CA72-4 may have a potential role as an adjunct to conventional biomarkers in disease monitoring of pancreatic, ovarian and colorectal carcinomas.
263 Background: In management of metastatic and recurrent cancers, measuring response is a constant challenge. CA72-4 is a tumor marker (TM) that has been found elevated in a variety of human adenocarcinomas, with reported sensitivities of up 50% and overall specificity of over 95%. Using the DRG TM-CA72-4 assay, we quantified the abnormality rate of TM CA72-4 compared with current FDA-approved TM in various cancers. Methods: We conducted a prospective, single center study by enrolling 96 patients between March 2013 and August 2016 with various de novo or previously diagnosed locally advanced, unresectable and/or metastatic cancers known to express CA72-4. Quantification of CA72-4 was performed according to manufacturer’s instructions using the DRG TM-CA72-4 ELISA kit, which was developed by DRG International (Germany) utilizing the CC-49 monoclonal mouse antibody directed against an epitope on the CA72-4 antigen. Positivity was calculated as greater than A) 0.8 U/mL or B) 4.0 U/mL based on systematic review of prior studies. Results: The positivity rates based on different cut-off points (0.8 U/mL vs 4 U/mL) and their corresponding FDA approved tumor markers are shown in the Table. Conclusions: Positivity rates of CA72-4 varied based on different assay cut-off levels with the highest positivity noted in the pancreatic, ovarian and colorectal carcinomas indicating a potential role for disease monitoring. [Table: see text]
Introduction In 2016, it is predicted that there will be 8,220 new cases of Chronic Myelogenous Leukemia (CML) in the United States, with an estimated 1,070 deaths from this disease (Siegel RL, et al, CA Cancer J Clin 2016, 66:7-30). Due to the prognostic significance of cytogenetic and molecular response to frontline Tyrosine Kinase Inhibitors (TKIs), expert panels such as the European LeukemiaNet and the National Comprehensive Cancer Network (NCCN) recommend strict guidelines to ensure adequate surveillance of patient's response to TKI therapy (Deininger M, et al, Blood 2009, 114: Abstract 1126). In this retrospective observational study, we studied adherence to current NCCN Guidelines in the management of CML. Methods Using both electronic and archived paper medical records, we identified 26 patients diagnosed with CML from 3/3/2003 to 12/9/2015 who were followed in a single community practice. Information at initial diagnosis regarding age, CML phase, spleen size, and initial TKI therapy selected were obtained. Monitoring parameters including frequency of follow-ups, complete blood counts, chromosomal analysis, molecular testing, and repeat bone marrow aspirates were reviewed. Evaluation for response to treatment with time to Complete Hematologic Response (CHR), time to Major Molecular Response (MMR), and time to Complete Molecular Response (CMR) were noted. Evaluations of treatment adherence and testing for BCR-ABL kinase mutations when milestones were missed or molecular progressions detected were recorded. Reasons for change in therapy and choice of subsequent treatment were also documented. Results The median age at diagnosis of CML was 53, with a male to female ratio of 1.6:1. In this group of 26 patients, only a single patient was diagnosed in the accelerated phase, the rest were in the chronic phase of CML. In 92%, clinical spleen size was logged. However, a single standardized method was not utilized which precluded calculation of Sokal scores for risk classification. In 88.5%, bone marrow aspirates were obtained to establish disease phase and enable bone marrow cytogenetic studies. Out of 26 patients, 16 (61.5%) were initially treated with imatinib, 6 (23%) were treated with dasatinib and 4 (15.4%) were treated with nilotinib. Attempts to achieve superior cytogenetic and deeper molecular response with dasatinib or nilotinib, coupled with lower rates of progression to advanced phases, were most frequently cited as reasons for choosing non-imatinib front line therapy. Only 50% of patients had complete compliance with periodic molecular testing at 3, 6 and 12 months during the first 2 years of diagnosis. The frequency of molecular and cytogenetic response assessments were often less than recommended. Only 2 of the patients studied underwent repeat bone marrow testing, with one enrolled in a clinical trial requiring periodic repeat bone marrow biopsies. The median time to achieve CHR was 27 days, median time to reach MMR was 26.5 weeks and median time to CMR was 7.9 months. Attempts to confirm patient compliance with oral TKI therapy were documented in 22 of the patients (84.6%). Three patients underwent testing for BCR-ABL kinase mutations at the time of molecular progression, however, none tested positive for resistance mutations. No patient had a hematological or cytogenetic relapse, and two patients switched from nilotinib to imatinib because of poor compliance due to toxicity. Conclusion Clinical practice guidelines promote evidence-based recommendations to guide clinicians in the management of CML. TKI therapy has evolved to be the primary treatment for chronic phase CML, and monitoring response to TKI therapy by setting cytogenetic and molecular milestones has improved quality of care and success with treatment. Unfortunately, real-world application of strict time lines for testing may not be feasible in all circumstances. Patient non-compliance with testing and marrow exams, interval illness and hospitalization, and errors in laboratory testing have served as barriers to adherence to NCCN guidelines. Despite a 50% compliance rate, there were no major untoward events (i.e. transformation to accelerated or blast phase) appreciated in this subset of patients. Disclosures No relevant conflicts of interest to declare.
Introduction Heparin induced Thrombocytopenia (HIT) is a life threatening condition that can lead to significant morbidity and mortality in hospitalized patients. Thrombocytopenia in the setting of unfractionated heparin (UFH) exposure is a common occurrence in hospitalized patients and its diagnosis and management is associated with increased costs to the healthcare system. There is a 5-10X decreased risk of HIT with low molecular weight heparin (LMWH)(Martel N, et al. Blood. 2005;106 (8):2710-2715) while the incidence with fondaparinux is much more rare (Warkentin TE et al; Blood 2005, 106: 3791-3796). We conducted a single center, retrospective study to assess the correlation of HIT antibody (Ab) testing to '4T' score and the associated financial burden in our institution. Method Data collection Using retrospective chart review, we identified 78 hospitalized patients between 11/11/15 and 6/7/16 from various departments that underwent HIT Ab testing. The '4T' score was calculated as per Table 1. Data including admission service, type and duration of anticoagulation (AC) prior to and after HIT testing, HIT Ab and Serotonin release assay (SRA) positivity, type and duration of non-heparin AC and days of hospitalization were collected. HIT Ab was measured using platelet factor 4 complexed polyvinyl sulfonate (PVS) coated to the wells of a microtiter plate (Labcorp Burlington Test 150075). Patients with positive HIT (Optic Density>0.4) were reflexed to confirmatory SRA (LabCorp Burlington Test 150018). Cost Analysis Pharmacy acquisition cost of non-heparin AC (argatroban /fondaparinux) used as empiric treatment during the HIT testing period was recorded. Pharmacy acquisition cost was also used to predict cost of prophylactic LMWH and fondaparinux for the same duration. Daily dose of continuous UFH was standardized to a 70Kg patient/day. The cost of testing for HIT incurred by the facility was obtained. Statistical analysis was done using ANOVA on VassarStats.net online computation. Results Seventy eight patients had HIT Ab evaluated (Table 2). 26.9% (n=21) had a positive HIT Ab test, and 2.5% had a positive SRA test (n=2). Of the 78 cases analyzed, 48 were categorized as low risk, 24 as intermediate, and 8 as high using the 4T score. HIT Ab testing was positive in 23.9% of low risk, 29% of intermediate risk and 37.5% of high risk patients. SRA was positive in only 2.5% of cases; 1 in the low risk and 1 in the high risk group (n=2) (Table 2). Breakdown of AC during hospital stay showed that 52% (n=41) had UFH on admission, 70% (n=29) of which was for DVT prophylaxis; however 56% (n=23) of these did not have heparin exposure within 100 days of admission. 18% (n=14) were placed on SCDs, 6 of which had no known heparin exposure within 100 days of admission. 23% (n=18) were exposed to prophylactic LMWH, 2.5% (n=2) to therapeutic LMWH, 1.2% (n=1) to dabigatran, apixaban and fondaparinux each (Table 3). Cost Analysis The total average cost per patient with suspected HIT requiring laboratory evaluation was $431.15 (n=78). If a patient required full dose non-heparin anticoagulation, the average cost increased to $1274.98 per patient (n=20) and average duration of anticoagulation was 4 days. Average length of hospitalization for patients suspected of HIT was 18.7 days. Using enoxaparin as an anticoagulation during this period would have cost on average $68.46 per patient, while the use of fondaparinux would cost $179.01. Conclusion Evaluation for HIT and empiric management poses a significant burden of expense on our strained healthcare system. The 4T score has been useful in predicting HIT positivity in other studies (Lo GK, J Thromb Haemost. 2006 Apr;4(4):759-65). In this study conducted in a real-world clinical setting however, we found the 4T score was not universally applied to calculate pretest probability. A suspicion of HIT cost on average $431 per patient per hospitalization. A positive HIT Ab lead to an expense of $955. Confirmed HIT by SRA, resulted in an expense of $1557 per patient per hospitalization. Of note, length of stay and patient discomfort was not included in the analysis. Improved education regarding pretest probability using 4T score is warranted, however using LMWH or non-heparin alternative as DVT prophylaxis may be the most cost-effective approach in today's cost-conscious, high-value healthcare system. Disclosures No relevant conflicts of interest to declare.
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