Kevin Oeffinger

Overview:

Kevin Oeffinger, MD, is a family physician, Professor in the Department of Medicine, and a member of the Duke Cancer Institute (DCI). He is founding Director of the DCI Center for Onco-Primary Care, and Director of the DCI Supportive Care and Survivorship Center. He has a long-standing track record of NIH-supported research in cancer screening and survivorship and has served in a leadership capacity in various cancer-focused and primary care-focused national committees and organizations, including the American Society of Clinical Oncology, the American Cancer Society, and the American Academy of Family Physicians. He is currently an Associate Editor for the Journal of the National Cancer Institute.

The three-fold mission of the DCI Center for Onco-Primary Care are are to: (1) deliver evidence-based, patient-centered, personalized health care across the cancer continuum by enhancing the interface between cancer specialists and primary care clinicians; (2) conduct innovative research with cutting-edge technology that can be translated to the community setting; and (3) train and educate the next generation of clinicians and researchers to extend this mission. 

Dr. Oeffinger's clinical expertise is managing survivors of pediatric and young adult cancer.

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in the Department of Family Medicine and Community Health

Family Medicine and Community Health
School of Medicine

Professor in Population Health Sciences

Population Health Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1984

University of Texas Health Science Center San Antonio

Family Medicine Internship and Residency

Baylor College of Medicine

Family Medicine Academic Fellowship

Baylor College of Medicine

Advanced Research Training, Epidemiology And Genetics, Radiation Epidemiology

National Cancer Institute

Grants:

EMPOWER Study: Promoting BC Screening in Women Who Survived Childhood Cancer

Administered By
Duke Cancer Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Improving Treatment of Cardiovascular Risk Factors in Childhood Cancer Survivors

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Childhood Cancer Survivor Study (CCSS)

Administered By
Duke Cancer Institute
Awarded By
St. Jude Children's Research Hospital
Role
Principal Investigator
Start Date
End Date

Generic Testing to Guide Pediatric Cancer Care and Follow Up: Using Anthracycline-associated Cardiac Toxicity as a Model for the Future

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Exercise and QUality diet After Leukemia

Administered By
Duke Cancer Institute
Awarded By
Sloan Kettering Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Rationale and design of a cardiac safety study for reduced cardiotoxicity surveillance during HER2-targeted therapy

Background: Echocardiograms are recommended every 3 months in patients receiving human epidermal growth factor 2 (HER2)-targeted therapy for surveillance of left ventricular ejection fraction (LVEF). Efforts to tailor treatment for HER2-positive breast cancer have led to greater use of non-anthracycline regimens that are associated with lower cardiotoxicity risk, raising into question the need for frequent cardiotoxicity surveillance for these patients. This study seeks to evaluate whether less frequent cardiotoxicity surveillance (every 6 months) is safe for patients receiving a non-anthracycline HER2-targeted treatment regimen. Methods/design: We will enroll 190 women with histologically confirmed HER2-positive breast cancer scheduled to receive a non-anthracycline HER2-targeted treatment regimen for a minimum of 12 months. All participants will undergo echocardiograms before and 6-, 12-, and 18-months after initiation of HER2-targeted treatment. The primary composite outcome is symptomatic heart failure (New York Heart Association class III or IV) or death from cardiovascular causes. Secondary outcomes include: 1) echocardiographic indices of left ventricular systolic function; 2) incidence of cardiotoxicity, defined by a ≥ 10% absolute reduction in left ventricular ejection fraction (LVEF) from baseline to < 53%; and 3) incidence of early interruption of HER2-targeted therapy. Conclusions: To our knowledge, this will be the first prospective study of a risk-based approach to cardiotoxicity surveillance. We expect findings from this study will inform the development of updated clinical practice guidelines to improve cardiotoxicity surveillance practices during HER2-positive breast cancer treatment. Trial registration: The trial was registered in the ClinicalTrials.gov registry (identifier NCT03983382) on June 12, 2019.
Authors
Yu, AF; Dang, CT; Jorgensen, J; Moskowitz, CS; DeFusco, P; Oligino, E; Oeffinger, KC; Liu, JE; Steingart, RM
MLA Citation
Yu, A. F., et al. “Rationale and design of a cardiac safety study for reduced cardiotoxicity surveillance during HER2-targeted therapy (Accepted).” Cardio Oncology, vol. 9, no. 1, Dec. 2023. Scopus, doi:10.1186/s40959-023-00163-4.
URI
https://scholars.duke.edu/individual/pub1569666
Source
scopus
Published In
Cardio Oncology (London, England)
Volume
9
Published Date
DOI
10.1186/s40959-023-00163-4

Specific causes of excess late mortality and association with modifiable risk factors among survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort.

BACKGROUND: 5-year survival after childhood cancer does not fully describe life-years lost due to childhood cancer because there are a large number of deaths occurring beyond 5-years (late mortality) related to cancer and cancer treatment. Specific causes of health-related (non-recurrence, non-external) late mortality and risk reduction through modifiable lifestyle and cardiovascular risk factors are not well described. Through using a well-characterised cohort of 5-year survivors of the most common childhood cancers, we evaluated specific health-related causes of late mortality and excess deaths compared with the general US population and identified targets to reduce future risk. METHODS: In this multi-institutional, hospital-based, retrospective cohort study, late mortality (death ≥5 years from diagnosis) and specific causes of death were evaluated in 34 230 5-year survivors of childhood cancer diagnosed at an age younger than 21 years from 1970 to 1999 at 31 institutions in the USA and Canada; median follow-up from diagnosis was 29 years (range 5-48) in the Childhood Cancer Survivor Study. Demographic, self-reported modifiable lifestyle (ie, smoking, alcohol, physical activity, and BMI) and cardiovascular risk factors (ie, hypertension, diabetes, and dyslipidaemia) associated with health-related mortality (which excludes death from primary cancer and external causes and includes death from late effects of cancer therapy) were evaluated. FINDINGS: 40-year cumulative all-cause mortality was 23·3% (95% CI 22·7-24·0), with 3061 (51·2%) of 5916 deaths from health-related causes. Survivors 40 years or more from diagnosis experienced 131 excess health-related deaths per 10 000 person-years (95% CI 111-163), including those due to the top three causes of health-related death in the general population: cancer (absolute excess risk per 10 000 person-years 54, 95% CI 41-68), heart disease (27, 18-38), and cerebrovascular disease (10, 5-17). Healthy lifestyle and absence of hypertension and diabetes were each associated with a 20-30% reduction in health-related mortality independent of other factors (all p values ≤0·002). INTERPRETATION: Survivors of childhood cancer are at excess risk of late mortality even 40 years from diagnosis, due to many of the leading causes of death in the US population. Modifiable lifestyle and cardiovascular risk factors associated with reduced risk for late mortality should be part of future interventions. FUNDING: US National Cancer Institute and the American Lebanese Syrian Associated Charities.
Authors
Dixon, SB; Liu, Q; Chow, EJ; Oeffinger, KC; Nathan, PC; Howell, RM; Leisenring, WM; Ehrhardt, MJ; Ness, KK; Krull, KR; Mertens, AC; Hudson, MM; Robison, LL; Yasui, Y; Armstrong, GT
MLA Citation
Dixon, Stephanie B., et al. “Specific causes of excess late mortality and association with modifiable risk factors among survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort.Lancet, vol. 401, no. 10386, Apr. 2023, pp. 1447–57. Pubmed, doi:10.1016/S0140-6736(22)02471-0.
URI
https://scholars.duke.edu/individual/pub1575504
PMID
37030315
Source
pubmed
Published In
Lancet
Volume
401
Published Date
Start Page
1447
End Page
1457
DOI
10.1016/S0140-6736(22)02471-0

Development and Validation of a Prediction Model for Kidney Failure in Long-Term Survivors of Childhood Cancer.

PURPOSE: Kidney failure is a rare but serious late effect following treatment for childhood cancer. We developed a model using demographic and treatment characteristics to predict individual risk of kidney failure among 5-year survivors of childhood cancer. METHODS: Five-year survivors from the Childhood Cancer Survivor Study (CCSS) without history of kidney failure (n = 25,483) were assessed for subsequent kidney failure (ie, dialysis, kidney transplantation, or kidney-related death) by age 40 years. Outcomes were identified by self-report and linkage with the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5,045) served as a comparator. Piecewise exponential models accounting for race/ethnicity, age at diagnosis, nephrectomy, chemotherapy, radiotherapy, congenital genitourinary anomalies, and early-onset hypertension estimated the relationships between potential predictors and kidney failure, using area under the curve (AUC) and concordance (C) statistic to evaluate predictive power. Regression coefficient estimates were converted to integer risk scores. The St Jude Lifetime Cohort Study and the National Wilms Tumor Study served as validation cohorts. RESULTS: Among CCSS survivors, 204 developed late kidney failure. Prediction models achieved an AUC of 0.65-0.67 and a C-statistic of 0.68-0.69 for kidney failure by age 40 years. Validation cohort AUC and C-statistics were 0.88/0.88 for the St Jude Lifetime Cohort Study (n = 8) and 0.67/0.64 for the National Wilms Tumor Study (n = 91). Risk scores were collapsed to form statistically distinct low- (n = 17,762), moderate- (n = 3,784), and high-risk (n = 716) groups, corresponding to cumulative incidences in CCSS of kidney failure by age 40 years of 0.6% (95% CI, 0.4 to 0.7), 2.1% (95% CI, 1.5 to 2.9), and 7.5% (95% CI, 4.3 to 11.6), respectively, compared with 0.2% (95% CI, 0.1 to 0.5) among siblings. CONCLUSION: Prediction models accurately identify childhood cancer survivors at low, moderate, and high risk for late kidney failure and may inform screening and interventional strategies.
Authors
Wu, NL; Chen, Y; Dieffenbach, BV; Ehrhardt, MJ; Hingorani, S; Howell, RM; Jefferies, JL; Mulrooney, DA; Oeffinger, KC; Robison, LL; Weil, BR; Yuan, Y; Yasui, Y; Hudson, MM; Leisenring, WM; Armstrong, GT; Chow, EJ
MLA Citation
Wu, Natalie L., et al. “Development and Validation of a Prediction Model for Kidney Failure in Long-Term Survivors of Childhood Cancer.J Clin Oncol, vol. 41, no. 12, Apr. 2023, pp. 2258–68. Pubmed, doi:10.1200/JCO.22.01926.
URI
https://scholars.duke.edu/individual/pub1566687
PMID
36795981
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
41
Published Date
Start Page
2258
End Page
2268
DOI
10.1200/JCO.22.01926

Clinician Perspectives on Managing Chronic Pain After Curative-Intent Cancer Treatment.

PURPOSE: Among cancer survivors who have completed curative-intent treatment, the high prevalence and adverse consequences of chronic pain are well documented. Yet, research on clinicians' experiences with and perspectives on managing chronic pain among cancer survivors is critically lacking. METHODS: We conducted semistructured interviews with 17 clinicians (six oncology, three palliative care, and eight primary care) affiliated with an academic medical center. Interview questions addressed clinicians' experiences with and perspectives on managing chronic pain (with or without opioid therapy) during the transition from active treatment to survivorship. A multidisciplinary team conducted content analysis of interview transcripts to identify and refine themes related to current practices and challenges in managing chronic pain in this context. RESULTS: Overall, clinicians perceived chronic pain to be relatively uncommon among cancer survivors. Identified challenges included a lack of clarity about which clinician (or clinicians) are best positioned to manage chronic pain among cancer survivors, and (relatedly) complexities introduced by long-term opioid management, with many clinicians describing this practice as outside their skill set. Additionally, although most clinicians recognized chronic pain as a biopsychosocial phenomenon, they described challenges with effectively managing psychosocial stressors, including difficulty accessing mental or behavioral health services for cancer survivors. CONCLUSION: Discovered challenges highlight unmet needs related to cancer survivor-clinician communication about chronic pain and the absence of a chronic pain management home for cancer survivors, including those requiring long-term opioid therapy. Research evaluating routine pain monitoring and accessible, tailored models of multimodal pain care in survivorship may help to address these challenges.
Authors
Check, DK; Jones, KF; Fish, LJ; Dinan, MA; Dunbar, TK; Farley, S; Ma, J; Merlin, JS; O'Regan, A; Oeffinger, KC
MLA Citation
Check, Devon K., et al. “Clinician Perspectives on Managing Chronic Pain After Curative-Intent Cancer Treatment.Jco Oncol Pract, vol. 19, no. 4, Apr. 2023, pp. e484–91. Pubmed, doi:10.1200/OP.22.00410.
URI
https://scholars.duke.edu/individual/pub1562333
PMID
36595729
Source
pubmed
Published In
Jco Oncol Pract
Volume
19
Published Date
Start Page
e484
End Page
e491
DOI
10.1200/OP.22.00410

Genome-Wide Association Study Identifies ROBO2 as a Novel Susceptibility Gene for Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors.

PURPOSE: Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests a modifying role of genetic susceptibility. Few previous studies have examined gene-anthracycline interactions. We addressed this gap using the Childhood Cancer Survivor Study (discovery) and the Children's Oncology Group (COG) study COG-ALTE03N1 (replication). METHODS: A genome-wide association study (Illumina HumanOmni5Exome Array) in 1,866 anthracycline-exposed Childhood Cancer Survivor Study participants (126 with heart failure) was used to identify single-nucleotide polymorphisms (SNPs) with either main or gene-environment interaction effect on anthracycline-related cardiomyopathy that surpassed a prespecified genome-wide threshold for statistical significance. We attempted replication in a matched case-control set of anthracycline-exposed childhood cancer survivors with (n = 105) and without (n = 160) cardiomyopathy from COG-ALTE03N1. RESULTS: Two SNPs (rs17736312 [ROBO2]) and rs113230990 (near a CCCTC-binding factor insulator [< 750 base pair]) passed the significance cutoff for gene-anthracycline dose interaction in discovery. SNP rs17736312 was successfully replicated. Compared with the GG/AG genotypes on rs17736312 and anthracyclines ≤ 250 mg/m2, the AA genotype and anthracyclines > 250 mg/m2 conferred a 2.2-fold (95% CI, 1.2 to 4.0) higher risk of heart failure in discovery and an 8.2-fold (95% CI, 2.0 to 34.4) higher risk in replication. ROBO2 encodes transmembrane Robo receptors that bind Slit ligands (SLIT). Slit-Robo signaling pathway promotes cardiac fibrosis by interfering with the transforming growth factor-β1/small mothers against decapentaplegic (Smad) pathway, resulting in disordered remodeling of the extracellular matrix and potentiating heart failure. We found significant gene-level associations with heart failure: main effect (TGF-β1, P = .007); gene*anthracycline interaction (ROBO2*anthracycline, P = .0003); and gene*gene*anthracycline interaction (SLIT2*TGF-β1*anthracycline, P = .009). CONCLUSION: These findings suggest that high-dose anthracyclines combined with genetic variants involved in the profibrotic Slit-Robo signaling pathway promote cardiac fibrosis via the transforming growth factor-β1/Smad pathway, providing credence to the biologic plausibility of the association between SNP rs17736312 (ROBO2) and anthracycline-related cardiomyopathy.
Authors
Wang, X; Singh, P; Zhou, L; Sharafeldin, N; Landier, W; Hageman, L; Burridge, P; Yasui, Y; Sapkota, Y; Blanco, JG; Oeffinger, KC; Hudson, MM; Chow, EJ; Armenian, SH; Neglia, JP; Ritchey, AK; Hawkins, DS; Ginsberg, JP; Robison, LL; Armstrong, GT; Bhatia, S
MLA Citation
Wang, Xuexia, et al. “Genome-Wide Association Study Identifies ROBO2 as a Novel Susceptibility Gene for Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors.J Clin Oncol, vol. 41, no. 9, Mar. 2023, pp. 1758–69. Pubmed, doi:10.1200/JCO.22.01527.
URI
https://scholars.duke.edu/individual/pub1559111
PMID
36508697
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
41
Published Date
Start Page
1758
End Page
1769
DOI
10.1200/JCO.22.01527