Hematologic and Hospitalization Outcomes in Patients with Chemotherapy-Induced Anemia (CIA) Treated with Erythropoiesis-Stimulating Agents (ESAs) in the Pre- Vs Post-National Coverage Determination (NCD) Time Periods.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2482-2482
Author(s):  
Elizabeth Apgar ◽  
Tanya M. Burton ◽  
Kay Larholt ◽  
Chris L. Pashos ◽  
Lorie Ellis ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Cancer Patients ◽  
Research Funding ◽  
Study Patient ◽  
Patient Specific ◽  
Tumor Type ◽  
Ortho Biotech ◽  
Blood Utilization ◽  
Time Periods ◽  
Hospital Days

Abstract Abstract 2482 Poster Board II-459 Background: National coverage limitations for ESA treatment in cancer patients with CIA were established by the Centers for Medicare & Medicaid Services in July 2007. Clinical outcomes based on ESA dosing described in the NCD have not been reported in prospective observational or clinical trial data. To understand hematologic and hospitalization outcomes in CIA patients treated in Pre- and Post-NCD time periods, an analysis of data from the D.O.S.E. (Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies) registry, an ongoing prospective observational study, was conducted. Methods: ESA-treated cancer patients with CIA were selected if they initiated ESA treatment 12/01/2005-04/01/2007 (Pre-NCD) or 10/01/2007-02/01/2009 (Post-NCD), had ≥ 2 ESA administrations, and had both a baseline and ≥ 1 transfusion-independent post-ESA initiation hemoglobin (Hb) assessment. Assessed outcomes included proportion of patients receiving blood transfusion, number of units/study patient, Hb levels (at baseline and at weeks 4, 8, 12, 16) and hospitalization rates (admissions, number of hospital days) adjusted for ESA therapeutic duration (defined as time (days) from first to last ESA administration + patient-specific ESA treatment interval). Results: This analysis included 836 patients (Pre-NCD 585; Post-NCD 251) from 54 sites. Patients in the Pre-NCD and Post-NCD cohorts were similar in gender distribution and weight. The Post-NCD cohort was significantly older (64.7 yrs vs. 61.9 yrs; p<0.01). The groups also differed significantly in overall tumor type distribution (p<0.0001). The Post-NCD group had a lower proportion of patients with breast cancer and higher proportion of patients with lung cancer and gynecologic malignancies. ESA treatment duration was significantly shorter in the Post-NCD group (mean days ± SD: Post-NCD 55.5 ± 32.7, Pre-NCD 65.8 ± 33.8, p<0.0001). The proportion of patients receiving blood transfusion was significantly greater in the Post-NCD group (Post-NCD 26.7%, Pre-NCD 15.6%, p=0.0002) as was blood utilization (Units/study patient: Post-NCD 0.9, Pre-NCD 0.4, p=0.0001). As shown in the table, Hb levels were significantly lower at all time points in the Post-NCD group. The rate of hospital admissions was significantly greater in the Post-NCD group [Admissions/100-patient ESA therapeutic days (95% CI): Post-NCD 0.42 (0.34, 0.53), Pre-NCD 0.28 (0.24, 0.33)] as was the number of hospital days [Hospital days/100-patient ESA therapeutic days (95% CI): Post-NCD 2.3 (2.1, 2.5), Pre-NCD 1.3 (1.2, 1.4)]. Conclusions: Significantly greater blood utilization and lower Hb levels were observed in ESA-treated CIA patients in the Post-NCD period compared to the Pre-NCD period. Rates of hospitalizations and hospital length of stay were also significantly greater in the Post-NCD group. Study of comparative hematologic and resource utilization outcomes before and after the NCD is warranted in additional clinical centers. Disclosures: Apgar: Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Burton:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Larholt:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Pashos:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Ellis:Centocor Ortho Biotech Services, LLC: Employment. Senbetta:Centocor Ortho Biotech Services, LLC: Employment. McKenzie:Centocor Ortho Biotech Services, LLC: Employment.

Blood and Resource Utilization in Cancer Patients with Chemotherapy-Induced Anemia (CIA) in the Pre- and Post-National Coverage Determination (NCD) Timeframes: Results From An Electronic Medical Record Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2472-2472
Author(s):  
Tanya Burton ◽  
Luke Boulanger ◽  
Kay Larholt ◽  
Chris L. Pashos ◽  
R. Scott McKenzie ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Resource Utilization ◽  
Research Funding ◽  
Treatment Patterns ◽  
Lower Proportion ◽  
Administrative Claims ◽  
Tumor Type ◽  
Ortho Biotech ◽  
Blood Utilization ◽  
The Impact

Abstract Abstract 2472 Poster Board II-449 Background: The Centers for Medicare & Medicaid Services issued erythropoiesis-stimulating agent (ESA) coverage limitations for cancer patients with CIA in July 2007 restricting ESA administration to those with hemoglobin (Hb) less than 10 g/dL and contingent on specific achieved Hb levels. Data assessing CIA patients regardless of ESA treatment pre- and post-NCD are scarce. This study evaluated Pre- and Post-NCD data in patients with CIA from a single oncology clinic in the northeastern United States to understand anemia treatment patterns, hematologic outcomes, and resource utilization. The oncology clinic, which is a part of a multi-specialty capitated integrated medical group, implemented the ESA NCD policy in September 2007. Methods: Medical, laboratory, and administrative claims data between 1/2005 and 4/2008 were retrospectively analyzed. Assessed patients had a diagnosis of malignant cancer (ICD-9-CM 140.XX-208.xx), received chemotherapy, and were anemic (Hb < 11 g/dL) during the chemotherapy treatment period. Patients diagnosed with myelodysplasia, acute leukemia, or chronic kidney disease who received dialysis, and those enrolled in ESA clinical trials were excluded. Data were categorized and analyzed in two time frames (Pre-NCD: 07/06-05/07, Post-NCD: 09/07-04/08). Baseline characteristics, ESA treatment patterns, hematologic outcomes (transfusion and available Hb levels), and resource utilization were assessed during the 20 week observation period following the index date of Hb < 11 g/dL. Results: 359 patients were identified (241 Pre-NCD; 118 Post-NCD). Baseline age, gender, race, weight, height, and distribution of tumor type were similar between groups. In the Post-NCD group, a significantly higher proportion of patients had comorbidities of congestive heart failure, coronary artery disease, and chronic obstructive pulmonary disease. The Post-NCD group had a significantly lower proportion of patients treated with ESAs (Pre-NCD 64%, Post-NCD 47%, p=0.0023). Among patients on ESA therapy (≥ 2 ESA injections), there was a trend toward shorter duration of ESA treatment in the Post-NCD arm [mean (SD): Pre-NCD 57.9 days (39.1), Post-NCD 47.3 days (38.1), p=0.08]. As noted in the table below, transfusion-independent Hb levels were lower in the Post-NCD group at baseline, Week 8, and Week 12. The proportion of patients transfused and blood utilization were similar in the Pre- and Post-NCD groups. The average number of oncology/hematology visits per patient was lower in the Post-NCD group [mean (SD): Pre-NCD 8.8 (5.9), Post-NCD 7.4 (6.5), p=0.01], however, a significantly higher proportion of patients in the Post-NCD period had a hospital admission (Pre-NCD 37.8%, Post-NCD 50.8%, p=0.02) or an emergency room (ER) visit (Pre-NCD 44.8%, Post-NCD 55.9%, p=0.048). Conclusion: Data from this single center observational study reported a lower proportion of patients initiated on ESAs, similar blood utilization, and an increased proportion of patients with hospitalization and ER visits in CIA patients with Hb < 11 g/dL in the Post-NCD as compared to the Pre-NCD time period. Further study assessing the impact of CIA NCD policy on healthcare resource utilization in multiple clinical centers is warranted. Disclosures: Burton: Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Boulanger:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Larholt:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Pashos:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. McKenzie:Centocor Ortho Biotech Services, LLC: Employment. Senbetta:Centocor Ortho Biotech Services, LLC: Employment. Lopez:Centocor Ortho Biotech Services, LLC: Employment. Sundaresan:Centocor Ortho Biotech Services, LLC: Consultancy. Preusse:Centocor Ortho Biotech Services, LLC: Consultancy. Seidler:Centocor Ortho Biotech Services, LLC: Consultancy.

Pre- and Post-National Coverage Determination (NCD) Hematologic Outcomes and Blood Utilization in Cancer Patients with Chemotherapy-Induced Anemia (CIA): Results From a Multicenter Chart Review.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2491-2491
Author(s):  
David H. Henry ◽  
Corey J. Langer ◽  
R. Scott McKenzie ◽  
Catherine Tak Piech ◽  
Mekré Senbetta ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Research Funding ◽  
Chart Review ◽  
Negative Binomial ◽  
Performance Status ◽  
Cancer Type ◽  
Tumor Type ◽  
Ecog Performance Status ◽  
Ortho Biotech ◽  
Blood Utilization

Abstract Abstract 2491 Poster Board II-468 Introduction: In July 2007, the Centers for Medicare & Medicaid Services issued erythropoiesis-stimulating agent (ESA) coverage limitations for cancer patients with CIA through an NCD, which limits ESA utilization in patients with CIA to hemoglobin (Hb) levels of less than 10 g/dL at ESA initiation and after the initial 4 weeks of treatment. The primary objective of this study was to compare transfusion rates in patients with breast, colorectal or lung cancer who developed CIA before and after the NCD, regardless of treatment with ESAs. Patients and Methods: Chart data from adult cancer patients with Medicare as their primary payer and treated at community oncology clinics were abstracted for 12 weeks following the beginning of a CIA episode, provided that the entire episode occurred either before or after the change in policy. CIA was defined as Hb level < 11 g/dL, while receiving chemotherapy or within 8 weeks (60 days) of the last dose of chemotherapy. Logistic regression was used to calculate the odds of transfusion following the Hb < 11 g/dL index date. A negative binomial model was used to assess the change in units of blood transfused per patient. Multivariate models controlled for differences in age, gender, cancer type, line of therapy, ECOG performance status, history of antecedent transfusion and exposure to platinum, anthracyclines, antimetabolites and plant alkaloids. Results: 1794 patients were identified (800 Pre-NCD and 994 Post-NCD) from 49 sites. Patient groups were similar with respect to age, gender, race, weight, tumor type, line of treatment and recent exposure to radiation or surgery. As shown in the table below, there were significant differences in the chemotherapy class exposure in the Post- vs. Pre-NCD period. In addition, Hb levels were lower in the Post-NCD period, with a decrease in the proportion of ESA-treated patients and ESA treatment duration. The odds of receiving a transfusion were significantly higher Post-NCD (OR 1.41, 95% CI; 1.05 - 1.89; p=0.02) with an overall increase in adjusted units transfused of 53% (OR 1.53, 95% CI; 1.15 - 2.04; p=0.003). The table below summarizes patient characteristics and unadjusted Hb and transfusion outcomes. Conclusion: This large multicenter chart review reported decreased frequency and duration of ESA administration in CIA patients with Hb < 11 g/dL in the Post-NCD period compared to the Pre-NCD period. This was accompanied by a modest but statistically significant increase in blood utilization and decrease in Hb values. Further studies are warranted to assess other outcomes. Disclosures: McKenzie: Centocor Ortho Biotech Services, LLC: Employment. Piech:Centocor Ortho Biotech Services, LLC: Employment. Senbetta:Centocor Ortho Biotech Services, LLC: Employment. Schulman:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding. Stepanski:Centocor Ortho Biotech Services, LLC: Consultancy, Research Funding.

Pre- vs. Post-National Coverage Determination (NCD) Blood Utilization and Hemoglobin Values among Medicare Patients Treated with Erythropoietic-Stimulating Agents (ESAs) for Chemotherapy-Induced Anemia (CIA)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1301-1301 ◽  
Author(s):  
Tanya Burton ◽  
Kay Larholt ◽  
Elizabeth Apgar ◽  
Chris Pashos ◽  
Brahim Bookhart ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Clinical Trial Data ◽  
Study Patient ◽  
P Value ◽  
Tumor Type ◽  
Time Period ◽  
Hospital Systems ◽  
Utilization Patterns ◽  
Blood Utilization ◽  
The Impact

Abstract Background: In July 2007, the Centers for Medicare and Medicaid Services issued ESA coverage limitations for cancer patients with CIA through a national coverage determination (NCD). Clinical outcomes based on ESA dosing described in the NCD have not been reported in prospective observational or clinical trial data. To understand hematologic outcomes in the Medicare population treated in pre- and post-NCD time period, an analysis of hematologic outcomes from the DOSE (Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies) registry, an ongoing prospective observational study, was conducted. Methods: ESA-treated cancer patients with CIA were selected based on Medicare primary coverage, available baseline hemoglobin (Hb) value, and receipt of at least two ESA administrations. Data were categorized into two timeframes based on date of initial ESA administration: pre-NCD (4/06-4/07) and post-NCD (10/07-5/08). Baseline demographics, Hb values during ESA treatment, and blood utilization patterns were analyzed. Results: 288 patients were identified (Pre-NCD – 230; Post-NCD – 58) from 41 sites. Patient groups were similar with respect to age, gender, weight, and tumor type. ESA treatment duration was significantly greater in the pre-NCD group (70 days vs. 54 days, p = 0.0011). As shown in the table, differences with regard to blood utilization and Hb values were observed between the Pre-NCD and Post-NCD populations. A significantly greater proportion of patients required a blood transfusion and the number of units administered per study patient was significantly higher in the Post-NCD group. Hb levels were significantly lower at all time points of observation in the Post-NCD group. Pre-NCD Post-NCD p-value Transfusion Outcomes Proportion of Patients Transfused 18.3% 32.8% p = 0.0157 Mean No. of Units per Study Patient 0.5 1.1 p = 0.0089 Hematologic Outcomes: Mean Hb (SD) Baseline 10.6 (0.8) 9.6 (0.5) &lt; 0.0001 Week 4 11.1 (1.3) 9.9 (1.1) &lt; 0.0001 Week 8 11.2 (1.3) 10.4 (1.3) 0.013 Week 12 11.1 (1.3) 9.8 (1.2) 0.0002 Week 16 11.0 (1.1) 9.7 (0.2) 0.018 Conclusion: Greater blood utilization and lower Hb values were observed in Medicare CIA patients treated with ESAs during the Post-NCD time period compared to the Pre- NCD time period. The impact of the NCD on patient outcomes is important to providers and hospital systems and warrants further research.

RAPID siRNA Screen for Identification of Therapeutic Gene Targets in Patients with Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3978-3978
Author(s):  
Jeffrey W Tyner ◽  
Marc Loriaux ◽  
Stephanie G Willis ◽  
Bill H Chang ◽  
Vincent T Bicocca ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Small Molecule ◽  
Therapeutic Intervention ◽  
Tyrosine Kinases ◽  
Research Funding ◽  
Hematologic Malignancies ◽  
Patient Specific ◽  
Functional Screening ◽  
Primary Cells ◽  
Gene Target

Abstract Abstract 3978 Poster Board III-914 A large percentage of cancer cases present without knowledge of the causative genetic events. Tyrosine kinases are frequently implicated in the pathogenesis of cancer, but identification of specific kinases as cancer targets has been a slow process. Inhibition of cancer-causing tyrosine kinases offers a promising avenue of therapy, however this strategy of targeted therapy will require a detailed understanding of the oncogenic targets in each cancer patient. Here, we present an RNAi-assisted protein target identification (RAPID) assay by which cells from leukemia patients are functionally screened with siRNA to determine tyrosine kinases that constitute amenable targets for therapeutic intervention. Combination of the RAPID screen with gene-specific therapeutic approaches promises to yield a powerful synthesis of methodologies by which cancer patients can be specifically treated on the basis of functionally diagnosed gene targets. Methods To detect gene targets necessary for viability of malignant cells, we screened primary cells from 150 patients with hematologic malignancies by electroporating siRNAs individually targeting each member of the tyrosine kinase gene family. Four days later, we measured cell viability and tabulated sensitivity to silencing of specific genes. Samples were also screened for sensitivity to small-molecule kinase inhibitors. The mechanism of oncogenesis was investigated for each positive result. Results In total, we have identified 40 patient-specific gene targets in primary leukemia samples. We demonstrate that siRNA screening can identify known oncogenic lesions such as K-RasG13D and JAK2V617F in primary cells from leukemia patients. The RAPID screen has also directed us towards a novel insertional mutation in the thrombopoietin receptor, MPL (1886InsGG). Additionally, we have detected FLT3 sensitivity in patients with FLT3-ITD and loss of heterozygosity, although not in FLT3-ITD heterozygous patients. Agreement between siRNA-sensitive gene targets and small-molecule inhibitor sensitivity profiles has been high. The mechanism of oncogenesis and its relation to the gene target has been established in select other samples with abnormalities including gene overexpression and patient-specific mis-splicing events. Conclusions We demonstrate that RNAi functional screening can determine sensitivity to individual genes in cells obtained directly from cancer patients. Thus, this technique offers the potential to match targeted therapies with patients in a personalized manner. Application of these technologies will enable efficient discovery of the genetic etiology of cancer as well as a means for gene-specific therapeutic intervention. Disclosures: Deininger: Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Calistoga: Research Funding; Genzyme: Research Funding. Druker:OHSU patent #843 - Mutate ABL Kinase Domains: Patents & Royalties; MolecularMD: Equity Ownership; Roche: Consultancy; Cylene Pharmaceuticals: Consultancy; Calistoga Pharmaceuticals: Consultancy; Avalon Pharmaceuticals: Consultancy; Ambit Biosciences: Consultancy; Millipore via Dana-Farber Cancer Institute: Patents & Royalties; Novartis, ARIAD, Bristol-Myers Squibb: Research Funding.

Blood Transfusion and Erythropoiesis Stimulating Agents (ESAs) Use In Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3357-3357
Author(s):  
Nicolas Batty ◽  
Elham Ghonimi ◽  
Lei Feng ◽  
Anas Younes ◽  
Rodriguez Alma ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Continuous Variables ◽  
Chop Chemotherapy ◽  
Chi Square ◽  
Period 2 ◽  
Time Period ◽  
Before And After ◽  
Time Periods

Abstract Abstract 3357 Background: The national coverage decision regarding reimbursement for usage of ESAs for chemotherapy-induced anemia (CIA) from the Centers for Medicare & Medicaid Services (CMS) underwent changes in early 2007. This study examines the rates of packed red blood cell (PRBC) transfusions and usage of ESAs before and after the changes of these health care regulations in patients with DLBCL treated with standard Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) chemotherapy. Methods: We retrospectively reviewed from records of patients seen at our center from March 2007 to January 2009 with previously untreated DLBCL, identified from a prospective database of the lymphoma registry at UT-MDACC. Eligibility for inclusion in this evaluation required treatment with at least 4 cycles of standard R-CHOP chemotherapy, one cycle given every three weeks, and adequate information regarding ESA and blood transfusion administration. Three time periods were identified based on 3 successive changes in billing coverage guidelines for ESAs. These changes were based upon reimbursement of ESAs for hemoglobin levels of ≤ 12 g/dl (Period 1), ≤ 11 g/dl (Period 2) and ≤ 10 g/dl (Period 3). The number of PRBC transfusions and number, dose, and type of ESA injections were reported per patient. We also evaluated the overall survival (OS) rates for patients in these three time intervals. Chi-square and Kruskal-Wallis tests were used to analyze categorical and continuous variables, respectively. The Kaplan-Meier and log-rank tests were used to estimate OS rates and evaluate the associations of PRBC transfusions and use of ESAs with OS, respectively. Results: 160 records were available for review, and 129 were included in this analysis. There were 77 patients in Period 1, 31 in Period 2, and 21 in Period 3. With a median follow-up time of 24.7 months (range 1 – 38), PRBCs and ESAs were administered to 43 and 34 patients, respectively. PRBC transfusion rates in each time period were: 29 (37.7%) for Period 1, 8 (25.8%) for Period 2, and 6 (28.6%) for Period 3 (p = 0.43). Patients receiving ESAs in each time period were 25 (33.3%), 5 (16.7%), and 4 (19%), respectively (p = 0.16). There were no differences in the rates of PRBC transfusions (p = 0.88) or use of ESAs (p = 0.36) for these patients over these time periods, although the latter observation may be due to small numbers of patients in each period group. The 2-year OS rate was 68% for those 43 who received transfusions compared to 94% for the 86 patients who did not require transfusions (p=0.001), while there was no statistical difference between OS rates for those 34 who did and the 95 patients who did not receive ESAs (87% vs 84%, p=0.97). Conclusions: The changes of CMS reimbursement for ESAs in patients with CIA may have decreased the use of ESAs, but in this study have not made any changes in the rates of PRBC transfusions in patients with DLBCL receiving standard R-CHOP chemotherapy. Furthermore, OS rates were lower in those requiring transfusions than in those who did not, but the use of ESAs appeared to have no effects on these results. Disclosures: Wang: Celgene: Research Funding; Onyx: Research Funding; Millenium: Research Funding; Novartis: Research Funding. Fowler:Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 73
Author(s):  
Christopher Boniface ◽  
Christopher Deig ◽  
Carol Halsey ◽  
Taylor Kelley ◽  
Michael B. Heskett ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Feasibility Study ◽  
Locally Advanced ◽  
Circulating Tumor Dna ◽  
Study Patient ◽  
Patient Specific ◽  
Clinical Recurrence ◽  
Tumor Dna

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n = 3) and rectal cancer (n = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28–41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

scholarly journals Tumor Specific cfDNA Predicts Treatment Response of Multiple Myeloma Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3188-3188
Author(s):  
David Vrabel ◽  
Jana Gregorova ◽  
Lenka Sedlarikova ◽  
Martina Almasi ◽  
Renata Bezděková ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Treatment Response ◽  
Peripheral Blood ◽  
Research Funding ◽  
Cell Fraction ◽  
Study Patient ◽  
Categorical Variables ◽  
Patient Specific ◽  
Number Of Patients

Abstract Introduction: Great progress achieved in treatment of multiple myeloma (MM) over the past decade changed overall perception of importance of minimal residual disease (MRD) assessment. Since new drugs induce deep responses, MRD must be evaluated using sensitive techniques, such as allele specific PCR (ASO-PCR), next-generation sequencing (NGS) or flow cytometry. MM is a genetically heterogeneous cancer of plasma cells characterized by multiple focal lesions in the bone marrow (BM). Hence, a single-site biopsy can create a sampling bias. In spite of this, BM samples are typically used for MRD analysis, but currently an alternative approach called liquid biopsies, which utilizes body fluids for analysis of various molecules and cells, is intensively studied. Cell-free DNA (cfDNA) as one type of the molecule which can be analyzed using liquid biopsy approach showed promising results previously. In our study, patient-specific, clonotypic rearrangement of immunoglobulin heavy chain (IgH) gene, identified in bone marrow samples, was used for qPCR analysis of cfDNA samples from peripheral blood. We demonstrate that dynamics and quantity of patient-specific, clonotypic IgH rearrangement found in cfDNA can predict the outcomes and response of MM patients. Methods: Total of 45 patients enrolled in the study. Samples of BM were collected at diagnosis, and CD138+ cell fraction was sorted using magnetic activated cell sorting. At diagnosis and at three-month intervals, samples of peripheral blood (PB) were collected for cfDNA extraction and analysis until a patient reached complete remission (CR). If CR was not reached, samples were collected for 24 months after diagnosis. Two more samples of PB were collected (CR+3, CR+6) if patients reached CR. Patient-specific VDJ rearrangement was identified using previously described PCR method from genomic DNA extracted from CD138+ cell fraction; based on the results, patient-specific primers and probes were designed for use in ASO-qPCR. Obtained data were evaluated by absolute and relative frequencies of categorical variables and median (minimum-maximum) of quantitative variables. Results: First, we assessed time to CR. Patients were classified according to the quantity of cfDNA measured at time of diagnosis into three groups: negative, PNQ (= positive non-quantifiable) and positive. As PNQ had a similar profile to negative-classified samples (in K-M plot), PNQ were grouped together with negative results except extremely high values (> 5, n = 2) which were reclassified from PNQ to positive group. The Kaplan-Meier estimates at 12 months were reported and supplemented by the 95% confidence interval derived using Greenwood formula. The results show that significantly higher number of patients classified as negative or PNQ with quantity < 5 have reached CR in contrast to patients classified as positive or PNQ with quantity > 5. The same trend applies to association of quantity of tumor-specific cfDNA with time to CR where Cox proportional-hazards model was adopted. Patients classified as negative or PNQ with quantity < 5 have significantly increased chance of achieving CR (2.7 times) in comparison to patients classified as positive or PNQ with quantity > 5. Conclusion: Our results demonstrate that MM patient-specific cfDNA fragments are released into the bloodstream and that patients either with no or very few DNA fragments have a higher chance of achieving better treatment response eventually. Work was supported by grant AZV 17-29343A Disclosures Hajek: Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Cancer Related Anemia in the Developing World: Risk Factors and Treatment Patterns

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4747-4747
Author(s):  
George Kunnackal John ◽  
Sirisha Sanamandra ◽  
Arun S. Shet
Keyword(s):  
Logistic Regression ◽  
Blood Transfusion ◽  
Cancer Patients ◽  
Tertiary Care ◽  
Binary Logistic Regression ◽  
Limited Resource ◽  
Study Patient ◽  
History Of ◽  
Hodgkin's Lymphomas ◽  
Cancer Related Anemia

Abstract Abstract 4747 Introduction: Cancer related anemia (CRA) is an important problem in limited resource settings due to highly prevalent rates of anemia and malnutrition in the population. Due to a high baseline prevalence of anemia in India (56.2% in females and 24.3% in males), we hypothesized that CRA would have a higher prevalence in India compared to the West. Methods: We used a cross sectional design to evaluate the prevalence of CRA in cancer patients admitted to a 1100 bedded tertiary care centre located in Bangalore, India between January 2005 and December 2007. Using a standardized questionnaire, we collected data from the medical records of patients that fulfilled the inclusion criteria of this study. Patient charts were identified by the ICD code and the data so obtained was further validated using histopathological records and cancer registry information. A total of 579 patients with cancers of the breast, cervix, prostate, head and neck, lung, Hodgkin's and non Hodgkin's lymphomas were included in this study. We excluded those patients with known hemoglobinopathies, HIV infection, patients on myelosuppressive therapy for indications other than cancer, patients with chronic renal disease, and pregnant women. Anemia was defined as Hb < 12g/dl and was further categorized as mild (10-11.9g/dl), moderate (8.0-9.9g/dl) and severe (<8.0g/dl) according to WHO criteria. Descriptive statistics were used to characterize anemic and non anemic patients. The chi square test of association was used to identify significant differences between the groups. Binary logistic regression was used with the presence of anemia as the dependant factor to calculate the crude and adjusted odds ratios for anemia. Results: Of the 579 patients admitted to the hospital, 300 patients (52%) had anemia. The majority of patients had mild anemia (31%) with 14% and 6% having moderate and severe anemia respectively. On bivariate analysis, gender (p=0.010), reason for admission (p<0.001), first admission for cancer (p=0.003), and fatigue as a presenting complaint (p=0.001) were significant differentiating factors between the anemic and non anemic groups. A previous history of or ongoing chemotherapy (p=<0.001), ongoing radiotherapy (p=0.017) and history of recent surgery (p=0.032) were factors that differentiated the two groups. After adjustment for potential confounders, on binary logistic regression analysis only gender, admission for surgery, and a presenting complaint of fatigue were significant factors for anemia. When compared to males, females cancer patients were more likely to be anemic (AOR=2.017, 95% CI 1.084–3.753; p=0.027). Compared to patients who did not present with fatigue, patients reporting fatigue during admission had a significantly higher risk for anemia (AOR=1.703, 95% CI 1.022–2.838; p=0.041). Surprisingly, patients being admitted for surgery had significantly lower odds of having anemia compared to patients admitted for diagnosis (AOR=0.469, 95% CI 0.228–0.966; p=0.040), although this could indicate prophylactic blood transfusion prior to surgery in this group. Only 33% of the 300 patients with cancer related anemia received treatment for the anemia. The most favored treatment method was blood transfusion (17%), while hematinic therapy (Iron tablets) and the combination of transfusion and hematinics were used in the remaining patients. Of note, none of the patients in this setting received erythropoietin stimulating agents (ESAs). Conclusions: CRA is a major complication in the management of cancer; however, its prevalence in South India is not higher than in developed countries. Female sex is associated with greater odds of having CRA which may reflect the higher baseline incidence of anemia in women in India. Since micronutrient deficiencies could contribute to high rates of CRA, the role of oral and parenteral iron for treatment independent of ESAs could be further explored. Additional studies to identify the etiology of CRA in these patients will help aid decisions on treatment in limited resource settings. Disclosures: No relevant conflicts of interest to declare.

Incidence of Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified As High-Risk in Guidelines for Myeloid Growth Factor Use: Importance of “Risk Factor Stacking”

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4824-4824
Author(s):  
Derek Weycker ◽  
Xiaoyan Li ◽  
Rich Barron ◽  
Hongsheng Wu ◽  
Phuong Khanh Morrow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Clinical Practice ◽  
High Risk ◽  
Febrile Neutropenia ◽  
Cancer Patients ◽  
Research Funding ◽  
Tumor Type ◽  
Employment Equity ◽  
Equity Ownership

Abstract Background: Clinical practice guidelines recommend primary prophylactic colony-stimulating factor (CSF) when risk of febrile neutropenia (FN) is ≥20%. Evaluating FN risk among patients who receive regimens that are not documented as high risk in guidelines can be challenging, as some patients may be at a high risk based on a combination of the regimen and their risk factors. Methods: A retrospective cohort design and data from two US private healthcare claims repositories (2003-2012) were employed. The study population comprised cancer patients aged ≥18 years who initiated a course of chemotherapy with a regimen classified as “low” or “intermediate”, or that was unclassified, in terms of FN risk based on guidelines for CSF use. For each subject, the first qualifying chemotherapy course, and each cycle and FN episode within the course, was identified; use of CSF prophylaxis also was identified. FN was ascertained using diagnosis codes for neutropenia, fever, and/or infection; for FN requiring outpatient care only, receipt of intravenous antimicrobials also was required. FN incidence proportion was evaluated during the course within cohorts stratified by tumor type and regimen, for all patients in each cohort and by FN risk factor. Risk factors—documented in guidelines and the published literature, and listed in the Table herein—were evaluated during the 12-month pre-chemotherapy period. Unadjusted relative risks of FN for patients with versus without risk factors, and by the number of risk factors (i.e., “risk factor stacking”), were estimated. Only results for the five most frequently observed tumor/regimen combinations are reported herein. Results: Among patients with one of the five most frequently observed tumor/regimen combinations (n=84,252), 74-97% had ≥1 risk factor for FN and 42-88% had ≥2 (Table). Among patients with ≥1 risk factor, FN incidence ranged from 11-25% (relative risk vs. those without risk factors, 1.4-2.1), and increased in a graded and monotonic fashion with the number of risk factors present (Figure). Conclusion: In this retrospective evaluation of nearly 85,000 cancer patients receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, the large majority had at least one risk factor for FN and many had two or more. FN incidence was found to be markedly elevated in these patients, especially those with multiple risk factors (i.e., “risk factor stacking”). Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Weycker: Amgen: Research Funding. Li:Amgen: Employment, Equity Ownership. Barron:Amgen: Employment, Equity Ownership. Wu:Amgen: Research Funding. Morrow:Amgen: Employment, Equity Ownership. Xu:Amgen: Employment, Equity Ownership. Reiner:Amgen: Employment, Equity Ownership. Garcia:Amgen: Employment, Equity Ownership. Mhatre:Amgen: Employment. Lyman:Amgen: Research Funding.

scholarly journals Indwelling Device-Associated Biofilms in Critically Ill Cancer Patients—Study Protocol

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 306
Author(s):  
Olguta Lungu ◽  
Ioana Grigoras ◽  
Olivia Simona Dorneanu ◽  
Catalina Lunca ◽  
Teodora Vremera ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Critically Ill ◽  
Pathogen Detection ◽  
Venous Catheter ◽  
Successful Outcome ◽  
Patient Specific ◽  
Clinical Value ◽  
Current Standard ◽  
Sepsis Management ◽  
Microorganism Identification

Health care-associated infections are a leading cause of inpatient complications. Rapid pathogen detection/identification is a major challenge in sepsis management that highly influences the successful outcome. The current standard of microorganism identification relies on bacterial growth in culture, which has several limitations. Gene sequencing research has developed culture-independent techniques for microorganism identification, with the aim to improve etiological diagnosis and, therefore, to change sepsis outcome. A prospective, observational, non-interventional, single-center study was designed that assesses biofilm-associated pathogens in a specific subpopulation of septic critically ill cancer patients. Indwelling device samples will be collected in septic patients at the moment of the removal of the arterial catheter, central venous catheter, endotracheal tube and urinary catheter. Concomitantly, clinical data regarding 4 sites (nasal, pharyngeal, rectal and skin) of pathogen colonization at the time of hospital/intensive care admission will be collected. The present study aims to offer new insights into biofilm-associated infections and to evaluate the infection caused by catheter-specific and patient-specific biofilm-associated pathogens in association with the extent of colonization. The analysis relies on the two following detection/identification techniques: standard microbiological method and next generation sequencing (NGS). Retrospectively, the study will estimate the clinical value of the NGS-based detection and its virtual potential in changing patient management and outcome, notably in the subjects with missing sepsis source or lack of response to anti-infective treatment.

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