Results from a Real-World Multicenter Analysis of 482 Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Look at Racial Differences.

BACKGROUND: Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients. OBJECTIVE: To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity. PATIENTS AND METHODS: Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months. RESULTS: We identified 482 patients with CLL [405 White (153 1L, 252 R/R), 37 Black (17 1L, 20 R/R), 40 other/unidentified]. At baseline, 58.5% of all patients (68.8% of Black patients) had hypertension. At a median follow-up of 28.2 months, 31.1% of patients overall discontinued ibrutinib, 16.2% due to adverse events (12.2% 1L, 18.8% R/R). Overall, 46.0% of patients experienced ≥ 1 dose hold (40.2% 1L, 49.8% R/R), and 28.8% of patients experienced ≥ 1 dose reduction (24.9% 1L, 31.4% R/R). Among Black patients, ibrutinib was discontinued in 24.3% of patients (17.6% 1L, 30.0% R/R), 8.1% due to disease progression and 5.4% due to adverse events; 40.5% of patients experienced ≥ 1 dose hold (35.3% 1L, 45.0% R/R), and 32.4% of patients experienced ≥ 1 dose reduction (23.5% 1L, 40.0% R/R). CONCLUSIONS: Toxicity and disease progression were the most common reasons for ibrutinib discontinuations in the overall population and among Black patients, respectively. Encouraging research participation of underrepresented patient groups will help clinicians better understand treatment outcomes.

Ibrutinib, a Bruton tyrosine kinase inhibitor, is an approved oral targeted therapy for the treatment of chronic lymphocytic leukemia (CLL). Patients treated with ibrutinib can experience side effects (referred to as adverse events) and may need to reduce the drug dose (referred to as dose reductions) or stop treatment (referred to as discontinuations) for a variety of reasons. A previous study showed that patients who were treated with ibrutinib experienced frequent dose reductions and discontinuations. This study described dose reductions and discontinuations in a larger patient population treated with ibrutinib and also described outcomes in Black patients. Patients with CLL treated with ibrutinib were identified from five medical centers and were followed for a minimum of 6 months. Patients experienced frequent dose reductions and discontinuations in routine clinical practice. The most common cause of discontinuations was adverse events in the overall patient population and disease progression in the Black patient population. Black patients treated with ibrutinib had similar rates of dose reductions and discontinuations as the overall patient population. Rates of dose reductions and discontinuations for patients with CLL treated with ibrutinib were higher in this real-world study than in clinical trials.

Long-term oncologic outcomes of robotic and open pancreatectomy in a national cohort of pancreatic adenocarcinoma.

BACKGROUND: Robotic pancreatectomy is gaining momentum; however, limited data exist on the long-term survival of this approach for pancreatic ductal adenocarcinoma (PDAC). The objective of this study is to compare the long-term oncologic outcomes of robotic pancreaticoduodenectomy (RPD) and robotic distal pancreatectomy (RDP) to open surgery in patients with PDAC. STUDY DESIGN: Robotic and open pancreatectomy for stages I-III PDAC were obtained from the 2010 to 2016 National Cancer Database. RESULTS: We identified 17 831 pancreaticoduodenectomies and 2718 distal pancreatectomies of which 626 (4%) and 332 (12%) were robotic, respectively. There was no difference in median overall survival between RPD (22.0 months) and open pancreatoduodenectomy (21.8 months; logrank P = .755). The adjusted hazard ratio [HR] was 1.014 (95% confidence interval [CI]: 0.903-1.139). The median overall survival for RDP (35.3 months) was higher than open distal pancreatectomy (ODP) (24.9 months; logrank P = .001). The adjusted HR suggests a benefit to RDP compared to ODP (HR, 0.744; 95% CI: 0.632-0.868) CONCLUSION: In a national cohort of resected pancreatic adenocarcinoma, the robotic platform was associated with similar long-term survival for pancreaticoduodenectomy, but improved survival for distal pancreatectomy.

Deviations from Expected Treatment of Pancreatic Cancer in Octogenarians: Analysis of Patient and Surgeon Factors.

BACKGROUND: Morbidity and mortality of pancreatectomy has improved and chemotherapeutic options for pancreatic cancer (PC) are growing, yet there is reluctance to treat octogenarians. This study examined the reasons for failure to treat and analyzes outcomes in octogenarians with PC. METHODS: Retrospective chart review 2005-2013. Demographics, tumor characteristics, treatment, reason for lack of treatment, Charlson comorbidity index (CCI), and survival were analyzed. Expected treatment for early-stage patients (I/II) included surgery ± chemotherapy ± radiation. Expected treatment for advanced stage patients (III/IV) was chemotherapy. RESULTS: A total of 431 octogenarians were analyzed. Mean age was 84.0 ± 3.4, 59.6 % female, and 44.1 % received no treatment. Patients with operable tumors (I = 31 [7.2 %]/II = 214 [49.7 %]) had surgery 39.2 % of the time. Age was a predictor of not receiving surgery (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.70-0.86; p = 0.0001), whereas CCI was not. The most common reason for no surgery was contraindication despite similar CCI. Median overall survival for early-stage patients was better in the surgical group (15.8 vs. 5.5 months) than nonsurgical group (p < 0.0001). Advanced patients (III = 54 [12.5 %]/IV = 132 [30.6 %]) had similarly low treatment rates (n = 65 [34.9 %]). Survival for advanced disease was best for treated patients (6.9 vs. 1.8 months; p < 0.0001). CCI did not differ between those receiving chemotherapy and not, although age was significantly different (p < 0.0001). CONCLUSIONS: There is significant deviation from expected treatment for octogenarians with PC. While no correlation existed between CCI and treatment, age correlated with therapy for nearly all stages. Chronological age, not comorbidity, may drive recommendation for treatment in elderly patients.

Novel method for benchmarking recruitment of African American cancer patients to clinical therapeutic trials.

PURPOSE: The National Cancer Institute (NCI) has historically evaluated the participation of underserved minorities within University of Pittsburgh Cancer Institute (UPCI) clinical trials in relation to the proportion of African Americans in the general population of the UPCI primary service area of Allegheny County (12%). This standard seemed to be unrealistically high as a result of a younger age distribution of African Americans within the county. METHODS: The proportions of African Americans within the following four separate county populations were compared using data from 2000 to 2004: general population; invasive cancer patients; invasive cancer patients diagnosed or treated at UPCI-affiliated facilities; and patients enrolled onto UPCI's clinical therapeutic trials. RESULTS: Although the proportion of African Americans within the general population was approximately 13%, only 9.8% of patients diagnosed with invasive cancers were African American. Approximately 9.5% of all cancer patients diagnosed or treated at UPCI facilities were African American, which is comparable to the county-wide percentage of African American cancer patients. Recruitment rate of African Americans to oncology clinical trials from within the UPCI patient population was 7.6%. The NCI benchmark did not reflect the actual invasive cancer incidence rate in African American patients. By comparing the percentage of African Americans contributing to cancer incidence with the percentage of African American cancer patients treated at research-affiliated institutions, a more appropriate benchmark was derived. CONCLUSION: The method developed by UPCI is recommended as a useful mechanism for benchmarking recruitment of African American cancer patients to clinical therapeutic trials at other cancer centers.

National Mesothelioma Virtual Bank: a standard based biospecimen and clinical data resource to enhance translational research.

BACKGROUND: Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. METHODS: The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid (caBIG, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. RESULT: The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. CONCLUSION: The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers.

The development and deployment of Common Data Elements for tissue banks for translational research in cancer - an emerging standard based approach for the Mesothelioma Virtual Tissue Bank.

BACKGROUND: Recent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) - compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC). METHODS: The purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML). RESULTS: Common Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions. CONCLUSION: The CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained.

Synoptic tool for reporting of hematological and lymphoid neoplasms based on World Health Organization classification and College of American Pathologists checklist.

BACKGROUND: Synoptic reporting, either as part of the pathology report or replacing some free text component incorporates standardized data elements in the form of checklists for pathology reporting. This ensures the pathologists make note of these findings in their reports, thereby improving the quality and uniformity of information in the pathology reports. METHODS: The purpose of this project is to develop the entire set of elements in the synoptic templates or "worksheets" for hematologic and lymphoid neoplasms using the World Health Organization (WHO) Classification and the College of American Pathologists (CAP) Cancer Checklists. The CAP checklists' content was supplemented with the most updated classification scheme (WHO classification), specimen details, staging as well as information on various ancillary techniques such as cytochemical studies, immunophenotyping, cytogenetics including Fluorescent In-situ Hybridization (FISH) studies and genotyping. We have used a digital synoptic reporting system as part of an existing laboratory information system (LIS), CoPathPlus, from Cerner DHT, Inc. The synoptic elements are presented as discrete data points, so that a data element such as tumor type is assigned from the synoptic value dictionary under the value of tumor type, allowing the user to search for just those cases that have that value point populated. RESULTS: These synoptic worksheets are implemented for use in our LIS. The data is stored as discrete data elements appear as an accession summary within the final pathology report. In addition, the synoptic data can be exported to research databases for linking pathological details on banked tissues. CONCLUSION: Synoptic reporting provides a structured method for entering the diagnostic as well as prognostic information for a particular pathology specimen or sample, thereby reducing transcription services and reducing specimen turnaround time. Furthermore, it provides accurate and consistent diagnostic information dictated by pathologists as a basis for appropriate therapeutic modalities. Using synoptic reports, consistent data elements with minimized typographical and transcription errors can be generated and placed in the LIS relational database, enabling quicker access to desired information and improved communication for appropriate cancer management. The templates will also eventually serve as a conduit for capturing and storing data in the virtual biorepository for translational research. Such uniformity of data lends itself to subsequent ease of data viewing and extraction, as demonstrated by rapid production of standardized, high-quality data from the hemopoietic and lymphoid neoplasm specimens.