Molecular Profile and FDG-PET Metabolic Volume at Staging in DLBCL--Response

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Successive occurrence of 2 Genetically distinct Burkitt lymphomas: pathophysiological significance and clinical consequences

Nous rapportons le cas exceptionnel d’un patient âgé de 25 ans qui a développé, en moins de 2 ans, 2 lymphomes de Burkitt (LB). La cytogénétique et les techniques de biologie moléculaire ont montré que les 2 LB étaient issus de 2 clones distincts

Valeur pronostique de la classification GCB/ABC déterminée par RT-MLPA associée à la TEP dans les lymphomes B diffus à grandes cellules

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TARGETED GENOTYPING OF CIRCULATING TUMOR DNA FOR CLASSICAL HODGKIN LYMPHOMA MONITORING: A PROSPECTIVE STUDY

International audienceAbout Related Information ePDFPDF Request permission Export citation Add to favorites Track citationShare a linkShare on Email Facebook Twitter LinkedIn RedditIntroduction: The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin Lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed.Methods: We developed a targeted Next‐Generation sequencing (NGS) panel for fast analysis (AmpliSeq® technology) of nine commonly mutated genes in biopsy and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow up at diagnosis and after 2 cycles of chemotherapy (C2). A dedicated bioinformatics pipeline to optimize detections of variants with low rates and minimize artefactual misinterpretations was built. Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD‐like [73.5%] and other regimens [5.2%, for elderly patients] were included in this non‐interventional study (NCT02815137).Results: Median age of the patients was 33.5 years (range 20‐86) with a predominance of male patients, scleronodular subtype and ECOG 0‐1 (53.3%, 70% and 88.3%, respectively). Variants were identified in 33 (55%) patients, precisely in 16/30 (53.3%) and 30/60 (50%) of available biopsy and ctDNA samples respectively. Concordance between genetic profiles of biopsy and ctDNA was accurate for 22/30 patients (73.3%). Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1were found in 11.7% (mean number of variants by sample [range]: 1 [0‐1]), 25% (1.1 [0‐2]), 21.7% (1.4 [0‐2]), 1.7% (1 [0‐1]), 25% (1.3 [0‐3]), 6.7% (1 [0‐1]), 15% (1.4 [0‐3]), 5% (1.3 [0‐2]) and 31.7% (1.8 [0‐7]) of all patients, respectively. Unsupervised hierarchical clustering was performed among the 9 genes to represent the association of alterations (See Figure 1).Higher level of [ctDNA] at diagnosis was associated with adverse characteristics: age ≥45 years, presence of anemia (hemoglobin <10.5g/dl), albuminemia <40g/l, sedimentation rate ≥50mm, stage III‐IV, lymphocytes count <0.6 G/L, presence of B symptoms, International prognostic Index ≥3, elevated LDH. The ITPKB and B2M mutated patients displayed more disseminated disease (≥ 4 median nodal areas versus [vs] 3 for non‐mutated patients, p = 0.005) and XPO1 mutations were associated with female sex (p = 0.042). Median VAF were higher in ctDNA than in biopsy (3.23% vs 2.15%, p = 0.023) and there was a moderate correlation between higher metabolic tumor volume (MTV) and higher [ctDNA] (r = 0.36, p = 0.005).Regarding early therapeutic response, 45 patients (83%, NA = 6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1‐3). Mean of DeltaSUVmax after C2 was ‐78.8%. We analyzed ctDNA after C2 for 45 patients (70%). A rapid clearance of ctDNA in all cases was observed after C2.Conclusions: Variants detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in complement to PET. [ctDNA] level and genotype are correlated with clinical characteristics and presentation.Keywords: classical Hodgkin lymphoma (cHL); minimal residual disease (MRD); molecular genetics.imag

Combined Genotype Analysis of Tumor and Cell-Free DNA By Ultra-Deep Targeted Sequencing: Correlation with PET-Scan Imaging in a Prospective Cohort of Diffuse Large B-Cell Lymphoma Patients.

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Combined Genotype Analysis of Tumor and Cell-Free DNA By Ultra-Deep Targeted Sequencing: Correlation with PET-Scan Imaging in a Prospective Cohort of Diffuse Large B-Cell Lymphoma Patients.

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Clinical and prognostic role of sarcopenia in elderly patients with classical Hodgkin lymphoma: a multicentre experience

BACKGROUND: Elderly classical Hodgkin lymphoma (cHL) (ecHL) is a rare disease with dismal prognosis and no standard treatment. Fitness‐based approaches may help design appropriate treatments. Sarcopenia has been associated with an increased risk of treatment‐related toxicities and worse survival in various solid tumours, but its impact in ecHL is unknown. The aim of this retrospective multicentre study was to investigate the prognostic role of sarcopenia in ecHL. METHODS: We included newly diagnosed >64 years old cHL patients who performed a baseline comprehensive geriatric assessment and high‐dose computed tomography (CT) or 18fluorine‐fluorodeoxyglucose positron emission tomography/CT before any treatment. Sarcopenia was measured as skeletal muscle index (SMI, cm(2)/m(2)) by the analysis of high‐dose CT or low‐dose positron emission tomography/CT images at the L3 level. The specific cut‐offs for the SMI were determined by receiver operator curve analysis and compared with those proposed in literature and studied in diffuse large B‐cell lymphoma. Survival functions [progression‐free survival [PFS] and overall survival (OS)] were calculated for the whole population and for different subgroups defined as per different sarcopenia cut‐off levels. RESULTS: We included 154 patients (median age 71 years old, 76 female). The median L3‐SMI was 42 cm(2)/m(2). The specific cut‐off derived in our male population was 45 cm(2)/m(2); using this cut‐off, 27 male patients (35%) were defined as sarcopenic. After a median follow‐up of 5.9 years, the overall 5‐year PFS and OS rates were 53% and 65%, respectively, and were significantly shorter in sarcopenic male patients compared with non‐sarcopenic (PFS 31% vs. 61%, P = 0.008; OS 51% vs. 74%, P = 0.042). Applying diffuse large B‐cell lymphoma‐derived sarcopenic thresholds, there were no significant differences between sarcopenic and non‐sarcopenic patients for both PFS and OS, with a sole exception of a significant reduced PFS in sarcopenic male patients using Namakura cut‐off. The comprehensive geriatric assessment‐determined frail functional status was an independent adverse prognostic factor for both female and male patients. CONCLUSIONS: Baseline evaluation of sarcopenia through radiological examinations performed for ecHL staging may help define a proportion of male patients with unfavourable outcome with current treatment strategies. Also the functional status evaluation could allow to identify a frail subgroup of patients with worse outcome