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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-08082023-150201
Document
Author
Full name
Roger Beltrati Coser
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Marques, Carlos Frederico Sparapan (President)
Bresciani, Claudio Jose Caldas
Nadal, Sidney Roberto
Segatelli, Vanderlei
Title in Portuguese
Marcadores inflamatórios do sangue periférico e resposta à terapia neoadjuvante em pacientes com neoplasia de reto
Keywords in Portuguese
Biomarcadores tumorais
Inflamação
Linfócitos
Monócitos
Neoplasias retais
Neutrófilos
Plaquetas
Terapia neoadjuvante
Abstract in Portuguese
INTRODUÇÃO: O câncer de reto apresenta elevada incidência no Brasil. Seu tratamento é complexo, multimodal e associado à elevada morbidade, com prejuízo para a qualidade de vida dos pacientes. Sabe-se que os pacientes submetidos à quimio e radioterapia neoadjuvante (nQRT) apresentam diferentes graus de resposta tumoral, variando desde a ausência de resposta até a resposta completa (RC), com desaparecimento do tumor. Há grande interesse no estudo de ferramentas que possam identificar esses pacientes (respondedores e não respondedores) antes de iniciar o tratamento. Dentre essas ferramentas, encontram-se os marcadores inflamatórios do sangue periférico: a razão neutrófilo-linfócito (RNL), a razão plaqueta-linfócito (RPL) e a razão linfócito-monócito (RLM), baseados na íntima relação entre inflamação e câncer. OBJETIVO: Estudar, dentre os pacientes com neoplasia de reto submetidos à nQRT, a relação entre os marcadores de resposta inflamatória sistêmica (RNL, RPL e RLM) e os graus de resposta ao tratamento neoadjuvante, de acordo com a classificação TRG. CASUÍSTICA E MÉTODOS: Foram avaliados, de forma retrospectiva, 396 pacientes uni-institucionais com neoplasia de reto submetidos à nQRT. A avaliação envolveu dados clínicos, laboratoriais e patológicos. Calculou-se RNL, RPL e RLM com base em dados de hemogramas pré-nQRT dos pacientes. Os pacientes foram estratificados por grau deresposta tumoral (TRG) à nQRT, com base no protocolo do Colégio Americano de Patologistas. RESULTADOS: As variáveis RNL, RPL, CEA, número de leucócitos, neutrófilos, eosinófilos e monócitos, além de tamanho do tumor e número de linfonodos comprometidos, apresentaram valores significativamente mais elevados entre os pacientes com resposta incompleta à nQRT (TRG 1-2-3). Também se observou maior percentual de pacientes do sexo masculino entre os pacientes com resposta incompleta à nQRT. Entre os pacientes com resposta completa (TRG 0), apresentaram valores significativamente mais elevados as variáveis: número de comorbidades, hemoblogina (Hb), hematócrito (Ht) e RLM, além de maior percentual de pacientes em uso de medicação anti-hipertensiva e antiagregante plaquetário/anticoagulante neste grupo de pacientes. As variáveis RNL, RPL e RLM apresentaram potencial preditivo de resposta à nQRT (p<0,001). RNL >2,08 mostrou risco relativo (RR) de 2,30 (IC95%: 1,60-3,31) para estimar resposta incompleta (TRG 1-2-3); RPL >129,36 mostrou RR de 1,79 (IC95%: 1,25-2,05) e a RLM >2,67 mostrou RR de 0,42 (IC95%: 0,26-0,66). No modelo linear generalizado múltiplo, RNL>2,08 associou-se, de forma independente, à ausência de RC (RR:1,19; IC95%: 1,07 - 1,28), p=0,001, com área sob a curva (AUC) de 0,659(IC95%: 0,599- 0,718). CONCLUSÃO: RNL, RPL, RLM são preditores de resposta à nQRT em pacientes com câncer de reto. RNL maior que 2,08 é fator preditivo independente para resposta patológica incompleta à nQRT. Estes achados agregam uma ferramenta de baixíssimo custo e amplamente disponível ao arsenal de manejo do câncer de reto, com foco na individualização do tratamento para obtenção do melhor resultado possível para cada paciente
Title in English
Peripheral blood inflammatory markers and response to neoadjuvant therapy in rectal cancer patients
Keywords in English
Biomarkers tumor
Blood platelets
Inflammation
Lymphocytes
Monocytes
Neoadjuvant therapy
Neutrophils
Rectal neoplasms
Abstract in English
INTRODUCTION: Rectal cancer has a high incidence in Brazil. Its treatment is complex, multimodal, associated with high morbidity and impact in patients quality of life. It is known that patients undergoing neoadjuvant chemoradiotherapy (nCRT) shows different degrees of tumor response, ranging from no response to complete response (CR). There is a search for tools that can correctly identify these patients (responders and nonresponders) before starting treatment. Among these tools, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the lymphocyte-to-monocyte ratio (LMR) constitutes peripheral blood systemic inflammatory markers, based on cancer-inflammation interactions. OBJECTIVE: To study, in selected rectal cancer patients, the association between systemic inflammatory markers (NLR, PLR and LMR) and response degrees to nCRT, according to the tumor response grade (TRG) classification. PATIENTS AND METHODS: Single institution retrospective study, evaluating 396 patients with rectal cancer submitted to nCRT. Clinical, laboratorial, and pathological data were obtained from patients electronic record. NLR, PLR and LMR were calculated based on pre-nCRT blood count data from each patient. Patients were stratified by TRG, according to the College of American Pathologists protocol. RESULTS: TRG 1-2-3 patients (incomplete response to nCRT) had statistically significant higher values of NLR, PLR, CEA, white blood cell count, neutrophil count, eosinophil count and monocyte count, as well as significantly higher tumor size, number of positive lymph nodes (LN) and percentage of male patients. Complete responders (TRG 0) had statistically significant higher values of comorbidity number, hemoglobin level (Hb), hematocrit level (Ht) and LMR, as well as significantly higher percentage of patients using anti-hypertensive drugs and platelet antiaggregant/anticoagulant drugs. NLR, PLR and LMR are potential predictors of nCRT complete response (p<0.001). To estimate TRG 1-2-3 (incomplete response): NLR >2.08 (RR: 2.30; 95%CI: 1.60-3.31); PLR >129.36 (RR: 1.79; 95%CI: 1.25-2.05) and LMR >2.67 (RR: 0.42; 95%CI: 0.26-0.66). In a multiple generalized linear model, NLR>2.08 was independently associated with incomplete response to nCRT (RR=1.19; 95%CI: 1.07 - 1.28), p=0.001; AUC: 0.659 (95%CI: 0.599 - 0.718). CONCLUSION: NLR, PLR and LMR are nCRT response predictors in patients with rectal cancer. NLR > 2.08 is an independent predictive factor for pathological incomplete response to nCRT. These findings add a very low-cost and widely available tool to the arsenal of rectal cancer management, focusing on treatment individualization to obtain the best possible outcome for each patient
 
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Publishing Date
2023-08-15
 
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