EXTRACELLULAR PH AS A PROGNOSTIC FACTOR IN THERMORADIOTHERAPY

Purpose: Tumor extracellular pH measurements in 26 human tumors were e valuated for the purpose of prognostic indication of response to therm oradiotherapy. Methods and Materials: Twenty-six patients (10 male, 16 female; mean age 62 years, range 18-89) were treated with external mi crowave hyperthermia (915 MHz) combined with radiation therapy. Tumor histologies included: 46% adenocarcinoma, 38% squamous cell carcinoma, 12% soft tissue sarcoma, and 4% malignant melanoma. The mean tumor de pth was 1.6 +/- 0.2 cm (range 0.4-3 cm) and the mean tumor volume was 73 +/- 11 cm(3) (range 1-192 cm(3)). The mean radiation dose administe red concurrently with hyperthermia was 39 +/- 1 Gy (range 24-60 Gy, me dian of 40 Gy), in 15 fractions (range 8-25), over 32 elapsed days (ra nge 15-43). The mean number of hyperthermia sessions administered was 5.4 +/- 0.5 (range 2-10). A battery operated pH meter and combination 21 ga recessed glass, beveled needle microelectrodes were used for tum or pH measurements. Calibration in pH buffers was performed before and after each pH measurement. The needle microelectrodes were 2.5 cm in length. Results: A complete response (CR) was obtained in 20 of 26 pat ients (77%) and a partial response in six (23%). The mean extracellula r tumor pH was 6.88 +/- 0.09 in CR patients while it was 7.24 +/- 0.09 in noncompletely responding (NCR) patients (p = 0.08). Logistic regre ssion analysis indicated that the probability of obtaining a complete response was influenced by the tumor volume (p = 0.02), tumor depth (p = 0.05), and extracellular tumor pH (p = 0.08). Lesions in the pH ran ge of 6.00-6.40 and lesions in the pH range of 6.41-6.80 exhibited a C R rate of 100%, while those lesions in the pH range of 6.81-7.20 exhib ited a CR of 90% and those in the pH range of 7.21-7.52 exhibited a CR of 50% (p = 0.002). In lesions with depth less than or equal to 1.5 c m, the CR rate was 100% when the tumor pH was < 7.15 and 75% when the tumor pH was greater than or equal to 7.15. In lesions with depth betw een 1.5 and 3 cm, the CR rate was 66% when the tumor pH was < 7.15 and 43% when the tumor pH was greater than or equal to 7.15 (p = 0.02). I n small tumors, that is, less than or equal to 20 cm(3), tumor pH incr eased with volume; whereas in larger tumors, that is, > 20 cm(3), tumo r pH decreased as a function of tumor volume. Conclusion: Tumor extrac ellular pH may be useful as a prognostic indicator of tumor response t o thermoradiotherapy.