No abstract

Conjugated linoleic acid (CLA) is widely used as a “nutraceutical” for weight loss. CLA has anticancer effects in preclinical models, and we demonstrated in vitro that this can be attributed to the suppression of fatty acid (FA) synthesis. We tested the hypothesis that administration of CLA to breast cancer patients would inhibit expression of markers related to FA synthesis in tumor tissue, and that this would suppress tumor proliferation. Women with Stage I–III breast cancer were enrolled into an open label study and treated with CLA (1:1 mix of 9c,11t- and 10t,12c-CLA isomers, 7.5 g/d) for ≥10 days before surgery. Fasting plasma CLA concentrations measured pre- and post-CLA administration, and pre/post CLA tumor samples were examined by immunohistochemistry for Spot 14 (S14), a regulator of FA synthesis, FA synthase (FASN), an enzyme of FA synthesis, and lipoprotein lipase (LPL), the enzyme that allows FA uptake. Tumors were also analyzed for expression of Ki-67 and cleaved caspase 3. 24 women completed study treatment, and 23 tumors were evaluable for the primary endpoint. The median duration of CLA therapy was 12 days, and no significant toxicity was observed. S14 expression scores decreased (p = 0.003) after CLA administration. No significant change in FASN or LPL expression was observed. Ki-67 scores declined (p = 0.029), while cleaved caspase 3 staining was unaffected. Decrements in S14 or Ki-67 did not correlate with fasting plasma CLA concentrations at surgery. Breast tumor tissue expression of S14, but not FASN or LPL, was decreased after a short course of treatment with 7.5 g/day CLA. This was accompanied by reductions in the proliferation index. CLA consumption was well-tolerated and safe at this dose for up to 20 days. Overall, CLA may be a prototype compound to target fatty acid synthesis in breast cancers with a “lipogenic phenotype”.

Purpose: Neoadjuvant therapy for pancreatic adenocarcinoma requires referral to multiple specialists before initiating therapy. We evaluated the effect of establishing a multidisciplinary clinic (MDC) for patients with newly diagnosed pancreatic adenocarcinoma on treatment access and time to therapy. Methods:Patients with newly diagnosed pancreatic adenocarcinoma diagnosed and treated at our center were included. Two patient groups were defined: preclinic represented those patients diagnosed before 2008 and MDC represented those patients diagnosed since 2009 who were treated in the newly created MDC and were initially candidates for neoadjuvant therapy. The primary outcomes were days from diagnosis to first treatment (initiation of chemotherapy or external beam radiation), days to completion of all required consultations, and number of visits needed before initiation of therapy.

274 Background: Neoadjuvant chemoradiation may play a role in improving the resectability and overall survival (OS) of patients with pancreatic adenocarcinoma. IMRT allows higher radiation doses to regions within a tumor while minimizing the dose to surrounding normal structures. Methods: Eighty-one patients with pancreatic adenocarcinoma completed neoadjuvant IMRT from 2003-2008. All were staged by CT scan, endoscopic ultrasound and laparoscopy. Based on defined resectability criteria, 14 were resectable (R), 38 considered borderline resectable (B) and 29 unresectable (U). Patients were categorized into 3 groups based on their neoadjuvant treatment. All patients received concurrent IMRT with gemcitabine (50mg/m2) twice weekly for 12 doses. IMRT prescription dose was 54 Gy in 28 fractions with a biologically effective dose of 64.47Gy10. All resected patients received intra-operative radiation (mean dose 14 Gy). Group 1 received neoadjuvant chemotherapy involving gemcitabine and docetaxel on days 1, 15, and 29 followed by IMRT. Group 2 received concurrent weekly cetuximab in addition to bi-weekly gemcitabine and IMRT. Group 3 received only concurrent gemcitabine twice weekly and IMRT. Four weeks after treatment completion, patients were evaluated with a CT scan in preparation for surgery. Results: Median OS for all patients was 22 months. The overall resectability rate after neoadjuvant IMRT was 63%. 78% of B and 39% of U patients underwent resection. 80% of all patients had an R0 resection. Median OS was 23 months for R, 28 months for B and 14 months for U patients (P = 0.002). Median OS was 18 months, 27 months and 18 months respectively for patients receiving gemcitabine-IMRT, gemcitabine-cetuximab and neoadjuvant gemcitabine/docetaxel plus concurrent gemcitabine-IMRT (P = 0.20). Median OS for R0 resections were 28 months compared to 24.3 months for patients with positive margins and 11.7 months for unresectable patients (P < 0.001). Conclusions: IMRT as part of a neoadjuvant treatment strategy for pancreatic adenocarcinoma is feasible and well tolerated. Neoadjuvant IMRT rendered a significant percentage of B patients resectable with an OS comparable to patients who were R at presentation. [Table: see text]