18F-FDG PET/CT Metabolic Parameters and Circulating Tumour DNA Mutation Abundance in Diffuse Large B-Cell Lymphoma: Correlation and Survival Analysis / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between 18Fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters and peripheral blood circulating tumour DNA (ctDNA) in patients with diffuse large B-cell lymphoma (DLBCL), and the prognostic value of these two types of parameters in predicting progression-free survival (PFS).@*METHODS@#Clinical, PET/CT and ctDNA data of DLBCL patients who underwent peripheral blood ctDNA testing and corresponding PET/CT scans during the same period were retrospectively analyzed. At the time of ctDNA sampling and PET scan, patients were divided into baseline and relapsed/refractory (R/R) groups according to different disease conditions. CtDNA mutation abundance was expressed as variant allele frequency (VAF), including maximum VAF (maxVAF) and mean VAF (meanVAF). Total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG) were obtained by the 41% maximum normalized uptake value method, and the distance between the two farthest lesions (Dmax) was used to assess the correlation between PET parameters and ctDNA mutation abundance using Spearman correlation analysis. The receiver operating characteristic (ROC) curves were used to obtain the optical cut-off values of those parameters in predicting PFS in the baseline and R/R groups, respectively. Survival curves were outlined using the Kaplan-Meier method and log-rank test was performed to compare survival differences.@*RESULTS@#A total of 67 DLBCL patients ［28 males and 39 females, median age 56.0(46.0, 67.0) years］ were included and divided into baseline group (29 cases) and R/R group (38 cases). Among these PET parameters, baseline TMTV, TLG, and Dmax were significantly correlated with baseline ctDNA mutation abundance, except for maximum standardized uptake value (SUVmax) (maxVAF vs TMTV: r=0.711; maxVAF vs TLG: r=0.709; maxVAF vs Dmax: r=0.672; meanVAF vs TMTV: r=0.682; meanVAF vs TLG: r=0.677; meanVAF vs Dmax: r=0.646). While in all patients, these correlations became weaker significantly. Among R/R patients, only TMTV had a weak correlation with meanVAF (r=0.376). ROC analysis showed that, the specificity of TMTV, TLG and Dmax in predicting PFS was better than mutation abundance, while the sensitivity of ctDNA mutation abundance was better. Except R/R patients, TMTV, TLG, Dmax, and VAF were significantly different at normal/elevated lactate dehydrogenase in baseline group and all patients (all P<0.05). Survival curves indicated that high TMTV (>109.5 cm3), high TLG (>2 141.3), high Dmax (>33.1 cm) and high VAF (maxVAF>7.74%, meanVAF>4.39%) were risk factors for poor PFS in baseline patients, while only high VAF in R/R patients (both maxVAF and meanVAF >0.61%) was a risk factor for PFS.@*CONCLUSION@#PET-derived parameters correlate well with ctDNA mutation abundance, especially in baseline patients. VAF of ctDNA predicts PFS more sensitively than PET metabolic parameters, while PET metabolic tumour burden with better specificity. TMTV, TLG and VAF all have good prognostic value for PFS. PET/CT combined with ctDNA has potential for further studies in prognostic assessment and personalized treatment.

Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma / Frequência da proteína Bcl-2 em pacientes com linfoma difuso de grandes células B de alto risco

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9 percent) were GCB-like and 49 (67.1 percent) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37 percent) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37 percent of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

CONTEXTO E OBJETIVO: A expressão gênica e imunoistoquímica do linfoma difuso de grandes células B (LDGCB) vem permitindo a identificação de importantes subgrupos prognósticos: LDGCB do centro germinativo (CG) e LDGCB de células B ativadas (CBA). Entretanto, existem poucos dados disponíveis com LDGCB de alto risco, sendo o prognóstico dos LDGCB do CG melhor que os LDGCB de CBA. A participação do Bcl-2 como preditor de sobrevida nos LDGCB não é clara e sua expressão é variável entre os dois subgrupos de LDGCB. Neste estudo é avaliada a frequência e o prognóstico da expressão da proteína Bcl-2 em LDGCB de alto risco. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo realizado entre portadores de LDGCB tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foi avaliado o impacto prognóstico da expressão das proteínas CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) e Bcl-2 por imunoistoquímica em LDGCB de alto risco. Foram avaliados, para todos os marcadores, 73 pacientes com idade de 18 a 60 anos. RESULTADOS: Vinte e quatro (32,9 por cento) pacientes foram classificados como LDGCB do CG e 49 (67,1 por cento) como LDGCB de CBA, sem diferença nas taxas de remissão completa, sobrevida livre de doença e sobrevida global. Vinte e sete (37 por cento) apresentaram expressão de Bcl-2, o qual foi o único fator preditivo independente de pior prognóstico de sobrevida global à análise multivariada. CONCLUSÃO: A expressão da proteína Bcl-2 ocorreu em 37 por cento dos portadores de LDGCB de alto risco, sem diferença entre os subgrupos de LDGCB do CG ou de CBA.

B cell lymphoma with unusual clinical cutaneous presentation.

Cutaneous B cell lymphoma (CBCL) is a lymphoproliferative disorder of neoplastic B cell of the skin. These are rarer than T cell lymphomas. Commonly, the presenting features of CBCL are plaques or nodules. Here is a case report of CBCL with a very unusual presentation of cutaneous horns. The patient was managed by a combination chemotherapy and local radiotherapy only. He is disease-free for about the last five years. The case has been presented because of its rarity and its management protocol.