Andrew G. Scarfe

Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.

Background: Surgery followed by adjuvant chemotherapy has been the standard of care for the treatment of stage III colon cancer since the early 1990’s. Despite this, large proportions of patients do not receive adjuvant chemotherapy. We aimed to identify physicians’ and patients’ reasons for treatment decisions. Methods: A retrospective population based study was conducted that included all surgically treated stage III colon cancer patients diagnosed in Alberta between 2002 and 2005 who had an oncologist-consult to discuss post-surgical treatment options. Patient demographics and stage were obtained from the Alberta Cancer Registry. Chart reviews were conducted to extract treatment details, the oncologists’ reasons for not recommending chemotherapy, and patients’ reasons for refusing chemotherapy. The number and proportion of patients who were not recommended or refused chemotherapy were calculated. Results: A total of 613 patients had surgery followed by an oncologist-consult. Overall, 168 (27%) patients did not receive chemotherapy. It was not recommended for 111 (18%) patients; the most frequent reason was presence of one or more co-morbidities (34%) or combination of co-morbidity and age or frailty (22%). Fifty-eight (9%) patients declined chemotherapy, 22% of whom declined due to concerns about toxicity. Conclusion: Some co-morbidities are clinical indications for not receiving adjuvant chemotherapy, however, the high percentage of patients who were not recommended adjuvant chemotherapy due to co-morbidities according to clinical notes but who had a low Charlson co-morbidity score suggests variation in practice patterns of consulting oncologists. In addition, patients’ reasons for refusing treatment need to be systematically assessed to ensure patients’ preferences and treatment benefits are properly weighed when making treatment decisions.