Center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1 and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics an risk of PSA recurrence over time. RESULTS: Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; three died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N-cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence or Gleason sum were noted for SNAIL, ZEB1, vimentin or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (P=0.043), National Comprehensive Cancer Network risk (P=0.013) and PSA recurrence (hazard ratio 1.07, P=0.016). CONCLUSIONS: The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.
Authors
Armstrong, AJ; Healy, P; Halabi, S; Vollmer, R; Lark, A; Kemeny, G; Ware, K; Freedland, SJ
MLA Citation
Armstrong, A. J., et al. “Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer..” Prostate Cancer Prostatic Dis, vol. 19, no. 1, Mar. 2016, pp. 40–45. Pubmed, doi:10.1038/pcan.2015.46.
URI
https://scholars.duke.edu/individual/pub1091610
PMID
26458958
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Volume
19
Published Date
Start Page
40
End Page
45
DOI
10.1038/pcan.2015.46

Clinical phenotypes associated with circulating tumor cell enumeration in metastatic castration-resistant prostate cancer.

BACKGROUND: The presence of ≥5 circulating tumor cells (CTCs) is prognostic for shorter survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, some men have low CTCs despite widespread disease, suggesting heterogeneity in CTC phenotype or detection. The aim of this study was to evaluate the association of CTC enumeration with clinical disease characteristics and overall survival in men with mCRPC at our institution. DESIGN: CTCs were enumerated using the CellSearch method in a prospective correlative study in men with mCRPC starting a new systemic therapy. The primary objective was to determine the clinical phenotype of the subset of men with mCRPC who have a poor prognosis and low CTCs. Secondary end points included associations of CTCs with survival and known prognostic biomarkers, before therapy and at progression. RESULTS: At baseline, median CTC count was 16 cells and prostate-specific antigen (PSA) level was 178 ng/ml. At progression, median CTC count was 42, PSA level was 245 ng/ml, levels of lactate dehydrogenase and alkaline phosphatase rose, and level of hemoglobin dropped. The median overall survival for this heavily pretreated population was 11.2 months, and the multivariable hazard ratio for death of men with CTCs<5 vs.≥5 was 0.43 (95% CI: 0.24-0.77). Median progression-free survival was 4.4 months. CTC enumeration modestly correlated with lactate dehydrogenase and alkaline phosphatase levels but only weakly correlated with PSA and hemoglobin levels. We were unable to identify a consistent subgroup of poor prognosis men with a low number of CTCs. CONCLUSION: CTC enumeration appears to be prognostic in men with mCRPC and describes a phenotype of hematogenous dissemination that cannot be predicted based on standard clinical and laboratory assessments.
Authors
Bitting, RL; Healy, P; Halabi, S; George, DJ; Goodin, M; Armstrong, AJ
MLA Citation
Bitting, Rhonda L., et al. “Clinical phenotypes associated with circulating tumor cell enumeration in metastatic castration-resistant prostate cancer..” Urol Oncol, vol. 33, no. 3, Mar. 2015, pp. 110.e1-110.e9. Pubmed, doi:10.1016/j.urolonc.2014.09.002.
URI
https://scholars.duke.edu/individual/pub1056234
PMID
25595577
Source
pubmed
Published In
Urol Oncol
Volume
33
Published Date
Start Page
110.e1
End Page
110.e9
DOI
10.1016/j.urolonc.2014.09.002

Research Areas:

Adenocarcinoma
Adenocarcinoma, Clear Cell
African Americans
Age Factors
Aged, 80 and over
Alkaline Phosphatase
Alleles
Arab countries
Area Under Curve
Biological Markers
Biomarkers, Pharmacological
Breast Neoplasms
Cancer Vaccines
Carcinoma
Carcinoma, Renal Cell
Case-Control Studies
Chemoprevention
Chemotherapy
Chi-Square Distribution
Clinical Trials, Phase II as Topic
Clinical trials
Cohort Studies
Computer Simulation
Confidence Intervals
Construction Materials
Contraceptives, Oral
DNA Damage
DNA Primers
DNA Repair
DNA, Neoplasm
Data Interpretation, Statistical
Decision Making
Decision Support Techniques
Diagnostic Imaging
Disease Progression
Disease-Free Survival
Drug Design
Dust
Efficiency, Organizational
Endpoint Determination
Equipment Design
Factor Analysis, Statistical
Family relationships
Gels
Gene Expression
Genes, Immunoglobulin
Genetic Predisposition to Disease
Genetics, Medical
Genotype
Germany
Graft vs Host Disease
HIV Infections
Hispanic Americans
Individualized Medicine
Kaplan-Meier Estimate
Ketoconazole
Lasso
Logistic Models
Lymphokines
Mining
Models, Biological
Models, Statistical
Models, Theoretical
Molecular Sequence Data
Multiprotein Complexes
Multivariate Analysis
Mutation
Neoplasms, Hormone-Dependent
Nomograms
Odds Ratio
Outcome Assessment (Health Care)
Ovarian Neoplasms
Personalized medicine
Population
Population Surveillance
Precision Medicine
Predictive Value of Tests
Pregnancy
Probability
Prognosis
Proportional Hazards Models
Prospective Studies
ROC Curve
Randomized Controlled Trials as Topic
Receptors, Progesterone
Registries
Reproducibility of Results
Research Design
Residence Characteristics
Retrospective Studies
Ribosomal Protein S6 Kinases
Risk
Risk Assessment
Risk Factors
Sample Size
Selective Estrogen Receptor Modulators
Sensitivity and Specificity
Statistics as Topic
Survival
Survival Analysis
Survival Rate
Tamoxifen
Translocation, Genetic
Treatment Failure
Treatment Outcome
Tumor Markers, Biological
United States
Urologic Neoplasms
Validation Studies as Topic
Vascular Endothelial Growth Factors