Level of Scientific Evidence Underlying Recommendations Arising From the National Comprehensive Cancer Network Clinical Practice Guidelines for Hematologic Malignancies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 509-509
Author(s):  
Benny Kusuma ◽  
Ronald S. Go
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Scientific Evidence ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Level Of Evidence ◽  
Nccn Guidelines ◽  
Large B Cell Lymphoma ◽  
Therapeutic Recommendations ◽  
Cancer Network

Abstract Abstract 509 Purpose: The level of scientific evidence on which the National Comprehensive Cancer Network (NCCN) guidelines are based has not been systematically investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are as follows: category I, high level of evidence with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. Results: Of the 1160 recommendations found in the 10 guidelines, the proportions of category I, IIA, IIB, and III EC were 3%, 93%, 4%, and 0%, respectively. Recommendations with category I were found in acute myeloid leukemia (4%), multiple myeloma (7%), Hodgkin's lymphoma (1%), diffuse large B-cell lymphoma (4%), follicular lymphoma (11%). Chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, marginal zone lymphoma, AIDS-related B-cell lymphoma, and Burkitt lymphoma did not have any category I recommendations. Three percent of all therapeutic recommendations were category I. Guideline with the highest proportion of category I therapeutic recommendations was for diffuse large B-cell lymphoma (46%). No category I recommendations were found on staging or surveillance. Conclusion: Recommendations issued in the NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. This underscores the urgent need and available opportunities to expand evidence base in oncology. Disclosures: No relevant conflicts of interest to declare.

Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Aakash Desai ◽  
Harry E Fuentes ◽  
Sri Harsha Tella ◽  
Caleb J Scheckel ◽  
Thejaswi Poonacha ◽  
...  
Keyword(s):  
Clinical Practice ◽  
National Comprehensive Cancer Network ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Scientific Evidence ◽  
Hematologic Malignancies ◽  
Level Of Evidence ◽  
Nccn Guidelines ◽  
Therapeutic Recommendations ◽  
Cancer Network

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines. Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance. Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines. Figure Disclosures No relevant conflicts of interest to declare.

Automated Analysis and Codification of Free Text Pathology Reports

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2394-2394
Author(s):  
Bill Long ◽  
Aliyah Rahemtullah ◽  
Christiana E. Toomey ◽  
Adam Ackerman ◽  
Jeremy S. Abramson ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Final Diagnosis ◽  
Hematologic Malignancies ◽  
Cancer Center ◽  
Pathology Report ◽  
Free Text ◽  
Large B Cell Lymphoma ◽  
Pathology Reports

Abstract Introduction: Epidemiologic research in hematologic malignancies has been dependent on three sources of data; SEER data, patients accrued to large clinical trials, and databases generated by individual providers or departments. Each of these sets of data have major limitations. In theory the adoption of computerized databases by pathology departments and the adoption of electronic medical records should have greatly expanded the ability to identify patients with particular types of malignancies. In practice the need to manually classify tens of thousands of free text pathology reports has made this resource unavailable. We have developed a computer program to extract and codify the final diagnoses described in free text pathology reports according to the World Health Organization (WHO) classification of hematologic malignancies. This enables us to identify sets of cases of desired pathologies for further study. Methods: A medical records review protocol was approved by the Dana Farber Harvard Cancer Center Institutional Review Board. Using our clinical lymphoma database we collected records of patients at Massachusetts General Hospital (MGH) Cancer Center who carried a diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).The program is modified from one developed to extract diagnoses from discharge summaries in a different context [Long, AMIA 2007]. The approach is to use punctuation and a few words (conjunctions and some common verbs) to divide the text into phrases and then use a search procedure to find the most specific matching concepts in the UMLS (Unified Medical Language System). The search uses all of the alternate phrases for each concept as included in the UMLS normalized string table, matched against normalized subphrases from the text. We mapped UMLS concepts to the desired WHO concepts. To ensure a complete list of UMLS concepts we used the hierarchical relations in the UMLS and examined both more specific and more general concepts for possible inclusion in the search. Since not all diseases in a report are part of the diagnosis, we developed pattern matching procedures to identify the parts of the pathology report containing the final diagnosis (as opposed to “note” or “clinical data” that might have patient specific clinical information that are not diagnosed in the current pathology report). The program also uses a strategy for identifying modifiers that change the sense of the diagnosis (“suggestive of”, “rule out”, “no”, etc.) to exclude diseases that are absent or only possible. Results: We used the system to identify cases of FL and DLBCL and compared the results to lists of cases generated manually. The current program was 90% accurate in automatically classifying pathology reports as describing follicular lymphoma. Of 150 cases of FL, the program found 133 (eg, MALIGNANT LYMPHOMA, FOLLICLE CENTER) and 3 were in reports not available to the program (133/147 90%). Of 100 DLBCL cases, 76 were available and 63 were found (83%) (eg, HISTIOCYTE-RICH LARGE B-CELL LYMPHOMA). There were several reasons for the missed cases. Most commonly (13) the diagnosis was not in the identified diagnosis section, either because the section was divided by a note or the diagnosis was in an addendum. Only 3 cases had phrases not found in the UMLS. For 2 others, the program missed because the phrase was not contiguous (eg, B-CELL LYMPHOMA, CONSISTENT WITH FOLLICLE CENTER CELL TYPE). In 5 of the DLBCL cases the stated final diagnosis was more general than the desired diagnoses and 2 of the FL cases were listed as “strongly suggestive” which the program concluded was not a definite diagnosis. Discussion: This program is useful for identifying desired cohorts of cases and can be improved with better identification of the sections containing the diagnosis, the addition of a few missing phrases as they are discovered, and the addition of techniques for handling common discontinuities in disease descriptions (eg, allowing “consistent with” in the phrase). We have shown that very simple natural language techniques are sufficient to extract most of the desired disease descriptions from free text reports, enabling automatic selection of cases and greatly enhancing the usefulness of large repositories of pathology reports.

scholarly journals Radiation for diffuse large B-cell lymphoma in the rituximab era: Analysis of the National Comprehensive Cancer Network lymphoma outcomes project

Cancer ◽  
2014 ◽  
Vol 121 (7) ◽  
pp. 1032-1039 ◽  
Author(s):  
Bouthaina S. Dabaja ◽  
Ann M. Vanderplas ◽  
Allison L. Crosby-Thompson ◽  
Gregory A. Abel ◽  
Myron S. Czuczman ◽  
...  
Keyword(s):  
National Comprehensive Cancer Network ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Cancer Network ◽  
Large B Cell

scholarly journals Statins Potentiate the Cytotoxic Effect of ABT-199 in Diffuse Large B Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3969-3969
Author(s):  
David A. Fruman ◽  
Jong-Hoon Scott Lee ◽  
Thanh-Trang T Vo ◽  
Shruti Bhatt ◽  
Jonathan H. Schatz ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Lymphoma Cells ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract BCL-2 is a key pro-survival protein that is highly expressed in many leukemias and lymphomas. ABT-199 (venetoclax) is a small molecule inhibitor of BCL-2 that has demonstrated impressive responses in chronic lymphocytic leukemia (CLL) leading to FDA approval for second line treatment of patients with 17p deletion. However, other hematologic malignancies are less responsive to ABT-199 as a single agent, suggesting that combinations of targeted therapies may be required to elicit more promising responses. We have investigated the potential of combining ABT-199 with HMG-CoA reductase (HMGCR) inhibitors (statins), which have known anti-cancer potential in hematologic malignancies. Using multiple chemically distinct statin compounds, we observed profound synergistic induction of apoptosis when combined with ABT-199 in both human diffuse large B cell lymphoma (DLBCL) as well as acute myeloid leukemia (AML) cell lines. This synergy was also seen in primary murine B lymphoma cells over-expressing MYC and BCL-2. Importantly, addition of exogenous mevalonate completely rescued cells from the combination, confirming on-target efficacy of HMGCR inhibition. Using BH3 profiling, we found that simvastatin significantly primed lymphoma cells for undergoing apoptosis (termed mitochondrial priming). Notably, the degree of priming correlated with its ability to synergize with ABT-199, suggesting that BH3 profiling may be used to predict patient responses. The combination did not synergize to kill normal human peripheral blood mononuclear cells from healthy donors, suggesting that statins may selectively prime cancer cells for apoptosis. Mechanistic studies support the hypothesis that statins synergize with ABT-199 by suppressing protein prenylation, particularly protein geranylgeranylation. In support, the addition of exogenous geranylgeranyl pyrophosphate (GGPP) completely rescued cells from the effects of simvastatin. Furthermore, selective inhibition of protein geranylgeranyl transferase (GGT) increased priming and was sufficient to recapitulate the effects of simvastatin in combination with ABT-199. Statins and GGT inhibitors increased the mitochondrial abundance of a subset of BH3-only pro-apoptotic proteins. Lastly, we have identified Rap1A de-prenylation as a marker of pharmacodynamic response to statins in vivo. Thus, this project highlights a novel combination for use in aggressive lymphomas, establishes its efficacy and tolerability using preclinical models, and provides proof-of-concept to warrant investigation of its clinical potential. Disclosures Letai: AbbVie: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Research Funding; Tetralogic: Consultancy, Research Funding.

Level of Scientific Evidence Underlying Recommendations Arising From the National Comprehensive Cancer Network Clinical Practice Guidelines

2011 ◽  
Vol 29 (2) ◽  
pp. 186-191 ◽  
Author(s):  
Thejaswi K. Poonacha ◽  
Ronald S. Go
Keyword(s):  
National Comprehensive Cancer Network ◽  
Guideline Development ◽  
Scientific Evidence ◽  
Evidence Base ◽  
Professional Organizations ◽  
Level Of Evidence ◽  
Nccn Guidelines ◽  
Therapeutic Recommendations ◽  
High Level ◽  
Cancer Network

Purpose The level of scientific evidence on which the National Comprehensive Cancer Network (NCCN) guidelines are based has not been systematically investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common cancers with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are as follows: category I, high level of evidence with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. Results Of the 1,023 recommendations found in the 10 guidelines, the proportions of category I, IIA, IIB, and III EC were 6%, 83%, 10%, and 1%, respectively. Recommendations with category I EC were found in kidney (20%), breast (19%), lung (6%), pancreatic (6%), non-Hodgkin's lymphoma (6%), melanoma (6%), prostate (4%), and colorectal (1%) guidelines. Urinary bladder and uterine guidelines did not have any category I recommendations. Eight percent of all therapeutic recommendations were category I. Guidelines with the highest proportions of category I therapeutic recommendations were for breast (30%) and kidney (28%) cancers. No category I recommendations were found on screening or surveillance. Conclusion Recommendations issued in the NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. This underscores the urgent need and available opportunities to expand evidence base in oncology.

MicroRNA Profiling of Low-Grade and Transformed Nodal Marginal Zone Lymphoma Reveals a Similar Signature Pattern Distinct from Diffuse Large B Cell Lymphoma

2014 ◽  
Vol 133 (2) ◽  
pp. 214-220 ◽  
Author(s):  
Niklas Gebauer ◽  
Christoph Thorns ◽  
Veronica Bernard ◽  
Andrea Senft ◽  
Arne Schillert ◽  
...  
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Marginal Zone Lymphoma ◽  
Low Grade ◽  
Large B Cell Lymphoma ◽  
Nodal Marginal Zone Lymphoma ◽  
Large B Cell

Background/Aims: As critical post-transcriptional regulators of gene expression, microRNAs are involved in several cellular processes of vital impact including cell growth and apoptosis. Many hematologic malignancies exhibit distinct microRNA signatures. MicroRNA implication in the pathogenesis of nodal marginal zone lymphoma (NMZL), however, remains widely elusive. Methods: Comprehensive morphologic, immunophenotypic and cytogenetic studies were carried out on a cohort of NMZL (n = 30) incorporating indolent as well as transformed MZL. In addition, microRNA signatures were generated, employing a quantitative real-time polymerase chain reaction approach. These were then compared to signatures from cases of diffuse large B cell lymphoma (DLBCL) alongside reactive lymph node controls. Results: While microRNA signatures of low-grade and transformed NMZL did not differ significantly, several microRNAs were differentially expressed between transformed NMZL and DLBCL, hinting at molecularly distinct mechanisms of lymphomagenesis and indicating the biological disparity of transformed NMZL from DLBCL. Conclusion: In the light of the unresolved issue regarding the classification of marginal zone-derived transformed B-cell neoplasms, microRNAs may be a valuable aid in discriminating NMZL from DLBCL. © 2014 S. Karger AG, Basel

scholarly journals Patient Case Studies and Panel Discussion: Lymphoma

2019 ◽  
Vol 17 (11.5) ◽  
pp. 1420-1423
Keyword(s):  
B Cell ◽  
Case Studies ◽  
Cell Lymphoma ◽  
Panel Discussion ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Peripheral T Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Poor Outcomes ◽  
Large B Cell

A heterogeneous group of diseases, lymphomas encompass a range of diagnoses that call for varied treatment approaches. Although some lymphomas require minimal intervention for cure or remission, others can be very difficult to treat and are associated with poor outcomes. At the NCCN 2019 Annual Congress: Hematologic Malignancies, a panel of experts used 3 case studies to develop an evidence-based approach for the treatment of patients with lymphomas. Moderated by Ranjana H. Advani, MD, the session focused on peripheral T-cell lymphoma, primary mediastinal large B-cell lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma.

scholarly journals Distribution of 9p24 Abnormalities in Hematologic Malignancies with an Emphasis on Diffuse Large B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1866-1866
Author(s):  
Dilan Patel ◽  
Jamie Riney ◽  
Andrew Hahn ◽  
Matthew K Stein ◽  
Michael G. Martin
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
T Cell Lymphoma ◽  
Histone Demethylases ◽  
Large B Cell Lymphoma ◽  
Mitelman Database ◽  
Large B Cell

Abstract Introduction: 9p24 contains genes that are critical for immune evasion and propagating cell division. The loci for PD-L1, PD-L2, JAK2, and the histone demethylases KDM4C/JMJD2C are linked on 9p24 (Van Roosbroeck et al. Genes, Chromosomes and Cancer 2016). Amplification or rearrangements of this region have been described in the pathogenesis of classical Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma (Ansell et al. New England Journal of Medicine 2015). Additionally, JAK2 amplification up-regulates PD-L1 and L2, which leads to increased T-cell inactivation and suggests synergy between these drug targets. The recent success of PD-1 blockade in numerous malignancies has led to the development and approval of PD-1 inhibitors in cHL as well as other cancers. Targeted therapies are approved for JAK2 inhibition, such as ruxolitinib, and are in development for histone demethylases, which illustrates the utility of identifying the 9p24 amplicon in hematologic malignancies (HM) (Van Roosbroeck et al. Genes, Chromsomes and Cancer 2016). The goal of this analysis is to better understand the distribution of 9p24 abnormalities across a broader range of leukemias and lymphomas in order to facilitate future studies of targeted therapy. Methods: The National Cancer Institute's Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer was queried for 9p24 breakpoint abnormalities within HM. Incidence of additions and rearrangements in chromosome 9p24 for all subtypes of HM listed in the Mitelman Database were calculated. Individual references were manually reviewed and pathologic data was extracted as available from the primary sources. Diffuse large B-cell lymphoma (DLBCL) cases were further assessed for co-incident rearrangement of MYC (8q24), BCL2 (18q21) and BCL6 (3q27) with 9p24. All subtypes with greater than 2% incidence of additions and/or rearrangements in chromosome 9p24 were reported. Results: 48,761 patients (pts) with HM across 74 lymphoid and myeloid subtypes were identified. 361 (<1%) pts had additions or rearrangements involving 9p24 across 53 subtypes of HM. 21 subtypes of HM had no 9p24 abnormalities. PTCL NOS had the highest incidence of aberrations (3.1% (6/193), 1.1% with additions and 2% with rearrangements) followed by cHL (2.7% (5/186), all additions) and DLBCL (2.7% (37/1413), 1.5% additions and 1.2% rearrangements) in malignancies with over 100 cases. Among DLBCL cases 9p24 was co-amplified/rearranged with MYC in 22% (8 cases), BCL6 27% (10), BCL2 14% (5) and in 3% (1) double-hit lymphomas. Minimal data was available on cell of origin; therefore, further analysis was not performed. No cases of DLBCL with 9p24 aberrations were T-cell rich DLBCL's (0/37). Among the rarer lymphomas, extranodal NK/T cell lymphoma (11%, 2/18) and intravascular B cell lymphoma (7%, 1/14) had higher incidences of 9p24 additions or rearrangements (Table 1). Conclusion: Amplifications and rearrangement of 9p24 are rare in HM within the Mitelman database. Our study suggests that patients with DLBCL, adult T-cell leukemia/lymphoma, extranodal NK/T cell lymphoma, intravascular B cell lymphoma, peripheral T-cell lymphoma, and extranodal marginal zone B-cell may be considered for further studies with FISH and aCGH to further define the incidence of 9p24 alterations and potentially for targeted clinical trials. 9p24 abnormalities did not correlate with previously described phenotypic subtypes of DLBCL. Disclosures No relevant conflicts of interest to declare.

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