The Role of Texture Analysis and Radiomics in Prediction of Bone Marrow Infiltration in Patients with Lymphoma

Abstract Background: T lymphoblastic leukemia/lymphoma (T-LBL) is highly aggressive. Although intensive chemotherapies such as acute lymphoblastic leukemia (ALL)-type regimens are commonly used, about half adult patients eventually relapse and die of T-LBL. Overwhelming evidences have confirmed the role of interim F-18 FDG PET/CT in Hodgkin lymphoma and many ongoing studies have implemented risk-adapted strategy determined by interim FDG-PET/CT. However, the role of interim FDG-PET/CT in T-LBL remains unclear. Materials and methods: 47 adult patients of T-LBL treated with ALL-like regimens were retrospectively reviewed. They were treated with modified Berlin-Frankfurt-Münster (BFM)-90 regimen (n=27), Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 regimen (n=5), hyperCVAD/MA regimen (n=12), or other unspecified regimens (n=3). Interim (defined as the period between induction therapy and re-induction therapy) FDG-PET/CT was done in all 47 patients and evaluated according to the International Harmonization Project (IHP) criteria. Results: The male to female ratio was 3:1, and 29.8% of patients were older than 30 years old. About 90% of patients had mediastinal mass at presentation and 53.2% had bone marrow infiltration. 85.1% of patients had advanced disease. After induction therapy, interim FDG-PET/CT was positive in 19 patients (40.4%), most of whom had residual disease in the mediastinal lesion. Subsequent treatments were not changed according to this interim PET/CT results. After a median follow up time of 28 months, the 2-year and 3-year progression free survival (PFS) rate were 39% and 30%, respectively, and the 2-year and 3-year overall survival (OS) rate were 54% and 45%, respectively. Using Kaplan-Meier survival analysis and log-rank test, it was found that interim FDG-PET/CT positivity correlated with significantly inferior PFS and OS (p=0.002 and 0.010, respectively). Furthermore, patients with higher age (>30) had inferior PFS and OS than younger patients (p=0.037 and 0.036, respectively). However, there were no significant relationship between PFS, OS and bone marrow infiltration, LDH level, and stages (p>0.05). Conclusions: Interim FDG-PET/CT may predict PFS and OS in adult patients of T-LBL treated with ALL-type regimens, which needs to be validated in prospective clinical trials. The optimal criteria for interim FDG-PET/CT evaluation and risk-adapted treatment strategy determined by interim FDG-PET/CT should be investigated in future clinical practice. Disclosures No relevant conflicts of interest to declare.

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Role of Bone Marrow Infiltration Detected by Sensitive Methods in Patients with Localized Neuroblastoma

Pediatric Cancer - Neuroblastoma ◽

10.1007/978-94-007-2418-1_24 ◽

2011 ◽

pp. 237-245

Author(s):

Maria Valeria Corrias

Keyword(s):

Bone Marrow ◽

Bone Marrow Infiltration ◽

Localized Neuroblastoma

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Bone Marrow Infiltration in Neuroblastoma: Characteristics of Infiltrating Cells and Role of the Microenvironment

Neuroblastoma ◽

10.5772/55774 ◽

2013 ◽

Author(s):

Fabio Morandi ◽

Paola Scaruffi ◽

Sara Stigliani ◽

Barbara Carlini ◽

Maria Valeria

Keyword(s):

Bone Marrow ◽

Bone Marrow Infiltration ◽

Infiltrating Cells

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Role of computed tomography texture analysis using dual-energy-based bone marrow imaging for multiple myeloma characterization: comparison with histology and established serologic parameters

European Radiology ◽

10.1007/s00330-020-07320-8 ◽

2020 ◽

Author(s):

Christian Philipp Reinert ◽

Eva Krieg ◽

Michael Esser ◽

Konstantin Nikolaou ◽

Hans Bösmüller ◽

...

Keyword(s):

Bone Marrow ◽

Texture Analysis ◽

Dual Energy ◽

Bone Marrow Infiltration ◽

Whole Body ◽

Imaging Biomarkers ◽

Textural Features ◽

Bone Marrow Biopsies ◽

Non Invasive ◽

Additional Imaging

Abstract Objective To identify textural features on dual-energy CT (DECT)–based bone marrow images in myeloma which correlate with serum markers of myeloma activity and the degree of medullary involvement. Methods A total of 110 patients (63.0 ± 11.0 years, 51 female) who underwent unenhanced whole-body DECT between September 2015 and February 2019 were retrospectively included, which was approved by our institutional ethics committee with a waiver of the informed consent requirement. All patients had current hematologic laboratory tests. Using DECT post-processing, non-calcium bone marrow images were reconstructed. The vertebral bodies T10–L5 were segmented for quantification of textural features, which were compared with serologic parameters and myeloma stages by the Mann-Whitney U test. In a subgroup of 56/110 patients with current bone marrow biopsies, textural features were correlated with the degree of bone marrow infiltration. Results First-order features were higher in patients with advanced stage of myeloma (p < .02), whereas the 2nd-order “gray-level co-occurrence matrix (GLCM) cluster prominence” was lower (p < .04). In patients with elevated serum-free light chains (SFLC) or kappa/lambda SFLC ratio above 1.56, the “entropy” and 2nd-order GLCM features were lower (p < .03). The degree of bone marrow infiltration correlated with 1st-order features (e.g., “uniformity”; rP = 0.49; p < .0001), whereas “entropy” and 2nd-order GLCM features were negatively correlated (e.g., “difference entropy”; rP = − 0.54; p < .0001). Conclusions CT textural features applied on non-calcium bone marrow images correlate well with myeloma-related serologic parameters and histology showing a more uniform tissue structure and higher attenuation with increasing medullary infiltration and could therefore be used as additional imaging biomarkers for non-invasive assessment of medullary involvement. Key Points • Texture analysis applied on dual-energy reconstructed non-calcium bone marrow images provides information about marrow structure and attenuation. • Myeloma-related serologic parameters and the degree of myeloma cell infiltration correlate with 1st- and 2nd-order features which could be useful as additional imaging biomarkers for non-invasive assessment of medullary involvement.

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Hevylite and Freelite Tests in Newly Diagnosed Multiple Myeloma: Clinical Utility and Correlations with Clinical Features

Blood ◽

10.1182/blood.v128.22.5625.5625 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5625-5625

Author(s):

Paola Omedé ◽

Valter Redoglia ◽

Monica Astolfi ◽

Alessandra Larocca ◽

Stefano Spada ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Light Chain ◽

Research Funding ◽

Chromosomal Abnormalities ◽

Advisory Board ◽

Bone Marrow Infiltration ◽

Newly Diagnosed

Abstract Introduction Heavy light chain (HLC) assay is a recently developed method that separately quantifies the k and L-bounded amounts of a given intact immunoglobulin (Ig). It allows an accurate quantification of both the involved/uninvolved Ig and permits to quantify even small monoclonal protein. Free light chain (FLC) and HLC can provide prognostic information for multiple myeloma patients. We evaluated the role of HLC and FLC tests in the assessment and evolution of the disease in newly diagnosed multiple myeloma (MM) patients. Methods From February 2011 to April 2014, 1510 patients aged ≤65 years with symptomatic newly diagnosed MM were enrolled in the EMN02/HO95 study. Details about treatments and preliminary results of the main study were previously reported (Cavo M et al, abs8000, J Clin Oncol 34, 2016). In this analysis, we focused on patients enrolled in Italy (N=718). Serum samples from each enrolled patient were collected at diagnosis, before starting maintenance, and thereafter every 6 months. Samples from 665 patients at diagnosis and 156 at pre-maintenance were analyzed. Involved HLC ratio (iHLCR) was calculated with the involved Ig (either G or A) as numerator. Involved FLC ratio (iFLCR) was calculated as K/L or L/K with the monoclonal chain as numerator. FLC ratio (FLCR) and HLC ratio (HLCR) were calculated as K/L. The analyses were performed using Spearman correlation. Results Median follow-up was 32 months. At baseline the type of paraprotein was IgG in 428 (298 IgG-k, 130 IgG-L), IgΑ in 123 (77 IgΑ-k, 46 IgΑ-L) or light chain in 104 patients (k 73, L 31); 10 patients were IgD or IgM. International Staging System (ISS) stages were well distributed in all the isotypes. The median involved HLC values were IgG-K 28.97, IgG-L 30.6, IgA-K 41.7, IgA-L 35.7 g/L, light chain K 2719.58 mg/L, and light chain L 3369.75 mg/L. HLC IgG was significantly correlated with B2-microglobulin (r=0.31), extensive bone marrow infiltration >60% (r=0.31) and hemoglobin (r=-0.39). HLC IgA was not correlated with any disease parameter. In light chain MM, iFLC was correlated to B2-microglobulin (r=0.41), creatinine (r=0.39), extensive bone marrow infiltration >60% (r=0.39) and hemoglobin (r=-0.36). The increase of iFLCR (≥ median value) was significantly associated with IgG, ISS III, anemia, extensive bone marrow infiltration and higher creatinine (p<0.001), but not with the presence of high risk chromosomal abnormalities. High iFLCR (> third quartile) was significantly associated with inferior TTP (median 43.4 versus NR, HR 1.75 95% CI 1.22-2.53, p 0.003). The increase of iHLCR (≥ median value) was significantly associated with ISS III, anemia, and extensive bone marrow infiltration (p<0.001), whereas the presence of high risk chromosomal abnormalities was not. At pre-maintenance, 17% of patients had an abnormal HLCR, whereas 82% had a normalization of HLCR. The normalization of HLCR before starting maintenance was significantly related with the achievement of complete response (CR) (p=0.02) and a trend towards a longer 3-years TTP was observed (83% versus 74%, Log-rank test 0.05). Before start of maintenance, 27% of patients had a normalization of FLCR. No significant correlation with response or outcome was observed for patients who had a normalization of FLCR. At pre-maintenance, 67% IgG or IgA MM patients were immunofixation (IFX) negative. Among them, 8% had still an abnormal HLCR compared to IFX positive patients (8% versus 36%, p<0.001). Conclusions This preliminary analysis confirms the prognostic role of high iFLCR and iHLCR in newly diagnosed MM patients. HLCR normalization may be a valuable parameter to better define CR and predict outcome. HLC can quantify even small monoclonal protein when immunofixation is negative. Further follow-up is needed to assess the prognostic impact of HLC and FLC on survival outcome. Updated results will be presented at the meeting. Disclosures Larocca: Janssen-Cilag: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Cavo:Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Millennium: Consultancy, Honoraria. Petrucci:Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria. Patriarca:Bristol-Myers Squibb: Other: Advisory board; Mundipharma: Other: Advisory board; MSD: Consultancy; Janssen-Cilag: Other: Advisory board; Celgene: Consultancy. Corradini:Takeda: Consultancy, Speakers Bureau; Celgene: Honoraria; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Servier: Honoraria; Gilead: Honoraria, Speakers Bureau; Gentium: Honoraria, Speakers Bureau. Sonneveld:Celgene: Other: Advisory board, Research Funding; Onyx: Other: Advisory board, Research Funding; Millennium: Other: Advisory board, Research Funding; Janssen-Cilag: Other: Advisory board, Research Funding. Boccadoro:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; SANOFI: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Abbivie: Honoraria; Mundipharma: Research Funding. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria.

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