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Background: Medullary thyroid carcinoma (MTC) accounts for 1-2% of all thyroid cancers. The clinical course of metastatic disease can be indolent. Our aim was to characterize the natural history of disease to evaluate the true proportion of patients who would be eligible for the currently available systemic therapies. Methods: The British Columbia Cancer Agency (BCCA) provides cancer care to a population of 4.6 million. A retrospective chart review was conducted of all patients with MTC referred to the BCCA from 1991 to 2013. Clinical characteristics, pathology, treatment and outcome data were collected. Relapse free survival and overall survival was determined for patients based on staging at the time of diagnosis. Results: Of the 98 patients referred to the BCCA during the study period, inherited mutations were found in 6% though 60% did not undergo genetic testing. Based on clinical SEER staging at diagnosis 50% had localized disease, 38% regional, and 12% had distant metastasis. 77% had complete surgical resection of which 25% received adjuvant radiation therapy. Five year relapse free survival (RFS) for localized and regional disease was 75% and 66%, respectively (p = 0.006). Initial treatment of 23 patients with locally unresectable and metastatic disease predominantly involved multiple modalities. Of the 37 patients with relapsed or metastatic MTC only 7 (19%) patients received one or more course of chemotherapy for metastatic disease: 1 temsirolimus, 2 adriamycin, 3 sunitinib, 3 sorafenib, and 3 vandetanib. Five year OS based on clinical SEER stage: localized 93%, regional 72% and distant 33% (p < 0.001). Conclusion: Localized and regional MTC treatment patterns reflect multidisciplinary management based on disease characteristics. Patients with distant disease had poor outcomes with 28% of patients dying from disease. In our cohort the minority of patients ultimately received systemic therapy due to timing and lack of TKI availability. [ABSTRACT FROM AUTHOR]

Background: Gefitinib, a small molecule tyrosine kinase inhibitor of the Epidermal Growth Factor Receptor (EGFR), has shown limited efficacy in the treatment of lung cancer. Recognized clinical predictors of response to this drug, specifically female, non-smoker, Asian descent, and adenocarcinoma, together suggest a genetic basis for drug response. Recent studies have addressed the relationship between response and either sequence mutations or increased copy number of specific receptor tyrosine kinases. We set out to examine the relationship between response and the molecular status of two such kinases, EGFR and HER2, in 39 patients treated with gefitinib at the BC Cancer Agency. Methods: Archival patient material was reviewed by a pathologist and malignant cells were selectively isolated by laser microdissection or manual recovery of cells from microscope slides. Genomic DNA was extracted from 37 such patient samples and exons 18-24, coding for the tyrosine kinase domain of EGFR, were amplified by PCR and sequenced. EGFR and HER2 copy number status were also assessed using FISH in 26 samples. Correlations between molecular features and drug response were assessed using the two-sided Fisher's exact test. Results: Mutations previously correlated with response were detected in five tumours, four with exon 19 deletions and one with an exon 21 missense L858R point mutation. Increased gene copy number was observed in thirteen tumours, seven with EGFR amplification, three with HER2 amplification, and three with amplification of both genes. In our study cohort, a correlation was not observed between response and EGFR mutations (exon 19 deletion p = 0.0889, we observed a single exon 21 mutation in a non-responder) or increases in EGFR or HER2 copy number (p = 0.552 and 0.437, respectively). Conclusion: Neither mutation of EGFR nor increased copy number of EGFR or HER2 was diagnostic of response to gefitinib in this cohort. However, validation of these features in a larger sample set is appropriate. Identification of additional predictive biomarkers beyond EGFR status may be necessary to accurately predict treatment outcome. [ABSTRACT FROM AUTHOR]