Credit Hours: CME 1.00

Target Audience:

Faculty, residents, fellows, and community physicians in General Internal Medicine and subspecialties.

Educational Objectives:

Upon completion of this activity, participants should be able to:

Improve patient outcomes through mismatch repair (MMR) testing in all GI malignancies.

Utilize and follow colon cancer guidelines for genetic testing based on patient history and MMR testing.

Recognize the GI tumor types which can be treated with checkpoint inhibition.
Recognize the roles of VEGFR TKIs in mRCC and the role of immune checkpoint inhibition

Suggested Additional Reading:

Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., et al. (2015). PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. The New England Journal of Medicine, 372(26), 2509–2520. http://doi.org/10.1056/NEJMoa1500596 Llosa, N. J., Cruise, M., Tam, A., Wicks, E. C., Hechenbleikner, E. M., Taube, J. M., et al. (2015). The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discovery, 5(1), 43–51. http://doi.org/10.1158/2159-8290.CD-14-0863

Xiao, Y., & Freeman, G. J. (2015). The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy. Cancer Discovery, 5(1), 16–18. http://doi.org/10.1158/2159-8290.CD-14-1397 Boutros, C., Tarhini, A., Routier, E., Lambotte, O., Ladurie, F. L., Carbonnel, F., et al. (2016). Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nature Reviews. Clinical Oncology, 13(8), 473–486. http://doi.org/10.1038/nrclinonc.2016.58 Pfirschke, C., Engblom, C., Rickelt, S., Cortez-Retamozo, V., Garris, C., Pucci, F., et al. (2016). Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. Immunity, 44(2), 343–354. http://doi.org/10.1016/j.immuni.2015.11.024

Weber, J. S., Yang, J. C., Atkins, M. B., & Disis, M. L. (2015). Toxicities of Immunotherapy for the Practitioner. Journal of Clinical Oncology, 33(18), 2092–2099. http://doi.org/10.1200/JCO.2014.60.0379

de Rosa, N., Rodriguez-Bigas, M. A., Chang, G. J., Veerapong, J., Borras, E., Krishnan, S., et al. (2016). DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 34(25), 3039–3046. http://doi.org/10.1200/JCO.2016.66.6826

Stadler, Z. K., Battaglin, F., Middha, S., Hechtman, J. F., Tran, C., Cercek, A., et al. (2016). Reliable Detection of Mismatch Repair Deficiency in Colorectal Cancers Using Mutational Load in Next-Generation Sequencing Panels. Journal of Clinical Oncology, 34(18), 2141–2147. http://doi.org/10.1200/JCO.2015.65.1067.

Hartman, D. J., Brand, R. E., Hu, H., Bahary, N., Dudley, B., Chiosea, S. I., et al. (2013). Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach. Human Pathology, 44(11), 2518–2528. http://doi.org/10.1016/j.humpath.2013.06.012.

Authors:

Leonard J. Appleman, MD, PhD — Associate Professor of Medicine, Division of Hematology/Oncology, Hillman Cancer Center
No relationships with industry relevant to the content of this educational activity have been disclosed.

Nathan Bahary, MD, PhD — Division of Hematology/Oncology, Associate Professor of Medicine, Associate Professor, Molecular Genetics and Biochemistry, Member, McGowan Institute of Regenerative Medicine Medical Director - Pancreatic Cancer Program Co-Director - UPMC Pancreatic Cancer Center of Excellence
Dr. Bahary receives research support from NewLinks Genetics and is a consult for Exelixis and BMS.

No other members of the planning committee, speakers, presenters, authors, content reviewers and/or anyone else in a position to control the content of this education activity have relevant financial relationships with any companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

This activity is approved for AMA PRA Category 1 Credit™

The University of Pittsburgh is an affirmative action, equal opportunity institution.