The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma.

BACKGROUND: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. METHODS: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013-2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. RESULTS: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)-better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). CONCLUSIONS: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.

31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration.

PURPOSE: The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. METHODS: Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score-matched to a cohort of non-31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling. RESULTS: Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients. CONCLUSION: In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.

Incidence of Benign Meningiomas in the United States: Current and Future Trends.

Background: Benign meningiomas are the most frequently reported central nervous system tumors in the United States, with increasing incidence in past decades. However, the future trajectory of this neoplasm remains unclear. Methods: We analyzed benign meningioma incidence of cases identified by any means (eg, radiographically with or without microscopic confirmation) in US Surveillance, Epidemiology, and End Results cancer registries among groups aged 35 to 84 years during 2004-2017 by sex and race and ethnicity using age-period-cohort models. We employed age-period-cohort forecasting models to glean insights regarding the etiology, distribution, and anticipated future (2018-2027) public health impact of this neoplasm. Results: In all groups, meningioma incidence overall increased through 2010, then stabilized. Temporal declines were statistically significant overall and in most groups. JoinPoint analysis of cohort rate-ratios identified substantial acceleration in White men born after 1963 (from 1.1% to 3.2% per birth year); cohort rate-ratios were stable or increasing in all groups and all birth cohorts. We forecast that meningioma incidence through 2027 will remain stable or decrease among groups aged 55-84 years but remain similar to current levels among groups aged 35-54 years. The case count of total meningioma burden in 2027 is expected to be approximately 30 470, similar to the expected case count of 27 830 in 2018. Conclusions: Between 2004 and 2017, overall incidence of benign meningioma increased and then stabilized or declined. For 2018-2027, our forecast is incidence will remain generally stable in younger age groups but decrease in older age groups. Nonetheless, the total future burden will remain similar to current levels because the population is aging.

Receipt of guideline-concordant care among young adult women with breast cancer.

BACKGROUND: Little is known about the real-world care of young adult (YA) females (aged 20-39 years) with breast cancer. This study describes factors associated with the receipt of guideline-concordant care (GCC) among YAs. METHODS: The authors identified 1259 YA women with invasive breast cancer diagnosed in 2013 in the National Cancer Institute's Patterns of Care study. Hospital records were re-abstracted, and treatment was verified. Using the National Comprehensive Cancer Network's 2013 breast cancer guidelines, the authors assessed the receipt of GCC by cancer subtype among a subset of YAs (n = 952). Associations between sociodemographic and clinical factors and GCC receipt were examined. RESULTS: Most YAs were 35 to 39 years old (51.2%) and partnered (56.4%); half had hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors. GCC was found for 81.7% of YAs. Relationships between sociodemographic and clinical factors and GCC receipt differed by subtype. Stage was the only significant predictor of GCC receipt for all subtypes (stage II vs III: odds ratio [OR] for HR+/HER2+, 0.20; 95% confidence interval [CI], 0.08-0.50; OR for HR-/HER2+, 0.13; 95% CI, 0.07-0.25; OR for HR-/HER2-, 3.86; 95% CI, 1.55-9.62; OR for HR+/HER2-, 2.81; 95% CI, 1.63-5.80). CONCLUSIONS: GCC is high among YAs with breast cancer. The effects of sociodemographic factors and treatment facility size on GCC differ by subtype. Consistent with recommendations, tumor biology, not age, is associated with GCC for all subtypes. Future studies should assess the effect of GCC on survival among YAs.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection.

Importance: Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. Objective: The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. Design, Setting, and Participants: The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Main Outcomes and Measures: Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. Results: The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. Conclusions and Relevance: In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Pathology Laboratory Policies and Procedures for Releasing Diagnostic Tissue for Cancer Research.

CONTEXT.­: The Surveillance, Epidemiology, and End Results (SEER) cancer registry program is currently evaluating the use of archival, diagnostic, formalin-fixed, paraffin-embedded (FFPE) tissue obtained through SEER cancer registries, functioning as honest brokers for deidentified tissue and associated data. To determine the feasibility of this potential program, laboratory policies for sharing tissue for research needed to be assessed. OBJECTIVE.­: To understand the willingness of pathology laboratories to share archival diagnostic tissue for cancer research and related policies. DESIGN.­: Seven SEER registries administered a 27-item questionnaire to pathology laboratories within their respective registry catchment areas. Only laboratories that processed diagnostic FFPE specimens and completed the questionnaire were included in the analysis. RESULTS.­: Of the 153 responding laboratories, 127 (83%) responded that they process FFPE specimens. Most (n = 88; 69%) were willing to share tissue specimens for research, which was not associated with the number of blocks processed per year by the laboratories. Most laboratories retained the specimens for at least 10 years. Institutional regulatory policies on sharing deidentified tissue varied considerably, ranging from requiring a full Institutional Review Board review to considering such use exempt from Institutional Review Board review, and 43% (55 of 127) of the laboratories did not know their terms for sharing tissue for research. CONCLUSIONS.­: This project indicated a general willingness of pathology laboratories to participate in research by sharing FFPE tissue. Given the variability of research policies across laboratories, it is critical for each SEER registry to work with laboratories in their catchment area to understand such policies and state legislation regulating tissue retention and guardianship.

Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection.

Importance There is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment. Objective The purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data. Design This was an observational descriptive cohort study. Participants The study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded. Main Outcomes/Measures Primary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities. Results We included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days. Conclusions Patients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up.

Development and Utility of the Observational Research in Oncology Toolbox: Cancer Medications Enquiry Database-Healthcare Common Procedure Coding System (HCPCS).

PURPOSE: Health-care claims are of increasing utility as a rich, real-world data resource for conducting treatment-related cancer research. However, multiple dynamic coding nomenclatures exist, leading to study variability. To promote increased standardization and reproducibility, the National Cancer Institute (NCI) developed the Cancer Medications Enquiry Database (CanMED)-Healthcare Common Procedure Coding System (HCPCS) within the Observational Research in Oncology Toolbox. METHODS: The CanMED-HCPCS includes codes for oncology medications that a) have a US Food and Drug Administration-approved indication for cancer treatment or treatment-related symptom management; b) are present in National Comprehensive Cancer Network guidelines; or c) carry an orphan drug designation for treatment or management of cancer. Included medications and their HCPCS codes were primarily identified based on Center for Medicare and Medicaid Services annual HCPCS Indices (2012-2018). To demonstrate the utility of the CanMED-HCPCS, use of systemic treatment for stage II-IV colorectal cancer patients included in the Surveillance, Epidemiology, and End Results-Medicare data (2007-2013) was assessed. RESULTS: The CanMED-HCPCS (v2018) includes 332 HCPCS codes for cancer-related medications: chemotherapy (156), immunotherapy (74), hormonal therapy (54), and ancillary therapy (48). Observed treatment trends within the NCI Surveillance, Epidemiology, and End Results-Medicare data were as expected; utilization of each treatment type increased with stage, and immunotherapy was largely confined to use among stage IV patients. CONCLUSION: The CanMED-HCPCS provides a comprehensive resource that can be used by the research community to facilitate systematic identification of medications within claims or electronic health data using the HCPCS nomenclature and greater reproducibility of cancer surveillance and health services research.

Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC): Assessment of Systemic Breast Cancer Treatment Patterns.

Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED-National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immunotherapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I-IIIA (20 701) and stage IIIB-IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promoting more standardized and efficient treatment-related cancer research.

Uptake of the 21-Gene Assay Among Women With Node-Positive, Hormone Receptor-Positive Breast Cancer.

BACKGROUND: This study assessed uptake of the Oncotype DX 21-gene assay over time and characterized which sociodemographic and clinical factors are associated with test uptake among women with lymph node-positive (LN+), hormone receptor-positive, HER2-negative breast cancer. METHODS: Invasive breast cancer cases diagnosed in 2010 through 2013 were included from a SEER database linked to 21-gene assay results performed at Genomic Health's Clinical Laboratory. Factors associated with 21-gene assay uptake were identified using a multivariable logistic regression model. RESULTS: Uptake of the 21-gene assay increased over time and differed by race, socioeconomic status (SES), and age. In the multivariable model, when clinical and SES variables were controlled for, racial differences in test uptake were no longer observed. Private insurance status was associated with higher odds of 21-gene assay uptake (Medicaid vs private insurance: adjusted odds ratio, 0.86; P=.02), and high area-level SES was associated with an increased odds of uptake (quintile 5 vs 1: adjusted odds ratio, 1.6; P<.001). Demographic factors such as age and marital status influenced test uptake, and use varied greatly by geographic region. Uptake of the 21-gene assay increased over time and preceded the assay's inclusion in the NCCN Guidelines for LN+ breast cancer. Differences in uptake by race, SES, and age have persisted over time. However, when clinical and SES variables were controlled for, racial differences in assay uptake were no longer observed. Socioeconomic variables, such as health insurance type and area-level SES, were associated with assay uptake. CONCLUSIONS: Future research should continue to document practice patterns related to the 21-gene assay. Given variation in testing associated with area-level SES, insurance coverage, and geographic region, interventions to understand and reduce differential uptake are needed to ensure equitable access to this genomic test.

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

[This corrects the article DOI: 10.1038/npjbcancer.2016.17.].

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

BACKGROUND: 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. METHODS: Joinpoint regression was used to examine changes in delay-adjusted prostate cancer incidence rates from population-based US cancer registries from 2000 to 2014 by age categories, race, and disease characteristics, including stage, PSA, Gleason score, and clinical extension. In addition, the analysis included trends for prostate cancer mortality between 1975 and 2015 by race and the estimation of PSA testing prevalence between 1987 and 2005. The annual percent change was calculated for periods defined by significant trend change points. RESULTS: For all age groups, overall prostate cancer incidence rates declined approximately 6.5% per year from 2007. However, the incidence of distant-stage disease increased from 2010 to 2014. The incidence of disease according to higher PSA levels or Gleason scores at diagnosis did not increase. After years of significant decline (from 1993 to 2013), the overall prostate cancer mortality trend stabilized from 2013 to 2015. CONCLUSIONS: After a decline in PSA test usage, there has been an increased burden of late-stage disease, and the decline in prostate cancer mortality has leveled off. Cancer 2018;124:2801-2814. © 2018 American Cancer Society.

Molecular Characterization and Mortality From Breast Cancer in Men.

Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor-positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer-specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

Quality Assessment of Tumor Size Data Collection for Pancreatic and Breast Cancer in SEER.

BACKGROUND AND OBJECTIVES: In 2017, the Surveillance, Epidemiology, and End Results (SEER) program piloted a reactive quality audit plan (r-QAP) to analyze Collaborative Stage (CS) tumor size in breast and pancreatic cancer. Preevaluation objectives were to establish procedures and analytic scope for SEER quality audits, cutoffs for data completeness/accuracy, and key decision checkpoints. METHODS: Tumor size data between 2004-2014 were selected from SEER registries for pancreatic and breast cancers, and initially assessed by site and registry for completeness. Further exploration was undertaken via cross tabulation in SEER with the American Joint Committee on Cancer (AJCC) 6th edition derived T data item to evaluate discrepancies between these closely related variables. RESULTS: For both cancer sites, completeness improved between 2004 and 2014, with the proportion of known tumor size values increasing from 60.6% to 79.2% in pancreatic cancer and from 94.0% to 95.9% in breast cancer. Tumor size plausibility categories were established wherein any tumor over 100 mm for pancreatic cancer or over 200 mm for breast cancer were considered highly unlikely. Only 2% of pancreas tumors and 0.1% of breast tumors were implausibly large per site-specific cutoffs. Less than 2% of all tumor size values were potentially discrepant in cross-tabulation with AJCC 6th edition derived T for each site. CONCLUSIONS: Most tumor size values appear to fall within acceptable ranges based on r-QAP activities, and implausibly large tumor size values are rare. Different natural histories and clinical presentation for pancreatic and breast cancer illustrate the need for site-specific cutoffs. Our results indicate that there are no major quality issues in the SEER research database for the CS tumor size data item in either pancreatic or breast cancer.

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

PURPOSE: The Oncotype DX® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. METHODS: In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. RESULTS: The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). CONCLUSIONS: Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

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.

Completeness of required site-specific factors for brain and CNS tumors in the Surveillance, Epidemiology and End Results (SEER) 18 database (2004-2012, varying).

Cancer registries are an important source of population-level information on brain tumor incidence and survival. Surveillance, Epidemiology, and End Results (SEER) registries currently collect data on specific required factors related to brain tumors as defined by the American Joint Commission on Cancer, including World Health Organization (WHO) grade, MGMT methylation and 1p/19q codeletion status. We assessed 'completeness', defined as having valid values over the time periods that they have been collected, overall, by year, histology, and registry. Data were obtained through a SEER custom data request for four factors related to brain tumors for the years 2004-2012 (3/4 factors were collected only from 2010 to 2012). SEER*Stat was used to generate frequencies of 'completeness' for each factor overall, and by year, histology and registry. The four factors varied in completeness, but increased over time. WHO grade has been collected the longest, and showed significant increases in completeness. Completeness of MGMT and 1p/19q codeletion was highest for glioma subtypes for which testing is recommended by clinical practice guidelines. Completeness of all factors varied by histology and cancer registry. Overall, several of the factors had high completeness, and all increased in completeness over time. With increasing focus on 'precision medicine' and the incorporation of molecular parameters into the 2016 WHO CNS tumor classification, it is critical that the data are complete, and factors collected at the population level are fully integrated into cancer reporting. It is critical that cancer registries continue to collect established and emerging prognostic and predictive factors.

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.

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

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.

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 $129.15 to $336.48 per enrolled patient. The estimated annual cost of screening was more than $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.