Valentina I. Petkov

Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992–2013

Background: Cancers are heterogeneous, comprising distinct tumor subtypes. Therefore, presenting the burden of cancer in the population and trends over time by these tumor subtypes is important to identify patterns and differences in the occurrence of these subtypes, especially to generalize findings to the U.S. general population. Methods: Using SEER Cancer Registry Data, we present incidence rates according to subtypes for diagnosis years (1992–2013) among men and women for five major cancer sites: breast (female only), esophagus, kidney and renal pelvis, lung and bronchus, and thyroid. We also describe estimates of 5-year relative survival according to subtypes and diagnosis year (1992–2008). We used Joinpoint models to identify years when incidence rate trends changed slope. Finally, recent 5-year age-adjusted incidence rates (2009–2013) are presented for each subtype by race and age. Results: Hormone receptor–positive and HER2-negative was the most common subtype (about 74%) of breast cancers. Adenocarcinoma made up about 69% of esophagus cases among men. Adenocarcinoma also is the most common lung subtype (43% in men and 52% in women). Ninety percent of thyroid subtypes were papillary. Distinct incidence and survival patterns emerged by these subtypes over time among men and women. Conclusions: Histologic or molecular subtype revealed different incidence and/or survival trends that are masked when cancer is considered as a single disease on the basis of anatomic site. Impact: Presenting incidence and survival trends by subtype, whenever possible, is critical to provide more detailed and meaningful data to patients, providers, and the public. Cancer Epidemiol Biomarkers Prev; 26(4); 632–41. ©2016 AACR.

Breast-Cancer-Specific Mortality in Patients Treated Based on the 21-Gene Assay: A SEER Population-Based Study

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N=38,568). Unadjusted 5-year BCSM were 0.4% (n=21,023; 95% confidence interval (CI), 0.3–0.6%), 1.4% (n=14,494; 95% CI, 1.1–1.7%), and 4.4% (n=3,051; 95% CI, 3.4–5.6%) for Recurrence Score <18, 18–30, and ⩾31 groups, respectively (P<0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P<0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N=4,691), 5-year BCSM (unadjusted) was 1.0% (n=2,694; 95% CI, 0.5–2.0%), 2.3% (n=1,669; 95% CI, 1.3–4.1%), and 14.3% (n=328; 95% CI, 8.4–23.8%) for Recurrence Score <18, 18–30, ⩾31 groups, respectively (P<0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials.

Effort Required in Eligibility Screening for Clinical Trials

PURPOSE Determining eligibility for a clinical trial (CT) typically requires a lengthy manual review of data for a single evaluation. The cost associated with eligibility screening is typically not compensated through contracts supporting CTs. METHODS We used a real-time tracking system that captures CT evaluations and provides information on evaluation outcomes and time spent on each eligibility screening by research staff. Using these data, we describe the effort and costs of eligibility screening overall and per enrolled patient for cancer CTs. The study sample included all completed eligibility assessment (evaluation) records for the 18-month study period. We used generalized multinomial modeling to predict evaluation outcomes and then used the resulting parameter coefficients to estimate the effort associated with each participant, adjusted for probability of being enrolled. From these data, we calculated cost associated with eligibility screening. RESULTS We found substantial variation in attributed cost by study type and phase. The cost of eligibility screening ranged by study phase from

Breast cancer specific mortality in patients with early-stage hormone receptor–positive invasive breast cancer and oncotype DX recurrence score results in the SEER database.

129.15 to

Automated determination of metastases in unstructured radiology reports for eligibility screening in oncology clinical trials.

336.48 per enrolled patient. The estimated annual cost of screening was more than

Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics: Recent Changes in Prostate Cancer Trends

90,000. CONCLUSION This study provides results based on prospectively captured effort to estimate the largely nonreimbursed costs of eligibility screening and suggests that screening can be a significant financial burden to an institution. Centers performing CTs may need to acknowledge the differences in screening costs for different study types when negotiating contracts with funding organizations. Information such as that captured here could support such negotiations to reduce the gap between reimbursed and nonreimbursed costs.

Adherence, Compliance, and Persistence with Osteoporosis Therapies

176 Background: NCIs SEER Program provides cancer incidence and survival statistics for ~28% of the US. New research models are needed to characterize the use and impact of genomic tests on patient outcomes. Genomic Health and SEER collaborated to electronically supplement SEER registries with Recurrence Score (RS) results, and have evaluated breast cancer specific mortality (BCSM) in early stage hormone receptor (HR)+ HER2- invasive breast cancer. METHODS Pts were eligible for pre-specified node negative (N-) disease analysis if HR+, HER2- (by RT-PCR), no prior malignancy, 40-85 years of age, and diagnosed between Jan 2004 (Oncotype DX available Jan 2004) and Dec 2011 (SEER survival analysis complete through 2012). BCSM was defined as previously described (Howlader et al, JNCI 2010). Additional analyses of BCSM were performed for pts with N+ disease. RESULTS Of 169,158 eligible N- pts, 38,568 (23%) had a RS, increasing from 2% in 2004 to 35% in 2011. Pts with RS had median age of 57yr, were 99.4% female, 84% white, 29% grade 1 & 54% grade 2, 25% < 1cm & 53% 1-2cm. Median FU was 39mo. 8,239 pts had > 5yrs follow-up. Among RS < 18 (N = 21,023), RS 18-30 (N = 14,494) and RS ≥ 31 (N = 3,051) pts, chemotherapy use was reported in 7%, 34%, & 69%, respectively, and 5yr N- BCSM was 0.4% (95% CI, 0.3-0.6), 1.4% (95% CI, 1.1-1.7) and 4.4% (95% CI,3.4-5.6), respectively. Multivariate showed that RS was significantly associated with BCSM after adjusting for age, grade, and tumor size (p < 0.001), and when stratified by treatment (p < 0.001). BCSM results in additional N- subgroups (e.g., socioeconomic), and in > 60,000 N+ pts will be presented. CONCLUSIONS 5yr survival outcomes are excellent in the over 21,000 N- pts with RS < 18 disease. RS ≥ 31 disease is associated with greater 5yr mortality despite addition of chemotherapy. The large sample size of this population-based observational study provides important information on prospective outcomes in subsets of pts that are often underrepresented in randomized clinical trials.

Author Correction: Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study

Enrolling adequate numbers of patients that meet protocol eligibility criteria in a timely manner is critical, yet clinical trial accrual continues to be problematic. One approach to meet these accrual challenges is to utilize technology to automatically screen patients for clinical trial eligibility. This manuscript reports on the evaluation of different automated approaches to determine the metastatic status from unstructured radiology reports using the Clinical Trials Eligibility Database Integrated System (CTED). The study sample included all patients (N = 5,523) with radiologic diagnostic studies (N = 10,492) completed in a two-week period. Eight search algorithms (queries) within CTED were developed and applied to radiology reports. The performance of each algorithm was compared to a reference standard which consisted of a physician’s review of the radiology reports. Sensitivity, specificity, positive, and negative predicted values were calculated for each algorithm. The number of patients identified by each algorithm varied from 187 to 330 and the number of true positive cases confirmed by physician review ranged from 171 to 199 across the algorithms. The best performing algorithm had sensitivity 94%, specificity 100%, positive predictive value 90%, negative predictive value 100%, and accuracy of 99%. Our evaluation process identified the optimal method for rapid identification of patients with metastatic disease through automated screening of unstructured radiology reports. The methods developed using the CTED system could be readily implemented at other institutions to enhance the efficiency of research staff in the clinical trials eligibility screening process.

SEER study of breast cancer specific mortality (BCSM) in patients with lobular tumors treated based on recurrence score results.

Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national‐level trends and their relations with prostate‐specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage‐specific, delay‐adjusted rates.

Breast cancer specific survival in patients with node-positive hormone receptor positive invasive breast cancer and Oncotype DX recurrence score results in the SEER database.

Medication adherence is particularly important in osteoporosis. While the terms adherence, compliance, and persistence may be confusing, the fact remains that many patients with osteoporosis do not take therapy as directed or for the prolonged period of time needed to treat this disorder. It is clear from studies of large populations that patients with osteoporosis must take about 75–80% of treatments in order to have fracture risk reduction. Unfortunately most patients have stopped therapy by 1–2 years after the original prescription. Strategies to improve persistence have only been modestly successful. Suggestions for increasing adherence are provided.