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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-25082023-115829
Document
Author
Full name
Marina Alessandra Pereira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Júnior, Ulysses Ribeiro (President)
Kassab, Paulo
Marques, Carlos Frederico Sparapan
Szor, Daniel José
Title in Portuguese
Avaliação da resposta patológica em pacientes com câncer gástrico submetidos à quimioterapia pré-operatória
Keywords in Portuguese
Linfonodos
Metástase neoplásica
Neoplasias gástricas
Patologia cirúrgica
Quimioterapia neoadjuvante
Sobrevida
Abstract in Portuguese
INTRODUÇÃO: A gastrectomia associada à linfadenectomia continua sendo o principal tratamento curativo no câncer gástrico (CG) localmente avançado. Na busca por melhores resultados, a quimioterapia (QT) pré-operatória associada ao tratamento cirúrgico têm sido amplamente utilizada, aumentando as taxas de ressecção curativa e sobrevida. Um dos principais parâmetros de avaliação da resposta à QT consiste na graduação da regressão tumoral (TRG), que visa categorizar a quantidade de alterações regressivas após o tratamento, para demonstrar informações prognósticas potenciais com base em achados histopatológicos. No entanto, o impacto prognóstico da resposta patológica (RP) e a ausência de um sistema TRG padronizado deixam a dúvida se somente a avaliação do tumor primário é capaz de refletir o risco de recorrência e sobrevida. OBJETIVO: Avaliar a resposta patológica no tumor primário (estômago) e nos linfonodos (LN) de pacientes com adenocarcinoma gástrico que receberam QT pré-operatória, e verificar a associação da regressão tumoral com a sobrevida. MÉTODOS: Avaliaram-se retrospectivamente todos os pacientes com CG tratados com QT pré-operatória seguido de gastrectomia potencialmente curativa. A presença de tumor residual foi graduada de 0-100% no tumor primário e nos LNs, e os casos foram então classificados para o grau de regressão de acordo com o TRG proposto pela AJCC/CAP, e adaptado aos linfonodos (LRG). Para análise, os pacientes foram definidos conforme a resposta no tumor primário em RP(+) (TRG0/1/2) e RP(-) (TRG3); e de acordo com a taxa de tumor nos LNs em Menor-TuLN e Maior-TuLN. RESULTADOS: Entre os 62 pacientes avaliados, 28 (45,2%) foram classificados como RP(+) e 34 (54,8%) como RP(-). A mediana de tumor residual observada nos casos foi de 80%, e dois pacientes apresentaram RP completa. Não houve diferença entre os grupos com relação a características clínicas, cirúrgicas e estádio ypTNM. A frequência de tumores difusos foi maior no grupo RP(+) (p=0,007), e 57,1% e 67,1% pacientes eram ypN+ no grupo RP(+) e RP(-), respectivamente (p=0,394). Entre os 58 casos avaliados para o LRG, 35 (60,3%) classificaram-se como Menor-TuLN e 23 (39,7%) como Maior-TuLN. Lesões de menor diâmetro, ausência de invasão linfática, venosa e perineural, e menor status ypT e ypTNM, associaram-se ao grupo Menor-TuLN. Não houve associação entre a RP no tumor primário e nos LNs (p=0,358). Menor-TuLN, e não a RP no tumor primário, foi um fator independente associado à melhor sobrevida livre de doença e sobrevida global. Pacientes com redução de estádio para ypN0 (LNs com regressão) tiveram sobrevida equivalente aos pacientes ypN0 sem regressão. CONCLUSÃO: A taxa de tumor nos LNs é o principal fator associado à sobrevida em pacientes com CG após QT. A RP no tumor primário, por sua vez, não apresentou impacto na sobrevida. A regressão tumoral no leito primário não está associada à resposta nos LN e a redução do estádio ypN
Title in English
Assessment of pathological response in patients with gastric cancer undergoing preoperative chemotherapy
Keywords in English
Lymph nodes
Neoadjuvant chemotherapy
Neoplasm metastasis
Stomach neoplasms
Surgical pathology
Survival
Abstract in English
INTRODUCTION: Gastrectomy associated with lymphadenectomy remains the main curative treatment in locally advanced gastric cancer (GC). In the search for better therapeutic results, preoperative chemotherapy (CMT) associated with surgery has been widely used, increasing curative resection rates and survival. One of the main parameters for evaluating CMT response is the tumor regression grading (TRG), which aims to determine the regressive changes after treatment and to demonstrate potential prognostic information based on histopathological findings. However, the prognostic impact of pathological response (PR), the absence of a standardized TRG system, the doubt whether only the assessment of the primary tumor can reflect survival and, furthermore, the identification of patients at risk of recurrence after surgery, remains a challenge in GC. OBJECTIVE: To evaluate the pathological response in the primary tumor (stomach) and lymph nodes (LN) of patients with gastric adenocarcinoma who received preoperative CMT, and verify the association of tumor regression with survival. METHODS: All patients with GC treated with preoperative CMT followed by curative gastrectomy were retrospectively evaluated. The presence of residual tumor was graded from 0-100% in primary tumor and LNs, and classified for the degree of regression according to the TRG proposed by the AJCC/CAP, and adapted to LN (LRG). For analysis, patients were defined according to primary tumor response in RP(+) (TRG0/1/2) and RP(-) (TRG3); and according to the tumor rate in the LNs as Minor-TuLN and Major-TuLN. RESULTS: Among the 62 patients evaluated, 28 (45.2%) were classified as PR(+) and 34 (54.8%) as PR(-). The median residual tumor in the cases was 80%, and two patients had complete PR. There was no difference between the groups regarding clinical and surgical characteristics and the ypTNM stage. The frequency of diffuse tumors was higher in the RP(+) group (p=0.007), and 57.1% and 67.1% of patients were ypN+ in the RP(+) and RP(-) groups, respectively (p=0.394). Among the 58 cases evaluated for the LRG, 35 (60.3%) were classified as Minor-TuLN and 23 (39.7%) as Major-TuLN. Lesser diameter lesions, absence of lymphatic, venous, and perineural invasion, and lower ypT and ypTNM status were associated with the Minor-TuLN group. There was no association between PR in the primary tumor and the LNs (p=0.358). Lower-TuLN, not PR in the primary tumor, was an independent factor associated with better disease-free survival and overall survival. Patients staging as ypN0 (LNs with regression) had survival equivalent to ypN0 patients without regression. CONCLUSION: Tumor rate in LNs is the main factor associated with survival in patients with GC after CMT. PR in the primary tumor, in turn, had no impact on survival. Tumor regression in the primary bed is not associated with LN response and ypN downstage
 
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Publishing Date
2023-08-30
 
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