Bell, Debra

4606 Background: Preclinical studies have indicated that TP is one of the most useful markers of tumor response to capecitabine; with elevated TP expression resulting in higher intratumor levels of 5-FU. TP level in the tumor may be associated directly with survival and may be up-regulated by XRT. Methods: Twenty patients (pts) who had newly diagnosed locally advanced pancreatic cancer, age ≥ 19 years, ECOG PS 0–2, and adequate organ function received 50.4 Gy XRT with capecitabine 1,600 mg/m2 M-F x 6 wks determined from our phase I study (JCO, Dec 2005). Following capecitabine-XRT, stable and responding pts received capecitabine 2,000mg/m2 x 14 days every 3 wks till progression. Restaging was performed every 9 wks. Tumor specimens were procured with EUS-FNA prior and week 2 after starting capecitabine-XRT to evaluate TP mRNA levels by RT-PCR. Results: TP levels were elevated post-XRT when compared to pre-XRT TP (p= 0.01). Each of the 20 pts had at least one observation of TP. Mean TP level of each pt was obtained by averaging the pre-XRT and post-XRT TP levels. If one value was missing, then the other value was used for the mean TP level. Mean TP level was significantly associated with survival using the Cox proportional hazards model (p= 0.0072). Pts were separated into two groups - those with high baseline TP level and those with lower TP level with a cut off value of 213.85 using median of mean TP level. It was observed that group with higher TP levels had better survival as compared to the group with lower TP levels. However, the survival curves of these two groups crossed over after 18 months. Conclusions: Our study suggests that the higher the TP level in tumor post-XRT, the better the survival. This is most probably due to a higher accumulation of 5-FU in tumor due to up-regulation of TP. Possible explanation for the two groups crossing over after 18 months may include heterogeneity in TP due to a difference in pharmacogenomics or idiosyncratic drug toxicity profile of capecitabine. Further studies of long-term effects of treatment with a larger number of pts are needed to study exact effects of capecitabine and XRT, and to evaluate the differential role of TP with survival. [Table: see text]

Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm2) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.