Citations

Abstract Introduction: The 21-gene Recurrence Score (RS) assay has been shown in retrospective studies to predict benefit of adjuvant chemotherapy (AC) in node positive (N+) breast cancer (BC) patients (pts). This study evaluates the trends and patterns of use of RS assay in N+, ER+/HER2-breast cancer and the impact of RS on decision to use AC in a real-world multi-institutional database. Methods: Pts with T1-T4c, N1mi-N3, ER+/HER2- BC diagnosed between 2010 and 2013, included in the National Cancer Data Base were analyzed. Pts who received neo-AC were excluded. Analyses included Cochrane-Armitage tests for trends and multivariable logistic regression assessing factors influencing RS testing and AC recommendations based on RS. Results: Among 73,049 pts, RS was obtained in 20.6%, increasing from 14.9% in 2010 to 24.4% in 2013 (p<0.001). RS testing was most common in N1mi (43.6%) and N1 (22.0%) and rare in N2/N3 (3.3%) BC. Of the 12,540 BC with quantitative RS results, 61.1% were low RS, 32.3% intermediate RS and 6.6% high RS. AC recommendation was less frequent in pts with RS testing compared to pts not tested (50.4% recommended AC vs 80.9%, p<0.001). In pts with N1mi/N1 BC, recommendation rates for AC were higher with higher RS (see table), however in N2/N3 BC, AC was recommended in the majority (71-88%) regardless of RS. Most pts (>85%) with RS 26-30 or high risk RS were recommended AC regardless of N stage. For pts with low risk RS, recommendation for AC increased significantly with increasing N stage (see table). On multivariable analysis, in pts with low risk RS, AC was more likely to be recommended in those with N1/N2+ stage (OR 2.3 and 9.1 vs N1mi), T2 and T3/T4 tumors (OR 1.3 and 2.2 vs T1 tumors), poorly differentiated tumors (OR 1.6) and younger age (OR 3.4 and 1.7, respectively, for <40 and 40-49 vs 50-59) (all p<0.001). Among pts with RS 18-25, AC was more likely to be recommended in those with higher tumor grade, younger age but the effect of N stage was less pronounced. Histology (IDC vs ILC) did not influence AC recommendation in any RS subset. Path N StageRS Risk GroupLow RiskIntermediate RiskHigh RiskRS<18RS 18-25RS 26-30RS>30N1mi AC No1,854 (75.9%)389 (36.9%)36 (14.6%)16 (7.0%)N1mi AC Yes590 (24.1%)666 (63.1%)210 (85.4%)212 (93.0%)N1 AC No3,000 (60.6%)699 (33.0%)75 (14.8%)33 (6.0%)N1 AC Yes1,954 (39.4%)1,422 (67.0%)431 (85.2%)518 (94.0%)N2/N3 AC No76 (29.0%)17 (16.7%)3 (12.5%)7 (14.9%)N2/N3 AC Yes186 (71.0%)85 (83.3%)21 (87.5%)40 (85.1%)p-value<0.001<0.0010.880.16 Conclusions: RS was obtained in about one fifth of pts with N+ ER+/HER2- BC, predominantly for N1mi and N1 disease. Overall, RS testing decreased frequency of recommendation of AC in N+ BC pts. The RS influenced use of AC particularly in N1mi and N1 pts, likely avoiding overtreatment of those with low risk RS and RS 18-25. Prospective data regarding RS to direct AC in N+ BC are awaited. Citation Format: Peethambaram PP, Hoskin TL, Heins CN, Habermann EB, Boughey JC. How 21-gene recurrence score assay is being used to individualize adjuvant chemotherapy recommendations in ER+/HER2 -node positive breast cancer -A national cancer data base study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-05.

Abstract Background: Negative margins are important in decreasing risk of local recurrence after breast conservation surgery. Further, positive margins on final pathology require a second operation, burdening patients and increasing costs. We identified factors predicting positive margins at lumpectomy prompting intraoperative re-excision in a large referral center. Methods With IRB approval we reviewed all breast cancer lumpectomy cases from January 2012 to December 2013. Associations between rates of positive margin (defined as tumor at ink) and patient and tumor factors were assessed using chi square tests and univariate and adjusted multivariable logistic regression, overall and stratified by DCIS or invasive cancer. Results 385 patients (105 DCIS and 280 invasive disease) were identified. Overall positive margin rate at lumpectomy requiring intraoperative re-excision was 62.3% and was higher in DCIS than in invasive disease (78.1% vs 56.4%, OR=2.78, p=0.001). Positive margin rates did not vary by surgeon, patient age, ER, PR or HER2 status of the tumor. On univariate analysis higher tumor grade was associated with a higher margin positive rate (grade 3 vs grade 1, OR=1.71, p=0.049). Within the 105 DCIS cases, no factors had statistically significantly different odds of positive margins on univariate or multivariable analysis. Within the 280 cases of invasive breast cancer, factors independently associated with lower odds of margin positivity were neoadjuvant chemotherapy (OR 0.30, p=0.037, relative to no neoadjuvant therapy) and seed localized excision (OR 0.24, p=0.03, relative to no localization). Multivariable Logistic Regression* Modeling DCISInvasive DiseaseVariableOdds RatioP-valueOdds RatioP-valueAge 50+ vs Age <502.860.111.590.23Grade 2 vs Grade 10.940.921.500.21Grade 3 vs Grade 13.250.121.580.37Estrogen Receptor Positive vs Negative3.950.221.640.42Progesterone Receptor Positive vs Negative0.840.871.110.84Her2 Positive vs Negative 1.270.68Stage T2 vs T1 2.540.45Stage T3 vs T1 2.180.69Ki67 <15% vs 15%+ 0.570.09Neoadjuvant Chemotherapy vs None 0.300.04Seed Localization vs No Localization 0.240.03Wire Localization vs No Localization 0.330.13Intraoperative Ultrasound vs No Localization 0.670.53*adjusted for individual surgeons (all p >0.05) Conclusion DCIS was associated with higher rate of positive margins at lumpectomy than invasive breast cancer. Within invasive disease, neoadjuvant chemotherapy and seed localization were associated with lower rates of margin positivity. Strategies to decrease positive margins would be best employed in cases of lumpectomy for DCIS and for invasive disease treated without neoadjuvant chemotherapy. Seed localization may be one strategy to lower positive margin rates. Citation Format: Boughey JC, Keeney MG, Glasgow AE, Keeney GL, Habermann EB. Tumor and procedural factors associated with positive margins at lumpectomy in women undergoing breast conservation surgery [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-08.

110 Background: Assessment of compliance with national quality guidelines for the management of melanoma may be complicated by controversy about selection of patients for nodal surgery and limited by a lack of data on quality metrics. Previous reports suggest suboptimal overall compliance, with sentinel lymph node biopsy (SLNB) not performed for many suitable patients and completion lymph node dissection (CLND) omitted in many biopsy-proven node-positive (LN+) cases. The purpose of this study was to assess compliance with national ASCO/SSO guidelines for lymph node (LN) surgery for T2 and T3 (intermediate thickness, 1.01-4.00 mm) primary cutaneous melanoma patients and elucidate factors associated with non-compliance. Methods: All cases of T2 and T3, M0 melanoma were identified from 2004-2010 SEER data. Multivariable logistic regression was utilized to identify independent predictors of compliance. Five-year cancer specific survival (CSS) was estimated using the Kaplan-Meier method. Results: Overall, 75.3% (6,609/8,782) of T2-T3 primary cutaneous melanoma patients underwent LN staging including SLNB in 6,330 (74.5%) of 8,492 clinically LN negative patients. Among these 6,609 patients, 1,279 (19.4%) had one or more LN+. 940 LN+ patients (73.4%) underwent CLND with removal of a mean (median, IQR) of 20.7 (18, 11-27) LNs. Compliance with LN staging and management guidelines was associated with truncal primary site (for SLNB), p<0.001 and with patient age <65 yrs and increasing number of metastatic LNs (for CLND), both p<0.0001. Compliance with CLND for LN+ patients was associated with improved 5 year CSS: 70.0% vs 64.6%, p<0.001. Conclusions: Compliance with guidelines for LN surgery in T2 and T3 melanoma is poor despite the well-defined benefit for this group of patients. These data suggest that non-compliance is multifactorial and not simply due to practice differences arising from the controversial aspects of melanoma management. Room for improvement exists. Assessment of modifiable factors associated with poor compliance, design of strategies to improve compliance and the development of performance measures around appropriate LN staging and management of T2 and T3 melanoma deserve further investigation.

445 Background: Radical cystectomy (RC) is the gold standard treatment for muscle-invasive and high-risk non-muscle invasive bladder cancer. However, the procedure has been associated with a high complication rate, including perioperative infection. In addition to resulting in patient morbidity, infections have been suggested as a quality metric. We sought to evaluate the incidence, risk factors, and timing of infection following RC. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried to identify patients undergoing RC for bladder cancer from 2005-2013 using CPT procedure and ICD-9 diagnosis codes. Infections (urinary tract infection (UTI), surgical site infection (SSI), and sepsis) within 30 days of RC were recorded. Characteristics including age, gender, ethnicity, body-mass index, diabetes, smoking status, renal function, steroid usage, albumin, receipt of perioperative transfusion, and operative time were abstracted, and relative risk of infection was assessed in univariate chi-squared analysis. Results: A total of 3,187 patients were identified, of whom 2604 (81.8%) were male, with a median age of 68.8 years (IQR 62, 77). Postoperative infection was diagnosed in 766 (24%) patients, at a median of 13 days (IQR 8, 19) after RC, with 44.4% occurring prior to hospital discharge. The most common type of infection was SSI (404; 12.7%), followed by sepsis (315; 9.9%), and UTI (309; 9.7%). Factors associated with increased overall infection risk were obesity (RR 1.32; 1.20-1.46; p < 0.001), receipt of a blood transfusion (RR 1.20; 1.10-1.31; p < 0.001), and increased operative time (RR for > 450 min 1.46; 1.26-1.70; p < 0.001). Risk factors for UTI in particular included obesity (RR 1.28; 1.11-1.47; p < 0.001), diabetes (RR 1.38; 1.09-1.75; p = 0.009), and increased operative time (RR for > 450 min 1.45; 1.18-1.78; p < 0.001). Conclusions: Approximately 25% of patients undergoing RC experience an infection within 30 days of surgery, most commonly SSI. Several modifiable risk factors were identified, including blood transfusion and prolonged operative time, that represent potential targets for care improvement.

284 Background: MM is an uncommon cancer with annual incidence of only 27,000 cases in the US. Our study determined the extent to which the number of MM patients treated annually in a treatment facility affected all-cause mortality. Methods: We used the National Cancer Data Base (NCDB) to identify adult patients with MM diagnosed from 2003-2011. NCDB is sourced from over 1,500 Commission on Cancer-accredited cancer registries representing 70% of cancer cases in the US. We classified treatment facilities by quartiles based on facility volume (mean patients/year): Quartile 1 (Q1: < 3.6), Quartile 2 (Q2: 3.6-6.1), Quartile 3 (Q3: 6.1-10.3) and Quartile 4 (Q4: > 10.3). We used hot deck imputation to account for missing data, Cox regression to analyze the association between facility volume and time-to-death, and random intercepts to adjust for multiple patients per facility. Results: There were 94,722 MM patients cared for at 1,333 facilities. Most patients (73.5%) were diagnosed and treated in the same facility. The median age at diagnosis was 67 years and 54.7% were males. The median annual facility volume was 6.1 patients/year (IQR: 3.6-10.3; range: 0.2-109.9). The distribution of patients according to facility volume was Q1 (5.2%), Q2 (12.6%), Q3 (21.9%) and Q4 (60.3%). The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months and Q4: 49.1 months. After multivariable analysis adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location), co-morbidity (Charlson-Deyo score), and disease-specific (year of diagnosis) factors, we show that facility volume remains an independent predictor of all-cause mortality. Compared to patients treated at Q4 facilities, patients treated at lower quartile facilities had a higher risk of death (Q3 HR: 1.16 [95% CI, 1.12-1.20]; Q2: 1.21 [1.17-1.26]; Q1: 1.27 [1.22-1.34]). We observed an inverse volume-outcome relationship up to an annual facility volume of approximately 60 patients. Conclusions: MM patients treated at higher volume facilities had lower risk of mortality compared to those treated at lower volume facilities.

64 Background: The goals of our Lymphoma Survivorship Clinic (SC) are to coordinate care, educate patients, and create a survivorship care plan (SCP). The aim of this study was to determine if patient-centered outcomes are improved after a SC visit. Methods: From 11/13-5/15, surveys were mailed to recently-treated lymphoma patients who were within 4 weeks of their last visit and in remission. Quality of life (QOL) was measured with PROMIS and distress was measured with the Impact of Events scale. Responses between those who attended SC and those who were eligible but did not attend were analyzed. Results: There were 96 surveys sent to the SC group; 59 were returned (61% response rate). Of the non-SC group, 140 surveys were sent and 84 were returned (60% response rate). Mean age was 57 years (range 23-77) in the SC group and 59 years (23-88) in the non-SC group. There were more females in the SC group (52% vs 30%) but no differences in race, marital status, education, or health literacy. Those who attended the SC were more likely to recall receiving a summary of cancer treatment and recommendations for follow-up care (90% SC vs. 75% non-SC, p = 0.03). Furthermore, SC attendees were more likely to “definitely” recall discussion on improving health or preventing illness (89% vs. 53%), getting help in making changes in habits/lifestyle (76% vs. 50%), diet (80% vs. 31%), and exercise (82% vs. 51%), all p < 0.001. There were no differences in discussions regarding smoking, follow-up testing, and symptom monitoring. The SC group was less likely to need more information regarding sexuality (6% vs 20%, p = 0.045). There were no differences in need for information regarding anxiety, fitness, familial cancer risk, fertility, complementary therapies, and social issues. The SC group was slightly more confident that they could get information or advice related to cancer (completely confident 76% vs. 61%, p = 0.07). There were no differences in QOL or distress. Conclusions: A Lymphoma SC visit increased receipt of SCP and provided more information on survivorship issues, particularly health behaviors, but did not improve QOL or distress. Further study is needed to determine if this leads to long-term health benefits.

236 Background: Patients (pts) with aggressive lymphoma are generally treated with curative intent and many become long-term survivors. There is little data on health behaviors after lymphoma diagnosis and their effect on QOL and long-term outcomes. Methods: Lymphoma pts were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and systematically followed. We measured QOL (FACT-G) and health behaviors (tobacco/alcohol use; diet/exercise habits) 3 years after diagnosis. For this study, “survivor” was defined as alive at 3 years from diagnosis with no active disease or treatment within the previous year. Results: From 2002-2012, 671 patients with aggressive lymphoma were enrolled, met survivor definition, and completed 3-year QOL and health behavior questionnaires. At 3-years, 31% of female (F) and 48% of male (M) reported a history of tobacco use for 6+ months. Of these, 13% of F and 7% of M were still smoking; 52% reported decreased use from baseline. 66% reported no change in alcohol intake at 3-years while 25% of F and 34% of M reported decreased intake. 60% often chose whole grains and 65% get 2+ servings of vegetables daily. 42% of F and 38% of M “somewhat” believed diet could change the course of their lymphoma. Most pts endorsed no significant change in diet as a result of diagnosis. Those who made changes did so primarily out of concern for “health problems other than cancer”. Overweight/obese responders were 72% pre- and 66% post-treatment. A desire to lose weight was reported by 55% of pts. 14% of F and 23% of M often engaged in regular physical activity (PA). Nearly 50% reported a decrease in PA. Pts with advanced stage (p = 0.006), age > 60 (p = 0.001), ECOG PS > 2 (p = 0.04), and worse prognostic score (p = 0.006) were more likely to report decreased PA since diagnosis. 68% of F and 61% of M intend to become more active in the next months. Regular PA (p = < 0.0001) was associated with higher QOL, while increased alcohol intake was associated with lower QOL (p = 0.009) at 3 years. Conclusions: Many survivors of aggressive NHL strive to adopt healthy behaviors and these behaviors are associated with higher QOL. Interventions aimed at emphasizing these behaviors may have potential to improve long-term outcomes and QOL.

PURPOSE: Previous studies in patients with non-Hodgkin’s lymphoma (NHL) and other malignancies have suggested that the presence of host infiltrates in the tumors of these patients may predict a better outcome. This study was undertaken to determine the prognostic importance of the presence of T cells in the biopsy specimens of patients with B-cell NHL.PATIENTS AND METHODS: Seventy-two patients with diffuse large B-cell NHL were prospectively evaluated at a single institution between 1987 and 1994. The percentage of CD3+, CD3+/HLA-DR+, CD4+, CD8+, and natural killer cells was determined by flow cytometry in the pretreatment diagnostic biopsy specimen and correlated with patient outcome.RESULTS: An increase in the percentage CD4+ T cells in the pretreatment tumor biopsies significantly correlated with patient outcome. The percent of CD4+ T cells was also highly correlated with CD3+/HLA-DR+, CD45RO+, and low l-selectin (CD62L) expression, indicating that the CD4+ T cells are activated memory T-helper cells. Those patients with increased numbers of CD4+ T cells, compared with other patients, had a significantly longer 5-year failure-free survival (72% v 43%, respectively; P = .04), as well as a significantly longer 5-year overall survival (65% v 38%, respectively; P = .05). When evaluated in a multivariate model, the International Prognostic Index and more than 20% infiltrating CD4+ T cells in the pretreatment biopsy were significant independent predictors of relapse-free and overall survival.CONCLUSION: The presence of increased numbers of activated CD4+ cells in the area of B-cell diffuse large-cell NHL predicts a better prognosis. This finding provides a strong rationale for the investigation of cellular immunotherapy in B-cell NHL.