RESUMEN
BACKGROUND: Nivolumab improves overall survival (OS) in patients with platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). In one study, however, Kaplan-Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3-6 months, suggesting that patients with initial resistance to immunotherapy might have better outcomes with cytotoxic treatment. Here, we explored the conditions and candidates which are predictive of nivolumab outcomes in R/M HNSCC. METHODS: We retrospectively reviewed the clinical records of 27 consecutive R/M HNSCC patients treated with nivolumab from 2014 to 2018. Tumor size was evaluated by RECIST ver.1.1. Tumor growth rate (Gr) was defined as 3log(D0/Dpre)/t, where D0 and Dpre are the sum of the diameters of the target lesions (SumTLs) at baseline and pre-baseline, and t is time, with 1t defined as 4 weeks. RESULTS: Twenty-five patients were enrolled. Survival was significantly worse in patients with disease progression within 3 months. Outcomes appeared poorer in patients with higher pre-treatment Gr and bigger SumTLs at baseline. We therefore explored the association between prognosis, Gr and SumTLs. Recursive partitioning analysis showed that the characteristics of patients with disease progression after 3 months were Gr < 0.76 and SumTLs < 31.0 mm. Further, Gr < 0.76 and SumTLs < 31.0 mm was associated with significantly longer PFS (p = 0.01) and OS (p < 0.01). CONCLUSIONS: These results suggest that Gr and SumTLs at baseline are significantly associated with OS and PFS in R/M HNSCC patients treated with nivolumab.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Nivolumab/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Anciano , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Resultado del Tratamiento , Carga TumoralRESUMEN
To investigate the clinical significance of p53 and p21WAF1/CIP1 in the advanced squamous cell carcinoma (SCC) of the pyriform sinus, we performed immunohistochemical staining of p53 and p21WAF1/CIP1 on the biopsy specimens from patients with stage III or stage IV SCC of the pyriform sinus. The results were compared with clinico-pathological features, including age, histological grade, TNM classification, number of neck lymph node metastases on histopathological examination (pLN) and prognosis. Specific staining for p53 and p21WAF1/CIP1 was detected in 36% and 32% of the specimens, respectively. Positive staining of p21WAF1/CIP1 was observed not only in the p53-negative specimens but also in the p53-positive specimens. Age (p < 0.05) and pLN (p < 0.001) were regarded as the significant prognostic factors. The 5-year survival rate of the p53-positive patients (55%) was significantly higher than that of the p53-negative patients (26.5%: p < 0.03). However, there is no significant difference between the p53 groups after controlling pLN. Although it was not statistically significant, the 5-year survival rate of the p21WAF1/CIP1-positive patients (58.8%) was higher than that of the p21WAF1/CIP1-negative patients (26.9%). These results suggest that expressions of p53 and p21WAF1/CIP1 are independent genetic alterations that may play different roles in the SCC of the pyriform sinus. Expression of p53 could not be regarded as an independent prognostic factor at this point. Further studies including the molecular biological analysis should be performed in order to determine the clinical role of p21WAF1/CIP1.
