Proton therapy offers additional sparing of critical organs for head and neck tumors compared to IMRT. However, proton beams are sensitive to changes in tissue densities, and anatomic change during the course of treatment may affect the proton dose distribution. This study investigates whether adaptive replanning is needed to compensate for anatomic change during therapy. Six patients, three with nasopharyngeal carcinoma and three with paranasal sinus cancer, treated with definitive or postoperative proton radiation therapy were analyzed retrospectively. A re-planning CT scan was acquired during mid-late course at a median dose of 53 Gy. The scans were registered rigidly to bony structures of the skull to remove the setup error. A deformable B-spline based registration was then performed to transfer structure contours from the planning CT to the re-planning CT. The original treatment plan was applied to the re-planning CT, and proton dose was re-calculated. Anatomic differences between the two CT scans were analyzed interactively, and dose distributions were evaluated by comparing isodose lines and distance-to-agreement analysis. Dose-volume histograms were compared using transferred contours on the re-planning CT and original contours on the pre-treatment CT. Autotransferred contours for critical organs were evaluated, and found to be satisfactory for critical structures. Target structures were re-delineated manually. Anatomic changes were observed in all six cases. The most significant change in the re-planning CT was the decrease in GTV volume with a median change of -12% (range, 0-36%). As a result of the increase in air in the sinuses, the average density within GTV was decreased from 93 +/- 11 Hounsfield unit (HU) to 37 +/- 36 HU (median, 43 HU). Of the 6 studied cases, the median change in the mean GTV dose was +1% (range, 0 - +1%). Hot spots larger than 1 cm3 within the GTV with dose increase of 6% and 7% were observed in 2 cases. The median GTV volume that received > 110% of the prescribed dose increased from 0.4% to 2.37%. The median of the maximum dose to the GTV nearly unchanged (79.28 vs. 79.44 Gy). There is no significant change in the CTV dose in all the studied cases. The median dose change to the Dmax of brainstem was +8% (range, 0 - +15%). The median dose change to the mean of the brainstem dose was +1.5% (range, -6% - +3%). The median dose change to the Dmax of optic chiasm and optic nerve (left or right), were -3% (range, -11% - 0) and -0.5% (range, -4.5% - +11%), respectively. Our study demonstrates that anatomic change during proton radiation therapy for base of skull tumor, especially tumor shrinkage in the sinuses, can occur. Increased heterogeneity of tissue densities within the GTV can result in hot spots. The results of six additional cases will be presented at the meeting.