James Thomas Symanowski

Margin re‐excision and local recurrence in invasive breast cancer: A cost analysis using a decision tree model

SSO‐ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re‐excising close margins results in decreased costs without compromising care.

HOXA4/HOXB3 gene expression signature as a biomarker of recurrence in patients with high-grade serous ovarian cancer following primary cytoreductive surgery and first-line adjuvant chemotherapy

OBJECTIVES Aberrant homeobox (HOX) gene expression is reported in high-grade serous ovarian carcinoma (HGSOC), however, its prognostic significance remains unclear. METHODS HOX genes associated with progression-free survival (PFS) in a discovery cohort of primary HGSOC samples with RNA sequencing data, and those previously reported to be associated with clinical outcomes, were selected for qPCR testing in an independent training cohort of primary HGSOC samples (n=71). A prognostic model for PFS was developed using univariate and multivariate Cox regression. Patients were stratified into risk groups that optimized the test statistic. The model was tested in an independent HGSOC cohort from The Cancer Genome Atlas (TCGA) (n=320). The effect of selected HOX genes on drug sensitivity and reactive oxygen species (ROS) accumulation was examined in vitro. RESULTS Of 23 HOX genes tested in the training cohort, HOXA4 (HR=1.20, 95% CI=1.07-1.34, P=0.002) and HOXB3 (HR=1.09, 95% CI=1.01-1.17, P=0.027) overexpression were significantly associated with shorter PFS in multivariate analysis. Based on the optimal cutoff of the HOXA4/HOXB3 risk score, median PFS was 16.9months (95% CI=14.6-21.2months) and not reached (>80months) for patients with high and low risk scores, respectively (HR=8.89, 95% CI=2.09-37.74, P<0.001). In TCGA, the HOXA4/HOXB3 risk score was significantly associated with disease-free survival (HR=1.44, 95% CI=1.00-2.09, P=0.048). HOXA4 or HOXB3 overexpression in ovarian cancer cells decreased sensitivity to cisplatin and attenuated the generation of cisplatin-induced ROS (P<0.05). CONCLUSIONS HOXA4/HOXB3 gene expression-based risk score may be useful for prognostic risk stratification and warrants prospective validation in HGSOC patients.

The effect of radiation therapy in the treatment of adult soft tissue sarcomas of the extremities: a long-term community-based cancer center experience

The aim of the study was to determine the effect of external beam radiotherapy (RT) in the treatment of extremity soft tissue sarcoma (STS) before or after limb‐sparing surgery (LSS) in a community‐based setting. Patients presenting to our institution from 1992 to 2010 and meeting eligibility criteria were stratified into low (G1) or high (G2, G3) pathologic grade and evaluated. Major complication events, including amputation, radiation‐induced sarcoma, and pathologic fracture, were assessed. Kaplan–Meier techniques and Cox proportional hazards regression models were used. One hundred and sixty‐two eligible patients underwent LSS for extremity STS (120 high grade, 42 low grade). Median time of follow‐up was 5.1 years (0.8–20.3 years). RT was administered to 111 patients. In unadjusted models, RT significantly decreased the risk of local recurrence (LR) in high‐grade STS patients (P = 0.005) and had a trend for improved recurrence‐free survival (RFS) (P = 0.069). In multivariable‐adjusted models, RT significantly improved time to LR (P = 0.001), RFS (P = 0.003), and overall survival (OS) (P = 0.003). Analysis of all patients showed those who underwent RT had a major complication rate (MCR) of 16.2%, compared to 3.9% in the no RT group (P = 0.037); however, the difference in MCR did not differ significantly when the analysis was restricted to high‐grade sarcomas. In our large experience of patients with extremity STS undergoing limb sparing surgery (LSS), RT significantly improved local recurrence (LR), RFS, and OS, in patients with high‐grade tumors. Efficacy benefits of RT should be weighed against potential complications. External beam RT should be considered in patients with resected high‐grade sarcomas.

Treatment registry for outcomes in patients with castration-resistant prostate cancer (TRUMPET): a methodology for real-world evidence and research

Aim: This study seeks to improve the understanding of treatment patterns and associated health-related quality of life (HRQoL), clinical outcomes and healthcare utilization in US patients with castration-resistant prostate cancer (CRPC). Patients & methods: Treatment Registry for Outcomes in CRPC Patients (TRUMPET) is a US-based, prospective, observational multicenter registry (NCT02380274) involving patients with CRPC and their caregivers. Patients initiating their first active treatment course will be enrolled from urology and medical oncology practices, with data captured up to 4 years. Results: Information on prescribing patterns, HRQoL, clinical outcomes and healthcare utilization will be collected. Conclusion: TRUMPET will enable scientific understanding of disease management in terms of HRQoL, clinical outcomes and healthcare utilization in clinical practice for patients with CRPC.

Breast cancer detection in axillary sentinel lymph nodes: the impact of the method of pathologic examination ☆

At Carolinas Medical Center, before 2008, axillary sentinel lymph nodes (SLNs) from breast cancer patients were evaluated with a single hematoxylin and eosin-stained slide. In 2008, the protocol changed to include a limited step sectioning at 500 μm. In this study, we compared the intraoperative and permanent section pathologic findings for SLN biopsies from 2006 to 2007 to those from 2009 to 2010. We hypothesized that evaluating 2 slides would increase the detection of micrometastases and isolated tumor cells (ITCs) on permanent sections and correspondingly decrease the sensitivity of intraoperative touch preparation cytology (IOTPC). From 2006 to 2007, 140 (23.5%) of 597 of SLN permanent sections contained tumor cells: 92 macrometastases (65.7%), 36 micrometastases (25.7%), and 12 ITCs 0.2 mm or less (8.6%). The sensitivity of IOTPC for 2006 to 2007 was 51.4% for any tumor cells and 71.7% for macrometastases. From 2009 to 2010, 160 (21.9%) of 730 SLN permanent sections were positive for any tumor cells: 76 macrometastases (47.5%), 55 micrometastases (34.4%), and 29 ITCs (18.1%). The sensitivity of IOTPC for 2009 to 2010 was 39.4% for any tumor cells and 76.3% for macrometastases. With limited step sectioning, we observed an approximately 10% increase in the detection of both micrometastases and ITCs in SLN. The increased detection of ITCs on permanent sections reached statistical significance (P = .018). However, under current clinical guidelines, patients with limited SLN involvement may not be required to undergo completion axillary lymph node dissection. The ability to detect SLN tumor deposits less than 2 mm must be balanced with the clinical utility of doing so.

Outcomes of a Structured Education Intervention for Latinas Concerning Breast Cancer and Mammography.

Objective: This study examined the utility of living room and church-based small group educational sessions on breast cancer and mammography, for under-served Latinas in North Carolina, USA. Design: Non-randomised, single arm design. Setting: A total of 329 self-selected Latinas participated in 31 small group educational classes in church and home locations in rural and urban settings, and underwent pre- and post-intervention testing of knowledge about breast cancer and mammography. Method: Participants completed educational surveys at baseline before intervention (329), immediately after intervention (329) and 3 months after intervention (223 participants). Results: Misconceptions still exist about breast cancer risk, prevalence and mammography use among Latinas, with the greatest knowledge deficit being in the domain of risk factors. Increases of knowledge were achieved when compared to baseline measures as a result of the interventions described in this paper, which were retained at 3 months re-testing. Many eligible women were not receiving mammograms due to financial barriers. Conclusions: Education sessions of the kind described in this paper are useful in enhancing retained knowledge in breast cancer education for US Latinas.

Abstract B41: Distribution of cytogenetic abnormalities in African American multiple myeloma patients may be unique for different geographic regions

Background: Multiple myeloma (MM) is the most common hematologic malignancy in the African American population, with an incidence more than 2 times higher than Caucasian population [Landgren O et al Blood 2006]. Historically, the African American MM patients have had better outcomes compared with other races [Ailawadhi S et al Br J Haematol 2012], but no biologic explanations exist for this observation. Greenberg et al [Blood Cancer J 2015] have recently reported on differences in commonly observed baseline cytogenetic abnormalities (CA) between African American and Caucasian MM patients seen at Mayo Clinic (Rochester, MN), Cook County Hospital (Chicago, IL) and University of Maryland (Baltimore, MD). We examined the MM cohort at our referral center to validate these observations. Patients and Methods: The Levine Cancer Institute MM database was interrogated for all patients presenting with MM between January 2012 and April 2015. Baseline clinical and pathology variables were compared between the African American and Caucasian cohorts. Continuous variables were compared using nonparametric rank tests, while incidences and proportions (e.g. CAs including t(11;14), t(4;14), monosomy13/del13q and del17p) were compared using Fisher9s exact tests. Results: A total of 662 patients were identified; excluding those with MGUS classification, 368 patients were included in the analysis (African Americans n = 130, Caucasian n = 238). The median age of African American MM patients was significantly younger than Caucasian MM patients (median age 60 years vs. 65 years, p=0.010), with similar gender distribution. There was a numerically larger proportion of African American patients with anemia (40.8% vs 30.8%, p =0.166), however, there was no significant difference in degree of BM plasmacytosis amongst the two groups. The overall distribution of MM patients by IMWG risk stratification (Chng et al, Leukemia 2013) was also similar between the two groups. The African American MM patients had a numerically higher incidence of a metaphase abnormality on conventional cytogenetics (21.7% vs. 13.9%, p =0.154). They had a significantly lower incidence of t(11;14) [7.7% vs. 16%, p=0.024], a numerically higher incidence of t(4;14) [6.2% vs. 3.8%, p=0.309], and similar incidence of deletion 13/del13q [22.3% vs. 18.9%, p=NS] and del17p [7.7% vs. 7.6%, p=NS]. Conclusions: The present dataset is the largest single institution report on CA racial differences in MM patients. We observed that unlike previous reports of lower incidence of t(4;14) or del17 p in African American MM patients by Greenberg et al, we have observed a higher incidence of t(4;14) and similar incidence of del17p in our experience compared to Caucasian MM patients. The different pattern of CA distribution compared to published literature may represent geographic heterogeneity and potentially influence survival outcomes. Citation Format: Preeya Patel, Manisha Bhutani, Kyle Madden, Myra R. Robinson, Rupali Bose, James Symanowski, Saad Z. Usmani. Distribution of cytogenetic abnormalities in African American multiple myeloma patients may be unique for different geographic regions. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B41.