- Email: [email protected]
Difficulties in assessing therapeutic results of clinical hyperthermia in an RTOG trial
164
Radiation
Oncology,
Biology,
Physics
October
1987, Volume
13, Supplement
1
144 DIFFICULTIES IN ASSESSING THERAPEUTIC RESULTS OF CLINICAL HYPERTAERMIAIN AN RTOG TRIAL. C.A. Perez, E. Pakuris Radiation
B. Gillespie, Therapy
N. Hornback,
Oncology
Group,
B. Emami, D. Moylan,
1101 Market
Street,
14th
W. Hans Baerwald, Fl.,
Philadelphia,
M.H. Seegenschmiedt,
M. Bauer,
PA 19107
Since February 1981, 287 patients with superficial measurable tumors have been randomized on an RTOG protocol involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (43V, 45-60 min). This is a report of 206 eligible patients with single lesions: 102 treated with radiotherapy alone (RT), 104 with radiotherapy plus hyperthermia (RT + HTA). Complete response has been observed in 28% of the patients on RT, and 29% of the patients on RT + HTA. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (< 3 or 2 3 cm) and site/histology (breast/adenocarcinoma, head & neck/squamous, or other site/histologies). For each of these subgroups, response rates (with sample sizes in parentheses) are given in the tables below. RT BreastlAden H&N/Squamous Other
33% (39) 32% (34) 17% (29)
RT+HTA
RT < 3 cm -> 3 cm
41% (37) 24% (33) 21% (34)
33% (24) 27% (77)
RT+HTA 50% (24) 22% (78)
It has been hypothesized that the response rate is higher in patients with smaller lesions (<3 cm) and in breast lesions since these lesions are easier to heat. However, evaluation of the relationship between thermal dose and tumor response is complicated by several factors. Problems encountered include the limited ability of current thermometry methods to map the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because rapid tumor regression may cause skin necrosis and be misinterpreted as persistent tumor. The impact of these factors on evaluation of the relationship between heat administration and tumor response will be discussed.
145 THE EFFECT OF HYPERTHERMIA ON THE EARLY- AND LATE-APPEARING II EFFECT ON THE RADIATION CARCINOGENESIS. CARCINOGENESIS. J. Kahn,
M. Urano,
M.D.,
Radiation
Medicine,
B.S. and L. Kenton,
Massachusetts
General
MOUSE
FOOT REACTIONS
AND ON THE RADIATION
B.S.
Hospital,
Boston,
MA
02114
It has been demonstrated that hyperthermia can enhance the response of mammalian cells to radiation. Thermal enhancement of radiation response of various normal tissues has been documented. Regarding the clinical trial of combined hyperthermia and radiotherapy, a critical question_ may be if thermal . . _ enhancement Another might be if hyperthermia also enhances the ratio differs between acute and late-responding tissues. incidence of radiation carcinogenesis. We have studied these questions using the mouse foot reaction and, in this meeting, the latter question will be focused. Animals were both sexes of C3Hf/Sed mice derived from our defined flora mouse colony. They were kept The mouse foot was irradiated with a I37 Cs under defined flora conditions throughout the experiments. unit with a field size of 3 cm diameter and a dose rate of = 7.5 Gy/min under clanp hypoxia, in air, or under Hyperthermia was given by immersing animal feet into a water bath where hyperbaric oxygen conditions (HPO). Tissue temperature was no more than D.l'C 43.5 + O.l"C was maintained bv a constant temperature circulator. Foot reactions were scored according to our numerical score method (1). below-the water bath temperature. Foot reactions developed first on = 14th post-irradiation day, reached a maximum on = day 21, and Foot reaction scores began to increase again between days 200 and 250, and stayed constant subsided slowly. or increased continuously. We called these reactions early- and late-appearing reactions, respectively (2). Radiation-induced neoplasm in the irradiated foot developed after day 250 with a median time (the time of A total of 258 tumors were developed in irradiated areas one-half of the irradiated tumors) of = 500 davs. Approximately 65% were fibrosarcomas. Other and histological exsninations were completed in 210 tumors. ma.ior histoloaical types include rhabdomvosarcoma (7%). undifferentiated sarcoma (12%). squamous cell carcinoma (6%j, and hemoangiosarcoma (5%). '_ Based on the tumor incidence in each dose group, 50% radiation carcinogenesis dose (RCD50 or the radiation dose which induces a tumor in one-half of the irradiated sites) was calculated by logit analysis. iven under hypoxic conditions, in air,.and under HP0 were 66.3 (95% RCD50 values for radiation alone and 22.2 (19.2-25.0) Gy, respectively. The TER values (thermal C.L.: 60.0-78.3), 37.7 (34.4-41.37 enhancement ratio) following hypoxlc irradiation for combined treatments: heat prior to radiation and heat These values were slightly smaller than after radiation (treatment interval was 20 min) were 2.48 and 2.00.
Radiation
Oncology,
Biology,
Physics
October
1987, Volume
13, Supplement
1
144 DIFFICULTIES IN ASSESSING THERAPEUTIC RESULTS OF CLINICAL HYPERTAERMIAIN AN RTOG TRIAL. C.A. Perez, E. Pakuris Radiation
B. Gillespie, Therapy
N. Hornback,
Oncology
Group,
B. Emami, D. Moylan,
1101 Market
Street,
14th
W. Hans Baerwald, Fl.,
Philadelphia,
M.H. Seegenschmiedt,
M. Bauer,
PA 19107
Since February 1981, 287 patients with superficial measurable tumors have been randomized on an RTOG protocol involving fractionated radiation therapy (4.00 Gy twice weekly for a total of 32.00 Gy), either alone or followed immediately by hyperthermia (43V, 45-60 min). This is a report of 206 eligible patients with single lesions: 102 treated with radiotherapy alone (RT), 104 with radiotherapy plus hyperthermia (RT + HTA). Complete response has been observed in 28% of the patients on RT, and 29% of the patients on RT + HTA. Response has been found in previous analyses of this and other RTOG studies to be significantly related to both maximum tumor diameter (< 3 or 2 3 cm) and site/histology (breast/adenocarcinoma, head & neck/squamous, or other site/histologies). For each of these subgroups, response rates (with sample sizes in parentheses) are given in the tables below. RT BreastlAden H&N/Squamous Other
33% (39) 32% (34) 17% (29)
RT+HTA
RT < 3 cm -> 3 cm
41% (37) 24% (33) 21% (34)
33% (24) 27% (77)
RT+HTA 50% (24) 22% (78)
It has been hypothesized that the response rate is higher in patients with smaller lesions (<3 cm) and in breast lesions since these lesions are easier to heat. However, evaluation of the relationship between thermal dose and tumor response is complicated by several factors. Problems encountered include the limited ability of current thermometry methods to map the temperature distribution in a tumor. Furthermore, differences in equipment and treatment practices among institutions add to the variability in heat administration data collected. In addition, tumor response may be difficult to judge because rapid tumor regression may cause skin necrosis and be misinterpreted as persistent tumor. The impact of these factors on evaluation of the relationship between heat administration and tumor response will be discussed.
145 THE EFFECT OF HYPERTHERMIA ON THE EARLY- AND LATE-APPEARING II EFFECT ON THE RADIATION CARCINOGENESIS. CARCINOGENESIS. J. Kahn,
M. Urano,
M.D.,
Radiation
Medicine,
B.S. and L. Kenton,
Massachusetts
General
MOUSE
FOOT REACTIONS
AND ON THE RADIATION
B.S.
Hospital,
Boston,
MA
02114
It has been demonstrated that hyperthermia can enhance the response of mammalian cells to radiation. Thermal enhancement of radiation response of various normal tissues has been documented. Regarding the clinical trial of combined hyperthermia and radiotherapy, a critical question_ may be if thermal . . _ enhancement Another might be if hyperthermia also enhances the ratio differs between acute and late-responding tissues. incidence of radiation carcinogenesis. We have studied these questions using the mouse foot reaction and, in this meeting, the latter question will be focused. Animals were both sexes of C3Hf/Sed mice derived from our defined flora mouse colony. They were kept The mouse foot was irradiated with a I37 Cs under defined flora conditions throughout the experiments. unit with a field size of 3 cm diameter and a dose rate of = 7.5 Gy/min under clanp hypoxia, in air, or under Hyperthermia was given by immersing animal feet into a water bath where hyperbaric oxygen conditions (HPO). Tissue temperature was no more than D.l'C 43.5 + O.l"C was maintained bv a constant temperature circulator. Foot reactions were scored according to our numerical score method (1). below-the water bath temperature. Foot reactions developed first on = 14th post-irradiation day, reached a maximum on = day 21, and Foot reaction scores began to increase again between days 200 and 250, and stayed constant subsided slowly. or increased continuously. We called these reactions early- and late-appearing reactions, respectively (2). Radiation-induced neoplasm in the irradiated foot developed after day 250 with a median time (the time of A total of 258 tumors were developed in irradiated areas one-half of the irradiated tumors) of = 500 davs. Approximately 65% were fibrosarcomas. Other and histological exsninations were completed in 210 tumors. ma.ior histoloaical types include rhabdomvosarcoma (7%). undifferentiated sarcoma (12%). squamous cell carcinoma (6%j, and hemoangiosarcoma (5%). '_ Based on the tumor incidence in each dose group, 50% radiation carcinogenesis dose (RCD50 or the radiation dose which induces a tumor in one-half of the irradiated sites) was calculated by logit analysis. iven under hypoxic conditions, in air,.and under HP0 were 66.3 (95% RCD50 values for radiation alone and 22.2 (19.2-25.0) Gy, respectively. The TER values (thermal C.L.: 60.0-78.3), 37.7 (34.4-41.37 enhancement ratio) following hypoxlc irradiation for combined treatments: heat prior to radiation and heat These values were slightly smaller than after radiation (treatment interval was 20 min) were 2.48 and 2.00.