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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2020.tde-09042021-094846
Document
Author
Full name
Matheus de Aquino Moreira Guimarães
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Peria, Fernanda Maris (President)
Arruda, Gustavo Viani
Kowalski, Luiz Paulo
Title in Portuguese
Avaliação da eficácia e de toxicidades da cisplatina radiossensibilizante de alta dose em pacientes com carcinoma epidermóide de cabeça e pescoço irressecáveis
Keywords in Portuguese
Câncer de cabeça e pescoço
Cisplatina
Quimioterapia
Radioterapia
Toxicidades
Abstract in Portuguese
Introdução: O câncer de cabeça e pescoço (CCP) é um grupo heterogêneo de neoplasias que pode apresentar prognóstico ruim quando diagnosticado em fases avançadas. O tratamento otimizado para lesões localmente avançadas e irressecáveis se baseia em radioterapia associada a quimioterapia (cisplatina 100mg/m²), entretanto, às custas de alto índice de toxicidade. Os ensaios clinicos randomizados que consolidaram este tratamento possuem critérios de inclusão estritos e que limitam sua validade à população diagnosticada com esta patologia na prática clínica diária, que habitualmente apresenta déficit nutricional, performance status comprometido e baixo suporte clínico-social. Objetivos: Trata-se de um estudo retrospectivo, que tem por finalidade avaliar se o tratamento definitivo com quimioradioterapia considerado padrão para doença localmente avançada (estadio III - IV irressecáveis) apresenta efetividade em nossa população, com destaque para os desfechos de taxa de resposta objetiva (TRO) sobrevida livre de progressão (SLP), sobrevida global (SG), toxicidades e analise das relações neutrófilo/linfócito e plaqueta/linfocito. Resultados: 52 pacientes preencheram os critérios de inclusão no estudo, os quais foram diagnosticados no período de 2012 a 2018. A TRO foi de 84,6%, com 50% destes apresentando resposta completa. A SLP e SG medianas foram de 35,3 (IC 95% 27,28 - 43,78) e 52 meses (IC 95% 41,32 - 62,8), respectivamente. A avaliação de toxicidades revelou eventos adversos em todos os pacientes, com 69,2% sendo grau 3 - 4. Realização de ≥2 ciclos de cisplatina (HR 3,57 [1,25 - 10,25] - p < 0,001), toxicidades grau 3 - 4 (HR 0,27 [0,09 - 0,8] - p 0,02) e escala de comorbidade de charlson (ECC) (HR 3,23 [1,26 - 8,29] - p < 0,001)se associaram ao desfecho de sobrevida. No quesito toxicidades, as variáveis de laserterapia profilática (HR 0,48 [IC 95% 0,27 - 0,86], p 0,001), relação plaqueta/linfócito (HR 0,82 [IC 0,74 - 0,92], p <0,01) e IMC (HR 0,27 [IC 95% 0,09 - 0,76], p 0,01) apresentaram significância em análise ajustada. Conclusão: O tratamento se mostrou efetivo em nossa amostra, com dados de SLP e SG próximos do estimado por outros estudos maiores, demonstrando um menor índice de toxicidades comparado à literatura; ≥2 ciclos de cisplatina, toxicidades 3 - 4 e ECC se correlacionaram com SG, enquanto laserterapia profilática, relação plaqueta/linfócito e IMC foram associadas a toxicidades grau 3 - 4.
Title in English
Effectiveness and toxicities evaluation of high dose cisplatin chemoradiotherapy in patients with unresectable head and neck epidermoid carcinoma
Keywords in English
Chemotherapy
Cisplatin
Head and neck cancer
Radiotherapy
Toxicities
Abstract in English
Introduction: Head and neck cancer (HNC) is a heterogeneous group of neoplasms, which can have a poor prognosis when diagnosed in advanced stages. Its optimized treatment for locally advanced and unresectable stages is based on radiotherapy associated with chemotherapy (cisplatin 100mg / m²), and it's associated with high toxicity. However, it is noteworthy that the randomized trials who evaluate this treatment have strict inclusion criteria and that limits its external validity to the population diagnosed with this pathology in daily clinical practice, which usually presents nutritional deficit, compromised status performance and low clinical and social support. Objectives: The present study is a retrospective study, which intends to assess whether the definitive treatment with chemoradiotherapy considered standard for locally advanced disease (stage III - IV unresectable) is effective in our population, with emphasis on the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicities and analysis of neutrophil / lymphocyte and platelet / lymphocyte relationships. Results: 52 patients met the inclusion criteria in the study, which were diagnosed from 2012 to 2018. ORR was 84.6%, with 50% of these showing complete response. The median PFS and OS were 35.3 (95% CI 27.28 - 43.78) and 52 months (95% CI 41.32 - 62.8), respectively. The toxicity assessment revealed adverse events in all patients, with 69.2% being grade 3 - 4. Achieviment of ≥2 cycles of cisplatin (HR 3.57 [1.25 - 10.25] - p <0.001), toxicities grade 3 - 4 (HR 0.27 [0.09 - 0.8] - p 0.02) and charlson's comorbidity scale (CCS) (HR 3.23 [1.26 - 8.29] - p <0.001) were associated with the survival outcome. Regarding toxicities, the variables of prophylactic laser therapy (HR 0.48 [95% CI 0.27 - 0.86], p 0.001), platelet / lymphocyte ratio (HR 0.82 [CI 0.74 - 0.92], p <0.01) and BMI (HR 0.27 [95% CI 0.09 - 0.76], p 0.01) showed significance in adjusted analysis. Conclusion: The treatment proved to be effective in our sample, with PFS and OS data close to that estimated by other larger studies, demonstrating a lower toxicity index compared to the literature; ≥2 cycles of cisplatin, toxicities 3 - 4 and ECC correlated with SG, while prophylactic laser therapy, platelet / lymphocyte ratio and BMI were associated with grade 3 - 4 toxicities.
 
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Publishing Date
2021-04-19
 
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