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Scientific paper presented
by Dr. James Bicher on the XVII ICHS Hyperthermia conference
EFFECT OF TUMOR STAGE AND FREQUENCY
OF TREATMENT ON LOCAL RESPONSE TO THERMORADIOTHERAPY
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.
BREAST AND CHEST
WALL
RESULTS
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%.
Table 1
BREAST AND
CHEST WALL TUMORS DISSEMINATED. ALL PATIENTS |
|
BREAST AND
CHEST WALL TUMORS.
LOCAL |
. |
|
5 TREATMENTS
A WEEK |
|
2 TREAT. A
WEEK |
. |
# PAT. |
% RES. |
|
. |
# PAT. |
% RES. |
|
# PAT. |
% RES. |
| CR+PR |
(18) |
78.0 |
|
CR+PR |
(20) |
80.0 |
|
(5) |
88.0 |
| CR |
0 |
0.0 |
|
CR |
11 |
44.0 |
|
2 |
33.0 |
| PR |
18 |
78.0 |
|
PR |
9 |
36.0 |
|
3 |
50.0 |
| NR |
5 |
22.0 |
|
NR |
5 |
20.0 |
|
1 |
17.0 |
| SD |
0 |
0.0 |
|
SD |
0 |
0.0 |
|
0 |
0.0 |
| TOTAL |
23 |
. |
|
TOTAL |
25 |
. |
|
6 |
. |
CR: Complete Response:
PR: partial Response: NR: No Response:
SD: Stable Disease
The CR rate for head and neck tumors treated daily was 77% and for those treated twice
weekly just 18%,(fig. 2).
HEAD AND NECK
Table 2
HEAD AND NECK
TUMORS
ALL PATIENTS |
|
HEAD AND NECK
TUMORS |
. |
|
5 TREATMENTS
A WEEK |
|
2 TREAT. A
WEEK |
. |
# PAT. |
% RES. |
|
. |
# PAT. |
% RES. |
|
# PAT. |
% RES. |
| CR+PR |
(19) |
79.0 |
|
CR+PR |
(13) |
100.0 |
|
(7) |
63.7 |
CR |
12 |
50.0 |
|
CR |
10 |
77.0 |
|
2 |
18.2 |
PR |
7 |
29.0 |
|
PR |
3 |
23.0 |
|
5 |
45.5 |
NR |
4 |
16.5 |
|
NR |
0 |
0.0 |
|
3 |
27.3 |
SD |
1 |
4.5 |
|
SD |
0 |
0.0 |
|
1 |
9.0 |
TOTAL |
24 |
. |
|
TOTAL |
13 |
. |
|
11 |
. |
DEEP TUMORS
Of 69 patients with primary or recurrent localized
deep tumors 30% had CR. This compares to a CR rate of 5% for those with disseminated
disease, (Figure 3), 8% with daily hyperthermia and 2% with twice a week treatment; the PR
rate with daily treatment was 70% versus 56% for twice a week treatment.
Table 3
DEEP LOCAL
TUMORS
PRIMARY AND RECURRENT |
|
DEEP
DISSEMINATED TUMORS |
. |
#
PATIENTS |
% RESPONSE |
|
. |
# PATIENTS |
% RESPONSE |
| CR+PR |
(52) |
75.0 |
|
CR+PR |
(75) |
64.7 |
CR |
21 |
30.0 |
|
CR |
6 |
5.2 |
PR |
31 |
45.0 |
|
PR |
69 |
59.5 |
NR |
14 |
20.5 |
|
NR |
40 |
34.5 |
SD |
3 |
4.5 |
|
SD |
1 |
0.8 |
TOTAL |
69 |
. |
|
TOTAL |
116 |
. |
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.
4. Urano, M.; Kahn, J.: "Differential Kinectics of thermal resistance
(thermotolerance) between murine normal and tumor tissue". Int J. Radiat Oncol
Biol Phys 12:89-93, 1986.
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