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 & Bioinformatics

Biostatistics & Bioinformatics
School of Medicine

Chief, Division of Biostatistics

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, Houston

Grants:

PCRP Clinical Consortium: Duke University Clinical Research Site

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Developing and Validating 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
Awarded By
Prostate Cancer Foundation
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

Publications:

Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine.

Background: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. Design setting and participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. Results and limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study. Conclusions: The study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies. Patient summary: To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials.
Authors
Jasu, J; Tolonen, T; Antonarakis, ES; Beltran, H; Halabi, S; Eisenberger, MA; Carducci, MA; Loriot, Y; Van der Eecken, K; Lolkema, M; Ryan, CJ; Taavitsainen, S; Gillessen, S; Högnäs, G; Talvitie, T; Taylor, RJ; Koskenalho, A; Ost, P; Murtola, TJ; Rinta-Kiikka, I; Tammela, T; Auvinen, A; Kujala, P; Smith, TJ; Kellokumpu-Lehtinen, P-L; Isaacs, WB; Nykter, M; Kesseli, J; Bova, GS
MLA Citation
Jasu, Juho, et al. “Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine.Eur Urol Open Sci, vol. 30, Aug. 2021, pp. 47–62. Pubmed, doi:10.1016/j.euros.2021.05.011.
URI
https://scholars.duke.edu/individual/pub1488979
PMID
34337548
Source
pubmed
Published In
Eur Urol Open Sci
Volume
30
Published Date
Start Page
47
End Page
62
DOI
10.1016/j.euros.2021.05.011

A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19: CCC19 Governance, Protocol, and Quality Assurance.

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.
Authors
COVID-19 and Cancer Consortium. Electronic address: jeremy.warner@vumc.org,; COVID-19 and Cancer Consortium,
MLA Citation
COVID-19 and Cancer Consortium. Electronic address: jeremy.warner@vumc.org, Enock, and Enock COVID-19 and Cancer Consortium. “A Systematic Framework to Rapidly Obtain Data on Patients with Cancer and COVID-19: CCC19 Governance, Protocol, and Quality Assurance.Cancer Cell, vol. 38, no. 6, Dec. 2020, pp. 761–66. Pubmed, doi:10.1016/j.ccell.2020.10.022.
URI
https://scholars.duke.edu/individual/pub1489863
PMID
33176160
Source
pubmed
Published In
Cancer Cell
Volume
38
Published Date
Start Page
761
End Page
766
DOI
10.1016/j.ccell.2020.10.022

Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.

Authors
Armstrong, AJ; Nixon, AB; Carmack, A; Yang, Q; Eisen, T; Stadler, WM; Jones, RJ; Garcia, JA; Vaishampayan, UN; Picus, J; Hawkins, RE; Hainsworth, JD; Kollmannsberger, CK; Logan, TF; Puzanov, I; Pickering, LM; Ryan, CW; Protheroe, A; George, DJ; Halabi, S
MLA Citation
Armstrong, Andrew J., et al. “Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non-Clear Cell Renal Cell Carcinoma.Clin Cancer Res, vol. 27, no. 12, June 2021, p. 3503. Pubmed, doi:10.1158/1078-0432.CCR-21-1636.
URI
https://scholars.duke.edu/individual/pub1486354
PMID
34117029
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
3503
DOI
10.1158/1078-0432.CCR-21-1636

Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer.

PURPOSE: Nearly all men with prostate cancer treated with androgen receptor (AR) signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including constitutive activation of the AR pathway, driven by AR genomic structural alterations, expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI resistance mechanisms is critical for optimizing therapy. MATERIALS AND METHODS: A novel liquid biopsy technology was used to collect mRNA from circulating tumor cells (CTCs) to measure expression of AR-Vs, AR targets, and neuroendocrine prostate cancer markers. An institutional review board-approved prospective cohort (N = 99) was used to identify patterns of gene expression. Two prospective multicenter phase II clinical trials of ARSIs for men with castration-resistant prostate cancer (ClinicalTrials.gov: NCT01942837 [enzalutamide, N = 21] and NCT02025010 [abiraterone, N = 27]) were used to further validate these findings. RESULTS: Hierarchical clustering of CTC transcripts identified two distinct clusters. Cluster 2 (C2) exhibited increased expression of AR-regulated genes and was associated with worse overall survival (median 8.6 v 22.4 months; P < .01; hazard ratio [HR] = 3.45 [1.9 to 6.14]). In multivariable analysis, C2 was prognostic independent of other clinicopathologic variables. AR-V status was not significant when accounting for C2. Upon further validation in pooled multicenter phase II trials, C2 was associated with worse overall survival (15.2 months v not reached; P < .01; HR = 8.43 [2.74 to 25.92]), prostate-specific antigen progression-free survival (3.6 v 12 months; P < .01; HR = 4.64 [1.53 to 14.11]), and radiographic progression-free survival (2.7 v 40.6 months; P < .01; HR = 4.64 [1.82 to 17.41]). CONCLUSION: We demonstrate that a transcriptional profile detectable in CTCs obtained from liquid biopsies can serve as an independent prognostic marker beyond AR-V7 in patients with metastatic prostate cancer and can be used to identify the emergence of multiple ARSI resistance mechanisms. This is currently being investigated in additional prospective trials.
Authors
Sperger, JM; Emamekhoo, H; McKay, RR; Stahlfeld, CN; Singh, A; Chen, XE; Kwak, L; Gilsdorf, CS; Wolfe, SK; Wei, XX; Silver, R; Zhang, Z; Morris, MJ; Bubley, G; Feng, FY; Scher, HI; Rathkopf, D; Dehm, SM; Choueiri, TK; Halabi, S; Armstrong, AJ; Wyatt, AW; Taplin, M-E; Zhao, SG; Lang, JM
MLA Citation
Sperger, Jamie M., et al. “Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer.J Clin Oncol, vol. 39, no. 26, Sept. 2021, pp. 2926–37. Pubmed, doi:10.1200/JCO.21.00169.
URI
https://scholars.duke.edu/individual/pub1487553
PMID
34197212
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
39
Published Date
Start Page
2926
End Page
2937
DOI
10.1200/JCO.21.00169

Prostate Cancer Racial Disparities: A Systematic Review by the Prostate Cancer Foundation Panel.

CONTEXT: Prostate cancer (PCa) is a complex disease that disproportionately impacts Black men in the USA. The structural factors that drive heterogeneous outcomes for patients of differing backgrounds are probably the same ones that result in population-level disparities. The relative contribution of drivers along the PCa disease continuum is an active area of investigation and debate. OBJECTIVE: To critically synthesize the available evidence on PCa disparities from a population-level perspective in comparison to data from "equal access and equal care settings" and to provide a consensus summary of the state of PCa disparities. EVIDENCE ACQUISITION: A plenary panel on PCa disparities presented at the Prostate Cancer Foundation meeting on October 24, 2019 and ensuing discussions are reported here. We used a systematic literature review approach and the Preferred Reporting Items for Systematic Reviews and Meta-analyses to select the most relevant publications. A total of 3333 publications between 2011 and 2021 were retrieved, of which 52 were included in the review; an additional 13 articles on screening guidelines, seminal clinical trials, and statistical methodology were used in the evidence synthesis. EVIDENCE SYNTHESIS: Race disparities in PCa are a result of a complex interaction between socioeconomic factors impacting access to care and ancestral/genetic factors that may influence tumor biology. Black men in the USA continue to have a nearly 1.8 times higher population-level mortality rate than White men. Failure to account for the race-specific incidence burden would continue to lead to residual disparity even after achieving relatively similar outcomes after primary treatment, resulting in a higher long-term mortality burden. Selection bias remains possible in PCa studies, which often rely on highly specific cohorts of Black men with higher use of health care resources that may not represent the average Black patient in the USA. Novel methods including mediation analysis and genetic ancestry rather than self-identified race can optimize analytical models investigating racial disparities and may lead to a better understanding of PCa genomic diversity and behavior. CONCLUSIONS: Our findings emphasize the importance of racially diverse studies, including precision -omics, prevention, and targeted therapy initiatives, to elucidate mechanisms underlying racial differences in outcomes and response to therapy. We propose novel approaches for studying and addressing PCa disparities. Contemporary methods, particularly in the domain of mediation analysis, can promote scientific rigor in understanding these disparities. PATIENT SUMMARY: Inaccurate data interpretation or lack of data altogether for Black men can impact policy and ultimately affect millions of individuals of African origin worldwide. Our review identifies a need to develop and prioritize a strategy for including Black and other men with prostate cancer in intervention studies and randomized clinical trials to halt the widening prostate cancer disparities.
Authors
Mahal, BA; Gerke, T; Awasthi, S; Soule, HR; Simons, JW; Miyahira, A; Halabi, S; George, D; Platz, EA; Mucci, L; Yamoah, K
MLA Citation
Mahal, Brandon A., et al. “Prostate Cancer Racial Disparities: A Systematic Review by the Prostate Cancer Foundation Panel.Eur Urol Oncol, Aug. 2021. Pubmed, doi:10.1016/j.euo.2021.07.006.
URI
https://scholars.duke.edu/individual/pub1495017
PMID
34446369
Source
pubmed
Published In
Eur Urol Oncol
Published Date
DOI
10.1016/j.euo.2021.07.006

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