Pharyngeal Carcinoma and Natural Killer Cell Activity Stimson P. Schantz, MD, Bruce H. Campbell, MD, and Dscar M. Gulllamandegui, MD, Houston, Texas There is increasing awareness of the significance of distant metastases in the head and neck cancer pa- tient. Before the 19609, the incidence of subclavicu- lar spread of disease was considered to be between 2 and 12 percent [l-3]. More recent reports have re- ported distant disease rates of 11 to 47 percent [4-8]. Although factors that contribute to the metastat- ic process are poorly understood, the relative risks of distant me&stases have been attributed to cer- tain parameters of disease status. One such parame- ter may relate to site of disease within the upper aerodigestive tract. Persons with pharyngeal lesions are at greatest risk. Distant metastases in patients with pharyngeal cancer vary from zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 13 to 83 percent depending on the method of analysis [4-6]. A potential contributing factor to distant metas- tases in patients with pharyngeal cancer may relate to the immunologic response of the host. Numerous studies have demonstrated the relationship be- tween impaired immunologic function and poor prognosis in head and neck cancer patients [9]. Few reports, however, have addressed a comparison of immune status with specific location of primary disease within the upper aerodigestive tract. This study was designed to assess natural killer cell activity in patients with pharyngeal cancer. The natural killer cell has been implicated in the control of distant metastatic disease [10,11]. It has been defined as a cell population capable of killing with- out previous sensitization and without regard to major histocompatibility. It is characterized mor- phologically as a large granular lymphocyte and has been shown to express distinct phenotypic markers, that is, Leu 7 and Leu 11 antigens [12-141. The importance of natural immune surveillance in the head and neck cancer patient is unknown. Studies have demonstrated that natural killer cell activitv is From the Department of Head and Neck Surgery, The University of Texas- M.D. Anderson Hosottal and Tumor Instiiute. Houston. Texas. Suooorted in part by a grant from the Kimberly Clark Co&ration,‘Neenah, V&consin. Requests for reprints should be addressed to Stimson P. Schantz, MD, Department of Head and Neck Surgery, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute. 6723 Sertner Avenue, Houston, Texas 77030. Presented at the 32nd Annual Meeting of the Society of Head and Neck Surgeons, Colorado Springs, Colorado, May 7-10. 1986. Volume 152, Dctobar 1986 diminished in head and neck cancer patients with lymph node metastases [15]. It similarly may be influenced by patterns of primary tumor growth as well as by treatment [16,17]. An understanding of natural killer cell activity in patients with pharyn- geal cancer may increase our awareness of factors contributing to the metastatic process. Material and Methods Patients with previously untreated squamous cell car- cinoma of the head and neck form the basis of this study. Factors that excluded patients from evaluation included concomitant serious illness, previous or active treatment including surgery, radiotherapy, or chemotherapy, and clinical evidence of distant metastatic disease. The medi- an age of the 42 patients with pharyngeal cancer who fulfilled these requirements was 58 (range 33 to 76 years). There were 33 men and 9 women. Sites of primary disease included the tonsil in 7 pa- tients, the soft palate in 7, the base of the tongue in 8, the pharyngeal wall in 10, and the pyriform sinus in 10. All sites are considered pharyngeal sites of disease by the American Joint Committee on Cancer Staging and End Results Reporting (1983) criteria. Clinical parameters were assessed prospectively and included, in addition to disease staging, an evaluation of tobacco and alcohol abuse, concurrent medical illness, and weight loss. Longitudinal evaluation was performed only in those patients rendered clinically free of disease after definitive treatment. Minimum follow-up was 6 months (mean 12 months) (range 6 to 38 months). Using these criteria, three patients were eliminated from the study because they did not undergo definitive therapy at our institution. In addition, five other patients were not followed for the required minimum of 6 months and were, therefore, eliminated. A total of 34 pharyngeal cancer patients fulfilled study criteria for longitudinal evalua- tion Patients were routinely assessed at 1 year post- treatment follow-up with chest radiography. The identifi- cation of distant metastases was made only by clinical methods. Autopsy findings were excluded from evalua- tion to ensure comparability of assessment. To establish potential differences in natural killer cell activity as a function of site, patients with either previous- 467