Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma

et al. (2013) Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma. PLoS ONE 8(1): e55327. doi:10.1371/journal.pone.0055327 Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma Hsuan-Ho Chen 0 Hung-Ming Wang 0 Kang-Hsing Fan 0 Chien-Yu Lin 0 Tzu-Chen Yen 0 Chun-Ta Liao 0 I-How Chen 0 Chung-Jan Kang 0 Shiang-Fu Huang 0 Jian-Xin Gao, Shanghai Jiao Tong University School of Medicine, China 0 1 Departments of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital , Linkou , Taiwan , Republic of China, 2 Internal Medicine, Division of Hematology/Oncology, Chang Gung Memorial Hospital , Linkou, Taiwan , Republic of China, 3 Radiation Oncology , Chang Gung Memorial Hospital , Linkou , Taiwan , Republic of China, 4 Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital , Linkou , Taiwan , Republic of China, 5 Head and Neck Oncology Group, Chang Gung Memorial Hospital , Linkou , Taiwan , Republic of China, 6 Chang Gung University , Linkou, Taiwan , Republic of China The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/ magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level $2.0 ng/ml and a CRP level $5.0 mg/L were significantly associated with clinical stage (P,0.001), clinical tumor status (P,0.001), and clinical nodal status (P,0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor ($8.6 mg/L) and lymph nodes ($5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC. - Head and neck cancer is the fourth most common cancer and leading cause of cancer-related deaths in Taiwan. [1] Amongst them, pharyngolaryngeal carcinoma (PLC) and oral cancer are prevalent and are associated with adverse lifestyles, including habitual tobacco, areca-quid (AQ) and alcohol use as well as human papilloma virus (HPV) infection. [2,3]. Knowledge of prognostic factors would be beneficial when evaluating and counseling patients with these cancers. Notably, HPV infection status has been strongly associated with the therapeutic response and survival of oropharyngeal cancer patients; however, it was not shown to be related to tumor stage or clinicopathological factors. [3] Preoperative squamous cell carcinoma antigen (SCC-Ag) level is a marker for pathologic lymph node metastasis, advanced tumor stage, and an increased rate of distant metastasis in patients with oral squamous cell carcinoma (OSCC). [4] Elevated serum CRP, a sensitive marker of inflammation and tissue damage, has been correlated with shorter survival in cancer patients [5,6,7,8] Importantly, the combined use of these two factors is useful in the stratification of OSCC patients receiving radical surgery. [9] However, their significance in patients with pharyngeal and laryngeal cancers has not been carefully addressed. Fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established tool for evaluating head and neck cancer. [10] The maximum standardized uptake valve (SUVmax) serves as a semi-quantitative simplified measurement of the tissue deoxyglucose metabolic rate and has been correlated with tumor proliferation rate, tumor grade and the expression of glucose transporters. [11] A high FDG uptake value is generally associated with a less favorable outcome. [12,13,14] For example, FDG uptake in breast cancer is correlated with markers of biological aggressiveness that can normally only be evaluated in vitro postoperatively, including mitotic count and the Ki-67 labeling index. [15] Accordingly, hypermetabolic breast tumors typically receive a poorer prognosis than those that are hypometabolic, demonstrating the relevance of FDG-PET/computed tomography (CT) analyses to tumor biology. [15]. Site of primary tumor Clinical N-status Treatment mode Surgery with adjuvant radiation Surgery with adjuvant chemoradiation Chemotherapy alone Concurrent chemoradiation Palliative treatment *SD: Standard deviation. doi:10.1371/journal.pone.0055327.t001 Patients and Methods Patients with Pharyngolaryngeal Cancer We retrospectively reviewed the charts of all patients newly diagnosed with PLC at our institute between June 2008 and Aug 2011. Patients with distant metastases at diagnosis or who were lost to follow up following diagnosis were excluded. Follow-up commenced at the time of cancer diagnosis and, for this study, completed at the earlier of either December 2011 or death. All patients were evaluated preoperatively with history, examination, routine bloods, chest radiograph, liver ultrasound, FDG-PET and either CT or magnetic resonance imaging (MRI) of the head and neck. [16]. Treatment of PLC All patients were staged as per American Joint Committee on Cancer guidelines (AJCC, 2010 edition; [17]) and treated according to their clinicopathological features. As previously described, chemotherapy was administered on an outpatient basis in 14-day cycles and comprised 50 mg/m2 cisplatin (P) on Day 1 followed by 800 mg/m2 oral tegafur (T) per day and 60 mg oral leucovorin (L) per day for 14 days (PTL regimen). [18] In the chemotherapy/radiotherapy group, chemotherapy was terminated after three cycles if there was little-or-no tumor response. In responders, PTL regimens were continued for up to six cycles before radiotherapy. Patients with good partial responses at the primary site after neoadjuvant chemotherapy received radiotherapy or CCRT for organ preservation. Radical surgery involved wide excision of primary tumors with at least 1 cm peripheral and deep surgical margins. Patients with a (...truncated)