BACKGROUND: There are currently no clinical or pathological parameters able to predict response to adjuvant radiotherapy (RT) in laryngeal squamous cell carcinoma (LSCC). Few studies have investigated the molecular pathways potentially capable of predicting said response. The mammalian target of rapamycin (mTOR) acts as a 'master switch' protein in cancer cells, modulating metabolism, the cell cycle, and apoptosis. Cancer treatment with mTOR inhibitors (rapamycin analogs, or rapalogs) has produced promising results in various malignancies (renal cell carcinoma, breast cancer, prostate cancer, leukemia, lymphoma, and melanoma). The novel aim of the present study was to ascertain the prognostic role of mTOR expression in a series of patients with LSCC treated with primary surgery followed by RT. METHODS: The retrospective study involved 25 consecutive patients with LSCC given postoperative RT. Immunohistochemical mTOR expression was evaluated in primary LSCC by image analysis. RESULTS: The locoregional recurrence rate was significantly higher in patients with LSCC whose mTOR expression was >2.5% (P = 0.013). After postoperative RT, the locoregional recurrence risk ratio was 3.25 in LSCCs with mTOR >2.5%. The different disease-free survival was significantly shorter in cases of LSCC with mTOR >2.5% (P = 0.029). CONCLUSIONS: mTOR should be studied as a potential predictor for identifying LSCCs at higher risk of early recurrence after postoperative RT. New therapeutic strategies should be investigated in LSCC, including the use of rapalogs associated with conventional chemotherapeutic regimens in combination with RT.
BACKGROUND: There are currently no clinical or pathological parameters able to predict response to adjuvant radiotherapy (RT) in laryngeal squamous cell carcinoma (LSCC). Few studies have investigated the molecular pathways potentially capable of predicting said response. The mammalian target of rapamycin (mTOR) acts as a 'master switch' protein in cancer cells, modulating metabolism, the cell cycle, and apoptosis. Cancer treatment with mTOR inhibitors (rapamycin analogs, or rapalogs) has produced promising results in various malignancies (renal cell carcinoma, breast cancer, prostate cancer, leukemia, lymphoma, and melanoma). The novel aim of the present study was to ascertain the prognostic role of mTOR expression in a series of patients with LSCC treated with primary surgery followed by RT. METHODS: The retrospective study involved 25 consecutive patients with LSCC given postoperative RT. Immunohistochemical mTOR expression was evaluated in primary LSCC by image analysis. RESULTS: The locoregional recurrence rate was significantly higher in patients with LSCC whose mTOR expression was >2.5% (P = 0.013). After postoperative RT, the locoregional recurrence risk ratio was 3.25 in LSCCs with mTOR >2.5%. The different disease-free survival was significantly shorter in cases of LSCC with mTOR >2.5% (P = 0.029). CONCLUSIONS:mTOR should be studied as a potential predictor for identifying LSCCs at higher risk of early recurrence after postoperative RT. New therapeutic strategies should be investigated in LSCC, including the use of rapalogs associated with conventional chemotherapeutic regimens in combination with RT.
Authors: Marco Lionello; A Lovato; A Staffieri; S Blandamura; C Turato; L Giacomelli; C Staffieri; G Marioni Journal: Eur Arch Otorhinolaryngol Date: 2013-09-25 Impact factor: 2.503