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In: European Journal of Haematology, Wiley, Vol. 85, No. 6 ( 2010-12), p. 552-553

Type of Medium: Online Resource

ISSN: 0902-4441

URL: Issue

URL: Article

DOI: 10.1111/ejh.2010.85.issue-6

DOI: 10.1111/j.1600-0609.2010.01513.x

Language: English

Publisher: Wiley

Publication Date: 2010

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1212-1212

Abstract: Background: This year, germline predisposition to haematological malignancy (HM) debuts in the World Health Organization classification of myeloid neoplasms and acute leukemia (Blood, 2016;127:2391). It has been 17 years since germline mutations in RUNX1 were found to lead to familial platelet disorder (FPD) with predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML) (Nat Genet. 1999;23:166). Now, nearly 80 families have been reported with damaging germline mutations or deletions affecting RUNX1 function, associated with FPD, making it an increasingly significant clinical presence. Although thrombocytopenia and platelet dysfunction are present in almost all RUNX1 mutant carriers, we and others have observed that the predisposition to HM varies between family members, with respect to age at diagnosis and the type of malignancy, and in some cases RUNX1 mutation carriers have no apparent HM development over their lifespan. The reasons for this heterogeneity are currently unknown. Aims: We are conducting an international collaborative study examining RUNX1 mutated families. The aim of the research project is to classify the range of phenotypes correlated with RUNX1 mutations comprehensively (including non-malignant phenotypes such as skin disorders) and to determine if the type of RUNX1 mutation and the presence of other germline and acquired mutations in relevant HM genes correlate with the likelihood of HM development, or the type of HM that develops. Across all of our data we aim to analyse clinically relevant information that will be used to inform prognosis and clinical management in germline RUNX1 mutation carriers. Results:From a review of the literature for previously characterised RUNX1 mutant families most mutations are predicted to be loss-of-function, with the combination of frameshift, stopgain, splicing and deletion accounting for the majority of alterations (57, 70%) compared to missense mutations (22, Figure 1). The most common sites of mutation are R201 and R204, affected by both missense and stopgain (10 total), which lie within the nuclear localisation signal at the end of the RUNT domain (Figure 1). We also surveyed in detail 12 RUNX1 pedigrees with both novel and previously described missense, frameshift, stopgain and deletion mutations and found that, while all families developed myeloid malignancies, 6 families also had individuals who developed lymphoid malignancy (most often Acute lymphoblastic leukemia (ALL)) which was heritable in sub-families, and subject to anticipation (e.g see IV-5 and V-5 in Figure 2). Consistent with population genome wide association studies identifying RUNX1 as a susceptibility locus for psoriasis (J Autoimmun. 2015;64:66), we find that skin conditions (psoriasis, eczema) are common, and present in germline RUNX1 carriers in 50% of our families; most commonly observed in families with stopgain and frameshift mutations. Genomic analysis of selected samples confirms that mutation of the other RUNX1 allele is the most commonly acquired mutation in germline RUNX1 mutation carriers developing HM. Alterations of chromosomes 21 and 7 are also common. DNMT3A and PHF6 acquired mutations were the next most frequently observed in tumors and mutations in U2AF1 and ASXL1 in the blood of RUNX1 carriers without HM were observed, suggestive of pre-HM clonal expansion. Finally, in a family with a novel R169I RUNX1 mutation, a rare germline ASXL1 variant (E1102D, 1.0% in ExAC) was found in two RUNX1 carriers who developed early onset AML. This variant is also significantly enriched in an MDS cohort unselected for family history compared to the general population (HR 1.3, p=0.02), as well as ASXL1 N986S (0.1% in ExAC, HR 3.3, p=0.0002) suggesting they operate as germline HM risk modifiers. Interestingly RUNX1 and ASXL1 acquired mutations often co-occur in sporadic MDS/AML and our data suggests this collaboration may also occur at the germline level. Conclusions:Annotation of skin phenotypes co-existent with a family history of haematological malignancy may assist in identifying RUNX1 mutant families. Both acquired and germline mutations in known HM genes may modify germline RUNX1 driven HM penetrance and phenotype. Our data suggest that screening of RUNX1 germline mutation carriers for germline and acquired variants in other HM genes could provide an important tool for defining risk and requires further investigation. Disclosures Owen: Pharmacyclics: Research Funding; Janssen: Honoraria; Roche: Honoraria, Research Funding; Novartis: Honoraria; Gilead: Honoraria, Research Funding; Lundbeck: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Abbvie: Honoraria. Godley:UpToDate: Honoraria; Onconova, Inc.: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1212.1212

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 324-324

Abstract: Abstract 324 Background: Diffuse large B-cell lymphoma (DLBCL) may be curable with current immuno-chemotherapy, however nearly 30% of patients fail to benefit from this therapeutic approach. Gene expression profiling studies identified lymphocyte as well as stroma-based mRNA signatures that are predictive of response to R-CHOP; however the need for optimally cryopreserved samples has limited their clinical applicability. MicroRNAs (miRNA) are highly preserved non-coding RNAs that act post-transcriptionally to regulate gene expression by binding to the 3′UTR of mRNAs. To date multiple studies have reported selective miRNAs expression at different lymphocyte differentiation stages, distinct expression in mRNA-defined DLBCL subgroups and have correlated the expression of “selected” miRNAs with disease outcomes. Herein, we have conducted a comprehensive profiling of miRNA expression in R-CHOP treated DLBCL patients and established a miRNA-based risk score that is predictive of response to therapy. Methods and results: We have postulated that a miRNA signature in DLBCL is predictive of survival post R-CHOP chemotherapy. To test this hypothesis, we analyzed the miRNA and mRNA signatures of R-CHOP sensitive “S” and resistant “R” DLBCLs (n=20). miRNAs were hybridized to the miRNA Affymetrix gene-chip (847 hsa-miRNA probes) and raw miRNA expression values were log2 transformed and normalized (miRNA-QC tool, Affymetrix). Comparison of normalized miRNAs expression in “S” versus “R” patients (Anova testing) identified 59 differentially expressed miRNAs (Fold change 〈 -1.5 or 〉 1.5 with a p value and FDR 〈 0.05). In order to establish a risk score based on the expression of these 59 miRNAs, column-dendrogram branches were then sorted left to right based on each patient's difference between the average log2-scale expression of the 37 up-regulated and the 12 down-regulated miRNAs: this difference is interpreted as an up-/down-regulated mean ratio (ie, geometric mean) on the log2 scale [Log2 Geometric mean ratio [GMR] up-/down-regulated miRNA = Log2 [(2^Σupr egulatedümiRNA/ni)/(2^ΣdownregulatedümiRNA/nii)] where ni and nii represent the number of up-regulated and down-regulated miRNAs. This univariate summary (ie, GMR) of the 59-miRNA expression profiles for each patient enabled accurate prediction of all S versus R patients. Patients with log2 GMR 〉 0 had a 6-years PFS rate of 100%, while all patients with log2 GMR 〈 0 relapsed (HR=0.293 [95% CI 0.132–0.647]). Cox regression was then used to model relapse free survival times from treatment as a function of miRNA expression. Separate regression models were also built looking at fit measures, proportionality assumption, and discrimination ability (Harrell C statistics) and only miRNA with a discrimination ability (Harrell C) of 〉 85% (n=12 miRNA) were used to calculate the log2 GMR of up-/down-regulated miRNAs. A simplified model based on 12 miRNAs (Sensitive vs Resistant: upregulated: hsa-let-7i; hsa-miR-130a; hsa-miR-199a-3p; hsa-199b-3p; hsa-miR-223; hsa-miR22; hsa-miR-24; hsa-miR-26b; hsa-miR-27a; hsa-miR-331-5p; downregulated: hsa-miR-1288) accurately predicted sensitivity or resistance to R-CHOP. With this 12 miRNAs model, only 1 patient in each group (S and R) was misclassified (Fig 1). In addition we have validated the differential expression of these miRNA by short-stem loop RT-PCR and found a strong correlation between the gene-chip and qRT-PCR results (correlation coefficient 0.717). mRNA profiling (U133A Plus2 array chip) was also performed on the whole lymph node sections; 176 genes were identified as differentially expressed between S and R patients with many of these genes belonging to the “stroma-1 and -2” DLBCL signature. Using the TargetScan miRNA target mRNA prediction tool, combinatory analysis of miRNA and mRNA expression profiles of DLBCL patients identified positive and negative correlations (P 〈 0.05) between differentially expressed miRNA and mRNAs. Lastly in a multivariate Cox regression analysis that included the IPI and the 12 miRNA based GMR risk score, both variables were independent predictors of survival post R-CHOP therapy. Conclusion: We believe that this log2 GMR score based on the 12 identified miRNA provides a robust method of predicting sensitivity to R-CHOP in DLBCL patients and it is currently being tested in a larger independent validation cohort. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.324.324

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Biomedicines, MDPI AG, Vol. 10, No. 9 ( 2022-09-07), p. 2211-

Abstract: Brain metastases are a devastating sequela of common primary cancers (e.g., lung, breast, and skin) and have limited effective therapeutic options. Previously, systemic chemotherapy failed to demonstrate significant benefit in patients with brain metastases, but in recent decades, targeted therapies and more recently immune checkpoint inhibitors (ICIs) have yielded promising results in preclinical and clinical studies. Furthermore, there is significant interest in harnessing the immunomodulatory effects of radiotherapy (RT) to synergize with ICIs. Herein, we discuss studies evaluating the impact of RT dose and fractionation on the immune response, early studies supporting the synergistic interaction between RT and ICIs, and ongoing clinical trials assessing the benefit of combination therapy in patients with brain metastases.

Type of Medium: Online Resource

ISSN: 2227-9059

URL: Article

DOI: 10.3390/biomedicines10092211

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2720867-9

In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-10-16)

Abstract: Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1 -mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1 :Cre; Erk5 fl/fl ( Erk5 fl/fl ) mice by ~6–8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5 fl/fl mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume. Although sex-specific differences were observed, histomorphometry measurements revealed that both bone resorption and bone formation parameters were increased in male Erk5 fl/fl mice compared to wild type (WT) littermates. Osteopenia occurs where the rate of bone resorption exceeds that of bone formation, so we investigated the role of the osteoclast compartment. We found that treatment of RANKL-stimulated primary bone marrow-derived macrophage (BMDM) cultures with small molecule ERK5 pathway inhibitors increased osteoclast numbers. Furthermore, osteoclast numbers and expression of osteoclast marker genes were increased in parallel with reduced Erk5 expression in cultures generated from Erk5 fl/fl mice compared to WT mice. Collectively, these results reveal a novel role for Erk5 during bone maturation and homeostasis in vivo .

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-017-13346-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2615211-3

In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 5027-5027

Abstract: Background Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant disease characterised by platelet abnormalities and risk of MDS/AML. FPD/AML results from germline mutations in RUNX1. The phenotype is heterogeneous with ∼35% of affected individuals developing MDS/AML. This clinical variability may obscure the diagnosis and prevent appropriate screening. We describe 2 families with novel C-terminal RUNX1 mutations and FPD/AML phenotypes, in which potentially affected siblings were used as haematopoietic stem cell transplant (HSCT) donors prior to identification of the inherited mutation. Methods DNA was collected from members of two families with histories of thrombocytopenia and MDS/AML. Direct PCR sequencing was performed on exons 1 and 3–8 of the RUNX1 gene. Results Pedigree 1 has 4 affected members from 2 generations. The proband (I-1) had a history of chronic thrombocytopenia and developed MDS at age 63 and died of AML at age 64. Her daughter (II-1) presented with MDS at age 37 and underwent 2 HSCTs from II-2, relapsing 8 months after the first and remaining well 6 years after the second HSCT. Individuals II-2 and II-3 were recently noted to have mild thrombocytopenia with normal bone marrow morphologies. DNA from blood and bone marrow of II-2 and II-3 revealed an out-of-frame 7 base pair (bp) deletion in exon 8 (1007_1013del) of RUNX1 at amino acid 336 (Gly336fsTer564). Pedigree 2 has 2 affected individuals from 2 generations. The proband (I-1) had a history of chronic thrombocytopenia since childhood. She developed MDS at age 52 and received an HSCT from her brother (I-2) in 2007 with normal engraftment and no early transplant complications. Her son (II-2) had presented with AML at age 8 and received an HSCT from his sister (II-1) at that time. He remains well 26 years later. DNA from blood and saliva of I-1 revealed a substitution of C for T in exon 7 (877C 〉 T) of [italic[RUNX1, resulting in a stop codon and an early-truncated protein at position 292 (Arg292Ter). Conclusions Two novel, C-terminal RUNX1 mutations are described in families with FPD/AML phenotypes. Both families were investigated after affected individuals received HSCT from siblings (who were also at risk of having inherited the mutation). The sibling donors exhibited normal or near-normal platelet counts prior to HSCT, obscuring a FPD/AML diagnosis. Therefore, all patients with MDS/AML should be screened for a family history of thrombocytopenia and/or MDS/AML and considered for investigation of RUNX1 mutations prior to HSCT. Figure Figure Figure Figure

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V110.11.5027.5027

Language: English

Publisher: American Society of Hematology

Publication Date: 2007

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2054-2054

Abstract: Introduction The BCL-2 inhibitor venetoclax has yielded promising results in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), both as monotherapy and in combination with rituximab. The CLL14 trial is a prospective, open-label, multicenter randomized phase III trial to compare the efficacy and safety of obinutuzumab and venetoclax with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Prior to opening the randomized phase, a run-in phase was performed to assess the tolerability of obinutuzumab and venetoclax in this particular patient population. Here, we report the final results on safety and efficacy of this run-in phase. Method The protocol specified to enroll 12 previously untreated patients with confirmed CLL and with coexisting medical conditions assessed by cumulative illness rating scale (CIRS) total score 〉 6 and/or estimated creatinine clearance (CrCl) 〈 70 mL/min requiring treatment according to iwCLL criteria into the run-in phase. All patients received 6 cycles of obinutuzumab and venetoclax followed by 6 additional cycles of venetoclax. Obinutuzumab was administered intravenously with 100 mg on day 1, 900 mg on day 2 (option to deliver 1000 mg on day 1), 1000 mg on day 8 and day 15 of cycle 1 and 1000 mg on day1 for cycles 2-6. A gradual weekly dose ramp-up of venetoclax with 20 mg, 50 mg, 100 mg, 200 mg up to 400 mg was administered starting at day 22 of cycle 1. Risk assessment for tumor lysis syndrome (TLS) based on absolute lymphocyte count and tumor burden was performed before treatment in order to direct prophylactic measures. Study defined stopping criteria for all 12 patients included: one treatment-related death or one grade 4 adverse event related to a clinical tumor lysis syndrome (TLS) despite protocol-specified prophylaxis. Adverse events were graded per the NCI CTCAE v.4 criteria. Final response to treatment including assessment for minimal residual disease (MRD) in peripheral blood by ASO-PCR was assessed per the iwCLL guidelines 3 months after the end of treatment, at month 15. Results Between December 2014 and April 2015, 13 previously untreated patients from Australia, Canada, Germany, New Zealand, United States and Spain were enrolled into the trial. Baseline patient characteristics are summarized in Table 1. The median age was 75 years (range 59 - 88) and 62% of the patients were classified as Binet stage C; 38% of the patients were assessed at medium risk and 62% at high risk for TLS. One patient developed a grade-4 infusion related reaction (IRR) during the first dose of obinutuzumab and was therefore withdrawn from the trial according to the protocol requirements. Eleven of 12 patients completed treatment. One patient discontinued treatment after 6 cycles of obinutuzumab and venetoclax and 2 additional cycles of venetoclax due to patient´s wish. All patients experienced at least one adverse event. The commonest adverse events are summarized in Table 2. No clinical TLS was reported. At month 15, 11 of 12 patients were evaluable for final response assessment. All patients responded to therapy. Complete remissions occurred in 7 of the 12 patients including one complete remission with incomplete bone marrow recovery. Ten of 12 patients had no detectable ( 〈 10-4) minimal residual disease (MRD) in peripheral blood and one patient was assessed intermediate (≥10-4 〈 10-2). At month 15, there were no events of disease progression or deaths, translating into an estimated progression-free survival of of 100%. Conclusions The treatment regimen developed for the experimental arm of the CLL14 trial comprising obinutuzumab monotherapy for one cycle followed by venetoclax and obinutuzumab in previously untreated, elderly patients with CLL and coexisting medical conditions appears well tolerated and effective. The target population in this trial consists of elderly patients with clinically meaningful comorbidities in addition to CLL. None of the protocol defined stopping safety criteria for the run-in phase of the trial were met. The treatment induced substantial responses with an unprecedentedly high number of MRD negative responses seen in all but one evaluable patients including those with poor prognostic features. The main phase of the CLL14 trial was opened in August 2015 and completed recruitment in August 2016 after 432 patients had been randomized. Disclosures Fischer: Hoffmann-LaRoche: Other: Travel grants. Al-Sawaf:Gilead: Other: Travel grants. Fink:AbbVie: Other: Travel grants; Mundipharma: Other: Travel grants; Celgene: Other: Travel grants, Research Funding; Hoffmann-LaRoche: Other: Travel grants. Dixon:Roche Products Limited: Employment, Equity Ownership. Bahlo:F. Hoffman-La Roche: Honoraria, Other: Travel grant. Warburton:Roche UK: Employment. Kipps:Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria. Weinkove:Avalia Immunotherapies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel grants; Janssen: Honoraria; Capital & Coast District Health Board: Employment; Malaghan Institute of Medical Research: Employment; Health Research Council of New Zealand: Research Funding; Australasian Leukaemia & Lymphoma Group: Membership on an entity's Board of Directors or advisory committees. Robinson:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Abbvie: Consultancy; Lundbeck: Consultancy; Gilead: Consultancy. Dreyling:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Opat:Roche: Consultancy, Honoraria, Other: Provision of subsidised drugs, Research Funding. Owen:Pharmacyclics: Research Funding; Janssen: Honoraria; Gilead: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Abbvie: Honoraria; Lundbeck: Honoraria, Research Funding; Novartis: Honoraria. López:Novartis: Consultancy; Abbvie: Consultancy; Merck Sharp & Dohme: Consultancy; Janssen: Consultancy; Roche: Consultancy; Gilead: Consultancy. Humphrey:Genentech, Inc.: Employment. Humerickhouse:AbbVie: Employment. Tausch:Amgen: Other: Travel support; Gilead: Other: Travel support, Speakers Bureau; Celgene: Other: Travel support. Eichhorst:Abbvie: Consultancy; Mundipharma: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau. Wendtner:Genetech: Consultancy, Honoraria, Research Funding; Hoffmann‐La Roche: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Munipharma: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Janssen‐Cilag: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria, Research Funding. Langerak:F. Hofmann-LaRoche, Genentech: Research Funding; InVivoScribe Technologies: Patents & Royalties: Royalties are provided to European Network (EuroClonality). Ritgen:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Boettcher:Roche: Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Stilgenbauer:Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding; GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding. Goede:Roche: Consultancy, Honoraria, Other: Travel grant, Research Funding; GlaxoSmithKline: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mobasher:Genentech, Inc.: Employment. Hallek:Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.2054.2054

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal of the National Comprehensive Cancer Network, Harborside Press, LLC, ( 2021-08-13)

Abstract: Background: Lung cancer is the leading cause of cancer-related death in the United States and globally, and many questions exist about treatment options. Harmonizing data across registries and other data collection efforts would yield a robust data infrastructure to help address many research questions. The purpose of this project was to develop a minimum set of patient and clinician relevant harmonized outcome measures that can be collected in non–small cell lung cancer (NSCLC) patient registries and clinical practice. Methods: Seventeen lung cancer registries and related efforts were identified and invited to submit outcome measures. Representatives from medical specialty societies, government agencies, health systems, health information technology groups, patient advocacy organizations, and industry formed a stakeholder panel to categorize the measures and harmonize definitions using the Agency for Healthcare Research and Quality’s supported Outcome Measures Framework (OMF). Results: The panel reviewed 66 outcome measures and identified a minimum set of 8 broadly relevant measures in the OMF categories of patient survival, clinical response, events of interest, and resource utilization. The panel harmonized definitions for the 8 measures through in-person and virtual meetings. The panel did not reach consensus on 1 specific validated instrument for capturing patient-reported outcomes. The minimum set of harmonized outcome measures is broadly relevant to clinicians and patients and feasible to capture across NSCLC disease stages and treatment pathways. A pilot test of these measures would be useful to document the burden and value of the measures for research and in clinical practice. Conclusions: By collecting the harmonized measures consistently, registries and other data collection systems could contribute to the development research infrastructure and learning health systems to support new research and improve patient outcomes.

Type of Medium: Online Resource

ISSN: 1540-1405 , 1540-1413

URL: Article

DOI: 10.6004/jnccn.2021.7021

Language: Unknown

Publisher: Harborside Press, LLC

Publication Date: 2021

In: Journal of Aerosol Medicine and Pulmonary Drug Delivery, Mary Ann Liebert Inc, Vol. 24, No. 1 ( 2011-02), p. 43-48

Type of Medium: Online Resource

ISSN: 1941-2711 , 1941-2703

URL: Article

DOI: 10.1089/jamp.2010.0822

Language: English

Publisher: Mary Ann Liebert Inc

Publication Date: 2011

detail.hit.zdb_id: 2417925-5

SSG: 15,3

In: JAMA Oncology, American Medical Association (AMA), Vol. 7, No. 12 ( 2021-12-01), p. 1856-

Type of Medium: Online Resource

ISSN: 2374-2437

URL: Article

DOI: 10.1001/jamaoncol.2021.4960

Language: English

Publisher: American Medical Association (AMA)

Publication Date: 2021