Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer Avraham Eisbruch, M.D., 1 Jonathan A. Ship, D.M.D., 2 Laura A. Dawson, M.D., 1 Hyungjin M. Kim, D.Sc., 3 Carol R. Bradford, M.D., 4 Jeffrey E. Terrell, M.D., 4 Douglas B. Chepeha, M.D., 4 Theodore N. Teknos, M.D., 4 Norman D. Hogikyan, M.D., 4 Yoshimi Anzai, M.D., 5 Lon H. Marsh, R.T.T., 1 Randall K. Ten Haken, Ph.D., 1 Gregory T. Wolf, M.D. 4 1 Department of Radiation Oncology, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA 2 New York University College of Dentistry, 345 East 24th Street, New York, New York 10010, USA 3 Department of Biostatistics, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, USA 4 Department of Otorhinolaryngology–Head and Neck Surgery, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA 5 Department of Radiology, University of Michigan, 1500 Medical Center Drive, Ann Arbor, Michigan 48109, USA Published Online: June 3, 2003 Abstract. The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requir- ing comprehensive bilateral neck irradiation (RT), and to assess the po- tential for improved xerostomia. Since 1994 techniques of target irradia- tion and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodi- cally after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands’ dose volume histo- grams (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of re- currence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmen- tal IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients ir- radiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locore- gional tumor recurrence patterns revealed that the large majority of recur- rences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tan- gible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is sug- gested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of ≤ 26 Gy should be a planning objective if sig- nificant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control. The underlying goal in the development of conformal and static multisegmental intensity modulation (IMRT) techniques is to im- prove the ratio of target to normal tissue dose, and thereby to in- crease the probability of uncomplicated locoregional tumor con- trol. In the treatment of head and neck cancer, we have made efforts to use these techniques to spare the major salivary glands while improving target irradiation. The major salivary glands (parotid, submandibular, and sublin- gual) produce about 90% of the salivary secretions, and the minor salivary glands produce the remainder [1]. Of the major glands, the parotid glands contribute the most saliva during stimulation (e.g., eating or drinking). Standard radiation for advanced extracranial head and neck tumors typically involves administering radiation to the major salivary glands bilaterally. In most cases this causes a marked reduction in saliva output. Permanent xerostomia is the most prevalent late side effect of irradiation for head and neck ma- lignancies and is cited by patients as a major cause of decreased quality of life [2–4]. In addition to its effects on subjective well- being, decreased saliva output causes alterations in speech and taste and difficulties with mastication and deglutition that create secondary nutritional deficiencies. Oral mucosal dryness creates a predisposition to fissures and ulcerations, and changes in the com- position of the oral flora lead to dental caries and infections [5]. The treatment of radiation-induced salivary gland dysfunction and xerostomia has been unsatisfactory. Saliva substitutes are gen- erally ineffective. Patients who have residual salivary function may benefit from stimulation of the glands by pilocarpine. but the se- quelae from chronic use of this cholinergic agent may limit its use- fulness [6]. The use of the radiation protector amifostine has been reported to result in salivary function improvement over time [7], and to have a significant protective effect on the salivary glands [8]. It re- quires intravenous (IV) drug infusions before each radiation fraction, increasing the cost and the logistic complexity of treatment. Correspondence to: Avraham Eisbruch, M.D., e-mail: eisbruch@ umich.edu WORLD Journal of SURGERY © 2003 by the Socie ´te ´ Internationale de Chirurgie World J. Surg. 27, 832–837, 2003 DOI: 10.1007/s00268-003-7105-6