scholarly journals Longitudinal CT Imaging to Explore the Predictive Power of 3D Radiomic Tumour Heterogeneity in Precise Imaging of Mantle Cell Lymphoma (MCL)

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 393
Catharina Silvia Lisson ◽  
Christoph Gerhard Lisson ◽  
Sherin Achilles ◽  
Marc Fabian Mezger ◽  
Daniel Wolf ◽  

The study’s primary aim is to evaluate the predictive performance of CT-derived 3D radiomics for MCL risk stratification. The secondary objective is to search for radiomic features associated with sustained remission. Included were 70 patients: 31 MCL patients and 39 control subjects with normal axillary lymph nodes followed over five years. Radiomic analysis of all targets (n = 745) was performed and features selected using the Mann Whitney U test; the discriminative power of identifying “high-risk MCL” was evaluated by receiver operating characteristics (ROC). The four radiomic features, “Uniformity”, “Entropy”, “Skewness” and “Difference Entropy” showed predictive significance for relapse (p < 0.05)—in contrast to the routine size measurements, which showed no relevant difference. The best prognostication for relapse achieved the feature “Uniformity” (AUC-ROC-curve 0.87; optimal cut-off ≤0.0159 to predict relapse with 87% sensitivity, 65% specificity, 69% accuracy). Several radiomic features, including the parameter “Short Axis,” were associated with sustained remission. CT-derived 3D radiomics improves the predictive estimation of MCL patients; in combination with the ability to identify potential radiomic features that are characteristic for sustained remission, it may assist physicians in the clinical management of MCL.

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1150
Magda Zanelli ◽  
Luca Stingeni ◽  
Maurizio Zizzo ◽  
Giovanni Martino ◽  
Francesca Sanguedolce ◽  

A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 inhibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multicentric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for which he is currently on antibiotic therapy.

2021 ◽  
pp. 028418512110258
Lan Li ◽  
Tao Yu ◽  
Jianqing Sun ◽  
Shixi Jiang ◽  
Daihong Liu ◽  

Background The number of metastatic axillary lymph nodes (ALNs) play a crucial role in the staging, prognosis and therapy of patients with breast cancer. Purpose To predict the number of metastatic ALNs in breast cancer via radiomics. Material and Methods We enrolled 197 patients with breast cancer who underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A total of 3386 radiomic features were extracted from the early- and delayed-phase subtraction images. To classify the number of metastatic ALNs, logistic regression was used to develop a radiomic signature and nomogram. Results The radiomic signature were constructed to distinguish the N0 group from the N+ (metastatic ALNs ≥ 1) group, which yielded area under the curve (AUC) values of 0.82 and 0.81 in the training and test group, respectively. Based on the radiomic signature and BI-RADS category, a nomogram was further developed and showed excellent predictive performance with AUC values of 0.85 and 0.89 in the training and test groups, respectively. Another radiomic signature was constructed to distinguish the N1 (1–3 ALNs) group from the N2–3 (≥4 metastatic ALNs) group and showed encouraging performance with AUC values of 0.94 and 0.84 in training and test group, respectively. Conclusions We developed a nomogram and a radiomic signature that can be used to predict ALN metastasis and distinguish the N1 from the N2-3 group. Both nomogram and radiomic signature may be potential tools to assist clinicians in assessing ALN metastasis in patients with breast cancer.

2020 ◽  
Vol Volume 13 ◽  
pp. 12163-12168
Chunmei Yang ◽  
Wen Lei ◽  
Hongqiong Xie ◽  
Gongqiang Wu ◽  
Juying Wei ◽  

2021 ◽  
pp. 016173462110353
Aylin Tahmasebi ◽  
Enze Qu ◽  
Alexander Sevrukov ◽  
Ji-Bin Liu ◽  
Shuo Wang ◽  

The purpose of this study was to evaluate an artificial intelligence (AI) system for the classification of axillary lymph nodes on ultrasound compared to radiologists. Ultrasound images of 317 axillary lymph nodes from patients referred for ultrasound guided fine needle aspiration or core needle biopsy and corresponding pathology findings were collected. Lymph nodes were classified into benign and malignant groups with histopathological result serving as the reference. Google Cloud AutoML Vision (Mountain View, CA) was used for AI image classification. Three experienced radiologists also classified the images and gave a level of suspicion score (1–5). To test the accuracy of AI, an external testing dataset of 64 images from 64 independent patients was evaluated by three AI models and the three readers. The diagnostic performance of AI and the humans were then quantified using receiver operating characteristics curves. In the complete set of 317 images, AutoML achieved a sensitivity of 77.1%, positive predictive value (PPV) of 77.1%, and an area under the precision recall curve of 0.78, while the three radiologists showed a sensitivity of 87.8% ± 8.5%, specificity of 50.3% ± 16.4%, PPV of 61.1% ± 5.4%, negative predictive value (NPV) of 84.1% ± 6.6%, and accuracy of 67.7% ± 5.7%. In the three external independent test sets, AI and human readers achieved sensitivity of 74.0% ± 0.14% versus 89.9% ± 0.06% ( p = .25), specificity of 64.4% ± 0.11% versus 50.1 ± 0.20% ( p = .22), PPV of 68.3% ± 0.04% versus 65.4 ± 0.07% ( p = .50), NPV of 72.6% ± 0.11% versus 82.1% ± 0.08% ( p = .33), and accuracy of 69.5% ± 0.06% versus 70.1% ± 0.07% ( p = .90), respectively. These preliminary results indicate AI has comparable performance to trained radiologists and could be used to predict the presence of metastasis in ultrasound images of axillary lymph nodes.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5302-5302
Remy Gressin ◽  
Anne Moreau ◽  
Nicolas Daguindau ◽  
Adrien Tempescul ◽  
Sylvain Carras ◽  

Abstract Background The proliferation index (PI), defined by KI67 protein expression has been identified as a key prognostic factor (PF) in mantle cell lymphoma (MCL) (1, 2). A GOELAMS/LYSA study (n = 113 patients) identified a cut point of 26% for KI67 positivity as an independent predictor of overall survival together with LDH levels, B symptoms and ECOG-PS, in MCL (GOELAMS index : GI). (1) Recently, the European MCL network confirmed the independent prognostic power of KI67 protein expression levels to predict OS in MCL (n = 508) and proposed a new score "MIPIc" (KI67cut-off of 30%). (2) While these scores show prognostic impact in the immuno-chemotherapy setting, with or without ASCT and / or maintenance therapy, their predictive power in the setting of targeted therapy remains uncertain. Objective The aim of this study was to test the predictive power of the MIPIc and GI prognostic indices in a cohort of elderly MCL patients treated by a proteasome-inhibitor-based immunochermotherapy regimen within a prospective phase II trial of the LYSA group (LyMa SA 2010 ; Rituximab, Bendamustine, Velcade and Dexamethasone regimen : RiBVD). (3) Material and method The final analysis of the LyMA SA 2010, presented at ASH 2014 (3), showed overall clinical and molecular response rates of 86.5% and 85%. The 24 months estimated OS and PFS was respectively 80% and 70%. (3) In order to assess the prognostic power of KI67 expression levels for OS, all survival data were updated. KI67 staining was performed and reviewed centrally by one pathologist of the LYSA-P, according to the European guidelines. (4) The MIPIc and GI scores were calculated and their impact on survival analyzed (Logrank). In addition, all 6 variables comprising the MIPc and the GI indices were assessed separately by univariate analyzes for prognostic value (these were LDH, ECOG and KI67 that are common to the 2 indices, and Age and WBC for the MIPIc and B Symptoms for GI). Finally a Logrank permitted to define 3 groups of patients with a high statistically impact on survivals with the 3 common variables of MIPIc and GI. Results Among the 74 elderly MCL patients treated in first line by the RiBVD regimen, 59 are alive with a median follow up of 40 months. Estimated OS and PFS at 36 months are respectively 78.4% and 65%. The MIB1 was evaluated on 58 samples for which the MIPIc and GI could be calculated for 57 patients (no LDH value for one patient). MIPIc and GI were not able to define relevant prognostic subgroups for OS (p =0.55 and 0.11). Only the 3 common variables LDH (N vs >N), ECOG (O-1 vs >1) and MIB1 (with a cut-off at 46% corresponding to the fourth quartile of MIB1 expression levels) were individually predictive of OS by univariate analysis (respectively with p=0.0006, p=0.048 and p=0.0031). With these three variables the Logrank test separated three groups that were statistically discriminant for OS and PFS: one group with 0 risk factors n=24 patients, 42%), a second group with one risk factor (n=20 patients, 32%) and the last group with 2 or 3 risk factors (n=13 patients, 23%). Hence the 3 year OS of these 3 groups was respectively 96%, 75% and 30% (p<0.0001). The 3 year PFS was 87.5%, 65% and 8% (p<0.0001) In Conclusion The proteasome-inhibitor-based immunochemotherapy regimen, RiBVD, induces prolonged survival of "High risk" patients, as defined by this modified MIPIc score. More proliferative disease, defined by a KI67 superior to 46%, combined with a high LDH level and/or a high PS defines a high subgroup of patients under the RiBVD regimen (median PFS and OS of respectively 15 and 10 months). Ref: 1 Gressin R, Haematologica 2010. 2 Hoster E et al, J Clin Oncol 2016. 3 Gressin R et al, ASH Blood 2014. 4 Klapper W, H Hematop 2009. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Cartron: Roche: Consultancy, Honoraria; Celgene: Honoraria; Gilead: Honoraria; Jansen: Honoraria. Dartigeas:Roche: Consultancy; Mundipharma: Other: travel grant. Dupuis:janssen: Honoraria; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Karlin:takeda: Consultancy; Bristol: Consultancy; celgene: Consultancy, Honoraria; janssen-cilag: Consultancy, Honoraria; amgen: Consultancy, Honoraria.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 323-323 ◽  
Frederick Racke ◽  
Sabrina Simpson ◽  
Beth Christian ◽  
Kristie A. Blum ◽  
Robert Hasserjian ◽  

Abstract Abstract 323 Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by treatment failures and short survival. At presentation, MCL is often widely disseminated. Occasionally, early lymphoma can be seen as in situ lesions involving the mantle zones of secondary follicles. The primary genetic lesion involved in the pathogenesis of the disease is the t(11;14)(q13;q32)/(IGH/CCND1) which leads to the overexpression of cyclin D1, a cell cycle regulatory protein that is not normally expressed in B-cells. However, MCL frequently has numerous additional chromosomal alterations making it one of the most genetically unstable lymphomas. Thus, while the IGH/CCND1 rearrangement is the critical initiating event, it appears that additional alterations are necessary to develop MCL. However, little is known about the latency period required to accumulate sufficient lesions to develop MCL. Recently, it has been appreciated that the initiating chromosomal events in other B-cell malignancies may precede the development of overt disease by many years. In particular, the defining chromosomal events in childhood ALL may be found in the heel sticks of children at birth, even if leukemia does not develop until a number of years later. We recently reported a unique case of mantle cell lymphoma arising simultaneously in the donor and recipient 12 years following allogeneic bone marrow transplantation for chronic myelogenous leukemia(J. Clin. Oncol., in press). This suggested that MCL may exhibit long latency periods prior to the development of frank lymphoma. In order to determine whether in situ MCL may be identified in patients with MCL, we identified 7 patients who were diagnosed with mantle cell lymphoma and who had previous pathological material available that contained lymphoid tissue and that was unrelated to the subsequent MCL. Remarkably, all 7 specimens showed evidence of in situ mantle cell lymphoma, as judged by cyclin D1 over-expression localized to lymphoid cells. Pathological specimens ranged from 2.1–15.5 years prior to the diagnosis of MCL. In all 7 specimens, cyclin D1 positive collections of lymphocytes were identified, 5 with distinct homing to mantle zones, one with follicular colonization and mantle homing, and 1 with a diffuse distribution. FISH studies were undertaken to identify cyclin D1 chromosomal translocations, and evidence of chromosomal translocations could be identified in 2/3 cases evaluated whereas no signals were seen in adjacent uninvolved lymphoid tissue. Taken together, the data presented strongly suggest that a long latency period following the initiating IGH/CCND1 translocation may occur in MCL with patients harboring in situ lesions for years prior to the development of clinical disease. These findings shed interesting new light on the natural history of MCL. Pre-lymphoma location Pattern of in situ MCL Latency (yrs) Lymphoma location CCND1 FISH in pre-lymphoma specimen Obturator node from radical prostatectomy CyclinD1+ focal colonized follicles, scattered cells in mantles 7.4 Sigmoid colon biopsy ND Duodenal serosal lymph node (perforated benign gastric ulcer) Diffuse scattered CyclinD1+ cells 2.1 Sigmoid colon biopsy ND Right neck subcutaneous lymph node (neurofibroma excision) CyclinD1+ cells in follicular mantles 3.2 Bone marrow biopsy ND Periesophageal lymph nodes from esophagectomy Several CyclinD1+ colonized primary follicles 8.0 Right cervical lymph node ND Axillary lymph node from mastectomy CyclinD1+ cells in follicular mantles 15.5 Mesenteric lymph node <5% positive signals Mesenteric lymph node dissection for colon cancer CyclinD1+ cells in follicular mantles 10.6 Base of tongue lesion Positive Cervical lymph node involved with T cell lymphoma CyclinD1+ cells in follicular mantles 3.1 Right axillary lymph node Positive Disclosures: No relevant conflicts of interest to declare.

2017 ◽  
Vol 89 (7) ◽  
pp. 93-98
N G Chernova ◽  
E E Zvonkov ◽  
A M Kovrigina ◽  
A B Sudarikov ◽  
D S Badmazhapova ◽  

Breast implant-associated anaplastic large-cell lymphoma will be identified as a separate nosological entity in the 2017 adapted WHO classification due to differences in its clinical presentations, pathogenesis, and prognosis with those of nodal and cutaneous anaplastic large-cell lymphomas. The paper gives a review of the literature and describes the authors’ own clinical case of common breast implant-associated anaplastic large-cell lymphoma involving breast tissue, axillary lymph nodes, anterior chest muscles, and bone marrow. The treatment policy chosen by the authors could achieve complete remission.

2021 ◽  
pp. 106689692110274
Lavina Loungani ◽  
Rajesh Mundhe ◽  
Roshan Chinoy

A 68-year-old male presents with generalized lymphadenopathy and fever of short duration. Axillary lymph node excision was performed and was sent for histopathological evaluation. Microscopic evaluation of the submitted lymph node revealed diffuse proliferation of intermediate-sized atypical lymphoid cells with round nuclei, irregular membranes, finely dispersed chromatin, and inconspicuous nucleoli. Mitotic figures were frequently seen. Immunohistochemical evaluation revealed diffuse expression of CD20, CD5, CD10, B-cell lymphoma 2 (Bcl2), and B-cell lymphoma 6 (Bcl6). Atypical lymphoid cells were negative for cyclin D1; however, showed diffuse and strong nuclear expression of SOX11. MIB1 proliferation index was high (Ki67: 90%-95%). Based on morphological features and immunohistochemical findings a diagnosis of “cyclin D1 negative aggressive blastoid variant of mantle cell lymphoma (MCL)” was offered. The classic morphology of MCL is seen in 90% of cases, while the remaining (∼10%) are considered as variants. A blastoid variant is an aggressive subtype that can lack expression of CD5 as well as cyclin D1, but instead expresses CD10, Bcl6, and CD23. SOX11 expression is seen in 90% cases of MCL and in almost 100% cases of cyclin D1 negative MCL. The current case highlights the unusual morphologic and aggressive variant of MCL and a significant role of SOX11 in its diagnosis.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 335-335 ◽  
Caroline Bodet-Milin ◽  
Clement Bailly ◽  
Michel Meignan ◽  
Alina Beriollo-Riedinger ◽  
Rene-Olivier Casasnovas ◽  

Abstract INTRODUCTION. FGD-PET has emerged as an important predictor of clinical outcome in lymphomas. However, its utility in everyday clinical practice in mantle cell lymphoma (MCL) remains uncertain because there is a lack of large prospective trials including FDG-PET results. To address this question, we conducted the LyMa-MRD project as an ancillary study in a prospective phase III trial in MCL (NCI NCT00921414; LyMa Trial). From Sept 2008 to Aug 2012, 299 previously untreated MCL patients (&lt;66yrs) were enrolled in the LyMa trial (a phase III international prospective trial, NCT00921414). Briefly, all patients received 4 courses of R-DHAP followed by ASCT using an R-BEAM conditioning regimen (n=257). After ASCT, patients were randomized between observation (obs) (n=120) versus Rituximab maintenance (RM) (n=119). The first planned interim-analysis, with a median follow-up of 40.6 months was presented at ASH 2014 and indicated superior progression-free survival (PFS) in the RM versus Obs arms (Le Gouill et al. ASH 2014). Sequential FDG-PET monitoring was optional and a predefined secondary objective and was performed throughout. Treatment strategy was not modified by FDG-PET results. Indeed, the population of the LyMa trial is the ideal population to investigate the predictive power of FDG-PET parameters at diagnosis and after induction in MCL. Herein, we present the first results performed from the database of first planed interim-analysis. METHOD. FDG-PET of 94 MCL patients have been independently and centrally reviewed by 2 lymphoma expert nuclear physicians. Quantitative metrics including SUVmax, SUVmean, SUVpeak, total lesion glycolysis (TLG) were extracted from the area with the highest uptake, at diagnosis and before ASCT (iPET). Visual analysis by the Deauville scale was also performed at iPET. The best cut-off values were determined for each metric using X-tile® analysis. Prognostic value was assessed using univariate analysis by Kaplan-Meier estimates of PFS. RESULTS. The studied population did not differ from the whole population of the LyMa trial (baseline characteristics, demographic data, staging, balance between observation vs maintenance and outcome). At diagnosis, univariate analysis showed a prognostic value on PFS of 4 metrics: SUVmax (p&lt;0.001), SUVmean (p&lt; 0.001), SUVpeak (p&lt;0.001), TLG (p=0.03). The best cut off for these 4 indices, were 11.4, 7.7, 8.7, and 65 respectively. Indeed, median PFS was not reach (NR) for patients with low SUVmax (n=63) as compared to only 26.3 months for patients with high SUVmax (p&lt;0.0001) (n=31). Results were similar for SUVpeak, SUVmean and TLG. The prognostic value of SUVmax was reinforced when combined with MIPI. Indeed, patients can be separated in 3 prognostic groups including a group of patients with a very good outcome (low SUVmax plus MIPI inter/low). Results of iTEP showed that ΔSUV before ASCT (defined as a decrease of SUVmax values from diagnosis to end of induction &gt; 29.65%) was predictive of PFS: median NR vs 42.3m (p=0.0051). In contrast FGD-PET before ASCT according to Deauville scale was only predictive for score 5 vs 1/2/3/4. Conclusion. The LyMa-PET project is the largest study addressing the question of FDG-PET in a homogeneously treated population of MCL. It shows for the first time that SUVmax (&lt;/&gt;11.4) at diagnosis and ΔSUV (&lt;/&gt;29.65%) provide predictive parameters for outcome in MCL. Update results and patients' outcome according to randomization arms will be updated for the time of the meeting. Disclosures No relevant conflicts of interest to declare.

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