This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7+/-9.7)% in the first week and decreases (42.4+/-7.0)% in the second week. Averaged StO(2) increases from (62.9+/-3.4)% baseline value to (70.4+/-3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7+/-7.0) [microM] to (73.3+/-8.3) [microM] at the end of the second week and to (63.0+/-8.1) [microM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.