scholarly journals Baseline Metabolic Tumor Volume in 18FDG-PET-CT Scans in Classical Hodgkin Lymphoma Using Semi-Automatic Segmentation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4049-4049
Author(s):  
Julia Driessen ◽  
Gerben J.C. Zwezerijnen ◽  
Jakoba J Eertink ◽  
Marie José Kersten ◽  
Anton Hagenbeek ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Automatic Segmentation ◽  
Visual Quality ◽  
Metabolic Tumor Volume ◽  
Advisory Committees ◽  
18Fdg Pet ◽  
Pet Ct ◽  
Segmentation Methods

Introduction Baseline metabolic tumor volume (bMTV) is increasingly studied as a prognostic factor for classical Hodgkin lymphoma (cHL). Before implementation as a clinical prognostic marker, it is important to investigate different methods for deriving bMTV since not all methods are suitable for each type of malignancy. Semi-automatic segmentation is influenced less by observer bias and variability compared to manual segmentation and might therefore be more reliable for assessing bMTV. However, not much is known about the use of different semi-automatic segmentation methods and how this influences the prognostic value of bMTV in cHL. Here we present a comparison of bMTV derived with 6 semi-automatic segmentation methods. In addition, a visual quality scoring of all segmentations is performed to gain insight into which segmentation methods could be used to determine bMTV in cHL. Methods We selected 61 baseline 18FDG-PET-CT scans that met specific quality criteria (http://EARL.EANM.org) from patients treated in the Transplant BRaVE study for relapsed/refractory cHL [Blood 2018 132:2923]. Six semi-automatic segmentation methods were applied using the Accurate tool, an in-house developed software application which has already been validated in other types of cancer, including diffuse large B-cell lymphoma [Eur Radiol 2019 06178:9, J Nucl Med. 2018;59(suppl 1):1753]. We compared two fixed thresholds (SUV4.0 and SUV2.5), two relative thresholds (A50P: a contrast corrected 50% of standard uptake value (SUV) peak, and 41max: 41% of SUVmax), and 2 majority vote methods, MV2 and MV3 selecting delineations of ≥2 and ≥3 of previously mentioned methods, respectively. Quality of the segmentation was scored using visual quality scores (QS) by two reviewers (JD, GZ): QS-1 for complete selections containing all visible tumor localizations; QS-2 when segmentations 'flood' into regions with physiological FDG uptake; QS-3 when segmentations do not select all visible lesions; or QS-4: a combination of QS-2 and QS-3. In addition, the quality of the delineation was rated: QS-A for good visual delineation of lesions; QS-B for too small delineation; and QS-C for too large delineation. All segmentations that had score QS-2 or QS-4 were manually adapted by erasing regions that flooded into areas with high physiological uptake. Figure 1 shows examples of the quality scores. We used Spearman's correlations to compare the bMTV of all semi-automatic methods. Comparison of quality scores was performed using chi-square tests. Results The median bMTV differed substantially among the segmentation methods, ranging from 24 mL for SUV4.0 to 88 mL for 41max (Table 1). However, there was a high significant correlation (p <0.0001) between all methods with spearman coefficients ranging between 0.77 and 0.93 (Table 2). The quality of the segmentation was best using the SUV2.5 threshold with QS-1 in 64% of scans and delineation was best for MV3 with QS-A in 56% (Table 3). The segmentation quality was significantly better when less than 5 lesions were present on a scan. A large difference was observed for SUV2.5 with score QS-1 in 91% of cases for scans with <5 lesions (n=22), compared to QS-1 in 49% for scans containing ≥5 lesions (n=39) (p <0.001; Table 3). The delineation quality did not depend on the number of lesions. However, for SUV2.5, A50P and MV3, the delineation was considered better when the SUVmax of selected volumes of interest (VOI) was <10, while SUV4.0 performed significantly better with a SUVmax ≥10 (Table 3). Conclusions We found a good correlation between all methods, suggesting that the segmentation method used will probably not influence the predictive value of bMTV. Ease of use was highest with a semi-automatic segmentation of bMTV using the SUV2.5 segmentation method. SUV2.5 had the best visual quality and needed least manual adaptation. To investigate possible implementation of bMTV in clinical practice, we will validate the quality of the segmentation methods and the predictive value of bMTV in a larger cohort of patients with other prognostic parameters including quantitative radiomics analysis of baseline PET-scans. Disclosures Kersten: Bristol-Myers Squibb: Honoraria, Research Funding; Gilead: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria; Mundipharma: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Miltenyi: Honoraria; Takeda Oncology: Research Funding; Kite Pharma: Honoraria, Research Funding. Zijlstra:Janssen: Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Assessment of Total Lesion Glycolysis and Metabolic Tumor Volume Improve the Clinical Value of Focal Lesion Assessment By FDG PET/CT in Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 724-724
Author(s):  
James E McDonald ◽  
Marcus M Kessler ◽  
Michael Gardner ◽  
Amy Buros ◽  
Sarah Waheed ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Metabolic Tumor Volume ◽  
Total Lesion Glycolysis ◽  
University Of Arkansas ◽  
Medical Sciences ◽  
Focal Lesions ◽  
Advisory Committees ◽  
Pet Ct

Abstract Introduction: Focal lesions are important anatomical features seen in the bone marrow of multiple myeloma patients that contribute to drug resistance and disease relapse. Fluroine-18 fluorodexyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semi-quantitative characterization of metabolic activity by calculation of glucose uptake reported as a standardized uptake value (SUV). Lesion count and SUV are predictors of outcome. Two additional variables, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) can also be assessed and have the potential to improve the value of this approach. The purpose of this study was to determine whether TLG and MTV can predict progression free survival (PFS) and overall survival (OS), and to determine whether they are superior to traditional assessment methods. Materials and Methods: 191 patients underwent whole body PET/CT in the Total Therapy 3A trial and were evaluated using 3 dimensional region of interest analysis with TLG, MTV, and standard measurement parameters derived for all focal lesions with peak SUV above the background red marrow signal. Survival analysis was performed using Kaplan-Meier and log-rank tests. Univariate and multivariate analyses were performed using Cox proportional hazards regression. Results: Baseline characteristics show that 43/191 patients (23%) had no detectable lesions by PET. 1-3 lesions were present in 55/191 (28%) of patients and over 3 lesions in 93/191 (49%) of patients. A baseline TLG >205g was seen in 18% (34/191) of patients, with a TLG >620g being seen in 7% (14/191). A baseline MTV >210cm3 was seen in 7% (14/191). The distribution of patients with high TLG scores between molecular subgroups was not even with patients in the PR, MF and HY subgroups having higher scores. The 3 year PFS and OS for patients with no PET focal lesions was 83.1% and 88.3%, for patients with 1-3 lesions was 83.9%, and 85.5%, and for patients with >3 lesions 59.6% and 63.5% (p<0.0001). The 3 year PFS and OS for patients with a baseline TLG of less than 205g was 82.8% and 86.0%, compared to patients with a baseline TLG between 205g and 620g of 75.0% and 80.0%, and to patients with a baseline TLG of greater than 620g of 14.3% and 21.4% (p<0.0001). A similar pattern was seen for complete response (CR) duration. The MTV also had prognostic importance with 3 year PFS and OS for patients with a baseline MTV of less than 210cm3 at 81.4% and 84.7%, compared to patients with a baseline MTV of greater than 210cm3 of 21.4% and 28.6% (p<0.0001). Pearson Correlation Coefficient (r) between MTV and TLG was 0.94232 (p-value <.0001). On univariate analysis baseline PET/CT with >3 focal lesions (HR 1.92, 95% CI 1.22-3.04, p=0.004), TLG >205g (HR 2.99, 95% CI 1.83-4.88, p<0.0001), baseline TLG > 620g (HR 6.90, 95% CI 3.67-12.97, p<0.0001), and MTV >210cm3 (HR 6.20, 95% CI 3.33-11.54, p<0.0001) were statistically significant in predicting OS and PFS. In multivariate analysis baseline TLG>620g retained prognostic significance for predicting PFS and OS together with high B2M, LDH and GEP based proliferation. Importantly baseline TLG >620g and baseline MTV >210cm3 were statistically more predictive of poor PFS and OS than baseline PET with >3 focal lesions in both univariate and multivariate models. Conclusion : TLG assessment is superior to counting the number of focal lesions. It is the optimum method for evaluating the extent of focal lesions and to predict clinical outcome. As this measurement can be standardized using FDA approved software, it should be utilized clinically and in trials going forward. Disclosures McDonald: University of Arkansas for Medical Sciences: Employment. Waheed:University of Arkansas for Medical Sciences: Employment. Ntambi:University of Arkansas for Medical Sciences: Employment. van Rhee:University of Arkansa for Medical Sciences: Employment. Zangari:University of Arkansas for Medical Sciences: Employment; Novartis: Research Funding; Onyx: Research Funding; Millennium: Research Funding. Heuck:Janssen: Other: Advisory Board; Millenium: Other: Advisory Board; Foundation Medicine: Honoraria; Celgene: Consultancy; University of Arkansas for Medical Sciences: Employment. Petty:University of Arkansas for Medical Sciences: Employment. Schinke:University of Arkansas for Medical Sciences: Employment. Thanendrarajan:University of Arkansas for Medical Sciences: Employment. Mitchell:Cancer Research and Biostatistics: Employment. Hoering:Cancer Research and Biostatistics: Employment. Barlogie:International Workshop on Waldenström's Macroglobulinemia: Other: Travel Stipend; ComtecMed- World Congress on Controversies in Hematology: Other: Travel Stipend; European School of Haematology- International Conference on Multiple Myeloma: Other: Travel Stipend; Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Myeloma Health, LLC: Patents & Royalties: Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC; Dana Farber Cancer Institute: Other: Travel Stipend; Multiple Myeloma Research Foundation: Other: Travel Stipend. Morgan:Weisman Institute: Honoraria; CancerNet: Honoraria; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Davies:Array-Biopharma: Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; Onyx-Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

scholarly journals A HIGH VISUAL QUALITY SPRITE GENERATOR USING INTELLIGENT BLENDING WITHOUT SEGMENTATION MASKS

2006 ◽  
Vol 20 (08) ◽  
pp. 1139-1158 ◽  
Author(s):  
I-SHENG KUO ◽  
LING-HWEI CHEN
Keyword(s):  
Moving Objects ◽  
Automatic Segmentation ◽  
Visual Quality ◽  
Experimental Result ◽  
Feature Point Extraction ◽  
Comparison Results ◽  
Segmentation Methods ◽  
Wu Method ◽  
Better Than

The sprite generator introduced in MPEG-4 blends frames by averaging, which will make places, that are always occupied by moving objects, look blurred. Thus, providing segmented masks for moving objects is suggested. Several researchers have employed automatic segmentation methods to produce moving object masks. Based on these masks, they used a reliability-based blending strategy to generate sprites. Since perfect segmentation is impossible, some ghost-like shadows will appear in the generated sprite. To treat this problem, in this paper, an intelligent blending strategy without needing segmentation masks is proposed. It is based on the fact that for each point in the generated sprite, the corresponding pixels in most frames belong to background and only few belong to moving objects. A counting schema is provided to make only background points participate in average blending. The experimental result shows that the visual quality of the generated sprite using the proposed blending strategy is close to that using manually segmented masks and is better than that generated by Lu-Gao-Wu method. No ghostlike shadows are produced. Furthermore, a uniform feature point extraction method is proposed to increase the precision of global motion estimation, the effectiveness of this part is presented by showing the comparison results with other existing method.

Interim FDG PET Imaging in CALGB 50203 Trial of Stage I/II Non-Bulky Hodgkin Lymphoma: Would Using Combined PET and CT Criteria Better Predict Response Than Each Test Alone?,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3644-3644 ◽  
Author(s):  
Lale Kostakoglu ◽  
Heiko Schoder ◽  
Nathan Hall ◽  
David J. Straus ◽  
Jeffrey L Johnson ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Fdg Pet ◽  
Research Funding ◽  
Roc Analysis ◽  
Stage I ◽  
Advisory Committees ◽  
Interim Pet ◽  
Number Of Patients ◽  
Pet Ct

Abstract Abstract 3644 Use of interim PET in Hodgkin Lymphoma (HL) for risk-adapted treatment has been confounded by a lack of standardized criteria for interpretation. The International Harmonisation Project (IHP) criteria (JCO 2007;25:571) have been validated and are widely used for restaging following therapy. Our objective was to validate the IHP criteria for response evaluation based on PET after two cycles and correlate with the “London”criteria and diagnostic CT-based (dCT) lesion size changes. Methods: Pts were accrued prospectively to CALGB 50203, a trial of doxorubicin, vinblastine and gemcitabine (AVG) for initial treatment of stage I-II non-bulky Hodgkin lymphoma (HL). All had FDG PET or PET/CT and a separate high-resolution dCT scan at baseline, after two cycles of AVG (PET-2 and dCT-2) and at the end of therapy. No treatment change was made based on the PET-2 results. Of 99 assessable pts, 88 had both PET-2 and dCT-2. The primary PET-2 interpretation was based on IHP criteria (uptake > mediastinal blood pool/background is positive), a secondary interpretation was performed using the 5 point London criteria (uptake > liver is positive). The percent decrease in the sum of the products of the diameter (%SPPD) was determined between baseline dCT and dCT-2. A receiver operator curve (ROC) analysis was performed to determine the best cut-off for %SPPD to define a positive and negative CT result. The PET-2 and dCT-2 (%SPPD change) data were correlated with progression free survival (PFS). Results: Sixty-four pts (73%) achieved a complete remission (CR)/CR unconfirmed (CRu), 23.9% a partial response (PR), and 3% had stable disease. After a median follow-up of 3.3 years (1.8–5.0 years), 23.9% of patients relapsed/progressed with an estimated 3-year PFS of 0.77 [CI 68,84]. Eleven of 24 (45.8%) PET-2 positive patients relapsed vs. 10 of 64 (15.6%) PET-2 negative patients (p=0.0004). The best cut-off determined from ROC analysis for %SPPD change was 65%. The comparative results for individual evaluation criteria are displayed in the Table. In the PET-2 positive group, a negative dCT-2 increased PFS by 27–35%, suggesting an influence from dCT-2 results. However, in the combinatorial analysis, some of the confidence intervals are large due to small number of patients in each individual group, particularly, when both PET-2 and dCT-2 were positive as well as when PET-2 was positive and dCT-2 was negative. Conclusions: Interim PET/CT after two cycles of chemotherapy using either IHP or London criteria has a high NPV in early stage non-bulky HL. However, the PPV of interim PET needs to be improved to guide clinical management. Combining PET-2 with %SPPD decrease after 2 cycles improves prediction of PFS compared to each test alone. These data provide a proof of concept for risk-adapted clinical trials and further studies are underway to confirm these findings in a larger population. Disclosures: Bartlett: seattle genetics: Research Funding. Cheson:Celphalon: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celegen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Research Funding.

Evaluation of Health Related Questionnaire Among Mycosis Fungoides and Lymphomatoid Papulosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5603-5603 ◽  
Author(s):  
Rakhshandra Talpur ◽  
Iris Wieser ◽  
Casey Wang ◽  
Lyons Genevieve ◽  
Madeleine Duvic
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Mycosis Fungoides ◽  
Research Funding ◽  
Brentuximab Vedotin ◽  
Function Score ◽  
Advisory Committees ◽  
Significant Difference ◽  
And Function

Abstract INTRODUCTION AND OBJECTIVES: Mycosis Fungoides (MF) andlymphomatoid papulosis (LyP) are relatively rare and itchy skin disorders. The cosmetic disfigurement and severe pruritus dramatically affects the patient's quality of life. The focus is to examine the validity and reliability of the skindex-29, M.D. Anderson symptom inventory (MDASI) and itch-related quality of life (IQOL) questionnaire in 62 patients in a phase II trial of Brentuximab Vedotin. MATERIALS AND METHODS: Patients completed survey questionnaires related to symptoms and quality-of-life several times over the course of Brentuximab Vedotin. We compared patients' baseline scores to their end-of-study (EOS) scores. Patients were grouped by diagnosis into Mycosis Fungoides and Lymphomatoid papulosis group. Questionnaires included skindex-29, focusing on the skin conditions the patient was bothered the most. (MDASI) for patients with cancer and following the symptoms of cancer and the itchy quality of life (I-QoL) questionnaire was developed to measure the symptoms associated with cancer therapeutic agents and their effect on daily activities. Scoring for the Skindex-29, M. D. Anderson Symptom Inventory (MDASI) and the Quality of Life (QOL) survey were done according to the questionnaire specific scoring guide. Responses were compared between 2 groups using the Wilcoxon rank-sum test. RESULTS Questionnaires from 62 patients (23 LyP and 39 MF) were studied at baseline and end of study. Patients were 33 males and 29 females with median age of 60 years (range: 27-86 years). The median overall survival (OS) was significant P = 0.041, when comparing patients with MF to LyP. The median survival time for patients from time of diagnosis with MF was 14.66 years and LyP was not reached. There was no significant difference in progression free survival (PFS) between MF and LyP. The median number of Brentuximab Vedotin cycles was 7 (1-19). Skindex-29 scales, showed change in emotion scale and function scale from baseline to EOS, both groups had a decrease, patients with LyP had a larger decrease in emotion score (P = 0.069) and function score (P =0.096) over the course of the study. There was no difference in the symptom scale from baseline to EOS. The patients with LyP had a larger decrease in function score from baseline to EOS. When comparing patients with MF to those with LyP for MDASI, there is no evidence of a difference, from baseline to EOS, in either symptom severity or symptom interference in daily life. In the IQOL when comparing the LyP patients' QOL responses from baseline to EOS, did not show significant difference. Table 1. Change in Skindex-29 scales, by group Skindex Scale MF LYP p-value Change from baseline to end-of-study: N Median Min Max N Median Min Max Emotion 35 -10 -65 35 20 -22.50 -61.94 12.5 0.0698 Symptoms 35 -7.14 -46.43 42.86 20 -10.71 -53.57 28.57 0.4782 Function 35 -2.08 -50.38 27.08 20 -16.29 -44.70 14.58 0.0962 Table 2. Change in MDASI scales, by Diagnosis MDASI Scale Item MF LYP p-value Change from baseline to end-of-study: N Median Mean Std. Dev Range N Median Mean Std. Dev Range Severity 35 0.23 0.18 1.96 (-5.85, 3.15) 21 0.38 0.46 1.61 (-1.69, 5.0) 0.9595 Interference 35 0.17 0.06 3.07 (-9.17, 5.17) 19 0.0 0.11 1.59 (-3.0, 4.67) 0.6764 CONCLUSIONS A significant improvement in emotions and functional part of skindex-29 was observed when comparing patients with MF to patients with LyP. While both groups had a decrease, the patients with LyP had a larger decrease in emotion and function score over the course of the study. Disclosures Duvic: Celgene: Membership on an entity's Board of Directors or advisory committees; Rhizen Pharma: Research Funding; Allos (spectrum): Research Funding; Therakos: Research Funding, Speakers Bureau; Soligenics: Research Funding; Huya Bioscience Int'l: Consultancy; Spatz Foundation: Research Funding; MiRagen Therapeutics: Consultancy; Eisai: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncoceutics: Research Funding; Array Biopharma: Consultancy; Cell Medica Ltd: Consultancy; Tetralogics SHAPE: Research Funding; Innate Pharma: Research Funding; Kyowa Hakko Kirin, Co: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Assessment of Quality of Life in the NCRI Spirit 2 Study Comparing Imatinib with Dasatinib in Patients with Newly-Diagnosed Chronic Phase Chronic Myeloid Leukaemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4024-4024 ◽  
Author(s):  
Alexander M. Labeit ◽  
Mhairi Copland ◽  
Leanne M. Cork ◽  
Corinne A. Hedgley ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Research Funding ◽  
Chronic Phase ◽  
Well Being ◽  
First Line ◽  
Advisory Committees ◽  
Significant Difference ◽  
Over Time

Abstract Background: Imatinib and dasatinib are established drugs in the first-line treatment of chronic myeloid leukemia (CML). Several studies, including SPIRIT2 have shown that first-line dasatinib (100mg once daily) has a superior complete cytogenetic and major molecular response rate compared to imatinib (400mg once daily), but no significant differences in progression-free or overall survival have been shown in any study. To date, there has been no direct comparison of quality of life (QoL) using generic and cancer-specific instruments for first-line treatment of chronic-phase CML with imatinib and dasatinib. SPIRIT2 (STI571 Prospective International Randomised Trial 2) is the first randomized clinical trial to incorporates generic and cancer-specific QoL measurement for first-line therapy. Methods: Quality of life is a secondary endpoint in the SPIRIT2 trial and has been assessed at baseline, and at 1, 2, 3, 6 and 12 months post trial entry and thereafter annually. The EQ-5D, FACT-G, FACT-BRM and the FACT-TOI have been used as QoL measures in this trial. The FACT-G covers cancer-specific QoL measure dimensions such as physical well-being, functional well-being, social and family well-being, emotional well-being and the FACT-BRM and the FACT-TOI different subsets of them. The QoL scores (EQ-5D, FACT-G, FACT-BRM, FACT-TOI) were calculated at different time points and comparison of the mean scores for both treatment groups was made. Results: A comparison between imatinib and dasatinib shows no significant difference in QoL in generic instruments and also in cancer-specific instruments. EQ-5D was 0.77 and 0.79 at baseline and 0.80 and 0.82 at one year for dasatinib and imatinib, respectively (2-3 basis points increase over 1 year). Similar results were obtained for the FACT-G, FACT-BRM and the FACT-TOI. There was a slight increase for the FACT-G (4-5 basis points), FACT-TOI (3-4 basis points) and FACT-BRM (8-10 basis points) after 1 year for both treatments, but this difference was not significant. The effects on the well-being and the emotional dimensions have been analysed for both drugs and there was no change over time, demonstrating results similar to the imatinib arm of the IRIS trial. Conclusions: Standard dose imatinib and dasatinib are both used as first-line treatments for CML and, despite different side effect profiles, there is no significant difference in QoL using the instruments described here between these two drugs over time. These data will allow the derivation of utility values to contribute to future health economic/technology appraisals. Additional analyses of how generic and cancer-specific measures of different QoL instruments change in CML patients over time in those patients that develop side effects, e.g. fluid retention with imatinib or pleural effusion with dasatinib will be presented. Disclosures Copland: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cork:BMS: Research Funding; Novartis: Research Funding; Roche: Research Funding; Ariad: Research Funding. Hedgley:Ariad: Research Funding; Roche: Research Funding; BMS: Research Funding; Novartis: Research Funding. Gills:Novartis: Research Funding; Ariad: Research Funding; BMS: Research Funding; Roche: Research Funding. Holyoake:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Bescoby:Roche: Research Funding; Ariad: Research Funding; BMS: Research Funding; Novartis: Research Funding. Pocock:Janssen: Honoraria. Clark:Novartis: Honoraria, Research Funding, Speakers Bureau; Pzifer: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding. O'Brien:Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Pzifer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding.

scholarly journals Health-Related Quality of Life in a Biologic Assignment Trial of Reduced Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 421-421
Author(s):  
Rachel Cusatis ◽  
Michael Martens ◽  
Ryotaro Nakamura ◽  
Corey Cutler ◽  
Wael Saber ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Health Related Quality ◽  
Advisory Committees ◽  
No Donor ◽  
Free Survival ◽  
Related Quality ◽  
Health Related

Abstract Introduction The Blood and Marrow Transplant Clinical Trials Network study (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial in older adults aged 50-75 with higher risk de novo MDS (IPSS Intermediate-2 or High) who were candidates for reduced-intensity conditioning (RIC) allogeneic HCT. The trial compared outcomes of those with a suitable HLA-identical sibling or unrelated donor (Donor arm) to those where no donor was identified (No Donor arm) within a search window of 90 days. The trial reported a survival benefit for patients in the Donor arm compared to the No Donor arm [Nakamura et al, JCO 2021, in press]. Here, we compare the health-related quality of life (QOL) for patients between the two arms through 36 months after enrollment. We also describe the predictors and trajectories of QOL. Methods English and Spanish-speaking subjects were invited to complete patient-reported outcome (PRO) measures, including the Functional Assessment of Cancer Therapy - General (FACT-G), the SF-36 yielding a Physical Component Score (PCS) and Mental Component Score (MCS), and the EQ-5D, at enrollment and every 6 months until 24 months, then 36 months after enrollment. Validation studies indicate a clinically meaningful difference of 5 points for FACT-G, PCS, and MCS and 2 points for associated subscales. To account for the missingness of assessments, including those missing due to death, we compared each score between arms using an inverse probability weighted - independent estimating equation (IPW-IEE) model, which models the scores in surviving patients while using IPW to account for baseline variables and follow-up outcomes that impact the likelihood of missingness. Since 4 scores were evaluated, a Bonferroni corrected significance level of 1.25% = 5% / 4 was used. Cox regression models were used to evaluate the impact of QOL measures on overall and leukemia free survival. The IPW-IEE models adjust for baseline score and follow-up assessment time as well as age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy; the Cox models adjusted for the 6 latter variables and treatment arm. Trajectories of QOL are shown by plotting mean +/- standard error by group over time. Results Between January 2014 and November 2018, 384 subjects (median age 66.7 years, range: 50.1-75.3) were enrolled at 34 centers and biologically assigned to Donor (n=261) or No Donor arm (n=123) by 90 days from enrollment. For the Donor arm the median duration from registration to HCT was 3.9 months (range 0.3-20.7). Completion rates were generally high at 65-78% of eligible survivors at each timepoint. At enrollment, 204 subjects (78.2%) in the Donor arm and 85 subjects (69.1%) in the No Donor arm completed at least one QOL form, with 4 patients unable to complete due to language (non-English or Spanish speaking). While there were some small differences at 18 months favoring the Donor arm, no clinically significant differences in PRO scores or subscales were seen between the arms at any timepoint (Figure 1) or in the scores over time. In general, similar trajectories for the Donor arm were seen for each PRO, with most decreasing or stable from baseline to 6 months and improving thereafter. Compared to published averages of U.S cancer populations, FACT-G means in both arms were higher beginning at 18 months. Baseline and 6-month PRO scores were the strongest predictors of later PRO scores despite adjusting for patient demographic and clinical factors. Overall survival was predicted by baseline FACT-G &lt;70 (HR=1.61, p&lt;.01) and PCS scores &lt;40 (HR=1.82, p&lt;0.001), while leukemia-free survival was predicted by baseline FACT-G &lt;70 (HR=1.61, p&lt;0.01) and PCS &lt;40 (HR=1.80, p&lt;0.002). No associations of PROs with AML transformation, relapse, or acute or chronic GVHD were found. Non-compliance with biologic assignment was less likely in Donor arm compared to No Donor, but baseline QOL was not a confounding factor. Conclusion In older adults with MDS, the survival advantage associated with Donor availability and HCT does not come at the cost of worse QOL in comparison to the No Donor arm. Baseline PRO scores were the strongest independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors. These results should reassure older patients and clinicians who prefer curative approaches to MDS. Figure 1 Figure 1. Disclosures Cutler: Mallinckrodt: Consultancy; Editas: Consultancy; CareDx: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; Cimeio: Consultancy; Deciphera: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Jazz: Consultancy. Saber: Govt. COI: Other. Lee: Takeda: Research Funding; Syndax: Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kadmon: Research Funding; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Janssen: Other; Incyte: Research Funding; AstraZeneca: Research Funding; Amgen: Research Funding. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy. Horowitz: Magenta: Consultancy, Research Funding; Astellas: Research Funding; Jazz Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Research Funding; CSL Behring: Research Funding; Gamida Cell: Research Funding; Allovir: Consultancy; Daiicho Sankyo: Research Funding; Amgen: Research Funding; bluebird bio: Research Funding; Chimerix: Research Funding; Actinium: Research Funding; Medac: Research Funding; Kiadis: Research Funding; Xenikos: Research Funding; Vor Biopharma: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Pharmacyclics: Research Funding; Pfizer, Inc: Research Funding; Orca Biosystems: Research Funding; Omeros: Research Funding; Novartis: Research Funding; Miltenyi Biotech: Research Funding; Mesoblast: Research Funding; Kite/Gilead: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding; Shire: Research Funding; Sobi: Research Funding; Stemcyte: Research Funding; Takeda: Research Funding; Tscan: Research Funding; Vertex: Research Funding.

scholarly journals A Phase II Study of Sequential Pembrolizumab (PEM) Followed By AVD for Frontline Treatment of Classical Hodgkin Lymphoma (CHL): Quantifying Response Following PEM Monotherapy with FDG-PET-Derived Metabolic Tumor Volume and Total Lesion Glycolysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1651-1651 ◽  
Author(s):  
Hatice Savas ◽  
Pamela Allen ◽  
Andrew M. Evens ◽  
Barbara Pro ◽  
Gary Dillehay ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Early Stage ◽  
Residual Activity ◽  
Metabolic Tumor Volume ◽  
Institutional Research ◽  
Research Support ◽  
Advisory Committees ◽  
Early Stage Disease ◽  
Advisory Role

Abstract Background: Pembrolizumab (PEM), a PD-1 inhibitor, is US FDA approved for the treatment of relapsed/refractory cHL based on results of a pivotal trial demonstrating an overall response rate of 69% and complete response (CR) rate of 22%. We hypothesized that PEM monotherapy would result in a higher CR rate (50%) in previously untreated patients owing to greater immunocompetence. Consequently, we initiated a phase 2 clinical trial of upfront sequential PEM and AVD (Adriamycin, Vinblastine, Dacarbazine) chemotherapy. While several of the initial patients had dramatic responses to PEM x's 3 on PET2, they only met Lugano criteria for partial responses. In an attempt to better reflect and quantify the response to checkpoint inhibition, we amended our protocol to include additional analysis of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) which have been investigated as predictors of response in cHL and DLBCL. Herein, we report an interim analysis of toxicity and efficacy, measured by Deauville score, MTV and TLG in the first 13 patients to complete PEM monotherapy. Methods: Patients ≥ 18 years of age with newly diagnosed cHL stages I-IV, including unfavorable early stage disease with at least one risk factor according to the NCCN criteria, were eligible. Patients had a pre-therapy PET-CT, followed by 3 cycles of PEM at 200 mg every 3 weeks and interim PET-CT (PET2) after single agent PEM for primary analysis. Subsequently, patients received 4-6 cycles of AVD chemotherapy based on initial stage. MTV representing the total volume of the metabolically active tumor in a volume of interest (VOI) was calculated using the fixed 41% SUVmax threshold corresponding to the dimensions of the tumor. TLG, combining the volumetric and metabolic information of FDG-PET, was calculated by multiplying the SUVmean of the segmented VOI and the MTV. These measurements were performed using SyngoVia software, Multi-foci segmentation tool (Siemens). Blinded central review of the visually assessed Deauville score was performed, and if different from the report by one of four nuclear medicine radiologists, a second central review was performed to adjudicate. Correlative studies include serum and biopsy samples pre/post PEM to assess immune biomarkers of response. Results: Fifteen patients were enrolled from September 2017, through a data cut off of July 10, 2018, at Northwestern University. Thirteen patients have completed lead-in PEM monotherapy and have undergone PET2. Median age was 30 years (range, 23-77). Eight patients had unfavorable early stage disease and 7 had advanced stage. Early stage risk factors included bulky disease (n=8), B-symptoms (n=5), and elevated ESR (n=5). Overall, therapy was well tolerated. Grade 3 events included lymphopenia (n=1) and diarrhea (n=1). Only one grade 4 immune-related adverse event (transaminitis) occurred, which resolved with steroid therapy and a delay in therapy. PET2 was scored as Deauville 2 or 3 in six cases including three with large mediastinal masses, and as D 4 or 5 in 7 cases with residual activity (Figure 1). PET2 MTV and TLG could be calculated for 12 of 13 cases, (MTV: 42 - 774 cm2, median 134 cm2; TLG: 257 - 5924; median 814). All 12 patients who completed a subsequent scan (PET3) after 2 cycles of AVD are now in a metabolic CR (Deauville 1-3), including all 7 cases with residual activity after PET2. Conclusion: These interim data suggest that upfront PEM x's 3 is highly active in previously untreated cHL. PEM monotherapy resulted in complete metabolic responses in some patients including those with large mediastinal masses, and near complete responses, best represented by the decline in MTV and TLG compared with Deauville scores or Lugano criteria. Our preliminary data suggest that MTV and TLG are useful additional interim indicators of biologic activity when assessing response after PD-1 inhibitor therapy. Disclosures Allen: Merck: Research Funding; Bayer: Consultancy. Evens:Bayer: Consultancy; Janssen: Consultancy; Affimed: Consultancy; Novartis: Consultancy; Tesaro: Research Funding; Abbvie: Consultancy; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy; Pharmacyclics International DMC: Membership on an entity's Board of Directors or advisory committees. Pro:kiowa: Honoraria; Takeda Pharmaceuticals: Honoraria, Other: Travel expenses; portola: Honoraria; Seattle Genetics: Consultancy, Other: Travel expenses, Research Funding. Advani:Millenium: Other: Institutional Research Support; Merck: Other: Institutional Research Support; Kura: Other: Institutional Research Support; Agensys: Other: Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Pharmacyclics: Other: Institutional Research Support; Cell Medica: Other: Consultancy/Advisory Role; Kyowa: Other: Consulting/Advisory Role; Janssen Pharmaceutical: Other: Institutional Research Support; Autolus: Other: Consultancy/Advisory Role; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support; Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; AstraZeneca: Other: Consultancy/Advisory Role; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Forty Seven, Inc: Other: Institutional Research Support; Celgene: Other: Institutional Research Support; Gilead/Kite: Other: Consultancy/Advisory Role; Infinity: Other: Institutional Research Support. Winter:Merck: Honoraria, Research Funding.

scholarly journals Use of Metabolic Tumor Volume (MTV) in Patients with Mantle Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5321-5321
Author(s):  
Daniel M Guidot ◽  
Ila Sethi ◽  
Jeffrey Switchenko ◽  
Daniel Lee ◽  
Loretta J. Nastoupil ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Post Transplant ◽  
Deauville Score ◽  
Pet Ct ◽  
Pre Treatment ◽  
Active Disease

Abstract Introduction Positron emission tomography/Computed tomography (PET/CT) imaging is utilized for initial staging and response assessment in aggressive non-Hodgkin lymphoma (NHL) but has been less useful for prognostic assessment. Metabolic tumor volume (MTV) is an objective measure calculated from PET/CT imaging that calculates the volume of active disease burden with demonstrated value in some forms of NHL. In particular, interim MTV has been shown to predict progression-free survival (PFS) in diffuse large B cell lymphoma (Yang et al. Annals of Hematology 2013) and in peripheral T-cell lymphoma (Jung et al. BMC Cancer 2015). We evaluated the prognostic impact of MTV in mantle cell lymphoma (MCL). Methods Patients with MCL who underwent autologous stem cell transplant (ASCT) in first remission at Emory who had available pre-treatment, post-induction/pre-transplant, or post-transplant PET/CT's were included. Basic demographic information and key clinical data were collected for each patient. MIM software was used to calculate MTV for all areas of active disease with a cut-off of SUV 4. Two additional predictors collected were Deauville score and total lesion glycolysis (TLG). Deauville score is a categorical scale from 1-5 assigned by a radiologist to estimate severity of disease frequently used in aggressive NHL and was calculated in all post-treatment studies. Zero was assigned for cases where incidental findings prevented application of the Deauville criteria but final impression was no active disease. TLG is a calculation of the total quantity of FDG consumed by the area of active disease. All images were reviewed by a nuclear medicine physician to assist with MTV/TLG assessment and to determine the Deauville score. Pre-treatment, pre-transplant, and post-transplant MTV were tested as independent predictors of overall survival (OS) and progression-free survival (PFS) using Cox proportional hazards models. Demographic and clinical variables were tested as well as Deauville score and TLG by the same means Results Forty patients with a combined total of 19 pre-treatment, 30 pre-transplant, and 30 post-transplant PET/CT scans were identified. Mean age at diagnosis was 58.9 (range 32-81), and 94.3% had stage III/IV disease. Mean MTV pre-treatment was 268 (range 0-3454). Following induction/pre-transplantation, 26 patients (87%) had MTV of 0 and 22 patients (73%) had Deauville score 0/1. Post-transplantation, 28 patients (93%) had MTV of 0 and 25 patients (83%) had Deauville score 0/1. Among demographic and clinical factors (Table 1 and 2), PFS was significantly associated with splenomegaly (HR = 3.87, p = 0.033), any lymph node >5cm (HR = 5.25, p = 0.003), and any lymph node >10cm (HR = 4.52, p = 0.041). OS was associated with age at diagnosis (HR = 0.88, p = 0.005). No particular cutoff value for pre-treatment MTV was found to define a statistically significant predictor of OS or PFS. Similarly, baseline TLG was not associated with PFS or OS. OS was significantly associated with post-transplant MTV (p = 0.043), post-transplant TLG (p = 0.043), and post-transplant Deauville score (p = 0.006). PFS was significantly associated with post-transplant Deauville score only (p < 0.001). Conclusions Study results give limited evidence that PET/CT images have predictive value for MCL patients post-transplant. MTV and TLG were 0 in 93% of post-transplant images, and Deauville was 0/1 in 83%. Still, post-transplant MTV, TLG, and Deauville score were associated with OS, and Deauville score was associated with PFS. While this study shows potential value in PET/CT images for MCL patients in the post-transplant period, it does not support the use of MTV or TLG over Deauville score. Disclosures Flowers: Millenium/Takeda: Research Funding; Roche: Consultancy, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; TG Therapeutics: Research Funding; Mayo Clinic: Research Funding; ECOG: Research Funding; AbbVie: Research Funding; Genentech: Consultancy, Research Funding; Infinity: Research Funding; Acerta: Research Funding; NIH: Research Funding; Gilead: Consultancy, Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Quality of Life and Caregiver Burden in Patients and Their Caregivers Undergoing Outpatient Autologous Stem Cell Transplantation Compared to Inpatient Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 62-62
Author(s):  
Vinita Dhir ◽  
Lara Zibdawi ◽  
Harminder K Paul ◽  
Osvaldo Espin-Garcia ◽  
Christine I Chen ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Research Funding ◽  
Indirect Costs ◽  
Opportunity Costs ◽  
Advisory Committees ◽  
Significant Difference ◽  
Lost Opportunity ◽  
Out Of Pocket Costs

Introduction Outpatient autologous stem cell transplantation (ASCT) has become standard of care in many centres due to limited inpatient resources and rising financial constraints. Outpatient ASCT involves family members/friends assuming some patient care responsibilities during the acute transplant period. Although this may be associated with reduced direct medical costs, little work has been done to ascertain the "out of pocket costs" and "lost opportunity costs" to patients and their caregivers. Outpatient transplantation is perceived to provide superior quality of life (QOL) for patients, but there is little evidence to support this. In addition to patients' QOL, there is limited data on the impact of these treatments on caregivers' QOL. Thus, our objectives were to compare the QOL of patients and their caregivers undergoing outpatient and inpatient ASCT, and to quantify indirect costs to them. Methods This is a single centre cohort study of consecutive patients with lymphoma and plasma cell disorders undergoing ASCT at Princess Margaret Cancer Centre from April 2016 - July 2019. Patients without a primary caregiver were still eligible to complete the QOL portion of the study. All patients completed four questionnaires: Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT); FACT-Fatigue (FACT-F); EQ-5D-3L; and a distress impact thermometer. Clinically meaningful differences between the groups and serially were defined as ≥ 4 points on the FACT-BMT and FACT-F, and ≥0.08 on the EQ-5D-3L. Caregivers completed three questionnaires: Caregiver Quality of Life Index-Care (C-QOLC), a distress impact thermometer, and a caregiver self-administered financial expenditure survey (C-SAFE). Indirect costs were defined as lost opportunity costs (i.e., wages) and out-of-pocket costs (e.g., parking, accommodations). Questionnaires were completed at 5 time points: D0 (prior to ASCT), D+7, D+14 (discharge from daily visits), D+28 (discharge from ASCT) and D+100 (follow-up). Results In total, 68 patients have been enrolled to date (41 outpatients and 27 inpatients), and 54 caregivers (38 outpatients and 16 inpatients). Median patient age was 57 yrs (range: 18-71), and 66% were male. Of the 68 patients, 69% had a diagnosis of multiple myeloma and 31% lymphoma. Majority of caregivers were spouses (74%). In the overall sample, FACT-F scores (fatigue) increased significantly at D+7, D+14, and D+28, with improvement at D+100 (all p&lt;0.05 and clinically meaningful). Compared to inpatients, outpatients had higher fatigue levels at D+7 and D+14 that were statistically significant (Figure 1), with D+14 being clinically significant as well. For all patients, QOL scores by FACT-BMT declined at D+7, but then improved to above baseline values at D+100 (p&lt;0.05) (Table 1). On the EQ-5D-3L, patients' self-reported overall best imaginable health status decreased at D+7 and D+14 relative to baseline (p&lt;0.05); no significant difference was observed at D+28 and D+100 (Figure 1). Health utility scores were also calculated from the EQ-5D-3L. There were no significant trends in the overall sample, but when comparing the two groups, outpatients had lower measures at D+14 that were statistically and clinically relevant. With respect to caregiver QOL, in the entire sample, QOL was higher at D+100 relative to baseline (p&lt;0.05) (Figure 2). There were no differences between the two groups. In addition, there was no statistically significant difference in lost opportunity costs (wages) between the two groups, however there was a trend towards higher lost opportunity costs in outpatient caregivers in the early ASCT process (D0, D+7, D+14). The mean overall costs (burden) for the primary caregiver in the acute first 100d phase of ASCT was C$4475. The indirect out-of-pocket costs by caregivers varied greatly, with an average of $58 at baseline (range $0-455) and $121 at D+28 (range $0-710). Conclusions There was significant deterioration of various QOL measures in all patients, irrespective of outpatient or inpatient status. Outpatients, however, reported significantly higher fatigue levels at D+7 and D+14. Caregiver QOL appears comparable between the two modalities, and appears to improve significantly by the follow-up period. The financial burden on caregivers, mostly driven by lost opportunity costs (wages), is high, with a trend towards higher burden in outpatient caregivers in the early parts of ASCT. Disclosures Chen: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria. Kridel:Gilead Sciences: Research Funding. Kukreti:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Kuruvilla:Celgene: Honoraria; Astra Zeneca: Honoraria; Seattle Genetics: Consultancy; Amgen: Honoraria; Roche: Consultancy; Karyopharm: Consultancy; Gilead: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Roche: Research Funding; Janssen: Research Funding; Merck: Consultancy; Gilead: Honoraria; BMS: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria; Roche: Honoraria; Seattle Genetics: Honoraria; Novartis: Honoraria; Merck: Honoraria. Reece:Otsuka: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Research Funding. Tiedemann:Amgen: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Celgene: Honoraria; BMS: Honoraria; Janssen: Honoraria. Trudel:Pfizer: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria; Janssen: Honoraria, Research Funding; Astellas: Research Funding; Genentech: Research Funding; Sanofi: Honoraria. Prica:Janssen: Honoraria; Celgene: Honoraria.

scholarly journals A New Simplified Prognostic Index Integrating the Type of Extra-Nodal Involvement and Age for Ann Arbor Stage IV Hodgkin Lymphoma Patients Diagnosed at TEP-Scanner Era: A Retrospective Analysis from Lymphoma Study Association (LYSA) Centers

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1629-1629
Author(s):  
Camille Golfier ◽  
Delphine Maucort-Boulch ◽  
Emmanuelle Nicolas-Virelizier ◽  
Cedric Rossi ◽  
Pierre Sesques ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Research Funding ◽  
Univariate Analysis ◽  
Prognostic Index ◽  
Stage Iv ◽  
Advisory Board ◽  
Liver Involvement ◽  
Advisory Committees ◽  
Pet Ct

Abstract Purpose International Prognostic Index (IPS) is the most widely used risk stratification index for advanced stage Hodgkin's lymphoma (HL). The use of (18F)-fluorodeoxyglucose PET/CT at diagnosis allows a better characterization of extra-nodal involvement (ENI). We investigated if the type of ENI could affect the prognosis of stage IV HL patients diagnosed with PET/CT and if a specific prognostic index could be defined for these patients (pts). Patients and methods We retrospectively analyzed 220 stage IV HL patients treated from 2005 to 2015 in three LYSA centers. We considered the local investigator interpretation based on the nuclear medicine physician PET/CT report. Regarding ENI, six subgroups were identified: involvement of lung and/or pericard and/or pleural, liver, diffuse and/or focal bone involvement, digestive system, and other involvements; we also considered bone marrow involvement based on the results of bone marrow biopsy. The main outcome was event free survival (EFS) defined by relapse, progression, death from any cause and initiation of a new therapy. For prognostication, we first evaluated the six variables of IPS-6 (corresponding to IPS without "stage IV" item) in this population. ENI was tested adjusted on the retained IPS variables. Univariate and multivariate Cox models were used to assess their prognostic ability for EFS. Cross-validation (10-fold) was used to select the more robust variables avoiding optimism. The finally selected variables constituted a score that was tested on overall survival (OS). Results Among the 220 stage IV patients, 135 (61%) were male. Median age was 33 years (range, 16-86) and 72 pts (33%) were ≥45 years. 130 pts (59%) presented constitutional symptoms. Nodular sclerosis subtype was observed in 163 pts (74%), mixed cellularity subtype in 25 pts (11%) and 47/157 pts (30%) presented EBV-positive HL. For biological parameters of IPS, 158 pts (80%) had low albumin level <4g/dL, 66 pts (30%) hemoglobin values <10.5g/dL, white blood cell (WBC) count was >15G/L in 42pts (19%) and lymphocyte count <600/mm3 in 75 pts (34%). The IPS-6 score was 0-2 in 93 pts (47%) and ≥3 in 104 pts (53%). ENI distribution according to PET/CT was: diffuse and/or focal bone involvement (155 pts, 71%), lung-pericard-pleural (94 pts, 43%), liver (37pts, 17%), digestive system (11 pts, 5%), 38 pts (17%) had other ENI; bone marrow involvement according to biopsy concerned 40 pts (21%). Only 1 extra-nodal site was involved in 49% of pts, 2 sites in 33%, 3 sites in 16% and 4 sites in 2%. With a median follow-up of 4.8 years, the 5-year EFS and OS rates were 73% and 89.9%, respectively for the whole cohort. The IPS-6 remained a strong prognostic index in our cohort. Patients with an IPS-0-2 and 3-6 had a 5-year EFS rate of 81.8% and 64% (p=0.008), respectively. The evaluation in univariate analysis of the prognostic value of each individual variable of IPS showed that only age influenced EFS (p=0.002) but albumin level (p=0.92), hemoglobin level (p=0.28), lymphocyte count (p=0.16), WBC count (p=0.10) and sex (p=0.21) had no significant prognostic effect. Regarding ENI, all 6 subgroups were studied: liver involvement was the only extra-nodal site with prognostic impact (HR=1.67 [0.92-3.04], p=0.093) in univariate analysis. We then performed a multivariate analysis integrating age and liver involvement: age was significantly associated with EFS (HR=2.20 [1.32-3.65], p=0.002); liver involvement also presented an influence on EFS (HR=1.72 [0.94-3.13], p=0.076). Thus, we developed a prognostic index with these two variables that defined two distinct risk groups: low risk (age <45 years or no liver involvement, N=206 pts, 94%) and high risk (age ≥45 years and liver involvement, N=14 pts, 6%) (HR=5.09 [2.64-9.85], p<10-3). 5-year EFS rates were respectively 76.8% and 17.9% (Figure 1A). This model also influenced OS with a 5-year OS rate of 91.8% and 61.4% for low and high risk groups, respectively (Figure 1B). Conclusions: For stage IV HL defined by PET/CT, we developed a simple prognostic score based on age (≥45y) and liver involvement that identify a subgroup of patients with a poor outcome. These findings need to be validated in independent cohorts. Based on these results, whether HL pathogenesis differs by ENI sites should be investigated. Disclosures Bachy: Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Amgen: Honoraria. Karlin:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Sarkozy:ROCHE: Consultancy. Traverse-Glehen:Takeda: Research Funding; Astra Zeneca: Other: Travel. Salles:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Servier: Honoraria, Other: Advisory Board; Novartis: Consultancy, Honoraria; BMS: Honoraria, Other: Advisory Board; Morphosys: Honoraria; Janssen: Honoraria, Other: Advisory Board; Abbvie: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Other: Advisory Board, Research Funding; Epizyme: Honoraria; Gilead: Honoraria, Other: Advisory Board; Acerta: Honoraria; Merck: Honoraria; Servier: Honoraria; Takeda: Honoraria. Casasnovas:Takeda: Consultancy; Gilead: Consultancy, Research Funding; AbbVie: Consultancy; Roche: Consultancy, Research Funding; Bristol-Meyers Squibb: Consultancy; Merck: Consultancy. Ghesquieres:Celgene: Consultancy; Gilead: Consultancy; Sanofi: Consultancy.

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