Prognostic and predictive factors in laryngeal cancer treated with radiotherapy

• Radiotherapy (RT) and surgery are the only two curative treatments for patients with laryngeal cancer (LC). RT has the advantage that it offers a possibility to preserve a functioning larynx and hence a functioning normal voice. The response of tumors to RT is heterogeneous, even within the same tumor stage. Methods for prediction of response to radiotherapy are lacking. Finding new clinical and biological factors for predicting the outcome of RT in LC may offer the possibility to individualize RT aiming to increase locoregional disease control and survival, and to decrease RT-related morbidity. The aim of this thesis was therefore to investigate some potential factors that may influence the outcome of RT in LC.The influence of the following factors for the outcome of RT in patients with LC was investigated: a reduction of overall treatment time (OTT) by accelerated RT, preradiotherapy hemoglobin level, tumor microvessel density (MVD), expression of the cell cycle-regulating and apoptosis inducing protein p53, expression of the cell proliferation marker Ki-67, expression of the epidermal growth factor receptor (EGFr) and histopathologic differentiation.Analyses of 214 patients with LC treated with primary radical RT at the Department of Oncology, Sahlgrenska University Hospital in Göteborg 19901998 showed that a shortening of OTT by hyperfractionated accelerated RT (HART) was beneficial for patients with T2N0M0 glottic cancer, giving local and locoregional control rates comparable to those for T1N0M0 tumors. For patients with advanced LC, no statistically significant difference in local or locoregional control was found between patients with T3 and T4 tumors treated with accelerated RT. The larynx preservation rate was 91% for the surviving patients. These latter results indicate that many locally advanced T4 tumors can be treated successfully with RT, and that T4 classification alone is not a sufficient criterion for excluding patients from larynx preservation with RT. Despite good results for loco-regional control, overall survival was poor. Independently of tumor stage, around 30% of patients died of intercurrent diseases, mainly new primary cancers, cardiovascular disease or pneumonia.Expression of MVD, p53, Ki-67 and EGFr, evaluated with IHC in pre-treatment tumor biopsies, did not influence radiotherapy outcome in this series of patients with LC.Preradiotherapy hemoglobin level was found to be a strong independent predictive factor, with patients with higher hemoglobin levels having significantly better locoregional control (p = 0,010) disease-free survival (p =0.007) and overall survival (p <0.001) compared to patients with low hemoglobin levels. In subgroup analysis, this was not seen in patients treated with accelerated RT, which indicate that the accelerated RT may to some degree compensate for the low hemoglobin level. Patients with well-differentiated tumors had significantly better overall survival compared to patients with moderately or poorly differentiated tumors (p = 0.003). In subgroup analysis this was only significant in patients treated with accelerated RT (p = 0.010). These results indicate that histopathologic differentiation may be used as tool in selecting patients with LC for accelerated RT.

Nyckelord

Laryngeal cancer

accelerated radiotherapy

predictive factors

pre-radiotherapy hemoglobin level

MVD

p53

Ki-67

EGFr

histopathologic differentiation.

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