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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-15062023-163234
Document
Author
Full name
Fernanda Maria Santos
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Rocha, Vanderson Geraldo (President)
Duarte, Paulo Schiavom
Buccheri, Valeria
Spector, Nelson
Title in Portuguese
Análise quantitativa do PET-CT ao diagnóstico e interim, como fator prognóstico dos desfechos clínicos de pacientes com linfoma de Hodgkin clássico: experiência de um único centro brasileiro
Keywords in Portuguese
Glicólise total das lesões
Linfoma de Hodgkin
Prognóstico
Tomografia por emissão de pósitron
Volume metabólico tumoral
Abstract in Portuguese
Atualmente o PET interim (PETi), em análise visual segundo o escore de Deauville (DS), é o fator prognóstico mais importante em linfoma de Hodgkin (LH), guiando as decisões terapêuticas. No entanto, os resultados dos estudos em PETi são heterogêneos, destacando que essa ferramenta prognóstica não é perfeita, sendo necessária a busca por novos fatores. O objetivo deste estudo é avaliar o valor prognóstico da análise quantitativa do PET-CT ao diagnóstico (PET0) e no PETi, definida como valor máximo de captação padronizado (SUVmax), volume metabólico tumoral total (TMTV) e glicólise total das lesões (TLG), numa coorte de vida real. Métodos: Pacientes (pts) registrados no Instituto do Câncer do Estado de São Paulo, com diagnóstico de LH clássico entre 2011-2017, estadiados com PET-CT e tratados com o protocolo ABVD, foram incluídos neste estudo retrospectivo. HIV+ foram excluídos. TMTV/TLG foram calculados utilizando o limite de 41% do SUVmax de cada lesão, segundo a Associação Europeia de Medicina Nuclear. Pacientes com PETi+ tiveram a redução percentual em relação ao PET0 calculada (SUVmax, TMTV e TLG). As variáveis foram dicotomizadas pelo método de Contal O'Quigley. Foram estimadas a sobrevida livre de progressão (SLP), a sobrevida global (SG) e a incidência acumulada de falha de tratamento (CIF), tendo o óbito como competidor. Modelo de Cox e de Fine-Gray foram utilizados para análise. Resultados: 234 pts foram incluídos, com idade mediana de 30 anos (14-79), sendo 56% do sexo feminino, 59,4% em estádio III/IV, 70,5% com sintoma B, 68,3% com escore de alto risco (critério GHSG) e 57% com massa bulky. Dos 210 pts com PETi realizados (90%), 52 (24.7%) eram positivos (DS 4-5). Com mediana de seguimento de 6,8 anos, a SG, SLP, CIF e óbito não relacionado à progressão/recaída estimados em 5 anos foi de 85,1%, 71,1%, 21,5% e 7,4%, respectivamente. Ao diagnóstico, pts com TLG1392.55 tiveram maior CIF (p=0,032). Não foi observado impacto estatisticamente significativo da análise quantitativa (SUVmax, TMTV ou TLG) na SLP ou SG. Na análise multivariada, somente o PETi+ (p< 0,001) e a proteína C reativa (PCR)(p=0,039) se mantiveram preditores de CIF, e o PETi+ (p=0,019), a idade dos pacientes 45 anos (p=0,011) e a PCR (p=0,043) foram associados com pior SLP. Na análise quantitaviva do PETi+ somente o SUVmax68,8 foi preditor de SLP (p=0,024). A análise combinada do PETi visual (DS) com a quantitativa (SUVmax68,8%) permitiu distinguir um grupo com melhor SLP dentre os pts com PETi+, sendo 77% para aqueles com SUV68,8 e 40% aos pts com SUVmax<68,8 (p=0,0028) em 5 anos. Conclusão: Numa coorte de vida real, constituída em sua maior parte por pts em estádio avançado e com grande volume tumoral, a análise quantitativa ao PET0 não foi preditora de SG, SLP ou CIF. No entanto, o SUVmax<68.8% foi estatisticamente associado com diminuição da SLP no subgrupo de pacientes com PETi+. Estes resultados devem ser confirmados em maiores series de pacientes e sugere a utilização do PETi+ com cálculo do SUVmax como instrumento para guiar tratamento em estudos clínicos futuros
Title in English
Quantitative PET-CT analysis at diagnosis and interim as a prognostic factor for clinical outcomes for patients with Classical Hodgkin lymphoma: a unicenter experience in Brazil
Keywords in English
Hodgkin lymphoma
Metabolic tumor volume
Positron-Emission Tomography
Prognosis
Total lesion glycolysis
Abstract in English
Currently, interim PET (iPET) in visual analysis according to the Deauville score (DS) is the most important prognostic factor in Hodgkin lymphoma (HL), used to guide treatment decisions. However, the results of iPET studies are heterogeneous highlighting the need of studies trying to improve the accuracy of iPET assessment. This study aimed to evaluate the prognostic value of PET quantitative analysis defined as the maximum standardize uptake value (SUVmax), total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) at baseline (PET0) and iPET in a real-life cohort of patients. Methods: Patients (pts) from Instituto do Cancer do Estado de Sao Paulo with classical HL diagnosis from 2011-2017, with PET-CT evaluation and treated with ABVD protocol were included in this retrospective study. HIV+ pts were excluded. TMTV/TLG were calculated using the 41% of SUVmax threshold method, as recommended by the European Association of Nuclear Medicine. For iPET+ pts, the percentage reduction compared to PET0 (SUVmax, TMTV and TLG) were calculated. Cutoffs for continuous variables were calculated using the method of Contal and O'Quigley. Cumulative incidence of treatment failure (CIF) was estimated and death was considered a competitive event. Progression free survival (PFS) and overall survival (OS) were also estimated. Cox and Fine-Gray model were used for analyses. Results: 234 pts were included and the median age was 30 (14-79) years old, 56% were female, 59.4% presented in clinical stage III/IV, 70.5% had B symptoms, 68,3% had high-risk score (GHSG criteria) and 57% had bulky disease. Of the 210 pts with iPET evaluation (90%), 52 (24.7%) were positive (DS 4-5). The median follow-up time was 6.8 years and the OS, PFS, CIF and non-disease-related death estimated at 5y were 85.1%, 71.1%, 21.5% and 7.4% respectively. At baseline, pts with TLG1392.55 had higher CIF (p=0.032). Neither SUVmax, nor TMTV and TLG at PET0 had an impact on PFS or OS. In multivariate analysis, only iPET+ (p< 0.001) and C-reactive protein (CPR)(p=0.039) were associated with CIF, and iPET+ (p=0.019), age 45 (p=0.011) and CPR (p=0.043) were associated with decreased PFS. In the quantitative analysis of iPET+ only SUVmax68.8 remained predictor of PFS (p=0.024). The combination of visual (DS) and quantitative (SUVmax 68.8%) iPET analysis allowed identifying a group of patients with better PFS among iPET+, in fact with 77% for those with SUVmax68.8% and 40% for pts with SUVmax<68.8% in 5 years (p=0.0028). Conclusion: In a real-life cohort, including pts with high-risk and high tumor burden, quantitative PET0 analysis was not predictor of PFS, OS, or CIF. However, the SUVmax<68.8% was statistically associated with decreased PFS defining a subgroup of patients with iPET+. This information requires confirmation in larger series of pts and may support future trials to guide treatment according to SUVmax in iPET+ results
 
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Publishing Date
2023-07-03
 
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