Impacto prognóstico de células tumorais circulantes e potencial papel preditor de resposta ao tratamento em carcinoma epidermóide de cabeça e pescoço localmente avançado / Prognostic impact and potential predictive role of circulating tumor cells in locally advanced head and neck squamous cell carcinoma
São Paulo; s.n; 2019. 157 p. ilust, tabelas.
Thesis
in Portuguese
| LILACS, Inca
| ID: biblio-1222818
Responsible library:
BR30.1
Localization: BR30.1
RESUMO
Introdução:
O papel prognóstico de células tumorais circulantes (CTCs) em câncer de cabeça e pescoço localmente avançado (CCPLA) ainda não está determinado, devido a resultados conflitantes em estudos prévios, a maioria utilizando técnicas dependentes de citoqueratina para identificação e contagem de CTCs. O objetivo primário deste estudo é determinar a taxa de detecção utilizando o método ISET, o papel prognóstico e potencial papel preditivo de CTCs em CCPLA.Métodos:
Prospectivamente amostras de sangue de pacientes com CCPLA não metastático, estágios III/IV, foram analisadas para CTCs antes e após o tratamento, em dois cenários cirurgia curativa inicial e radioterapia (RT) adjuvante e candidatos a estratégia não cirúrgica (irressecáveis ou preservação de órgão) com RT concomitante a quimioterapia (QT) ou cetuximabe, precedida ou não por QT de indução (QTI).Resultados:
Foram incluídos 83 pacientes e a taxa de detecção de CTCs baseline foi de 94% (78/83). A contagem de CTCs se correlacionou significativamente com sobrevida, com um aumento relativo de 18% no risco de óbito (HR=1,18; CI95% 1,06-1,31; p<0,001), 16% no risco de progressão (HR=1,16; CI95% 1,04-1,28; p=0,004) e uma redução de 26% na chance de resposta completa ao tratamento (OR=0.74; CI95% 0.58-0.95; p=0.022) para cada aumento de uma CTC. Pacientes com CTCs < 6,5/mL apresentaram estimativa de sobrevida global (SG) em dois anos de 85,6% x 22,9% para CTCs ≥ 6.5/mL (HR=0,18; CI95% 0,06-0,49; P<0,0001) e pacientes com CTCs ≤ 3.8/mL uma estimativa de sobrevida livre de progressão (SLP) em dois anos de 71,8% x 37% para CTCs > 3.8/mL (HR=0,32; CI95%0,15-0,67; p=0,001). Após o tratamento, contagens altas de CTCs (ponto de corte 6,6/mL) se correlacionaram significativamente com pior SG (HR=0,12; CI95% 0,06-0,40; p<0,001) e SLP (HR=0,19; CI95% 0,06-0,59; p=0,001). No subgrupo de tratamento não cirúrgico (n=67), presença de microêmbolos (ME) se correlacionou significativamente com pior SG (HR=3,01; CI95% 1,06-8,52; p=0,029) e SLP (HR=3,84; CI95% 1,62-9,11; p<0,001). Neste subgrupo, CTCs altas (>3,8/mL) e ME foram identificados como potenciais preditores do benefício de QTI. Expressão de MRP-7 em ME baseline se relacionou a pior SG (HR=3,49; CI95% 1,01-12,04; p=0,047) e SLP (HR=3,62; CI95% 1,08-12,13; p=0,037) e expressão de TFGßRI nas CTCs após o tratamento a pior SG (HR=3,60; 1,03-12,59; p=0,032). Expressão de ß-tubulina III nas CTCs se relacionou a pior SG em pacientes recebendo QTI (p=0.012). Pacientes com cinética favorável de CTCs tiveram melhor SG (HR=0,22; IC95% 0,07-0,67; p=0,004) e SLP (HR=0,33; CI95% 0,13-0,84; p=0,015).Conclusões:
Contagem de CTCs baseline se correlacionaram com sobrevida e resposta ao tratamento e, junto com ME, são potenciais fatores preditivos do benefício de QTI. Contagens de CTCs altas após o tratamento e cinética desfavorável também foram prognósticos. Expressão de biomarcadores em CTCs e ME tem papel prognóstico e preditivo em CCPLAABSTRACT
Introduction:
The prognostic role of circulating tumor cells (CTCs) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) is yet to be determined, with conflicting results in previous trials, the majority utilizing cytokeratin dependent techniques for identification and counting of CTCs. The primary objective of this study is to determine the detection rates using the ISET method, the prognostic and potential predictive role of CTCs in LAHNSCC patients (pts) treated with a curative intent.Methods:
In this prospective study, peripheral blood samples of pts with non-metastatic LAHNSCC, stages III/IV, were analyzed for CTCs before and after treatment, in two scenarios curative surgical resection and adjuvant radiotherapy (RT) and candidates for a non-surgical strategy (unresectable or organ preservation) with RT concurrent with chemotherapy (CT) or cetuximab, preceded or not by induction CT (ICT).Results:
Eighty-three pts were included, and the detection rate of baseline CTCs was 94% (78/83). The CTCs counts were significantly correlated with survival, with an a relative increase of 18% in the risk of death (HR=1.18; CI95% 1.06-1.31; p<0.001), 16% in the risk of progression (HR=1.16; CI95% 1.04-1.28; p=0.004) and a reduction of 26% in the odds of complete response to treatment (OR=0.74; CI95% 0.58-0.95; p=0.022) for each increase of one CTC. Pts with CTCs < 6,5/mL had an estimated two year overall survival (OS) of 85.6% x 22.9% for CTCs ≥ 6.5/mL (HR=0.18; CI95% 0.06-0.49; P<0.0001) and pts with CTCs ≤ 3.8/mL had an estimated two year progression free survival (PFS) of 71.8% x 37% for CTCs > 3.8/mL (HR=0.32; CI95%0.15-0.67; p=0.001). After treatment, high CTCs counts (cut-off 6,6/mL) were significantly correlated with worse OS (HR=0.12; CI95% 0.06-0.40; p<0.001) and PFS (HR=0.19; CI95% 0.06-0.59; p=0.001). In the non-surgical subgroup (n=67), the presence of microemboli (ME) was correlated with a significantly worse OS (HR=3.01; CI95% 1.06-8.52; p=0.029) and PFS (HR=3.84; CI95% 1.62-9.11; p<0.001). In this subgroup, high CTCs counts (>3,8/mL) and ME were identified as potential predictive factors for efficacy of ICT. Baseline expression of MRP-7 in ME was related to a worse OS (HR=3.49; CI95% 1.01-12.04; p=0.047) and PFS (HR=3.62; CI95% 1.08-12.13; p=0.037) and TFGßRI expression in CTCs after treatment to a worse OS (HR=3.60; 1.03-12.59; p=0.032). ß-tubulin III expression in CTCs was related to a worse OS in pts receiving ICT (p=0.012). Patients with favorable kinetics of CTCs had better OS (HR=0.22; IC95% 0.07-0.67; p=0.004) and PFS (HR=0.33; CI95% 0.13-0.84; p=0.015).Conclusions:
Baseline CTCs counts were correlated with survival and response to treatment and, along with ME, potential predictive factors of ICT benefit. High CTCs counts after treatment and unfavorable kinetics were also prognostic. Biomarker expression in the CTCs and ME have prognostic and predicitive role in LAHNSCC
Full text:
Available
Collection:
International databases
Database:
LILACS
/
Inca
Main subject:
Carcinoma, Squamous Cell
/
Biomarkers, Tumor
/
Head and Neck Neoplasms
/
Neoplastic Cells, Circulating
Type of study:
Observational study
/
Prognostic study
/
Risk factors
Limits:
Adult
/
Aged
/
Humans
/
Male
Language:
Portuguese
Year:
2019
Document type:
Thesis