Michael Kelley

Overview:

1.     A major theme throughout my career has been the biology of and improving outcomes for patients with lung cancer.  Early publications examined the relationship between specific genetic alterations in lung cancer and clinically relevant applications including differential drug sensitivity, differentiation of metastases from second primary cancers, and application of patient-specific mutations as epitopes for immunotherapy.  Correlation of alteration of p16 with drug sensitivity led to identification of a class of CDK4 inhibitor. I served as the primary investigator or co-investigator in all of these studies.  I led a study that demonstrated that tubulin mutations are uncommon in lung cancer and described the artifactual detection of pseudogenes as the origin of a prior report claiming association of tubulin mutation with taxane sensitivity, thus correcting the scientific record. 

2.   A second area of continuing interest in lung cancer is the conduct of therapeutic and prevention clinical trials.  These trials have primarily been translation of hypotheses derived primarily from laboratory-based biological observations including the GRP autocrine growth factor in small cell lung cancer, a phase I study of a pulmonary toxin in non-small cell lung cancer, mutation-specific immunotherapy, and a putative chemopreventive agent for smokers.  More recently, I have been an active member of the Respiratory Committee of CALGB/Alliance including serving as principal investigator on a trial testing the addition of irinotecan to treatment of patients with small cell lung cancer. 

3.  Through my clinical practice, I identified a large family with the May-Hegglin anomaly, an autosomal dominant platelet condition characterized as thrombocytopenia, leukocyte inclusions, and giant platelets.  While the condition had been described in the early 1900s, the genetic basis was unknown.  I conceptualized and led a project to identify the underlying molecular basis of this frequently misdiagnosed disorder through classical genetics.  I then extended that observation to related genetic conditions (now known as MYH9-assocaited disorders) characterized by varying degrees of hematological abnormalities, hearing loss and renal disease.  Analysis of the spectrum of observed mutations and phenotypes resulted in identification of a genotype-phenotype association for the most medically significant aspects of the disorders.  Working with Dan Kiehart’s lab, we described the effect of commonly observed mutations of MYH9 on assembly of non-muscle myosin.  An animal model of the most common MYH9 mutation was created in my lab and demonstrated hematological abnormalities similar to those found in humans. 

4.  I described genetic linkage for a rare familial cancer syndrome characterized by very high penetrance of chordoma.  Subsequent linkage analysis resolved a phenotype mis-assignment and resulted in identification of germline gene duplication of the T-box gene, Brachyury in about half of affected families.  I then confirmed another groups report that a common coding region SNP of the Brachyury gene as well as additional genetic variants are associated with an increased risk for development of chordoma independent of amplification of the Brachyury gen.   To study the biology of chordoma, I established the origin of existing putative chordoma cell lines and working criteria for identification of possible new chordoma cell lines.  Using two confirmed chordoma cell lines, I screened all regulatory-approved drugs for anti-growth activity to determine whether any could be repurposed for clinical use in patients. 

5.  Beginning in 2007, I began to transition my career to a leadership position within the Department of Veterans Affairs as the National Program Director for Oncology.  This led to opportunities to utilize the vast and detailed clinical data sets of nearly 1 million patients with cancer to address questions that have been difficult to study either through randomized trials or in less robust datasets.  The use of surgery to treat early stage non-small cell lung cancer is a standard treatment for which I observed a racial disparity.  The lower rate of use of surgery among African Americans was not explained by association with comorbidity.  In another study, I described the rate of use of adjuvant chemotherapy as having increased temporally after publication of randomized trials showing a modest benefit to its use.  I showed that initially this chemotherapy was primarily carboplatin-based, despite all positive trials having used cisplatin.  Cisplatin use has subsequently increased though there is not a demonstrable improvement is survival associated with its use.  I also showed that survival overall, regardless of use of chemotherapy, has improved suggesting that the application of clinical trial data for adjuvant chemotherapy is improving outcome.  In a related study, I found that elderly patients benefit as much as younger patients from adjuvant chemotherapy.  Patients with stage III non-small cell lung cancer are frequently treated with concurrent chemoradiotherapy, for which there are two commonly used chemotherapy regimens: cisplatin-etoposide and carboplatin-paclitaxel.  I examined the outcome and toxicity of patients treated with these two regimens and found that while there was no significant difference in survival, there was more toxicity associated with cisplatin-etoposide.  This finding may impact one current clinical guideline recommendation that favors cisplatin-etoposide over carboplatin-paclitaxel.  Finally, in stage IV disease, a similar observation was made that cisplatin-based chemotherapy is associated with greater toxicity but not improved survival. 

Complete List of Published Work in MyBibliography:   http://www.ncbi.nlm.nih.gov/sites/myncbi/michael.kelley.1/bibliography/43511621/public/?sort=date&direction=descending

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1985

University of Michigan at Ann Arbor

Medical Resident, Medicine

Duke University

Grants:

Measurement of Hypoxia in Non-Small Cell Lung Carcinoma

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

Quit-smoking program for lung cancer patients' families

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

IPA - Bradley Hintze

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Chordoma Foundation Brachyury Mouse Model Project

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Chordoma Genetically Engineered Mouse Model

Administered By
Medicine, Medical Oncology
Role
Principal Investigator
Start Date
End Date

Publications:

VA Cancer Research: A Legacy and A Future.

Authors
Bates, SE; Kelley, MJ
MLA Citation
Bates, Susan E., and Michael J. Kelley. “VA Cancer Research: A Legacy and A Future..” Semin Oncol, vol. 46, no. 4–5, Aug. 2019, pp. 305–07. Pubmed, doi:10.1053/j.seminoncol.2019.11.001.
URI
https://scholars.duke.edu/individual/pub1423489
PMID
31818371
Source
pubmed
Published In
Semin Oncol
Volume
46
Published Date
Start Page
305
End Page
307
DOI
10.1053/j.seminoncol.2019.11.001

Association of Mutational Profile and Human Papillomavirus Status in Patients with Head and Neck Squamous Cell Carcinoma

Authors
Doerstling, S; Winski, D; Hintze, B; Poonnen, PJ; Duffy, JE; Snowdon, J; George, J; Jackson, GP; Weeraratne, D; Spector, NL; Kelley, MJ; Vashistha, V
MLA Citation
Doerstling, S., et al. “Association of Mutational Profile and Human Papillomavirus Status in Patients with Head and Neck Squamous Cell Carcinoma.” Journal of Molecular Diagnostics, vol. 21, no. 6, ELSEVIER SCIENCE INC, 2019, pp. 1204–1204.
URI
https://scholars.duke.edu/individual/pub1422425
Source
wos
Published In
The Journal of Molecular Diagnostics
Volume
21
Published Date
Start Page
1204
End Page
1204

Racial Differences in Treatment and Survival among Veterans and Non-Veterans with Stage I NSCLC: An Evaluation of Veterans Affairs and SEER-Medicare Populations.

BACKGROUND: Surgery is the preferred treatment for stage I non-small cell lung cancer (NSCLC), with radiation reserved for those not receiving surgery. Previous studies have shown lower rates of surgery among Blacks with stage I NSCLC than among Whites. METHODS: Black and White men ages ≥65 years with stage I NSCLC diagnosed between 2001 and 2009 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and Veterans Affairs (VA) cancer registry. Logistic regression and Cox proportional hazards models were used to examine associations between race, treatment, and survival. RESULTS: Among the patients in the VA (n = 7,895) and SEER (n = 8,744), the proportion of Blacks was 13% and 7%, respectively. Overall, 16.2% of SEER patients (15.4% of Whites, 26.0% of Blacks) and 24.5% of VA patients received no treatment (23.4% of Whites, 31.4% of Blacks). In both cohorts, Blacks were less likely to receive any treatment compared with Whites [ORadj = 0.57; 95% confidence interval (CI), 0.47-0.69 for SEER-Medicare; ORadj = 0.68; 95% CI, 0.58-0.79 for VA]. Among treated patients, Blacks were less likely than Whites to receive surgery only (ORadj = 0.57; 95% CI, 0.47-0.70 for SEER-Medicare; ORadj = 0.73; 95% CI, 0.62-0.86 for VA), but more likely to receive chemotherapy only and radiation only. There were no racial differences in survival. CONCLUSIONS: Among VA and SEER-Medicare patients, Blacks were less likely to get surgical treatment. Blacks and Whites had similar survival outcomes when accounting for treatment. IMPACT: This supports the hypothesis that equal treatment correlates with equal outcomes and emphasizes the need to understand multilevel predictors of lung cancer treatment disparities.
Authors
Williams, CD; Alpert, N; Redding, TS; Bullard, AJ; Flores, RM; Kelley, MJ; Taioli, E
MLA Citation
Williams, Christina D., et al. “Racial Differences in Treatment and Survival among Veterans and Non-Veterans with Stage I NSCLC: An Evaluation of Veterans Affairs and SEER-Medicare Populations..” Cancer Epidemiol Biomarkers Prev, Oct. 2019. Pubmed, doi:10.1158/1055-9965.EPI-19-0245.
URI
https://scholars.duke.edu/individual/pub1416576
PMID
31624076
Source
pubmed
Published In
Cancer Epidemiol Biomarkers Prev
Published Date
DOI
10.1158/1055-9965.EPI-19-0245

Genomic analysis of metastatic solid tumors in veterans: Findings from the VHA National Precision Oncology Program.

Authors
Poonnen, P; Duffy, J; Hintze, BJ; Shukla, M; Brettin, TS; Conrad, NR; Yoo, H; Guertin, CM; Looney, JA; Vashistha, V; Kelley, MJ; Spector, NL
MLA Citation
Poonnen, Pradeep, et al. “Genomic analysis of metastatic solid tumors in veterans: Findings from the VHA National Precision Oncology Program..” Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 3074–3074. Crossref, doi:10.1200/jco.2019.37.15_suppl.3074.
URI
https://scholars.duke.edu/individual/pub1414962
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
3074
End Page
3074
DOI
10.1200/jco.2019.37.15_suppl.3074

Implementation of the VA Symptom Assessment Scale (VSAS): Five-year experience.

Authors
Friedman, DR; Patil, V; Rasmussen, KM; Sauer, BC; Kelley, MJ; Halwani, AS
MLA Citation
Friedman, Daphne Ruth, et al. “Implementation of the VA Symptom Assessment Scale (VSAS): Five-year experience..” Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. e23120–e23120. Crossref, doi:10.1200/jco.2019.37.15_suppl.e23120.
URI
https://scholars.duke.edu/individual/pub1415695
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
e23120
End Page
e23120
DOI
10.1200/jco.2019.37.15_suppl.e23120