Citations

5004 Background: Since 1999, patients with low-risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. We assess survival, sites of recurrence, morbidity, and cost per up-staged case in this low-risk cohort. Methods: Consecutive patients with Mayo-defined low-risk EC managed without (non-LND) and with LND were compared. Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. 30-day cost analyses were equated to 2010 Medicare dollars. Results: Among 1,393 consecutive surgically managed EC cases, 385 (27.6%) met the Mayo low-risk criteria, accounting for 34.1% of type I EC. The 5-year CSS of the low-risk cases was 98.6 %. There were 80 LND cases (median # nodes, 29) and 305 non-LND cases. Complications within 30 days occurred in 37.5% and 19.3% of LND and non-LND cases, respectively (P<0.001). Nodal metastasis was identified in a single LND case (1.3%). There were 11 recurrences, 6 of which were vaginal. Not a single recurrence was detected in the pelvic or paraaortic nodal areas in these 385 patients, with a median follow-up of 5.4 years. The estimated prevalence (combining surgery and surveillance) of lymph node metastasis was 0.3%. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). Patients were more than seven times as likely to die of co-morbidities than from EC. The 30-day median cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $439,990 if performed via endoscopy and $327,866 via laparotomy. If the 305 non-LND cases had been subjected to LND, an estimated additional $1,418,189 would have been expended. Conclusions: For patients with low-risk EC as defined by the Mayo criteria, lymphadenectomy dramatically increases morbidity and 30-day cost of care without discernible short- or long-term benefits: CSS was 99% with a 0.3% rate of nodal metastasis. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Abstract Background: Different molecules within coffee may be pro-carcinogenic, while others may have anti-oxidant and anti-neoplastic effects. Hence, it can be hypothesized that coffee may have differing risk associations with specific colorectal cancer (CRC) subtypes. The aim of this study was to evaluate associations between coffee consumption and incident CRC overall, by anatomic subsite, and by molecularly defined tumor subtypes, in the population-based Iowa Women's Health Study (IWHS). Methods: IWHS participants, ages 55-69 years, provided dietary intake estimates using self-reported food frequency questionnaires at baseline (1986). From 35,216 women included the final analysis, 1298 developed CRC (673 with proximal CRC, 597 with distal CRC) through December 31, 2002 (end of the IWHS molecular epidemiology project study period). Archived, paraffin-embedded tissue specimens for 732 representative CRC cases were collected and analyzed to determine if coffee consumption (none or &lt;1 cup/month, &lt;1 cup/week, 1 cup/day, 2-3 cups/day and ≥4 cups/day) was associated with microsatellite instability (MSI-L/MSS or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive), BRAF mutation status (BRAF-wildtype or BRAF-mutated), KRAS mutation status (KRAS-wildtype and KRAS-mutated), p53 protein expression level (p53 absent, low or high) and estrogen receptor β protein expression level (ERβ absent, low or high). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) with adjustment for age, smoking, alcohol use, diabetes, body mass index and waist-hip ratio, physical activity, estrogen use, dietary intake of fat, calcium, vitamin E, sucrose, red meat and methionine. P-values were not adjusted for multiple testing. Results: There was no significant difference in the risk of overall (RR, 1.05; 95% CI, 0.85-1.29; Ptrend=0.50), proximal (RR, 0.91; 95% CI, 0.68-1.21; Ptrend=0.57) or distal CRC (RR, 1.18; 95% CI, 0.86-1.64; Ptrend=0.19) in women who consumed ≥4 cups of coffee/day (caffeinated or decaffeinated), as compared to non-consumers. By CRC molecular subtypes for these same two exposure groups, women with ≥4 cups of coffee/day were more likely to develop ERβ-low CRC (RR, 2.98; 95% CI, 1.04-8.51; Ptrend=0.06), though no significant associations were observed for caffeinated or decaffeinated coffee specifically. In contrast, women who consumed ≥4 cups of decaffeinated coffee/day were less likely to develop MSI-L/MSS (RR, 0.57; 95% CI, 0.36-0.92; Ptrend=0.04) and BRAF-WT (RR, 0.69; 95% CI, 0.44-1.06; Ptrend=0.06) CRCs than non-consumers. Women who consumed ≥4 cups of caffeinated coffee/day were also less likely to develop p53-low CRCs (RR, 0.53; 95% CI, 0.24-1.15; Ptrend=0.02). Null associations were observed between decaffeinated coffee consumption and risk of CIMP-, KRAS- and p53- defined CRC subtypes, as well as between caffeinated coffee consumption and risk of MSI-, BRAF-, CIMP- or KRAS-defined CRC subtypes. Conclusion: In this prospective cohort study of older women, though coffee consumption was not associated with risk of overall or site-specific CRC, unique associations were observed with molecularly defined CRC subtypes, supporting a need for further investigation of the potential pro- and anti-carcinogenic effects of coffee constituents on biologic targets involved in colorectal carcinogenesis. Citation Format: Siddharth Singh, Robert Vierkant, Lori Tillmans, Alice Wang, Daniel Weisenberger, Peter Laird, Maki Inoue-Choi, Andrea Mariani, Charles Lynch, Kristin Anderson, Amy French, Robert Haile, Lisa Harnack, John Potter, Susan Slager, Thomas Smyrk, Stephen Thibodeau, James Cerhan, Paul Limburg. Coffee consumption and colorectal cancer risk by molecularly defined subtypes in a prospective cohort study of older women. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A44.

INTRODUCTION: To compare two published risk stratification criteria (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC). METHODS: Patients who underwent surgery for EC between 1/1/2004-9/30/2013 and had endometrioid histology without stage IV disease were included and classified as either low-risk or at-risk for LD using two independent risk stratification systems. LD was defined as positive nodes at time of surgery or lymph node recurrence within 2 years of surgery after negative lymph node assessment (LNA) or when LNA was not performed. False positive (FP) and false negative (FN) rates for each risk model were calculated. RESULTS: Among 1103 patients, 81 (7.3%) had LD (72 positive LN and 9 LN recurrences). Most patients (90.2%) had stage I disease. Integration of the Milwaukee Model was associated with a low at-risk rate for LD (38.1%) but a relatively high FN rate (13.6%, 95% CI 7.0-23.0). Conversely, the traditional Mayo Criteria using a tumor diameter (TD) cutoff of ≤2 cm (vs >2 cm) had a higher at-risk rate for LD (69.5%) but a FN rate of 0.0% (95% CI, 0-4.5). Modifying Mayo Criteria using a TD cutoff of ≤3 cm (vs >3 cm) identified fewer women at-risk than using ≤2 cm cutoff (56.8% vs. 69.5%), but had a higher FN rate of 3.7% (95% CI, 0.8-10.4). CONCLUSIONS: The Milwaukee Model had the lowest at-risk rate of LD but an unacceptable FN rate. Modifying the Mayo Criteria by increasing the TD cutoff from the traditional ≤2 cm to ≤3 cm would spare an estimated 12.7% of patients LNA, but the accompanying FN rate is unacceptably high. The traditional Mayo Criteria for low-risk EC remains the most accurate in determining which patients LNA can be omitted.

Abstract In this review, we aimed to provide insight into the microbiome and its association with endometrial and ovarian cancer and their risk factors. We reviewed the literature focusing on the relationship between the microbiome and cancer, as well as the relationship between gynecologic diseases and cancers. The human body contains different kinds of microorganisms in various body parts, which is termed the microbiome . The number of microorganisms that live in and on the human body is greater than that of the human germ and somatic cells by 10‐fold. The relationship between a human and their microbiome is complex; it is also one of the most important components of homeostasis. Impairment of microbiome–host homeostasis has been associated with obesity, several cancers, preterm labor, inflammatory and allergic conditions and neurodevelopmental disorders. Direct and strong causal relationships have been established for several cancers and microorganisms, such as gastric lymphoma and Helicobacter pylori infection. Interestingly, eradication of the infectious agents has also been shown to be therapeutic. The association between cancer and the microbiome, however, is more complicated than a 1 bacteria–1 cancer model, and a shift in a healthy microbiome can result in various cancers via inflammation, change in microenvironment or DNA‐damaging toxins. The human microbiome is an integral part of homeostasis. Understanding the mechanisms that cause dysbiosis will enable us to elucidate the pathways that result in malignancy and investigate new treatment modalities.

Abstract Background Advances in next-generation DNA sequencing technologies are now enabling detailed characterization of sequence variations in cancer genomes. With whole-genome sequencing, variations in coding and non-coding sequences can be discovered. But the cost associated with it is currently limiting its general use in research. Whole-exome sequencing is used to characterize sequence variations in coding regions, but the cost associated with capture reagents and biases in capture rate limit its full use in research. Additional limitations include uncertainty in assigning the functional significance of the mutations when these mutations are observed in the non-coding region or in genes that are not expressed in cancer tissue. Results We investigated the feasibility of uncovering mutations from expressed genes using RNA sequencing datasets with a method called Variant Detection in RNA(VaDiR) that integrates 3 variant callers, namely: SNPiR, RVBoost, and MuTect2. The combination of all 3 methods, which we called Tier 1 variants, produced the highest precision with true positive mutations from RNA-seq that could be validated at the DNA level. We also found that the integration of Tier 1 variants with those called by MuTect2 and SNPiR produced the highest recall with acceptable precision. Finally, we observed a higher rate of mutation discovery in genes that are expressed at higher levels. Conclusions Our method, VaDiR, provides a possibility of uncovering mutations from RNA sequencing datasets that could be useful in further functional analysis. In addition, our approach allows orthogonal validation of DNA-based mutation discovery by providing complementary sequence variation analysis from paired RNA/DNA sequencing datasets.