RESUMO
Translational Relevance: Evaluation of targeted therapies is urgently needed for the majority of patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC) who progress after immunochemotherapy. Erlotinib, a targeted inhibitor of epidermal growth factor receptor pathway, lacks FDA approval in HNSCC due to inadequate tumor response. This study identifies two potential avenues to improve tumor response to erlotinib among patients with HNSCC. For the first time, this study shows that an increased erlotinib dose of 300 mg in smokers is well-tolerated and produces similar plasma drug concentration as the regular dose of 150 mg in non-smokers, with increased study-specific defined tumor response. The study also highlights the opportunity for improved patient selection for erlotinib treatment by demonstrating that early in-treatment [18]FDG PET/CT is a potential predictor of tumor response, with robust statistical correlations between metabolic changes on early in-treatment PET (4-7 days through treatment) and anatomic response measured by end-of-treatment CT. Purpose: Patients with advanced HNSCC failing immunochemotherapy have no standard treatment options. Accelerating the investigation of targeted drug therapies is imperative. Treatment with erlotinib produced low response rates in HNSCC. This study investigates the possibility of improved treatment response through patient smoking status-based erlotinib dose optimization, and through early in-treatment [18]FDG PET evaluation to differentiate responders from non-responders. Experimental design: In this window-of-opportunity study, patients with operable HNSCC received neoadjuvant erlotinib with dose determined by smoking status: 150 mg (E150) for non-smokers and 300 mg (E300) for active smokers. Plasma erlotinib levels were measured using mass spectrometry. Patients underwent PET/CT before treatment, between days 4-7 of treatment, and before surgery (post-treatment). Response was measured by diagnostic CT and was defined as decrease in maximum tumor diameter by ≥ 20% (responders), 10-19% (minimum-responders), and < 10% (non-responders). Results: Nineteen patients completed treatment, ten of whom were smokers. There were eleven responders, five minimum-responders, and three non-responders. Tumor response and plasma erlotinib levels were similar between the E150 and E300 patient groups. The percentage change on early PET/CT and post-treatment PET/CT compared to pre-treatment PET/CT were significantly correlated with the radiologic response on post-treatment CTs: R=0.63, p=0.0041 and R=0.71, p=0.00094, respectively. Conclusion: This pilot study suggests that early in-treatment PET/CT can predict response to erlotinib, and treatment with erlotinib dose adjusted according to smoking status is well-tolerated and may improve treatment response in HNSCC. These findings could help optimize erlotinib treatment in HNSCC and should be further investigated. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00601913, identifier NCT00601913.
RESUMO
PURPOSE: A prospective, single institution study was conducted to evaluate the role of positron emission tomography with fluoro-deoxyglucose (FDG) before and after definitive radiation therapy for patients with head-and-neck cancer. Correlation with CT or MRI imaging and pathologic findings at the time of planned neck dissection was made. METHODS AND MATERIALS: Twelve patients with AJCC Stages III-IV cancer of the head and neck received CT or MRI and PET imaging before treatment with definitive radiation therapy. One month after completion of treatment, repeat CT or MRI and PET imaging was obtained. All images were reviewed independently by radiologists who were blind to the results of the other modality. Patients then underwent planned neck dissection. Pathologic correlation with posttreatment scans allowed calculation of the sensitivity, specificity, negative predictive value, and the positive predictive value for both CT/MRI and PET. RESULTS: Comparison of CT/MRI to PET obtained before definitive RT revealed both primary tumor and nodal disease were detected by both modalities in all cases where primary tumor was known. After RT, comparison of CT/MRI imaging to findings of neck dissection revealed a sensitivity of 90%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 50%. Comparison of PET imaging with pathologic findings demonstrated sensitivity of 45%, specificity of 100%, positive predictive value of 100%, and a negative predictive value of 14%. CONCLUSIONS: In this small series of patients, the presence of a positive PET 1 month after RT accurately indicated the presence of residual disease in all cases; however, a negative PET indicated absence of disease in only 14%. Further investigation is warranted before FDG-PET should be used to determine whether post-RT neck dissection should be omitted.