A Personalized Medicine Approach to Lung Cancer and Melanoma.
Cindy Vnencak-Jones, Zengliu Su, Laurel Fohn, Cheryl Coffin, Adriana Gonzalez, Doha Itani, Chanjuan Shi, Jeffrey Sosman, William Pao. Vanderbilt University Medical Center, Nashville, TN
Background: Collectively ∼300,000 new cases of lung cancer and melanoma will be diagnosed in the US in 2010. Long term survival for patients with metastatic disease is poor. Therapy targeted against aberrant tumor proteins has demonstrated promising results, but only subsets of tumors harbor such aberrations. To facilitate personalized cancer medicine, we developed and implemented clinical DNA-based molecular profiling on all non-squamous non-small cell lung cancer and melanoma patients treated at our institution. This approach identifies patient specific tumor mutations, enables personalized targeted therapy and intends to optimize treatment and improve outcome.
Design: A multidisciplinary team developed and implemented this process. Lung and melanoma specific DNA-based assays using the SNaPshot multiplex kit (Applied Biosystems) and fluorescent PCR coupled with fragment analysis were designed to detect common somatic mutations linked with outcomes to existing or emerging targeted therapies. Each assay was vigorously tested and validated within a research lab prior to transition into the clinical lab and the performance and sensitivity of each assay was independently verified in the clinical lab. Implementation of the initiative involved: establishment of a detailed process of tissue submission; education of clinicians, pathologists and laboratory staff and development of an effective reporting system within the electronic medical record.
Results: The lung cancer panel includes analysis of ∼40 mutations (including indels) in 9 genes: EGFR, HER2, KRAS, BRAF, PIK3CA, MEK, NRAS, AKT1 and PTEN. The melanoma panel detects 43 mutations in 6 genes: BRAF, KIT, NRAS, GNAQ, GNA11, and CTNNB1. Sensitivity of the assays is 5%, lab turn around times is 8 days and 3% of samples have been rejected for insufficient material or gave no results. Mutation frequencies are similar to that quoted in the literature, and results have been used to guide treatment options. Logistical challenges have included: delays in tissue block acquisition from outside facilities; improper submission of specimens; incomplete reflex testing for all specimens and insufficient staffing and equipment.
Conclusions: In < 1 year, a collaborative and multidisciplinary team launched a personalized cancer medicine initiative in which lung cancers and melanomas are routinely profiled for disease-specific mutations linked to targeted therapies. This practice can now be expanded to other disease processes to facilitate adoption of genetically-informed medicine to improve clinical outcome.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 1, 2011 8:45 AM
Platform Session: Section H 1, Tuesday Morning