scholarly journals Evaluation of the Prognostic Utility of Bone Marrow Biopsy in Diffuse Large B-Cell Lymphoma: A SEER-Medicare Linked Database Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Danny Luan ◽  
Yiyuan Wu ◽  
Jordan S. Goldstein ◽  
Sarah C. Rutherford ◽  
John P. Leonard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Temporal Trends ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Pet Ct

Background: Positron emission tomography-computed tomography (PET-CT) has become the primary modality for initial staging in diffuse large B-cell lymphoma (DLBCL) [Barrington et al, J Clin Oncol 2014; Cheson et al, J Clin Oncol 2014]. Recently, the role of a staging bone marrow biopsy (BMB) has become less clear. A meta-analysis suggested that PET-CT can miss bone marrow involvement [Adams et al, Eur J Nucl Med Mol Imaging 2014], but recent guidelines on staging suggested that BMB should be optional. We analyzed temporal trends in use of different screening modalities and evaluated the association between patient outcomes and staging modality (PET-CT with BMB compared to either PET-CT without BMB or CT with BMB) in patients with DLBCL in SEER-Medicare. We hypothesized that use of PET-CT as screening would increase over time and that use of BMB would decrease over time. We also hypothesized that use of BMB would not be associated with an improvement in overall survival in patients staged with PET-CT. Methods: 70,858 patients diagnosed with DLBCL in SEER-Medicare were identified with ICD-O-3 SEER histology codes 9680 and 9684. In this analysis, we included 7,159 patients who were diagnosed between 2002 and 2015, were treated with first-line rituximab, cyclophosphamide, vincristine, and doxorubicin chemotherapy regimens, and had claims for PET-CT and/or BMB within 30 days on either side of diagnosis. The patients were divided into screening categories of patients receiving PET-CT without BMB (PET-CT w/o BMB), patients receiving BMB with CT (i.e., no PET-CT) (CT w/ BMB), and patients receiving both screening modalities (PET-CT w/ BMB). Overall survival (OS) was calculated from date of diagnosis to death. Kaplan-Meier (KM) curves were used to estimate survival probabilities across screening categories and log-rank tests (LRT) were used to statistically evaluate differences between OS curves. Cox proportional hazards (CoxPH) models were used to estimate hazard ratios prior to and following adjustment for confounders. Results: 2,059 patients received PET-CT w/o BMB, 1,539 received CT w/ BMB, and 3,561 received PET-CT w/ BMB. Proportions of patients receiving PET-CT w/ BMB and PET-CT w/o BMB increased across years of diagnosis (36.7 to 51.9% and 17.4 to 36.1%, respectively, between 2002-2005 and 2013-2015), while the proportion of patients receiving CT w/ BMB decreased across years of diagnosis (45.8 to 12.0%) (Table 1). Similarly, the proportion of patients receiving BMB independent of imaging modality also decreased (28.8% to 16.8%). In bivariate analyses, categories of screening were significantly associated with age category, sex, year of diagnosis, race, stage, nodal status, poor performance status, Charlson Comorbidity Index (CCI), number of first-line cycles, and geographic classification, with receipt of PET-CT w/ BMB being more common in patients who are younger, male, diagnosed in later years in urban settings, and received >4 first-line cycles, with earlier stage at diagnosis, nodal disease, good performance status, and lower CCI (Table 1). In unadjusted KM analysis, median survival among patients receiving PET-CT w/ BMB was 8.7 years, compared to 8.1 and 7.6 years among patients receiving PET-CT w/o BMB and CT w/ BMB, respectively (LRT P<0.0001; Figure 1). In fully adjusted CoxPH models, patients receiving PET-CT w/ BMB did not have a significantly better OS compared to those receiving PET-CT w/o BMB (HR: 0.93; 95% CI, 0.84-1.02; P=0.1075). Separately, patients receiving CT w/ BMB had a significantly worse OS compared to those receiving PET-CT w/o BMB (HR: 1.13; 95% CI, 1.02-1.26; P=0.0212), even though OS was not significantly associated with year of diagnosis (P=0.6613). Conclusions: In this SEER-Medicare cohort of 7,159 patients with newly diagnosed DLBCL, we found temporal trends supporting increased use of pretreatment staging PET-CT and decreased use of BMB. We also found that use of PET-CT w/ BMB did not provide a survival benefit as compared to use of PET-CT w/o BMB. These data would suggest that use of BMB could be spared in patients newly diagnosed with DLBCL over the age of 65, unless otherwise clinically indicated. Interestingly, the finding of no OS benefit across years of diagnosis suggests that improvements in outcomes in recent trials may be due to patient selection. Given the limitations associated with registry data, the study warrants replication in more complete DLBCL data sets. Disclosures Rutherford: Genentech/Roche: Research Funding; Karyopharm: Consultancy, Research Funding; Regeneron: Research Funding; Celgene: Consultancy; Kite: Consultancy; Dova: Consultancy; Seattle Genetics: Consultancy; AstraZeneca: Consultancy; LAM Therapeutics: Research Funding; Heron: Consultancy; Juno: Consultancy. Leonard:Miltenyi: Consultancy; Karyopharm: Consultancy; Gilead/Kite: Consultancy; Sutro: Consultancy; Bayer: Consultancy; BMS/Celgene: Consultancy; MEI Pharma: Consultancy; Epizyme: Consultancy; Roche/Genentech: Consultancy; Regeneron: Consultancy; ADC Therapeutics: Consultancy; GenMab: Consultancy; AstraZeneca: Consultancy. Martin:Kite: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Bayer: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; Celgene: Consultancy; Teneobio: Consultancy.

An International Collaborative Study of Outcome and Prognostic Factors in Patients with Secondary CNS Involvement By Diffuse Large B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1874-1874 ◽  
Author(s):  
Tarec Christoffer El-Galaly ◽  
Chan Yoon Cheah ◽  
Mette Dahl Bendtsen ◽  
Gita Thanarasjasingam ◽  
Roopesh Kansara ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Systemic Disease ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Cns Involvement ◽  
First Line ◽  
Advisory Committees ◽  
Large B Cell Lymphoma

Abstract Background: Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically <6 months. However, data in patients that develop SCNS following primary therapy that contains a rituximab-based-regimen as well as the impact of more intensified treatment for SCNS are limited. Aims: The aims of this study were to i) describe the natural history of SCNS in a large cohort of patients treated with immunochemotherapy, and ii) determine prognostic factors after SCNS. Patients and methods: We performed a retrospective study of patients diagnosed with SCNS during or after frontline immunochemotherapy (R-CHOP or equivalently effective regimens). SCNS was defined as new involvement of the CNS (parenchymal, leptomeningeal, and/or eye) in patients without known CNS involvement at the time of first pathologic diagnosis of DLBCL. Patients were identified from local databases and/or regional/national registries in Denmark, Canada (British Columbia), Australia, Israel, US (University of Iowa/Mayo Clinic SPORE), and England (Guy's and St. Thomas' Hospital, London). Clinico-pathologic and treatment characteristics at the time of SCNS were collected from medical records. Results: In total, 281 patients with SCNS diagnosed between 2001 and 2016 were included. Median age at SCNS was 64 (range 20-93) years and male:female ratio was 1.3. SCNS occurred as part of first relapse in 244 (87%) patients and 112 (40%) had documented concurrent systemic disease at the time of SCNS. The median time from initial DLBCL diagnosis to SCNS was 9 months, which was similar for patients treated with (N=76, 27%) or without upfront CNS prophylaxis (N=205, 73%) (10 vs 9 Mo; P=0.3). The median post-SCNS OS was 4 months (interquartile range 2-13) and the 2yr survival rate was 20% (95% CI 15-25) for the entire cohort. Associations between clinicopathologic features, management strategy, and post-SCNS survival are shown in Table 1, which excludes patients who did not receive any treatment against SCNS, patients treated with steroids alone, and a patient with unavailable treatment information (n=43, 15%). In multivariable analysis, performance status >1, concurrent leptomeningeal and parenchymal involvement, SCNS developing before completion of 1st line treatment, and combined systemic and CNS involvement by DLBCL were associated with inferior outcomes. Upfront CNS prophylaxis did not influence post-SCNS OS. High-dose methotrexate (HDMTX) and/or platinum based treatment regimens (i.e. ICE, DHAP, or GDP [+/- IT treatment and/or radiotherapy], N=163) for SCNS were associated with reduced risk of death (HR 0.45 [0.32-0.62, P<0.01]). The 2yr post-SCNS survival for patients treated with HDMTX and/or platinum-based regimens (N=163) was 29% (95% CI 22-37). For patients with isolated parenchymal SCNS, single modality treatment with radiotherapy resulted in 2-yr OS of 19% (95% CI 8-35). For the subgroup of 49 patients treated with HDMTX- and/or platinum-based regimens for isolated SCNS after 1st line DLBCL treatment and with performance status 0 or 1, the 2yr post-SCNS survival was 46% (95% CI 31-59). Overall, 9% of the patients received HDT with ASCT as part of salvage therapy at the time of SCNS. Amongst 36 SCNS patients without systemic involvement and in CR following intensive treatment (HDMTX and/or platinum-based treatments), 11 patients consolidated with HDT had similar outcomes to 25 patients treated without consolidating HDT (P=0.9, Fig 1) Conclusions: Outcomes for patients with SCNS remain poor in this large international cohort of patients from the immunochemotherapy era. Combined parenchymal and leptomeningeal disease, presence of systemic disease concurrent with SCNS, performance status >1, and SCNS developing during first line treatment were independently associated with inferior OS. However, a significant fraction of patients with isolated SCNS after first line DLBCL treatment and with good performance status may achieve long-term remissions after intensive regimens for SCNS. Disclosures El-Galaly: Roche: Consultancy, Other: travel funding. Cheah:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Speaker's Bureau. Kansara:Celgene: Honoraria. Connors:Bristol Myers Squib: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Millennium Takeda: Research Funding; Seattle Genetics: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Opat:Roche: Consultancy, Honoraria, Other: Provision of subsidised drugs, Research Funding. Seymour:Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding.

scholarly journals Prognostic significance of bone marrow infiltration detected by PET-CT in newly diagnosed diffuse large B cell lymphoma

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 19072-19080 ◽  
Author(s):  
Jin-Hua Liang ◽  
Jin Sun ◽  
Li Wang ◽  
Lei Fan ◽  
Yao-Yu Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Bone Marrow Infiltration ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Large B Cell

Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma

2011 ◽  
Vol 91 (5) ◽  
pp. 687-695 ◽  
Author(s):  
Junshik Hong ◽  
Yukyung Lee ◽  
Yeonjeong Park ◽  
Seog Gyun Kim ◽  
Kyung Hoon Hwang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Large B Cell

Role of FDG-PET/CT in Detecting Lymphomatous Bone Marrow Involvement in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5204-5204
Author(s):  
Junshik Hong ◽  
Yukyung Lee ◽  
Seog Gyun Kim ◽  
Kyung Hoon Hwang ◽  
Soon Ho Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Large B Cell

Abstract Abstract 5204 Backgrounds: As a bone marrow bopsy (BMB) is a painful and invasive procedure with a restrictive reliability as only a limited area of the bone marrow (BM) can be evaluated, role of FDG-PET/CT to demonstrate lymphomatous BM involvement as an alternative or at least a complementary to BMB is an area of interest. Several previous studies exist but most of them included heterogeneous types of lymphomas with various treatments. Patients and methods: To evaluate the role of FDG-PET/CT in detecting BM involvement, pre-treatment bilateral BMBs and FDG-PET/CT scans of 89 patients with diffuse large B-cell lymphoma (DLBCL) treated with standard immunochemotherapy, rituximab-CHOP were reviewed and analyzed. Uptake more than liver parenchyma intensity on FDG-PET/CT was interpreted as 'with a possibility' of involvement. The final interpretation on the possibility of BM involvement in each patient was reported after discussion among three nuclear medicine physicians and results of BMB were blinded at the time of FDG-PET/CT review. Fourteen patients (15.7%) had lymphomatous involvement based on BMB (BMB+) and 17 patients (19.1%) had the possibility of BM involvement on FDG-PET/CT (FDG-PET/CT+). Seventy-two patients (80.8%) had concordant results between BMB and FDG-PET/CT (7 patients were positive for both and 65 patients were negative for both), but 17 patients (19.2%) had a discordant interpretation (7 patients were BMB+ and FDG-PET/CT-, and 10 for BMB- and FDG-PET/CT+; table 1). Although BMB+ patients had an inferior 2-year EFS (37.0% vs. 79.8%, p < 0.001) and OS (36.3% vs. 81.0%, p < 0.001) compared to BMB- patients, no differences in EFS (62.6% vs. 72.7%, p = 0.185) and OS (59.4% vs. 78.0%, p = 0.146) were shown between FDG-PET/CT+ and FDG-PET/CT- patients. Six of 7 patients with BMB+ and FDG-PET/CT+ had a diffuse involvement on FDG-PET/CT whereas 9 of 10 patients with BMB- and FDG-PET/CT+ had a focal BM involvement on FDG-PET/CT (table 2). Six of 7 patients with diffuse involvement on FDG-PET/CT were BMB+ whereas only 1 of 10 patients with focal BM involvement on FDG-PET/CT were BMB+ (table 2). It is likely therefore that patients with diffuse BM involvement on FDG-PET/CT had higher probability for BMB+ and they might have poorer survival than those with focal BM involvement. Conclusion: The results suggest that FDG-PET/CT had a limited value to detect BM involvement in patients with DLBCL. It may not be justified to upgrade patient's Ann Arbor stage to IV according to focal hypermetabolic BM lesion on FDG-PET/CT. Until additional results on the role of FDG-PET/CT in detecting BM involvement available, FDG-PET/CT should be used as an adjuvant rather than an alternative in detecting BM involvement in patients with newly diagnosed DLBCL. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Extranodal Diffuse Large B-Cell Lymphoma in the Era of Immunochemotherapy and PET/CT Staging

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1630-1630
Author(s):  
Tarec Christoffer El-Galaly ◽  
Diego Villa ◽  
Musa Alzahrani ◽  
Jakob Werner Hansen ◽  
Laurie H. Sehn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Extranodal Disease ◽  
Large B Cell

Abstract Background: Extranodal disease is common in diffuse large B-cell lymphoma (DLBCL), and involvement of more than one extranodal site is associated with a worse outcome. 18F-fluorodeoxyglucose PET/CT (PET/CT) is the current state-of-the-art for staging of DLBCL, and has shown to be much more sensitive for the detection of extranodal involvement than a stand-alone CT scan. Therefore, a re-evaluation of the clinical significance of extranodal disease among PET/CT staged DLBCL patients is warranted. Patients and Methods: We retrospectively included patients from Aalborg (2007-2012), Copenhagen (2009-2012), and British Columbia (2011-2012) in the present study. The inclusion criteria were, i) newly diagnosed DLBCL, ii) R-CHOP or R-CHOP like first-line treatment, and iii) PET/CT staging. The written PET/CT files were reviewed for disease stage and extranodal sites of involvement. The relationship between number of involved sites, extranodal locations and outcome were assessed with simple Cox regression analyses. Extranodal locations with p<0.1 in univariate analysis were entered in a multivariable Cox regression analysis together with the following International Prognostic Index (IPI) factors: age > 60 years, elevated LDH, ECOG performance score >1. Results: A total of 444 patients with a median age of 65 years (range 16-90) and a male:female ratio of 1.3 were included in the study. Of these patients 28% (n=98) had Ann Arbor stage I disease, 16% (n=72) stage II disease, 16% (n=71) stage III disease, and 46% stage IV disease (n= 203). LDH was elevated in 51% (n=224), and 17% (n=74) had ECOG performance status >1. B-symptoms were present in 37% (n=164) and 26% (n=114) had a bulky mass =/> 10 cm. With a median follow-up of 2.4 years (range 0.5-6.5) in patients still alive at the time of analysis, the 3-year OS and PFS were 73% and 69%, respectively. Extranodal disease was diagnosed in 286 (64%) of the patients. The anatomic locations of extranodal disease and their relations to outcome are shown in Table I. Figure 1A and B show the PFS and OS curves when patients are grouped according to the number of involved extranodal sites. Patients with one or two extranodal sites of involvement had similar outcome (3-year PFS 68% vs. 70%), whereas all patients with involvement of more than three extranodal sites progressed. Conclusions: Extranodal involvement is diagnosed in more than half of all newly diagnosed DLBCL patients staged with PET/CT. Bone/bone marrow involvement was the most common site and associated with a worse outcome. Thus, detection of these lesions with PET/CT is clinically important. The presence of extranodal disease is generally associated with a worse outcome, but our data suggest that the optimal cut-off for prognostication in PET/CT staged patients may be more than two sites rather than more than one site, as according to the IPI. Abstract 1630 Table1: Extranodal DLBCL and their relationship with outcome in PET/CT staged patients treated with R-CHOP. Empty boxes represent variables not included in multivariate models. Site Frequency, n (%) HR, univariate HR, multivariate PFS OS PFS OS Lung 33 (7%) 1.56, p=0.002 1.46, p=0.26 Not significant Liver 34 (8%) 2.39, p=0.001 2.43, p=0.002 Not significant Not significant Bone/bone marrow (PET/CT) 127 (29%) 2.49, p<0.001 2.53, p<0.001 1.77, p=0.007 1.66, p=0.03 Bone marrow indolent NHL (biopsy) 28 (6%) 0.86, p=0.70 0.94, p=0.87 Bone marrow DLBCL (biopsy) 43 (10%) 2.55, p<0.001 2.66, p<0.001 Not significant Not significant Gastrointestinal 35 (8%) 1.27, p=0.43 1.02, p=0.96 Kidney 13 (3%) 2.10, p=0.06 1.63, p=0.29 Not significant Soft tissue and muscle 46 (10%) 1.18, p=0.58 1.17, p=0.64 Paranasal sinus 15 (3%) 1.57, p=0.28 1.69, p=0.25 Pleural fluid 16 (4%) 2.82, p=0.005 3.23, p=0.003 2.43, p=0.02 2.53, p=0.02 Testicular 13/252 (5%) 2.42, p=0.22 1.81, p=0.41 Female genitals 10/192 (5%) 3.38, p=0.006 3.76, p=0.003 Figure 1A and B: PFS (Figure 1A) and OS (Figure 1B) in patients grouped according to the number of extranodal sites involved: zero (blue), 1 (green), 2 (grey), 3 (purple), >4 (red). Figure 1A and B:. PFS (Figure 1A) and OS (Figure 1B) in patients grouped according to the number of extranodal sites involved: zero (blue), 1 (green), 2 (grey), 3 (purple), >4 (red). Disclosures No relevant conflicts of interest to declare.

scholarly journals 18f-FDG PET/CT Baseline Rdiomics Features Improve the Prediction of Treatment Outcome in Diffuse Large B-Cell Lymphoma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Jakoba J Eertink ◽  
Tim van de Brug ◽  
Sanne E Wiegers ◽  
Gerben J.C. Zwezerijnen ◽  
Elisabeth Pfaehler ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Clinical Predictors ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Aim/Introduction Up to one third of diffuse large B-cell lymphoma (DLBCL) patients experience relapse or fail to achieve complete remission during first-line treatment. Identification of poor prognosis patients might be further improved by radiomics. Radiomics analysis of imaging data provides quantitative features of tumor characteristics such as intensity, shape, volume, texture and intra- and inter-lesion heterogeneity. The objective of this study was to assess the added value of baseline quantitative radiomics features in DLBCL patients compared to currently used clinical characteristics such as the IPI score. Materials and Methods 317 newly diagnosed DLBCL patients with baseline 18F-FDG PET/CT scans from the HOVON84 trial (Lugtenburg et al, JCO 2020) were included. Lesions were delineated using a fully automated preselection of 18F-FDG avid structures defined by a SUV ≥ 4.0 and volume &gt;3mL. Missed lesions were added and non-tumour regions were removed (accurate tool, https://petralymphoma.org). Next, 490 radiomics features were extracted from the volume of interest using RaCat software (Pfaehler et al, 2019). To reduce feature space dimensions, we made a preselection of clinically most relevant radiomics features based on literature (SUVmax, SUVmean, SUVpeak, total lesion glycolysis, metabolic tumor volume (MTV), dissemination features and sphericity) and used logistic regression with backward feature selection to predict 2-year time to progression (TTP), defined as time from baseline PET/CT to progression. Patients who died without progression were censored at date of death. Furthermore, we tested the predictive value of known clinical predictors (age (cut off: &gt;60 years), WHO performance status (cut-off: ≥ 1 and ≥2), Ann Arbor stage, extranodal involvement (cut-off: ≥ 1 and &gt;1), lactate dehydrogenase (LDH) level and bulky disease (≥ 10 cm)) and of a model that combined radiomics and clinical parameters. Model performance was assessed using repeated cross-validation (5 folds, 2000 repeats) yielding the mean receiver-operator-characteristics curve integral (AUC). High- and low-risk groups were defined based on prevalence of events, diagnostic performance was assessed using positive- and negative predictive values. Patients censored before 2 years of follow-up were excluded for the prediction models and diagnostic performance. Results The categorical IPI score yielded in a cross-validated AUC (CV-AUC) of 0.68 (Figure 1). The highest performance for the radiomics model was observed for the natural logarithms of MTV and SUVpeak and the maximal distance between the largest lesion and any other lesion (Dmaxbulk), which yielded in a cross-validated AUC (CV-AUC) of 0.75±0.07, which was significantly higher than the discriminative power of the MTV model (CV-AUC: 0.66±0.08, p=0.01). LDH/upper limit of normal, WHO performance status ≥1 and extranodal involvement ≥1 showed the highest performance for the clinical prediction model with a CV-AUC of 0.71±0.08. When combining radiomics features with clinical predictors, the highest performance was observed for the natural logarithms of MTV and SUVpeak, Dmaxbulk, WHO performance status ≥ 1 and age, with a CV-AUC of 0.77±0.07, which was significantly higher than the IPI model (p=0.003). Adding radiomics features to clinical predictors increased the positive predictive value with 15%, with more accurate selection of high-risk patients compared to the IPI model (progression at 2-year TTP: 28.3% vs 43.8%, respectively). Conclusion Combining quantitative radiomics features extracted from baseline 18F-FDG PET/CT scans with components of the IPI score significantly improved identification of patients at risk of relapse at baseline. Adding radiomics features can significantly increase the efficiency of clinical trials in poor prognosis patients. Figure Disclosures Lugtenburg: Incyte: Honoraria; Celgene: Honoraria; Genmab: Honoraria; Genentech: Honoraria; Roche: Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Zijlstra:Roche: Research Funding.

scholarly journals Relapses after Achieving EFS24 in Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 454-454 ◽  
Author(s):  
Yucai Wang ◽  
Umar Farooq ◽  
Brian K. Link ◽  
Mehrdad Hefazi ◽  
Cristine Allmer ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Newly Diagnosed ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: The addition of Rituximab to chemotherapy has significantly improved the outcome of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients treated with immunochemotherapy for DLBCL who achieve EFS24 (event-free for 2 years after diagnosis) have an overall survival equivalent to that of the age- and sex-matched general population. Relapses after achieving EFS24 have been considered to be unusual but have been understudied. We sought to define the rate, clinical characteristics, treatment pattern, and outcomes of such relapses. Methods: 1448 patients with newly diagnosed DLBCL from March 2002 to June 2015 were included. Patients were enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, treated per physician choice (predominantly R-CHOP immunochemotherapy) and followed prospectively. An event was defined as progression or relapse, unplanned re-treatment after initial therapy, or death from any cause. Cumulative incidence of relapse and non-relapse mortality after achieving EFS24 were analyzed as competing events using Gray's test in the EZR software. Post-relapse survival was defined as time from relapse to death from any cause and analyzed using Kaplan-Meier method in SPSS (V22). Results: Among the 1448 patients, 1260 (87%) had DLBCL alone at diagnosis, and 188 (13%) had concurrent indolent lymphoma (follicular lymphoma 115, marginal zone lymphoma 18, chronic lymphocytic leukemia 14, lymphoplasmacytic lymphoma 4, unspecified 37) at diagnosis. After a median follow-up of 83.9 months, 896 patients achieved EFS24. For all 896 patients who achieved EFS24, the cumulative incidence of relapse (CIR) was 5.7%, 9.3% and 13.2%, respectively, at 2, 5 and 10 years after achieving EFS24. Patients with concurrent indolent lymphoma at diagnosis had a higher CIR compared to those with DLBCL alone at diagnosis (10.2 vs 4.8% at 2 years, 15.7 vs 8.0% at 5 years, 28.8 vs 9.7% at 10 years, P<0.001; Figure 1). There were a total of 84 patients who relapsed after achieving EFS24. The median age at initial diagnosis was 66 years (range 35-92), and 48 (57%) were male. At diagnosis, 11 (13%) had ECOG PS >1, 37 (50%) had LDH elevation, 62 (74%) were stage III-IV, 14 (17%) had more than 1 extranodal site, and 26 (31%) were poor risk by R-IPI score. There were 58 patients with DLBCL alone at diagnosis who relapsed after achieving EFS24, and 38 (75%) relapsed with DLBCL, 13 (25%) relapsed with indolent lymphoma (predominantly follicular lymphoma), and pathology was unknown in 7 patients. In contrast, there were 26 patients with concurrent indolent lymphoma at diagnosis who relapsed after achieving EFS24, and 9 (41%) relapsed with DLBCL, 13 (59%) relapsed with indolent lymphoma, and pathology was unknown in 4 patients. In the 47 patients who relapsed with DLBCL after achieving EFS24, 45% received intensive salvage chemotherapy, 19% received regular intensity chemotherapy, 9% received CNS directed chemotherapy, and 36% went on to receive autologous stem cell transplant (ASCT). In the 26 patients who relapsed with indolent lymphoma after achieving EFS24, 27% were initially observed, 54% received regular intensity chemotherapy, 4% received intensive salvage chemotherapy, and 19% received ASCT after subsequent progression. The median post-relapse survival (PRS) for all patients with a relapse after achieving EFS24 was 38.0 months (95% CI 27.5-48.5). The median PRS for patients who relapsed with DLBCL and indolent lymphoma after achieving EFS24 were 29.9 (19.9-39.9) and 89.9 (NR-NR) months, respectively (P=0.002; Figure 2). Conclusions: Relapses after achieving EFS24 in patients with DLBCL were uncommon in the rituximab era. Patient with DLBCL alone at diagnosis can relapse with either DLBCL or indolent lymphoma (3:1 ratio). Patients with concurrent DLBCL and indolent lymphoma at diagnosis had a significantly higher CIR, and relapses with DLBCL and indolent lymphoma were similar (2:3 ratio). Even with high intensity salvage chemotherapy and consolidative ASCT, patients who relapsed with DLBCL had a significantly worse survival compared to those who relapsed with indolent lymphoma. Late relapses with DLBCL remain clinically challenging, with a median survival of 2.5 years after relapse. Figure 1. Figure 1. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Takeda: Research Funding; Pfizer: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Merck & Co: Research Funding; Bristol-Myers Squibb: Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

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