Michael John Kelley, MD

Professor of Medicine
Member of the Duke Cancer Institute
Campus mail 508 Fulton St; Hem-Onc 111G, Durham, NC 27705
Phone (919) 286-6944
Email address michael.kelley@duke.edu

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

Education and Training

  • Medical Resident, Medicine, Duke University, 1985 - 1988
  • M.D., University of Michigan at Ann Arbor, 1985

Publications

Allo, Mina, Lin Gu, Vishal Vashistha, Ashlyn Press, Michael Kelley, and Christina Williams. “Utilization of second-line immuno-oncology agents and associated health outcomes among united states veterans with advanced non-small cell lung cancer.” In Journal for Immunotherapy of Cancer, Vol. 7. BMC, 2019.

Scholars@Duke

Doerstling, S., D. Winski, B. Hintze, P. J. Poonnen, J. E. Duffy, J. Snowdon, J. George, et al. “Association of Mutational Profile and Human Papillomavirus Status in Patients with Head and Neck Squamous Cell Carcinoma.” In Journal of Molecular Diagnostics, 21:1204–1204. ELSEVIER SCIENCE INC, 2019.

Scholars@Duke

Williams, Christina D., Naomi Alpert, Thomas S. Redding, A Jasmine Bullard, Raja M. Flores, Michael J. Kelley, and Emanuela Taioli. “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, October 17, 2019. https://doi.org/10.1158/1055-9965.EPI-19-0245.

PMID
31624076
Full Text

Smith, Claire E. P., Arif H. Kamal, Monica Kluger, Patty Coke, and Michael J. Kelley. “National Trends in End-of-Life Care for Veterans With Advanced Cancer in the Veterans Health Administration: 2009 to 2016..” J Oncol Pract 15, no. 6 (June 2019): e568–75. https://doi.org/10.1200/JOP.18.00559.

PMID
31046573
Full Text

Poonnen, Pradeep, Jill Duffy, Bradley J. Hintze, Maulik Shukla, Thomas S. Brettin, Neal R. Conrad, Hyunseung Yoo, et al. “Genomic analysis of metastatic solid tumors in veterans: Findings from the VHA National Precision Oncology Program..” In Journal of Clinical Oncology, 37:3074–3074. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.15_suppl.3074.

Full Text

Friedman, Daphne Ruth, Vikas Patil, Kelli Marie Rasmussen, Brian C. Sauer, Michael J. Kelley, and Ahmad Sami Halwani. “Implementation of the VA Symptom Assessment Scale (VSAS): Five-year experience..” In Journal of Clinical Oncology, 37:e23120–e23120. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.15_suppl.e23120.

Full Text

Spiegel, Daphna Y., Matthew J. Boyer, Julian C. Hong, Christina D. Williams, Michael J. Kelley, Harvey Moore, Joseph K. Salama, and Manisha Palta. “Long-term Clinical Outcomes of Nonoperative Management With Chemoradiotherapy for Locally Advanced Rectal Cancer in the Veterans Health Administration..” Int J Radiat Oncol Biol Phys 103, no. 3 (March 1, 2019): 565–73. https://doi.org/10.1016/j.ijrobp.2018.10.018.

PMID
30359718
Full Text

Sokolova, Alexandra, Heather H. Cheng, Bradley J. Hintze, Michael J. Kelley, Neil L. Spector, Jill Duffy, Julie Ann Lynch, Matthew Rettig, and Robert B. Montgomery. “The Veterans Health Administration Precision Oncology Program for Advanced Prostate Cancer Patients: Expanding tumor NGS opportunities to a broader patient population..” In Journal of Clinical Oncology, 37:193–193. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.7_suppl.193.

Full Text

Zullig, Leah L., Karen M. Goldstein, Kellie J. Sims, Christina D. Williams, Michael Chang, Dawn Provenzale, and Michael J. Kelley. “Cancer Among Women Treated in the Veterans Affairs Healthcare System..” J Womens Health (Larchmt) 28, no. 2 (February 2019): 268–75. https://doi.org/10.1089/jwh.2018.6936.

PMID
29920139
Full Text

Hong, Julian C., Matthew J. Boyer, Daphna Y. Spiegel, Christina D. Williams, Betty C. Tong, Scott L. Shofer, Michael J. Moravan, Michael J. Kelley, and Joseph K. Salama. “Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry..” J Natl Compr Canc Netw 17, no. 2 (February 2019): 127–39. https://doi.org/10.6004/jnccn.2018.7090.

PMID
30787126
Full Text

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