Facilitating clinical research through automation: Combining optical character recognition with natural language processing.

BACKGROUND/AIMS: Performance status is crucial for most clinical research, as an eligibility criterion, a comorbidity covariate, or a trial endpoint. Yet information on performance status often is embedded as free text within a patient's electronic medical record, rather than coded directly, thereby making this concept extremely difficult to extract for research. Furthermore, performance status information frequently resides in outside reports, which are scanned into the electronic medical record along with thousands of clinic notes. The image format of scanned documents also is a major obstacle to the search and retrieval of information, as natural language processing cannot be applied to unstructured text within an image. We, therefore, utilized optical character recognition software to convert images to a searchable format, allowing the application of natural language processing to identify pertinent performance status data elements within scanned electronic medical records. METHODS: Our study cohort consisted of 189 subjects diagnosed with diffuse large B-cell lymphoma for whom performance status was a required data element for analysis of prognostic factors related to recurrence and survival. Manual abstraction of performance status was previously conducted by a clinical Subject Matter Expert, serving as the gold standard. Leveraging our data warehouse, we extracted relevant scanned electronic medical record documents and applied optical character recognition to these images using the ABBYY FineReader software. The Linguamatics i2e natural language processing software was then used to run queries for performance status against the corpus of electronic medical record documents. We evaluated our optical character recognition/natural language processing pipeline for accuracy and reduction in data extraction effort. RESULTS: We found that there was high accuracy and reduced time for extraction of performance status data by applying our optical character recognition/natural language processing pipeline. The transformed scanned documents from a random sample of patients yielded excellent precision, recall, and F score, with <1% incorrect results. Time savings from a second cohort showed that median time to review documents for patients with performance status data present was reduced by a third. The major time savings was in the review of those documents that in fact did not contain performance status information: median of 18 minutes versus 108 minutes for manual review, an 83% reduction in data abstraction effort. CONCLUSION: By applying this optical character recognition/natural language processing pipeline, we achieved significant operational improvement and reduced time for information retrieval to support clinical research. Our study demonstrated that optical character recognition software provides an effective mechanism to transform scanned electronic medical record images to allow the application of natural language processing, yielding highly accurate data abstraction. We conclude that our optical character recognition/natural language processing pipeline can greatly facilitate research data abstraction by providing a highly focused data review, eliminating unnecessary manual review of the entire chart, and thus freeing time for abstracting other data elements requiring more human interpretation.

Intestinal organoids: roadmap to the clinic.

Recent advances in intestinal organoid research, along with encouraging preclinical proof-of-concept studies, have revealed significant therapeutic potential for induced pluripotent stem cell (iPSC)-derived organoids in the healing and replacement of severely injured or diseased bowel (Finkbeiner et al. Biol Open 4: 1462-1472, 2015; Kitano et al. Nat Commun 8: 765, 2017; Cruz-Acuna et al. Nat Cell Biol 19: 1326-1335, 2017). To fully realize the tremendous promise of stem cell organoid-based therapies, careful planning aligned with significant resources and efforts must be devoted demonstrating their safety and efficacy to meet critical regulatory requirements. Early recognition of the inherent preclinical and clinical obstacles that occur with the novel use of pluripotent stem cell-derived products will accelerate their bench-to-bedside translation (Neofytou et al. J Clin Invest 125: 2551-2557, 2015; O'Brien et al. Stem Cell Res Ther 6: 146, 2015; Ouseph et al. Cytotherapy 17: 339-343, 2015). To overcome many of these hurdles, a close and effective collaboration is needed between experts from various disciplines, including basic and clinical research, product development and manufacturing, quality assurance and control, and regulatory affairs. Therefore, the purpose of this article is to outline the critical areas and challenges that must be addressed when transitioning laboratory-based discovery, through an investigational new drug (IND) application to first-in-human clinical trial, and to encourage investigators to consider the required regulatory steps from the earliest stage of the translational process. The ultimate goal is to provide readers with a draft roadmap that they could use while navigating this exciting cell therapy space.

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. METHODS: Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). RESULTS: Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. CONCLUSIONS: This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

Treating Second Breast Events After Breast-Conserving Surgery for Ductal Carcinoma in Situ.

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor-positive SBE contingent on AET use for the initial DCIS diagnosis.

Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer.

BACKGROUND: The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. METHODS: This study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. RESULTS: Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. CONCLUSIONS: Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. © 2016 American Cancer Society.

Comparison of referring and final pathology for patients with T-cell lymphoma in the National Comprehensive Cancer Network.

BACKGROUND: T-cell lymphomas (TCLs) are uncommon in the United States. The accurate diagnosis of TCL is challenging and requires morphologic interpretation, immunophenotyping, and molecular techniques. The authors compared pathologic diagnoses at referring centers with diagnoses from expert hematopathology review to determine concordance rates and to characterize the usefulness of second-opinion pathology review for TCL. METHODS: Patients in the National Comprehensive Cancer Network non-Hodgkin lymphoma database with peripheral TCL, not otherwise specified (PTCL-NOS), angioimmunoblastic TCL (AITL), and anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma (ALCL) were eligible if they had prior tissue specimens examined at a referring institution. Pathologic concordance was evaluated using available pathology and diagnostic testing reports and provider progress notes. The etiology of discordance and the potential impact on treatment were examined. RESULTS: Among 131 eligible patients, 57 (44%) had concordant results, totaling 64% of the 89 patients who were referred with a final diagnosis. Thirty-two patients (24%) had discordant results, representing 36% of those who were referred with a final diagnosis. The rates of discordance among patients with of PTCL-NOS, AITL, ALK-negative ALCL, and ALK-positive ALCL were 19%, 33%, 34%, and 6%, respectively. In 14 patients (44% of discordant results), pathologic reclassification could have resulted in a different therapeutic strategy. Forty-two patients (32%) were referred for classification with a provisional diagnosis. CONCLUSIONS: In a large cohort of patients with TCL who were referred to National Comprehensive Cancer Network centers, the likelihood of a concordant final diagnosis at a referring institution was low. As current and future therapies target TCL subsets, these data suggest that patients with suspected TCLs would benefit from evaluation by an expert hematopathologist.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. METHODS: Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. RESULTS: There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). CONCLUSIONS: TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Socioeconomic and clinical factors are key to uncovering disparity in accrual onto therapeutic trials for breast cancer.

To monitor and address disparity in accrual, patient participation in cancer clinical trials is routinely summarized by race/ethnicity. To investigate whether confounding obscures racial/ethnic disparity in participation, all women with breast cancer treated by medical oncologists at City of Hope Comprehensive Cancer Center from 2004 through 2009 were classified by birthplace and self-reported race/ethnicity, and followed for accrual onto therapeutic trials through 2010. Undetectable on univariate analysis, significantly reduced participation by subjects of African, Asian, Eastern European, Latin American, and Middle Eastern ancestries was revealed after accounting for age, socioeconomic factors, tumor and oncologist characteristics, and intrapractice clustering of patients.

Smoking status and survival in the national comprehensive cancer network non-small cell lung cancer cohort.

BACKGROUND: The objectives of this study were to evaluate survival among current smokers, former smokers, and never smokers who are diagnosed with non-small cell lung cancer (NSCLC). METHODS: The study included patients who participated in the National Comprehensive Cancer Network's NSCLC Database Project. Current, former, and never smokers were compared with respect to overall survival by fitting Cox regression models. RESULTS: Data from 4200 patients were examined, including 618 never smokers, 1483 current smokers, 380 former smokers who quit 1 to 12 months before diagnosis, and 1719 former smokers who quit >12 months before diagnosis. Among patients with stage I, II, and III disease, only never smokers had better survival than current smokers (hazard ratio, 0.47 [95% confidence interval, 0.26-0.85] vs 0.51 [95% confidence interval, 0.38-0.68], respectively). Among patients with stage IV disease, the impact of smoking depended on age: Among younger patients (aged ≤55 years), being a never smoker and a former smoker for ≥12 months increased survival. After age 85 years, smoking status did not have a significant impact on overall survival. CONCLUSIONS: Patients who were smoking at the time of diagnosis had worse survival compared with never smokers. Among younger patients with stage IV disease, current smokers also had worse survival compared with former smokers who quit >12 months before diagnosis. It is likely that tumor biology plays a major role in the differences observed; however, to improve survival, it is prudent to encourage all smokers to quit smoking if they are diagnosed with NSCLC.

A multicenter study to standardize reporting and analyses of fluorescence-activated cell-sorted murine intestinal epithelial cells.

Fluorescence-activated cell sorting (FACS) is an essential tool for studies requiring isolation of distinct intestinal epithelial cell populations. Inconsistent or lack of reporting of the critical parameters associated with FACS methodologies has complicated interpretation, comparison, and reproduction of important findings. To address this problem a comprehensive multicenter study was designed to develop guidelines that limit experimental and data reporting variability and provide a foundation for accurate comparison of data between studies. Common methodologies and data reporting protocols for tissue dissociation, cell yield, cell viability, FACS, and postsort purity were established. Seven centers tested the standardized methods by FACS-isolating a specific crypt-based epithelial population (EpCAM+/CD44+) from murine small intestine. Genetic biomarkers for stem/progenitor (Lgr5 and Atoh 1) and differentiated cell lineages (lysozyme, mucin2, chromogranin A, and sucrase isomaltase) were interrogated in target and control populations to assess intra- and intercenter variability. Wilcoxon's rank sum test on gene expression levels showed limited intracenter variability between biological replicates. Principal component analysis demonstrated significant intercenter reproducibility among four centers. Analysis of data collected by standardized cell isolation methods and data reporting requirements readily identified methodological problems, indicating that standard reporting parameters facilitate post hoc error identification. These results indicate that the complexity of FACS isolation of target intestinal epithelial populations can be highly reproducible between biological replicates and different institutions by adherence to common cell isolation methods and FACS gating strategies. This study can be considered a foundation for continued method development and a starting point for investigators that are developing cell isolation expertise to study physiology and pathophysiology of the intestinal epithelium.

Clinicopathologic and sociodemographic factors associated with late relapse triple negative breast cancer in a multivariable logistic model: A multi-institution cohort study.

BACKGROUND: Most metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features. METHODS: We included patients diagnosed with stage I-III TNBC between 1998 and 2012 at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p < 0.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts. RESULTS: A total 2210 TNBC patients with at least five years follow-up and no relapse before 5 years were included. In final multivariable model, lrTNBC was significantly associated with higher stage at diagnosis (adjusted Odds Ratio [aOR] for stage III vs I, 10.9; 95% Confidence Interval [CI], 7.5-15.9; p < 0.0001) and BMI (aOR for obese vs normal weight, 1.4; 95% CI, 1.0-1.8; p = 0.03). Final model performance was consistent between training (70%) and validation (30%) cohorts. CONCLUSIONS: A risk prediction model incorporating stage, BMI, and age at diagnosis offers potential utility for identification of patients at risk of development of lrTNBC and warrants further investigation.

Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study.

INTRODUCTION: In gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status. METHODS: We evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups. RESULTS: Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002). CONCLUSIONS: Presenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.

Radiation therapy at the end of life in patients with incurable nonsmall cell lung cancer.

BACKGROUND: Receipt of chemotherapy at the end of life (EOL) is considered an indicator of poor quality of care for medical oncology. The objective of this study was to characterize the use of radiotherapy (RT) in patients with nonsmall cell lung cancer (NSCLC) during the same period. METHODS: Treatment characteristics of patients with incurable NSCLC who received RT at the EOL, defined as within 14 days of death, were analyzed from the National Comprehensive Cancer Network NSCLC Outcomes Database. RESULTS: Among 1098 patients who died, 10% had received EOL RT. Patients who did and did not receive EOL RT were similar in terms of sex, race, comorbid disease, and Eastern Cooperative Oncology Group performance status. On multivariable logistic regression analysis, independent predictors of receiving EOL RT included stage IV disease (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.09-3.83) or multiorgan involvement (OR, 1.75; 95% CI, 1.08-2.84) at diagnosis, age <65 years at diagnosis (OR, 1.85; 95% CI, 1.21-2.83), and treating institution (OR, 1.24-5.94; P = .02). Nearly 50% of EOL RT recipients did not complete it, most commonly because of death or patient preference. CONCLUSIONS: In general, EOL RT was received infrequently, was delivered more commonly to younger patients with more advanced disease, and often was not completed as planned. There also was considerable variation in its use among National Comprehensive Cancer Network institutions. Next steps include expanding this research to other cancers and settings and investigating the clinical benefit of such treatment.

Pathologic characteristics of second breast cancers after breast conservation for ductal carcinoma in situ.

BACKGROUND: The number of women diagnosed with ductal carcinoma in situ (DCIS) is increasing. Although many eventually develop a second breast cancer (SBC), little is known about the characteristics of SBCs. The authors described the characteristics of SBC and examined associations between the pathologic features of SBC and index DCIS cases. METHODS: Women were identified in the National Comprehensive Cancer Network Outcomes Database who were diagnosed with DCIS from 1997 to 2008 and underwent lumpectomy and who subsequently developed SBC (including DCIS or invasive disease that occurred in the ipsilateral or contralateral breast). The Fisher exact test and the Spearman test were used to examine associations between the pathologic characteristics of SBC and index DCIS cases. RESULTS: Among 2636 women who underwent lumpectomy for DCIS, 150 (5.7%) experienced an SBC after a median of 55.5 months of follow-up. Of these 150 women, 105 (70%) received adjuvant radiotherapy, and 50 (33.3%) received tamoxifen for their index DCIS. SBCs were ipsilateral in 54.7% of women and invasive in 50.7% of women. Among the index DCIS cases, 60.6% were estrogen receptor (ER)-positive, and 54% were high grade, whereas 77.5% of SBCs were ER-positive, and 48.2% were high grade. Tumor grade (P = .003) and ER status (P = .02) were associated significantly between index DCIS and SBC, whereas tumor size was not (P = .87). CONCLUSIONS: After breast conservation for DCIS, SBC in either breast exhibited pathologic characteristics similar to the index DCIS, suggesting that women with DCIS may be at risk for developing subsequent breast cancers of a similar phenotype.

Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network.

BACKGROUND: The objective of this study was to describe clinicopathologic features, patterns of recurrence, and survival according to breast cancer subtype with a focus on triple-negative tumors. METHODS: In total, 15,204 women were evaluated who presented to National Comprehensive Cancer Network centers with stage I through III breast cancer between January 2000 and December 2006. Tumors were classified as positive for estrogen receptor (ER) and/or progesterone receptor (PR) (hormone receptor [HR]-positive) and negative for human epidermal growth factor receptor 2 (HER2); positive for HER2 and any ER or PR status (HER2-positive); or negative for ER, PR, and HER2 (triple-negative). RESULTS: Subtype distribution was triple-negative in 17% of women (n = 2569), HER2-positive in 17% of women (n = 2602), and HR-positive/HER2-negative in 66% of women (n = 10,033). The triple-negative subtype was more frequent in African Americans compared with Caucasians (adjusted odds ratio, 1.98; P < .0001). Premenopausal women, but not postmenopausal women, with high body mass index had an increased likelihood of having the triple-negative subtype (P = .02). Women with triple-negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs 48%; P < .0001) and were more likely to present with higher tumor classification, but they were less likely to have lymph node involvement. Relative to HR-positive/HER2-negative tumors, triple-negative tumors were associated with a greater risk of brain or lung metastases; and women with triple-negative tumors had worse breast cancer-specific and overall survival, even after adjusting for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy (overall survival: adjusted hazard ratio, 2.72; 95% confidence interval, 2.39-3.10; P < .0001). The difference in the risk of death by subtype was most dramatic within the first 2 years after diagnosis (overall survival for 0-2 years: OR, 6.10; 95% confidence interval, 4.81-7.74). CONCLUSIONS: Triple-negative tumors were associated with unique risk factors and worse outcomes compared with HR-positive/HER2-negative tumors.

The effect of age on delay in diagnosis and stage of breast cancer.

BACKGROUND: Young women with breast cancer are more likely to present with more advanced disease and are more likely to die as a result of breast cancer than their older counterparts. We sought to examine the relationship among young age (≤40 years), the likelihood of a delay in diagnosis, and stage. METHODS: We examined data from women with newly diagnosed stage I-IV breast cancer presenting to one of eight National Comprehensive Cancer Network centers in January 2000 to December 2007. Delay in diagnosis was defined as time from initial sign or symptom to breast cancer diagnosis >60 days. RESULTS: Among 21,818 women with breast cancer eligible for analysis, 2,445 were aged ≤40 years at diagnosis. Young women were not more likely to have a delay in diagnosis >60 days (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.98-1.19) after adjustment for type of initial sign or symptom. Young women were only modestly more likely to present with higher stage disease after a similar adjustment (OR, 1.18; 95% CI, 1.07-1.31). Women presenting with symptomatic disease, more common in younger women, were more likely to have a delay in diagnosis (OR, 3.31; 95% CI, 3.08-3.56) and higher stage (OR, 4.31; 95% CI 4.05-4.58). CONCLUSION: Young age is not an independent predictor of delay in diagnosis of breast cancer and only modestly is associated with higher stage disease. Presenting with symptoms of breast cancer predicts delay and higher stage at diagnosis.

Time to diagnosis and breast cancer stage by race/ethnicity.

We examined differences in time to diagnosis by race/ethnicity, the relationship between time to diagnosis and stage, and the extent to which it explains differences in stage at diagnosis across racial/ethnic groups. Our analytic sample includes 21,427 non-Hispanic White (White), Hispanic, non-Hispanic Black (Black) and non-Hispanic Asian/Pacific Islander (Asian) women diagnosed with stage I to IV breast cancer between January 1, 2000 and December 31, 2007 at one of eight National Comprehensive Cancer Network centers. We measured time from initial abnormal mammogram or symptom to breast cancer diagnosis. Stage was classified using AJCC criteria. Initial sign of breast cancer modified the association between race/ethnicity and time to diagnosis. Among symptomatic women, median time to diagnosis ranged from 36 days among Whites to 53.6 for Blacks. Among women with abnormal mammograms, median time to diagnosis ranged from 21 days among Whites to 29 for Blacks. Blacks had the highest proportion (26 %) of Stage III or IV tumors. After accounting for time to diagnosis, the observed increased risk of stage III/IV breast cancer was reduced from 40 to 28 % among Hispanics and from 113 to 100 % among Blacks, but estimates remained statistically significant. We were unable to fully account for the higher proportion of late-stage tumors among Blacks. Blacks and Hispanics experienced longer time to diagnosis than Whites, and Blacks were more likely to be diagnosed with late-stage tumors. Longer time to diagnosis did not fully explain differences in stage between racial/ethnicity groups.

First-line systemic therapy practice patterns and concordance with NCCN guidelines for patients diagnosed with metastatic NSCLC treated at NCCN institutions.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) allow many systemic therapy options for patients with metastatic non-small cell lung cancer (NSCLC). This analysis uses the NCCN NSCLC Outcomes Database to report on first-line therapy practice patterns and concordance with NCCN Guidelines. The analysis was limited to patients diagnosed with metastatic NSCLC between September 2006 and November 2009 at 1 of 8 participating NCCN Member Institutions. Patient characteristics, regimens used, and guidelines concordance were analyzed. Institutional variation and changes in practice over time were also measured. A total of 1717 patients were included in the analysis. Of these, 1375 (80%) were treated with systemic therapy, most often in the form of a carboplatin-based doublet (51%) or carboplatin-based doublet with targeted therapy (17%). Overall, 76% of patients received care that was concordant with NCCN Guidelines. Among patients with good performance status (n = 167), the most common reasons for not receiving first-line therapy were that therapy was not recommended (39%) or death occurred before treatment (33%). The most common reason for receiving nonconcordant drug therapy was the administration of pemetrexed or erlotinib before its incorporation into the NCCN Guidelines for first-line therapy (53%). Most patients in this cohort received care that was concordant with NCCN Guidelines. The NSCLC Outcomes Database is a valuable resource for evaluating practice patterns and concordance with NCCN Guidelines among patients with NSCLC.

Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.