James I. Bicher, M.D., Ralph S. Wolfstein, M.D., Boris Burmistrovich, M.D., and Tressia Keen, M.N.

Valley Cancer Institute, Los Angeles, California, U.S.A.

INTRODUCTION

    A previous report compared our treatment results giving hyperthermia combined with each radiotherapy fraction versus twice a week with daily radiotherapy. A significant advantage for daily hyperthermia was demonstrated (1,2). This suggests that thermotolerance may not be an important factor in the clinic despite laboratory studies that definitively demonstrate resistance of treated cells to a second heat insult even weeks later (3,4).In analyzing results for patients treated subsequent to our earlier report we have again compared daily versus twice weekly hyperthermia treatment; and in addition we have looked at tumor response in localized versus disseminated disease.

MATERIALS AND METHODS

    Radiotherapy was given five days a week. Dosage varied widely, depending on multiple factors, including particularly consideration of previous irradiation. Hyperthermia was delivered either daily or twice weekly using either ultrasound or 915 MHZ Microwave equipment. Patients completing treatment between 1989 and 1994 are the subject of this report. These include 54 patients with breast and chest wall lesions of whom 23 had disseminated disease, 24 head and neck tumors, and 187 patients with deep tumors 118 with disseminated disease.

    Of 31 patients with locoregional breast or chest wall disease, 45% had complete response (CR) and 39% partial response (PR). Those with local disease given daily hyperthermia had a CR rate of 44% compared with 33% for twice weekly treatment (Figure 1). Of 23 who also had disseminated disease 78% had PR. None with disseminated disease had CR; the PR rate with daily hyperthermia was 81% and with twice weekly treatment 57%.

The CR rate for head and neck tumors treated daily was 77% and for those treated twice weekly just 18%,(fig. 2).

 DISCUSSION

    We continue to find a significant advantage for giving hyperthermia daily versus twice a week. Thermotolerance does not appear to be a critical factor in clinical hyperthermia practice, but the reason for this remains unclear. As previously stated, tumor heating is not homogeneous and the inhomogeneity in different treatment sessions may account for different cells in different resistance stages being treated in each session.

    The variation of results for locoregional versus disseminated disease was quite dramatic - CR 45% versus 0% for breast and chest wall and CR 30% versus. 5% for deep tumors. For this important new observation any explanation is strictly speculative, but obviously patients at an advanced stage in their disease respond poorly to localized treatment. Furthermore, failure to consider this factor in clinical studies of Hyperthermia effectiveness may explain sometimes erratic results in clinical trials.

 REFERENCES

1. Bicher, H.; Wolfstein, R.; Lewinsky, B; et al: "Microwave hyperthermia as an adjunct to radiation therapy: summary experience of 256 multi fraction treatment cases". Int. J. Radiat. Oncol. Biol. Phys. 12:1667-1671, 1986.

2. Arcangeli, G.; Cividalli, A.; Nervi, C.; et al: "Tumor control and therapeutic gain with different schedules of combined radiotherapy and local external hyperthermia in human cancer". Int J. Radiat Oncol Biol Phys 9:1125-1134, 1983.

3. Urano, M.; Maher, J.; Kahn, J.; et al: "Studies on fractionated hyperthermia in experimental animal systems III. uneven daily doses". Int J. Radiat Oncol Biol Phys 9:717-772, 1983.