New Predictors of Response to Neoadjuvant Chemotherapy and Survival for Invasive Thymoma: a Retrospective Analysis

Background. Cell-cycle protein (p27, p21, and p53) expression can predict response to neoadjuvant chemotherapy and prognosis in some neoplasms. This study evaluated whether these markers could also be effective in invasive thymoma during a multimodality treatment. Methods. Between 1989 and 2008, 33 patients with invasive thymoma underwent surgical resection after neoadjuvant chemotherapy. Expression of p27, p21, and p53 was assessed using immunohistochemistry in specimens retrieved pre and post chemotherapy. Factors influencing response to neoadjuvant chemotherapy and survival were investigated by univariate and multivariate analysis. Good response was defined as complete disappearance of tumor at imaging or necrosis > 90% at pathologic studies. Results. Twelve patients disclosed an imaging good response. Complete resection was possible in 17 patients, 9 of whom had presented imaging good response and 11 of whom had revealed pathologic good response. On univariate analysis both imaging and pathologic poor responses were significantly associated with incomplete resection (P = 0.04 and P = 0.03, respectively) and preneoadjuvant triple combination of p27 low, p21 low, and p53 high expressions (P = 0.001 and P < 0.0001, respectively), the last factor being the only one selected on logistic regression (P = 0.01 and P = 0.005, respectively). Longterm survival analysis was negatively influenced by triple combination of p27, p21, and p53 (P < 0.0001) and incomplete resection (P < 0.0001), which were also selected on Cox's regression (P = 0.004 and P = 0.02, respectively). Conclusions. The triple combination of p27 low, p21 low, and p53 high expressions was the most significant predictor of imaging and pathologic poor responses to neoadjuvant chemotherapy in invasive thymoma. This combination together with incomplete resection was also the most significant negative predictor of long-term survival.