Abstract 4147: Non-invasive deep tissue temperature measurement during neoadjuvant chemotherapy reveals apoptosis and metabolism changes in breast cancer during therapy
Authors: Chung So Hyun , Chance Britton , Mehta Rita , Tromberg Bruce J. , Yodh Arjun G. 
Published: August 2014

Metabolism of mitochondria can be monitored by measuring thermogenic activity. A linear increase of heating rate vs. rate of oxygen utilization for NADH oxidation has been shown [Poe, Arch. Biochem. Biophy., 1967]. Moreover, the heat generation increases four-fold in the uncoupled apoptotic state compared to resting state of mitochondria, as a successful anticancer drug opens the ion channel pore or increase membrane permeability [Estabrook, 1967, Johnstone, Cell 2002]. During apoptosis, more numerous and smaller mitochondria are yielded, which might also explain increase of heat generation. In this study we explore these issues: Diffuse Optical Spectroscopy Imaging (DOSI) monitors absolute temperature of a breast with infiltrating ductal carcinoma (IDC), as well as oxy- and deoxy-hemoglobin concentration.

DOSI employs low power near-infrared light to quantify tissues. The diffusion model affords quantitative determination of tissue chromophore absorption spectra by separating scattering and absorption effects. Especially, the water peak appear at 935-1000nm provides information about tissue water concentration, state and absolute temperature as shown by Chung et al [PMB 2008, 2010]. In this case study, we measured a 63 year old subject who had IDC in both breasts. She received neoadjuvant chemotherapy with two different regimens: Adriamycin+Cytoxan (AC, one and half months) and Carboplatin+Abraxane+Avastin (CAA, 3 months). The patient was measured 19 times along the course of therapy: at pre-treatment, 8 points during AC, 9 points during CAA, and after completion of the therapy. She was a pathological complete responder. All points on a spectroscopic image of the lesion breast were used for the average and standard deviation of each quantity at each time point.

After some fluctuations in the early stage, the temperature was observed to increase up to 39.5±1.2°C by the last phase of AC dose, showing 4.6% increase/day. During CAA, the temperature decreased eventually at a rate of -1%/day. After completion of the therapy, the temperature changed only about -0.6% to 36.9±0.7°C. In two time windows just before the end of AC and in the middle of CAA, oxy-hemoglobin increased with the temperature.

The four fold increase of temperature during AC suggests the uncoupling of mitochondria due to apoptosis, an effect which appears as both an increase of temperature and deoxy-hemoglobin concentration. Then, possible massive cell death is indicated by the decrease of temperature. During AC therapy, possible aerobic glycolysis followed metabolic increase due to apoptosis, and then massive cell death followed. Overall, although preliminary, this study suggests the potential of DOSI measured temperature and other quantitative physiological components as a non-invasive and longitudinal monitor of apoptosis process during neoadjuvant chemotherapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4147. doi:10.1158/1538-7445.AM2011-4147